Evaluation of trends in pH in the Yampa River, northwestern Colorado, 1950-2000

USGS Publications Warehouse

Chafin, Daniel T.

2002-01-01

In 1999, the U.S. Geological Survey began a study of pH trends in the Yampa River from near its headwaters to its mouth. The study was prompted by an apparent historical increase in measured pH at the Yampa River near Maybell, from an average of about 7.6 in the 1950's and 1960's to about 8.3 in the 1980's and 1990's. If real, further increase could cause more frequent exceedances of the Colorado water-quality standard of 9.0 and adversely affect aquatic life in the Yampa River Basin, including Dinosaur National Monument. The principal conclusion of this study is that this apparent historical increase in measured pH was caused mostly by changes in measurement protocol. Synoptic sampling during August 16-19, 1999, a period of relatively warm weather and base flow, showed that late afternoon pH of the Yampa River ranged from 8.46 to 9.20. The largest pH (9.20) exceeded the Colorado water-quality standard and was measured at Yampa River above Elk River, about 1.8 miles downstream from the Steamboat Springs Regional Waste Water Treatment Plant outfall, where nutrient enrichment caused photosynthesis by algae to dominate. Here, the dissolved oxygen concentration was 161 percent of saturation and carbon dioxide (CO2 was at 26 percent of saturation. At Yampa River downstream from a diversion near Hayden, 16.3 miles downstream, the effects of photosynthesis were still dominant, though attenuated by reaeration and dilution with freshwater from the Elk River. About 37.2 miles farther downstream, at Yampa River below Craig, which is about 6.2 miles downstream from the Craig Waste Water Treatment Plant, the effects of photosynthesis increased slightly, and pH rose to 8.80. Respiration plus oxidation of organic matter became dominant at Yampa River at Deerlodge Park in Dinosaur National Monument, where pH was 8.51, dissolved oxygen concentration was at 109 percent of saturation, and CO2 was at 189 percent of saturation. Respiration plus oxidation of organic matter, though diminished, apparently extended to the mouth of the Yampa River. Diurnal measurements on the Yampa River during August 23-26, 1999, show that the effects of photosynthesis and respiration plus oxidation of organic matter decreased downstream with distance from the developed urban area in the eastern part of the basin. Larger night-time values of pH in Dinosaur National Monument at Deerlodge Park and at the mouth of the Yampa River indicate that source waters varied with respect to capacity for respiration plus oxidation and photo-synthesis, that photosynthesis was minor, and that pH was largely controlled by respiration plus oxidation of organic matter. Synoptic sampling was repeated during March 13-16, 2000, when discharge was larger in response to late-winter melting of snow and ice at lower altitudes in the basin. Concentrations of nitrite plus nitrate were about 9 times greater in the Yampa River during March 2000 than during August 1999, and the largest increase (greater than 1,200 percent) was at Yampa River below Craig. At and downstream from Steamboat Springs, Colorado, pH at Yampa River sites averaged 8.85 during synoptic sampling in March 2000 compared to 8.70 in August 1999, with the partial pressure of carbon dioxide gas (PCO2) averaging 67 percent of saturation (compared to 99 percent during August 1999). The apparently larger effects of photosynthesis on pH and dissolved oxygen concentrations during March 2000 compared to August 1999 probably were caused by (1) slower rates of exchange of CO2 into and dissolved oxygen out of the river because of colder and deeper water and (2) slower rates of CO2 production and oxygen consumption resulting from slower rates of respiration by organisms and from slower rates of aerobic decomposition of organic matter in the colder river water and streambed sediment. Hypothetical thermodynamic simulations were done for samples collected in the lower Yampa River Basin to simulate the same amount of photosynthesis th

Increasing Malonyl-CoA Derived Product through Controlling the Transcription Regulators of Phospholipid Synthesis in Saccharomyces cerevisiae.

PubMed

Chen, Xiaoxu; Yang, Xiaoyu; Shen, Yu; Hou, Jin; Bao, Xiaoming

2017-05-19

Malonyl-CoA is a precursor of a variety of compounds such as polyketides and flavonoids. In Saccharomyces cerevisiae, malonyl-CoA concentration is tightly regulated and therefore maintained at a very low level, limiting the production of malonyl-CoA-derived chemicals. Here we manipulated the phospholipid synthesis transcriptional regulators to control the malonyl-CoA levels and increase the downstream product. Through manipulating different regulators including Ino2p, Ino4p, Opi1p, and a series of synthetic Ino2p variants, combining with studying the inositol and choline effect, the engineered strain achieved a 9-fold increase of the titer of malonyl-CoA-derived product 3-hydroxypropionic acid, which is among the highest improvement relative to previously reported strategies. Our study provides a new strategy to regulate malonyl-CoA availability and will contribute to the production of other highly valued malonyl-CoA-derived chemicals.

Cyanidin-3-O-β-glucoside regulates fatty acid metabolism via an AMP-activated protein kinase-dependent signaling pathway in human HepG2 cells

PubMed Central

2012-01-01

Background Hepatic metabolic derangements are key components in the development of fatty liver disease. AMP-activated protein kinase (AMPK) plays a central role in controlling hepatic lipid metabolism through modulating the downstream acetyl CoA carboxylase (ACC) and carnitine palmitoyl transferase 1 (CPT-1) pathway. In this study, cyanidin-3-O-β-glucoside (Cy-3-g), a typical anthocyanin pigment was used to examine its effects on AMPK activation and fatty acid metabolism in human HepG2 hepatocytes. Results Anthocyanin Cy-3-g increased cellular AMPK activity in a calmodulin kinase kinase dependent manner. Furthermore, Cy-3-g substantially induced AMPK downstream target ACC phosphorylation and inactivation, and then decreased malonyl CoA contents, leading to stimulation of CPT-1 expression and significant increase of fatty acid oxidation in HepG2 cells. These effects of Cy-3-g are largely abolished by pharmacological and genetic inhibition of AMPK. Conclusion This study demonstrates that Cy-3-g regulates hepatic lipid homeostasis via an AMPK-dependent signaling pathway. Targeting AMPK activation by anthocyanin may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease. PMID:22243683

SGLT2 Inhibitors: Glucotoxicity and Tumorigenesis Downstream the Renal Proximal Tubule?

PubMed

Bertinat, Romina; Nualart, Francisco; Yáñez, Alejandro J

2016-08-01

At present, diabetes mellitus is the main cause of end-stage renal disease. Effective glycaemic management is the most powerful tool to delay the establishment of diabetic complications, such as diabetic kidney disease. Together with reducing blood glucose levels, new anti-diabetic agents are expected not only to control the progression but also to restore known defects of the diabetic kidney. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are promising anti-diabetic agents that reduce hyperglycaemia by impairing glucose reabsorption in proximal tubule of the kidney and increasing glucosuria. SGLT2 inhibitors have shown to reduce glucotoxicity in isolated proximal tubule cells and also to attenuate expression of markers of overall kidney damage in experimental animal models of diabetes, but the actual renoprotective effect for downstream nephron segments is still unknown and deserves further attention. Here, we briefly discuss possible undesired effects of enhanced glucosuria and albuminuria in nephron segments beyond the proximal tubule after SGLT2 inhibitor treatment, offering new lines of research to further understand the renoprotective action of these anti-diabetic agents. Strategies blocking glucose reabsorption by renal proximal tubule epithelial cells (RPTEC) may be protective for RPTEC, but downstream nephron segments will still be exposed to high glucose and albumin levels through the luminal face. The actual effect of constant enhanced glucosuria over distal nephron segments remains to be established. J. Cell. Physiol. 231: 1635-1637, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Role of plasma membrane-associated AKAPs for the regulation of cardiac IK1 current by protein kinase A.

PubMed

Seyler, Claudia; Scherer, Daniel; Köpple, Christoph; Kulzer, Martin; Korkmaz, Sevil; Xynogalos, Panagiotis; Thomas, Dierk; Kaya, Ziya; Scholz, Eberhard; Backs, Johannes; Karle, Christoph; Katus, Hugo A; Zitron, Edgar

2017-05-01

The cardiac I K1 current stabilizes the resting membrane potential of cardiomyocytes. Protein kinase A (PKA) induces an inhibition of I K1 current which strongly promotes focal arrhythmogenesis. The molecular mechanisms underlying this regulation have only partially been elucidated yet. Furthermore, the role of A-kinase anchoring proteins (AKAPs) in this regulation has not been examined to date. The objective of this project was to elucidate the molecular mechanisms underlying the inhibition of I K1 by PKA and to identify novel molecular targets for antiarrhythmic therapy downstream β-adrenoreceptors. Patch clamp and voltage clamp experiments were used to record currents and co-immunoprecipitation, and co-localization experiments were performed to show spatial and functional coupling. Activation of PKA inhibited I K1 current in rat cardiomyocytes. This regulation was markedly attenuated by disrupting PKA-binding to AKAPs with the peptide inhibitor AKAP-IS. We observed functional and spatial coupling of the plasma membrane-associated AKAP15 and AKAP79 to Kir2.1 and Kir2.2 channel subunits, but not to Kir2.3 channels. In contrast, AKAPyotiao had no functional effect on the PKA regulation of Kir channels. AKAP15 and AKAP79 co-immunoprecipitated with and co-localized to Kir2.1 and Kir2.2 channel subunits in ventricular cardiomyocytes. In this study, we provide evidence for coupling of cardiac Kir2.1 and Kir2.2 subunits with the plasma membrane-bound AKAPs 15 and 79. Cardiac membrane-associated AKAPs are a functionally essential part of the regulatory cascade determining I K1 current function and may be novel molecular targets for antiarrhythmic therapy downstream from β-adrenoreceptors.

Gross CO2 and CH4 emissions from the Nam Ngum and Nam Leuk sub-tropical reservoirs in Lao PDR.

PubMed

Chanudet, Vincent; Descloux, Stéphane; Harby, Atle; Sundt, Håkon; Hansen, Bjørn Henrik; Brakstad, Odd; Serça, Dominique; Guerin, Frédéric

2011-11-15

Gross CO2 and CH4 emissions (degassing and diffusion from the reservoir) and the carbon balance were assessed in 2009-2010 in two Southeast Asian sub-tropical reservoirs: the Nam Ngum and Nam Leuk Reservoirs (Lao PDR). These two reservoirs are within the same climatic area but differ mainly in age, size, residence time and initial biomass stock. The Nam Leuk Reservoir was impounded in 1999 after partial vegetation clearance and burning. However, GHG emissions are still significant 10 years after impoundment. CH4 diffusive flux ranged from 0.8 (January 2010) to 11.9 mmol m(-2) d(-1) (April 2009) and CO2 diffusive flux ranged from -10.6 (October 2009) to 38.2 mmol m(-2) d(-1) (April 2009). These values are comparable to other tropical reservoirs. Moreover, degassing fluxes at the outlet of the powerhouse downstream of the turbines were very low. The tentative annual carbon balance calculation indicates that this reservoir was a carbon source with an annual carbon export (atmosphere+downstream river) of about 2.2±1.0 GgC yr(-1). The Nam Ngum Reservoir was impounded in 1971 without any significant biomass removal. Diffusive and degassing CO2 and CH4 fluxes were lower than for other tropical reservoirs. Particularly, CO2 diffusive fluxes were always negative with values ranging from -21.2 (April 2009) to -2.7 mmol m(-2) d(-1) (January 2010). CH4 diffusive flux ranged from 0.1 (October 2009) to 0.6 mmol m(-2) d(-1) (April 2009) and no degassing downstream of the turbines was measured. As a consequence of these low values, the reservoir was a carbon sink with an estimated annual uptake of - 53±35 GgC yr(-1). Copyright © 2011 Elsevier B.V. All rights reserved.

Functional characterisation of HvCO1, the barley (Hordeum vulgare) flowering time ortholog of CONSTANS.

PubMed

Campoli, Chiara; Drosse, Benedikt; Searle, Iain; Coupland, George; von Korff, Maria

2012-03-01

Variation in photoperiod response is a major factor determining plant development and the agronomic performance of crops. The genetic control of photoperiodic flowering has been elucidated in the model plant Arabidopsis, and many of the identified genes are structurally conserved in the grasses. In this study, HvCO1, the closest barley ortholog of the key photoperiod response gene CONSTANS in Arabidopsis, was over-expressed in the spring barley Golden Promise. Over-expression of HvCO1 accelerated time to flowering in long- and short-day conditions and caused up-regulation of HvFT1 mRNA under long-day conditions. However, the transgenic plants retained a response to photoperiod, suggesting the presence of photoperiod response factors acting downstream of HvCO1 transcription. Analysis of a population segregating for HvCO1 over-expression and natural genetic variation at Ppd-H1 demonstrated that Ppd-H1 acts downstream of HvCO1 transcription on HvFT1 expression and flowering. Furthermore, variation at Ppd-H1 did not affect diurnal expression of HvCO1 or HvCO2. Over-expression of HvCO1 increased transcription of the spring allele of Vrn-H1 in long- and short-day conditions, while genetic variation at Ppd-H1 did not affect Vrn-H1 expression. Over-expression of HvCO1 and natural genetic variation at Ppd-H1 accelerated inflorescence development and stem elongation. Thus, HvCO1 probably induces flowering by activating HvFT1 whilst Ppd-H1 regulates HvFT1 independently of HvCO1 mRNA, and all three genes also appear to have a strong effect in promoting inflorescence development. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Carbon dioxide emissions from the flat bottom and shallow Nam Theun 2 Reservoir: drawdown area as a neglected pathway to the atmosphere

NASA Astrophysics Data System (ADS)

Deshmukh, Chandrashekhar; Guérin, Frédéric; Vongkhamsao, Axay; Pighini, Sylvie; Oudone, Phetdala; Sopraseuth, Saysoulinthone; Godon, Arnaud; Rode, Wanidaporn; Guédant, Pierre; Oliva, Priscia; Audry, Stéphane; Zouiten, Cyril; Galy-Lacaux, Corinne; Robain, Henri; Ribolzi, Olivier; Kansal, Arun; Chanudet, Vincent; Descloux, Stéphane; Serça, Dominique

2018-03-01

Freshwater reservoirs are a significant source of CO2 to the atmosphere. CO2 is known to be emitted at the reservoir surface by diffusion at the air-water interface and downstream of dams or powerhouses by degassing and along the river course. In this study, we quantified total CO2 emissions from the Nam Theun 2 Reservoir (Lao PDR) in the Mekong River watershed. The study started in May 2009, less than a year after flooding and just a few months after the maximum level was first reached and lasted until the end of 2013. We tested the hypothesis that soils from the drawdown area would be a significant contributor to the total CO2 emissions.Total inorganic carbon, dissolved and particulate organic carbon and CO2 concentrations were measured in 4 pristine rivers of the Nam Theun watershed, at 9 stations in the reservoir (vertical profiles) and at 16 stations downstream of the monomictic reservoir on a weekly to monthly basis. CO2 bubbling was estimated during five field campaigns between 2009 and 2011 and on a weekly monitoring, covering water depths ranging from 0.4 to 16 m and various types of flooded ecosystems in 2012 and 2013. Three field campaigns in 2010, 2011 and 2013 were dedicated to the soils description in 21 plots and the quantification of soil CO2 emissions from the drawdown area. On this basis, we calculated total CO2 emissions from the reservoir and carbon inputs from the tributaries. We confirm the importance of the flooded stock of organic matter as a source of carbon (C) fuelling emissions. We show that the drawdown area contributes, depending on the year, from 40 to 75 % of total annual gross emissions in this flat and shallow reservoir. Since the CO2 emissions from the drawdown zone are almost constant throughout the years, the large interannual variations result from the significant decrease in diffusive fluxes and downstream emissions between 2010 and 2013. This overlooked pathway in terms of gross emissions would require an in-depth evaluation for the soil organic matter and vegetation dynamics to evaluate the actual contribution of this area in terms of net modification of gas exchange in the footprint of the reservoir, and how it could evolve in the future.

Modified rice bran hemicellulose inhibits vascular endothelial growth factor-induced angiogenesis in vitro via VEGFR2 and its downstream signaling pathways

PubMed Central

ZHU, Xia; OKUBO, Aya; IGARI, Naoki; NINOMIYA, Kentaro; EGASHIRA, Yukari

2016-01-01

Angiogenesis is implicated in diverse pathological conditions such as cancer, rheumatoid arthritis, psoriasis, atherosclerosis, and retinal neovascularization. In the present study, we investigated the effects of modified rice bran hemicellulose (MRBH), a water-soluble hemicellulose preparation from rice bran treated with shiitake enzymes, on vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and its mechanism. We found that MRBH significantly inhibited VEGF-induced tube formation in human umbilical vein endothelial cells (HUVECs) co-cultured with human dermal fibroblasts. We also observed that MRBH dose-dependently suppressed the VEGF-induced proliferation and migration of HUVECs. Furthermore, examination of the anti-angiogenic mechanism indicated that MRBH reduced not only VEGF-induced activation of VEGF receptor 2 but also of the downstream signaling proteins Akt, extracellular signal-regulated protein kinase 1/2, and p38 mitogen-activated protein kinase. These findings suggest that MRBH has in vitro anti-angiogenic effects that are partially mediated through the inhibition of VEGF signaling. PMID:28439487

Anthropogenic impacts on the optical characteristics and biodegradability of dissolved and particulate organic matter in the Han River watershed, South Korea

NASA Astrophysics Data System (ADS)

Shirina Begum, Most; Jin, Hyojin; Yoon, Tae Kyung; Park, Ji-Hyung

2016-04-01

To understand how anthropogenic perturbations such as dams and pollution modify the chemical characteristics and biological transformations of riverine organic matter during transit through urbanized watersheds, we compared the optical characteristics and biodegradability of dissolved organic matter (DOM) and particulate organic matter (POM) along different reaches and urban tributary streams of the Han River watershed during short-term incubations. Laboratory incubations were conducted for 5-7 days at 20-25 oC with filtered or unfiltered water samples collected from up-, mid-, and downstream reaches with different levels of anthropogenic perturbations and three urban streams along the downstream reach that receive effluents from waste water treatment facilities in the metropolitan Seoul. Optical parameters such as ultraviolet absorbance at 254 nm, absorption coefficients at 254 nm and 350 nm, fluorescence index, humic-like fluorescence, microbial humic-like fluorescence, and protein-like fluorescence, and spectral slope at 350-400 nm were significantly correlated with increasing concentration of biodegradable dissolved organic carbon (BDOC) in filtered and unfiltered sample along the Han River up-, mid-, down-, and urban streams. The concentrations of BDOC in the urban streams were 6-12 times higher than in the filtered and unfiltered main-stem river samples, with significantly higher values in presence of POM in the unfiltered samples than in the filtered samples. In a separate 5-day incubation experiment with the unfiltered water sample from a downstream location of the Han River and its urban tributary water in isolation or mixed , the rate of concurrent biodegradation of both DOM and POM, as measured by the cumulative rate of CO2 production, was higher in the mixture than the average rate of the separately incubated samples, indicating the priming effect of mixed organic materials on the biodegradation of allochthonous organic materials from the other site. Greater amounts of CO2 were produced in all the samples than could be explained by BDOC alone, indicating the role of POM as a source of CO2. Faster and more intense changes in the consumed or produced components detected in the differential images between the fluorescence excitation emission matrices collected at intervals also suggested activated organic matter processing and CO2 production upon mixing the mainstem and tributary organic matter. Overall results suggest that dams and urban water pollution leave idiosyncratic imprints in the optical characteristics of DOM along waterways of the dammed and urbanized watershed and that inputs of anthropogenic organic materials via urban tributary streams can exert a strong priming effect on the biodegradation of both DOM and POM downstream.

Labile trace metal contribution of the runoff collector to a semi-urban river.

PubMed

Villanueva, J D; Granger, D; Binet, G; Litrico, X; Huneau, F; Peyraube, N; Le Coustumer, P

2016-06-01

In this study, the distribution of labile trace metals (LTMs; Cd, Co, Cr, Cu, Ni, Pb, and Zn) in a semi-urban runoff collector was examined to assess its influence to a natural aqueous system (Jalle River, Bordeaux, France). This river is of high importance as it is part of a natural reserve dedicated to conserving aquatic flora and fauna. Two sampling campaigns with a differing precipitation condition (period 1, spring season; and period 2, summer season associated with storms) were considered. Precipitation and water flow were monitored. The collector is active as it is receptive to precipitation changes. It influences the river through discharging water, contributing LTMs, and channeling the mass fluxes. During period 2 where precipitation rate is higher, 25 % of the total water volume of the river was supplied by the collector. LTMs were detected at the collector. Measurements were done by using diffusive gradient in thin films (DGT) probes deployed during 1, 7, and 14 days in each period. The results showed that in an instantaneous period (day 1 or D1), most of these trace metals are above the environmental quality standards (Cd, Co, Cr, and Zn). The coefficient of determination (r (2) > 0.50) employed confirmed that the LTM concentrations in the downstream can be explained by the collector. While Co and Cr are from the upstream and the collector, Cd, Cu, and Zn are mostly provided by the collector. Ni, however, is mostly delivered by the upstream. Using the concentrations observed, the river can be affected by the collector in varying ways: (1) adding effect, resulting from the mix of the upstream and the collector (if upstream ˂ downstream); (2) diluted (if upstream ˃ downstream); and (3) conservative or unaffected (upstream ~ downstream). The range of LTM mass fluxes that the collector holds are as follows: (1) limited range or ˂10 g/day, Cd (0.04-1.75 g/day), Co (0.08-05.42 g/day), Ni (0.06-1.45 g/day), and Pb (0.08-9.89 g/day); (2) moderate range or 11-50 g/day, Cr (0.23-33.26 g/day) and Cu (0.77-37.88 g/day); and (3) wide range or ˃50 g/day, Zn (26.33-676.61 g/day). Hence, the collector is a major source of concern in terms of contamination. This is as the water with considerable LTMs is channeled openly to the river without any treatment.

Local Circuits of V1 Layer 4B Neurons Projecting to V2 Thick Stripes Define Distinct Cell Classes and Avoid Cytochrome Oxidase Blobs

PubMed Central

Yarch, Jeff; Federer, Frederick

2017-01-01

Decades of anatomical studies on the primate primary visual cortex (V1) have led to a detailed diagram of V1 intrinsic circuitry, but this diagram lacks information about the output targets of V1 cells. Understanding how V1 local processing relates to downstream processing requires identification of neuronal populations defined by their output targets. In primates, V1 layers (L)2/3 and 4B send segregated projections to distinct cytochrome oxidase (CO) stripes in area V2: neurons in CO blob columns project to thin stripes while neurons outside blob columns project to thick and pale stripes, suggesting functional specialization of V1-to-V2 CO streams. However, the conventional diagram of V1 shows all L4B neurons, regardless of their soma location in blob or interblob columns, as projecting selectively to CO blobs in L2/3, suggesting convergence of blob/interblob information in L2/3 blobs and, possibly, some V2 stripes. However, it is unclear whether all L4B projection neurons show similar local circuitries. Using viral-mediated circuit tracing, we have identified the local circuits of L4B neurons projecting to V2 thick stripes in macaque. Consistent with previous studies, we found the somata of this L4B subpopulation to reside predominantly outside blob columns; however, unlike previous descriptions of local L4B circuits, these cells consistently projected outside CO blob columns in all layers. Thus, the local circuits of these L4B output neurons, just like their extrinsic projections to V2, preserve CO streams. Moreover, the intra-V1 laminar patterns of axonal projections identify two distinct neuron classes within this L4B subpopulation, including a rare novel neuron type, suggestive of two functionally specialized output channels. SIGNIFICANCE STATEMENT Conventional diagrams of primate primary visual cortex (V1) depict neuronal connections within and between different V1 layers, but lack information about the cells' downstream targets. This information is critical to understanding how local processing in V1 relates to downstream processing. We have identified the local circuits of a population of cells in V1 layer (L)4B that project to area V2. These cells' local circuits differ from classical descriptions of L4B circuits in both the laminar and functional compartments targeted by their axons, and identify two neuron classes. Our results demonstrate that both local intra-V1 and extrinsic V1-to-V2 connections of L4B neurons preserve CO-stream segregation, suggesting that across-stream integration occurs downstream of V1, and that output targets dictate local V1 circuitry. PMID:28077720

Recycling of paper: accounting of greenhouse gases and global warming contributions.

PubMed

Merrild, Hanna; Damgaard, Anders; Christensen, Thomas H

2009-11-01

Greenhouse gas (GHG) emissions have been established for recycling of paper waste with focus on a material recovery facility (MRF). The MRF upgrades the paper and cardboard waste before it is delivered to other industries where new paper or board products are produced. The accounting showed that the GHG contributions from the upstream activities and operational activities, with global warming factors (GWFs) of respectively 1 to 29 and 3 to 9 kg CO(2)-eq. tonne(- 1) paper waste, were small in comparison wih the downstream activities. The GHG contributions from the downstream reprocessing of the paper waste ranged from approximately 490 to 1460 kg CO(2)-eq. tonne( -1) of paper waste. The system may be expanded to include crediting of avoided virgin paper production which would result in GHG contributions from -1270 to 390 kg CO(2)-eq. tonne(- 1) paper waste. It may also be assumed that the wood not used for virgin paper production instead is used for production of energy that in turn is assumed to substitute for fossil fuel energy. This would result in GHG contributions from -1850 to -4400 kg CO(2)-eq. tonne(- 1) of paper waste. These system expansions reveal very large GHG savings, suggesting that the indirect upstream and operational GHG contributions are negligible in comparison with the indirect downstream emissions. However, the data for reprocessing of paper waste and the data for virgin paper production are highly variable. These differences are mainly related to different energy sources for the mills, both in regards to energy form (heat or electricity) and fuel (biomass or fossil fuels).

Effects of elevated [CO2] on maize defence against mycotoxigenic Fusarium verticillioides

PubMed Central

Vaughan, Martha M; Huffaker, Alisa; Schmelz, Eric A; Dafoe, Nicole J; Christensen, Shawn; Sims, James; Martins, Vitor F; Swerbilow, Jay; Romero, Maritza; Alborn, Hans T; Allen, Leon HARTWELL; Teal, Peter EA

2014-01-01

Maize is by quantity the most important C4 cereal crop; however, future climate changes are expected to increase maize susceptibility to mycotoxigenic fungal pathogens and reduce productivity. While rising atmospheric [CO2] is a driving force behind the warmer temperatures and drought, which aggravate fungal disease and mycotoxin accumulation, our understanding of how elevated [CO2] will effect maize defences against such pathogens is limited. Here we report that elevated [CO2] increases maize susceptibility to Fusarium verticillioides proliferation, while mycotoxin levels are unaltered. Fumonisin production is not proportional to the increase in F. verticillioides biomass, and the amount of fumonisin produced per unit pathogen is reduced at elevated [CO2]. Following F. verticillioides stalk inoculation, the accumulation of sugars, free fatty acids, lipoxygenase (LOX) transcripts, phytohormones and downstream phytoalexins is dampened in maize grown at elevated [CO2]. The attenuation of maize 13-LOXs and jasmonic acid production correlates with reduced terpenoid phytoalexins and increased susceptibility. Furthermore, the attenuated induction of 9-LOXs, which have been suggested to stimulate mycotoxin biosynthesis, is consistent with reduced fumonisin per unit fungal biomass at elevated [CO2]. Our findings suggest that elevated [CO2] will compromise maize LOX-dependent signalling, which will influence the interactions between maize and mycotoxigenic fungi. Elevated [CO2] increases maize susceptibility to Fusarium verticillioides proliferation but mycotoxin levels are unaltered. The attenuation of maize 13-LOXs and JA production correlates with reduced terpenoid phytoalexins and increased susceptibility. Furthermore, the attenuated induction of 9-LOXs, which have been suggested to stimulate mycotoxin biosynthesis, is consistent with reduced fumonisin per unit fungal biomass at elevated [CO2]. PMID:24689748

Acclimatization of the Crustose Coralline Alga Porolithon onkodes to Variable pCO2

PubMed Central

Johnson, Maggie D.; Moriarty, Vincent W.; Carpenter, Robert C.

2014-01-01

Ocean acidification (OA) has important implications for the persistence of coral reef ecosystems, due to potentially negative effects on biomineralization. Many coral reefs are dynamic with respect to carbonate chemistry, and experience fluctuations in pCO2 that exceed OA projections for the near future. To understand the influence of dynamic pCO2 on an important reef calcifier, we tested the response of the crustose coralline alga Porolithon onkodes to oscillating pCO2. Individuals were exposed to ambient (400 µatm), high (660 µatm), or variable pCO2 (oscillating between 400/660 µatm) treatments for 14 days. To explore the potential for coralline acclimatization, we collected individuals from low and high pCO2 variability sites (upstream and downstream respectively) on a back reef characterized by unidirectional water flow in Moorea, French Polynesia. We quantified the effects of treatment on algal calcification by measuring the change in buoyant weight, and on algal metabolism by conducting sealed incubations to measure rates of photosynthesis and respiration. Net photosynthesis was higher in the ambient treatment than the variable treatment, regardless of habitat origin, and there was no effect on respiration or gross photosynthesis. Exposure to high pCO2 decreased P. onkodes calcification by >70%, regardless of the original habitat. In the variable treatment, corallines from the high variability habitat calcified 42% more than corallines from the low variability habitat. The significance of the original habitat for the coralline calcification response to variable, high pCO2 indicates that individuals existing in dynamic pCO2 habitats may be acclimatized to OA within the scope of in situ variability. These results highlight the importance of accounting for natural pCO2 variability in OA manipulations, and provide insight into the potential for plasticity in habitat and species-specific responses to changing ocean chemistry. PMID:24505305

CO2-EOR:Approaching an NCNO classification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nunez-Lopez, Vanessa; Gil-Egui, Ramon

2017-09-20

This presentation provides an overview of progress made under the sponsored project and provides valuable input into the following questions: 1. Is CO2-EOR a valid option for greenhouse gas emission reduction? 2. How do different injection strategies affect EOR's Carbon Balance? 3. What is the impact of different gas separation processes on EOR emissions? 4. What is the impact of the downstream emissions on the Carbon Balance?

Chlorobenzene degeradation by non-thermal plasma combined with EG-TiO2/ZnO as a photocatalyst: Effect of photocatalyst on CO2 selectivity and byproducts reduction.

PubMed

Ghorbani Shahna, Farshid; Bahrami, Abdulrahman; Alimohammadi, Iraj; Yarahmadi, Rassuol; Jaleh, Babak; Gandomi, Mastaneh; Ebrahimi, Hossein; Ad-Din Abedi, Kamal

2017-02-15

The non-thermal plasma (NTP) technique, which suffers from low selectivity in complete oxidation of volatile organic compounds to CO 2 and H 2 O, creates unwanted and harmful byproducts. NTP in concert with photocatalyst can resolve this limitation due to additional oxidation. TiO 2 and ZnO nanoparticles were coated on the surface of the expanded graphite and placed downstream of the NTP reactor under UV light. In this study, to compare the performance of NTP and the combined system, chlorobenzene removal, selectivity of CO 2 and byproducts formation were investigated. The results showed that the combined system enhanced both the removal efficiency and CO 2 selectivity. The output gas of the NTP reactor contained chlorobenzene, phosgene, O 3 , NO, NO 2 , CO, CO 2 , HCL and CL. The bulk of these byproducts was oxidized on the surface of the nanocomposite; as a result, the content of the byproducts in the output gas of the combined system decreased dramatically. The removal efficiency and CO 2 selectivity increased by rising the applied voltage and residence time because the collision between active species and pollutant molecules increases. Based on these results, the combined system is preferred due to a higher performance and lower formation of harmful byproducts. Copyright © 2016 Elsevier B.V. All rights reserved.

Methods and apparatus for carbon dioxide removal from a fluid stream

DOEpatents

Wei, Wei; Ruud, James Anthony; Ku, Anthony Yu-Chung; Ramaswamy, Vidya; Liu, Ke

2010-01-19

An apparatus for producing hydrogen gas wherein the apparatus includes a reactor. In one embodiment, the reactor includes at least two conversion-removal portions. Each conversion-removal portion comprises a catalyst section configured to convert CO in the stream to CO.sub.2 and a membrane section located downstream of and in flow communication with the catalyst section. The membrane section is configured to selectively remove the CO.sub.2 from the stream and to be in flow communication with a sweep gas.

Recycling of plastic: accounting of greenhouse gases and global warming contributions.

PubMed

Astrup, Thomas; Fruergaard, Thilde; Christensen, Thomas H

2009-11-01

Major greenhouse gas (GHG) emissions related to plastic waste recycling were evaluated with respect to three management alternatives: recycling of clean, single-type plastic, recycling of mixed/contaminated plastic, and use of plastic waste as fuel in industrial processes. Source-separated plastic waste was received at a material recovery facility (MRF) and processed for granulation and subsequent downstream use. In the three alternatives, plastic was assumed to be substituting virgin plastic in new products, wood in low-strength products (outdoor furniture, fences, etc.), and coal or fuel oil in the case of energy utilization. GHG accounting was organized in terms of indirect upstream emissions (e.g. provision of energy, fuels, and materials), direct emissions at the MRF (e.g. fuel combustion), and indirect downstream emissions (e.g. avoided emissions from production of virgin plastic, wood, or coal/oil). Combined, upstream and direct emissions were estimated to be roughly between 5 and 600 kg CO(2)-eq. tonne( -1) of plastic waste depending on treatment at the MRF and CO(2) emissions from electricity production. Potential downstream savings arising from substitution of virgin plastic, wood, and energy fuels were estimated to be around 60- 1600 kg CO(2)-eq. tonne( -1) of plastic waste depending on substitution ratios and CO(2) emissions from electricity production. Based on the reviewed data, it was concluded that substitution of virgin plastic should be preferred. If this is not viable due to a mixture of different plastic types and/or contamination, the plastic should be used for energy utilization. Recycling of plastic waste for substitution of other materials such as wood provided no savings with respect to global warming.

The combination of Cassia obtusifolia L. and Foeniculum vulgare M. exhibits a laxative effect on loperamide-induced constipation of rats

PubMed Central

Jang, Seung Hee

2018-01-01

Chronic constipation is a functional gastrointestinal disease that is detrimental to the quality of patient life. Cassia obtusifolia L. (CO) and Foeniculum vulgare M. (FV) are commonly used as medicinal foods in many countries. We aimed to examine the laxative effect and their underlying mechanism of CO and FV mixture on loperamide (lop)-induced constipated rats. To determine the laxative effects of these compounds, Sprague-Dawley rats were divided into six groups: the control, lop-induced constipated (2mg/kg), and three doses (100, 300, and 500mg/kg) of CO and FV mixture-, and Bisacodyl (bis, 3.3mg/kg)-treated groups. The mixture of CO and FV and bis were orally administered once a day for 4 weeks. For induction of constipation, the lop were treated with a dose of 2 mg/kg twice a day on the 3rd week after treatments of CO and FV extracts and bis. The results were revealed that the CO and FV mixture has the laxative effects more than those in CO and FV-alone treatments on constipated rats by determining the stool parameters, including stool number and weight. Indeed, stool parameters, such as, stool number, weight, and water contents and colonic peristalsis from the intestinal transit length and ratio were dramatically improved by CO and FV mixture treatment. Histological study also revealed that CO and FV mixture enhanced the thicknesses of mucosa and muscular layers of the colon in constipated rats. For their underlying mechanism, the mRNAs and proteins expression of muscarinic acetylcholine receptors (mAchR) M2 and M3 and their downstream signaling were preserved by CO and FV mixture treatment in constipated rats. Therefore, this study suggests that treatment with CO and FV mixture has beneficial effects against constipation. We further suggest that CO and FV mixture may be utilized as an alternative therapeutic strategy for constipation. PMID:29621360

Implications for carbon processing beneath the Greenland Ice Sheet from dissolved CO2 and CH4 concentrations of subglacial discharge

NASA Astrophysics Data System (ADS)

Pain, A.; Martin, J.; Martin, E. E.

2017-12-01

Subglacial carbon processes are of increasing interest as warming induces ice melting and increases fluxes of glacial meltwater into proglacial rivers and the coastal ocean. Meltwater may serve as an atmospheric source or sink of carbon dioxide (CO2) or methane (CH4), depending on the magnitudes of subglacial organic carbon (OC) remineralization, which produces CO2 and CH4, and mineral weathering reactions, which consume CO2 but not CH4. We report wide variability in dissolved CO2 and CH4 concentrations at the beginning of the melt season (May-June 2017) between three sites draining land-terminating glaciers of the Greenland Ice Sheet. Two sites, located along the Watson River in western Greenland, drain the Isunnguata and Russell Glaciers and contained 1060 and 400 ppm CO2, respectively. In-situ CO2 flux measurements indicated that the Isunnguata was a source of atmospheric CO2, while the Russell was a sink. Both sites had elevated CH4 concentrations, at 325 and 25 ppm CH4, respectively, suggesting active anaerobic OC remineralization beneath the ice sheet. Dissolved CO2 and CH4 reached atmospheric equilibrium within 2.6 and 8.6 km downstream of Isunnguata and Russell discharge sites, respectively. These changes reflect rapid gas exchange with the atmosphere and/or CO2 consumption via instream mineral weathering. The third site, draining the Kiagtut Sermiat in southern Greenland, had about half atmospheric CO2 concentrations (250 ppm), but approximately atmospheric CH4 concentrations (2.1 ppm). Downstream CO2 flux measurements indicated ingassing of CO2 over the entire 10-km length of the proglacial river. CO2 undersaturation may be due to more readily weathered lithologies underlying the Kiagtut Sermiat compared to Watson River sites, but low CH4 concentrations also suggest limited contributions of CO2 and CH4 from OC remineralization. These results suggest that carbon processing beneath the Greenland Ice Sheet may be more variable than previously recognized. Variations control whether discharge is a source or sink of atmospheric CO2 or CH4, but gas concentrations could be further modified by instream reactions. Increased meltwater fluxes should enhance the importance of greenhouse gas fluxes from subglacial discharge, and heighten the need to constrain variability in subglacial carbon processing.

Glycosaminoglycan-Mediated Downstream Signaling of CXCL8 Binding to Endothelial Cells

PubMed Central

Derler, Rupert; Weber, Corinna; Strutzmann, Elisabeth; Miller, Ingrid; Kungl, Andreas

2017-01-01

The recruitment of leukocytes, mediated by endothelium bound chemokine gradients, is a vital process in inflammation. The highly negatively charged, unbranched polysaccharide family of glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate mediate chemokine immobilization. Specifically the binding of CXCL8 (interleukin 8) to GAGs on endothelial cell surfaces is known to regulate neutrophil recruitment. Currently, it is not clear if binding of CXCL8 to GAGs leads to endothelial downstream signaling in addition to the typical CXCR1/CXCR2 (C-X-C motif chemokine receptor 1 and 2)-mediated signaling which activates neutrophils. Here we have investigated the changes in protein expression of human microvascular endothelial cells induced by CXCL8. Tumor necrosis factor alpha (TNFα) stimulation was used to mimic an inflammatory state which allowed us to identify syndecan-4 (SDC4) as the potential proteoglycan co-receptor of CXCL8 by gene array, real-time PCR and flow cytometry experiments. Enzymatic GAG depolymerization via heparinase III and chondroitinase ABC was used to emulate the effect of glycocalyx remodeling on CXCL8-induced endothelial downstream signaling. Proteomic analyses showed changes in the expression pattern of a number of endothelial proteins such as Zyxin and Caldesmon involved in cytoskeletal organization, cell adhesion and cell mobility. These results demonstrate for the first time a potential role of GAG-mediated endothelial downstream signaling in addition to the well-known CXCL8-CXCR1/CXCR2 signaling pathways in neutrophils. PMID:29207576

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rittmann, Bruce; Krajmalnik‐Brown, Rosa; Zevin, Alexander

The grandest challenge facing human society today is providing large amounts of energy and industrial chemicals that are renewable and carbon-neutral. An outstanding opportunity lies in employing photosynthetic microorganisms, which have the potential to generate energy and chemical feedstock from sunlight and CO 2 at rates 10 to 100 times greater than plants. Major challenges for solar-powered production using photosynthetic microorganisms are associated with the harvesting and downstream processing of biomass to yield the usable energy or material feedstock e.g. The technical challenges and costs of downstream processing could be avoided if, powered by solar energy, the photosynthetic microorganisms weremore » to convert CO 2 directly to the desired product, which they release for direct harvesting. This approach creates a true photosynthetic factory, our goal for Photosynthetic Factory Direct! Our team is able to genetically modify the cyanobacterium Synechocystis sp. PCC 6803 so that it produces and excretes a range of renewable energy and chemical products directly from CO 2 and sunlight. Essential to realizing the potential of the photosynthetic factory is an engineered Advanced Photobioreactor (APBR) for reliable synthesis and harvest of the products.« less

Co-Compartmentation of Terpene Biosynthesis and Storage via Synthetic Droplet.

PubMed

Zhao, Cheng; Kim, YongKyoung; Zeng, Yining; Li, Man; Wang, Xin; Hu, Cheng; Gorman, Connor; Dai, Susie Y; Ding, Shi-You; Yuan, Joshua S

2018-03-16

Traditional bioproduct engineering focuses on pathway optimization, yet is often complicated by product inhibition, downstream consumption, and the toxicity of certain products. Here, we present the co-compartmentation of biosynthesis and storage via a synthetic droplet as an effective new strategy to improve the bioproduct yield, with squalene as a model compound. A hydrophobic protein was designed and introduced into the tobacco chloroplast to generate a synthetic droplet for terpene storage. Simultaneously, squalene biosynthesis enzymes were introduced to chloroplasts together with the droplet-forming protein to co-compartmentalize the biosynthesis and storage of squalene. The strategy has enabled a record yield of squalene at 2.6 mg/g fresh weight without compromising plant growth. Confocal fluorescent microscopy imaging, stimulated Raman scattering microscopy, and droplet composition analysis confirmed the formation of synthetic storage droplet in chloroplast. The co-compartmentation of synthetic storage droplet with a targeted metabolic pathway engineering represents a new strategy for enhancing bioproduct yield.

Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts.

PubMed

Kretschmer, Inga; Freudenberger, Till; Twarock, Sören; Yamaguchi, Yu; Grandoch, Maria; Fischer, Jens W

2016-02-19

The aim of this study was to characterize the interaction of KYSE-410, an esophageal squamous cell carcinoma cell line, and fibroblasts with respect to the extracellular matrix component hyaluronan (HA) and chemokine expression. KYSE-410 cells induced the mRNA expression of HA synthase 2 (Has2) in normal skin fibroblasts (SF) only in direct co-cultures. Parallel to Has2 mRNA, Has2 antisense RNA (Has2os2) was up-regulated in co-cultures. Knockdown of LEF1, a downstream target of Wnt signaling, abrogated Has2 and Has2os2 induction. After knockdown of Has2 in SF, significantly less α-smooth muscle actin expression was detected in co-cultures. Moreover, it was investigated whether the phenotype of KYSE-410 was affected in co-culture with SF and whether Has2 knockdown in SF had an impact on KYSE-410 cells in co-culture. However, no effects on epithelial-mesenchymal transition markers, proliferation, and migration were detected. In addition to Has2 mRNA, the chemokine CCL5 was up-regulated and CCL11 was down-regulated in SF in co-culture. Furthermore, co-cultures of KYSE-410 cells and cancer-associated fibroblasts (CAF) were investigated. Similar to SF, Has2 and Ccl5 were up-regulated and Ccl11 was down-regulated in CAF in co-culture. Importantly and in contrast to SF, inhibiting HA synthesis by 4-methylumbelliferone abrogated the effect of co-culture on Ccl5 in CAF. Moreover, HA was found to promote adhesion of CD4(+) but not CD8(+) cells to xenogaft tumor tissues. In conclusion, direct co-culture of esophageal squamous cell carcinoma and fibroblasts induced stromal HA synthesis via Wnt/LEF1 and altered the chemokine profile of stromal fibroblasts, which in turn may affect the tumor immune response. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts*

PubMed Central

Kretschmer, Inga; Freudenberger, Till; Twarock, Sören; Yamaguchi, Yu; Grandoch, Maria; Fischer, Jens W.

2016-01-01

The aim of this study was to characterize the interaction of KYSE-410, an esophageal squamous cell carcinoma cell line, and fibroblasts with respect to the extracellular matrix component hyaluronan (HA) and chemokine expression. KYSE-410 cells induced the mRNA expression of HA synthase 2 (Has2) in normal skin fibroblasts (SF) only in direct co-cultures. Parallel to Has2 mRNA, Has2 antisense RNA (Has2os2) was up-regulated in co-cultures. Knockdown of LEF1, a downstream target of Wnt signaling, abrogated Has2 and Has2os2 induction. After knockdown of Has2 in SF, significantly less α-smooth muscle actin expression was detected in co-cultures. Moreover, it was investigated whether the phenotype of KYSE-410 was affected in co-culture with SF and whether Has2 knockdown in SF had an impact on KYSE-410 cells in co-culture. However, no effects on epithelial-mesenchymal transition markers, proliferation, and migration were detected. In addition to Has2 mRNA, the chemokine CCL5 was up-regulated and CCL11 was down-regulated in SF in co-culture. Furthermore, co-cultures of KYSE-410 cells and cancer-associated fibroblasts (CAF) were investigated. Similar to SF, Has2 and Ccl5 were up-regulated and Ccl11 was down-regulated in CAF in co-culture. Importantly and in contrast to SF, inhibiting HA synthesis by 4-methylumbelliferone abrogated the effect of co-culture on Ccl5 in CAF. Moreover, HA was found to promote adhesion of CD4+ but not CD8+ cells to xenogaft tumor tissues. In conclusion, direct co-culture of esophageal squamous cell carcinoma and fibroblasts induced stromal HA synthesis via Wnt/LEF1 and altered the chemokine profile of stromal fibroblasts, which in turn may affect the tumor immune response. PMID:26699196

A novel acetylation cycle of transcription co-activator Yes-associated protein that is downstream of Hippo pathway is triggered in response to SN2 alkylating agents.

PubMed

Hata, Shoji; Hirayama, Jun; Kajiho, Hiroaki; Nakagawa, Kentaro; Hata, Yutaka; Katada, Toshiaki; Furutani-Seiki, Makoto; Nishina, Hiroshi

2012-06-22

Yes-associated protein (YAP) is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes. Although cytoplasmic retention of YAP is known to be mediated by Hippo pathway-dependent phosphorylation, post-translational modifications that regulate YAP in the nucleus remain unclear. Here we report the discovery of a novel cycle of acetylation/deacetylation of nuclear YAP induced in response to S(N)2 alkylating agents. We show that after treatment of cells with the S(N)2 alkylating agent methyl methanesulfonate, YAP phosphorylation mediated by the Hippo pathway is markedly reduced, leading to nuclear translocation of YAP and its acetylation. This YAP acetylation occurs on specific and highly conserved C-terminal lysine residues and is mediated by the nuclear acetyltransferases CBP (CREB binding protein) and p300. Conversely, the nuclear deacetylase SIRT1 is responsible for YAP deacetylation. Intriguingly, we found that YAP acetylation is induced specifically by S(N)2 alkylating agents and not by other DNA-damaging stimuli. These results identify a novel YAP acetylation cycle that occurs in the nucleus downstream of the Hippo pathway. Intriguingly, our findings also indicate that YAP acetylation is involved in responses to a specific type of DNA damage.

A Novel Acetylation Cycle of Transcription Co-activator Yes-associated Protein That Is Downstream of Hippo Pathway Is Triggered in Response to SN2 Alkylating Agents*

PubMed Central

Hata, Shoji; Hirayama, Jun; Kajiho, Hiroaki; Nakagawa, Kentaro; Hata, Yutaka; Katada, Toshiaki; Furutani-Seiki, Makoto; Nishina, Hiroshi

2012-01-01

Yes-associated protein (YAP) is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes. Although cytoplasmic retention of YAP is known to be mediated by Hippo pathway-dependent phosphorylation, post-translational modifications that regulate YAP in the nucleus remain unclear. Here we report the discovery of a novel cycle of acetylation/deacetylation of nuclear YAP induced in response to SN2 alkylating agents. We show that after treatment of cells with the SN2 alkylating agent methyl methanesulfonate, YAP phosphorylation mediated by the Hippo pathway is markedly reduced, leading to nuclear translocation of YAP and its acetylation. This YAP acetylation occurs on specific and highly conserved C-terminal lysine residues and is mediated by the nuclear acetyltransferases CBP (CREB binding protein) and p300. Conversely, the nuclear deacetylase SIRT1 is responsible for YAP deacetylation. Intriguingly, we found that YAP acetylation is induced specifically by SN2 alkylating agents and not by other DNA-damaging stimuli. These results identify a novel YAP acetylation cycle that occurs in the nucleus downstream of the Hippo pathway. Intriguingly, our findings also indicate that YAP acetylation is involved in responses to a specific type of DNA damage. PMID:22544757

The acid and alkalinity budgets of weathering in the Andes-Amazon system: Insights into the erosional control of global biogeochemical cycles

NASA Astrophysics Data System (ADS)

Torres, Mark A.; West, A. Joshua; Clark, Kathryn E.; Paris, Guillaume; Bouchez, Julien; Ponton, Camilo; Feakins, Sarah J.; Galy, Valier; Adkins, Jess F.

2016-09-01

The correlation between chemical weathering fluxes and denudation rates suggests that tectonic activity can force variations in atmospheric pCO2 by modulating weathering fluxes. However, the effect of weathering on pCO2 is not solely determined by the total mass flux. Instead, the effect of weathering on pCO2 also depends upon the balance between 1) alkalinity generation by carbonate and silicate mineral dissolution and 2) sulfuric acid generation by the oxidation of sulfide minerals. In this study, we explore how the balance between acid and alkalinity generation varies with tectonic uplift to better understand the links between tectonics and the long-term carbon cycle. To trace weathering reactions across the transition from the Peruvian Andes to the Amazonian foreland basin, we measured a suite of elemental concentrations (Na, K, Ca, Mg, Sr, Si, Li, SO4, and Cl) and isotopic ratios (87Sr/86Sr and δ34S) on both dissolved and solid phase samples. Using an inverse model, we quantitatively link systematic changes in solute geochemistry with elevation to downstream declines in sulfuric acid weathering as well as the proportion of cations sourced from silicates. With a new carbonate-system framework, we show that weathering in the Andes Mountains is a CO2 source whereas foreland weathering is a CO2 sink. These results are consistent with the theoretical expectation that the ratio of sulfide oxidation to silicate weathering increases with increasing erosion. Altogether, our results suggest that the effect of tectonically-enhanced weathering on atmospheric pCO2 is strongly modulated by sulfide mineral oxidation.

Process boundaries of irreversible scCO2 -assisted phase separation in biphasic whole-cell biocatalysis.

PubMed

Brandenbusch, Christoph; Glonke, Sebastian; Collins, Jonathan; Hoffrogge, Raimund; Grunwald, Klaudia; Bühler, Bruno; Schmid, Andreas; Sadowski, Gabriele

2015-11-01

The formation of stable emulsions in biphasic biotransformations catalyzed by microbial cells turned out to be a major hurdle for industrial implementation. Recently, a cost-effective and efficient downstream processing approach, using supercritical carbon dioxide (scCO2 ) for both irreversible emulsion destabilization (enabling complete phase separation within minutes of emulsion treatment) and product purification via extraction has been proposed by Brandenbusch et al. (2010). One of the key factors for a further development and scale-up of the approach is the understanding of the mechanism underlying scCO2 -assisted phase separation. A systematic approach was applied within this work to investigate the various factors influencing phase separation during scCO2 treatment (that is pressure, exposure of the cells to CO2 , and changes of cell surface properties). It was shown that cell toxification and cell disrupture are not responsible for emulsion destabilization. Proteins from the aqueous phase partially adsorb to cells present at the aqueous-organic interface, causing hydrophobic cell surface characteristics, and thus contribute to emulsion stabilization. By investigating the change in cell-surface hydrophobicity of these cells during CO2 treatment, it was found that a combination of catastrophic phase inversion and desorption of proteins from the cell surface is responsible for irreversible scCO2 mediated phase separation. These findings are essential for the definition of process windows for scCO2 -assisted phase separation in biphasic whole-cell biocatalysis. © 2015 Wiley Periodicals, Inc.

A Novel Method for Determining the Gas Transfer Velocity of Carbon Dioxide in Streams

NASA Astrophysics Data System (ADS)

McDowell, M. J.; Johnson, M. S.

2016-12-01

Characterization of the global carbon cycle relies on the accurate quantification of carbon fluxes into and out of natural and human-dominated ecosystems. Among these fluxes, carbon dioxide (CO2) evasion from surface water has received increasing attention in recent years. However, limitations of current methods, including determination of the gas transfer velocity (k), compromise our ability to evaluate the significance of CO2 fluxes between freshwater systems and the atmosphere. We developed an automated method to determine gas transfer velocities of CO2 (kCO2), and tested it under a range of flow conditions for a first-order stream of a headwater catchment in southwestern British Columbia, Canada. Our method uses continuous in situ measurements of CO2 concentrations using two non-dispersive infrared (NDIR) sensors enclosed in water impermeable, gas permeable membranes (Johnson et al., 2010) downstream from a gas diffuser. CO2 was injected into the stream at regular intervals via a compressed gas tank connected to the diffuser. CO2 injections were controlled by a datalogger at fixed time intervals and in response to storm-induced changes in streamflow. Following the injection, differences in CO2 concentrations at known distances downstream from the diffuser relative to pre-injection baseline levels allowed us to calculate kCO2. Here we present relationships between kCO2 and hydro-geomorphologic (flow velocity, streambed slope, stream width, stream depth), atmospheric (wind speed and direction), and water quality (stream temperature, pH, electrical conductivity) variables. This method has advantages of being automatable and field-deployable, and it does not require supplemental gas chromatography, as is the case for propane injections typically used to determine k. The dataset presented suggests the potential role of this method to further elucidate the role that CO2 fluxes from headwater streams play in the global carbon cycle. Johnson, M. S., Billett, M. F., Dinsmore, K. J., Wallin, M., Dyson, K. E., & Jassal, R. S. (2010). Direct and continuous measurement of dissolved carbon dioxide in freshwater aquatic systems—method and applications. Ecohydrology, 3(1), 68-78. http://doi.org/10.1002/eco.95

Supercritical CO2 Cleaning for Planetary Protection and Contamination Control

NASA Technical Reports Server (NTRS)

Lin, Ying; Zhong, Fang; Aveline, David; Anderson, Mark; Chung, Shirley; Mennella, Jerami; Schubert, Wayne

2010-01-01

We have designed and built a prototype Supercritical CO? Cleaning (SCC) system at JPL. The key features of the system are: 1) the parts inside a high-pressure vessel can be rotated at high speeds; 2) the same thermodynamic condition is maintained during First-In First-Out flushing to keep solvent power constant; and 3) the boil-off during decompression is induced in a separate vessel downstream. Our goal is to demonstrate SCC's ability to remove trace amounts of microbial and organic contaminants down to parts per billion levels from spacecraft material surfaces for future astrobiology missions. The initial cleaning test results showed that SCC can achieve cleanliness levels of 0.01 microgram/cm(sup 2) or less for hydrophobic contaminants such as dioctyl phthalate and silicone and it is less effective in the removal and inactivation of the hydrophilic bacterial spores as expected. However, with the use of a polar co-solvent, the efficacy may improve dramatically. The same results were obtained using liquid CO?. This opens up the possibility of using subcritical cleaning conditions, which may prove to be more compatible with certain spacecraft hardware.

Sterol regulatory element-binding protein 1 inhibitors decrease pancreatic cancer cell viability and proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siqingaowa,; Sekar, Sathiya; Gopalakrishnan, Venkat

Sterol regulatory element-binding protein1 (SREBP1) is a key regulatory factor that controls lipid homeostasis. Overactivation of SREBP1 and elevated lipid biogenesis are considered the major characteristics in malignancies of prostate cancer, endometrial cancer, and glioblastoma. However, the impact of SREBP1 activation in the progression of pancreatic cancer has not been explored. The present study examines the effect of suppression of SREBP1 activation by its inhibitors like fatostatin and PF429242 besides analyzing the impact of inhibitory effects on SREBP1 downstream signaling cascade such as fatty acid synthase (FAS), hydroxymethylglutaryl-CoA reductase (HMGCoAR), stearoyl-CoA desaturase-1 (SCD-1), and tumor suppressor protein p53 in MIAmore » PaCa-2 pancreatic cancer cells. Both fatostatin and PF429242 inhibited the growth of MIA PaCa-2 cells in a time and concentration-dependent manner with maximal inhibition attained at 72 h time period with IC{sub 50} values of 14.5 μM and 24.5 μM respectively. Detailed Western blot analysis performed using fatostatin and PF429242 at 72 h time point led to significant decrease in the levels of the active form of SREBP1 and its downstream signaling proteins such as FAS, SCD-1 and HMGCoAR and the mutant form of tumor suppressor protein, p53, levels in comparison to the levels observed in vehicle treated control group of MIA PaCa-2 pancreatic cells over the same time period. Our in vitro data suggest that SREBP1 may contribute to pancreatic tumor growth and its inhibitors could be considered as a potential target in the management of pancreatic cancer cell proliferation. - Highlights: • A significant increase in SREBP1 levels was observed in MIA PaCa-2 cells. • Fatostatin and PF429242 suppress SREBP1 activation and its downstream signaling proteins expression. • The inhibition of SREBP1reduces tumor suppressor protein p53 in MIA PaCa-2 cells. • SREBP1 inhibition may be beneficial in treatment of pancreatic cancer.« less

Curcumin-induced heme oxygenase-1 expression prevents H2O2-induced cell death in wild type and heme oxygenase-2 knockout adipose-derived mesenchymal stem cells.

PubMed

Cremers, Niels A J; Lundvig, Ditte M S; van Dalen, Stephanie C M; Schelbergen, Rik F; van Lent, Peter L E M; Szarek, Walter A; Regan, Raymond F; Carels, Carine E; Wagener, Frank A D T G

2014-10-08

Mesenchymal stem cell (MSC) administration is a promising adjuvant therapy to treat tissue injury. However, MSC survival after administration is often hampered by oxidative stress at the site of injury. Heme oxygenase (HO) generates the cytoprotective effector molecules biliverdin/bilirubin, carbon monoxide (CO) and iron/ferritin by breaking down heme. Since HO-activity mediates anti-apoptotic, anti-inflammatory, and anti-oxidative effects, we hypothesized that modulation of the HO-system affects MSC survival. Adipose-derived MSCs (ASCs) from wild type (WT) and HO-2 knockout (KO) mice were isolated and characterized with respect to ASC marker expression. In order to analyze potential modulatory effects of the HO-system on ASC survival, WT and HO-2 KO ASCs were pre-treated with HO-activity modulators, or downstream effector molecules biliverdin, bilirubin, and CO before co-exposure of ASCs to a toxic dose of H2O2. Surprisingly, sensitivity to H2O2-mediated cell death was similar in WT and HO-2 KO ASCs. However, pre-induction of HO-1 expression using curcumin increased ASC survival after H2O2 exposure in both WT and HO-2 KO ASCs. Simultaneous inhibition of HO-activity resulted in loss of curcumin-mediated protection. Co-treatment with glutathione precursor N-Acetylcysteine promoted ASC survival. However, co-incubation with HO-effector molecules bilirubin and biliverdin did not rescue from H2O2-mediated cell death, whereas co-exposure to CO-releasing molecules-2 (CORM-2) significantly increased cell survival, independently from HO-2 expression. Summarizing, our results show that curcumin protects via an HO-1 dependent mechanism against H2O2-mediated apoptosis, and likely through the generation of CO. HO-1 pre-induction or administration of CORMs may thus form an attractive strategy to improve MSC therapy.

Cultivation of the Marine Macroalgae Chaetomorpha linum in Municipal Wastewater for Nutrient Recovery and Biomass Production.

PubMed

Ge, Shijian; Champagne, Pascale

2017-03-21

Compared to microalgae, macroalgae are larger in size, thereby imposing lower separation and drying costs. This study demonstrates the feasibility of cultivating macroalgae Chaetomorpha linum in different types of municipal wastewaters, their ability to remove nutrient and their biomass composition for downstream biofuel production. Screening experiments indicated that C. linum grew well on primary (PW) and secondary wastewaters (SW), as well as centrate wastewater (CW) diluted to less than 20%. In a subsequent experiment, a step feeding approach was found to significantly increase biomass productivity to 10.7 ± 0.2 g AFDW·m -2 ·d -1 (p < 0.001), a 26.5% improvement in comparison to the control with single feeding, when grown on 10-CW; meanwhile, nitrogen and phosphorus removal efficiencies rose to 86.8 ± 1.1% (p < 0.001) and 92.6 ± 0.2% (p < 0.001), respectively. The CO 2 -supplemented SW cultures (10.1 ± 0.4 g AFDW·m -2 ·d -1 ) were 1.20 times more productive than the corresponding controls without CO 2 supplementation (p < 0.001); however, similar improvements were not observed in PW (p = 0.07) and 10-CW cultures (p = 0.07). Moreover, wastewater type and nutrient concentration influenced biomass composition (protein, carbohydrate and lipid). These findings indicate that the application of the macroalgae C. linum could represent an effective wastewater treatment alternative that could also provide a feedstock for downstream processing to biofuels.

1. VIEW OF DOWNSTREAM SIDE OF DIVERSION DAM ON THE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. VIEW OF DOWNSTREAM SIDE OF DIVERSION DAM ON THE SNAKE RIVER, LOOKING NORTHEAST. NOTE HEADGATE STRUCTURE ON NORTH BANK, SPILLWAY ON LEFT SIDE OF DAM, AND SPLASH LOGS ON DOWNSTREAM SIDE OF DAM. - Snake River Ditch, Headgate on north bank of Snake River, Dillon, Summit County, CO

Modeling of Compositional Effects of Foam Assisted CO2 Storage Processes

NASA Astrophysics Data System (ADS)

Naderi Beni, A.; Varavei, A.; Farajzadeh, R.; Delshad, M.

2012-12-01

Foaming of carbon dioxide (CO2, e.g. from fossil-fuel power plants) has been proposed as a possible strategy to resolve the limitations of direct disposal of CO2 into (saline) aquifers. Such limitations include gravity segregation that may damage the caprock and aquifer rock property alteration as a result of geochemical interactions. Foam may also block the CO2 leakage paths, resulting in an overall storage security enhancement. In this regard, specific aspects of composition and type of gas (N2 vs. CO2) may affect the foaming properties of gas-surfactant systems. The aim of this study is to determine these effects on the foaming properties of gas-surfactant solutions. To this end, we study the physics of foam assisted CO2 storage by modeling coreflood experiments. Different options such as simplified population balance foam model and a table-look-up approach were used to couple the fluid flow and mass transport equations in a reservoir simulator. Both laboratory and numerical results show that three regions along the flow direction can be distinguished: (i) an upstream region characterized by low liquid saturation, (ii) a region downstream of the foam front where the liquid saturation is still unchanged with a value of one and (iii) a frontal region characterized by a mixing of flowing foam and liquid, exhibiting fine fingering effects. It is also shown that the extent of the fingering behavior caused by the rock heterogeneity depends on foam strength. Additionally, permeation of gas through foam films is a strong function of water salinity and appears to have significant impact on foam in CO2 storage. It further turns out that the amount of dissolved CO2 in brine can be considerable and, therefore, the effect of water solubility cannot be neglected in simulation studies. In summary, the differences in the foaming behavior of nitrogen and carbon dioxide can be explained by the differences in their physical properties of solubility in water, interfacial tension, pH effect, and wettability. Among which solubility seems to be the most critical one because (1) the amount of available CO2 for foaming will be lower due to its higher dissolution compared to N2 at similar conditions and (2) it significantly affects gas permeability coefficient and thus the foam stability.

The "WFD-effect" on upstream-downstream relations in international river basins - insights from the Rhine and the Elbe basins

NASA Astrophysics Data System (ADS)

Moellenkamp, S.

2007-06-01

The upstream-downstream relationship in international river basins is a traditional challenge in water management. Water use in upstream countries often has a negative impact on water use in downstream countries. This is most evident in the classical example of industrial pollution in upstream countries hindering drinking water production downstream. The European Water Framework Directive (WFD) gives new impetus to the river basin approach and to international co-operation in European catchments. It aims at transforming a mainly water quality oriented management into a more integrated approach of ecosystem management. After discussing the traditional upstream-downstream relationship, this article shows that the WFD has a balancing effect on upstream-downstream problems and that it enhances river basin solidarity in international basins. While it lifts the downstream countries to the same level as the upstream countries, it also leads to new duties for the downstream states. Following the ecosystem approach, measures taken by downstream countries become increasingly more important. For example, downstream countries need to take measures to allow for migrating fish species to reach upstream stretches of river systems. With the WFD, fish populations receive increased attention, as they are an important indicator for the ecological status. The European Commission acquires a new role of inspection and control in river basin management, which finally also leads to enhanced cooperation and solidarity among the states in a basin. In order to achieve better water quality and to mitigate upstream-downstream problems, also economic instruments can be applied and the WFD does not exclude the possibility of making use of financial compensations, if at the same time the polluter pays principle is taken into account. The results presented in this article originate from a broader study on integrated water resources management conducted at Bonn University and refer to the Rhine and Elbe basins (Moellenkamp, 2006).

Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells.

PubMed

Korkut, Anil; Wang, Weiqing; Demir, Emek; Aksoy, Bülent Arman; Jing, Xiaohong; Molinelli, Evan J; Babur, Özgün; Bemis, Debra L; Onur Sumer, Selcuk; Solit, David B; Pratilas, Christine A; Sander, Chris

2015-08-18

Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs.

Effect of acute acid-base disturbances on the phosphorylation of phospholipase C-γ1 and Erk1/2 in the renal proximal tubule

PubMed Central

Skelton, Lara A; Boron, Walter F

2015-01-01

The renal proximal tubule (PT) plays a major role in whole-body pH homeostasis by secreting H+ into the tubule lumen. Previous work demonstrated that PTs respond to basolateral changes in [CO2] and [] by appropriately altering H+ secretion—responses blocked by the ErbB inhibitor PD168393, or by eliminating signaling through AT1 angiotensin receptors. In the present study, we analyze phosphorylation of three downstream targets of both ErbBs and AT1: phospholipase C-γ1 (PLC-γ1), extracellular-regulated kinase 1 (Erk1), and Erk2. We expose rabbit PT suspensions for 5 and 20 min to our control (Ctrl) condition (5% CO2, 22 mmol/L , pH 7.40) or one of several conditions that mimic acid-base disturbances. We found that each disturbance produces characteristic phosphorylation patterns in the three enzymes. For example, respiratory acidosis (elevated [CO2], normal []) at 20 min decreases PLC-γ1 phosphorylation at tyrosine-783 (relative to Ctrl). Metabolic acidosis (normal [CO2], decreased []) for 5 min increases Erk1 phosphorylation (p-Erk1) but not p-Erk2, whereas metabolic alkalosis (normal [CO2], elevated []) for 5 min decreases p-Erk1 and p-Erk2. In the presence of CO2/, PD168393 blocks only two of eight induced decreases in phosphorylation. In two cases in which disturbances have no remarkable effects on phosphorylation, PD168393 unmasks decreases and in two others, increases. These drug effects provide insight into the roles of PD168393-sensitive kinases. Our results indicate that PLC-γ1.pY783, p-Erk1, and p-Erk2 in the PT change in characteristic ways in response to acute acid-base disturbances, and thus presumably contribute to the transduction of acid-base signals. PMID:25780091

Recycling of metals: accounting of greenhouse gases and global warming contributions.

PubMed

Damgaard, Anders; Larsen, Anna W; Christensen, Thomas H

2009-11-01

Greenhouse gas (GHG) emissions related to recycling of metals in post-consumer waste are assessed from a waste management perspective; here the material recovery facility (MRF), for the sorting of the recovered metal. The GHG accounting includes indirect upstream emissions, direct activities at the MRF as well as indirect downstream activities in terms of reprocessing of the metal scrap and savings in terms of avoided production of virgin metal. The global warming factor (GWF) shows that upstream activities and the MRF causes negligible GHG emissions (12.8 to 52.6 kg CO(2)-equivalents tonne(-1) recovered metal) compared to the reprocessing of the metal itself (360-1260 kg CO(2)-equivalents tonne(-1) of recovered aluminium and 400- 1020 kg CO(2)-equivalents tonne(- 1) of recovered steel).The reprocessing is however counterbalanced by large savings of avoided virgin production of steel and aluminium. The net downstream savings were found to be 5040-19 340 kg CO(2)-equivalents tonne(-1) of treated aluminium and 560-2360 kg CO(2)-equivalents tonne(-1) of treated steel. Due to the huge differences in reported data it is hard to compare general data on the recovery of metal scrap as they are very dependent on the technology and data choices. Furthermore, the energy used in both the recovery process as well as the avoided primary production is crucial. The range of avoided impact shows that recovery of metals will always be beneficial over primary production, due to the high energy savings, and that the GHG emissions associated with the sorting of metals are negligible.

Physiological impacts of elevated carbon dioxide and ocean acidification on fish.

PubMed

Heuer, Rachael M; Grosell, Martin

2014-11-01

Most fish studied to date efficiently compensate for a hypercapnic acid-base disturbance; however, many recent studies examining the effects of ocean acidification on fish have documented impacts at CO2 levels predicted to occur before the end of this century. Notable impacts on neurosensory and behavioral endpoints, otolith growth, mitochondrial function, and metabolic rate demonstrate an unexpected sensitivity to current-day and near-future CO2 levels. Most explanations for these effects seem to center on increases in Pco2 and HCO3- that occur in the body during pH compensation for acid-base balance; however, few studies have measured these parameters at environmentally relevant CO2 levels or directly related them to reported negative endpoints. This compensatory response is well documented, but noted variation in dynamic regulation of acid-base transport pathways across species, exposure levels, and exposure duration suggests that multiple strategies may be utilized to cope with hypercapnia. Understanding this regulation and changes in ion gradients in extracellular and intracellular compartments during CO2 exposure could provide a basis for predicting sensitivity and explaining interspecies variation. Based on analysis of the existing literature, the present review presents a clear message that ocean acidification may cause significant effects on fish across multiple physiological systems, suggesting that pH compensation does not necessarily confer tolerance as downstream consequences and tradeoffs occur. It remains difficult to assess if acclimation responses during abrupt CO2 exposures will translate to fitness impacts over longer timescales. Nonetheless, identifying mechanisms and processes that may be subject to selective pressure could be one of many important components of assessing adaptive capacity. Copyright © 2014 the American Physiological Society.

DIC transport in "flashy" streams - constraints from time series ionic- and δ13C data from the Manoa River (Hawaii)

NASA Astrophysics Data System (ADS)

Hagedorn, B.

2016-12-01

Hawaiian streams are flashy in nature because watersheds are small and steep and receive intense and unevenly distributed rainfall. As a result, stream chemistry is characterized by considerable spatiotemporal variability. To examine how rainfall and streamflow affect the solute content of the Manoa River in Hawaii, time-series geochemical data collected during 17 sampling campaigns in spring-fall of 2010 were evaluated in a coupled δ13CDIC/major ion inversion model. Spatially, the stream is characterized by a distinct shift from a low HCO3 (43 mg/L), low pCO2 (3,760 ppmv) and heavy δ13CDIC (-6.5‰) fingerprint in the upper reaches to a high HCO3 (91 mg/L), high pCO2 (8,961 ppmv) and light δ13CDIC (-11.7‰) signature in the lowlands. These trends are attributed to (1) progressive weathering of exposed aluminosilicates, and (2) downstream enrichment in CO2 from organic matter decay in the soil zone. Solute (i.e., nitrate) yields from nitric acid weathering are generally low (<1% of TDS), even in the developed lowlands, where runoff of nitrate and ammonium-enriched urban effluent has historically been documented. Data furthermore indicate a significant positive correlation between δ13CDIC and rainfall rates in the mid-stream section of the river which is consistent with an atmospheric CO2 dilution effect during high rainfall events. This dilution effect needs to be accounted for to reliably describe the role of volcanic island river systems in global assessments of CO2 consumption via silicate weathering and CO2 degassing.

Microbial fixation of CO2 in water bodies and in drylands to combat climate change, soil loss and desertification.

PubMed

Rossi, Federico; Olguín, Eugenia J; Diels, Ludo; De Philippis, Roberto

2015-01-25

The growing concern for the increase of the global warming effects due to anthropogenic activities raises the challenge of finding novel technological approaches to stabilize CO2 emissions in the atmosphere and counteract impinging interconnected issues such as desertification and loss of biodiversity. Biological-CO2 mitigation, triggered through biological fixation, is considered a promising and eco-sustainable method, mostly owing to its downstream benefits that can be exploited. Microorganisms such as cyanobacteria, green algae and some autotrophic bacteria could potentially fix CO2 more efficiently than higher plants, due to their faster growth. Some examples of the potential of biological-CO2 mitigation are reported and discussed in this paper. In arid and semiarid environments, soil carbon sequestration (CO2 fixation) by cyanobacteria and biological soil crusts is considered an eco-friendly and natural process to increase soil C content and a viable pathway to soil restoration after one disturbance event. Another way for biological-CO2 mitigation intensively studied in the last few years is related to the possibility to perform carbon dioxide sequestration using microalgae, obtaining at the same time bioproducts of industrial interest. Another possibility under study is the exploitation of specific chemotrophic bacteria, such as Ralstonia eutropha (or picketii) and related organisms, for CO2 fixation coupled with the production chemicals such as polyhydroxyalkanoates (PHAs). In spite of the potential of these processes, multiple factors still have to be optimized for maximum rate of CO2 fixation by these microorganisms. The optimization of culture conditions, including the optimal concentration of CO2 in the provided gas, the use of metabolic engineering and of dual purpose systems for the treatment of wastewater and production of biofuels and high value products within a biorefinery concept, the design of photobioreactors in the case of phototrophs are some of the issues that, among others, have to be addressed and tested for cost-effective CO2 sequestration. Copyright © 2013 Elsevier B.V. All rights reserved.

Co-Compartmentation of Terpene Biosynthesis and Storage via Synthetic Droplet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Cheng; Kim, YongKyoung; Zeng, Yining

Traditional bioproduct engineering focuses on pathway optimization, yet is often complicated by product inhibition, downstream consumption, and the toxicity of certain products. Here, we present the co-compartmentation of biosynthesis and storage via a synthetic droplet as an effective new strategy to improve the bioproduct yield, with squalene as a model compound. A hydrophobic protein was designed and introduced into the tobacco chloroplast to generate a synthetic droplet for terpene storage. Simultaneously, squalene biosynthesis enzymes were introduced to chloroplasts together with the droplet-forming protein to co-compartmentalize the biosynthesis and storage of squalene. The strategy has enabled a record yield of squalenemore » at 2.6 mg/g fresh weight without compromising plant growth. Confocal fluorescent microscopy imaging, stimulated Raman scattering microscopy, and droplet composition analysis confirmed the formation of synthetic storage droplet in chloroplast. The co-compartmentation of synthetic storage droplet with a targeted metabolic pathway engineering represents a new strategy for enhancing bioproduct yield.« less

Co-Compartmentation of Terpene Biosynthesis and Storage via Synthetic Droplet

DOE PAGES

Zhao, Cheng; Kim, YongKyoung; Zeng, Yining; ...

2018-02-13

Traditional bioproduct engineering focuses on pathway optimization, yet is often complicated by product inhibition, downstream consumption, and the toxicity of certain products. Here, we present the co-compartmentation of biosynthesis and storage via a synthetic droplet as an effective new strategy to improve the bioproduct yield, with squalene as a model compound. A hydrophobic protein was designed and introduced into the tobacco chloroplast to generate a synthetic droplet for terpene storage. Simultaneously, squalene biosynthesis enzymes were introduced to chloroplasts together with the droplet-forming protein to co-compartmentalize the biosynthesis and storage of squalene. The strategy has enabled a record yield of squalenemore » at 2.6 mg/g fresh weight without compromising plant growth. Confocal fluorescent microscopy imaging, stimulated Raman scattering microscopy, and droplet composition analysis confirmed the formation of synthetic storage droplet in chloroplast. The co-compartmentation of synthetic storage droplet with a targeted metabolic pathway engineering represents a new strategy for enhancing bioproduct yield.« less

Effects of hydrostatic pressure and supercritical carbon dioxide on the viability of Botryococcus braunii algae cells.

PubMed

Yildiz-Ozturk, Ece; Ilhan-Ayisigi, Esra; Togtema, Arnoud; Gouveia, Joao; Yesil-Celiktas, Ozlem

2018-05-01

In bio-based industries, Botryococcus braunii is identified as a potential resource for production of hydrocarbons having a wide range of applications in chemical and biopolymer industries. For a sustainable production platform, the algae cultivation should be integrated with downstream processes. Ideally the algae are not harvested, but the product is isolated while cultivation and growth is continued especially if the doubling time is slow. Consequently, hydrocarbons can be extracted while keeping the algae viable. In this study, the effects of pressure on the viability of B. braunii cells were tested hydrostatically and under supercritical CO 2 conditions. Viability was determined by light microscopy, methylene blue uptake and by re-cultivation of the algae after treatments to follow the growth. It was concluded that supercritical CO 2 was lethal to the algae, whereas hydrostatic pressure treatments up to 150 bar have not affected cell viability and recultivation was successful. Copyright © 2018 Elsevier Ltd. All rights reserved.

Opposing effects of folding and assembly chaperones on evolvability of Rubisco.

PubMed

Durão, Paulo; Aigner, Harald; Nagy, Péter; Mueller-Cajar, Oliver; Hartl, F Ulrich; Hayer-Hartl, Manajit

2015-02-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the fixation of CO2 in photosynthesis. Despite its pivotal role, Rubisco is an inefficient enzyme and thus is a key target for directed evolution. Rubisco biogenesis depends on auxiliary factors, including the GroEL/ES-type chaperonin for folding and the chaperone RbcX for assembly. Here we performed directed evolution of cyanobacterial form I Rubisco using a Rubisco-dependent Escherichia coli strain. Overexpression of GroEL/ES enhanced Rubisco solubility and tended to expand the range of permissible mutations. In contrast, the specific assembly chaperone RbcX had a negative effect on evolvability by preventing a subset of mutants from forming holoenzyme. Mutation F140I in the large Rubisco subunit, isolated in the absence of RbcX, increased carboxylation efficiency approximately threefold without reducing CO2 specificity. The F140I mutant resulted in a ∼55% improved photosynthesis rate in Synechocystis PCC6803. The requirement of specific biogenesis factors downstream of chaperonin may have retarded the natural evolution of Rubisco.

The e-beam sustained CO2 laser amplifier

NASA Technical Reports Server (NTRS)

Brown, M. J.; Shaw, S. R.; Evans, M. H.; Smith, I. M.; Holman, W.

1990-01-01

The design features of an e-beam sustained CO2 amplifier are described. The amplifier is designed specifically as a catalyst test-bed to study the performance of room temperature precious metal CO-oxidation catalysts under e-beam sustained operation. The amplifier has been designed to provide pulse durations of 30 microseconds in a discharge volume of 2 litres. With a gas flow velocity of 2 metres per second, operation at repetition rates of 10 Hz is accommodated. The system is designed for sealed-off operation and a catalyst bed is housed in the gas circulation system downstream from the discharge region. CO and oxygen monitors are used for diagnosis of gas composition in the amplifier so that catalyst performance can be monitored in situ during sealed lifetests.

DETERMINATION OF SULFUR DIOXIDE, NITROGEN OXIDES, AND CARBON DIOXIDE IN EMISSIONS FROM ELECTRIC UTILITY PLANTS BY ALKALINE PERMANGANATE SAMPLING AND ION CHROMATOGRAPHY

EPA Science Inventory

A manual 24-h integrated method for determining SO2, NOx, and CO2 in emissions from electric utility plants was developed and field tested downstream from an SO2 control system. Samples were collected in alkaline potassium permanganate solution contained in restricted-orifice imp...

Economic Assessment of Supercritical CO2 Extraction of Waxes as Part of a Maize Stover Biorefinery.

PubMed

Attard, Thomas M; McElroy, Con Robert; Hunt, Andrew J

2015-07-31

To date limited work has focused on assessing the economic viability of scCO2 extraction to obtain waxes as part of a biorefinery. This work estimates the economic costs for wax extraction from maize stover. The cost of manufacture (COM) for maize stover wax extraction was found to be € 88.89 per kg of wax, with the fixed capital investment (FCI) and utility costs (CUT) contributing significantly to the COM. However, this value is based solely on scCO2 extraction of waxes and does not take into account the downstream processing of the biomass following extraction. The cost of extracting wax from maize stover can be reduced by utilizing pelletized leaves and combusting the residual biomass to generate electricity. This would lead to an overall cost of € 10.87 per kg of wax (based on 27% combustion efficiency for electricity generation) and €4.56 per kg of wax (based on 43% combustion efficiency for electricity generation). A sensitivity analysis study showed that utility costs (cost of electricity) had the greatest effect on the COM.

Economic Assessment of Supercritical CO2 Extraction of Waxes as Part of a Maize Stover Biorefinery

PubMed Central

Attard, Thomas M.; McElroy, Con Robert; Hunt, Andrew J.

2015-01-01

To date limited work has focused on assessing the economic viability of scCO2 extraction to obtain waxes as part of a biorefinery. This work estimates the economic costs for wax extraction from maize stover. The cost of manufacture (COM) for maize stover wax extraction was found to be €88.89 per kg of wax, with the fixed capital investment (FCI) and utility costs (CUT) contributing significantly to the COM. However, this value is based solely on scCO2 extraction of waxes and does not take into account the downstream processing of the biomass following extraction. The cost of extracting wax from maize stover can be reduced by utilizing pelletized leaves and combusting the residual biomass to generate electricity. This would lead to an overall cost of €10.87 per kg of wax (based on 27% combustion efficiency for electricity generation) and €4.56 per kg of wax (based on 43% combustion efficiency for electricity generation). A sensitivity analysis study showed that utility costs (cost of electricity) had the greatest effect on the COM. PMID:26263976

An Experimental Study of CO2-Brine Relative Permeability in Sandstone

NASA Astrophysics Data System (ADS)

Chen, X.; DiCarlo, D. A.

2013-12-01

Accurate determinations of CO2-brine relative permeability are important for modeling potential CO2 storage scenarios. The most common assumption is that CO2-brine relative permeability is likely to be similar to oil-brine relative permeability for water-wet rocks. But recent measurements of CO2-brine relative permeability have differed greatly from oil-brine relative permeability; particularly, the measurements show a very low CO2 end point relative permeability (kr,CO2=0.1~0.2) and a relatively high residual water saturation (Swr>0.4) ( Lee et al. 2010, Zuo et al. 2012, Akbarabadi et al. 2013 and etc.). It has been hypothesized that the differences are related to CO2-brine having a different contact angle from oil-brine. In this study, we hypothesize that the differences are caused by large capillary end effects resulted from the very low CO2 viscosity. We conduct steady-state CO2-brine flow experiments in 2-foot-long and 2.8-inch-diamter Berea sandstone cores at 20 °C and 1500 psi. Four pressure taps drilled on a core allow both the total pressure drop and that across five individual sections to be measured. Three experiments, two drainage and one imbibition, have been conducted so far. Our results show: (1) The relative permeability to both brine and CO2 of the last section (downstream, 15 cm long) is significantly smaller than that of any of the middle three sections. This testifies that the capillary end effect makes the relative permeability under-measured at the end of a core. (2) The values of the middle three sections are very close to each other, which indicate the middle part of our core is free of capillary end effect. (3) The CO2 end point relative permeability is 0.3~0.5, which is much higher than the recent measurements. (4) The brine end point relative permeability during imbibition is about 0.08, which is close to literature data. Reference: Lee, Y.S, Kim, K. H. and Lee, T.H. et al. Analysis of CO2 Endpoint Relative Permeability and Injectivity by Change in Pressure, Temperature, and Phase in Saline Aquifer, 2010 Energy Sources, Part A, 32: 83-99 Zuo, L., Krevor, S. and Falta, R. W. et al. An experimental study of CO2 exsolution and relative permeability measurements during CO2 saturated water depressurization. Transport in Porous Media, 2012, 91: 459-478 Akbarabadi, M. and Piri, M. Relative permeability hysteresis and capillary trapping characteristics of supercritical CO2/brine systems: an experimental study at reservoir conditions. Advances in Water Resources, 2013 52: 190-206

Effects of dissolved CO2 on Shallow Freshwater Microbial Communities simulating a CO2 Leakage Scenario

NASA Astrophysics Data System (ADS)

Gulliver, D. M.; Lowry, G. V.; Gregory, K.

2013-12-01

Geological carbon sequestration is likely to be part of a comprehensive strategy to minimize the atmospheric release of greenhouse gasses, establishing a concern of sequestered CO2 leakage into overlying potable aquifers. Leaking CO2 may affect existing biogeochemical processes and therefore water quality. There is a critical need to understand the evolution of CO2 exposed microbial communities that influence the biogeochemistry in these freshwater aquifers. The evolution of microbial ecology for different CO2 exposure concentrations was investigated using fluid-slurry samples obtained from a shallow freshwater aquifer (55 m depth, 0.5 MPa, 22 °C, Escatawpa, MS). The microbial community of well samples upstream and downstream of CO2 injection was characterized. In addition, batch vessel experiments were conducted with the upstream aquifer samples exposed to varying pCO2 from 0% to 100% under reservoir temperature and pressure for up to 56 days. The microbial community of the in situ experiment and the batch reactor experiment were analyzed with 16S rRNA clone libraries and qPCR. In both the in situ experiment and the batch reactor experiment, DNA concentration did not correlate with CO2 exposure. Both the in situ experiment and the batch reactors displayed a changing microbial community with increased CO2 exposure. The well water isolate, Curvibacter, appeared to be the most tolerant genus to high CO2 concentrations in the in situ experiments and to mid-CO2 concentrations in the batch reactors. In batch reactors with pCO2 concentrations higher than experienced in situ (pCO2 = 0.5 MPa), Pseudomonas appeared to be the most tolerant genus. Findings provide insight into a dynamic biogeochemical system that will alter with CO2 exposure. Adapted microbial populations will eventually give rise to the community that will impact the metal mobility and water quality. Knowledge of the surviving microbial populations will enable improved models for predicting the fate of CO2 following leakage and lead to better strategies for ensuring the quality of potable aquifer water.

Carbon dioxide degassing at the groundwater-stream-atmosphere interface: isotopic equilibration and hydrological mass balance in a sandy watershed

NASA Astrophysics Data System (ADS)

Deirmendjian, Loris; Abril, Gwenaël

2018-03-01

Streams and rivers emit significant amounts of CO2 and constitute a preferential pathway of carbon transport from terrestrial ecosystems to the atmosphere. However, the estimation of CO2 degassing based on the water-air CO2 gradient, gas transfer velocity and stream surface area is subject to large uncertainties. Furthermore, the stable isotope signature of dissolved inorganic carbon (δ13C-DIC) in streams is strongly impacted by gas exchange, which makes it a useful tracer of CO2 degassing under specific conditions. For this study, we characterized the annual transfers of dissolved inorganic carbon (DIC) along the groundwater-stream-river continuum based on DIC concentrations, stable isotope composition and measurements of stream discharges. We selected a homogeneous, forested and sandy lowland watershed as a study site, where the hydrology occurs almost exclusively through drainage of shallow groundwater (no surface runoff). We observed the first general spatial pattern of decreases in pCO2 and DIC and an increase in δ13C-DIC from groundwater to stream orders 1 and 2, which was due to the experimentally verified faster degassing of groundwater 12C-DIC compared to 13C-DIC. This downstream enrichment in 13C-DIC could be modelled by simply considering the isotopic equilibration of groundwater-derived DIC with the atmosphere during CO2 degassing. A second spatial pattern occurred between stream orders 2 and 4, consisting of an increase in the proportion of carbonate alkalinity to the DIC accompanied by the enrichment of 13C in the stream DIC, which was due to the occurrence of carbonate rock weathering downstream. We could separate the contribution of these two processes (gas exchange and carbonate weathering) in the stable isotope budget of the river network. Thereafter, we built a hydrological mass balance based on drainages and the relative contribution of groundwater in streams of increasing order. After combining with the dissolved CO2 concentrations, we quantified CO2 degassing for each stream order for the whole watershed. Approximately 75% of the total CO2 degassing from the watershed occurred in first- and second-order streams. Furthermore, from stream order 2-4, our CO2 degassing fluxes compared well with those based on stream hydraulic geometry, water pCO2, gas transfer velocity, and stream surface area. In first-order streams, however, our approach showed CO2 fluxes that were twice as large, suggesting that a fraction of degassing occurred as hotspots in the vicinity of groundwater resurgence and was missed by conventional stream sampling.

Unsteady High Turbulence Effects on Turbine Blade Film Cooling Heat Transfer Performance Using a Transient Liquid Crystal Technique

NASA Technical Reports Server (NTRS)

Han, J. C.; Ekkad, S. V.; Du, H.; Teng, S.

2000-01-01

Unsteady wake effect, with and without trailing edge ejection, on detailed heat transfer coefficient and film cooling effectiveness distributions is presented for a downstream film-cooled gas turbine blade. Tests were performed on a five-blade linear cascade at an exit Reynolds number of 5.3 x 10(exp 5). Upstream unsteady wakes were simulated using a spoke-wheel type wake generator. Coolant blowing ratio was varied from 0.4 to 1.2; air and CO2 were used as coolants to simulate different density ratios. Surface heat transfer and film effectiveness distributions were obtained using a transient liquid crystal technique; coolant temperature profiles were determined with a cold wire technique. Results show that Nusselt numbers for a film cooled blade are much higher compared to a blade without film injection. Unsteady wake slightly enhances Nusselt numbers but significantly reduces film effectiveness versus no wake cases. Nusselt numbers increase only slic,htly but film cooling, effectiveness increases significantly with increasing, blowing ratio. Higher density coolant (CO2) provides higher effectiveness at higher blowing ratios (M = 1.2) whereas lower density coolant (Air) provides higher 0 effectiveness at lower blowing ratios (M = 0.8). Trailing edge ejection generally has more effect on film effectiveness than on the heat transfer, typically reducing film effectiveness and enhancing heat transfer. Similar data is also presented for a film cooled cylindrical leading edge model.

Investigation of Desiccants and CO2 Sorbents for Advanced Exploration Systems 2015-2016

NASA Technical Reports Server (NTRS)

Knox, James C.; Cmarik, Gregory E.; Watson, David

2016-01-01

Design of advanced carbon dioxide removal systems begins with the study of sorbents. Specifically, new CO2 sorbents and desiccants need to be studied to enable greater productivity from existing and future spaceflight systems. This presentation will discuss the studies used as input for selecting future CO2 sorbent materials. Also, the adjoining issues of understanding the effects of water co-adsorption and material selection for desiccant beds will be discussed. Current sorbents for CO2 removal are based on 5A zeolites, but a transition to sorbents derived from 13X will be necessary as CO2 levels in cabin air become leaner. Unfortunately, these 13X zeolites are more susceptible to long-term performance loss due to water co-adsorption than 5A due at achievable regeneration temperatures. A study on how impactful the presence of trace water will be to the cyclic operation of small-scale beds will be discussed. Also, methods to recover the performance of beds in a space environment after a major moisture adsorption event will be discussed. The information obtained from the water co-adsorption studies will play a major part in selecting a CO2 sorbent for advanced removal systems. Pellet structural properties play another major role in the selection process. One factor for long-term, hands-off operation of a system is pellet integrity. Maintaining integrity means preventing pellet fracture and the generation of fines due to various thermal and mechanical means which would eventually clog filters or damage downstream systems. Either of these problems require significant shutdowns and maintenance operations and must be avoided. Therefore, study of high-integrity pellets and design of new pellets will be discussed.

The effect of fuel inlet turbulence intensity on H2/CH4 flame structure of MILD combustion using the LES method

NASA Astrophysics Data System (ADS)

Afarin, Yashar; Tabejamaat, Sadegh

2013-06-01

Large eddy simulations (LES) are employed to investigate the effect of the inlet turbulence intensity on the H2/CH4 flame structure in a hot and diluted co-flow stream which emulates the (Moderate or Intense Low-oxygen Dilution) MILD combustion regime. In this regard, three fuel inlet turbulence intensity profiles with the values of 4%, 7% and 10% are superimposed on the annular mixing layer. The effects of these changes on the flame structure under the MILD condition are studied for two oxygen concentrations of 3% and 9% (by mass) in the oxidiser stream and three hot co-flow temperatures 1300, 1500 and 1750 K. The turbulence-chemistry interaction of the numerically unresolved scales is modelled using the (Partially Stirred Reactor) PaSR method, where the full mechanism of GRI-2.11 represents the chemical reactions. The influences of the turbulence intensity on the flame structure under the MILD condition are studied by using the profile of temperature, CO and OH mass fractions in both physical and mixture fraction spaces at two downstream locations. Also, the effects of this parameter are investigated by contours of OH, HCO and CH2O radicals in an area near the nozzle exit zone. Results show that increasing the fuel inlet turbulence intensity has a profound effect on the flame structure particularly at low oxygen mass fraction. This increment weakens the combustion zone and results in a decrease in the peak values of the flame temperature and OH and CO mass fractions. Furthermore, increasing the inlet turbulence intensity decreases the flame thickness, and increases the MILD flame instability and diffusion of un-burnt fuel through the flame front. These effects are reduced by increasing the hot co-flow temperature which reinforces the reaction zone.

Effects of Concrete Channels on Stream Biogeochemistry, Maryland Coastal Plain

NASA Astrophysics Data System (ADS)

Prestegaard, K. L.; Gilbert, L.; Phemister, K.

2005-05-01

In the 1950's and 60's, extensive networks of cement-lined channels were built in suburban watersheds near Washington, D.C. to convey storm water to downstream locations. These cement-lined stream channels limit interactions between surface and groundwater and they provide sources of alkalinity in Maryland Coastal Plain watersheds that normally have low alkalinity. This project was designed to 1) compare base flow water chemistry in headwater reaches of urban and non-urban streams, and 2) to evaluate downstream changes in water chemistry in channelized urban streams in comparison with non-urban reference streams. During a drought year, headwater streams in both urban and non-urban sites had significant concentrations of Fe(II) that were discharged from groundwater sources and rapidly oxidized by iron-oxidizing bacteria. During a wet year, the concentrations of Fe(II) were higher in headwater urban streams than in the non-urban streams. This suggests that impervious surfaces in headwater urban watersheds prevent the recharge of oxygen-rich waters during storm events, which maintains iron-rich groundwater discharge to the stream. Downstream changes in water chemistry are prominent in cement-lined urban channels because they are associated with distinctive microbial communities. The headwater zones of channelized streams are dominated by iron-ozidizing bacteria, that are replaced downstream by manganese-oxidizing zones, and replaced further downstream by biofilms dominated by photosynthesizing cyanobacteria. The reaches dominated by cyanobacteria exhibit diurnal changes in pH due to uptake of CO2 for photosynthesis. Diurnal changes range from 7.5 to 8.8 in the summer months to 7.0 to 7.5 in the cooler months, indicating both the impact of photosynthesis and the additional source of alkalinity provided by concrete. The dissolved oxygen, pH, and other characteristics of tributaries dominated by cyanobacteria are similar to the water chemistry characteristics observed in much larger urban river channels further downstream. These downstream redox zonations, microbial habitats, and pH characteristics observed in channelized tributaries are very different from non-urban watersheds in the Maryland Coastal Plain, which have pH values less than 7 and do not have the prominent redox zonations and associated microbial habitats. These downstream changes in redox chemistry and pH in urban stream channels have implications for the transport and retention of heavy metals in urban streams.

Geochemical detection of carbon dioxide in dilute aquifers

PubMed Central

2009-01-01

Background Carbon storage in deep saline reservoirs has the potential to lower the amount of CO2 emitted to the atmosphere and to mitigate global warming. Leakage back to the atmosphere through abandoned wells and along faults would reduce the efficiency of carbon storage, possibly leading to health and ecological hazards at the ground surface, and possibly impacting water quality of near-surface dilute aquifers. We use static equilibrium and reactive transport simulations to test the hypothesis that perturbations in water chemistry associated with a CO2 gas leak into dilute groundwater are important measures for the potential release of CO2 to the atmosphere. Simulation parameters are constrained by groundwater chemistry, flow, and lithology from the High Plains aquifer. The High Plains aquifer is used to represent a typical sedimentary aquifer overlying a deep CO2 storage reservoir. Specifically, we address the relationships between CO2 flux, groundwater flow, detection time and distance. The CO2 flux ranges from 103 to 2 × 106 t/yr (0.63 to 1250 t/m2/yr) to assess chemical perturbations resulting from relatively small leaks that may compromise long-term storage, water quality, and surface ecology, and larger leaks characteristic of short-term well failure. Results For the scenarios we studied, our simulations show pH and carbonate chemistry are good indicators for leakage of stored CO2 into an overlying aquifer because elevated CO2 yields a more acid pH than the ambient groundwater. CO2 leakage into a dilute groundwater creates a slightly acid plume that can be detected at some distance from the leak source due to groundwater flow and CO2 buoyancy. pH breakthrough curves demonstrate that CO2 leaks can be easily detected for CO2 flux ≥ 104 t/yr within a 15-month time period at a monitoring well screened within a permeable layer 500 m downstream from the vertical gas trace. At lower flux rates, the CO2 dissolves in the aqueous phase in the lower most permeable unit and does not reach the monitoring well. Sustained pumping in a developed aquifer mixes the CO2-affected water with the ambient water and enhances pH signal for small leaks (103 t/yr) and reduces pH signal for larger leaks (≥ 104t/yr). Conclusion The ability to detect CO2 leakage from a storage reservoir to overlying dilute groundwater is dependent on CO2 solubility, leak flux, CO2 buoyancy, and groundwater flow. Our simulations show that the most likely places to detect CO2 are at the base of the confining layer near the water table where CO2 gas accumulates and is transported laterally in all directions, and downstream of the vertical gas trace where groundwater flow is great enough to transport dissolved CO2 laterally. Our simulations show that CO2 may not rise high enough in the aquifer to be detected because aqueous solubility and lateral groundwater transport within the lower aquifer unit exceeds gas pressure build-up and buoyancy needed to drive the CO2 gas upwards. PMID:19323832

Geochemical detection of carbon dioxide in dilute aquifers.

PubMed

Carroll, Susan; Hao, Yue; Aines, Roger

2009-03-26

Carbon storage in deep saline reservoirs has the potential to lower the amount of CO2 emitted to the atmosphere and to mitigate global warming. Leakage back to the atmosphere through abandoned wells and along faults would reduce the efficiency of carbon storage, possibly leading to health and ecological hazards at the ground surface, and possibly impacting water quality of near-surface dilute aquifers. We use static equilibrium and reactive transport simulations to test the hypothesis that perturbations in water chemistry associated with a CO2 gas leak into dilute groundwater are important measures for the potential release of CO2 to the atmosphere. Simulation parameters are constrained by groundwater chemistry, flow, and lithology from the High Plains aquifer. The High Plains aquifer is used to represent a typical sedimentary aquifer overlying a deep CO2 storage reservoir. Specifically, we address the relationships between CO2 flux, groundwater flow, detection time and distance. The CO2 flux ranges from 10(3) to 2 x 10(6) t/yr (0.63 to 1250 t/m2/yr) to assess chemical perturbations resulting from relatively small leaks that may compromise long-term storage, water quality, and surface ecology, and larger leaks characteristic of short-term well failure. For the scenarios we studied, our simulations show pH and carbonate chemistry are good indicators for leakage of stored CO2 into an overlying aquifer because elevated CO2 yields a more acid pH than the ambient groundwater. CO2 leakage into a dilute groundwater creates a slightly acid plume that can be detected at some distance from the leak source due to groundwater flow and CO2 buoyancy. pH breakthrough curves demonstrate that CO2 leaks can be easily detected for CO2 flux >or= 10(4) t/yr within a 15-month time period at a monitoring well screened within a permeable layer 500 m downstream from the vertical gas trace. At lower flux rates, the CO2 dissolves in the aqueous phase in the lower most permeable unit and does not reach the monitoring well. Sustained pumping in a developed aquifer mixes the CO2-affected water with the ambient water and enhances pH signal for small leaks (10(3) t/yr) and reduces pH signal for larger leaks (>or= 10(4) t/yr). The ability to detect CO2 leakage from a storage reservoir to overlying dilute groundwater is dependent on CO2 solubility, leak flux, CO2 buoyancy, and groundwater flow. Our simulations show that the most likely places to detect CO2 are at the base of the confining layer near the water table where CO2 gas accumulates and is transported laterally in all directions, and downstream of the vertical gas trace where groundwater flow is great enough to transport dissolved CO2 laterally. Our simulations show that CO2 may not rise high enough in the aquifer to be detected because aqueous solubility and lateral groundwater transport within the lower aquifer unit exceeds gas pressure build-up and buoyancy needed to drive the CO2 gas upwards.

Perturbation biology nominates upstream–downstream drug combinations in RAF inhibitor resistant melanoma cells

PubMed Central

Korkut, Anil; Wang, Weiqing; Demir, Emek; Aksoy, Bülent Arman; Jing, Xiaohong; Molinelli, Evan J; Babur, Özgün; Bemis, Debra L; Onur Sumer, Selcuk; Solit, David B; Pratilas, Christine A; Sander, Chris

2015-01-01

Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs. DOI: http://dx.doi.org/10.7554/eLife.04640.001 PMID:26284497

Stable isotope geochemical study of Pamukkale travertines: New evidences of low-temperature non-equilibrium calcite-water fractionation

NASA Astrophysics Data System (ADS)

Kele, Sándor; Özkul, Mehmet; Fórizs, István; Gökgöz, Ali; Baykara, Mehmet Oruç; Alçiçek, Mehmet Cihat; Németh, Tibor

2011-06-01

In this paper we present the first detailed geochemical study of the world-famous actively forming Pamukkale and Karahayit travertines (Denizli Basin, SW-Turkey) and associated thermal waters. Sampling was performed along downstream sections through different depositional environments (vent, artificial channel and lake, terrace-pools and cascades of proximal slope, marshy environment of distal slope). δ 13C travertine values show significant increase (from + 6.1‰ to + 11.7‰ PDB) with increasing distance from the spring orifice, whereas the δ 18O travertine values show only slight increase downstream (from - 10.7‰ to - 9.1‰ PDB). Mainly the CO 2 outgassing caused the positive downstream shift (~ 6‰) in the δ 13C travertine values. The high δ 13C values of Pamukkale travertines located closest to the spring orifice (not affected by secondary processes) suggest the contribution of CO 2 liberated by thermometamorphic decarbonation besides magmatic sources. Based on the gradual downstream increase of the concentration of the conservative Na +, K +, Cl -, evaporation was estimated to be 2-5%, which coincides with the moderate effect of evaporation on the water isotope composition. Stable isotopic compositions of the Pamukkale thermal water springs show of meteoric origin, and indicate a Local Meteoric Water Line of Denizli Basin to be between the Global Meteoric Water Line (Craig, 1961) and Western Anatolian Meteoric Water Line (Şimşek, 2003). Detailed evaluation of several major and trace element contents measured in the water and in the precipitated travertine along the Pamukkale MM section revealed which elements are precipitated in the carbonate or concentrated in the detrital minerals. Former studies on the Hungarian Egerszalók travertine (Kele et al., 2008a, b, 2009) had shown that the isotopic equilibrium is rarely maintained under natural conditions during calcite precipitation in the temperature range between 41 and 67 °C. In this paper, besides the detailed geochemical analyses along downstream sections, we present new evidences of non-equilibrium calcite-water fractionation in lower temperature range (13.3 to 51.3 °C). Our measurements and calculations on natural hot water travertine precipitations at Pamukkale and Egerszalók revealed that the δ 18O travertine is equal with the δ 18O HCO3 at the orifice of the thermal springs, which means that practically there is no oxygen isotope fractionation between these two phases. High rate of CO 2 degassing with rapid precipitation of carbonate could be responsible for this as it was theoretically supposed by O'Neil et al. (1969). Thus, for the determination of the deposition temperature of a fossil travertine deposit we propose to use the water-bicarbonate oxygen isotope equilibrium fractionation instead of the water-travertine fractionation, which can result 8-9 °C difference in the calculated values. Our study is the first detailed empirical proof of O'Neil's hypothesis on a natural carbonate depositing system. The presented observations can be used to identify more precisely the deposition temperature of fossil travertines during paleoclimate studies.

Transition of microbiological and sedimentological features associated with the geochemical gradient in a travertine mound in northern Sumatra, Indonesia

NASA Astrophysics Data System (ADS)

Sugihara, Chiya; Yanagawa, Katsunori; Okumura, Tomoyo; Takashima, Chizuru; Harijoko, Agung; Kano, Akihiro

2016-08-01

Modern travertines, carbonate deposits in Ca-rich hydrothermal water with high pCO2, often display a changing environment along the water path, with corresponding variability in the microbial communities. We investigated a travertine-bearing hot spring at the Blue Pool in northern Sumatra, Indonesia. The thermal water of 62 °C with high H2S (200 μM) and pCO2 ( 1 atm) developed a travertine mound 70 m wide. The concentrations of the gas components H2S and CO2, decrease immediately after the water is discharged, while the dissolved oxygen, pH, and aragonite saturation increase in the downstream direction. Responding to the geochemical gradient in the water, the surface biofilms change color from white to pink, light-green, dark-green, and brown as the water flows from the vent; this corresponds to microbial communities characterized by chemolithoautotrophs (Halothiobacillaceae), purple sulfur bacteria (Chromatiaceae), Anaerolineaceae, and co-occurrence of green non-sulfur bacteria (Chloroflexales)-Cyanobacteria, and green sulfur bacteria (Chlorobiales), respectively. In an environment with a certain level of H2S (> 1 μM), sulfur digestion and anoxygenic photosynthesis can be more profitable than oxygenic photosynthesis by Cyanobacteria. The precipitated carbonate mineral consists of aragonite and calcite, with the proportion of aragonite increasing downstream due to the larger Mg2 +/Ca2 + ratio in the water or the development of thicker biofilm. Where the biofilm is well developed, the aragonite travertines often exhibit laminated structures that were likely associated with the daily metabolism of these bacteria. The microbiological and sedimentological features at the Blue Pool may be the modern analogs of geomicrobiological products in the early Earth. Biofilm of anoxygenic photosynthetic bacteria had the potential to form ancient stromatolites that existed before the appearance of cyanobacteria.

Vortex Generators in a Streamline-Traced, External-Compression Supersonic Inlet

NASA Technical Reports Server (NTRS)

Baydar, Ezgihan; Lu, Frank K.; Slater, John W.; Trefny, Charles J.

2017-01-01

Vortex generators within a streamline-traced, external-compression supersonic inlet for Mach 1.66 were investigated to determine their ability to increase total pressure recovery and reduce total pressure distortion. The vortex generators studied were rectangular vanes arranged in counter-rotating and co-rotating arrays. The vane geometric factors of interest included height, length, spacing, angle-of-incidence, and positions upstream and downstream of the inlet terminal shock. The flow through the inlet was simulated numerically through the solution of the steady-state, Reynolds-averaged Navier-Stokes equations on multi-block, structured grids using the Wind-US flow solver. The vanes were simulated using a vortex generator model. The inlet performance was characterized by the inlet total pressure recovery and the radial and circumferential total pressure distortion indices at the engine face. Design of experiments and statistical analysis methods were applied to quantify the effect of the geometric factors of the vanes and search for optimal vane arrays. Co-rotating vane arrays with negative angles-of-incidence positioned on the supersonic diffuser were effective in sweeping low-momentum flow from the top toward the sides of the subsonic diffuser. This distributed the low-momentum flow more evenly about the circumference of the subsonic diffuser and reduced distortion. Co-rotating vane arrays with negative angles-of-incidence or counter-rotating vane arrays positioned downstream of the terminal shock were effective in mixing higher-momentum flow with lower-momentum flow to increase recovery and decrease distortion. A strategy of combining a co-rotating vane array on the supersonic diffuser with a counter-rotating vane array on the subsonic diffuser was effective in increasing recovery and reducing distortion.

The role of priming effects on the conversion of blue carbon to CO2 in the coastal zone

NASA Astrophysics Data System (ADS)

Morrison, E.; Ward, N. D.; Arellano, A. R.; Liu, Y.; Rivas-Ubach, A.; Ogram, A.; Osborne, T.; Vaughn, D.; Bianchi, T. S.

2017-12-01

Coastal ecosystems are recognized as valuable but vulnerable carbon (C) sinks, and the C stored in these systems is often referred to as blue C. These systems face many threats, particularly along low-relief coastlines such as Florida, which are susceptible to erosion and C loss as sea levels rise. Peat-derived organic matter (OM) may be degraded within downstream estuarine systems, and its degradation may be enhanced in the presence of labile algal-derived OM via microbial priming effects. To investigate the role of microbial priming effects on the degradation of peat-derived blue C, incubations were established and a suite of analyses were conducted to evaluate changes in peat-derived OM, CO2 production, metabolites, and microbial community structure (via metagenomic sequencing) over the course of the experiment. Four treatments were established: seawater with peat and algal leachate (SWPA), seawater and peat leachate (SWP), seawater and algal leachate (SWA), and seawater alone (SW). Treatments containing peat leachate (SWPA and SWP) harbored greater total DOC concentrations compared to SWA and SW treatments. Over the course of the incubation, CO2 concentrations increased in all treatments, with the highest CO2 levels in treatments with algal-derived DOM (SWA and SWPA). Both treatments with algal-derived DOM (SWA and SWPA) showed an increase in 13C-labeled CO2 over the course of the incubation, and stable isotope mass balance indicated that the conversion of peat-derived OC to CO2 occurred approximately 30% faster with the presence of algal-derived DOC. Aromaticity indices from absorption spectra were significantly lower in the SWP treatment when compared to the SWPA treatment. Dissolved organic matter molecular formulae detected by Fourier-transformed ion cyclotron resonance spectrometry indicated an increase in the degradation of peat-derived compounds when algal material was present. Overall, these findings suggest that there is an increase in microbial degradation of peat when in the presence of algal-derived DOM, which may drive the conversion of blue carbon stocks to CO2 when exported to estuarine systems.

Hydro-geophysical responses to the injection of CO2 in core plugs of Berea sandstone

NASA Astrophysics Data System (ADS)

Song, I.; Park, K. G.

2017-12-01

We have built a laboratory-scale core flooding system to measure the relative permeability of a core sample and the acoustic response to the CO2 saturation degree at in situ condition of pressure and temperature down to a few kilometer depths. The system consisted of an acoustic velocity core holder (AVC model from the Core Laboratories) between upstream where CO2 and H2O were injected separately and downstream where the mixed fluids came out of a core sample. Core samples with 4 cm in diameter and 5 cm in length of Berea sandstone were in turn placed in the core holder for confining and axial pressures. The flooding operations of the multiphase fluids were conducted through the sample at 40ºC in temperature and 8 MPa in backpressure. CO2 and H2O in the physical condition were injected separately into a sample at constant rate with various ratios. The two phases were mixed during flowing through the sample. The mixed fluids out of the sample were separated again by their different densities in a chamber equipped with a level gauge of the interface. From the level change of the water in the separator, we measured the volume of water coming out of the sample for each test with a constant ratio of the injection rates. Then it was possible to calculate the saturation degree of CO2 from the difference between input volume and output volume of water. The differential pressure between upstream and downstream was directly measured to calculate the relative permeability as a function of the CO2 saturation degree. We also conducted ultrasonic measurements using piezoelectric sensors on the end plugs. An electric pulse was given to a sensor on one end of sample, and then ultrasonic waves were recorded from the other end. The various ratios of injection rate of CO2 and H2O into Berea sandstone yielded a range of 0.1-0.7 in CO2 saturation degree. The relative permeability was obtained at the condition of steady-state flow for given stages from the velocity of each phase and the pressure gradient. The arrival time of P-wave became retarded and its amplitude became smaller as the degree of CO2 saturation increases. However no change was observed in S-wave in both characters. According to our results, time-lapse measurements of P-wave signals can be a monitoring tool of the subsurface migration of CO2, thus of detecting even its leakage.

High NO2/NOx emissions downstream of the catalytic diesel particulate filter: An influencing factor study.

PubMed

He, Chao; Li, Jiaqiang; Ma, Zhilei; Tan, Jianwei; Zhao, Longqing

2015-09-01

Diesel vehicles are responsible for most of the traffic-related nitrogen oxide (NOx) emissions, including nitric oxide (NO) and nitrogen dioxide (NO2). The use of after-treatment devices increases the risk of high NO2/NOx emissions from diesel engines. In order to investigate the factors influencing NO2/NOx emissions, an emission experiment was carried out on a high pressure common-rail, turbocharged diesel engine with a catalytic diesel particulate filter (CDPF). NO2 was measured by a non-dispersive ultraviolet analyzer with raw exhaust sampling. The experimental results show that the NO2/NOx ratios downstream of the CDPF range around 20%-83%, which are significantly higher than those upstream of the CDPF. The exhaust temperature is a decisive factor influencing the NO2/NOx emissions. The maximum NO2/NOx emission appears at the exhaust temperature of 350°C. The space velocity, engine-out PM/NOx ratio (mass based) and CO conversion ratio are secondary factors. At a constant exhaust temperature, the NO2/NOx emissions decreased with increasing space velocity and engine-out PM/NOx ratio. When the CO conversion ratios range from 80% to 90%, the NO2/NOx emissions remain at a high level. Copyright © 2015. Published by Elsevier B.V.

The potential impact of new Andean dams on Amazon fluvial ecosystems

PubMed Central

Melack, John M.; Dunne, Thomas; Barthem, Ronaldo B.; Goulding, Michael; Paiva, Rodrigo C. D.; Sorribas, Mino V.; Silva, Urbano L.; Weisser, Sabine

2017-01-01

Increased energy demand has led to plans for building many new dams in the western Amazon, mostly in the Andean region. Historical data and mechanistic scenarios are used to examine potential impacts above and below six of the largest dams planned for the region, including reductions in downstream sediment and nutrient supplies, changes in downstream flood pulse, changes in upstream and downstream fish yields, reservoir siltation, greenhouse gas emissions and mercury contamination. Together, these six dams are predicted to reduce the supply of sediments, phosphorus and nitrogen from the Andean region by 69, 67 and 57% and to the entire Amazon basin by 64, 51 and 23%, respectively. These large reductions in sediment and nutrient supplies will have major impacts on channel geomorphology, floodplain fertility and aquatic productivity. These effects will be greatest near the dams and extend to the lowland floodplains. Attenuation of the downstream flood pulse is expected to alter the survival, phenology and growth of floodplain vegetation and reduce fish yields below the dams. Reservoir filling times due to siltation are predicted to vary from 106–6240 years, affecting the storage performance of some dams. Total CO2 equivalent carbon emission from 4 Andean dams was expected to average 10 Tg y-1 during the first 30 years of operation, resulting in a MegaWatt weighted Carbon Emission Factor of 0.139 tons C MWhr-1. Mercury contamination in fish and local human populations is expected to increase both above and below the dams creating significant health risks. Reservoir fish yields will compensate some downstream losses, but increased mercury contamination could offset these benefits. PMID:28832638

Efficient computation of co-transcriptional RNA-ligand interaction dynamics.

PubMed

Wolfinger, Michael T; Flamm, Christoph; Hofacker, Ivo L

2018-05-04

Riboswitches form an abundant class of cis-regulatory RNA elements that mediate gene expression by binding a small metabolite. For synthetic biology applications, they are becoming cheap and accessible systems for selectively triggering transcription or translation of downstream genes. Many riboswitches are kinetically controlled, hence knowledge of their co-transcriptional mechanisms is essential. We present here an efficient implementation for analyzing co-transcriptional RNA-ligand interaction dynamics. This approach allows for the first time to model concentration-dependent metabolite binding/unbinding kinetics. We exemplify this novel approach by means of the recently studied I-A 2 ' -deoxyguanosine (2 ' dG)-sensing riboswitch from Mesoplasma florum. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Radiative Emission and Absorption on the Propagation and Extinction of Premixed Gas Flames

NASA Technical Reports Server (NTRS)

Ju, Yiguang; Masuya, Goro; Ronney, Paul D.

1998-01-01

Premixed gas flames in mixtures of CH4, O2, N2, and CO2 were studied numerically using detailed chemical and radiative emission-absorption models to establish the conditions for which radiatively induced extinction limits may exist independent of the system dimensions. It was found that reabsorption of emitted radiation led to substantially higher burning velocities and wider extinction limits than calculations using optically thin radiation models, particularly when CO2, a strong absorber, is present in the unburned gas, Two heat loss mechanisms that lead to flammability limits even with reabsorption were identified. One is that for dry hydrocarbon-air mixtures, because of the differences in the absorption spectra of H2O and CO2, most of the radiation from product H2O that is emitted in the upstream direction cannot be absorbed by the reactants. The second is that the emission spectrum Of CO2 is broader at flame temperatures than ambient temperature: thus, some radiation emitted near the flame front cannot be absorbed by the reactants even when they are seeded with CO2 Via both mechanisms, some net upstream heat loss due to radiation will always occur, leading to extinction of sufficiently weak mixtures. Downstream loss has practically no influence. Comparison with experiment demonstrates the importance of reabsorption in CO2 diluted mixtures. It is concluded that fundamental flammability limits can exist due to radiative heat loss, but these limits are strongly dependent on the emission-absorption spectra of the reactant and product -gases and their temperature dependence and cannot be predicted using gray-gas or optically thin model parameters. Applications to practical flames at high pressure, in large combustion chambers, and with exhaust-gas or flue-gas recirculation are discussed.

Using Combined X-ray Computed Tomography and Acoustic Resonance to Understand Supercritical CO2 Behavior in Fractured Sandstone

NASA Astrophysics Data System (ADS)

Kneafsey, T. J.; Nakagawa, S.

2015-12-01

Distribution of supercritical (sc) CO2 has a large impact on its flow behavior as well as on the properties of seismic waves used for monitoring. Simultaneous imaging of scCO2 distribution in a rock core using X-ray computed tomography (CT) and measurements of seismic waves in the laboratory can help understand how the distribution evolves as scCO2 invades through rock, and the resulting seismic signatures. To this end, we performed a series of laboratory scCO2 core-flood experiments in intact and fractured anisotropic Carbon Tan sandstone samples. In these experiments, we monitored changes in the CO2 saturation distribution and sonic-frequency acoustic resonances (yielding both seismic velocity and attenuation) over the course of the floods. A short-core resonant bar test system (Split-Hopkinson Resonant Bar Apparatus) custom fit into a long X-ray transparent pressure vessel was used for the seismic measurements, and a modified General Electric medical CT scanner was used to acquire X-ray CT data from which scCO2 saturation distributions were determined. The focus of the experiments was on the impact of single fractures on the scCO2 distribution and the seismic properties. For this reason, we examined several cases including 1. intact, 2. a closely mated fracture along the core axis, 3. a sheared fracture along the core axis (both vertical and horizontal for examining the buoyancy effect), and 4. a sheared fracture perpendicular to the core axis. For the intact and closely mated fractured cores, Young's modulus declined with increasing CO2 saturation, and attenuation increased up to about 15% CO2 saturation after which attenuation declined. For cores having wide axial fractures, the Young's modulus was lower than for the intact and closely mated cases, however did not change much with CO2 pore saturation. Much lower CO2 pore saturations were achieved in these cases. Attenuation increased more rapidly however than for the intact sample. For the core-perpendicular fracture, the Young's modulus decreased quickly with increasing CO2 saturation. Attenuation increased with increasing CO2 saturation until the CO2 front reached the fracture, after which it fell to below that for the brine-saturated case, increasing again as the CO2 invaded the downstream core region.

The impact of Indonesian peatland degradation on downstream marine ecosystems and the global carbon cycle.

PubMed

Abrams, Jesse F; Hohn, Sönke; Rixen, Tim; Baum, Antje; Merico, Agostino

2016-01-01

Tropical peatlands are among the most space-efficient stores of carbon on Earth containing approximately 89 Gt C. Of this, 57 Gt (65%) are stored in Indonesian peatlands. Large-scale exploitation of land, including deforestation and drainage for the establishment of oil palm plantations, is changing the carbon balance of Indonesian peatlands, turning them from a natural sink to a source via outgassing of CO2 to the atmosphere and leakage of dissolved organic carbon (DOC) into the coastal ocean. The impacts of this perturbation to the coastal environment and at the global scale are largely unknown. Here, we evaluate the downstream effects of released Indonesian peat carbon on coastal ecosystems and on the global carbon cycle. We use a biogeochemical box model in combination with novel and literature observations to investigate the impact of different carbon emission scenarios on the combined ocean-atmosphere system. The release of all carbon stored in the Indonesian peat pool, considered as a worst-case scenario, will increase atmospheric pCO2 by 8 ppm to 15 ppm within the next 200 years. The expected impact on the Java Sea ecosystems is most significant on the short term (over a few hundred years) and is characterized by an increase of 3.3% in phytoplankton, 32% in seagrass biomass, and 5% decrease in coral biomass. On the long term, however, the coastal ecosystems will recover to reach near pre-excursion conditions. Our results suggest that the ultimate fate of the peat carbon is in the deep ocean with 69% of it landing in the deep DIC pool after 1000 years, but the effects on the global ocean carbonate chemistry will be marginal. © 2015 John Wiley & Sons Ltd.

The Role of Sulfide Oxidation Impairment in the Pathogenesis of Primary CoQ Deficiency.

PubMed

Quinzii, Catarina M; Luna-Sanchez, Marta; Ziosi, Marcello; Hidalgo-Gutierrez, Agustin; Kleiner, Giulio; Lopez, Luis C

2017-01-01

Coenzyme Q (CoQ) is a lipid present in all cell membranes. One of the multiple metabolic functions of CoQ is to transport electrons in the reaction catalyzed by sulfide:quinone oxidoreductase (SQOR), the first enzyme of the oxidation pathway of sulfides (hydrogen sulfide, H 2 S). Early evidence of a defect in the metabolism of H 2 S in primary CoQ deficiency came from yeast studies in Schizosaccharomyces pombe strains defective for dps1 and ppt1 (homologs of PDSS1 and COQ2 , respectively), which have H 2 S accumulation. Our recent studies in human skin fibroblasts and in murine models of primary CoQ deficiency show that, also in mammals, decreased CoQ levels cause impairment of H 2 S oxidation. Patient fibroblasts carrying different mutations in genes encoding proteins involved in CoQ biosynthesis show reduced SQOR activity and protein levels proportional to the levels of CoQ. In Pdss2 kd / kd mice, kidney, the only organ clinically affected, shows reduced SQOR levels and downstream enzymes, accumulation of H 2 S, and glutathione depletion. Pdss2 kd / kd mice have also low levels of thiosulfate in plasma and urine, and increased C4-C6 acylcarnitines in blood, due to inhibition of short-chain acyl-CoA dehydrogenase. Also in Coq9 R 239 X mice, the symptomatic organ, cerebrum, shows accumulation of H 2 S, reduced SQOR, increase in thiosulfate sulfurtransferase and sulfite oxidase, and reduction in the levels of glutathione and glutathione enzymes, leading to alteration of the biosynthetic pathways of glutamate, serotonin, and catecholamines. Coq9 R 239 X mice have also reduced blood pressure, possible consequence of H 2 S-induced vasorelaxation. Since liver is not clinically affected in Pdss2 and Coq9 mutant mice, the effects of the impairment of H 2 S oxidation in this organ were not investigated, despite its critical role in metabolism. In conclusion, in vitro and in vivo studies of CoQ deficient models provide evidence of tissue-specific H 2 S oxidation impairment, an additional pathomechanism that should be considered in the understanding and treatment of primary CoQ deficiency.

Reviews and syntheses: Anthropogenic perturbations to carbon fluxes in Asian river systems - concepts, emerging trends, and research challenges

NASA Astrophysics Data System (ADS)

Park, Ji-Hyung; Nayna, Omme K.; Begum, Most S.; Chea, Eliyan; Hartmann, Jens; Keil, Richard G.; Kumar, Sanjeev; Lu, Xixi; Ran, Lishan; Richey, Jeffrey E.; Sarma, Vedula V. S. S.; Tareq, Shafi M.; Xuan, Do Thi; Yu, Ruihong

2018-05-01

Human activities are drastically altering water and material flows in river systems across Asia. These anthropogenic perturbations have rarely been linked to the carbon (C) fluxes of Asian rivers that may account for up to 40-50 % of the global fluxes. This review aims to provide a conceptual framework for assessing the human impacts on Asian river C fluxes, along with an update on anthropogenic alterations of riverine C fluxes. Drawing on case studies conducted in three selected rivers (the Ganges, Mekong, and Yellow River) and other major Asian rivers, the review focuses on the impacts of river impoundment and pollution on CO2 outgassing from the rivers draining South, Southeast, and East Asian regions that account for the largest fraction of river discharge and C exports from Asia and Oceania. A critical examination of major conceptual models of riverine processes against observed trends suggests that to better understand altered metabolisms and C fluxes in anthropogenic land-water-scapes, or riverine landscapes modified by human activities, the traditional view of the river continuum should be complemented with concepts addressing spatial and temporal discontinuities created by human activities, such as river impoundment and pollution. Recent booms in dam construction on many large Asian rivers pose a host of environmental problems, including increased retention of sediment and associated C. A small number of studies that measured greenhouse gas (GHG) emissions in dammed Asian rivers have reported contrasting impoundment effects: decreased GHG emissions from eutrophic reservoirs with enhanced primary production vs. increased emissions from the flooded vegetation and soils in the early years following dam construction or from the impounded reaches and downstream estuaries during the monsoon period. These contrasting results suggest that the rates of metabolic processes in the impounded and downstream reaches can vary greatly longitudinally over time as a combined result of diel shifts in the balance between autotrophy and heterotrophy, seasonal fluctuations between dry and monsoon periods, and a long-term change from a leaky post-construction phase to a gradual C sink. The rapid pace of urbanization across southern and eastern Asian regions has dramatically increased municipal water withdrawal, generating annually 120 km3 of wastewater in 24 countries, which comprises 39 % of the global municipal wastewater production. Although municipal wastewater constitutes only 1 % of the renewable surface water, it can disproportionately affect the receiving river water, particularly downstream of rapidly expanding metropolitan areas, resulting in eutrophication, increases in the amount and lability of organic C, and pulse emissions of CO2 and other GHGs. In rivers draining highly populated metropolitan areas, lower reaches and tributaries, which are often plagued by frequent algal blooms and pulsatile CO2 emissions from urban tributaries delivering high loads of wastewater, tended to exhibit higher levels of organic C and the partial pressure of CO2 (pCO2) than less impacted upstream reaches and eutrophic impounded reaches. More field measurements of pCO2, together with accurate flux calculations based on river-specific model parameters, are required to provide more accurate estimates of GHG emissions from the Asian rivers that are now underrepresented in the global C budgets. The new conceptual framework incorporating discontinuities created by impoundment and pollution into the river continuum needs to be tested with more field measurements of riverine metabolisms and CO2 dynamics across variously affected reaches to better constrain altered fluxes of organic C and CO2 resulting from changes in the balance between autotrophy and heterotrophy in increasingly human-modified river systems across Asia and other continents.

Aerodynamic Interactions between Pairs of Vertical-Axis Wind Turbines

NASA Astrophysics Data System (ADS)

Brownstein, Ian; Dabiri, John

2017-11-01

Increased power production has been observed in downstream vertical-axis wind turbines (VAWTs) when positioned offset from the wake of upstream turbines. This effect was found to exist in both laboratory and field environments with pairs of co- and counter-rotating turbines. It is hypothesized that the observed power production enhancement is due to flow acceleration adjacent to the upstream turbine caused by bluff body blockage, which increases the incident freestream velocity on appropriately positioned downstream turbines. This type of flow acceleration has been observed in computational and laboratory studies of VAWTs and will be further investigated here using 3D-PTV measurements around pairs of laboratory-scale VAWTs. These measurements will be used to understand the mechanisms behind the performance enhancement effect and seek to determine optimal separation distances and angles between turbines based on turbine design parameters. These results will lead to recommendations for optimizing the power production of VAWT wind farms which utilize this effect.

Air-water CO2 and CH4 fluxes along a river-reservoir continuum: Case study in the Pengxi River, a tributary of the Yangtze River in the Three Gorges Reservoir, China.

PubMed

Huang, Yang; Yasarer, Lindsey M W; Li, Zhe; Sturm, Belinda S M; Zhang, Zengyu; Guo, Jinsong; Shen, Yu

2017-05-01

Water surface greenhouse gas (GHG) emissions in freshwater reservoirs are closely related to limnological processes in the water column. Affected by both reservoir operation and seasonal changes, variations in the hydro-morphological conditions in the river-reservoir continuum will create distinctive patterns in water surface GHG emissions. A one-year field survey was carried out in the Pengxi River-reservoir continuum, a part of the Three Gorges Reservoir (TGR) immediately after the TGR reached its maximum water level. The annual average water surface CO 2 and CH 4 emissions at the riverine background sampling sites were 6.23 ± 0.93 and 0.025 ± 0.006 mmol h -1  m -2 , respectively. The CO 2 emissions were higher than those in the downstream reservoirs. The development of phytoplankton controlled the downstream decrease in water surface CO 2 emissions. The presence of thermal stratification in the permanent backwater area supported extensive phytoplankton blooms, resulting in a carbon sink during several months of the year. The CH 4 emissions were mainly impacted by water temperature and dissolved organic carbon. The greatest water surface CH 4 emission was detected in the fluctuating backwater area, likely due to a shallower water column and abundant organic matter. The Pengxi River backwater area did not show significant increase in water surface GHG emissions reported in tropical reservoirs. In evaluating the net GHG emissions by the impoundment of TGR, the net change in the carbon budget and the contribution of nitrogen and phosphorus should be taken into consideration in this eutrophic river-reservoir continuum.

Statins impact primary embryonic mouse neural stem cell survival, cell death, and fate through distinct mechanisms.

PubMed

Carson, Ross A; Rudine, Anthony C; Tally, Serena J; Franks, Alexis L; Frahm, Krystle A; Waldman, Jacob K; Silswal, Neerupma; Burale, Suban; Phan, James V; Chandran, Uma R; Monaghan, A Paula; DeFranco, Donald B

2018-01-01

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway (CBP), and are used for the prevention of cardiovascular disease. The anti-inflammatory effects of statins may also provide therapeutic benefits and have led to their use in clinical trials for preeclampsia, a pregnancy-associated inflammatory condition, despite their current classification as category X (i.e. contraindicated during pregnancy). In the developing neocortex, products of the CBP play essential roles in proliferation and differentiation of neural stem-progenitor cells (NSPCs). To understand how statins could impact the developing brain, we studied effects of pravastatin and simvastatin on primary embryonic NSPC survival, proliferation, global transcription, and cell fate in vitro. We found that statins dose dependently decrease NSPC expansion by promoting cell death and autophagy of NSPCs progressing through the G1 phase of the cell cycle. Genome-wide transcriptome analysis demonstrates an increase in expression of CBP genes following pravastatin treatment, through activation of the SREBP2 transcription factor. Co-treatment with farnesyl pyrophosphate (FPP), a CBP metabolite downstream of HMG-CoA reductase, reduces SREBP2 activation and pravastatin-induced PARP cleavage. Finally, pravastatin and simvastatin differentially alter NSPC cell fate and mRNA expression during differentiation, through a non-CBP dependent pathway.

In situ measurements of oxide particles in boron-containing diffusion flames

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turns, S.R.; Funari, M.J.; Khan, A.

1989-02-01

Particulate matter in axisymmetric laminar diffusion flames produced by burning mixtures of either CO and trimethylborate (TMB) or CH/sub 4/ and TMB with air were investigated using laser light-scattering techniques. Boron oxide particle sizes and number densities were determined at various heights in the flames using polarization ratio and relative intensity measurements, respectively. In the CO/TMB flames, two distinct particle-laden regions were found. The first region was located on the rich side of the luminous flame zone and initially appeared as a narrow annulus, which grew in width downstream until the particles filled the core. A second thin annular zonemore » appeared on the air side of the flame zone, starting approximately at the height of the luminous green flame tip and continuing to grow downstream. Particle sizes did not vary significantly with location in the flames, with diameters of approximately 0.09 and 0.15 ..mu..m in the 95% CO/5% TMB and 90% CO/10% TMB flames, respectively. Corresponding peak number densities were approximately 1.5 X 10/sup 10/ and 6 X 10/sup 9/ cm/sup -3/. The CH/sub 4//TMB flames were considerably different than the CO/TMB flames. The presence of significant quantities of water vapor presumably contributed to the formation of HBO/sub 2/(g) in favor of condensed-phase B/sub 2/O/sub 3/. At locations where oxide particles did form, they were closer to the flame centerline than the soot-containing regions. Computations of equilibrium yields of condensed-phase oxide were in qualitative agreement with the experimental results.« less

High Pressure Biomass Gasification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agrawal, Pradeep K

2016-07-29

According to the Billion Ton Report, the U.S. has a large supply of biomass available that can supplement fossil fuels for producing chemicals and transportation fuels. Agricultural waste, forest residue, and energy crops offer potential benefits: renewable feedstock, zero to low CO 2 emissions depending on the specific source, and domestic supply availability. Biomass can be converted into chemicals and fuels using one of several approaches: (i) biological platform converts corn into ethanol by using depolymerization of cellulose to form sugars followed by fermentation, (ii) low-temperature pyrolysis to obtain bio-oils which must be treated to reduce oxygen content via HDOmore » hydrodeoxygenation), and (iii) high temperature pyrolysis to produce syngas (CO + H 2). This last approach consists of producing syngas using the thermal platform which can be used to produce a variety of chemicals and fuels. The goal of this project was to develop an improved understanding of the gasification of biomass at high pressure conditions and how various gasification parameters might affect the gasification behavior. Since most downstream applications of synags conversion (e.g., alcohol synthesis, Fischer-Tropsch synthesis etc) involve utilizing high pressure catalytic processes, there is an interest in carrying out the biomass gasification at high pressure which can potentially reduce the gasifier size and subsequent downstream cleaning processes. It is traditionally accepted that high pressure should increase the gasification rates (kinetic effect). There is also precedence from coal gasification literature from the 1970s that high pressure gasification would be a beneficial route to consider. Traditional approach of using thermogravimetric analyzer (TGA) or high-pressure themogravimetric analyzer (PTGA) worked well in understanding the gasification kinetics of coal gasification which was useful in designing high pressure coal gasification processes. However, similar approach for biomass gasification was not very useful and was the impetus for this study. Specifically, we aimed this study at three broad objectives: (i) defining operating conditions at which C 2-C 4 hydrocarbons are formed since these represent loss of carbon efficiency, (ii) understanding the formation of tar species which create downstream processing difficulties in addition of carbon efficiency loss, and (iii) kinetics of biomass gasification where it would be possible to understand the effect of operating conditions and gas phase composition.« less

Effects of berberine and cinnamic acid on palmitic acid-induced intracellular triglyceride accumulation in NIT-1 pancreatic β cells.

PubMed

Zhao, Li; Jiang, Shu-Jun; Lu, Fu-Er; Xu, Li-Jun; Zou, Xin; Wang, Kai-Fu; Dong, Hui

2016-07-01

To investigate the effects of berberine (BBR) and cinnamic acid (CA), the main active components in Jiaotai Pill (, JTP), on palmitic acid (PA)-induced intracellular triglyceride (TG) accumulation in NIT-1 pancreatic β cells. Cells were incubated in culture medium containing PA (0.25 mmol/L) for 24 h. Then treatments with BBR (10 μmol/L), CA (100 μmol/L) and the combination of BBR and CA (BBR+CA) were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase (AMPK) protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), phosphorylation acetyl-coA carboxylase (pACC), carnitine acyl transferase 1 (CPT-1) and sterol regulating element binding protein 1c (SREBP-1c) were determined by Western blot or real time polymerase chain reaction. PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-1. Meanwhile, AMPK downstream lipogenic genes including SREBP-1c mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR+CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic β cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study. It can be concluded that in vitro, BBR and BBR+CA could inhibit PA-induced lipid accumulation by decreasing lipogenesis and increasing lipid oxidation in NIT-1 pancreatic β cells.

A new model for magnesium chemistry in the upper atmosphere.

PubMed

Plane, John M C; Whalley, Charlotte L

2012-06-21

This paper describes the kinetic study of a number of gas-phase reactions involving neutral Mg-containing species, which are important for the chemistry of meteor-ablated magnesium in the upper mesosphere/lower thermosphere region. The study is motivated by the very recent observation of the global atomic Mg layer around 90 km, using satellite-born UV-visible spectroscopy. In the laboratory, Mg atoms were produced thermally in the upstream section of a fast flow tube and then converted to the molecular species MgO, MgO(2), OMgO(2), and MgCO(3) by the addition of appropriate reagents. Atomic O was added further downstream, and Mg was detected at the downstream end of the flow tube by laser-induced fluorescence. The following rate coefficients were determined at 300 K: k(MgO + O → Mg + O(2)) = (6.2 ± 1.1) × 10(-10); k(MgO(2) + O → MgO + O(2)) = (8.4 ± 2.8) × 10(-11); k(MgCO(3) + O → MgO(2) + CO(2)) ≥ 4.9 × 10(-12); and k(MgO + CO → Mg + CO(2)) = (1.1 ± 0.3) × 10(-11) cm(3) molecule(-1) s(-1). Electronic structure calculations of the relevant potential energy surfaces combined with RRKM theory were performed to interpret the experimental results and also to explore the likely reaction pathways that convert MgCO(3) and OMgO(2) into long-lived reservoir species such as Mg(OH)(2). Although no reaction was observed in the laboratory between OMgO(2) and O, this is most likely due to the rapid recombination of O(2) with the product MgO(2) to form the relatively stable O(2)MgO(2). Indeed, one significant finding is the role of O(2) in the mesosphere, where it initiates holding cycles by recombining with radical species such as MgO(2) and MgOH. A new atmospheric model was then constructed which combines these results together with recent work on magnesium ion-molecule chemistry. The model is able to reproduce satisfactorily some of the key features of the Mg and Mg(+) layers, including the heights of the layers, the seasonal variations of their column abundances, and the unusually large Mg(+)/Mg ratio.

Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells.

PubMed

Zhou, Weibo; Simpson, P Jeanette; McFadden, Jill M; Townsend, Craig A; Medghalchi, Susan M; Vadlamudi, Aravinda; Pinn, Michael L; Ronnett, Gabriele V; Kuhajda, Francis P

2003-11-01

C75, an inhibitor of fatty acid synthase (FAS), induces apoptosis in cultured human cancer cells. Its proposed mechanism of action linked high levels of malonyl-CoA after FAS inhibition to potential downstream effects including inhibition of carnitine palmitoyltransferase-1 (CPT-1) with resultant inhibition of fatty acid oxidation. Recent data has shown that C75 directly stimulates CPT-1 increasing fatty acid oxidation in MCF-7 human breast cancer cells despite inhibitory concentrations of malonyl-CoA. In light of these findings, we have studied fatty acid metabolism in MCF7 human breast cancer cells to elucidate the mechanism of action of C75. We now report that: (a) in the setting of increased fatty acid oxidation, C75 inhibits fatty acid synthesis; (b) C273, a reduced form of C75, is unable to inhibit fatty acid synthesis and is nontoxic to MCF7 cells; (c) C75 and 5-(tetradecyloxy)-2-furoic acid (TOFA), an inhibitor of acetyl-CoA carboxylase, both cause a significant reduction of fatty acid incorporation into phosphatidylcholine, the major membrane phospholipid, within 2 h; (d) pulse chase studies with [(14)C]acetate labeling of membrane lipids show that both C75 and TOFA accelerate the decay of (14)C-labeled lipid from membranes within 2 h; (e) C75 also promotes a 2-3-fold increase in oxidation of membrane lipids within 2 h; and (f) because interference with phospholipid synthesis during S phase is known to trigger apoptosis in cycling cells, we performed double-labeled terminal deoxynucleotidyltransferase-mediated nick end labeling and BrdUrd analysis with both TOFA and C75. C75 triggered apoptosis during S phase, whereas TOFA did not. Moreover, application of TOFA 2 h before C75 blocked the C75 induced apoptosis, whereas etomoxir did not. Taken together these data indicate that FAS inhibition and its downstream inhibition of phospholipid production is a necessary part of the mechanism of action of C75. CPT-1 stimulation does not likely play a role in the cytotoxic response. The continued ability of TOFA to rescue cancer cells from C75 cytotoxicity implies a proapoptotic role for malonyl-CoA independent of CPT-1 that selectively targets cancer cells as they progress into S phase.

Influence of infrastructure on water quality and greenhouse gas dynamics in urban streams

NASA Astrophysics Data System (ADS)

Smith, Rose M.; Kaushal, Sujay S.; Beaulieu, Jake J.; Pennino, Michael J.; Welty, Claire

2017-06-01

Streams and rivers are significant sources of nitrous oxide (N2O), carbon dioxide (CO2), and methane (CH4) globally, and watershed management can alter greenhouse gas (GHG) emissions from streams. We hypothesized that urban infrastructure significantly alters downstream water quality and contributes to variability in GHG saturation and emissions. We measured gas saturation and estimated emission rates in headwaters of two urban stream networks (Red Run and Dead Run) of the Baltimore Ecosystem Study Long-Term Ecological Research project. We identified four combinations of stormwater and sanitary infrastructure present in these watersheds, including: (1) stream burial, (2) inline stormwater wetlands, (3) riparian/floodplain preservation, and (4) septic systems. We selected two first-order catchments in each of these categories and measured GHG concentrations, emissions, and dissolved inorganic and organic carbon (DIC and DOC) and nutrient concentrations biweekly for 1 year. From a water quality perspective, the DOC : NO3- ratio of streamwater was significantly different across infrastructure categories. Multiple linear regressions including DOC : NO3- and other variables (dissolved oxygen, DO; total dissolved nitrogen, TDN; and temperature) explained much of the statistical variation in nitrous oxide (N2O, r2 = 0.78), carbon dioxide (CO2, r2 = 0.78), and methane (CH4, r2 = 0.50) saturation in stream water. We measured N2O saturation ratios, which were among the highest reported in the literature for streams, ranging from 1.1 to 47 across all sites and dates. N2O saturation ratios were highest in streams draining watersheds with septic systems and strongly correlated with TDN. The CO2 saturation ratio was highly correlated with the N2O saturation ratio across all sites and dates, and the CO2 saturation ratio ranged from 1.1 to 73. CH4 was always supersaturated, with saturation ratios ranging from 3.0 to 2157. Longitudinal surveys extending form headwaters to third-order outlets of Red Run and Dead Run took place in spring and fall. Linear regressions of these data yielded significant negative relationships between each gas with increasing watershed size as well as consistent relationships between solutes (TDN or DOC, and DOC : TDN ratio) and gas saturation. Despite a decline in gas saturation between the headwaters and stream outlet, streams remained saturated with GHGs throughout the drainage network, suggesting that urban streams are continuous sources of CO2, CH4, and N2O. Our results suggest that infrastructure decisions can have significant effects on downstream water quality and greenhouse gases, and watershed management strategies may need to consider coupled impacts on urban water and air quality.

Procollagen Lysyl Hydroxylase 2 Expression Is Regulated by an Alternative Downstream Transforming Growth Factor β-1 Activation Mechanism*

PubMed Central

Gjaltema, Rutger A. F.; de Rond, Saskia; Rots, Marianne G.; Bank, Ruud A.

2015-01-01

PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2) hydroxylates lysine residues in collagen telopeptides and is essential for collagen pyridinoline cross-link formation. PLOD2 expression and subsequent pyridinoline cross-links are increased in fibrotic pathologies by transforming growth factor β-1 (TGFβ1). In this report we examined the molecular processes underlying TGFβ1-induced PLOD2 expression. We found that binding of the TGFβ1 pathway related transcription factors SMAD3 and SP1-mediated TGFβ1 enhanced PLOD2 expression and could be correlated to an increase of acetylated histone H3 and H4 at the PLOD2 promoter. Interestingly, the classical co-activators of SMAD3 complexes, p300 and CBP, were not responsible for the enhanced H3 and H4 acetylation. Depletion of SMAD3 reduced PLOD2 acetylated H3 and H4, indicating that another as of yet unidentified histone acetyltransferase binds to SMAD3 at PLOD2. Assessing histone methylation marks at the PLOD2 promoter depicted an increase of the active histone mark H3K79me2, a decrease of the repressive H4K20me3 mark, but no role for the generally strong transcription-related modifications: H3K4me3, H3K9me3 and H3K27me3. Collectively, our findings reveal that TGFβ1 induces a SP1- and SMAD3-dependent recruitment of histone modifying enzymes to the PLOD2 promoter other than the currently known TGFβ1 downstream co-activators and epigenetic modifications. This also suggests that additional activation strategies are used downstream of the TGFβ1 pathway, and hence their unraveling could be of great importance to fully understand TGFβ1 activation of genes. PMID:26432637

Use of highly alkaline conditions to improve cost-effectiveness of algal biotechnology.

PubMed

Canon-Rubio, Karen A; Sharp, Christine E; Bergerson, Joule; Strous, Marc; De la Hoz Siegler, Hector

2016-02-01

Phototrophic microorganisms have been proposed as an alternative to capture carbon dioxide (CO2) and to produce biofuels and other valuable products. Low CO2 absorption rates, low volumetric productivities, and inefficient downstream processing, however, currently make algal biotechnology highly energy intensive, expensive, and not economically competitive to produce biofuels. This mini-review summarizes advances made regarding the cultivation of phototrophic microorganisms at highly alkaline conditions, as well as other innovations oriented toward reducing the energy input into the cultivation and processing stages. An evaluation, in terms of energy requirements and energy return on energy invested, is performed for an integrated high-pH, high-alkalinity growth process that uses biofilms. Performance in terms of productivity and expected energy return on energy invested is presented for this process and is compared to previously reported life cycle assessments (LCAs) for systems at near-neutral pH. The cultivation of alkaliphilic phototrophic microorganisms in biofilms is shown to have a significant potential to reduce both energy requirements and capital costs.

Biofuels from microalgae.

PubMed

Li, Yanqun; Horsman, Mark; Wu, Nan; Lan, Christopher Q; Dubois-Calero, Nathalie

2008-01-01

Microalgae are a diverse group of prokaryotic and eukaryotic photosynthetic microorganisms that grow rapidly due to their simple structure. They can potentially be employed for the production of biofuels in an economically effective and environmentally sustainable manner. Microalgae have been investigated for the production of a number of different biofuels including biodiesel, bio-oil, bio-syngas, and bio-hydrogen. The production of these biofuels can be coupled with flue gas CO2 mitigation, wastewater treatment, and the production of high-value chemicals. Microalgal farming can also be carried out with seawater using marine microalgal species as the producers. Developments in microalgal cultivation and downstream processing (e.g., harvesting, drying, and thermochemical processing) are expected to further enhance the cost-effectiveness of the biofuel from microalgae strategy.

Sunlight Controls Water Column Processing of Carbon in Arctic Freshwaters

NASA Astrophysics Data System (ADS)

Cory, R. M.; Ward, C. P.; Crump, B. C.; Kling, G. W.

2014-12-01

Carbon (C) in thawing permafrost soils may have global impacts on climate change, yet controls on its processing and fate are poorly understood. The dominant fate of dissolved organic C (DOC) released from soils to inland waters is either complete oxidation to CO2 or partial oxidation and river export to oceans. Both processes are most often attributed to bacterial respiration, but we recently showed that photochemical oxidation exceeds rates of respiration and accounts for 70-95% of total DOC processed in the water column of arctic lakes and rivers. While the overall dominance of photochemical processing in streams and lakes remained, the fate of DOC varied consistently by water type. In small streams DOC was mainly mineralized by sunlight to CO2, while in lakes the main fate of DOC was partial photo-oxidation. Large rivers were intermediate between these end members, and photo-mineralization to CO2 was about equal to or less than partial photo-oxidation. We suggest this pattern is a result of light-exposure history, where DOC leached from soils into headwater streams has little prior light exposure and is labile to complete photo-oxidation, but as light exposure increases moving downstream and into lakes with longer residence times the DOC photo-lability declines. Thus as easily photo-mineralized moieties are removed, DOC fate shifts toward partial photo-oxidation and downstream export in rivers and lakes. At the basin scale, photochemical processing of DOC is about one third of the total CO2 released from surface waters, and is thus an important, newly measured component of the Arctic C budget. We also suggest that these photochemical transformations of DOC will occur in any shallow surface water, and could be important for better understanding inland water carbon cycling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eckert, C. A.; Sullivan, R.; Johnson, C.

CO2 and H2 are promising feedstocks for production of valuable biocompounds. Ralstonia eutropha utilizes these feedstocks to generate energy (ATP) and reductant (NAD(P)H) via oxidation of H2 by a membrane-bound (MBH) and a soluble hydrogenase (SH) for CO2 fixation by the Calvin-Benson-Bassham (CBB) cycle. Increased expression of the enzyme that fixes CO2 (RubisCO) resulted in 6-fold activity improvement in vitro, while increased expression of the MBH operon or the SH operon plus MBH operon maturation factors necessary for activity resulted in a 10-fold enhancement. Current research involves genetic manipulation of two endogenous cbb operons for increased expression, analysis of expressionmore » and activity of CBB/MBH/SH, cofactor ratios, and downstream products during autotrophic growth in control versus enhanced strains, and development of strategies for long-term, optimal overexpression. These studies will improve our understanding of autotrophic metabolism and provide a chassis strain for autotrophic production of biodiesel and other valuable carbon biocompounds.« less

Vibrational kinetics in CO electric discharge lasers - Modeling and experiments

NASA Technical Reports Server (NTRS)

Stanton, A. C.; Hanson, R. K.; Mitchner, M.

1980-01-01

A model of CO laser vibrational kinetics is developed, and predicted vibrational distributions are compared with measurements. The experimental distributions were obtained at various flow locations in a transverse CW discharge in supersonic (M = 3) flow. Good qualitative agreement is obtained in the comparisons, including the prediction of a total inversion at low discharge current densities. The major area of discrepancy is an observed loss in vibrational energy downstream of the discharge which is not predicted by the model. This discrepancy may be due to three-dimensional effects in the experiment which are not included in the model. Possible kinetic effects which may contribute to vibrational energy loss are also examined.

Laser characterization of the unsteady 2-D ion flow field in a Hall thruster with breathing mode oscillations

NASA Astrophysics Data System (ADS)

Lucca Fabris, Andrea; Young, Christopher; MacDonald-Tenenbaum, Natalia; Hargus, William, Jr.; Cappelli, Mark

2016-10-01

Hall thrusters are a mature form of electric propulsion for spacecraft. One commonly observed low frequency (10-50 kHz) discharge current oscillation in these E × B devices is the breathing mode, linked to a propagating ionization front traversing the channel. The complex time histories of ion production and acceleration in the discharge channel and near-field plume lead to interesting dynamics and interactions in the central plasma jet and downstream plume regions. A time-resolved laser-induced fluorescence (LIF) diagnostic non-intrusively measures 2-D ion velocity and relative ion density throughout the plume of a commercial BHT-600 Hall thruster manufactured by Busek Co. Low velocity classes of ions observed in addition to the main accelerated population are linked to propellant ionization outside of the device. Effects of breathing mode dynamics are shown to persist far downstream where modulations in ion velocity and LIF intensity are correlated with discharge current oscillations. This work is sponsored by the U.S. Air Force Office of Scientific Research with Dr. M. Birkan as program manager. C.Y. acknowledges support from the DOE NSSA Stewardship Science Graduate Fellowship under contract DE-FC52-08NA28752.

The footprint of CO2 leakage in the water-column: Insights from numerical modeling based on a North Sea gas release experiment

NASA Astrophysics Data System (ADS)

Vielstädte, L.; Linke, P.; Schmidt, M.; Sommer, S.; Wallmann, K.; McGinnis, D. F.; Haeckel, M.

2013-12-01

Assessing the environmental impact of potential CO2 leakage from offshore carbon dioxide storage sites necessitates the investigation of the corresponding pH change in the water-column. Numerical models have been developed to simulate the buoyant rise and dissolution of CO2 bubbles in the water-column and the subsequent near-field dispersion of dissolved CO2 in seawater under ocean current and tidal forcing. In order to test and improve numerical models a gas release experiment has been conducted at 80 m water-depth within the Sleipner area (North Sea). CO2 and Kr (used as inert tracer gas) were released on top of a benthic lander at varying gas flows (<140 kg/day) and bubble sizes (de: 1-6 mm). pCO2 and pH were measured by in situ sensors to monitor the spread of the solute in different vertical heights and distances downstream of the artificial leak. The experiment and numerical analysis show that the impact of such leakage rates is limited to the near-field bottom waters, due to the rapid dissolution of CO2 bubbles in seawater (CO2 is being stripped within the first two to five meters of bubble rise). In particular, small bubbles, which will dissolve close to the seafloor, may cause a dangerous low-pH environment for the marine benthos. However, on the larger scale, the advective transport by e.g. tidal currents, dominates the CO2 dispersal in the North Sea and dilutes the CO2 peak quickly. The model results show that at the small scales (<100 m) of the CO2 plume the lateral eddy diffusion (~0.01 m2/s) has only a negligible effect. Overall, we can postulate that CO2 leakage at a rate of ~ 100 kg per day as in our experiment will only have a localized impact on the marine environment, thereby reducing pH substantially (by 0.4 units) within a diameter of less than 50 m around the release spot (depending on the duration of leakage and the current velocities). Strong currents and tidal cycles significantly reduce the spreading of low-pH water masses into the far-field by efficiently diluting the amount of CO2 in ambient seawater.

Osmopriming-induced salt tolerance during seed germination of alfalfa most likely mediates through H2O2 signaling and upregulation of heme oxygenase.

PubMed

Amooaghaie, Rayhaneh; Tabatabaie, Fatemeh

2017-07-01

The present study showed that osmopriming or pretreatment with low H 2 O 2 doses (2 mM) for 6 h alleviated salt-reduced seed germination. The NADPH oxidase activity was the main source, and superoxide dismutase (SOD) activity might be a secondary source of H 2 O 2 generation during osmopriming or H 2 O 2 pretreatment. Hematin pretreatment similar to osmopriming improved salt-reduced seed germination that was coincident with the enhancement of heme oxygenase (HO) activity. The semi-quantitative RT-PCR confirmed that osmopriming or H 2 O 2 pretreatment was able to upregulate heme oxygenase HO-1 transcription, while the application of N,N-dimethyl thiourea (DMTU as trap of endogenous H 2 O 2 ) and diphenyleneiodonium (DPI as inhibitor of NADPHox) not only blocked the upregulation of HO but also reversed the osmopriming-induced salt attenuation. The addition of CO-saturated aqueous rescued the inhibitory effect of DMTU and DPI on seed germination and α-amylase activity during osmopriming or H 2 O 2 pretreatment, but H 2 O 2 could not reverse the inhibitory effect of ZnPPIX (as HO inhibitor) or Hb (as CO scavenger) that indicates that the CO acts downstream of H 2 O 2 in priming-driven salt acclimation. The antioxidant enzymes and proline synthesis were upregulated in roots of seedlings grown from primed seeds, and these responses were reversed by adding DMTU, ZnPPIX, and Hb during osmopriming. These findings for the first time suggest that H 2 O 2 signaling and upregulation of heme oxygenase play a crucial role in priming-driven salt tolerance.

Heterogeneous catalytic process for alcohol fuels from syngas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minahan, D.M.; Nagaki, D.A.

1995-12-31

This project is focused on the discovery and evaluation of novel heterogeneous catalyst for the production of oxygenated fuel enhancers from synthesis gas. Catalysts have been studied and optimized for the production of methanol and isobutanol mixtures which may be used for the downstream synthesis of MTBE or related oxygenates. Higher alcohols synthesis (HAS) from syngas was studied; the alcohols that are produced in this process may be used for the downstream synthesis of MTBE or related oxygenates. This work has resulted in the discovery of a catalyst system that is highly selective for isobutanol compared with the prior art.more » The catalysts operate at high temperature (400{degrees}C), and consist of a spinel oxide support (general formula AB{sub 2}O{sub 4}, where A=M{sup 2+} and B = M{sup 3+}), promoted with various other elements. These catalysts operate by what is believed to be an aldol condensation mechanism, giving a product mix of mainly methanol and isobutanol. In this study, the effect of product feed/recycle (methanol, ethanol. n-propanol, isopropanol, carbon dioxide and water) on the performance of 10-DAN-55 (spinel oxide based catalyst) at 400{degrees}C, 1000 psi, GHSV = 12,000 and syngas (H{sub 2}/CO) ratio = 1:2 (alcohol addition) and 1:1 (carbon dioxide and water addition) was studied. The effect of operation at high temperatures and pressures on the performance of an improved catalyst formulation was also examined.« less

[Phylogenetic analysis of CO I gene of Oncomelania snails from project of afforestation for schistosomiasis control in marshland endemic regions].

PubMed

Xu, Yu-Mei; Zhang, Shi-Qing; Zhu, Chuan-Gang

2012-04-01

To investigate the genetic difference of cytochrome oxidase I (CO I ) of Oncomelania snails from the project of afforestation for schistosomiasis control in marshland regions, so as to explore the effects of different ecological environments. The snails were collected from 3 different areas, Anqing, Tongling, Wuwei, i.e. the upstream, midstream and downstream regions along the Yangtz River in Anhui Province. Genomic DNA was extracted from the snails, and CO I gene fragments were amplified by PCR, then purified and sequenced. The sequences were edited by using Blast. The CO I genes of O. h. minima and Biomphalaria glabrata were used as the reference of exogenous gene. The genetic distances of the various regions were calculated by the Kimura method and phylogenetic trees were constructed with UPGMA and the NJ method of MEGA (3.1) software. The amplified CO I gene of the snail was a fragment about 700 bp including 2 primers in length. There were little genetic diversity among the different areas, the identities were higher than or equal to 98%. The genetic distances indicated that the distance between the projects of afforestation and woodland in Anqing was 0.003, while Tongling was 0.019, Wuwei was 0.007. The distances among the three projects of afforestation were 0.003-0.012. The two phylogenetic trees were constructed by the methods of UPGMA and NJ respectively, which took on very similar topo-structure in which isolates of Biomphalaria glabrata located in one clade and all the others in the other one. In the other one clade, O. H. minima located in one clade. There was little genetic diversity among Anqing, Tongling, Wuwei clusters. The afforestations of Anqing and Wuwei clustered into one group, while the woodlands of Anqing and Wuwei appeared as another group. There is a little genetic diversity of the snail cytochrome oxidase I (CO I ) in different ecological environments among the upstream, midstream and downstream regions along the Yangtz River in Anhui Province.

Low Reynolds Number Droplet Combustion In CO2 Enriched Atmospheres In Microgravity

NASA Technical Reports Server (NTRS)

Hicks, M. C.

2003-01-01

The effect of radiative feedback from the gas phase in micro-gravity combustion processes has been of increasing concern because of the implications in the selection and evaluation of appropriate fire suppressants. The use of CO2, an optically thick gas in the infrared region of the electromagnetic spectrum, has garnered widespread acceptance as an effective fire suppressant for most ground based applications. Since buoyant forces often dominate the flow field in 1-g environments the temperature field between the flame front and the fuel surface is not significantly affected by gas phase radiative absorption and re-emission as these hot gases are quickly swept downstream. However, in reduced gravity environments where buoyant-driven convective flows are negligible and where low-speed forced convective flows may be present at levels where gas phase radiation becomes important, then changes in environment that enhance gas phase radiative effects need to be better understood. This is particularly true in assessments of flammability limits and selection of appropriate fire suppressants for future space applications. In recognition of this, a ground-based investigation has been established that uses a droplet combustion configuration to systematically study the effects of enhanced gas phase radiation on droplet burn rates, flame structure, and radiative output from the flame zone.

Stability of IRA-45 solid amine resin as a function of carbon dioxide absorption and steam desorption cycling

NASA Technical Reports Server (NTRS)

Wood, Peter C.; Wydeven, Theodore

1987-01-01

The removal of CO2 from the NASA Space Station's cabin atmosphere, which may be undertaken by a solid-amine water (steam)-desorbed system, is presently evaluated with a view to long-term amine resin stability and adsorption/desorption cycling by means of an automated laboratory flow-testing facility. While the CO2-adsorption capacity of the IRA-45 amine resin used gradually decreased over time, the rate of degradation significantly decreased after the first 10 cycles. Attention is given to the presence (and possible need for removal) of trimethylamine in the process air downstream of the resin bed.

Sources of solutes to the proglacial Watson River (Akuliarusiarsuup Kuua) near Kangerlussuaq, West Greenland

NASA Astrophysics Data System (ADS)

Deuerling, K. M.; Martin, J. B.; Martin, E. E.; Scribner, C. A.

2013-12-01

Chemical weathering of silicate rocks in glacial forelands is a potential sink for atmospheric CO2 and therefore may impact long-term climate variability. Physical weathering in glacial environments enhances the rate of chemical weathering, particularly through subglacial production of rock flour with a high surface area to volume ratio. This reactive material is transported to and chemically weathered within the proglacial system, increasing concentrations of solutes as water flows downstream. Water from proglacial rivers may also acquire solutes and draw down atmospheric CO2 through reactions driven by hyporheic zone (HZ) exchange in the broad, braided reaches of the river channel. However, few studies have addressed this process and none to date have directly examined porewater contributions. We address these questions in the Watson River/Akuliarusiarsuup Kuua (WR), which flows approximately 40 km from its headwaters, through the town of Kangerlussuaq, and into Søndre Strømfjord. We have collected river water samples five times from six sites over the 2012 and 2013 summer melt seasons and three transects of PW from sand flats located along the river. Specific conductivity (SpC), pH, and dissolved ion concentrations increase downstream, consistent with ongoing chemical weathering reactions along the flow path. Relative abundances of Na+, K+, and SiO2 increase downstream relative to Ca2+ and Mg2+ concentrations. These signals indicate preferential dissolution of biotite and/or alkali feldspar. Additionally, 206Pb/204Pb ratios become more nonradiogenic downstream, lending further evidence to dissolution of readily weathered minerals. Over the course of the melt season, SpC, pH, and dissolved ion concentrations decrease, consistent with the increase in discharge due to supraglacial melting. The greatest downstream SpC increase (~2x) occurs where the river exits largely bedrock channeled flow and enters the braided portion at the Sandflugtdalen. In general, PW samples in the sand flats indicate weathering reactions occur near the river channel and the influence of evaporation becomes more important at distal sites. Porewater SpC increases by 4 times over river water values 20 cm below the water table at the sample sites 3.5 and 7 m from the river and then increases more than an order of magnitude at 70 cm below the water table. Sites 11 m from the river channel display SpC profiles that are elevated above the river values at shallow depths and then decrease with depth, likely reflecting evaporation at shallow depths. These trends may also reflect chemical weathering of sediments in the HZ. For the solutes in the HZ to have an effect on the composition of the WR, they must exchange with the river. This process could occur through diel fluctuations in the river stage resulting from extensive ice melt during the day. Near peak river flow, the estimated head gradient was 0.4 cm/m from the river to the bank. Pressure data from CTD sensors installed in the HZ indicate a diel signal similar to the river, though muted. These findings suggest that dilute river water enters the HZ at high flow and drains at low flow, thereby providing solutes to the river.

Basin scale controls on CO2 and CH4 emissions from the Upper Mississippi River

USGS Publications Warehouse

Crawford, John T.; Loken, Luke C.; Stanley, Emily H.; Stets, Edward G.; Dornblaser, Mark M.; Striegl, Robert G.

2016-01-01

The Upper Mississippi River, engineered for river navigation in the 1930s, includes a series of low-head dams and navigation pools receiving elevated sediment and nutrient loads from the mostly agricultural basin. Using high-resolution, spatially resolved water quality sensor measurements along 1385 river kilometers, we show that primary productivity and organic matter accumulation affect river carbon dioxide and methane emissions to the atmosphere. Phytoplankton drive CO2to near or below atmospheric equilibrium during the growing season, while anaerobic carbon oxidation supports a large proportion of the CO2 and CH4 production. Reductions of suspended sediment load, absent of dramatic reductions in nutrients, will likely further reduce net CO2emissions from the river. Large river pools, like Lake Pepin, which removes the majority of upstream sediments, and large agricultural tributaries downstream that deliver significant quantities of sediments and nutrients, are likely to persist as major geographical drivers of greenhouse gas emissions.

Diffusive mixing through velocity profile variation in microchannels

NASA Astrophysics Data System (ADS)

Yakhshi-Tafti, Ehsan; Cho, Hyoung J.; Kumar, Ranganathan

2011-03-01

Rapid mixing does not readily occur at low Reynolds number flows encountered in microdevices; however, it can be enhanced by passive diffusive mixing schemes. This study of micromixing of two miscible fluids is based on the principle that (1) increased velocity at the interface of co-flowing fluids results in increased diffusive mass flux across their interface, and (2) diffusion interfaces between two liquids progress transversely as the flow proceeds downstream. A passive micromixer is proposed that takes advantage of the peak velocity variation, inducing diffusive mixing. The effect of flow variation on the enhancement of diffusive mixing is investigated analytically and experimentally. Variation of the flow profile is confirmed using micro-Particle Image Velocimetry (μPIV) and mixing is evaluated by color variations resulting from the mixing of pH indicator and basic solutions. Velocity profile variations obtained from μPIV show a shift in peak velocities. The mixing efficiency of the Σ-micromixer is expected to be higher than that for a T-junction channel and can be as high as 80%. The mixing efficiency decreases with Reynolds number and increases with downstream length, exhibiting a power law.

The effect of fuel/air mixer design parameters on the continuous and discrete phase structure in the reaction-stabilizing region

NASA Astrophysics Data System (ADS)

Ateshkadi, Arash

The demands on current and future aero gas turbine combustors are demanding a greater insight into the role of the injector/dome design on combustion performance. The structure of the two-phase flow and combustion performance associated with practical injector/dome hardware is thoroughly investigated. A spray injector with two radial inflow swirlers was custom-designed to maintain tight tolerances and strict assembly protocol to isolate the sensitivity of performance to hardware design. The custom set is a unique modular design that (1) accommodates parametric variation in geometry, (2) retains symmetry, and (3) maintains effective area. Swirl sense and presence of a venturi were found to be the most influential on fuel distribution and Lean Blowout. The venturi acts as a fuel-prefilming surface and constrains the highest fuel mass concentration to an annular ring near the centerline. Co-swirl enhances the radial dispersion of the continuous phase and counter-swirl increases the level of mixing that occurs in the downstream region of the mixer. The smallest drop size distributions were found to occur with the counter-swirl configuration with venturi. In the case of counter-swirl without venturi the high concentration of fluid mass is found in the center region of the flow. The Lean Blowout (LBO) equivalence ratio was lower for counter-swirl due to the coupling of the centerline recirculation zone with the location of high fuel concentration emanating from smaller droplets. In the co-swirl configuration a more intense reaction was found near the mixer exit leading to the lowest concentration of NOx, CO and UHC. An LBO model with good agreement to the measured values was developed that related, for the first time, specific hardware parameters and operating condition to stability performance. A semi-analytical model, which agreed best with co-swirl configurations, was modified and used to describe the axial velocity profile downstream of the mixer exit. The development of these two models exemplifies the use of mathematical expressions to guide the design and development procedure for mixer geometry that meet the stringent demands on increasing combustion performance.

HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer

PubMed Central

Choi, Yiseul; Ko, Young San; Park, Jinju; Choi, Youngsun; Kim, Younghoon; Pyo, Jung-Soo; Jang, Bo Gun; Hwang, Douk Ho; Kim, Woo Ho; Lee, Byung Lan

2016-01-01

AIM To investigated the relationships between HER2, c-Jun N-terminal kinase (JNK) and protein kinase B (AKT) with respect to metastatic potential of HER2-positive gastric cancer (GC) cells. METHODS Immunohistochemistry was performed on tissue array slides containing 423 human GC specimens. Using HER2-positve GC cell lines SNU-216 and NCI-N87, HER2 expression was silenced by RNA interference, and the activations of JNK and AKT were suppressed by SP600125 and LY294002, respectively. Transwell assay, Western blot, semi-quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining were used in cell culture experiments. RESULTS In GC specimens, HER2, JNK, and AKT activations were positively correlated with each other. In vitro analysis revealed a positive regulatory feedback loop between HER2 and JNK in GC cell lines and the role of JNK as a downstream effector of AKT in the HER2/AKT signaling pathway. JNK inhibition suppressed migratory capacity through reversing EMT and dual inhibition of JNK and AKT induced a more profound effect on cancer cell motility. CONCLUSION HER2, JNK and AKT in human GC specimens are positively associated with each other. JNK and AKT, downstream effectors of HER2, co-operatively contribute to the metastatic potential of HER2-positive GC cells. Thus, targeting of these two molecules in combination with HER2 downregulation may be a good approach to combat HER2-positive GC. PMID:27895401

Does elevated CO 2 alter silica uptake in trees?

DOE PAGES

Fulweiler, Robinson W.; Maguire, Timothy J.; Carey, Joanna C.; ...

2015-01-13

Human activities have greatly altered global carbon (C) and Nitrogen (N) cycling. In fact, atmospheric concentrations of carbon dioxide (CO 2) have increased 40% over the last century and the amount of N cycling in the biosphere has more than doubled. In an effort to understand how plants will respond to continued global CO 2 fertilization, longterm free-air CO 2 enrichment experiments have been conducted at sites around the globe. Here we examine how atmospheric CO 2 enrichment and N fertilization affects the uptake of silicon (Si) in the Duke Forest, North Carolina, a stand dominated by Pinus taeda (loblollymore » pine), and five hardwood species. Specifically, we measured foliar biogenic silica concentrations in five deciduous and one coniferous species across three treatments: CO 2 enrichment, N enrichment, and N and CO 2 enrichment. We found no consistent trends in foliar Si concentration under elevated CO 2, N fertilization, or combined elevated CO 2 and N fertilization. However, two-thirds of the tree species studied here have Si foliar concentrations greater than well-known Si accumulators, such as grasses. Based on net primary production values and aboveground Si concentrations in these trees, we calculated forest Si uptake rates under control and elevated CO 2 concentrations. Due largely to increased primary production, elevated CO 2 enhanced the magnitude of Si uptake between 20 and 26%, likely intensifying the terrestrial silica pump. This uptake of Si by forests has important implications for Si export from terrestrial systems, with the potential to impact C sequestration and higher trophic levels in downstream ecosystems.« less

Numerical Investigation of Vortex Generator Flow Control for External-Compression Supersonic Inlets

NASA Astrophysics Data System (ADS)

Baydar, Ezgihan

Vortex generators (VGs) within external-compression supersonic inlets for Mach 1.6 were investigated to determine their ability to increase total pressure recovery and reduce total pressure distortion. Ramp and vane-type VGs were studied. The geometric factors of interest included height, length, spacing, angle-of-incidence, and positions upstream and downstream of the inlet terminal shock. The flow through the inlet was simulated numerically through the solution of the steady-state, Reynolds-averaged Navier-Stokes equations on multi-block, structured grids using the Wind-US flow solver. The inlet performance was characterized by the inlet total pressure recovery and the radial and circumferential total pressure distortion indices at the engine face. Previous research of downstream VGs in the low-boom supersonic inlet demonstrated improvement in radial distortion up to 24% while my work on external-compression supersonic inlets improved radial distortion up to 86%, which is significant. The design of experiments and statistical analysis methods were applied to quantify the effect of the geometric factors of VGs and search for optimal VG arrays. From the analysis, VG angle-of-incidence and VG height were the most influential factors in increasing total pressure recovery and reducing distortion. The study on the two-dimensional external-compression inlet determined which passive flow control devices, such as counter-rotating vanes or ramps, reduce high distortion levels and improve the health of the boundary layer, relative to the baseline. Downstream vanes demonstrate up to 21% improvement in boundary layer health and 86% improvement in radial distortion. Upstream vanes demonstrated up to 3% improvement in boundary layer health and 9% improvement in radial distortion. Ramps showed no improvement in boundary layer health and radial distortion. Micro-VGs were preferred for their reduced viscous drag and improvement in total pressure recovery at the AIP. Although traditional VGs energize the flow with stronger vortex structures compared to micro-VGs, the AIP is affected with overwhelming amounts of reduced and enhanced flow regions. In summary, vanes are exceptional in reducing radial distortion and improving the health of the boundary layer compared to the ramps. In the study of the STEX inlet, vane-type vortex generators were the preferred devices for boundary layer flow control. In the supersonic diffuser, co-rotating vane arrays and counter-rotating vane arrays did not show improvement. In the subsonic diffuser, co-rotating vane arrays with negative angles-of-incidence and counter-rotating vane arrays were exceptional in reducing radial distortion and improving total pressure recovery. Downstream co-rotating vanes demonstrated up to 41% improvement in radial distortion whereas downstream counter-rotating vanes demonstrated up to 73% improvement. For downstream counter-rotating vanes, a polynomial trend between VG height and radial distortion indicate that increasing VG height improves inlet distortion. In summary, downstream vanes are exceptional in improving total pressure recovery compared to upstream vanes.

Biotin-dependent functions in adiposity: a study of monozygotic twin pairs.

PubMed

Järvinen, E; Ismail, K; Muniandy, M; Bogl, L H; Heinonen, S; Tummers, M; Miettinen, S; Kaprio, J; Rissanen, A; Ollikainen, M; Pietiläinen, K H

2016-05-01

Biotin acts as a coenzyme for carboxylases regulating lipid and amino-acid metabolism. We investigated alterations of the biotin-dependent functions in obesity and the downstream effects of biotin restriction in adipocytes in vitro. Twenty-four monozygotic twin pairs discordant for body mass index (BMI). Mean within-pair difference (heavy-lean co-twin, Δ) of BMI was 6.0 kg m(-2) (range 3.1-15.2 kg m(-)(2)). Adipose tissue (AT) DNA methylation, gene expression of AT and adipocytes, and leukocytes (real-time quantitative PCR), serum biotin, C-reactive protein (CRP) and triglycerides were measured in the twins. Human adipocytes were cultured in low and control biotin concentrations and analyzed for lipid droplet content, mitochondrial morphology and mitochondrial respiration. The gene expression levels of carboxylases, PCCB and MCCC1, were upregulated in the heavier co-twins' leukocytes. ΔPCCB (r=0.91, P=0.0046) and ΔMCCC1 (r=0.79, P=0.036) correlated with ΔCRP within-pairs. Serum biotin levels were lower in the heavier (274 ng l(-1)) than in the lean co-twins (390 ng l(-1), P=0.034). ΔBiotin correlated negatively with Δtriglycerides (r=-0.56, P=0.045) within-pairs. In AT, HLCS and ACACB were hypermethylated and biotin cycle genes HLCS and BTD were downregulated (P<0.05). Biotin-dependent carboxylases were downregulated (ACACA, ACACB, PCCB, MCCC2 and PC; P<0.05) in both AT and adipocytes of the heavier co-twins. Adipocytes cultured in low biotin had decreased lipid accumulation, altered mitochondrial morphology and deficient mitochondrial respiration. Biotin-dependent functions are modified by adiposity independent of genetic effects, and correlate with inflammation and hypertriglyceridemia. Biotin restriction decreases lipid accumulation and respiration, and alters mitochondrial morphology in adipocytes.

Controls on the Origin and Cycling of Riverine Dissolved Inorganic Carbon in the Brazos River, Texas

NASA Astrophysics Data System (ADS)

Zeng, F.; Masiello, C. A.; Hockaday, W. C.

2008-12-01

Rivers are generally supersaturated in CO2 with respect to the atmosphere. However, there is little agreement on the sources and turnover times of excess CO2 in river waters. This is likely due to varying dominant controls on carbon sources (e.g. geologic setting, climate, land use, or human activities). In this study, we measured carbon isotopic signatures (δ13C and Δ14C) of riverine dissolved inorganic carbon (DIC), as well as solid state cross polarization/magic angle spinning (CP/MAS) 13C nuclear magnetic resonance (NMR) of particulate organic carbon (POC), to determine carbon sources fuelling respiration of the Brazos River in Texas. We found that sources of riverine CO2 varied significantly along the length of the Brazos. In the middle Brazos (between Graham and Waco), which is partially underlain by limestone, riverine DIC had average Δ14C of 74 ‰ and δ13C of -7.5 ‰, suggesting that riverine CO2 is derived almost entirely from contemporary carbon (less than 5 years old) with little evidence of carbonate input, probably due to the damming upstream of Waco. In the lower Brazos (downstream of Bryan), riverine DIC was highly depleted in 14C (average Δ14C = -148.5 ‰) and enriched in 13C (average δ13C= -9.32 ‰), indicative of the presence of old carbonate. Since there is no carbonate bedrock in contact with the river in this area, the most likely source of old carbonate is the shell used in road and building construction throughout the 19th century. Our results suggest that the effect of human activities superimposes and even surpasses the effect of natural controls (e.g. geologic setting and climate) on C cycling in the Brazos.

Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake

PubMed Central

Gao, Su; Kinzig, Kimberly P.; Aja, Susan; Scott, Karen A.; Keung, Wendy; Kelly, Sandra; Strynadka, Ken; Chohnan, Shigeru; Smith, Wanli W.; Tamashiro, Kellie L. K.; Ladenheim, Ellen E.; Ronnett, Gabriele V.; Tu, Yajun; Birnbaum, Morris J.; Lopaschuk, Gary D.; Moran, Timothy H.

2007-01-01

Hypothalamic fatty acid metabolism has recently been implicated in the controls of food intake and energy homeostasis. We report that intracerebroventricular (ICV) injection of leptin, concomitant with inhibiting AMP-activated kinase (AMPK), activates acetyl-CoA carboxylase (ACC), the key regulatory enzyme in fatty acid biosynthesis, in the arcuate nucleus (Arc) and paraventricular nucleus (PVN) in the hypothalamus. Arc overexpression of constitutively active AMPK prevents the Arc ACC activation in response to ICV leptin, supporting the hypothesis that AMPK lies upstream of ACC in leptin's Arc intracellular signaling pathway. Inhibiting hypothalamic ACC with 5-tetradecyloxy-2-furoic acid, a specific ACC inhibitor, blocks leptin-mediated decreases in food intake, body weight, and mRNA level of the orexigenic neuropeptide NPY. These results show that hypothalamic ACC activation makes an important contribution to leptin's anorectic effects. Furthermore, we find that ICV leptin up-regulates the level of malonyl-CoA (the intermediate of fatty acid biosynthesis) specifically in the Arc and increases the level of palmitoyl-CoA (a major product of fatty acid biosynthesis) specifically in the PVN. The rises of both levels are blocked by 5-tetradecyloxy-2-furoic acid along with the blockade of leptin-mediated hypophagia. These data suggest malonyl-CoA as a downstream mediator of ACC in leptin's signaling pathway in the Arc and imply that palmitoyl-CoA, instead of malonyl-CoA, could be an effector in relaying ACC signaling in the PVN. Together, these findings highlight site-specific impacts of hypothalamic ACC activation in leptin's anorectic signaling cascade. PMID:17956983

Harvesting of Chlorella sorokiniana by co-culture with the filamentous fungus Isaria fumosorosea: A potential sustainable feedstock for hydrothermal gasification.

PubMed

Mackay, Stephen; Gomes, Eduardo; Holliger, Christof; Bauer, Rolene; Schwitzguébel, Jean-Paul

2015-06-01

Despite recent advances in down-stream processing, production of microalgae remains substantially limited because of economical reasons. Harvesting and dewatering are the most energy-intensive processing steps in their production and contribute 20-30% of total operational cost. Bio-flocculation of microalgae by co-cultivation with filamentous fungi relies on the development of large structures that facilitate cost effective harvesting. A yet unknown filamentous fungus was isolated as a contaminant from a microalgal culture and identified as Isaria fumosorosea. Blastospores production was optimized in minimal medium and the development of pellets, possibly lichens, was followed when co-cultured with Chlorella sorokiniana under strict autotrophic conditions. Stable pellets (1-2mm) formed rapidly at pH 7-8, clearing the medium of free algal cells. Biomass was harvested with large inexpensive filters, generating wet slurry suitable for hydrothermal gasification. Nutrient rich brine from the aqueous phase of hydrothermal gasification supported growth of the fungus and may increase the process sustainability. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Role of Sulfide Oxidation Impairment in the Pathogenesis of Primary CoQ Deficiency

PubMed Central

Quinzii, Catarina M.; Luna-Sanchez, Marta; Ziosi, Marcello; Hidalgo-Gutierrez, Agustin; Kleiner, Giulio; Lopez, Luis C.

2017-01-01

Coenzyme Q (CoQ) is a lipid present in all cell membranes. One of the multiple metabolic functions of CoQ is to transport electrons in the reaction catalyzed by sulfide:quinone oxidoreductase (SQOR), the first enzyme of the oxidation pathway of sulfides (hydrogen sulfide, H2S). Early evidence of a defect in the metabolism of H2S in primary CoQ deficiency came from yeast studies in Schizosaccharomyces pombe strains defective for dps1 and ppt1 (homologs of PDSS1 and COQ2, respectively), which have H2S accumulation. Our recent studies in human skin fibroblasts and in murine models of primary CoQ deficiency show that, also in mammals, decreased CoQ levels cause impairment of H2S oxidation. Patient fibroblasts carrying different mutations in genes encoding proteins involved in CoQ biosynthesis show reduced SQOR activity and protein levels proportional to the levels of CoQ. In Pdss2kd/kd mice, kidney, the only organ clinically affected, shows reduced SQOR levels and downstream enzymes, accumulation of H2S, and glutathione depletion. Pdss2kd/kd mice have also low levels of thiosulfate in plasma and urine, and increased C4–C6 acylcarnitines in blood, due to inhibition of short-chain acyl-CoA dehydrogenase. Also in Coq9R239X mice, the symptomatic organ, cerebrum, shows accumulation of H2S, reduced SQOR, increase in thiosulfate sulfurtransferase and sulfite oxidase, and reduction in the levels of glutathione and glutathione enzymes, leading to alteration of the biosynthetic pathways of glutamate, serotonin, and catecholamines. Coq9R239X mice have also reduced blood pressure, possible consequence of H2S-induced vasorelaxation. Since liver is not clinically affected in Pdss2 and Coq9 mutant mice, the effects of the impairment of H2S oxidation in this organ were not investigated, despite its critical role in metabolism. In conclusion, in vitro and in vivo studies of CoQ deficient models provide evidence of tissue-specific H2S oxidation impairment, an additional pathomechanism that should be considered in the understanding and treatment of primary CoQ deficiency. PMID:28790927

Complementary cereals and legumes for health: Synergistic interaction of sorghum flavones and cowpea flavonols against LPS-induced inflammation in colonic myofibroblasts.

PubMed

Agah, Shima; Kim, Hyemee; Mertens-Talcott, Susanne U; Awika, Joseph M

2017-07-01

Cereals and legumes are traditionally consumed together in many cultures, and may provide complementary health benefits beyond what is known about improved indispensable amino acid intake. Here, we use an in vitro model of inflammatory pathways to investigate whether the different flavonoids in sorghum and cowpea could synergistically reduce inflammation. Interactive effect of combining apigenin and quercetin, as well as extracts (70% acetone, v/v) from a flavone-dominated white sorghum and flavonol-dominated white cowpea, against LPS-induced NF-κB and downstream cytokines (TNF-α, IL-6, IL-8) gene and protein expression was evaluated using the CCD18Co colon myofibroblasts. Combination of apigenin and quercetin, and sorghum and cowpea extracts synergistically downregulated LPS-induced NF-κB gene and protein expression in a dose-dependent manner, with additive effect producing IC 50 values that were 14.6 and 14.0 times, respectively, higher than 1:1 combined treatments. Similar strong synergistic interactions were observed for the downstream cytokines (IC 50 values for additive effect 8.3-21 times higher than combined treatments). Furthermore, the ratios of the different combined treatments significantly affected the magnitude of synergy. Combining the structurally related cereal flavones and legume flavonols elicit strong synergistic anti-inflammatory response in LPS-stimulated nonmalignant colonocytes, likely by targeting interdependent mechanisms. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Hippo signaling pathway in liver regeneration and tumorigenesis.

PubMed

Hong, Lixin; Cai, Yabo; Jiang, Mingting; Zhou, Dawang; Chen, Lanfen

2015-01-01

The Hippo signaling pathway is an evolutionarily conserved signaling module that plays critical roles in liver size control and tumorigenesis. The Hippo pathway consists of a core kinase cascade in which the mammalian Ste20-like kinases (Mst1/2, orthologs of Drosophila Hippo) and their cofactor Salvador (Sav1) form a complex to phosphorylate and activate the large tumor suppressor (Lats1/2). Lats1/2 kinases in turn phosphorylate and inhibit the transcription co-activators, the Yes-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ), two major downstream effectors of the Hippo pathway. Losses of the Hippo pathway components induce aberrant hepatomegaly and tumorigenesis, in which YAP coordinates regulation of cell proliferation and apoptosis and plays an essential role. This review summarizes the current findings of the regulation of Hippo signaling in liver regeneration and tumorigenesis, focusing on how the loss of tumor suppressor components of the Hippo pathway results in liver cancers and discussing the molecular mechanisms that regulate the expression and activation of its downstream effector YAP in liver tumorigenesis. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Efficient antitumor effect of co-drug-loaded nanoparticles with gelatin hydrogel by local implantation

PubMed Central

Zhang, Hao; Tian, Yong; Zhu, Zhenshu; Xu, Huae; Li, Xiaolin; Zheng, Donghui; Sun, Weihao

2016-01-01

Tetrandrine (Tet) could enhance the antitumor effect of Paclitaxel (Ptx) by increasing intracellular Reactive Oxygen Species (ROS) levels, which leads to the possibility of co-delivery of both drugs for synergistic antitumor effect. In the current study, we reported an efficient, local therapeutic strategy employing effective Tet and Ptx delivery with a nanoparticle-loaded gelatin system. Tet- and Ptx co-loaded mPEG-PCL nanoparticles (P/T-NPs) were encapsulated into the physically cross-linked gelatin hydrogel and then implanted on the tumor site for continuous drug release. The drug-loaded gelatin hydrogel underwent a phase change when the temperature slowly increased. In vitro study showed that Tet/Ptx-loaded PEG-b-PCL nanoparticles encapsulated within a gelatin hydrogel (P/T-NPs-Gelatin) inhibited the growth and invasive ability of BGC-823 cells more effectively than the combination of free drugs or P/T-NPs. In vivo study validated the therapeutic potential of P/T-NPs-Gelatin. P/T-NPs-Gelatin significantly inhibited the activation of p-Akt and the downstream anti-apoptotic Bcl-2 protein and also inducing the activation of pro-apoptotic Bax protein. Moreover, the molecular-modulating effect of P/T-NPs-Gelatin on related proteins varied slightly under the influence of NAC, which was supported by the observations of the tumor volumes and weights. Based on these findings, local implantation of P/T-NPs-Gelatin may be a promising therapeutic strategy for the treatment of gastric cancer. PMID:27226240

Direct Experiments on the Ocean Disposal of Fossil Fuel CO2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barry, James, P.

2010-05-26

Funding from DoE grant # FG0204-ER63721, Direct Experiments on the Ocean Disposal of Fossil Fuel CO2, supposed several postdoctoral fellows and research activities at MBARI related to ocean CO2 disposal and the biological consequences of high ocean CO2 levels on marine organisms. Postdocs supported on the project included Brad Seibel, now an associate professor at the University of Rhode Island, Jeff Drazen, now an associate professor at the University of Hawaii, and Eric Pane, who continues as a research associate at MBARI. Thus, the project contributed significantly to the professional development of young scientists. In addition, we made significant progressmore » in several research areas. We continued several deep-sea CO2 release experiments using support from DoE and MBARI, along with several collaborators. These CO2 release studies had the goal of broadening our understanding of the effects of high ocean CO2 levels on deep sea animals in the vicinity of potential release sites for direct deep-ocean carbon dioxide sequestration. Using MBARI ships and ROVs, we performed these experiments at depths of 3000 to 3600 m, where liquid CO2 is heavier than seawater. CO2 was released into small pools (sections of PVC pipe) on the seabed, where it dissolved and drifted downstream, bathing any caged animals and sediments in a CO2-rich, low-pH plume. We assessed the survival of organisms nearby. Several publications arose from these studies (Barry et al. 2004, 2005; Carman et al. 2004; Thistle et al. 2005, 2006, 2007; Fleeger et al. 2006, 2010; Barry and Drazen 2007; Bernhard et al. 2009; Sedlacek et al. 2009; Ricketts et al. in press; Barry et al, in revision) concerning the sensitivity of animals to low pH waters. Using funds from DoE and MBARI, we designed and fabricated a hyperbaric trap-respirometer to study metabolic rates of deep-sea fishes under high CO2 conditions (Drazen et al, 2005), as well as a gas-control aquarium system to support laboratory studies of the effects of high CO2 waters on marine animals (Barry et al. 2008). This system is capable of controlling oxygen, pH, and temperature of seawater for use in studies of the physiological responses of animals under acidified conditions. We have investigated the tolerance of deep- and shallow-living crabs to high CO2 levels (Pane and Barry 2007; Pane et al. 2008), and are now working on brachiopods (Barry et al. in prep.) and a comparison of deep and shallow living sea urchins. This research program, supported in part by DoE has contributed to a number of other publications authored or co-authored by Barry (Caldeira et al. 2005; Brewer and Barry 2008; Barry et al. 2006, 2010a,b,c; National Research Council, in press; Hoffman et al. in press) as well as over 40 invited talks since 2004, including Congressional briefings and testimony at U.S. Senate Hearings on Ocean Acidification. Through the grant period, the research emphasis shifted from studies of the effects of direct deep-sea carbon dioxide sequestration on deep-sea animals, to a broader conceptual framework of the effects of ocean acidification (whether purposeful or passive) on the physiology and survival of deep and shallow living marine animals. We feel that this has been a very productive program and are grateful to DoE for its support.« less

Comparison of two closed-path cavity-based spectrometers for measuring air-water CO2 and CH4 fluxes by eddy covariance

NASA Astrophysics Data System (ADS)

Yang, Mingxi; Prytherch, John; Kozlova, Elena; Yelland, Margaret J.; Parenkat Mony, Deepulal; Bell, Thomas G.

2016-11-01

In recent years several commercialised closed-path cavity-based spectroscopic instruments designed for eddy covariance flux measurements of carbon dioxide (CO2), methane (CH4), and water vapour (H2O) have become available. Here we compare the performance of two leading models - the Picarro G2311-f and the Los Gatos Research (LGR) Fast Greenhouse Gas Analyzer (FGGA) at a coastal site. Both instruments can compute dry mixing ratios of CO2 and CH4 based on concurrently measured H2O, temperature, and pressure. Additionally, we used a high throughput Nafion dryer to physically remove H2O from the Picarro airstream. Observed air-sea CO2 and CH4 fluxes from these two analysers, averaging about 12 and 0.12 mmol m-2 day-1 respectively, agree within the measurement uncertainties. For the purpose of quantifying dry CO2 and CH4 fluxes downstream of a long inlet, the numerical H2O corrections appear to be reasonably effective and lead to results that are comparable to physical removal of H2O with a Nafion dryer in the mean. We estimate the high-frequency attenuation of fluxes in our closed-path set-up, which was relatively small ( ≤ 10 %) for CO2 and CH4 but very large for the more polar H2O. The Picarro showed significantly lower noise and flux detection limits than the LGR. The hourly flux detection limit for the Picarro was about 2 mmol m-2 day-1 for CO2 and 0.02 mmol m-2 day-1 for CH4. For the LGR these detection limits were about 8 and 0.05 mmol m-2 day-1. Using global maps of monthly mean air-sea CO2 flux as reference, we estimate that the Picarro and LGR can resolve hourly CO2 fluxes from roughly 40 and 4 % of the world's oceans respectively. Averaging over longer timescales would be required in regions with smaller fluxes. Hourly flux detection limits of CH4 from both instruments are generally higher than the expected emissions from the open ocean, though the signal to noise of this measurement may improve closer to the coast.

Effect of Jet Injection Angle and Number of Jets on Mixing and Emissions From a Reacting Crossflow at Atmospheric Pressure

NASA Technical Reports Server (NTRS)

St.John, D.; Samuelsen, G. S.

2000-01-01

The mixing of air jets into hot, fuel-rich products of a gas turbine primary zone is an important step in staged combustion. Often referred to as "quick quench," the mixing occurs with chemical conversion and substantial heat release. An experiment has been designed to simulate and study this process, and the effect of varying the entry angle (0 deg, 22.5 deg and 45 deg from normal) and number of the air jets (7, 9, and 11) into the main flow, while holding the jet-to-crossflow mass-low ratio, MR, and momentum-flux ratio, J, constant (MR = 2.5;J = 25). The geometry is a crossflow confined in a cylindrical duct with side-wall injection of jets issuing from orifices equally spaced around the perimeter. A specially designed reactor, operating on propane, presents a uniform mixture to a module containing air jet injection tubes that can be changed to vary orifice geometry. Species concentrations of O2, CO, CO2, NO(x) and HC were obtained one duct diameter upstream (in the rich zone), and primarily one duct radius downstream. From this information, penetration of the jet, the spatial extent of chemical reaction, mixing, and the optimum jet injection angle and number of jets can be deduced.

Resistively-Heated Microlith-based Adsorber for Carbon Dioxide and Trace Contaminant Removal

NASA Technical Reports Server (NTRS)

Roychoudhury, S.; Walsh, D.; Perry, J.

2005-01-01

An integrated sorber-based Trace Contaminant Control System (TCCS) and Carbon Dioxide Removal Assembly (CDRA) prototype was designed, fabricated and tested. It corresponds to a 7-person load. Performance over several adsorption/regeneration cycles was examined. Vacuum regenerations at effective time/temperature conditions, and estimated power requirements were experimentally verified for the combined CO2/trace contaminant removal prototype. The current paper details the design and performance of this prototype during initial testing at CO2 and trace contaminant concentrations in the existing CDRA, downstream of the drier. Additional long-term performance characterization is planned at NASA. Potential system design options permitting associated weight, volume savings and logistic benefits, especially as relevant for long-duration space flight, are reviewed. The technology consisted of a sorption bed with sorbent- coated metal meshes, trademarked and patented as Microlith by Precision Combustion, Inc. (PCI). By contrast the current CO2 removal system on the International Space Station employs pellet beds. Preliminary bench scale performance data (without direct resistive heating) for simultaneous CO2 and trace contaminant removal was reviewed in SAE 2004-01-2442. In the prototype, the meshes were directly electrically heated for rapid response and accurate temperature control. This allowed regeneration via resistive heating with the potential for shorter regeneration times, reduced power requirement, and net energy savings vs. conventional systems. A novel flow arrangement, for removing both CO2 and trace contaminants within the same bed, was demonstrated. Thus, the need for a separate trace contaminant unit was eliminated resulting in an opportunity for significant weight savings. Unlike the current disposable charcoal bed, zeolites for trace contaminant removal are amenable to periodic regeneration.

Continuous Turbidity Monitoring in the Indian Creek Watershed, Tazewell County, Virginia, 2006-08

USGS Publications Warehouse

Moyer, Douglas; Hyer, Kenneth

2009-01-01

Thousands of miles of natural gas pipelines are installed annually in the United States. These pipelines commonly cross streams, rivers, and other water bodies during pipeline construction. A major concern associated with pipelines crossing water bodies is increased sediment loading and the subsequent impact to the ecology of the aquatic system. Several studies have investigated the techniques used to install pipelines across surface-water bodies and their effect on downstream suspended-sediment concentrations. These studies frequently employ the evaluation of suspended-sediment or turbidity data that were collected using discrete sample-collection methods. No studies, however, have evaluated the utility of continuous turbidity monitoring for identifying real-time sediment input and providing a robust dataset for the evaluation of long-term changes in suspended-sediment concentration as it relates to a pipeline crossing. In 2006, the U.S. Geological Survey, in cooperation with East Tennessee Natural Gas and the U.S. Fish and Wildlife Service, began a study to monitor the effects of construction of the Jewell Ridge Lateral natural gas pipeline on turbidity conditions below pipeline crossings of Indian Creek and an unnamed tributary to Indian Creek, in Tazewell County, Virginia. The potential for increased sediment loading to Indian Creek is of major concern for watershed managers because Indian Creek is listed as one of Virginia's Threatened and Endangered Species Waters and contains critical habitat for two freshwater mussel species, purple bean (Villosa perpurpurea) and rough rabbitsfoot (Quadrula cylindrical strigillata). Additionally, Indian Creek contains the last known reproducing population of the tan riffleshell (Epioblasma florentina walkeri). Therefore, the objectives of the U.S. Geological Survey monitoring effort were to (1) develop a continuous turbidity monitoring network that attempted to measure real-time changes in suspended sediment (using turbidity as a surrogate) downstream from the pipeline crossings, and (2) provide continuous turbidity data that enable the development of a real-time turbidity-input warning system and assessment of long-term changes in turbidity conditions. Water-quality conditions were assessed using continuous water-quality monitors deployed upstream and downstream from the pipeline crossings in Indian Creek and the unnamed tributary. These paired upstream and downstream monitors were outfitted with turbidity, pH (for Indian Creek only), specific-conductance, and water-temperature sensors. Water-quality data were collected continuously (every 15 minutes) during three phases of the pipeline construction: pre-construction, during construction, and post-construction. Continuous turbidity data were evaluated at various time steps to determine whether the construction of the pipeline crossings had an effect on downstream suspended-sediment conditions in Indian Creek and the unnamed tributary. These continuous turbidity data were analyzed in real time with the aid of a turbidity-input warning system. A warning occurred when turbidity values downstream from the pipeline were 6 Formazin Nephelometric Units or 15 percent (depending on the observed range) greater than turbidity upstream from the pipeline crossing. Statistical analyses also were performed on monthly and phase-of-construction turbidity data to determine if the pipeline crossing served as a long-term source of sediment. Results of this intensive water-quality monitoring effort indicate that values of turbidity in Indian Creek increased significantly between the upstream and downstream water-quality monitors during the construction of the Jewell Ridge pipeline. The magnitude of the significant turbidity increase, however, was small (less than 2 Formazin Nephelometric Units). Patterns in the continuous turbidity data indicate that the actual pipeline crossing of Indian Creek had little influence of downstream water quality; co

Methane-rich water induces cucumber adventitious rooting through heme oxygenase1/carbon monoxide and Ca(2+) pathways.

PubMed

Cui, Weiti; Qi, Fang; Zhang, Yihua; Cao, Hong; Zhang, Jing; Wang, Ren; Shen, Wenbiao

2015-03-01

Methane-rich water triggered adventitious rooting by regulating heme oxygenase1/carbon monoxide and calcium pathways in cucumber explants. Heme oxygenase1/carbon monoxide (HO1/CO) and calcium (Ca(2+)) were reported as the downstream signals in auxin-induced cucumber adventitious root (AR) formation. Here, we observed that application of methane-rich water (MRW; 80% saturation) obviously induced AR formation in IAA-depleted cucumber explants. To address the universality, we checked adventitious rooting in soybean and mung bean explants, and found that MRW (50 and 10% saturation, respectively) exhibited the similar inducing results. To further determine if the HO1/CO system participated in MRW-induced adventitious rooting, MRW, HO1 inducer hemin, its activity inhibitor zinc protoporphyrin IX (ZnPP), and its catalytic by-products CO, bilirubin, and Fe(2+) were used to detect their effects on cucumber adventitious rooting in IAA-depleted explants. Subsequent results showed that MRW-induced adventitious rooting was blocked by ZnPP and further reversed by 20% saturation CO aqueous solution. However, the other two by-products of HO1, bilirubin and Fe(2+), failed to induce AR formation. Above responses were consistent with the MRW-induced increases of HO1 transcript and corresponding protein level. Further molecular evidence indicted that expression of marker genes, including auxin signaling-related genes and cell cycle regulatory genes, were modulated by MRW alone but blocked by the cotreatment with ZnPP, the latter of which could be significantly rescued by the addition of CO. By using the Ca(2+)-channel blocker and Ca(2+) chelator, the involvement of Ca(2+) pathway in MRW-induced adventitious rooting was also suggested. Together, our results indicate that MRW might serve as a stimulator of adventitious rooting, which was partially mediated by HO1/CO and Ca(2+) pathways.

Nonlinearity Analysis for Efficient Modelling of Long-Term CO2 Storage

NASA Astrophysics Data System (ADS)

Li, Boxiao; Benson, Sally; Tchelepi, Hamdi

2014-05-01

Numerical simulation is widely used to predict the long-term fate of the injected CO2 in a storage formation. Performing large-scale simulations is often limited by the computational speed, where convergence failure of Newton iterations is one of the main bottlenecks. In order to design better numerical schemes and faster nonlinear solvers for modelling long-term CO2 storage, the nonlinearity in the simulations has to be analysed thoroughly, and the cause of convergence failures has to be identified clearly. We focus on the transport of CO2 and water in the presence of viscous, gravity, and heterogeneous capillary forces. We investigate the nonlinearity of the discrete transport equation obtained from finite-volume discretization with single-point phase-based upstream weighting, which is the industry standard. In particular, we study the discretized flux expressed as a function of saturations at the upstream and downstream (with respect to the total velocity) of each gridblock interface. We analyse the locations and complexity of the unit-flux, zero-flux, and inflection lines on the numerical flux. The unit- and zero-flux lines, referred to as kinks, correspond to a change of the flow direction, which often occurs when strong buoyancy and capillarity are present. We observe that these kinks and inflection lines are major sources of nonlinear convergence difficulties. We find that kinks create more challenges than inflection lines, especially when their locations depend on both the upstream and downstream saturations of the total velocity. When the flow is driven by viscous and gravity forces (e.g., during CO2 injection), one kink will occur in the numerical flux and its location depends only on the upstream saturation. However, when capillarity is dominant (e.g., during the post-injection period), two kinks will occur and both are functions of the upstream and downstream saturations, causing severe convergence difficulties particularly when heterogeneity is present. Our analysis of the numerical flux theoretically describes the cause of the convergence failures for simulating long-term CO2 storage. This understanding provides useful guidance in designing numerical schemes and nonlinear solvers that overcome the convergence bottlenecks. For example, to reduce the nonlinearity introduced by the two kinks in the presence of capillarity, we modify the method of Cances (2009) to discretize the capillary flux. Consequently, only one kink will occur even for coupled viscous, buoyancy, and heterogeneous capillary forces, and the kink depends only on the upstream saturation of the total velocity. An efficient nonlinear solver that is a significant refinement of the works of Jenny et al. (2009) and Wang and Tchelepi (2013) has also been proposed and demonstrated. References [1] C. Cances. Finite volume scheme for two-phase flows in heterogeneous porous media involving capillary pressure discontinuities. ESAIM:M2AN., 43, 973-1001, (2009). [2] P. Jenny, H.A. Tchelepi, and S.H. Lee. Unconditionally convergent nonlinear solver for hyperbolic conservation laws with S-shaped flux functions. J. Comput. Phys., 228, 7497-7512, (2009). [3] X. Wang and H.A. Tchelepi. Trust-region based solver for nonlinear transport in heterogeneous porous media. J. Comput. Phys., 253, 114-137, (2013).

Involvement of PI3K/Akt Signaling Pathway and Its Downstream Intracellular Targets in the Antidepressant-Like Effect of Creatine.

PubMed

Cunha, Mauricio P; Budni, Josiane; Ludka, Fabiana K; Pazini, Francis L; Rosa, Julia Macedo; Oliveira, Ágatha; Lopes, Mark W; Tasca, Carla I; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

2016-07-01

Creatine has been proposed to exert beneficial effects in the management of depression, but the cell signaling pathways implicated in its antidepressant effects are not well established. This study investigated the involvement of PI3K/Akt signaling pathway and its downstream intracellular targets in the antidepressant-like effect of creatine. The acute treatment of mice with creatine (1 mg/kg, po) increased the Akt and P70S6K phosphorylation, and HO-1, GPx and PSD95 immunocontents. The pretreatment of mice with LY294002 (10 nmol/mouse, icv, PI3K inhibitor), wortmannin (0.1 μg/mouse, icv, PI3K inhibitor), ZnPP (10 μg/mouse, icv, HO-1 inhibitor), or rapamycin (0.2 nmol/mouse, icv, mTOR inhibitor) prevented the antidepressant-like effect of creatine (1 mg/kg, po) in the TST. In addition, the administration of subeffective dose of either the selective GSK3 inhibitor AR-A014418 (0.01 μg/mouse, icv), the nonselective GSK3 inhibitor lithium chloride (10 mg/kg, po), or the HO-1 inductor CoPP (0.01 μg/mouse, icv), in combination with a subeffective dose of creatine (0.01 mg/kg, po) reduced the immobility time in the TST as compared with either drug alone. No treatment caused significant changes in the locomotor activity of mice. These results indicate that the antidepressant-like effect of creatine in the TST depends on the activation of Akt, Nrf2/HO-1, GPx, and mTOR, and GSK3 inhibition.

Carbon allocation to major metabolites in illuminated leaves is not just proportional to photosynthesis when gaseous conditions (CO2 and O2 ) vary.

PubMed

Abadie, Cyril; Bathellier, Camille; Tcherkez, Guillaume

2018-04-01

In gas-exchange experiments, manipulating CO 2 and O 2 is commonly used to change the balance between carboxylation and oxygenation. Downstream metabolism (utilization of photosynthetic and photorespiratory products) may also be affected by gaseous conditions but this is not well documented. Here, we took advantage of sunflower as a model species, which accumulates chlorogenate in addition to sugars and amino acids (glutamate, alanine, glycine and serine). We performed isotopic labelling with 13 CO 2 under different CO 2 /O 2 conditions, and determined 13 C contents to compute 13 C-allocation patterns and build-up rates. The 13 C content in major metabolites was not found to be a constant proportion of net fixed carbon but, rather, changed dramatically with CO 2 and O 2 . Alanine typically accumulated at low O 2 (hypoxic response) while photorespiratory intermediates accumulated under ambient conditions and at high photorespiration, glycerate accumulation exceeding serine and glycine build-up. Chlorogenate synthesis was relatively more important under normal conditions and at high CO 2 and its synthesis was driven by phosphoenolpyruvate de novo synthesis. These findings demonstrate that carbon allocation to metabolites other than photosynthetic end products is affected by gaseous conditions and therefore the photosynthetic yield of net nitrogen assimilation varies, being minimal at high CO 2 and maximal at high O 2 . © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy.

PubMed

Rose, Jason J; Wang, Ling; Xu, Qinzi; McTiernan, Charles F; Shiva, Sruti; Tejero, Jesus; Gladwin, Mark T

2017-03-01

Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15-40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.

Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy

PubMed Central

Xu, Qinzi; Shiva, Sruti

2017-01-01

Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15–40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development. PMID:27753502

From bottles to stream reaches and networks: Consequences of scale in how we interpret the function of freshwaters in the carbon cycle

NASA Astrophysics Data System (ADS)

Hotchkiss, E. R.

2017-12-01

Freshwater biological processes can alter the quantity and quality of organic carbon (OC) inputs from land before they are transported downstream, but the relative role of hydrologic transport and in-stream processing is still not well quantified at the scale of fluvial networks. Despite much research on the role of biology and hydrology in governing the form and fate of C in inland waters, conclusions about the function of freshwater ecosystems in modifying OC still largely depend on where we draw our ecosystem boundaries, i.e., the spatial scale of measurements used to assess OC transformations. Here I review freshwater OC uptake rates derived from bioassay incubations, synoptic modeling, reach-scale experiments, and ecosystem OC spiraling estimates. Median OC uptake velocities from standard bioassay incubations (0.02 m/d) and synoptic modeling (0.04 m/d) are 1-2 orders of magnitude lower than reach-scale experimental DOC additions and ecosystem OC spiraling estimates (2.2 and 0.27 m/d, respectively) in streams and rivers. Together, ecosystem metabolism and OC fluxes can be used to estimate the distance OC travels before being consumed and respired as CO2 through biological processes (i.e., OC spiraling), allowing for a more mechanistic understanding of the role of ecosystem processes and hydrologic fluxes in modifying downstream OC transport. Beyond the reach scale, data from stream network and stream-lake-river modeling simulations show how we may use linked sampling sites within networks to better understand the integrated sources and fate of OC in freshwaters. We currently underestimate the role of upstream processes in contributing to downstream fluxes: moving from single-ecosystem comparisons to linked-ecosystem simulations increases the contribution of in situ OC processing to CO2 emissions from 30% to >40%. Insights from literature reviews, ecosystem process measurements, and model simulations provide a framework for future considerations of integrated C transport, transformations, and fate when scaling patterns and processes in inland waters.

pPKCδ activates SC35 splicing factor during H9c2 myoblastic differentiation.

PubMed

Zara, Susi; Falconi, Mirella; Rapino, Monica; Zago, Michela; Orsini, Giovanna; Mazzotti, Giovanni; Cataldi, Amelia; Teti, Gabriella

2011-01-01

Although Protein Kinase C (PKC) isoforms' role in the neonatal and adult cardiac tissue development and ageing has been widely described "in vivo", the interaction of such enzymes with specific nuclear substrates needs to be investigated. The aim of our research has been the study of the expression, localization and interaction with the splicing factor SC35 of PKC isoforms (α, δ, ε, ζ) and their potential role in modulating the transcription machinery. H9c2 cells induced to myoblast differentiation in the presence of 1% Horse Serum (HS) have represented our experimental model. The expression of PKC isoforms, their distribution and interaction with SC35 have been evaluated by western blotting, co-immunoprecipitation and double gold immunolabeling for transmission and scanning electron microscopy. Our results show PKCδ as the most expressed isoform in differentiated cells. Surprisingly, the distribution of PKCδ and SC35 does not show any significant modification between 10%FBS and 1%HS treated samples and no co-localization is observed. Moreover the interaction between the phosphorylated form of PKCδ (pPKCδ) and SC35 increases, is distributed and co-localizes within the nucleus of differentiated H9c2. These data represent reasonable evidence of pPKCδ mediated SC35 splicing factor activation, suggesting its direct effect on transcription via interaction with the transcription machinery. Furthermore, this co-localization represents a crucial event resulting in downstream changes in transcription of components which determine the morphological modifications related to cardiomyoblast differentiated phenotype.

CH4 emissions from European Major Population Centers: Results from aircraft-borne CH4 in-situ observations during EMeRGe-Europe campaign 2017

NASA Astrophysics Data System (ADS)

Roiger, A.; Klausner, T.; Schlager, H.; Ziereis, H.; Huntrieser, H.; Baumann, R.; Eirenschmalz, L.; Joeckel, P.; Mertens, M.; Fisher, R.; Bauguitte, S.; Young, S.; Andrés Hernández, M. D.

2017-12-01

Urban environments represent large and diffuse area sources of CH4 including emissions from pipeline leaks, industrial/sewage treatment plants, and landfills. However, there is little knowledge about the exact magnitude of these emissions and their contribution to total anthropogenic CH4. Especially in the context of an urbanizing world, a better understanding of the methane footprint of urban areas is crucial, both with respect to mitigation and projection of climate impacts. Aircraft-borne in-situ measurements are particularly useful to both quantify emissions from such area sources, as well as to study their impact on the regional distribution. However, airborne CH4 observations downstream of European cities are especially sparse.Here we report from aircraft-borne CH4 in-situ measurements as conducted during the HALO aircraft campaign EMeRGe (Effect of Megacities on the Transport and Transformation of Pollutants on the Regional to Global Scales) in July 2017, which was led by the University of Bremen, Germany. During seven research flights, emissions from a variety of European (Mega)-cities were probed at different altitudes from 3km down to 500m, including measurements in the outflows of London, Rome, Po Valley, Ruhr and Benelux. We will present and compare the CH4 distribution measured downstream of the various studied urban hot-spots. With the help of other trace gas measurements (including e.g. CO2, CO, O3, SO2), observed methane enhancements will be attributed to the different potential source types. Finally, by the combination of in-situ measurements and regional model simulations using the EMAC-MECO(n) model, the contribution of emissions from urban centers to the regional methane budget over Europe will be discussed.

Continuous production of biodiesel from microalgae by extraction coupling with transesterification under supercritical conditions.

PubMed

Zhou, Dan; Qiao, Baoquan; Li, Gen; Xue, Song; Yin, Jianzhong

2017-08-01

Raw material for biodiesel has been expanded from edible oil to non-edible oil. In this study, biodiesel continuous production for two kinds of microalgae Chrysophyta and Chlorella sp. was conducted. Coupling with the supercritical carbon dioxide extraction, the oil of microalgae was extracted firstly, and then sent to the downstream production of biodiesel. The residue after decompression can be reused as the material for pharmaceuticals and nutraceuticals. Results showed that the particle size of microalgae, temperature, pressure, molar ration of methanol to oil, flow of CO 2 and n-hexane all have effects on the yield of biodiesel. With the optimal operation conditions: 40mesh algae, extraction temperature 60°C, flow of n-hexane 0.4ml/min, reaction temperature: 340°C, pressure: 18-20MPa, CO 2 flow of 0.5L/min, molar ration of methanol to oil 84:1, a yield of 56.31% was obtained for Chrysophyta, and 63.78% for Chlorella sp. due to the higher lipid content. Copyright © 2017. Published by Elsevier Ltd.

Connectivity and effects of streams and wetlands on downstream waters: A review and synthesis of the scientific evidence

USDA-ARS?s Scientific Manuscript database

The purpose of this document is to review and synthesize more than 850 publications from the peer-reviewed literature pertaining to three questions: 1) What are the physical, chemical, and biological connections to and effects of ephemeral, intermittent, and perennial streams on downstream waters? 2...

μPIV measurements of two-phase flows of an operated direct methanol fuel cell

NASA Astrophysics Data System (ADS)

Burgmann, Sebastian; Blank, Mirja; Panchenko, Olha; Wartmann, Jens

2013-05-01

In direct methanol fuel cells (DMFCs), two-phase flows appear in the channels of the anode side (CO2 bubbles in a liquid water-methanol environment) as well as of the cathode side (water droplets or films in an ambient air flow). CO2 bubbles or water droplets may almost completely fill the cross-section of a channel. The instantaneous effect of the formation of two-phase flows on the cell performance has not been investigated in detail, yet. In the current project, the micro particle image velocimetry (μPIV) technique is used to elucidate the corresponding flow phenomena on the anode as well as on the cathode side of a DMFC and to correlate those phenomena with the performance of the cell. A single-channel DMFC with optical access at the anode and the cathode side is constructed and assembled that allows for μPIV measurements at both sides as well as a detailed time-resolved cell voltage recording. The appearance and evolution of CO2 bubbles on the anode side is qualitatively and quantitatively investigated. The results clearly indicate that the cell power increases when the free cross-section area of the channel is decreased by huge bubbles. Methanol is forced into the porous gas diffusion layer (GDL) between the channels and the membrane is oxidized to CO2, and hence, the fuel consumption is increased and the cell performance rises. Eventually, a bubble forms a moving slug that effectively cleans the channel from CO2 bubbles on its way downstream. The blockage effect is eliminated; the methanol flow is not forced into the GDL anymore. The remaining amount of methanol in the GDL is oxidized. The cell power decreases until enough CO2 is produced to eventually form bubbles again and the process starts again. On the other hand under the investigated conditions, water on the cathode side only forms liquid films on the channels walls rather than channel-filling droplets. Instantaneous changes of the cell power due to liquid water formation could not be observed. The timescales of the two-phase flow on the cathode side are significantly larger than on the anode side. However, the μPIV measurements at the cathode side demonstrate the ability of feeding gas flows in microchannels with liquid tracer particles and the ability to measure in two-phase flows in such a configuration.

MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2

PubMed Central

2010-01-01

Background Neuroblastoma is a paediatric cancer of the sympathetic nervous system. The single most important genetic indicator of poor clinical outcome is amplification of the MYCN transcription factor. One of many down-stream MYCN targets is miR-184, which is either directly or indirectly repressed by this transcription factor, possibly due to its pro-apoptotic effects when ectopically over-expressed in neuroblastoma cells. The purpose of this study was to elucidate the molecular mechanism by which miR-184 conveys pro-apoptotic effects. Results We demonstrate that the knock-down of endogenous miR-184 has the opposite effect of ectopic up-regulation, leading to enhanced neuroblastoma cell numbers. As a mechanism of how miR-184 causes apoptosis when over-expressed, and increased cell numbers when inhibited, we demonstrate direct targeting and degradation of AKT2, a major downstream effector of the phosphatidylinositol 3-kinase (PI3K) pathway, one of the most potent pro-survival pathways in cancer. The pro-apoptotic effects of miR-184 ectopic over-expression in neuroblastoma cell lines is reproduced by siRNA inhibition of AKT2, while a positive effect on cell numbers similar to that obtained by the knock-down of endogenous miR-184 can be achieved by ectopic up-regulation of AKT2. Moreover, co-transfection of miR-184 with an AKT2 expression vector lacking the miR-184 target site in the 3'UTR rescues cells from the pro-apoptotic effects of miR-184. Conclusions MYCN contributes to tumorigenesis, in part, by repressing miR-184, leading to increased levels of AKT2, a direct target of miR-184. Thus, two important genes with positive effects on cell growth and survival, MYCN and AKT2, can be linked into a common genetic pathway through the actions of miR-184. As an inhibitor of AKT2, miR-184 could be of potential benefit in miRNA mediated therapeutics of MYCN amplified neuroblastoma and other forms of cancer. PMID:20409325

Tradeoffs in Greenhouse Gas Fluxes from Aquatic Ecosystems Along a Rural to Urban Gradient are Driven by N Loading

NASA Astrophysics Data System (ADS)

McDowell, W. H.; Potter, J.

2017-12-01

The effects of urbanization on net greenhouse gas (GHG) exchange from streams and rivers to the atmosphere are poorly understood. Previous work on a few small suburban streams in New Hampshire shows that N2O concentration is strongly seasonal, increases with wetland contact, and can be highest in streams with low CH4 production. Here we expand on these observations using 4 years of weekly samples in multiple headwater streams and a single downstream main stem site. Our results show that within a single drainage network, CH4 concentrations are higher downstream than in any of the small tributaries studied, which span a range of land use and wetland coverage. Methane is also very strongly seasonal in concentration in the tributaries (peaking in late summer), but is aseasonal in the main stem. In contrast, N2O concentrations are strongly seasonal at all sites, but peak in early winter and are much higher in more urban tributaries than the main stem. Urbanization results in a flipping of GHG concentrations, with highest N2O and lowest CH4 in the most urban watershed. CO2 shows no strong patterns with respect to landscape position, urbanization, or season. We examined multiple biogeochemical drivers of net CH4 and N2O production, and found that the increased NO3 concentration associated with urbanization is a good predictor of N2O concentrations in many streams.

Enhanced extraction of butyric acid under high-pressure CO2 conditions to integrate chemical catalysis for value-added chemicals and biofuels.

PubMed

Chun, Jaesung; Choi, Okkyoung; Sang, Byoung-In

2018-01-01

Extractive fermentation with the removal of carboxylic acid requires low pH conditions because acids are better partitioned into the solvent phase at low pH values. However, this requirement conflicts with the optimal near-neutral pH conditions for microbial growth. CO 2 pressurization was used, instead of the addition of chemicals, to decrease pH for the extraction of butyric acid, a fermentation product of Clostridium tyrobutyricum , and butyl butyrate was selected as an extractant. CO 2 pressurization (50 bar) improved the extraction efficiency of butyric acid from a solution at pH 6, yielding a distribution coefficient ( D ) 0.42. In situ removal of butyric acid during fermentation increased the production of butyric acid by up to 4.10 g/L h, an almost twofold increase over control without the use of an extraction process. In situ extraction of butyric acid using temporal CO 2 pressurization may be applied to an integrated downstream catalytic process for upgrading butyric acid to value-added chemicals in an organic solvent.

Surface-water and groundwater interactions in an extensively mined watershed, upper Schuylkill River, Pennsylvania, USA

USGS Publications Warehouse

Cravotta, Charles A.; Goode, Daniel J.; Bartles, Michael D.; Risser, Dennis W.; Galeone, Daniel G.

2014-01-01

Streams crossing underground coal mines may lose flow, while abandoned mine drainage (AMD) restores flow downstream. During 2005-12, discharge from the Pine Knot Mine Tunnel, the largest AMD source in the upper Schuylkill River Basin, had near-neutral pH and elevated concentrations of iron, manganese, and sulfate. Discharge from the tunnel responded rapidly to recharge but exhibited a prolonged recession compared to nearby streams, consistent with rapid infiltration and slow release of groundwater from the mine. Downstream of the AMD, dissolved iron was attenuated by oxidation and precipitation while dissolved CO2 degassed and pH increased. During high-flow conditions, the AMD and downstream waters exhibited decreased pH, iron, and sulfate with increased acidity that were modeled by mixing net-alkaline AMD with recharge or runoff having low ionic strength and low pH. Attenuation of dissolved iron within the river was least effective during high-flow conditions because of decreased transport time coupled with inhibitory effects of low pH on oxidation kinetics. A numerical model of groundwater flow was calibrated using groundwater levels in the Pine Knot Mine and discharge data for the Pine Knot Mine Tunnel and the West Branch Schuylkill River during a snowmelt event in January 2012. Although the calibrated model indicated substantial recharge to the mine complex took place away from streams, simulation of rapid changes in mine pool level and tunnel discharge during a high flow event in May 2012 required a source of direct recharge to the Pine Knot Mine. Such recharge produced small changes in mine pool level and rapid changes in tunnel flow rate because of extensive unsaturated storage capacity and high transmissivity within the mine complex. Thus, elimination of stream leakage could have a small effect on the annual discharge from the tunnel, but a large effect on peak discharge and associated water quality in streams.

Choice and Design of Adjuvants for Parenteral and Mucosal Vaccines

PubMed Central

Savelkoul, Huub F. J.; Ferro, Valerie A.; Strioga, Marius M.; Schijns, Virgil E. J. C.

2015-01-01

The existence of pathogens that escape recognition by specific vaccines, the need to improve existing vaccines and the increased availability of therapeutic (non-infectious disease) vaccines necessitate the rational development of novel vaccine concepts based on the induction of protective cell-mediated immune responses. For naive T-cell activation, several signals resulting from innate and adaptive interactions need to be integrated, and adjuvants may interfere with some or all of these signals. Adjuvants, for example, are used to promote the immunogenicity of antigens in vaccines, by inducing a pro-inflammatory environment that enables the recruitment and promotion of the infiltration of phagocytic cells, particularly antigen-presenting cells (APC), to the injection site. Adjuvants can enhance antigen presentation, induce cytokine expression, activate APC and modulate more downstream adaptive immune reactions (vaccine delivery systems, facilitating immune Signal 1). In addition, adjuvants can act as immunopotentiators (facilitating Signals 2 and 3) exhibiting immune stimulatory effects during antigen presentation by inducing the expression of co-stimulatory molecules on APC. Together, these signals determine the strength of activation of specific T-cells, thereby also influencing the quality of the downstream T helper cytokine profiles and the differentiation of antigen-specific T helper populations (Signal 3). New adjuvants should also target specific (innate) immune cells in order to facilitate proper activation of downstream adaptive immune responses and homing (Signal 4). It is desirable that these adjuvants should be able to exert such responses in the context of mucosal administered vaccines. This review focuses on the understanding of the potential working mechanisms of the most well-known classes of adjuvants to be used effectively in vaccines. PMID:26344951

Modeling CO2 degassing and pH in a stream-aquifer system

USGS Publications Warehouse

Choi, J.; Hulseapple, S.M.; Conklin, M.H.; Harvey, J.W.

1998-01-01

Pinal Creek, Arizona receives an inflow of ground water with high dissolved inorganic carbon (57-75 mg/l) and low pH (5.8-6.3). There is an observed increase of in-stream pH from approximately 6.0-7.8 over the 3 km downstream of the point of groundwater inflow. We hypothesized that CO2 gas-exchange was the most important factor causing the pH increase in this stream-aquifer system. An existing transport model, for coupled ground water-surface water systems (OTIS), was modified to include carbonate equilibria and CO2 degassing, used to simulate alkalinity, total dissolved inorganic carbon (C(T)), and pH in Pinal Creek. Because of the non-linear relation between pH and C(T), the modified transport model used the numerical iteration method to solve the non-linearity. The transport model parameters were determined by the injection of two tracers, bromide and propane. The resulting simulations of alkalinity, C(T) and pH reproduced, without fitting, the overall trends in downstream concentrations. A multi-parametric sensitivity analysis (MPSA) was used to identify the relative sensitivities of the predictions to six of the physical and chemical parameters used in the transport model. MPSA results implied that C(T) and pH in stream water were controlled by the mixing of ground water with stream water and CO2 degassing. The relative importance of these two processes varied spatially depending on the hydrologic conditions, such as stream flow velocity and whether a reach gained or lost stream water caused by the interaction with the ground water. The coupled transport model with CO2 degassing and generalized sensitivity analysis presented in this study can be applied to evaluate carbon transport and pH in other coupled stream-ground water systems.An existing transport model for coupled groundwater-surface water systems was modified to include carbonate equilibria and CO2 degassing. The modified model was used to simulate alkalinity, total dissolved inorganic carbon (CT) and pH in Pinal Creek. The model used the numerical iteration method to solve the nonlinear relation between pH and CT. A multi-parametric sensitivity analysis (MPSA) was used to identify the relative sensitivities of the predictions to six of the physical and chemical parameters used in the transport model. MPSA results implied that CT and pH in the stream water were controlled by the mixing of groundwater with stream water and CO2 degassing.

Lignocellulosic biorefinery as a model for sustainable development of biofuels and value added products.

PubMed

De Bhowmick, Goldy; Sarmah, Ajit K; Sen, Ramkrishna

2018-01-01

A constant shift of society's dependence from petroleum-based energy resources towards renewable biomass-based has been the key to tackle the greenhouse gas emissions. Effective use of biomass feedstock, particularly lignocellulosic, has gained worldwide attention lately. Lignocellulosic biomass as a potent bioresource, however, cannot be a sustainable alternative if the production cost is too high and/ or the availability is limited. Recycling the lignocellulosic biomass from various sources into value added products such as bio-oil, biochar or other biobased chemicals in a bio-refinery model is a sensible idea. Combination of integrated conversion techniques along with process integration is suggested as a sustainable approach. Introducing 'series concept' accompanying intermittent dark/photo fermentation with co-cultivation of microalgae is conceptualised. While the cost of downstream processing for a single type of feedstock would be high, combining different feedstocks and integrating them in a bio-refinery model would lessen the production cost and reduce CO 2 emission. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hot-melt co-extrusion: requirements, challenges and opportunities for pharmaceutical applications.

PubMed

Vynckier, An-Katrien; Dierickx, Lien; Voorspoels, Jody; Gonnissen, Yves; Remon, Jean Paul; Vervaet, Chris

2014-02-01

Co-extrusion implies the simultaneous hot-melt extrusion of two or more materials through the same die, creating a multi-layered extrudate. It is an innovative continuous production technology that offers numerous advantages over traditional pharmaceutical processing techniques. This review provides an overview of the co-extrusion equipment, material requirements and medical and pharmaceutical applications. The co-extrusion equipment needed for pharmaceutical production has been summarized. Because the geometrical design of the die dictates the shape of the final product, different die types have been discussed. As one of the major challenges at the moment is shaping the final product in a continuous way, an overview of downstream solutions for processing co-extrudates into drug products is provided. Layer adhesion, extrusion temperature and viscosity matching are pointed out as most important requirements for material selection. Examples of medical and pharmaceutical applications are presented and some recent findings considering the production of oral drug delivery systems have been summarized. Co-extrusion provides great potential for the continuous production of fixed-dose combination products which are gaining importance in pharmaceutical industry. There are still some barriers to the implementation of co-extrusion in the pharmaceutical industry. The optimization of downstream processing remains a point of attention. © 2013 Royal Pharmaceutical Society.

Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grbčić, Petra; Tomljanović, Ivana; Klobučar, Marko

Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells. Here, we report that co-administration of 5-FU andmore » SKI-II at low sub-toxic concentrations of 20 μM and 5 μM, respectively, synergistically inhibit cell proliferation, markedly reduce cell migration and the clonogenic survival, and increase apoptosis induction in HepG2 cells. Additional Western blot analyses have shown that possible mechanisms underlying enhanced sensitivity to 5-FU induced by dual Sphk 1/2 inhibition could include abrogation of FAK-regulated IGF-1R activity and down-regulation of osteopontin expression culminating in the inhibition of NF-κB activity and its downstream signalling mediated by sirtuin 1 and p38 MAPK. Our results clearly show that pharmacological blockade of both Sphk isoforms represents a promising strategy to boost the anti-tumour efficacy of 5-FU and provide a rationale for further in vivo studies into the possible use of SKI-II inhibitor as an adjunct to 5-FU treatment in HCC. - Highlights: • Pharmacological inhibition of sphingosine kinase 1/2 augments cytotoxic effects of 5-FU in HepG2 cells. • Co-administration of 5-FU and SKI-II synergistically inhibits cell proliferation, reduces cell migration and clonogenic survival and increases apoptosis induction in HepG2 cells. • The mechanism underlying chemosensitization effects includes attenuation of FAK/IGF-1R and osteopontin signaling leading to the inhibition of NF-κB activity and its downstream targets SIRT1 and p38 MAPK.« less

Tollmien-Schlichting/vortex interactions in compressible boundary layer flows

NASA Technical Reports Server (NTRS)

Blackaby, Nicholas D.

1993-01-01

The weakly nonlinear interaction of oblique Tollmien-Schlichting waves and longitudinal vortices in compressible, high Reynolds number, boundary-layer flow over a flat plate is considered for all ranges of the Mach number. The interaction equations comprise of equations for the vortex which is indirectly forced by the waves via a boundary condition, whereas a vortex term appears in the amplitude equation for the wave pressure. The downstream solution properties of interaction equations are found to depend on the sign of an interaction coefficient. Compressibility is found to have a significant effect on the interaction properties; principally through its impact on the waves and their governing mechanism, the triple-deck structure. It is found that, in general, the flow quantities will grow slowly with increasing downstream co-ordinate; i.e. in general, solutions do not terminate in abrupt, finite-distance 'break-ups'.

Intracellular implantation of enzymes in hollow silica nanospheres for protein therapy: cascade system of superoxide dismutase and catalase.

PubMed

Chang, Feng-Peng; Chen, Yi-Ping; Mou, Chung-Yuan

2014-11-01

An approach for enzyme therapeutics is elaborated with cell-implanted nanoreactors that are based on multiple enzymes encapsulated in hollow silica nanospheres (HSNs). The synthesis of HSNs is carried out by silica sol-gel templating of water-in-oil microemulsions so that polyethyleneimine (PEI) modified enzymes in aqueous phase are encapsulated inside the HSNs. PEI-grafted superoxide dismutase (PEI-SOD) and catalase (PEI-CAT) encapsulated in HSNs are prepared with quantitative control of the enzyme loadings. Excellent activities of superoxide dismutation by PEI-SOD@HSN are found and transformation of H2 O2 to water by PEI-CAT@HSN. When PEI-SOD and PEI-CAT are co-encapsulated, cascade transformation of superoxide through hydrogen peroxide to water was facile. Substantial fractions of HSNs exhibit endosome escape to cytosol after their delivery to cells. The production of downstream reactive oxygen species (ROS) and COX-2/p-p38 expression show that co-encapsulated SOD/CAT inside the HSNs renders the highest cell protection against the toxicant N,N'-dimethyl-4,4'-bipyridinium dichloride (paraquat). The rapid cell uptake and strong detoxification effect on superoxide radicals by the SOD/CAT-encapsulated hollow mesoporous silica nanoparticles demonstrate the general concept of implanting catalytic nanoreactors in biological cells with designed functions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MEK1 inhibits cardiac PPARα activity by direct interaction and prevents its nuclear localization.

PubMed

el Azzouzi, Hamid; Leptidis, Stefanos; Bourajjaj, Meriem; van Bilsen, Marc; da Costa Martins, Paula A; De Windt, Leon J

2012-01-01

The response of the postnatal heart to growth and stress stimuli includes activation of a network of signal transduction cascades, including the stress activated protein kinases such as p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK) and the extracellular signal-regulated kinase (ERK1/2) pathways. In response to increased workload, the mitogen-activated protein kinase kinase (MAPKK) MEK1 has been shown to be active. Studies embarking on mitogen-activated protein kinase (MAPK) signaling cascades in the heart have indicated peroxisome-proliferators activated-receptors (PPARs) as downstream effectors that can be regulated by this signaling cascade. Despite the importance of PPARα in controlling cardiac metabolism, little is known about the relationship between MAPK signaling and cardiac PPARα signaling. Using co-immunoprecipitation and immunofluorescence approaches we show a complex formation of PPARα with MEK1 and not with ERK1/2. Binding of PPARα to MEK1 is mediated via a LXXLL motif and results in translocation from the nucleus towards the cytoplasm, hereby disabling the transcriptional activity of PPARα. Mice subjected to voluntary running-wheel exercise showed increased cardiac MEK1 activation and complex formation with PPARα, subsequently resulting in reduced PPARα activity. Inhibition of MEK1, using U0126, blunted this effect. Here we show that activation of the MEK1-ERK1/2 pathway leads to specific inhibition of PPARα transcriptional activity. Furthermore we show that this inhibitory effect is mediated by MEK1, and not by its downstream effector kinase ERK1/2, through a mechanism involving direct binding to PPARα and subsequent stimulation of PPARα export from the nucleus.

10 CFR 431.76 - Uniform test method for the measurement of energy efficiency of commercial warm air furnaces.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 431.75) you must locate one or two sampling tubes within six inches downstream from the flue....75). If you use an open end tube, it must project into the flue one-third of the chimney connector diameter. If you use other methods of sampling CO2, you must place the sampling tube so as to obtain an...

High-efficiency power production from natural gas with carbon capture

NASA Astrophysics Data System (ADS)

Adams, Thomas A.; Barton, Paul I.

A unique electricity generation process uses natural gas and solid oxide fuel cells at high electrical efficiency (74%HHV) and zero atmospheric emissions. The process contains a steam reformer heat-integrated with the fuel cells to provide the heat necessary for reforming. The fuel cells are powered with H 2 and avoid carbon deposition issues. 100% CO 2 capture is achieved downstream of the fuel cells with very little energy penalty using a multi-stage flash cascade process, where high-purity water is produced as a side product. Alternative reforming techniques such as CO 2 reforming, autothermal reforming, and partial oxidation are considered. The capital and energy costs of the proposed process are considered to determine the levelized cost of electricity, which is low when compared to other similar carbon capture-enabled processes.

Effects of Consumer Interactions on Benthic Resources and Ecosystem Processes in a Neotropical Stream

PubMed Central

Marshall, Michael C.; Binderup, Andrew J.; Zandonà, Eugenia; Goutte, Sandra; Bassar, Ronald D.; El-Sabaawi, Rana W.; Thomas, Steven A.; Flecker, Alexander S.; Kilham, Susan S.; Reznick, David N.; Pringle, Cathy M.

2012-01-01

The effect of consumers on their resources has been demonstrated in many systems but is often confounded by trophic interactions with other consumers. Consumers may also have behavioral and life history adaptations to each other and to co-occurring predators that may additionally modulate their particular roles in ecosystems. We experimentally excluded large consumers from tile periphyton, leaves and natural benthic substrata using submerged electrified frames in three stream reaches with overlapping consumer assemblages in Trinidad, West Indies. Concurrently, we assessed visits to (non-electrified) control frames by the three most common large consumers–primarily insectivorous killifish (Rivulus hartii), omnivorous guppies (Poecilia reticulata) and omnivorous crabs (Eudaniela garmani). Consumers caused the greatest decrease in final chlorophyll a biomass and accrual rates the most in the downstream reach containing all three focal consumers in the presence of fish predators. Consumers also caused the greatest increase in leaf decay rates in the upstream reach containing only killifish and crabs. In the downstream reach where guppies co-occur with predators, we found significantly lower benthic invertebrate biomass in control relative to exclosure treatments than the midstream reach where guppies occur in the absence of predators. These data suggest that differences in guppy foraging, potentially driven by differences in their life history phenotype, may affect ecosystem structure and processes as much as their presence or absence and that interactions among consumers may further mediate their effects in these stream ecosystems. PMID:23028865

Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway.

PubMed

Ziosi, Marcello; Di Meo, Ivano; Kleiner, Giulio; Gao, Xing-Huang; Barca, Emanuele; Sanchez-Quintero, Maria J; Tadesse, Saba; Jiang, Hongfeng; Qiao, Changhong; Rodenburg, Richard J; Scalais, Emmanuel; Schuelke, Markus; Willard, Belinda; Hatzoglou, Maria; Tiranti, Valeria; Quinzii, Catarina M

2017-01-01

Coenzyme Q (CoQ) is an electron acceptor for sulfide-quinone reductase (SQR), the first enzyme of the hydrogen sulfide oxidation pathway. Here, we show that lack of CoQ in human skin fibroblasts causes impairment of hydrogen sulfide oxidation, proportional to the residual levels of CoQ. Biochemical and molecular abnormalities are rescued by CoQ supplementation in vitro and recapitulated by pharmacological inhibition of CoQ biosynthesis in skin fibroblasts and ADCK3 depletion in HeLa cells. Kidneys of Pdss2 kd/kd mice, which only have ~15% residual CoQ concentrations and are clinically affected, showed (i) reduced protein levels of SQR and downstream enzymes, (ii) accumulation of hydrogen sulfides, and (iii) glutathione depletion. These abnormalities were not present in brain, which maintains ~30% residual CoQ and is clinically unaffected. In Pdss2 kd/kd mice, we also observed low levels of plasma and urine thiosulfate and increased blood C4-C6 acylcarnitines. We propose that impairment of the sulfide oxidation pathway induced by decreased levels of CoQ causes accumulation of sulfides and consequent inhibition of short-chain acyl-CoA dehydrogenase and glutathione depletion, which contributes to increased oxidative stress and kidney failure. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Reactive transport of CO2-rich fluids in simulated wellbore interfaces: Experiments and models exploring behaviour on length scales of 1 to 6 m

NASA Astrophysics Data System (ADS)

Wolterbeek, T. K. T.; Raoof, A.; Peach, C. J.; Spiers, C. J.

2016-12-01

Defects present at casing-cement interfaces in wellbores constitute potential pathways for CO2 to migrate from geological storage systems. It is essential to understand how the transport properties of such pathways evolve when penetrated by CO2-rich fluids. While numerous studies have explored this problem at the decimetre length-scale, the 1-10-100 m scales relevant for real wellbores have received little attention. The present work addresses the effects of long-range reactive transport on a length scale of 1-6 m. This is done by means of a combined experimental and modelling study. The experimental work consisted of flow-through tests, performed on cement-filled steel tubes, 1-6 m in length, containing artificially debonded cement-interfaces. Four tests were performed, at 60-80 °C, imposing flow-through of CO2-rich fluid at mean pressures of 10-15 MPa, controlling the pressure difference at 0.12-4.8 MPa, while measuring flow-rate. In the modelling work, we developed a numerical model to explore reactive transport in CO2-exposed defects on a similar length scale. The formulation adopted incorporates fluid flow, advective and diffusive solute transport, and CO2-cement chemical reactions. Our results show that long-range reactive transport strongly affects the permeability evolution of CO2-exposed defects. In the experiments, sample permeability decreased by 2-4 orders, which microstructural observations revealed was associated with downstream precipitation of carbonates, possibly aided by migration of fines. The model simulations show precipitation in initially open defects produces a sharp decrease in flow rate, causing a transition from advection to diffusion-dominated reactive transport. While the modelling results broadly reproduce the experimental observations, it is further demonstrated that non-uniformity in initial defect aperture has a profound impact on self-sealing behaviour and system permeability evolution on the metre scale. The implication is that future reactive transport models and wellbore scale analyses must include defects with variable aperture in order to obtain reliable upscaling relations.

A Novel Method of Measuring the Phase Behavior and Rheology of Polyethylene Solutions Using a Multi-Pass Rheometer

NASA Astrophysics Data System (ADS)

Lee, Karen; Lacombe, Y.; Cheluget, E.

2008-07-01

The Advanced SCLAIRTECH™ Technology process is used to manufacture Linear Low Density Polyethylene using solution polymerization. In this process ethylene is polymerized in an inert solvent, which is subsequently evaporated and recycled. The reactor effluent in the process is a polymer solution containing the polyethylene product, which is separated from the solvent and unconverted ethylene/co-monomer before being extruded and pelletized. The design of unit operations in this process requires a detailed understanding of the thermophysical properties, phase behaviour and rheology of polymer containing streams at high temperature and pressure, and over a wide range of composition. This paper describes a device used to thermo-rheologically characterize polymer solutions under conditions prevailing in polymerization reactors, downstream heat exchangers and attendant phase separation vessels. The downstream processing of the Advanced SCLAIRTECH™ Technology reactor effluent occurs at temperatures and pressures near the critical point of the solvent and co-monomer mixture. In addition, the process trajectory encompasses regions of liquid-liquid and liquid-liquid-vapour co-existence, which are demarcated by a `cloud point' curve. Knowing the location of this phase boundary is essential for the design of downstream devolatilization processes and for optimizing operating conditions in existing plants. In addition, accurate solution rheology data are required for reliable equipment sizing and design. At NOVA Chemicals, a robust high-temperature and high-pressure-capable version of the Multi-Pass Rheometer (MPR) is used to provide data on solution rheology and phase boundary location. This sophisticated piece of equipment is used to quantify the effects of solvent types, comonomer, and free ethylene concentration on the properties of the reactor effluent. An example of the experimental methodology to characterize a polyethylene solution with hexane solvent, and the ethylene dosing technique developed for the MPR will be described. ™Advanced SCLAIRTECH is a trademark of NOVA Chemicals.

Large-eddy substitution via vortex cancellation for wall turbulence control

NASA Technical Reports Server (NTRS)

Mcginley, C. B.; Beeler, G. B.

1985-01-01

A system of co-rotating longitudinal vortices was used to introduce streamline (as opposed to wall) curvature into a turbulent wall flow. Two methods of vortex cancellation, unwinding and self-annihilation, were tested as a means of removing the vortices once they had processed most of the incoming turbulent boundary layer. Vortex unwinding, which uses vorticity of the opposite sign, was shown to be a viable method for cancelling the co-rotating vortices. Vortex self-annihilation, caused by interference effects resulting from a close initial spanwise vortex spacing, eliminated the vortices within 60 delta downstream. In each case, reductions in boundary layer entrainment were found once the vortices were cancelled.

Lithium and carbon isotopes in river catchment: combined tracers to constrain chemical weathering processes

NASA Astrophysics Data System (ADS)

Rad, S.; Rive, K.; Assayag, N.; Dictor, M.; Garcin, M.

2012-12-01

Water-rock interactions produced in river catchment are accompanied by fractionation or changes in stable isotopes such as H, Li, C and O during chemical weathering processes. Li is a fluid-mobile element that tends to preferentially partition into the fluid phase during water-rock interaction. The relative mass difference between the two isotopes is considerable, generating large mass dependent fractionation during chemical weathering processes. The CO2 dissolves into the water providing the main acid that attack the rock during chemical weathering. Carbon stable isotopes and concentration of Dissolved Inorganic Carbon (DIC) in the river catchment can be used to determine the origin and consumption rates of CO2. In the present work, stable isotopes were analyzed in Allier River, one of the major river basins of France. The lithology is dominated by granite rocks within current upstream, while it is mainly basaltic and Oligocene sediments in the downstream with hydrothermal manifestations. We propose a new isotopic approach by combining δ7Li and δ13CDIC analyses in river catchment waters. A first method has been applied to volcanic tropical environments with Li concentrations correlated to δ13CDIC (Rad et al., 2011). Here, we have completed this approach by lithium isotopes. Water samples were collected during several field trips. Our results show a large variation in Li isotopes and C isotopes within the catchment from 3.3 ‰ to 30.3 ‰ and from -17.9‰ to -3.5‰, respectively. Chemical weathering rates linearly increase from upstream to downstream over 400km distance, whereas Li isotope signatures decrease and global C signature increases. This is due to low water-rock interaction dominated in upstream, whereas the downstream is punctually impacted by hydrothermalism. From Li and C isotopes, our results show 4 groups reflecting different chemical weathering processes: the first group with high fractionation of Li and C, for Li, the heavy lithium partitioned into surface waters, leaving lighter lithium behind in the weathered products, the signature of C is mainly due to organic matter or partially due to biochemical interaction with assimilation of CO2 by microorganism. The second group involves atmospheric equilibrium with CO2 degassing with organic origin or "cold" CO2 degassing with important fraction of Li. The third group present high fractionation of C, reflecting presence of superficial C with organic origin, with low fractionation of Li underling the hydrothermalism impact. Finally a fourth group with low fractionation mainly due to high temperature water-rock interaction. Therefore, the combination of the two tracers, Li and C isotopes, offers a powerful tool to discriminate chemical weathering processes from sources of alteration during water-rock interactions under multi-lithology terrains. Reference: Rad, S., Rivé, K., Allègre, C.J., 2011. Weathering regime associated with subsurface circulation on volcanic islands. Aquat. Geochem. 17, 3, 221-241.

Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport.

PubMed

Yang, Chendong; Ko, Bookyung; Hensley, Christopher T; Jiang, Lei; Wasti, Ajla T; Kim, Jiyeon; Sudderth, Jessica; Calvaruso, Maria Antonietta; Lumata, Lloyd; Mitsche, Matthew; Rutter, Jared; Merritt, Matthew E; DeBerardinis, Ralph J

2014-11-06

Alternative modes of metabolism enable cells to resist metabolic stress. Inhibiting these compensatory pathways may produce synthetic lethality. We previously demonstrated that glucose deprivation stimulated a pathway in which acetyl-CoA was formed from glutamine downstream of glutamate dehydrogenase (GDH). Here we show that import of pyruvate into the mitochondria suppresses GDH and glutamine-dependent acetyl-CoA formation. Inhibiting the mitochondrial pyruvate carrier (MPC) activates GDH and reroutes glutamine metabolism to generate both oxaloacetate and acetyl-CoA, enabling persistent tricarboxylic acid (TCA) cycle function. Pharmacological blockade of GDH elicited largely cytostatic effects in culture, but these effects became cytotoxic when combined with MPC inhibition. Concomitant administration of MPC and GDH inhibitors significantly impaired tumor growth compared to either inhibitor used as a single agent. Together, the data define a mechanism to induce glutaminolysis and uncover a survival pathway engaged during compromised supply of pyruvate to the mitochondria. Copyright © 2014 Elsevier Inc. All rights reserved.

Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport

PubMed Central

Yang, Chendong; Ko, Bookyung; Hensley, Christopher T.; Jiang, Lei; Wasti, Ajla T.; Kim, Jiyeon; Sudderth, Jessica; Calvaruso, Maria Antonietta; Lumata, Lloyd; Mitsche, Matthew; Rutter, Jared; Merritt, Matthew E.; DeBerardinis, Ralph J.

2014-01-01

Summary Alternative modes of metabolism enable cells to resist metabolic stress. Inhibiting these compensatory pathways may produce synthetic lethality. We previously demonstrated that glucose deprivation stimulated a pathway in which acetyl-CoA was formed from glutamine downstream of glutamate dehydrogenase (GDH). Here we show that import of pyruvate into the mitochondria suppresses GDH and glutamine-dependent acetyl-CoA formation. Inhibiting the mitochondrial pyruvate carrier (MPC) activates GDH and re-routes glutamine metabolism to generate both oxaloacetate and acetyl-CoA, enabling persistent tricarboxylic acid (TCA) cycle function. Pharmacological blockade of GDH elicited largely cytostatic effects in culture, but these effects became cytotoxic when combined with MPC inhibition. Concomitant administration of MPC and GDH inhibitors significantly impaired tumor growth compared to either inhibitor used as a single agent. Together, the data define a mechanism to induce glutaminolysis and uncover a survival pathway engaged during compromised supply of pyruvate to the mitochondria. PMID:25458842

Jet Mixing in a Reacting Cylindrical Crossflow

NASA Technical Reports Server (NTRS)

Leong, M. Y.; Samuelsen, G. S.; Holdeman, J. D.

1995-01-01

This paper addresses the mixing of air jets into the hot, fuel-rich products of a gas turbine primary zone. The mixing, as a result, occurs in a reacting environment with chemical conversion and substantial heat release. The geometry is a crossflow confined in a cylindrical duct with side-wall injection of jets issuing from round orifices. A specially designed reactor, operating on propane, presents a uniform mixture without swirl to mixing modules consisting of 8, 9, 10, and 12 holes at a momentum-flux ratio of 57 and a jet-to-mainstream mass-flow ratio of 2.5. Concentrations of O2, CO2, CO, and HC are obtained upstream, downstream, and within the orifice plane. O2 profiles indicate jet penetration while CO2, CO, and HC profiles depict the extent of reaction. Jet penetration is observed to be a function of the number of orifices and is found to affect the mixing in the reacting system. The results demonstrate that one module (the 12-hole) produces near-optimal penetration defined here as a jet penetration closest to the module half-radius, and hence the best uniform mixture at a plane one duct radius from the orifice leading edge.

Integrated Biomass Gasification with Catalytic Partial Oxidation for Selective Tar Conversion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Lingzhi; Wei, Wei; Manke, Jeff

Biomass gasification is a flexible and efficient way of utilizing widely available domestic renewable resources. Syngas from biomass has the potential for biofuels production, which will enhance energy security and environmental benefits. Additionally, with the successful development of low Btu fuel engines (e.g. GE Jenbacher engines), syngas from biomass can be efficiently used for power/heat co-generation. However, biomass gasification has not been widely commercialized because of a number of technical/economic issues related to gasifier design and syngas cleanup. Biomass gasification, due to its scale limitation, cannot afford to use pure oxygen as the gasification agent that used in coal gasification.more » Because, it uses air instead of oxygen, the biomass gasification temperature is much lower than well-understood coal gasification. The low temperature leads to a lot of tar formation and the tar can gum up the downstream equipment. Thus, the biomass gasification tar removal is a critical technology challenge for all types of biomass gasifiers. This USDA/DOE funded program (award number: DE-FG36-O8GO18085) aims to develop an advanced catalytic tar conversion system that can economically and efficiently convert tar into useful light gases (such as syngas) for downstream fuel synthesis or power generation. This program has been executed by GE Global Research in Irvine, CA, in collaboration with Professor Lanny Schmidt's group at the University of Minnesota (UoMn). Biomass gasification produces a raw syngas stream containing H2, CO, CO2, H2O, CH4 and other hydrocarbons, tars, char, and ash. Tars are defined as organic compounds that are condensable at room temperature and are assumed to be largely aromatic. Downstream units in biomass gasification such as gas engine, turbine or fuel synthesis reactors require stringent control in syngas quality, especially tar content to avoid plugging (gum) of downstream equipment. Tar- and ash-free syngas streams are a critical requirement for commercial deployment of biomass-based power/heat co-generation and biofuels production. There are several commonly used syngas clean-up technologies: (1) Syngas cooling and water scrubbing has been commercially proven but efficiency is low and it is only effective at small scales. This route is accompanied with troublesome wastewater treatment. (2) The tar filtration method requires frequent filter replacement and solid residue treatment, leading to high operation and capital costs. (3) Thermal destruction typically operates at temperatures higher than 1000oC. It has slow kinetics and potential soot formation issues. The system is expensive and materials are not reliable at high temperatures. (4) In-bed cracking catalysts show rapid deactivation, with durability to be demonstrated. (5) External catalytic cracking or steam reforming has low thermal efficiency and is faced with problematic catalyst coking. Under this program, catalytic partial oxidation (CPO) is being evaluated for syngas tar clean-up in biomass gasification. The CPO reaction is exothermic, implying that no external heat is needed and the system is of high thermal efficiency. CPO is capable of processing large gas volume, indicating a very compact catalyst bed and a low reactor cost. Instead of traditional physical removal of tar, the CPO concept converts tar into useful light gases (eg. CO, H2, CH4). This eliminates waste treatment and disposal requirements. All those advantages make the CPO catalytic tar conversion system a viable solution for biomass gasification downstream gas clean-up. This program was conducted from October 1 2008 to February 28 2011 and divided into five major tasks. - Task A: Perform conceptual design and conduct preliminary system and economic analysis (Q1 2009 ~ Q2 2009) - Task B: Biomass gasification tests, product characterization, and CPO tar conversion catalyst preparation. This task will be conducted after completing process design and system economics analysis. Major milestones include identification of syngas cleaning requirements for proposed system design, identification and selection of tar compounds and 2 mixtures for use in CPO tests, and preparation of CPO catalysts for validation. (Q3 2009 ~ Q4 2009) - Task C: Test CPO with biomass gasification product gas. Optimize CPO performance with selected tar compounds. Optimize CPO performance with multi-component mixtures. Milestones include optimizing CPO catalysts design, collecting CPO experimental data for next stage kinetic modeling and understanding the effect of relative reactivities on ultimate tar conversion and syngas yields. (Q1 2010 ~ Q3 2010) - Task D: Develop tar CPO kinetic model with CPO kinetic model and modeling results as deliverables. (Q3 2010 ~ Q2 2011) - Task E: Project management and reporting. Milestone: Quarterly reports and presentations, final report, work presented at national technical conferences (Q1 2009 ~ Q2 2011) At the beginning of the program, IP landscaping was conducted to understand the operation of various types of biomass gasifiers, their unique syngas/tar compositions and potential tar mitigation options using the catalytic partial oxidation technology. A process simulation model was developed to quantify the system performance and economics impact of CPO tar removal technology. Biomass gasification product compositions used for performance evaluation tests were identified after literature review and system modeling. A reaction system for tar conversion tests was designed, constructed, with each individual component shaken-down in 2009. In parallel, University of Minnesota built a lab-scale unit and evaluated the tar removal performance using catalytic reforming. Benzene was used as the surrogate compound. The biomass gasification raw syngas composition was provided by GE through system studies. In 2010, GE selected different tar compounds and evaluated the tar removal effectiveness of the CPO catalyst. The catalytic performance was evaluated under different operating conditions, including catalyst geometry, S/C ratio, O/C ratio, GHSV, and N2 dilution. An understanding of how to optimize catalytic tar removal efficiency by varying operating conditions has been developed. GE collaborated with UoMn in examining inorganic impurities effects. Catalysts were pre-impregnated with inorganic impurities commonly present in biomass gasification syngas, including Si, Ca, Mg, Na, K, P and S. UoMn performed catalyst characterization and has acquired fundamental understandings of impurities effect on catalytic tar removal. Based on experimental data and the proposed reaction pathway, GE constructed a model to predict kinetic performance for biomass gasification tar cleanup process. Experimental data (eg. tar conversion, reactor inlet and outlet temperatures, product distribution) at different operating conditions were used to validate the model. A good fit between model predictions and experimental data was found. This model will be a valuable tool in designing the tar removal reactor and identifying appropriate operating conditions. We attended the 2011 DOE Biomass Program Thermochemical Platform Review held in Denver, CO from February 16 to 18 and received very positive comments from the review panel. Further, syngas utility and biomass to power/fuel companies expressed strong interest in our tar removal technology.« less

The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways*

PubMed Central

Kovacevic, Zaklina; Menezes, Sharleen V.; Sahni, Sumit; Kalinowski, Danuta S.; Bae, Dong-Hun; Lane, Darius J. R.; Richardson, Des R.

2016-01-01

N-MYC downstream-regulated gene-1 (NDRG1) is a potent growth and metastasis suppressor that acts through its inhibitory effects on a wide variety of cellular signaling pathways, including the TGF-β pathway, protein kinase B (AKT)/PI3K pathway, RAS, etc. To investigate the hypothesis that its multiple effects could be regulated by a common upstream effector, the role of NDRG1 on the epidermal growth factor receptor (EGFR) and other members of the ErbB family, namely human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3), was examined. We demonstrate that NDRG1 markedly decreased the expression and activation of EGFR, HER2, and HER3 in response to the epidermal growth factor (EGF) ligand, while also inhibiting formation of the EGFR/HER2 and HER2/HER3 heterodimers. In addition, NDRG1 also decreased activation of the downstream MAPKK in response to EGF. Moreover, novel anti-tumor agents of the di-2-pyridylketone class of thiosemicarbazones, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone and di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone, which markedly up-regulate NDRG1, were found to inhibit EGFR, HER2, and HER3 expression and phosphorylation in cancer cells. However, the mechanism involved appeared dependent on NDRG1 for di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone, but was independent of this metastasis suppressor for di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone. This observation demonstrates that small structural changes in thiosemicarbazones result in marked alterations in molecular targeting. Collectively, these results reveal a mechanism for the extensive downstream effects on cellular signaling attributed to NDRG1. Furthermore, this study identifies a novel approach for the treatment of tumors resistant to traditional EGFR inhibitors. PMID:26534963

Experimental study on the CO2-flow mechanism in the two different sandstones

NASA Astrophysics Data System (ADS)

Imasato, M.; Honda, H.; Kitamura, K.

2016-12-01

It is important to discuss the flow properties of CO2 in the reservoir for estimations of storage potential and safety of CCS operation. In this study, we conducted the CO2-injection tests into two different types of porous sandstones with extremely low CO2 flow rate (10µl/min) under supercritical CO2 conditions. It was measured CO2 saturation (SCO2) and differential pressure (ΔP) between upstream and downstream of specimen. It was also monitored P-wave velocity (Vp) and electrical impedance (Z) for the monitoring of CO2 behavior in the specimen. We set three Vp measurement lines in different height for monitoring the movement of CO2 front. The results of ΔP measurement indicated that the Berea sandstone showed no obvious change, but the Ainoura sandstone was increasing gradually and peaked in 73 hours. After that, ΔP of the Ainoura sandstone started reducing. Both sandstones showed stepwise Vp-reduction from the bottom Vp-measurement line, which is near CO2 injection end. There are large differences of CO2 arrival time at the bottom line between Berea and Ainoura sandstone. In case of Ainoura sandstone, it took 29 hours to reduce Vp which is the nearest to CO2 injection end, but in case of Berea sandstone, it took 3.3 hours. This is also confirmed the arrival time at the top channel, 2.5 hours in the Berea sandstone and 11 hours in the Ainoura sandstone. The impedances of both sandstones indicted the gradual increment. It took 25 hours to become constant in the Berea sandstone and 148 hours in the Ainoura sandstone. SCO2 of the Berea sandstone was about 6% and Ainoura sandstone reached over 20%. These results suggest that it is due to the difference of the pore structure of Berea sandstone and Ainoura sandstone.

Fatty Acid Synthase Mediates the Epithelial-Mesenchymal Transition of Breast Cancer Cells

PubMed Central

Li, Junqin; Dong, Lihua; Wei, Dapeng; Wang, Xiaodong; Zhang, Shuo; Li, Hua

2014-01-01

This study aimed to investigate the role of fatty acid synthase (FASN) in the epithelial-mesenchymal transition (EMT) of breast cancer cells. MCF-7 cells and MCF-7 cells overexpressing mitogen-activated protein kinase 5 (MCF-7-MEK5) were used in this study. MCF-7-MEK5 cells showed stable EMT characterized by increased vimentin and decreased E-cadherin expression. An In vivo animal model was established using the orthotopic injection of MCF-7 or MCF-7-MEK5 cells. Real-time quantitative PCR and western blotting were used to detect the expression levels of FASN and its downstream proteins liver fatty acid-binding protein (L-FABP) and VEGF/VEGFR-2 in both in vitro and in vivo models (nude mouse tumor tissues). In MCF-7-MEK5 cells, significantly increased expression of FASN was associated with increased levels of L-FABP and VEGF/VEGFR-2. Cerulenin inhibited MCF-7-MEK5 cell migration and EMT, and reduced FASN expression and down-stream proteins L-FABP, VEGF, and VEGFR-2. MCF-7-MEK5 cells showed higher sensitivity to Cerulenin than MCF-7 cells. Immunofluorescence revealed an increase of co-localization of FASN with VEGF on the cell membrane and with L-FABP within MCF-7-MEK5 cells. Immunohistochemistry further showed that increased percentage of FASN-positive cells in the tumor tissue was associated with increased percentages of L-FABP- and VEGF-positive cells and the Cerulenin treatment could reverse the effect. Altogether, our results suggest that FASN is essential to EMT possibly through regulating L-FABP, VEGF and VEGFR-2. This study provides a theoretical basis and potential strategy for effective suppression of malignant cells with EMT. PMID:24520215

Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK

PubMed Central

Niu, Yucun; Li, Songtao; Na, Lixin; Feng, Rennan; Liu, Liyan; Li, Ying; Sun, Changhao

2012-01-01

Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism. PMID:22292039

Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules.

PubMed

Pradip, De; Bouzyk, Mark; Dey, Nandini; Leyland-Jones, Brian

2013-01-01

Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.

Responses of macroinvertebrate community metrics to a wastewater discharge in the Upper Blue River of Kansas and Missouri, USA

USGS Publications Warehouse

Poulton, Barry C.; Graham, Jennifer L.; Rasmussen, Teresa J.; Stone, Mandy L.

2015-01-01

The Blue River Main wastewater treatment facility (WWTF) discharges into the upper Blue River (725 km2), and is recently upgraded to implement biological nutrient removal. We measured biotic condition upstream and downstream of the discharge utilizing the macroinvertebrate protocol developed for Kansas streams. We examined responses of 34 metrics to determine the best indicators for discriminating site differences and for predicting biological condition. Significant differences between sites upstream and downstream of the discharge were identified for 15 metrics in April and 12 metrics in August. Upstream biotic condition scores were significantly greater than scores at both downstream sites in April (p = 0.02), and in August the most downstream site was classified as non-biologically supporting. Thirteen EPT taxa (Ephemeroptera, Plecoptera, Trichoptera) considered intolerant of degraded stream quality were absent at one or both downstream sites. Increases in tolerance metrics and filtering macroinvertebrates, and a decline in ratio of scrapers to filterers all indicated effects of increased nutrient enrichment. Stepwise regressions identified several significant models containing a suite of metrics with low redundancy (R2 = 0.90 - 0.99). Based on the rapid decline in biological condition downstream of the discharge, the level of nutrient removal resulting from the facility upgrade (10% - 20%) was not enough to mitigate negative effects on macroinvertebrate communities.

Heat-Irrigate Effect' of Radiofrequency Ablation on Relevant Regional Hepatocyte in Living Swine Liver-Initial Study on Pathology.

PubMed

Jiang, Kai; Chen, Jiye; Liu, Yang; Liu, Jiang; Liu, Aijun; Dong, Jiahong; Huang, Zhiqiang

2015-05-01

Radiofrequency ablation (RFA) is one of the effective methods for HCC treatment. However, because of the "heat-sink effect" (HSE), it is very difficult to achieve a complete ablation in intrahepatic tumors. This study establishes the animal model of RFA on living swine liver and observes the 'heat-irrigate effect' on relevant regional hepatocytes. Three liver segments of 6 Guangxi Bama mini-pigs were selected to be ablated closed to segmental outflow vessel under surveillance of sonography for 6 min, and pathological changes of relevant downstream region were observed. We observed an elliptic shape of ablated area with diameter of 2.2 ± 1.1 cm on gross liver. Thermal damage was seen in downstream regional of relevant portal vein under microscope. However, adjacent area around the vessel was remained intact. In conclusion, the 'heat-irrigate effect' in RFA could cause thermal damage along the downstream region of relevant portal vein and this influence decreased gradually toward the surface.

IGF-1 attenuates LPS induced pro-inflammatory cytokines expression in buffalo (Bubalus bubalis) granulosa cells.

PubMed

Onnureddy, K; Ravinder; Onteru, Suneel Kumar; Singh, Dheer

2015-03-01

Interaction between immune and endocrine system is a diverse process influencing cellular function and homeostasis in animals. Negative energy balance (NEB) during postpartum period in dairy animals usually suppresses these systems resulting in reproductive tract infection and infertility. These negative effects could be due to competition among endocrine and immune signaling pathways for common signaling molecules. The present work studied the effect of IGF-1 (50 ng/ml) on LPS (1 μg/ml) mediated pro-inflammatory cytokine expression (IL-1β, TNF-α, IL-6) and aromatase (CYP19A1) genes' expressions as well as proliferation of buffalo granulosa cells. The crosstalk between LPS and IGF-1 was also demonstrated through studying the activities of downstream signaling molecules (ERK1/2, Akt, NF-κB) by western blot and immunostaining. Gene expression analysis showed that IGF-1 significantly reduced the LPS induced expression of IL-1β, TNF-α and IL-6. LPS alone inhibited the CYP19A1 expression. However, co-treatment with IGF-1 reversed the inhibitory effect of LPS on CYP19A1 expression. LPS alone did not affect granulosa cell proliferation, but co-treatment with IGF-1, and IGF-1 alone enhanced the proliferation. Western blot results demonstrated that LPS caused the nuclear translocation of the NF-κB and increased the phosphorylation of ERK1/2 and Akt maximum at 15 min and 60 min, respectively. Nonetheless, co-treatment with IGF-1 delayed LPS induced phosphorylation of ERK1/2 (peak at 120 min), while promoting early Akt phosphorylation (peak at 5 min) with no effect on NF-κB translocation. Overall, IGF-1 delayed and reversed the effects of LPS, suggesting that high IGF-1 levels may combat infection during critical periods like NEB in postpartum dairy animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

TCF21 and the environmental sensor aryl-hydrocarbon receptor cooperate to activate a pro-inflammatory gene expression program in coronary artery smooth muscle cells

PubMed Central

Nguyen, Trieu; Iyer, Dharini; Liu, Boxiang; Wang, Ting; Sazonova, Olga; Matic, Ljubica Perisic; Maegdefessel, Lars; Quertermous, Thomas

2017-01-01

Both environmental factors and genetic loci have been associated with coronary artery disease (CAD), however gene-gene and gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human genetic approaches. We have previously identified the transcription factor TCF21 as the causal CAD gene at 6q23.2 and characterized its downstream transcriptional network that is enriched for CAD GWAS genes. Here we investigate the hypothesis that TCF21 interacts with a downstream target gene, the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (e.g., tobacco smoke). Perturbation of TCF21 expression in human coronary artery smooth muscle cells (HCASMC) revealed that TCF21 promotes expression of AHR, its heterodimerization partner ARNT, and cooperates with these factors to upregulate a number of inflammatory downstream disease related genes including IL1A, MMP1, and CYP1A1. TCF21 was shown to bind in AHR, ARNT and downstream target gene loci, and co-localization was noted for AHR-ARNT and TCF21 binding sites genome-wide in regions of HCASMC open chromatin. These regions of co-localization were found to be enriched for GWAS signals associated with cardio-metabolic as well as chronic inflammatory disease phenotypes. Finally, we show that similar to TCF21, AHR gene expression is increased in atherosclerotic lesions in mice in vivo using laser capture microdissection, and AHR protein is localized in human carotid atherosclerotic lesions where it is associated with protein kinases with a critical role in innate immune response. These data suggest that TCF21 can cooperate with AHR to activate an inflammatory gene expression program that is exacerbated by environmental stimuli, and may contribute to the overall risk for CAD. PMID:28481916

Protein kinase CK2 interacts with adiponectin receptor 1 and participates in adiponectin signaling.

PubMed

Heiker, John T; Wottawah, Cornelia M; Juhl, Cathleen; Kosel, David; Mörl, Karin; Beck-Sickinger, Annette G

2009-06-01

Adiponectin is an adipokine with anti-atherogenic, anti-diabetic and insulin sensitizing properties. Its effects on energy homeostasis, glucose and lipid metabolism are mediated by two ubiquitously expressed seven-transmembrane receptors, AdipoR1 and -R2. With the exception of APPL1 and RACK1, no intracellular binding partners of adiponectin receptors are reported and thus signaling pathways downstream of these receptors remain largely unknown. To incorporate adiponectins protective potential in drug development it is essential to understand adiponectin signaling cascades in detail. A yeast two-hybrid approach employing AdipoR1s cytoplasmatic N-terminus led to the identification of the regulatory subunit of protein kinase CK2. We confirmed the interaction in co-immunoprecipitation, ELISA experiments and co-localization analysis in mammalian cells. Furthermore we could localize the interaction site in an N-terminal basic region close to the transmembrane domain. In adiponectin stimulation experiments of C2C12 mouse myotubes and MCF7 cells incorporating CK2 inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benz-imidazole (DMAT) we found a modulator role of CK2 in adiponectin signaling. Accordingly we identified the regulatory subunit of protein kinase CK2 as a novel intracellular partner of AdipoR1 and have strong evidence of CK2 as an effector molecule in adiponectin signaling. Since CK2 is involved in signaling cascades of other adipokines and hormones, e.g. leptin and insulin, our findings suggest a possible key function in crosstalk between adiponectin and insulin signaling pathways and could provide further insight into the anti-diabetic effects of adiponectin.

Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Calcium Binding Properties and Allosteric Regulation of Downstream Regulatory Element Antagonist Modulator (DREAM).

PubMed

Zhang, Jun; Li, Jing; Craig, Theodore A; Kumar, Rajiv; Gross, Michael L

2017-07-18

Downstream regulatory element antagonist modulator (DREAM) is an EF-hand Ca 2+ -binding protein that also binds to a specific DNA sequence, downstream regulatory elements (DRE), and thereby regulates transcription in a calcium-dependent fashion. DREAM binds to DRE in the absence of Ca 2+ but detaches from DRE under Ca 2+ stimulation, allowing gene expression. The Ca 2+ binding properties of DREAM and the consequences of the binding on protein structure are key to understanding the function of DREAM. Here we describe the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis to investigate the Ca 2+ binding properties and the subsequent conformational changes of full-length DREAM. We demonstrate that all EF-hands undergo large conformation changes upon calcium binding even though the EF-1 hand is not capable of binding to Ca 2+ . Moreover, EF-2 is a lower-affinity site compared to EF-3 and -4 hands. Comparison of HDX profiles between wild-type DREAM and two EF-1 mutated constructs illustrates that the conformational changes in the EF-1 hand are induced by long-range structural interactions. HDX analyses also reveal a conformational change in an N-terminal leucine-charged residue-rich domain (LCD) remote from Ca 2+ -binding EF-hands. This LCD domain is responsible for the direct interaction between DREAM and cAMP response element-binding protein (CREB) and regulates the recruitment of the co-activator, CREB-binding protein. These long-range interactions strongly suggest how conformational changes transmit the Ca 2+ signal to CREB-mediated gene transcription.

Seasonal and spatial variations in surface pCO2 and air-sea CO2 flux in the Chesapeake Bay

NASA Astrophysics Data System (ADS)

Cai, W. J.; Chen, B.

2017-12-01

Bay-wide observations of surface water partial pressure of carbon dioxide (pCO2) were conducted in May, June, August, and October 2016 to study the spatial and seasonal variations in surface pCO2 and to estimate air-sea CO2 flux in the Chesapeake Bay. Overall, high surface pCO2 in the upper-bay decreased downstream rapidly below the atmospheric value near the bay bridge in the mid-bay and then increased slightly to the lower-bay where pCO2 approached the atmospheric level. Over the course of a year, pCO2 was higher than 1000 µatm in the upper bay and the highest pCO2 (2500 µatm) was observed in August. Significant biologically-induced pCO2 undersaturation was observed at the upper part of the mid-bay in August with pCO2 as low as 50 µatm and oversaturated DO% of 200%. In addition to biological control, vertical mixing and upwelling controlled by wind direction and tidal stage played an important role in controlling surface pCO2 in the mid-bay as is evidenced by co-occurrence of high pCO2 with low temperature and low oxygen or high salinity from the subsurface. These physical processes occurred regularly and in short time scale of hours, suggesting they must be considered in the assessment of annual air-sea CO2 flux. Seasonally, the upper-bay acted as a source for atmospheric CO2 over the course of a year. The boundary of upper and mid bay transited from a CO2 source to a sink from May to August and was a source again in October due to strong biological production in summer. In contrast, the mid-bay represented as a CO2 source with large temporal variation due to dynamic hydrographic settings. The lower-bay transited from a weak sink in May to equilibrated with the atmosphere from June to August, while became a source again in October. Moreover, the CO2 flux could be reversed very quickly under episodic severe weather events. Thus further research, including the influence of severe weather and subsequent bloom, is needed to get better understanding of the carbon cycling in the Chesapeake Bay.

Identification of a 3-hydroxy-3-methylglutaryl-CoA reductase gene highly expressed in the root tissue of Taraxacum kok-saghyz

USDA-ARS?s Scientific Manuscript database

Kazak dandelion (Taraxacum kok-saghyz, Tk) is a rubber-producing plant currently being investigated as a source of natural rubber for industrial applications. Like many other isoprenoids, rubber is a downstream product of the mevalonate pathway. The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) en...

Effects of Exercise on AMPK Signaling and Downstream Components to PI3K in Rat with Type 2 Diabetes

PubMed Central

Cao, Shicheng; Li, Bowen; Yi, Xuejie; Chang, Bo; Zhu, Beibei; Lian, Zhenzhen; Zhang, Zhaoran; Zhao, Gang; Liu, Huili; Zhang, He

2012-01-01

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague–Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and downstream components of phosphatidylinositol 3-kinase (PI3K) signaling pathways in the soleus. As a result, blood glucose, triglyceride, total cholesterol, and free fatty acid were significantly increased, whereas insulin level progressively declined in diabetic rats. Interestingly, chronic and acute exercise reduced blood glucose, increased phosphorylation and expression of AMPKα1/2 and the isoforms AMPKα1 and AMPKα2, and decreased phosphorylation and expression of AMPK substrate, acetyl CoA carboxylase (ACC). Chronic exercise upregulated phosphorylation and expression of AMPK upstream kinase, LKB1. But acute exercise only increased LKB1 expression. In particular, exercise reversed the changes in protein kinase C (PKC)ζ/λ phosphorylation, and PKCζ phosphorylation and expression. Additionally, exercise also increased protein kinase B (PKB)/Akt1, Akt2 and GLUT4 expression, but AS160 protein expression was unchanged. Chronic exercise elevated Akt (Thr308) and (Ser473) and AS160 phosphorylation. Finally, we found that exercise increased peroxisome proliferator-activated receptor-γ coactivator 1 (PGC1) mRNA expression in the soleus of diabetic rats. These results indicate that both chronic and acute exercise influence the phosphorylation and expression of components of the AMPK and downstream to PIK3 (aPKC, Akt), and improve GLUT4 trafficking in skeletal muscle. These data help explain the mechanism how exercise regulates glucose homeostasis in diabetic rats. PMID:23272147

Effect of fuel composition and differential diffusion on flame stabilization in reacting syngas jets in turbulent cross-flow

DOE PAGES

Minamoto, Yuki; Kolla, Hemanth; Grout, Ray W.; ...

2015-07-24

Here, three-dimensional direct numerical simulation results of a transverse syngas fuel jet in turbulent cross-flow of air are analyzed to study the influence of varying volume fractions of CO relative to H 2 in the fuel composition on the near field flame stabilization. The mean flame stabilizes at a similar location for CO-lean and CO-rich cases despite the trend suggested by their laminar flame speed, which is higher for the CO-lean condition. To identify local mixtures having favorable mixture conditions for flame stabilization, explosive zones are defined using a chemical explosive mode timescale. The explosive zones related to flame stabilizationmore » are located in relatively low velocity regions. The explosive zones are characterized by excess hydrogen transported solely by differential diffusion, in the absence of intense turbulent mixing or scalar dissipation rate. The conditional averages show that differential diffusion is negatively correlated with turbulent mixing. Moreover, the local turbulent Reynolds number is insufficient to estimate the magnitude of the differential diffusion effect. Alternatively, the Karlovitz number provides a better indicator of the importance of differential diffusion. A comparison of the variations of differential diffusion, turbulent mixing, heat release rate and probability of encountering explosive zones demonstrates that differential diffusion predominantly plays an important role for mixture preparation and initiation of chemical reactions, closely followed by intense chemical reactions sustained by sufficient downstream turbulent mixing. The mechanism by which differential diffusion contributes to mixture preparation is investigated using the Takeno Flame Index. The mean Flame Index, based on the combined fuel species, shows that the overall extent of premixing is not intense in the upstream regions. However, the Flame Index computed based on individual contribution of H 2 or CO species reveals that hydrogen contributes significantly to premixing, particularly in explosive zones in the upstream leeward region, i.e. at the preferred flame stabilization location. Therefore, a small amount of H 2 diffuses much faster than CO, creating relatively homogeneous mixture pockets depending on the competition with turbulent mixing. These pockets, together with high H 2 reactivity, contribute to stabilizing the flame at a consistent location regardless of the CO concentration in the fuel for the present range of DNS conditions.« less

Algal Nitrate Assimilation and Productivity in an Urban, Concrete-Lined Stream Dominated by Tertiary Treated Municipal Waste-Water

NASA Astrophysics Data System (ADS)

Kent, R. H.; Burton, C. A.

2001-12-01

This study examined the extent and variabiltity of nitrate loss in a 2.85 km reach of Cucamonga Creek, which is concrete-lined and dominated by treated municipal waste-water. Primary production was measured to determine if the loss could be attributed to algal assimilation. Samples for nitrite plus nitrate analysis were collected at the top and bottom of the study reach every hour throughout the 24-hour sampling period; samples for analyses of other parameters were collected less frequently. Water temperature, dissolved oxygen (DO), pH and specific conductance were monitored continuously throughout the sampling period using in-stream probes. During the two weeks prior to the study, periphyton samples were collected periodically at four stations along the reach for standing crop measurements and a growth rate time-series using Chlorophyll A and ash-free-dry mass. Water samples from the upstream station were compared to those taken an hour later (the approximate travel time) at the downstream station. Nitrate concentrations were lower at the downstream station in 21 of 25 of the paired samples, indicating nearly continuous loss in the reach. The total loss of NO3 for the day was about 0.71 g as N/m2. Most of the loss occurred during daylight hours, with the peak occurring at midday. During the night, CO2 concentrations were relatively constant at about 25 mg/L. Concentrations began to decline at sunrise, and declined to 0 mg/L at the lower site after midday. Peak nitrate loss occurred at about the same time as the CO2 concentration was at its minimum. DO declined slightly during the night, began to rise at sunrise, reached a peak during midday, and declined in late afternoon through evening; pH followed a similar pattern. Net primary productivity, as measured by the differences in DO between the two sites was 13 g O2/m2 for the day. Using the Redfield ratio, the predicted nitrate assimilation is about 0.66 g NO3 as N/m2. The continuous loss of nitrate between the two sites; the comparability between the observed loss in nitrate and that predicted using the Redfield ratio; and the timing of changes in nitrate loss, DO, pH and CO2 indicate that nitrate loss in this concrete-lined channel was primarily due to algal assimilation. The timing of the peak nitrate loss relative to the depletion of CO2 suggests that CO2 may be limiting photosynthesis, and therefore assimilation of nitrate by algae.

Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.

PubMed

Osaki, Yoshinori; Nakagawa, Yoshimi; Miyahara, Shoko; Iwasaki, Hitoshi; Ishii, Akiko; Matsuzaka, Takashi; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Sone, Hirohito; Ohashi, Ken; Ishibashi, Shun; Yamada, Nobuhiro; Shimano, Hitoshi

2015-10-23

HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs. Copyright © 2015 Elsevier Inc. All rights reserved.

MidAmerican's Walter Scott, Jr. Energy Center Unit 4 earns Power's highest honor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peltier, R.

MidAmerican Energy Co. and its project partners are convinced that supercritical coal-firing technology's inherently higher efficiency and lower CO{sub 2} emissions no longer come with a price: reduced reliability. Unit 4 of the Walter Scott, Jr. Energy Center (WSEC) entered into service in June 2006 doubling the capacity of the PRB-coal fuelled plant to 1,600 MW. This is the first major new supercritical plant in the US in more than 15 years. The design of the boiler and the air pollution control systems downstream are described and illustrated. Unit 4 won the 2007 Plant of the Year awarded by Powermore » magazine. 11 figs.« less

Monitoring, field experiments, and geochemical modeling of Fe(II) oxidation kinetics in a stream dominated by net-alkaline coal-mine drainage, Pennsylvania, USA

USGS Publications Warehouse

Cravotta, Charles A.

2015-01-01

Watershed-scale monitoring, field aeration experiments, and geochemical equilibrium and kinetic modeling were conducted to evaluate interdependent changes in pH, dissolved CO2, O2, and Fe(II) concentrations that typically take place downstream of net-alkaline, circumneutral coal-mine drainage (CMD) outfalls and during aerobic treatment of such CMD. The kinetic modeling approach, using PHREEQC, accurately simulates observed variations in pH, Fe(II) oxidation, alkalinity consumption, and associated dissolved gas concentrations during transport downstream of the CMD outfalls (natural attenuation) and during 6-h batch aeration tests on the CMD using bubble diffusers (enhanced attenuation). The batch aeration experiments demonstrated that aeration promoted CO2 outgassing, thereby increasing pH and the rate of Fe(II) oxidation. The rate of Fe(II) oxidation was accurately estimated by the abiotic homogeneous oxidation rate law −d[Fe(II)]/dt = k1·[O2]·[H+]−2·[Fe(II)] that indicates an increase in pH by 1 unit at pH 5–8 and at constant dissolved O2 (DO) concentration results in a 100-fold increase in the rate of Fe(II) oxidation. Adjusting for sample temperature, a narrow range of values for the apparent homogeneous Fe(II) oxidation rate constant (k1′) of 0.5–1.7 times the reference value of k1 = 3 × 10−12 mol/L/min (for pH 5–8 and 20 °C), reported by Stumm and Morgan (1996), was indicated by the calibrated models for the 5-km stream reach below the CMD outfalls and the aerated CMD. The rates of CO2 outgassing and O2ingassing in the model were estimated with first-order asymptotic functions, whereby the driving force is the gradient of the dissolved gas concentration relative to equilibrium with the ambient atmosphere. Although the progressive increase in DO concentration to saturation could be accurately modeled as a kinetic function for the conditions evaluated, the simulation of DO as an instantaneous equilibrium process did not affect the model results for Fe(II) or pH. In contrast, the model results for pH and Fe(II) were sensitive to the CO2 mass transfer rate constant (kL,CO2a). The value of kL,CO2a estimated for the stream (0.010 min−1) was within the range for the batch aeration experiments (0–0.033 min−1). These results indicate that the abiotic homogeneous Fe(II) oxidation rate law, with adjustments for variations in temperature and CO2 outgassing rate, may be applied to predict changes in aqueous iron and pH for net-alkaline, ferruginous waters within a stream (natural conditions) or a CMD treatment system (engineered conditions).

Supercritical CO2 Cleaning System for Planetary Protection and Contamination Control Applications

NASA Technical Reports Server (NTRS)

Lin, Ying; Zhong, Fang; Aveline, David C.; Anderson, Mark S.

2012-01-01

Current spacecraft-compatible cleaning protocols involve a vapor degreaser, liquid sonication, and alcohol wiping. These methods are not very effective in removing live and dead microbes from spacecraft piece parts of slightly complicated geometry, such as tubing and loosely fitted nuts and bolts. Contamination control practices are traditionally focused on cleaning and monitoring of particulate and oily residual. Vapor degreaser and outgassing bakeout have not been proven to be effective in removing some less volatile, hydrophilic biomolecules of significant relevance to life detection. A precision cleaning technology was developed using supercritical CO2 (SCC). SCC is used as both solvent and carrier for removing organic and particulate contaminants. Supercritical fluid, like SCC, is characterized by physical and thermal properties that are between those of the pure liquid and gas phases. The fluid density is a function of the temperature and pressure. Its solvating power can be adjusted by changing the pressure or temperature, or adding a secondary solvent such as alcohol or water. Unlike a regular organic solvent, SCC has higher diffusivities, lower viscosity, and lower surface tension. It readily penetrates porous and fibrous solids and can reach hard-to-reach surfaces of the parts with complex geometry. Importantly, the CO2 solvent does not leave any residue. The results using this new cleaning device demonstrated that both supercritical CO2 with 5% water as a co-solvent can achieve cleanliness levels of 0.01 mg/cm2 or less for contaminants of a wide range of hydrophobicities. Experiments under the same conditions using compressed Martian air mix, which consists of 95% CO2, produced similar cleaning effectiveness on the hydrophobic compounds. The main components of the SCC cleaning system are a high-pressure cleaning vessel, a boil-off vessel located downstream from the cleaning vessel, a syringe-type high-pressure pump, a heat exchanger, and a back pressure regulator (BPR). After soaking the parts to be cleaned in the clean vessel for a period, the CO2 with contaminants is flushed out of the cleaning vessel using fresh CO2 in a first-in-first-out (FIFO) method. The contaminants are either precipitating out in the boil-off container or being trapped in a filter subsystem. The parts to be cleaned are secured in a basket inside and can be rotated up to 1,400 rpm by a magnetic drive. The fluid flows within the vessel generate tangential forces on the parts surfaces, enhancing the cleaning effectiveness and shortening the soaking time. During the FIFO flushing, the pump subsystem pushes fresh CO2 into the cleaning vessel at a constant flow rate between 0.01 and 200 mL/min, while the BPR regulates the pressure in the cleaning vessel to within 0.1 bar by controlling the needle position in an outlet valve. The fresh CO2 gas flows through the heat exchanger at a given temperature before entering the cleaning vessel. A platinum resistance thermometer (PRT) reads the cleaning vessel interior temperature that can be controlled to within 0.1 K. As a result, cleaning vessel temperature remains constant during the FIFO flushing. There is no change in solvent power during FIFO flushing since both temperature and pressure inside the cleaning vessel remain unchanged, thus minimizing contaminants left behind. During decompression, both temperature and pressure are strictly controlled to prevent bubbles from generating in the cleaning vessel that could stir up the contaminants that sank to the bottom by gravity.

Pan-cancer transcriptomic analysis associates long non-coding RNAs with key mutational driver events

PubMed Central

Ashouri, Arghavan; Sayin, Volkan I.; Van den Eynden, Jimmy; Singh, Simranjit X.; Papagiannakopoulos, Thales; Larsson, Erik

2016-01-01

Thousands of long non-coding RNAs (lncRNAs) lie interspersed with coding genes across the genome, and a small subset has been implicated as downstream effectors in oncogenic pathways. Here we make use of transcriptome and exome sequencing data from thousands of tumours across 19 cancer types, to identify lncRNAs that are induced or repressed in relation to somatic mutations in key oncogenic driver genes. Our screen confirms known coding and non-coding effectors and also associates many new lncRNAs to relevant pathways. The associations are often highly reproducible across cancer types, and while many lncRNAs are co-expressed with their protein-coding hosts or neighbours, some are intergenic and independent. We highlight lncRNAs with possible functions downstream of the tumour suppressor TP53 and the master antioxidant transcription factor NFE2L2. Our study provides a comprehensive overview of lncRNA transcriptional alterations in relation to key driver mutational events in human cancers. PMID:28959951

The sensing of respiratory gases in fish: Mechanisms and signalling pathways.

PubMed

Perry, S F; Tzaneva, V

2016-04-01

Chemoreception in fish is critical for sensing changes in the chemical composition of the external and internal environments and is often the first step in a cascade of events leading to cardiorespiratory and metabolic adjustments. Of paramount importance is the ability to sense changes in the levels of the three respiratory gases, oxygen (O2), carbon dioxide (CO2) and ammonia (NH3). In this review, we discuss the role of piscine neuroepithelial cells (NEC), putative peripheral chemoreceptors, as tri-modal sensors of O2, CO2 and NH3. Where possible, we elaborate on the signalling pathways linking NEC stimulation to afferent responses, the potential role of neurotransmitters in activating downstream neuronal pathways and the impact of altered levels of the respiratory gases on NEC structure and function. Although serotonin, the major neurotransmitter contained within NECs, is presumed to be the principal agent eliciting the reflex responses to altered levels of the respiratory gases, there is accumulating evidence for the involvement of "gasomitters", a class of gaseous neurotransmitters which includes nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H2S). Recent data suggest that CO inhibits and H2S stimulates NEC activity whereas NO can either be inhibitory or stimulatory depending on developmental age. Copyright © 2015 Elsevier B.V. All rights reserved.

Aberrantly activated AREG-EGFR signaling is required for the growth and survival of CRTC1-MAML2 fusion-positive mucoepidermoid carcinoma cells.

PubMed

Chen, Z; Chen, J; Gu, Y; Hu, C; Li, J-L; Lin, S; Shen, H; Cao, C; Gao, R; Li, J; Ha, P K; Kaye, F J; Griffin, J D; Wu, L

2014-07-17

Salivary gland tumors (SGT) are a group of highly heterogeneous head and neck malignancies with widely varied clinical outcomes and no standard effective treatments. The CRTC1-MAML2 fusion oncogene, encoded by a recurring chromosomal translocation t(11;19)(q14-21;p12-13), is a frequent genetic alteration found in >50% of mucoepidermoid carcinomas (MEC), the most common malignant SGT. In this study, we aimed to define the role of the CRTC1-MAML2 oncogene in the maintenance of MEC tumor growth and to investigate critical downstream target genes and pathways for therapeutic targeting of MEC. By performing gene expression analyses and functional studies via RNA interference and pharmacological modulation, we determined the importance of the CRTC1-MAML2 fusion gene and its downstream AREG-EGFR signaling in human MEC cancer cell growth and survival in vitro and in vivo using human MEC xenograft models. We found that CRTC1-MAML2 fusion oncogene was required for the growth and survival of fusion-positive human MEC cancer cells in vitro and in vivo. The CRTC1-MAML2 oncoprotein induced the upregulation of the epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) by co-activating the transcription factor CREB, and AREG subsequently activated EGFR signaling in an autocrine manner that promoted MEC cell growth and survival. Importantly, CRTC1-MAML2-positive MEC cells were highly sensitive to EGFR signaling inhibition. Therefore, our study revealed that aberrantly activated AREG-EGFR signaling is required for CRTC1-MAML2-positive MEC cell growth and survival, suggesting that EGFR-targeted therapies will benefit patients with advanced, unresectable CRTC1-MAML2-positive MEC.

In situ measurements of microbially-catalyzed nitrification and nitrate reduction rates in an ephemeral drainage channel receiving water from coalbed natural gas discharge, Powder River Basin, Wyoming, USA

USGS Publications Warehouse

Harris, S.H.; Smith, R.L.

2009-01-01

Nitrification and nitrate reduction were examined in an ephemeral drainage channel receiving discharge from coalbed natural gas (CBNG) production wells in the Powder River Basin, Wyoming. CBNG co-produced water typically contains dissolved inorganic nitrogen (DIN), primarily as ammonium. In this study, a substantial portion of discharged ammonium was oxidized within 50??m of downstream transport, but speciation was markedly influenced by diel fluctuations in dissolved oxygen (> 300????M). After 300??m of transport, 60% of the initial DIN load had been removed. The effect of benthic nitrogen-cycling processes on stream water chemistry was assessed at 2 locations within the stream channel using acrylic chambers to conduct short-term (2-6??h), in-stream incubations. The highest ambient DIN removal rates (2103????mol N m- 2 h- 1) were found at a location where ammonium concentrations > 350????M. This occurred during light incubations when oxygen concentrations were highest. Nitrification was occurring at the site, however, net accumulation of nitrate and nitrite accounted for < 12% of the ammonium consumed, indicating that other ammonium-consuming processes were also occurring. In dark incubations, nitrite and nitrate consumption were dominant processes, while ammonium was produced rather than consumed. At a downstream location nitrification was not a factor and changes in DIN removal rates were controlled by nitrate reduction, diel fluctuations in oxygen concentration, and availability of electron donor. This study indicates that short-term adaptation of stream channel processes can be effective for removing CBNG DIN loads given sufficient travel distances, but the long-term potential for nitrogen remobilization and nitrogen saturation remain to be determined.

Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules.

PubMed

Millhouse, Emma; Jose, Anto; Sherry, Leighann; Lappin, David F; Patel, Nisha; Middleton, Andrew M; Pratten, Jonathan; Culshaw, Shauna; Ramage, Gordon

2014-06-28

Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties. An in vitro multi-species biofilm containing S. mitis, F. nucleatum, P. gingivalis and A. actinomycetemcomitans was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level. CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA. CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.

Molecular mechanism of transcription inhibition by phage T7 gp2 protein.

PubMed

Mekler, Vladimir; Minakhin, Leonid; Sheppard, Carol; Wigneshweraraj, Sivaramesh; Severinov, Konstantin

2011-11-11

Escherichia coli T7 bacteriophage gp2 protein is a potent inhibitor of host RNA polymerase (RNAP). gp2 inhibits formation of open promoter complex by binding to the β' jaw, an RNAP domain that interacts with downstream promoter DNA. Here, we used an engineered promoter with an optimized sequence to obtain and characterize a specific promoter complex containing RNAP and gp2. In this complex, localized melting of promoter DNA is initiated but does not propagate to include the point of the transcription start. As a result, the complex is transcriptionally inactive. Using a highly sensitive RNAP beacon assay, we performed quantitative real-time measurements of specific binding of the RNAP-gp2 complex to promoter DNA and various promoter fragments. In this way, the effect of gp2 on RNAP interaction with promoters was dissected. As expected, gp2 greatly decreased RNAP affinity to downstream promoter duplex. However, gp2 also inhibited RNAP binding to promoter fragments that lacked downstream promoter DNA that interacts with the β' jaw. The inhibition was caused by gp2-mediated decrease of the RNAP binding affinity to template and non-template strand segments of the transcription bubble downstream of the -10 promoter element. The inhibition of RNAP interactions with single-stranded segments of the transcription bubble by gp2 is a novel effect, which may occur via allosteric mechanism that is set in motion by the gp2 binding to the β' jaw. Copyright © 2011 Elsevier Ltd. All rights reserved.

Transcription co-activator SAYP mediates the action of STAT activator.

PubMed

Panov, Vladislav V; Kuzmina, Julia L; Doronin, Semen A; Kopantseva, Marina R; Nabirochkina, Elena N; Georgieva, Sofia G; Vorobyeva, Nadezhda E; Shidlovskii, Yulii V

2012-03-01

Jak/STAT is an important signaling pathway mediating multiple events in development. We describe participation of metazoan co-activator SAYP/PHF10 in this pathway downstream of STAT. The latter, via its activation domain, interacts with the conserved core of SAYP. STAT is associated with the SAYP-containing co-activator complex BTFly and recruits BTFly onto genes. SAYP is necessary for stimulating STAT-driven transcription of numerous genes. Mutation of SAYP leads to maldevelopments similar to those observed in STAT mutants. Thus, SAYP is a novel co-activator mediating the action of STAT.

Inhibition of intracellular lipolysis promotes human cancer cell adaptation to hypoxia

PubMed Central

Zhang, Xiaodong; Saarinen, Alicia M; Hitosugi, Taro; Wang, Zhenghe; Wang, Liguo; Ho, Thai H

2017-01-01

Tumor tissues are chronically exposed to hypoxia owing to aberrant vascularity. Lipid droplet (LD) accumulation is a hallmark of hypoxic cancer cells, yet how LDs form and function during hypoxia remains poorly understood. Herein, we report that in various cancer cells upon oxygen deprivation, HIF-1 activation down-modulates LD catabolism mediated by adipose triglyceride lipase (ATGL), the key enzyme for intracellular lipolysis. Proteomics and functional analyses identified hypoxia-inducible gene 2 (HIG2), a HIF-1 target, as a new inhibitor of ATGL. Knockout of HIG2 enhanced LD breakdown and fatty acid (FA) oxidation, leading to increased ROS production and apoptosis in hypoxic cancer cells as well as impaired growth of tumor xenografts. All of these effects were reversed by co-ablation of ATGL. Thus, by inhibiting ATGL, HIG2 acts downstream of HIF-1 to sequester FAs in LDs away from the mitochondrial pathways for oxidation and ROS generation, thereby sustaining cancer cell survival in hypoxia. PMID:29256392

Vortex coupling in trailing vortex-wing interactions

NASA Astrophysics Data System (ADS)

Chen, C.; Wang, Z.; Gursul, I.

2018-03-01

The interaction of trailing vortices of an upstream wing with rigid and flexible downstream wings has been investigated experimentally in a wind tunnel, using particle image velocimetry, hot-wire, force, and deformation measurements. Counter-rotating upstream vortices exhibit increased meandering when they are close to the tip of the downstream wing. The upstream vortex forms a pair with the vortex shed from the downstream wing and then exhibits large displacements around the wing tip. This coupled motion of the pair has been found to cause large lift fluctuations on the downstream wing. The meandering of the vortex pair occurs at the natural meandering frequency of the isolated vortex, with a low Strouhal number, and is not affected by the frequency of the large-amplitude wing oscillations if the downstream wing is flexible. The displacement of the leading vortex is larger than that of the trailing vortex; however, it causes highly correlated variations of the core radius, core vorticity, and circulation of the trailing vortex with the coupled meandering motion. In contrast, co-rotating vortices do not exhibit any increased meandering.

A Family with Severe Insulin Resistance and Diabetes Mellitus due to a Missense Mutation in AKT2

PubMed Central

George, Stella; Rochford, Justin J.; Wolfrum, Christian; Gray, Sarah L.; Schinner, Sven; Wilson, Jenny C.; Soos, Maria A.; Murgatroyd, Peter R.; Williams, Rachel M.; Acerini, Carlo L.; Dunger, David B.; Barford, David; Umpleby, A. Margot; Wareham, Nicholas J.; Davies, Huw Alban; Schafer, Alan J.; Stoffel, Markus; O’Rahilly, Stephen; Barroso, Ines

2008-01-01

Inherited defects in signaling pathways downstream of the insulin receptor have long been suggested to contribute to human Type 2 diabetes mellitus. Here we describe a mutation in the gene encoding the protein kinase AKT2/PKBβ in a family that shows autosomal dominant inheritance of severe insulin resistance and diabetes mellitus. Expression of the mutant kinase in cultured cells disrupted insulin signaling to metabolic end-points and inhibited the function of co-expressed, wild type AKT. These findings demonstrate the central importance of AKT signaling to insulin sensitivity in humans. PMID:15166380

Src-dependent EGFR transactivation regulates lung inflammation via downstream signaling involving ERK1/2, PI3Kδ/Akt and NFκB induction in a murine asthma model.

PubMed

El-Hashim, Ahmed Z; Khajah, Maitham A; Renno, Waleed M; Babyson, Rhema S; Uddin, Mohib; Benter, Ibrahim F; Ezeamuzie, Charles; Akhtar, Saghir

2017-08-30

The molecular mechanisms underlying asthma pathogenesis are poorly characterized. In this study, we investigated (1) whether Src mediates epidermal growth factor receptor (EGFR) transactivation; (2) if ERK1/2, PI3Kδ/Akt and NF-κB are signaling effectors downstream of Src/EGFR activation; and (3) if upstream inhibition of Src/EGFR is more effective in downregulating the allergic inflammation than selective inhibition of downstream signaling pathways. Allergic inflammation resulted in increased phosphorylation of EGFR, Akt, ERK1/2 and IκB in the lung tissues from ovalbumin (OVA)-challenged BALB/c mice. Treatment with inhibitors of Src (SU6656) or EGFR (AG1478) reduced EGFR phosphorylation and downstream signaling which resulted in the inhibition of the OVA-induced inflammatory cell influx in bronchoalveolar lavage fluid (BALF), perivascular and peribronchial inflammation, fibrosis, goblet cell hyper/metaplasia and airway hyper-responsiveness. Treatment with pathway-selective inhibitors for ERK1/2 (PD89059) and PI3Kδ/Akt (IC-87114) respectively, or an inhibitor of NF-κB (BAY11-7085) also reduced the OVA-induced asthmatic phenotype but to a lesser extent compared to Src/EGFR inhibition. Thus, Src via EGFR transactivation and subsequent downstream activation of multiple pathways regulates the allergic airway inflammatory response. Furthermore, a broader upstream inhibition of Src/EGFR offers an attractive therapeutic alternative in the treatment of asthma relative to selectively targeting the individual downstream signaling effectors.

Mercury contamination from mine and natural sources in Harley Gulch, downstream from the Abbott and Turkey Run Mercury Mines, Lake County, California

NASA Astrophysics Data System (ADS)

Hothem, R. L.; Rytuba, J. J.; Goldstein, D.; Brussee, B.

2011-12-01

The Abbott and Turkey Run Mercury (Hg) mine area in central California has released Hg tailings into the Harley Gulch watershed since 1862. Harley Gulch flows into Cache Creek which is a significant source of Hg into San Francisco Bay Delta. Thermal mine water effluent emanating from the Turkey Run adit flows into the upper part of the watershed. Despite remediation efforts, Hg tailings and enriched sediment remain in the Harley Gulch wetlands and in the creek downstream from the mine area. Water, sediment, and biota have been sampled from below the mine area to 15 km downstream to the confluence with Cache Creek in order to assess the impact of Hg on water quality and biota. Two previously unrecognized natural sources of Hg in the watershed are connate groundwater with elevated levels of Hg, and biogenic sediment composed of phytoplankton that accumulates in the upper part of the watershed during the dry season. The connate groundwater source contains isotopically-heavy Mg-Ca-Cl-CO3-SO4 water that has elevated concentrations of Ba, W, Ti, and Hg. This water first enters Harley Gulch in the central part of the wetland immediately downstream from the mine area and continues to contribute water downstream for a distance of 1.5 km. It is both chemically and isotopically distinct from the thermal mine water effluent from the Turkey Run adit. The biogenic source consists of blooms of phytoplankton that accumulate to a thickness of up to 0.2 m. Phytoplankton have a large bioaccumulation factor of Hg and monomethyl mercury (MMeHg) that results in a high concentrations of Hg and MMeHg (Hg: 5-25 μg/g, MMeHg 5.2 ng/g) in the biogenic sediment. The tan biogenic sediment at the surface consists of living diatoms and below it is a layer of black reduced biogenic sediment consisting of diatom fragments with micron- to submicron-sized FeS, HgS, and barite grains. Sulfate-reducing bacteria reduce sulfate to sulfide in the pore waters of the biogenic sediment that reacts with dissolved Fe to form FeS. Hg released from the diatoms into the pore fluid reacts with sulfide to form micron- to submicron-sized particles of HgS. The decrease in sulfate concentration resulting from sulfate reduction results in precipitation of barite. The resulting biogenic sediment is composed primarily of diatoms with a minor component of CaCO3 and clay and is transported downstream during periods of high flow. Composites of aquatic invertebrates collected from the upper two sites of the Harley Gulch wetland included larval damselflies (Coenagrionidae), adult predaceous diving beetles (Dytiscidae), and larval water scavenger beetles (Hydrophilidae). The percentage of MMeHg was low in all samples, the concentrations of MMeHg (113 - 604 ng/g, wet mass) were moderate, and the total Hg concentrations were extremely high (1,240 - 9,940 ng/g). The concentrations of both MMeHg and Hg were lower at downstream sites in both damselflies and diving beetles compared with the wetlands and the areas where connate groundwater enters the creek in the upper part of the watershed. As with these biological taxa, concentrations of both Hg and MMeHg in water and sediment were lower at the downstream sites.

Peptide-Conjugated Nanoparticles Reduce Positive Co-stimulatory Expression and T Cell Activity to Induce Tolerance.

PubMed

Kuo, Robert; Saito, Eiji; Miller, Stephen D; Shea, Lonnie D

2017-07-05

Targeted approaches to treat autoimmune diseases would improve upon current therapies that broadly suppress the immune system and lead to detrimental side effects. Antigen-specific tolerance was induced using poly(lactide-co-glycolide) nanoparticles conjugated with disease-relevant antigen to treat a model of multiple sclerosis. Increasing the nanoparticle dose and amount of conjugated antigen both resulted in more durable immune tolerance. To identify active tolerance mechanisms, we investigated downstream cellular and molecular events following nanoparticle internalization by antigen-presenting cells. The initial cell response to nanoparticles indicated suppression of inflammatory signaling pathways. Direct and functional measurement of surface MHC-restricted antigen showed positive correlation with both increasing particle dose from 1 to 100 μg/mL and increasing peptide conjugation by 2-fold. Co-stimulatory analysis of cells expressing MHC-restricted antigen revealed most significant decreases in positive co-stimulatory molecules (CD86, CD80, and CD40) following high doses of nanoparticles with higher peptide conjugation, whereas expression of a negative co-stimulatory molecule (PD-L1) remained high. T cells isolated from mice immunized against myelin proteolipid protein (PLP 139-151 ) were co-cultured with antigen-presenting cells administered PLP 139-151 -conjugated nanoparticles, which resulted in reduced T cell proliferation, increased T cell apoptosis, and a stronger anti-inflammatory response. These findings indicate several potential mechanisms used by peptide-conjugated nanoparticles to induce antigen-specific tolerance. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Effects of metals on a montane aquatic system evaluated using an integrated assessment approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beltman, D.; Lipton, J.; Cacela, D.

Surface water, benthic invertebrates, aufwuchs, and sediments were sampled in a Rocky Mountain stream impacted by a cobalt-copper mine. A randomized study design was employed to ensure valid inferences beyond the areas sampled. As, Co, and Cu concentrations in all media downstream of the mine were 1--3 orders of magnitude greater than concentrations upstream, and concentrations in invertebrates were greater than those that adversely affect trout via dietary intake. Correlational analysis shows that bioaccumulation mechanisms and pathways between the different media differ from element to element; the differences are related to geochemical characteristics of the elements. The benthic invertebrate communitymore » is severely impacted for at least 50 km downstream of the mine: Ephemeropteran density, number of taxa, and total biomass are as low as 0.1% of values upstream. Other indices of the effects of metals on invertebrate communities that have been used elsewhere were ineffective in detecting these severe impacts. The integrated assessment approach used in this study provides information on contaminant sources, exposure pathways and mechanisms, and impacts to the stream ecosystem at several organizational levels.« less

Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju, E-mail: anjubansaldipas@gmail.com

High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl{sub 2}), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl{sub 2} supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl{sub 2} supplementation in rats augmentedmore » the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl{sub 2} supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ► We supplemented rats with CoCl{sub 2} for 15 days along with training. ► CoCl{sub 2} supplementation augmented endurance performance and aerobic respiration. ► It increased glucose uptake and metabolism in muscle. ► It enhanced mitochondrial biogenesis in red gastrocnemius muscle.« less

Techno-Economic Analysis of a Secondary Air Stripper Process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heberle, J.R.; Nikolic, Heather; Thompson, Jesse

We present results of an initial techno-economic assessment on a post-combustion CO2 capture process developed by the Center for Applied Energy Research (CAER) at the University of Kentucky using Mitsubishi Hitachi Power Systems’ H3-1 aqueous amine solvent. The analysis is based on data collected at a 0.7 MWe pilot unit combined with laboratory data and process simulations. The process adds a secondary air stripper to a conventional solvent process, which increases the cyclic loading of the solvent in two ways. First, air strips additional CO2 from the solvent downstream of the conventional steam-heated thermal stripper. This extra stripping of CO2more » reduces the lean loading entering the absorber. Second, the CO2-enriched air is then sent to the boiler for use as secondary air. This recycling of CO2 results in a higher concentration of CO2 in the flue gas sent to the absorber, and hence a higher rich loading of the solvent exiting the absorber. A process model was incorporated into a full-scale supercritical pulverized coal power plant model to determine the plant performance and heat and mass balances. The performance and heat and mass balance data were used to size equipment and develop cost estimates for capital and operating costs. Lifecycle costs were considered through a levelized cost of electricity (LCOE) assessment based on the capital cost estimate and modeled performance. The results of the simulations show that the CAER process yields a regeneration energy of 3.12 GJ/t CO2, a $53.05/t CO2 capture cost, and LCOE of $174.59/MWh. This compares to the U.S. Department of Energy’s projected costs (Case 10) of regeneration energy of 3.58 GJ/t CO2 , a $61.31/t CO2 capture cost, and LCOE of $189.59/MWh. For H3-1, the CAER process results in a regeneration energy of 2.62 GJ/tCO2 with a stripper pressure of 5.2 bar, a capture cost of $46.93/t CO2, and an LCOE of $164.33/MWh.« less

Simulations of Ground and Space-Based Oxygen Atom Experiments

NASA Technical Reports Server (NTRS)

Cline, Jason; Braunstein, Matthew; Minton, Timothy

2003-01-01

Contents include the following: 1. SS calculations show multi-collision effect can affect both downstream measurements and flux at surface. 2. Pulsed calculations at nominal source fluxes show that the flux to the surface is close to that expected from theory, but more information is needed. 3. Pulsed calculations needed more resolution to determine whether downstream flux correction is necessary. 4. Higher pulsed fluxes should show multi-collision effects more clearly.

Coupled Biogeochemical and Hydrodynamic Measurements over a Palauan Seagrass Bed: Can Seagrasses Mitigate Local Acidification Stress?

NASA Astrophysics Data System (ADS)

Hirsh, H.; Torres, W.; Shea, M.

2016-02-01

Interest in seagrass beds as a tool to locally mitigate ocean acidification is growing rapidly. Much of the interest in seagrasses is motivated by their root structure, which is able to sequester carbon over interannual and longer timescales. Far less is known about their biogeochemistry on shorter diel timescales, yet we know that diel cycle variation in CO2 chemistry on coral reefs can be quite substantial. Understanding short-term seagrass biogeochemistry is critical to evaluating if, and how, seagrasses may eventually be utilized to mitigate OA on coral reefs. We present the results of a high-resolution, 24-hour control volume experiment conducted in the Republic of Palau covering a 50m x 100m seagrass bed. Our dataset includes diel cycles of hydrodynamic (current profiles and turbulence), biogeochemical (pH, pCO2, TA, DIC, and O2), and environmental (temperature and salinity) parameters. We use these coupled hydrodynamic-biogeochemical measurements to estimate ecosystem metabolism and better quantify the capacity of seagrass to mitigate local acidification through the photosynthetic uptake of CO2. Combining our field observations with box model predictions allows us to gain better insight into the mechanisms that control seagrass metabolism and their ability to buffer CO2 for downstream corals.

Mass spectrometric screening and identification of acidic metabolites in fulvic acid fractions of contaminated groundwater.

PubMed

Jobelius, Carsten; Frimmel, Fritz H; Zwiener, Christian

2014-05-01

The anaerobic microbial degradation of aromatic and heterocyclic compounds is a prevalent process in contaminated groundwater systems. The introduction of functional groups into the contaminant molecules often results in aromatic and heterocyclic and succinic acids. These metabolites can be used as indicators for prevailing degradation processes. Therefore, there is a strong interest in developing analytical methods for screening and identification of these metabolites. In this study, neutral loss scans (NLS) by liquid chromatography-electrospray ionization/tandem mass spectrometry with losses of CO2 (NL ∆m/z = 44) and C2H4(CO2)2 (NL ∆m/z = 116) were applied for the first time successfully to screen selectively for acidic and succinic metabolites of aromatic and heterocyclic contaminants in two fulvic acid fractions from a contaminated site and a downstream region of a tar oil-polluted groundwater. Identification of these preselected signals was performed by high-resolution mass spectrometry with a liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry instrument. High-resolution mass and mass fragmentation data were then compared with a list of known metabolites from a literature search or matched with chemical databases supported with in silico fragmentation. Based on authentic analytical standards, several compounds from NLS were identified (e.g., 4-hydroxy-3-methylbenzoic acid, benzylsuccinic acid, naphthyl-2-methylsuccinic acid, 2-carboxyindane, and 2-carboxybenzothiophene) and tentatively identified (e.g., benzofuranmethylsuccinic acid and dihydrocarboxybenzothiophene) as aromatic, phenolic, heterocyclic, and succinic acids. The acidic metabolites were found exclusively in the contaminated region of the aquifer which indicates active biodegradation processes and no relevant occurrence of acidic metabolites in the downstream region.

The modules of trans-acyltransferase assembly lines redefined with a central acyl carrier protein.

PubMed

Vander Wood, Drew A; Keatinge-Clay, Adrian T

2018-06-01

Here, the term "module" is redefined for trans-acyltransferase (trans-AT) assembly lines to agree with how its domains cooperate and evolutionarily co-migrate. The key domain in both the polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) modules of assembly lines is the acyl carrier protein (ACP). ACPs not only relay growing acyl chains through the assembly line but also collaborate with enzymes in modules, both in cis and in trans, to add a specific chemical moiety. A ketosynthase (KS) downstream of ACP often plays the role of gatekeeper, ensuring that only a single intermediate generated by the enzymes of a module is passed downstream. Bioinformatic analysis of 526 ACPs from 33 characterized trans-AT assembly lines reveals ACPs from the same module type generally clade together, reflective of the co-evolution of these domains with their cognate enzymes. While KSs downstream of ACPs from the same module type generally also clade together, KSs upstream of ACPs do not-in disagreement with the traditional definition of a module. Beyond nomenclature, the presented analysis impacts our understanding of module function, the evolution of assembly lines, pathway prediction, and assembly line engineering. © 2018 Wiley Periodicals, Inc.

Dual-hormone stress reactivity predicts downstream war-zone stress-evoked PTSD.

PubMed

Josephs, Robert A; Cobb, Adam R; Lancaster, Cynthia L; Lee, Han-Joo; Telch, Michael J

2017-04-01

The crucial role of the hypothalamic-pituitary-adrenal axis (HPA) in stress-related homeostasis suggests dysregulated HPA involvement in the pathogenesis of post-traumatic stress disorder (PTSD), yet most studies examining linkages between HPA axis measures and PTSD have yielded null findings. One untested explanation for this inconsistency is a failure to account for simultaneous adrenal and gonadal influence. Here we tested the singular and interactive effects of cortisol (C R ) and testosterone (T R ) reactivity as moderators of war-zone stress evoked PTSD emergence in the war-zone. U.S. soldiers (N=120) scheduled for deployment to Iraq completed pre-deployment measures of C R and T R stress reactivity to a CO 2 inhalation challenge. Once deployed, monthly assessments of exposure to traumatic war-zone stressors and PTSD symptoms were collected via a web-based assessment system. Cortisol hypo-reactivity potentiated the pathogenic impact of war-zone stressors only in soldiers for whom the CO 2 challenge did not elevate testosterone, suggesting that the dual hormone stress reactivity profile of blunted cortisol and testosterone may confer increased risk for PTSD emergence by potentiating the pathogenic effects of war-zone stressors. Findings underscore the utility of assessing both HPA and HPG stress reactivity when assessing PTSD vulnerability and may help inform efforts for enhanced soldier screening and inoculation to war-zone stressors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection of triclocarban and two co-contaminating chlorocarbanilides in US aquatic environments using isotope dilution liquid chromatography tandem mass spectrometry.

PubMed

Sapkota, Amir; Heidler, Jochen; Halden, Rolf U

2007-01-01

The antimicrobial compound triclocarban (TCC; 3,4,4'-trichlorocarbanilide; CAS# 101-20-2) is a high-production-volume chemical, recently suggested to cause widespread contamination of US water resources. To test this hypothesis, we developed an isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry method for ultratrace analysis of TCC (0.9 ng/L detection limit) and analyzed low-volume water samples (200 mL) along with primary sludge samples from across the United States. All river water samples (100%) collected downstream of wastewater treatment plants had detectable levels of TCC, as compared to 56% of those taken upstream. Concentrations of TCC (mean+/-standard deviation) downstream of sewage treatment plants (84+/-110 ng/L) were significantly higher (P<0.05; Wilcoxon rank sum test) than those of samples taken upstream (12+/-15 ng/L). Compared to surface water, mean TCC concentrations found in dried, primary sludge obtained from municipal sewage treatment plants in five states were six orders of magnitude greater (19,300+/-7100 microg/kg). Several river samples contained a co-contaminant, identified based on its chromatographic retention time, molecular base ion, and MS/MS fragmentation behavior as 4,4'-dichlorocarbanilide (DCC; CAS# 1219-99-4). In addition to TCC and DCC, municipal sludge contained a second co-contaminant, 3,3',4,4'-tetrachlorocarbanilide (TetraCC; CAS# 4300-43-0). Both newly detected compounds were present as impurities (0.2%(w/w) each) in technical grade TCC (99%). Application of the new method for chlorocarbanilide analysis yielded TCC occurrence data for 13 US states, confirmed the role of sewage treatment plants as environmental inputs of TCC, and identified DCC and TetraCC as previously unrecognized pollutants released into the environment alongside TCC.

Up-scaling Stream Ecosystem Processes to Predict the Effects of Land Cover Change at a Watershed Scale in the Atlantic Tropical Rainforest.

NASA Astrophysics Data System (ADS)

Tromboni, F.; Feijó de Lima, R.; Silva-Júnior, E. F.; Lourenço-Amorim, C.; Zandoná, E.; Moulton, T. P.; Da Silva, B. S.; Silva-Araújo, M.; Thomas, S. A.

2015-12-01

Riparian land-cover change (LCC) causes a cascade of subsequent hierarchical effects that propagate through abiotic compartments until reaching the biota, altering stream ecosystem functioning. Due to the movement of water downstream, these lateral effects co-occur with longitudinal influences. We investigated both the lateral and longitudinal effects of deforestation in four streams in the Atlantic tropical rainforest of Brazil. We collected physical-chemical, geomorphic, hydrological data and samples of macroinvertebrates assemblages. We then categorized land cover at different scales (from different riparian and reach buffer sizes to sub and total watershed) using a SPOT-5 satellite image and ArcGIS. We also carried out a series of experiments along the streams to understand: 1) the mechanisms by which LCC affects periphyton and how these changes alter metabolism and nutrient uptake rates; 2) the downstream distance at which periphyton and the associated variables change in the transitions from one riparian category to the other. We used (i) a path analysis to test if our hypothesized land-cover cascade model described our data and (ii) non-linear models to describe the longitudinal effect on each variable. Our results showed that deforestation produced a range of physical changes at different spatial scale, longitudinally altering periphyton taxonomic composition (taxa depending on light), stoichiometry (nutritionally richer with increasing deforestation) and growth rates (greater in deforested). Macroinvertebrate assemblages behaved similarly to chlorophyll a in response to forest loss. Respiration rate increased with deforestation probably due to higher nutrient concentrations but primary production did not increase. Models were used to upscale LCC impacts on ecosystem processes from local scale experiments to landscape and our work has important implications for socio-economic decisions concerning ecosystem management and conservation.

Responses of shortfin eel (Anguilla australis) exposed in situ to pulp and paper effluent.

PubMed

van den Heuvel, Michael R; Landman, Michael J; Tremblay, Louis A

2006-10-01

The responses of shortfin eel (Anguilla australis) to discharges from two pulp and paper mills, municipal wastewater, and a geothermal power plant wastewater were examined. Eels were caged at 3 sites along the Tarawera River, North Island, New Zealand, to explore effects of a 3-wk exposure down a contamination gradient (Ref --> D1 --> D2). Most of the observed effects were seen in eels caged at the furthest downstream site (D2), below all the discharge areas. General hematology in eels was unaffected, as measures did not differ markedly at the two downstream sites compared with the reference site. At D2, eels were significantly lighter per unit length (reduced condition factor), although liver and spleen size (LSI and SSI) were unaffected. Significantly elevated circulating sex steroid concentrations (testosterone and estradiol) were measured in D2 eels and increasing sex steroid levels at both sites downstream of the reference site were observed. Significant ethoxyresorufin O-deethylase (EROD) activity induction was seen in D2 eels and bile chemistry showed significant accumulation of pyrene and retene equivalents. However, significantly greater concentrations of total resin acids were found in the bile of eels from the intermediate site (D1), between the two pulp and paper mills. The higher polycyclic aromatic hydrocarbon (PAH) equivalents found in the bile of D2 eels suggest that resin acid neutrals, particularly retene, are responsible for some of the effects observed in eels at the furthest downstream exposure site. Levels of pulp and paper mill extractives in sediment, including the PAH retene, support this conclusion.

Branchial CO(2) receptors and cardiorespiratory adjustments during hypercarbia in Pacific spiny dogfish (Squalus acanthias).

PubMed

McKendry, J E; Milsom, W K; Perry, S F

2001-04-01

Adult Pacific spiny dogfish (Squalus acanthias) were exposed to acute (approximately 20 min) hypercarbia while we monitored arterial blood pressure, systemic vascular resistance (R(S)), cardiac output (V(b)) and frequency (fh) as well as ventilatory amplitude (V(AMP)) and frequency (f(V)). Separate series of experiments were conducted on control, atropinized (100 nmol kg(-1)) and branchially denervated fish to investigate putative CO(2)-chemoreceptive sites on the gills and their link to the autonomic nervous system and cardiorespiratory reflexes.In untreated fish, moderate hypercarbia (water CO(2 )partial pressure; Pw(CO2)=6.4+/-0.1 mmHg) (1 mmHg=0.133 kPa) elicited significant increases in V(AMP) (of approximately 92 %) and f(V) (of approximately 18 %) as well as decreases in fh (of approximately 64 %), V.(b) (approximately 29 %) and arterial blood pressure (of approximately 11 %); R(S) did not change significantly. Denervation of the branchial branches of cranial nerves IX and X to the pseudobranch and each gill arch eliminated all cardiorespiratory responses to hypercarbia. Prior administration of the muscarinic receptor antagonist atropine also abolished the hypercarbia-induced ventilatory responses and virtually eliminated all CO(2)-elicited cardiovascular adjustments. Although the atropinized dogfish displayed a hypercarbic bradycardia, the magnitude of the response was significantly attenuated (36+/-6 % decrease in fh in controls versus 9+/-2 % decrease in atropinized fish; means +/- s.e.m.).Thus, the results of the present study reveal the presence of gill CO(2) chemoreceptors in dogfish that are linked to numerous cardiorespiratory reflexes. In addition, because all cardiorespiratory responses to hypercarbia were abolished or attenuated by atropine, the CO(2) chemoreception process and/or one or more downstream elements probably involve cholinergic (muscarinic) neurotransmission.

Microalgae-mediated simultaneous treatment of toxic thiocyanate and production of biodiesel.

PubMed

Ryu, Byung-Gon; Kim, Jungmin; Yoo, Gursong; Lim, Jun-Taek; Kim, Woong; Han, Jong-In; Yang, Ji-Won

2014-04-01

In this work, a method for simultaneously degrading the toxic pollutant, thiocyanate, and producing microalgal lipids using mixed microbial communities was developed. Aerobic activated sludge was used as the seed culture and thiocyanate was used as the sole nitrogen source. Two cultivation methods were sequentially employed: a lithoautotrophic mode and a photoautotrophic mode. Thiocyanate hydrolysis and a nitrification was found to occur under the first (lithoautotrophic) condition, while the oxidized forms of nitrogen were assimilated by the photoautotrophic consortium and lipids were produced under the second condition. The final culture exhibited good settling efficiency (∼ 70% settling over 10 min), which can benefit downstream processing. The highest CO2 fixation rate and lipid productivity were observed with 2.5% and 5% CO2, respectively. The proposed integrated algal-bacterial system appears to be a feasible and even beneficial option for thiocyanate treatment and production of microbial lipids. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simultaneous knockdown of BRAF and expression of INK4A in melanoma cells leads to potent growth inhibition and apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao Yanhua; Zhang Yan; Yang Zhen

2008-06-06

Abnormal BRAF and p16INK4A co-exist in 60% of melanomas. BRAF mutation also occurs in 80% of benign nevi where it turns-on p16INK4A resulting in proliferative senescence; loss of p16INK4A removes the inhibitory block leading to melanoma development. Since only melanomas with wild-type BRAF have amplified CDK4 and cyclin D1 genes, p16INK4A-CDK4/6-cyclin D pathway is viewed as linearly downstream of BRAF. Thus, co-occurrence of aberrant BRAF and INK4A may be remnant of changes during melanoma formation without functional significance. To explore this notion, we simultaneously knocked down BRAF (via siRNA) and expressed INK4A cDNA in melanoma cells and observed enhanced growthmore » inhibition. Notably, although each alone had no statistically significant effect on apoptosis, co-expression of BRAF siRNA and INK4A cDNA caused potent apoptosis, which was associated with up-regulation of BIM and down-regulation of BCL2. Our results suggest that aberrant BRAF and INK4A cooperate to promote proliferation and survival of melanoma cells.« less

STRUCTURAL VARIATION OF MOLECULAR GAS IN THE SAGITTARIUS ARM AND INTERARM REGIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sawada, Tsuyoshi; Hasegawa, Tetsuo; Sugimoto, Masahiro

We have carried out survey observations toward the Galactic plane at l Almost-Equal-To 38 Degree-Sign in the {sup 12}CO and {sup 13}CO J = 1-0 lines using the Nobeyama Radio Observatory 45 m telescope. A wide area (0.{sup 0}8 Multiplication-Sign 0.{sup 0}8) was mapped with high spatial resolution (17''). The line of sight samples the gas in both the Sagittarius arm and the interarm regions. The present observations reveal how the structure and physical conditions vary across a spiral arm. We classify the molecular gas in the line of sight into two distinct components based on its appearance: the brightmore » and compact B component and the fainter and diffuse (i.e., more extended) D component. The B component is predominantly seen at the spiral arm velocities, while the D component dominates at the interarm velocities and is also found at the spiral arm velocities. We introduce the brightness distribution function and the brightness distribution index (BDI, which indicates the dominance of the B component) in order to quantify the map's appearance. The radial velocities of BDI peaks coincide with those of high {sup 12}CO J = 3-2/{sup 12}CO J = 1-0 intensity ratio (i.e., warm gas) and H II regions, and tend to be offset from the line brightness peaks at lower velocities (i.e., presumably downstream side of the arm). Our observations reveal that the gas structure at small scales changes across a spiral arm: bright and spatially confined structures develop in a spiral arm, leading to star formation at the downstream side, while extended emission dominates in the interarm region.« less

Evaluation of changes in atmospheric and oceanic fluxes during continental ice sheet retreat

NASA Astrophysics Data System (ADS)

Martin, J.; Martin, E. E.; Deuerling, K. M.

2017-12-01

Extensive land areas were exposed across North America, Eurasia, and to a lesser extent Greenland as continental ice sheets retreated following the last glacial maximum. A transect of watersheds from the coast to the western Greenland Ice Sheet (GrIS) provides an opportunity to evaluate possible changes in oceanic solute fluxes and atmospheric CO2 exchange as ice sheets retreat. We evaluate these fluxes in one proglacial watershed (draining ice sheet runoff) and four deglaciated watersheds (draining local precipitation and permafrost melt). Sr isotope ratios indicate bedrock near the coast has experienced greater weathering than near the ice sheet. A mass balance model of the major element composition of stream water indicates weathering in deglaciated watersheds is dominated by carbonic acid dissolution of carbonate minerals near the ice sheet that switches to carbonic acid alteration of silicate minerals near the coast. In addition, weathering by sulfuric acid, derived from oxidative dissolution of sulfide minerals, increases from the ice sheet to the coast. These changes in the weathered minerals and weathering acids impact CO2 sequestration associated with weathering. Weathering consumes 350 to 550 µmol CO2/L in watersheds near the ice sheet, but close to the coast, consumes only 15 µmol CO2/L in one watershed and sources 140 µmol CO2/L to the atmosphere at another coastal watershed. The decreasing CO2 weathering sink from the GrIS to coast reflects decreased carbonic acid weathering and increased sulfuric acid weathering of carbonate minerals. The proglacial stream shows downstream variations in composition from mixing of two water sources, with only minor in-stream weathering, which consumes < 0.1 µmol CO2/L. Discharge from the deglaciated watersheds is currently unknown but their higher solute concentrations and CO2 exchange than proglacial systems suggest deglaciated watersheds dominate atmospheric fluxes of CO2 and oceanic solute fluxes. These results imply that the initial CO2 drawdown associated with weathering of freshly exposed, fine-grained glacial sediment in deglaciated watersheds will decrease as the extent of weathering increases. As a result, weathering in this environment may become a source of atmospheric CO2 that could enhance CO2 induced global warming.

Streamflow gain-loss characteristics of Elkhead Creek downstream from Elkhead Reservoir near Craig, Colorado, 2009

USGS Publications Warehouse

Ruddy, Barbara C.

2010-01-01

The U.S. Geological Survey (USGS), in cooperation with the Colorado Water Conservation Board, the Upper Colorado River Endangered Fish Recovery Program (UCREFRP), Colorado Division of Water Resources, and City of Craig studied the gain-loss characteristics of Elkhead Creek downstream from Elkhead Reservoir to the confluence with the Yampa River during August through October 2009. Earlier qualitative interpretation of streamflow data downstream from the reservoir indicated that there could be a transit loss of nearly 10 percent. This potential loss could be a significant portion of the releases from Elkhead Reservoir requested by UCREFRP during late summer and early fall for improving critical habitat for endangered fish downstream in the Yampa River. Information on the gain-loss characteristics was needed for the effective management of the reservoir releases. In order to determine streamflow gain-loss characteristics for Elkhead Creek, eight measurement sets were made at four strategic instream sites and at one diversion from August to early October 2009. An additional measurement set was made after the study period during low-flow conditions in November 2009. Streamflow measurements were made using an Acoustic Doppler Velocimeter to provide high accuracy and consistency, especially at low flows. During this study, streamflow ranged from about 5 cubic feet per second up to more than 90 cubic feet per second with step increments in between. Measurements were made at least 24 hours after a change in reservoir release (streamflow) during steady-state conditions. The instantaneous streamflow measurements and the streamflow volume comparisons show the reach of Elkhead Creek immediately downstream from Elkhead Reservoir to the streamflow-gaging station 09246500, Elkhead Creek near Craig, CO, is neither a gaining nor losing reach. The instantaneous measurements immediately downstream from the dam and the combined measurements of Norvell ditch plus streamflow-gaging station 09246500 are mostly within the plus or minus 5-percent measurement error of each other. The variability of data is such that sometimes the streamflow is greater upstream than downstream and sometimes the streamflow is greater downstream than upstream. Streamflow volumes were calculated for multiple time periods as determined by a change in release from the reservoir. Streamflow volumes were greater downstream than upstream for all but one time period. The predominance of greater streamflows downstream is due to the difference between the USGS instantaneous measurements and record computation with the Supervisory Control and Data Acquisition (SCADA) record at the dam. Immediately following an increase in streamflow from the reservoir, the downstream volume was smaller than the upstream volume, but this was an artifact of the traveltime between the two sites and possibly small amounts of water entering the streambank. Traveltimes were shorter at higher streamflows and when streamflow was increasing.

Dana-Farber Cancer Institute: Identification of Therapeutic Targets Across Cancer Types | Office of Cancer Genomics

Cancer.gov

The Dana Farber Cancer Institute CTD2 Center focuses on the use of high-throughput genetic and bioinformatic approaches to identify and credential oncogenes and co-dependencies in cancers. This Center aims to provide the cancer research community with information that will facilitate the prioritization of targets based on both genomic and functional evidence, inform the most appropriate genetic context for downstream mechanistic and validation studies, and enable the translation of this information into therapeutics and diagnostics.

Role of the median preoptic nucleus in the chronic hypotensive effect of losartan in sodium-replete normal rats.

PubMed

Ployngam, Trasida; Katz, Stephen S; Collister, John P

2010-01-01

1. We have shown previously that the chronic hypotensive effect of the angiotensin II AT1 receptor antagonist losartan is mediated, in part, by the subfornical organ (SFO). However, the neural pathway(s) mediating this central effect of losartan downstream from the SFO has not been completely elucidated. 2. The present study was designed to test the hypothesis that the median preoptic nucleus (MnPO) is a crucial part of the neural pathway necessary for the chronic hypotensive effect of losartan. To test this hypothesis, male Sprague-Dawley rats were subjected to either Sham or electrolytic lesion of the MnPO (MnPOx). Rats were instrumented with radiotelemetric transducers and aortic flow probes for the continuous measurement of mean arterial pressure (MAP) and heart rate and cardiac output (CO), respectively. Total peripheral resistance (TPR) was calculated as MAP/CO. After 3 days of baseline measurements, rats were infused intraperitoneally with losartan (10 mg/kg per day) via an osmotic minipump at a rate of 5 microL/min. 3. The data revealed that, by Day 9 of losartan treatment, MAP had decreased 34 +/- 2 mmHg in MnPOx rats (n = 9), whereas the MAP of Sham-lesioned rats (n = 8) had only decreased 24 +/- 3 mmHg. These findings were accompanied by a greater decrease in TPR in MnPOx compared with Sham rats (-0.464 vs-0.237 mmHg/mL per min, respectively), whereas CO remained unchanged throughout the study protocol. 4. These results do not support the hypothesis that an intact MnPO is necessary to mediate the full chronic hypotensive effect of losartan in normal rats. Instead, they appear to suggest that the MnPO may play an important role in buffering the profound hypotension induced by losartan.

Effects of Packstock Use and Backpackers on Water Quality in Yosemite National Park, California

NASA Astrophysics Data System (ADS)

Forrester, H.; Clow, D. W.; Roche, J. W.; Heyvaert, A.

2016-12-01

Visitor use, primarily backpacker camping, packstock (horse and mule) trail use, and packstock grazing, in designated Wilderness, increases the potential for negative effects on water quality. To determine the effects of visitor use on water quality in Wilderness in Yosemite National Park, we collected and analyzed surface-water samples for water quality indicators, consisting of fecal indicator bacteria (Escherichia coli), nutrients (nitrogen, phosphorus), suspended sediment concentration (SSC), and hormones (e.g. estrogen compounds) during the summers of 2012-2014. We collected samples upstream and downstream from different types of visitor use at routine intervals (weekly or biweekly) and during storms. Additionally, we sampled upstream and downstream from meadows, and targeted different types of visitor use during a park-wide synoptic sampling campaign (n=63). At packstock stream crossings, statistically significant (P≤0.05) increases in Escherichia coli (E. coli) and SSC occurred downstream from crossings compared to upstream conditions during routine sampling (median difference: 3 CFU 100ml-1, and >0.3 mg l-1, respectively) and during storms (median difference: 32 CFU 100ml-1, and 2.9 mg l-1). At backpacker campsites, during routine sampling, significant increases occurred downstream from backpacker camping for E. coli (median difference: 1 CFU 100ml-1), and estrogen hormones were detected. At packstock grazing areas, which are located in meadows, no significant increases were detected for any of the measured water quality indicators downstream from grazing. Most synoptic sample concentrations were near or below detection limits. Our results indicate that under current use levels: 1) packstock trail use and backpacker camping are associated with detectable effects on water quality, which are most pronounced during storms; 2) increases in water quality indicators were not detected downstream from meadows where packstock were grazed; and 3) environmental processes in meadows provide a valuable ecosystem service by reducing human related sources of microbial contamination.

Nicotine Induces Podocyte Apoptosis through Increasing Oxidative Stress

PubMed Central

Lan, Xiqian; Lederman, Rivka; Eng, Judith M.; Shoshtari, Seyedeh Shadafarin Marashi; Saleem, Moin A.; Malhotra, Ashwani; Singhal, Pravin C.

2016-01-01

Background Cigarette smoking plays an important role in the progression of chronic kidney disease (CKD). Nicotine, one of the major components of cigarette smoking, has been demonstrated to increase proliferation of renal mesangial cells. In this study, we examined the effect of nicotine on podocyte injury. Methods To determine the expression of nicotinic acetylcholine receptors (nAChR subunits) in podocytes, cDNAs and cell lysate of cultured human podocytes were used for the expression of nAChR mRNAs and proteins, respectively; and mouse renal cortical sections were subjected to immunofluorescant staining. We also studied the effect of nicotine on podocyte nephrin expression, reactive oxygen species (ROS) generation (via DCFDA loading followed by fluorometric analysis), proliferation, and apoptosis (morphologic assays). We evaluated the effect of nicotine on podocyte downstream signaling including phosphorylation of ERK1/2, JNK, and p38 and established causal relationships by using respective inhibitors. We used nAChR antagonists to confirm the role of nicotine on podocyte injury. Results Human podocytes displayed robust mRNA and protein expression of nAChR in vitro studies. In vivo studies, mice renal cortical sections revealed co-localization of nAChRs along with synaptopodin. In vitro studies, nephrin expression in podocyte was decreased by nicotine. Nicotine stimulated podocyte ROS generation; nonetheless, antioxidants such as N-acetyl cysteine (NAC) and TEMPOL (superoxide dismutase mimetic agent) inhibited this effect of nicotine. Nicotine did not modulate proliferation but promoted apoptosis in podocytes. Nicotine enhanced podocyte phosphorylation of ERK1/2, JNK, and p38, and their specific inhibitors attenuated nicotine-induced apoptosis. nAChR antagonists significantly suppressed the effects of nicotine on podocyte. Conclusions Nicotine induces podocyte apoptosis through ROS generation and associated downstream MAPKs signaling. The present study provides insight into molecular mechanisms involved in smoking associated progression of chronic kidney disease. PMID:27907022

Development of attrition resistant iron-based Fischer-Tropsch catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2000-09-20

The Fischer-Tropsch (F-T) reaction provides a way of converting coal-derived synthesis gas (CO+H{sub 2}) to liquid fuels. Since the reaction is highly exothermic, one of the major problems in control of the reaction is heat removal. Recent work has shown that the use of slurry bubble column reactors (SBCRs) can largely solve this problem. The use of iron-based catalysts is attractive not only due to their low cost and ready availability, but also due to their high water-gas shift activity which makes it possible to use these catalysts with low H{sub 2}/CO ratios. However, a serious problem with use ofmore » Fe catalysts in a SBCR is their tendency to undergo attrition. This can cause fouling/plugging of downstream filters and equipment, makes the separation of catalyst from the oil/wax product very difficult if not impossible, and results a steady loss of catalyst from the reactor. The objective of this research is to develop robust iron-based Fischer-Tropsch catalysts that have suitable activity, selectivity and stability to be used in the slurry bubble column reactor. Specifically we aim to develop to: (1) improve the performance and preparation procedure of the high activity, high attrition resistant, high alpha iron-based catalysts synthesized at Hampton University (2) seek improvements in the catalyst performance through variations in process conditions, pretreatment procedures and/or modifications in catalyst preparation steps and (3) investigate the performance in a slurry reactor. The effort during the reporting period has been devoted to effects of pretreating procedures, using H{sub 2}, CO and syngas (H{sub 2}/CO = 0.67) as reductants, on the performance (activity, selectivity and stability with time) of a precipitated iron catalyst (100Fe/5Cu/4.2K/10SiO{sub 2} on a mass basis ) during F-T synthesis were studied in a fixed-bed reactor.« less

GUIDANCE2: accurate detection of unreliable alignment regions accounting for the uncertainty of multiple parameters.

PubMed

Sela, Itamar; Ashkenazy, Haim; Katoh, Kazutaka; Pupko, Tal

2015-07-01

Inference of multiple sequence alignments (MSAs) is a critical part of phylogenetic and comparative genomics studies. However, from the same set of sequences different MSAs are often inferred, depending on the methodologies used and the assumed parameters. Much effort has recently been devoted to improving the ability to identify unreliable alignment regions. Detecting such unreliable regions was previously shown to be important for downstream analyses relying on MSAs, such as the detection of positive selection. Here we developed GUIDANCE2, a new integrative methodology that accounts for: (i) uncertainty in the process of indel formation, (ii) uncertainty in the assumed guide tree and (iii) co-optimal solutions in the pairwise alignments, used as building blocks in progressive alignment algorithms. We compared GUIDANCE2 with seven methodologies to detect unreliable MSA regions using extensive simulations and empirical benchmarks. We show that GUIDANCE2 outperforms all previously developed methodologies. Furthermore, GUIDANCE2 also provides a set of alternative MSAs which can be useful for downstream analyses. The novel algorithm is implemented as a web-server, available at: http://guidance.tau.ac.il. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Impacts of global changes on the biogeochemistry and environmental effects of dissolved organic matter at the land-ocean interface: a review.

PubMed

Zhuang, Wan-E; Yang, Liyang

2018-02-01

Dissolved organic matter (DOM) is an important component in the biogeochemistry and ecosystem function of aquatic environments at the highly populated land-ocean interface. The mobilization and transformation of DOM at this critical interface are increasingly affected by a series of notable global changes such as the increasing storm events, intense human activities, and accelerating glacier loss. This review provides an overview of the changes in the quantity and quality of DOM under the influences of multiple global changes. The profound implications of changing DOM for aquatic ecosystem and human society are further discussed, and future research needs are suggested for filling current knowledge gaps. The fluvial export of DOM is strongly intensified during storm events, which is accompanied with notable changes in the chemical composition and reactivity of DOM. Land use not only changes the mobilization of natural DOM source pools within watersheds but also adds DOM of distinct chemical composition and reactivity from anthropogenic sources. Glacier loss brings highly biolabile DOM to downstream water bodies. The changing DOM leads to significant changes in heterotrophic activity, CO 2 out gassing, nutrient and pollutant biogeochemistry, and disinfection by-product formation. Further studies on the source, transformations, and downstream effects of storm DOM, temporal variations of DOM and its interactions with other pollutants in human-modified watersheds, photo-degradability of glacier DOM, and potential priming effects, are essential for better understanding the responses and feedbacks of DOM at the land-ocean interface under the impacts of global changes.

Light-to-moderate ethanol feeding augments AMPK-α phosphorylation and attenuates SREBP-1 expression in the liver of rats.

PubMed

Nammi, Srinivas; Roufogalis, Basil D

2013-01-01

Fatty liver disease, a hepatic manifestation of metabolic syndrome, is one of the major causes of chronic liver diseases. Epidemiological studies suggest that regular light-to-moderate ethanol consumption lowers the risk of developing metabolic disorders including dislipidemia, insulin resistance, type 2 diabetes and fatty liver disease. However, the mechanism(s) of the protective effect of light-to-moderate ethanol consumption on the liver remains unknown. In the present study, we investigated the effects of light (6%, 0.94 g/kg/day) and moderate (12%, 1.88 g/kg/day) ethanol feeding in rats for 3 weeks on the circulating and hepatic biochemical profiles and on the hepatic protein expression and phosphorylation status of adenosine monophosphate-activated protein kinase-α (AMPK-α) and other down-stream targets of this enzyme including sterol regulatory element-binding protein-1 (SREBP-1), SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase). Despite no significant difference in food-intake among the groups, light ethanol treatment significantly increased the body weight compared to control rats. Serum glucose, insulin, total cholesterol, triglycerides, phospholipids and hepatic cholesterol and triglycerides were not significantly different among the groups. However, serum free fatty acids were significantly reduced with light ethanol treatment. Both light and moderate ethanol treatment significantly increased the hepatic levels of phosphorylated AMPK-α protein and this was associated with significant reduction of SREBP-1 protein expression, suggesting an enhanced fatty acid oxidation. In addition, light ethanol treatment significantly decreased the SCAP protein expression in the liver. However, liver HMG-CoA protein expression was not significantly different with ethanol consumption. Chronic light-to-moderate ethanol consumption increased AMPK activation which was associated with decreased expression of SREBP-1 and SCAP in the liver. Thus, our studies provide mechanistic evidence for the earlier epidemiological studies that indicate light-to-moderate ethanol intake lowers the risk of development of fatty liver disease and other metabolic disorders. Our studies demonstrate that the protective effects of light-to-moderate ethanol arise at least in part by increased phosphorylation of AMPK-α and decreased SREBP-1 expression in the liver. Further studies are warranted to determine the effects of light-to-moderate ethanol on intracellular up-stream and down-stream targets of AMPK and also on the implications of light-to-moderate ethanol in protecting non-alcoholic fatty liver disease.

Emissions of carbon dioxide and methane from a headwater stream network of interior Alaska

USGS Publications Warehouse

Crawford, John T.; Striegl, Robert G.; Wickland, Kimberly P.; Dornblaser, Mark M.; Stanley, Emily H.

2013-01-01

Boreal ecosystems store significant quantities of organic carbon (C) that may be vulnerable to degradation as a result of a warming climate. Despite their limited coverage on the landscape, streams play a significant role in the processing, gaseous emission, and downstream export of C, and small streams are thought to be particularly important because of their close connection with the surrounding landscape. However, ecosystem carbon studies do not commonly incorporate the role of the aquatic conduit. We measured carbon dioxide (CO2) and methane (CH4) concentrations and emissions in a headwater stream network of interior Alaska underlain by permafrost to assess the potential role of stream gas emissions in the regional carbon balance. First-order streams exhibited the greatest variability in fluxes of CO2 and CH4,and the greatest mean pCO2. High-resolution time series of stream pCO2 and discharge at two locations on one first-order stream showed opposing pCO2 responses to storm events, indicating the importance of hydrologic flowpaths connecting CO2-rich soils with surface waters. Repeated longitudinal surveys on the stream showed consistent areas of elevated pCO2 and pCH4, indicative of discrete hydrologic flowpaths delivering soil water and groundwater having varying chemistry. Up-scaled basin estimates of stream gas emissions suggest that streams may contribute significantly to catchment-wide CH4 emissions. Overall, our results indicate that while stream-specific gas emission rates are disproportionately high relative to the terrestrial landscape, both stream surface area and catchment normalized emission rates were lower than those documented for the Yukon River Basin as a whole. This may be due to limitations of C sources and/or C transport to surface waters.

Automated microfluidic platform for studies of carbon dioxide dissolution and solubility in physical solvents.

PubMed

Abolhasani, Milad; Singh, Mayank; Kumacheva, Eugenia; Günther, Axel

2012-05-07

We present an automated microfluidic (MF) approach for the systematic and rapid investigation of carbon dioxide (CO(2)) mass transfer and solubility in physical solvents. Uniformly sized bubbles of CO(2) with lengths exceeding the width of the microchannel (plugs) were isothermally generated in a co-flowing physical solvent within a gas-impermeable, silicon-based MF platform that is compatible with a wide range of solvents, temperatures and pressures. We dynamically determined the volume reduction of the plugs from images that were accommodated within a single field of view, six different downstream locations of the microchannel at any given flow condition. Evaluating plug sizes in real time allowed our automated strategy to suitably select inlet pressures and solvent flow rates such that otherwise dynamically self-selecting parameters (e.g., the plug size, the solvent segment size, and the plug velocity) could be either kept constant or systematically altered. Specifically, if a constant slug length was imposed, the volumetric dissolution rate of CO(2) could be deduced from the measured rate of plug shrinkage. The solubility of CO(2) in the physical solvent was obtained from a comparison between the terminal and the initial plug sizes. Solubility data were acquired every 5 min and were within 2-5% accuracy as compared to literature data. A parameter space consisting of the plug length, solvent slug length and plug velocity at the microchannel inlet was established for different CO(2)-solvent pairs with high and low gas solubilities. In a case study, we selected the gas-liquid pair CO(2)-dimethyl carbonate (DMC) and volumetric mass transfer coefficients 4-30 s(-1) (translating into mass transfer times between 0.25 s and 0.03 s), and Henry's constants, within the range of 6-12 MPa.

Dual roles for CoAA and its counterbalancing isoform CoAM in human kidney cell tumorigenesis

PubMed Central

Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y.; Tsai, Ming-Jer; W. O’Malley, Bert

2008-01-01

Co-Activator Activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein we show that CoAA is a dual-function coregulator that inhibits G1/S transition in human kidney cells and suppresses anchorage independent growth and xenograft tumor formation. Suppression occurs in part by downregulating c-myc and its downstream effectors ccnd1 and skp2, and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene, c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, Coactivator Modulator (CoAM), antagonizes CoAA-induced G1/S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma as compared to normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice-isoform. This is so far the only example of a nuclear receptor coregulator involved in suppression of kidney cancer, and suggests potentially significant new roles for coregulators in renal cancer biology. PMID:18829545

Alterations in ubiquitin ligase Siah-2 and its corepressor N-CoR after P-MAPA immunotherapy and anti-androgen therapy: new therapeutic opportunities for non-muscle invasive bladder cancer

PubMed Central

Garcia, Patrick Vianna; Apolinário, Letícia Montanholi; Böckelmann, Petra Karla; Nunes, Iseu da Silva; Duran, Nelson; Fávaro, Wagner José

2015-01-01

The present study describes the role of the ubiquitin ligase Siah-2 and corepressor N-CoR in controlling androgen receptor (AR) and estrogen receptors (ERα and ERβ) signaling in an appropriate animal model (Fischer 344 female rats) of non-muscle invasive bladder cancer (NMIBC), especially under conditions of anti-androgen therapy with flutamide. Furthermore, this study describes the mechanisms of a promising therapeutic alternative for NMIBC based on Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) intravesical immunotherapy combined with flutamide, involving the interaction among steroid hormone receptors, their regulators and Toll-like receptors (TLRs). Our results demonstrated that increased Siah-2 and AR protein levels and decreased N-CoR, cytochrome P450 (CYP450) and estrogen receptors levels played a critical role in the urothelial carcinogenesis, probably leading to escape of urothelial cancer cells from immune system attack. P-MAPA immunotherapy led to distinct activation of innate immune system TLRs 2 and 4-mediated, resulting in increase of interferon signaling pathway, which was more effective in recovering the immunosuppressive tumor immune microenvironment and in recovering the bladder histology features than BCG (Bacillus Calmette-Guerin) treatments. The AR blockade therapy was important in the modulating of downstream molecules of TLR2 and TLR4 signaling pathway, decreasing the inflammatory cytokines signaling and enhancing the interferon signaling pathway when associated with P-MAPA. Taken together, the data obtained suggest that interferon signaling pathway activation and targeting AR and Siah-2 signals by P-MAPA intravesical immunotherapy alone and/ or in combination with AR blockade may provide novel therapeutic approaches for NMIBC. PMID:26191134

Alterations in ubiquitin ligase Siah-2 and its corepressor N-CoR after P-MAPA immunotherapy and anti-androgen therapy: new therapeutic opportunities for non-muscle invasive bladder cancer.

PubMed

Garcia, Patrick Vianna; Apolinário, Letícia Montanholi; Böckelmann, Petra Karla; da Silva Nunes, Iseu; Duran, Nelson; Fávaro, Wagner José

2015-01-01

The present study describes the role of the ubiquitin ligase Siah-2 and corepressor N-CoR in controlling androgen receptor (AR) and estrogen receptors (ERα and ERβ) signaling in an appropriate animal model (Fischer 344 female rats) of non-muscle invasive bladder cancer (NMIBC), especially under conditions of anti-androgen therapy with flutamide. Furthermore, this study describes the mechanisms of a promising therapeutic alternative for NMIBC based on Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) intravesical immunotherapy combined with flutamide, involving the interaction among steroid hormone receptors, their regulators and Toll-like receptors (TLRs). Our results demonstrated that increased Siah-2 and AR protein levels and decreased N-CoR, cytochrome P450 (CYP450) and estrogen receptors levels played a critical role in the urothelial carcinogenesis, probably leading to escape of urothelial cancer cells from immune system attack. P-MAPA immunotherapy led to distinct activation of innate immune system TLRs 2 and 4-mediated, resulting in increase of interferon signaling pathway, which was more effective in recovering the immunosuppressive tumor immune microenvironment and in recovering the bladder histology features than BCG (Bacillus Calmette-Guerin) treatments. The AR blockade therapy was important in the modulating of downstream molecules of TLR2 and TLR4 signaling pathway, decreasing the inflammatory cytokines signaling and enhancing the interferon signaling pathway when associated with P-MAPA. Taken together, the data obtained suggest that interferon signaling pathway activation and targeting AR and Siah-2 signals by P-MAPA intravesical immunotherapy alone and/ or in combination with AR blockade may provide novel therapeutic approaches for NMIBC.

Detection of ethene and other hydrocarbons in gas turbine engine exhaust using non-intrusive FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Arrigone, Giovanni M.; Welch, Michael A.; Hilton, Moira; Miller, Michael N.; Wilson, Christopher W.

2003-04-01

As part of the EU funded project AEROJET2, a number of gas turbine engine tests were performed in different facilities around Europe. At Farnborough, UK a Spey engine was used to test a suite of prototype optically based instrumentation designed to measure exhaust gas emissions without using extractive probe systems. In addition to the AEROJET 2 prototype instrumentation, a Bruker Equinox 55 Fourier transform infrared (FTIR) spectrometer was used to obtain infrared spectra of the exhaust plume both in emission and absorption mode. The Bruker FTIR spectrometer was fitted with a periscope system so that different lines of sight could be monitored in the plume in a vertical plane 25 cm downstream from the nozzle exit and 20 cm upstream of the center line of sight of the AEROJET 2 prototype instrumentation. DERA (now QinetiQ) provided exhaust gas analysis data for different engine running conditions using samples extracted from the plume with an intrusive probe. The probe sampled along a horizontal plane across the centerline of the engine 45 cm downstream of the nozzle exit. The Bruker spectrometer used both InSb (indium antimonide) and MCT (mercury-cadmium-telluride) detectors to maximize the sensitivity across the IR range 600-4000 cm-1. Typically, CO2 and H2O IR signatures dominate the observed spectra of the plume. However, the engine tests showed that at low power engine conditions spectral features associated with CO around 2147 cm-1 and with hydrocarbons could be observed at around 3000 cm-1. In particular the presence of ethene (C2H2) was detected from observation of its characteristic in and out of plane vibration mode at 949 cm-1. At high engine powers the presence of NO was detected at 1900.3 cm-1. Species concentrations were calculated using a slab model for each line of sight compared against reference spectra. The engine plume was assumed to be symmetric about the centerline. On this basis, data from the extractive sampling gas analysis that had been obtained by traversing the probe across a horizontal plane through the centerline could be compared with non-intrusive measurements made by scanning vertically. Adjustments have been made to account for the 20 cm downstream offset in measurement planes of the probe and the spectrometer behind the nozzle exit.

Plant responses to increasing CO2 reduce estimates of climate impacts on drought severity.

PubMed

Swann, Abigail L S; Hoffman, Forrest M; Koven, Charles D; Randerson, James T

2016-09-06

Rising atmospheric CO2 will make Earth warmer, and many studies have inferred that this warming will cause droughts to become more widespread and severe. However, rising atmospheric CO2 also modifies stomatal conductance and plant water use, processes that are often are overlooked in impact analysis. We find that plant physiological responses to CO2 reduce predictions of future drought stress, and that this reduction is captured by using plant-centric rather than atmosphere-centric metrics from Earth system models (ESMs). The atmosphere-centric Palmer Drought Severity Index predicts future increases in drought stress for more than 70% of global land area. This area drops to 37% with the use of precipitation minus evapotranspiration (P-E), a measure that represents the water flux available to downstream ecosystems and humans. The two metrics yield consistent estimates of increasing stress in regions where precipitation decreases are more robust (southern North America, northeastern South America, and southern Europe). The metrics produce diverging estimates elsewhere, with P-E predicting decreasing stress across temperate Asia and central Africa. The differing sensitivity of drought metrics to radiative and physiological aspects of increasing CO2 partly explains the divergent estimates of future drought reported in recent studies. Further, use of ESM output in offline models may double-count plant feedbacks on relative humidity and other surface variables, leading to overestimates of future stress. The use of drought metrics that account for the response of plant transpiration to changing CO2, including direct use of P-E and soil moisture from ESMs, is needed to reduce uncertainties in future assessment.

Plant responses to increasing CO2 reduce estimates of climate impacts on drought severity

PubMed Central

Koven, Charles D.; Randerson, James T.

2016-01-01

Rising atmospheric CO2 will make Earth warmer, and many studies have inferred that this warming will cause droughts to become more widespread and severe. However, rising atmospheric CO2 also modifies stomatal conductance and plant water use, processes that are often are overlooked in impact analysis. We find that plant physiological responses to CO2 reduce predictions of future drought stress, and that this reduction is captured by using plant-centric rather than atmosphere-centric metrics from Earth system models (ESMs). The atmosphere-centric Palmer Drought Severity Index predicts future increases in drought stress for more than 70% of global land area. This area drops to 37% with the use of precipitation minus evapotranspiration (P-E), a measure that represents the water flux available to downstream ecosystems and humans. The two metrics yield consistent estimates of increasing stress in regions where precipitation decreases are more robust (southern North America, northeastern South America, and southern Europe). The metrics produce diverging estimates elsewhere, with P-E predicting decreasing stress across temperate Asia and central Africa. The differing sensitivity of drought metrics to radiative and physiological aspects of increasing CO2 partly explains the divergent estimates of future drought reported in recent studies. Further, use of ESM output in offline models may double-count plant feedbacks on relative humidity and other surface variables, leading to overestimates of future stress. The use of drought metrics that account for the response of plant transpiration to changing CO2, including direct use of P-E and soil moisture from ESMs, is needed to reduce uncertainties in future assessment. PMID:27573831

Depletion of abundant plant RuBisCO protein using the protamine sulfate precipitation method.

PubMed

Kim, Yu Ji; Lee, Hye Min; Wang, Yiming; Wu, Jingni; Kim, Sang Gon; Kang, Kyu Young; Park, Ki Hun; Kim, Yong Chul; Choi, In Soo; Agrawal, Ganesh Kumar; Rakwal, Randeep; Kim, Sun Tae

2013-07-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is the most abundant plant leaf protein, hampering deep analysis of the leaf proteome. Here, we describe a novel protamine sulfate precipitation (PSP) method for the depletion of RuBisCO. For this purpose, soybean leaf total proteins were extracted using Tris-Mg/NP-40 extraction buffer. Obtained clear supernatant was subjected to the PSP method, followed by 13% SDS-PAGE analysis of total, PS-supernatant and -precipitation derived protein samples. In a dose-dependent experiment, 0.1% w/v PS was found to be sufficient for precipitating RuBisCO large and small subunits (LSU and SSU). Western blot analysis confirmed no detection of RuBisCO LSU in the PS-supernatant proteins. Application of this method to Arabidopsis, rice, and maize leaf proteins revealed results similar to soybean. Furthermore, 2DE analyses of PS-treated soybean leaf displayed enriched protein profile for the protein sample derived from the PS-supernatant than total proteins. Some enriched 2D spots were subjected to MALDI-TOF-TOF analysis and were successfully assigned for their protein identity. Hence, the PSP method is: (i) simple, fast, economical, and reproducible for RuBisCO precipitation from the plant leaf sample; (ii) applicable to both dicot and monocot plants; and (iii) suitable for downstream proteomics analysis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Industrial symbiosis: corn ethanol fermentation, hydrothermal carbonization, and anaerobic digestion.

PubMed

Wood, Brandon M; Jader, Lindsey R; Schendel, Frederick J; Hahn, Nicholas J; Valentas, Kenneth J; McNamara, Patrick J; Novak, Paige M; Heilmann, Steven M

2013-10-01

The production of dry-grind corn ethanol results in the generation of intermediate products, thin and whole stillage, which require energy-intensive downstream processing for conversion into commercial animal feed products. Hydrothermal carbonization of thin and whole stillage coupled with anaerobic digestion was investigated as alternative processing methods that could benefit the industry. By substantially eliminating evaporation of water, reductions in downstream energy consumption from 65% to 73% were achieved while generating hydrochar, fatty acids, treated process water, and biogas co-products providing new opportunities for the industry. Processing whole stillage in this manner produced the four co-products, eliminated centrifugation and evaporation, and substantially reduced drying. With thin stillage, all four co-products were again produced, as well as a high quality animal feed. Anaerobic digestion of the aqueous product stream from the hydrothermal carbonization of thin stillage reduced chemical oxygen demand (COD) by more than 90% and converted 83% of the initial COD to methane. Internal use of this biogas could entirely fuel the HTC process and reduce overall natural gas usage. Copyright © 2013 Wiley Periodicals, Inc.

Transcription co-activator SAYP mediates the action of STAT activator

PubMed Central

Panov, Vladislav V.; Kuzmina, Julia L.; Doronin, Semen A.; Kopantseva, Marina R.; Nabirochkina, Elena N.; Georgieva, Sofia G.; Vorobyeva, Nadezhda E.; Shidlovskii, Yulii V.

2012-01-01

Jak/STAT is an important signaling pathway mediating multiple events in development. We describe participation of metazoan co-activator SAYP/PHF10 in this pathway downstream of STAT. The latter, via its activation domain, interacts with the conserved core of SAYP. STAT is associated with the SAYP-containing co-activator complex BTFly and recruits BTFly onto genes. SAYP is necessary for stimulating STAT-driven transcription of numerous genes. Mutation of SAYP leads to maldevelopments similar to those observed in STAT mutants. Thus, SAYP is a novel co-activator mediating the action of STAT. PMID:22123744

Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis?

PubMed

Gerdes, N; Zirlik, A

2011-11-01

A plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front-runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co-inhibitory signals. In addition, many of these proteins enfold T cell-independent pro-atherogenic functions on a variety of cell types. Accordingly they represent potential targets for immune-modulatory and/or anti-inflammatory therapy of atherosclerosis. This review focuses on the diverse role of co-stimulatory molecules of the B7 and tumour necrosis factor (TNF)-superfamily and their downstream signalling effectors in atherosclerosis. In particular, the contribution of CD28/CD80/CD86/CTLA4, ICOS/ICOSL, PD-1/PDL-1/2, TRAF, CD40/CD154, OX40/OX40L, CD137/CD137L, CD70/CD27, GITR/GITRL, and LIGHT to arterial disease is reviewed. Finally, the potential for a therapeutic exploitation of these molecules in the treatment of atherosclerosis is discussed.

Ecological and water quality impairment resulting from the New Idria Mercury Mine and natural sources in the San Carlos and Silver Creek watersheds, central California

NASA Astrophysics Data System (ADS)

Rytuba, J. J.; Hothem, R.; Goldstein, D.; Brussee, B.

2011-12-01

The New Idria Mercury Mine in central California is the second largest mercury (Hg) deposit in North America and has been proposed as a US EPA Superfund Site based on ecological impairment to the San Carlos and Silver Creek watersheds. Water, sediment, and biota were sampled in San Carlos Creek in the mine area and downstream for 25 km into the watershed termed Silver Creek. Release of acid rock drainage (ARD) and erosion of mine tailings have impacted the watershed during 120 years of mining and since the mine was closed in 1972. The watershed can be divided into three segments based on water and sediment composition, Hg sources and concentrations, and biodiversity of aquatic invertebrates. Creek waters in segment no. 1 above the mine area consist of Mg-Ca-CO3 meteoric water with pH 8.73. Hg concentrations are elevated in both sediment (100μg/g), and in waters (60 ng/L) because of erosion of Hg mine tailings in the upper part of the watershed. Invertebrate biodiversity is the highest of the sites sampled in the watershed, with seven families (six orders) of aquatic invertebrates collected and six other families observed. In the mine area isotopically heavy ARD (pH 2.7) with high levels of Fe(II), SO4, and total Hg (HgT: 76.7 ng/L) enters and mixes with meteoric creek water, constituting from 10-15% of the water in the 10-km long second creek segment downstream from the mine. Oxidation of Fe(II) from ARD results in precipitation of FeOOH which is transported and deposited as an Fe precipitate that has high Hg and MMeHg concentration (Hg: 15.7-79 μg/g, MMeHg: 0.31 - 1.06 ng/g). Concentrations of HgT are uniformly high (1530-2890 ng/L) with particulate Hg predominant. MMeHg ranges from 0.21-0.99 ng/L. In the area just downstream from the ARD source, biodiversity of invertebrates was low, with only one taxa (water striders) available in sufficient numbers and mass (> 1 g)_to be sampled. Biodiversity further downstream was also low, with only up to 2 families present at each site. In the third segment of the watershed, from 10 to 25 km downstream, water chemistry changes due to an input of isotopically heavy connate groundwater with elevated SO4, Cl, CO3, Ba, Ca, Ti, and Hg. HgT concentrations decrease systematically downstream from 680 to 20 ng/L. In the dry season, phytoplankton blooms in this segment of the creek result in accumulation of biogenic sediment up to 0.25 m thick that is composed of diatoms and chemically precipitated CaCO3. The tan surface layer consists of living diatoms. Below it is a black sediment composed of diatom fragments and micron to submicron size grains of FeS, HgS, and barite. Phytoplankton has high Hg and MMeHg bioaccumulation factors which results in high levels of Hg in the biogenic sediment. The expired diatoms release Hg to the pore waters of the sediment that reacts with sulfide generated by sulfate reducing bacteria and is precipitated as HgS. The Hg enriched biogenic sediment (4.5-14.4 μg/g) is a natural source of HgS to the watershed. In this creek segment, biodiversity is variable depending on riparian and in-stream habitat. The number of aquatic invertebrates present in sufficient numbers and mass for collection and analysis ranged from 2 to 7.

Effects and quantification of acid runoff from sulfide-bearing rock deposited during construction of Highway E18, Norway

USGS Publications Warehouse

Hindar, Atle; Nordstrom, D. Kirk

2015-01-01

The Highway E18 between the cities of Grimstad and Kristiansand, southern Norway, constructed in the period 2006–2009, cuts through sulfide-bearing rock. The geology of this area is dominated by slowly-weathering gneiss and granites, and oxidation of fresh rock surfaces can result in acidification of surface water. Sulfide-containing rock waste from excavations during construction work was therefore deposited in three waste rock deposits off-site. The deposits consist of 630,000–2,360,000 metric tons of waste rock material. Shell sand and limestone gravel were added in layers in adequate amounts to mitigate initial acid runoff in one of the deposits. The shell sand addition was not adequate in the two others. The pH in the effluents from these two was reduced from 4.9–6.5 to 4.0–4.6, and Al concentrations increased from below 0.4 mg/L to 10–20 mg/L. Stream concentrations of trace metals increased by a factor of 25–400, highest for Ni, and then in decreasing order for Co, Mn, Cd, Zn and Cu. Concentrations of As, Cr and Fe remained unchanged. Ratios of Co/Ni and Cd/Zn indicate that the metal sources for these pair of metals are sphalerite and pyrite, respectively. Based on surveys and established critical limits for Al, surface waters downstream became toxic to fish and invertebrates. The sulfur release rates were remarkably stable in the monitoring period at all three sites. Annual sulfur release was 0.1–0.4% of the total amount of sulfur in the deposit, indicating release periods of 250–800 years. Precipitates of Al-hydroxysulfates, well-known from mining sites, were found at the base of the deposits, in streams and also along the ocean shore-line. The effects of added neutralization agents in the deposits and in treatment areas downstream gradually decreased, as indicated by reduced stream pH over time. Active measures are needed to avoid harmful ecological effects in the future.

Analysis and optimization of chlorocarbon incineration through use of a detailed reaction mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, W.; Booty, M.R.; Magee, R.S.

1995-12-01

Chemical species profiles are calculated by using a detailed reaction mechanism and a reactor code that simulates a well-mixed, three-zone incineration process. The chemical systems include CH{sub 3}Cl/CH{sub 4} and CH{sub 2}Cl{sub 2}/CH{sub 4} oxidation in air at fuel equivalence ratios {phi} from 0.8 to 1.1, with additives injected at downstream positions. Combustion is characterized for temperature, principal organic hazardous constituent (POHC), and product of incomplete combustion (PIC) levels. Major PICs comprise Cl, CL{sub 2}, CO, HOCl, and COCl{sub 2} and are calculated versus time, temperature, fuel equivalence ratio, and feed conditions. Steam, H{sub 2}O{sub 2}, O{sub 2}, air, andmore » other species are injected as additives in the burnout region to discern changes i the combustion chemistry. Steam addition improves or decreases the CO/CO{sub 2} ratio at an additive mole fraction of 0.1. Atomic Cl is the active radical species of highest concentration in the initial high-temperature reaction zone when CH{sub 3}Cl is the POHC at a feed concentration above 1,200 ppm and {phi} {le} 1. Cl{sub 2} is found to be a major PIC under fuel-lean and stoichiometric conditions, while CO is a major PIC under fuel-rich conditions. Reduction of combined CO and Cl{sub 2} levels in the incinerator stack effluent is achieved by operation at stoichiometric conditions or slightly fuel-lean with the controlled addition of high-temperature steam.« less

A transport model for the deterministic stresses associated with turbomachinery blade row interactions

NASA Astrophysics Data System (ADS)

van de Wall, Allan George

The unsteady process resulting from the interaction of upstream vortical structures with a downstream blade row in turbomachines can have a significant impact on the machine efficiency. A transport model assuming incompressible flow and using linear theory was developed to take this process into account in the computation of time-average multistage turbomachinery flows. The upstream vortical structures are transported by the mean flow of the downstream blade row, redistributing the time-average unsteady kinetic energy (Uke ) associated with the incoming disturbance. The model was applied to compressor and turbine geometry. For compressors, the Uke associated with upstream 2-D wakes and 3-D tip clearance flows is reduced as a result of the interaction with a downstream blade row. This reduction results from inviscid effects as well as viscous effects and reduces the loss associated with the upstream disturbance. Any disturbance passing through a compressor blade row results in a smaller loss than if the disturbance was mixed-out prior to entering the blade row. For turbines, the Uke associated with upstream 2-D wakes and 3-D tip clearance flows are significantly amplified by inviscid effects as a result of the interaction with a downstream turbine blade row. Viscous effects act to reduce the amplification of the Uke by inviscid effects but results in a substantial loss. Any disturbance passing through a turbine blade row results in a larger loss than if the disturbance was mixedout prior to entering the blade row.

Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab

PubMed Central

Luo, Jingtao; Hong, Yun; Lu, Yang; Qiu, Songbo; Chaganty, Bharat K. R.; Zhang, Lun; Wang, Xudong; Li, Qiang; Fan, Zhen

2016-01-01

Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing the Warburg effect and leading to inhibition of cancer cell metabolism. AMP-activated protein kinase (AMPK) is activated after cetuximab treatment, and a sustained AMPK activity is a mechanism contributing to cetuximab resistance. Here, we investigated how acetyl-CoA carboxylase (ACC), a downstream target of AMPK, rewires cancer metabolism in response to cetuximab treatment. We found that introduction of experimental ACC mutants lacking the AMPK phosphorylation sites (ACC1_S79A and ACC2_S212A) into head and neck squamous cell carcinoma (HNSCC) cells protected HNSCC cells from cetuximab-induced growth inhibition. HNSCC cells with acquired cetuximab resistance contained not only high levels of T172-phosphorylated AMPK and S79-phosphorylated ACC1 but also an increased level of total ACC. These findings were corroborated in tumor specimens of HNSCC patients treated with cetuximab. Cetuximab plus TOFA (an allosteric inhibitor of ACC) achieved remarkable growth inhibition of cetuximab-resistant HNSCC xenografts. Our data suggest a novel paradigm in which cetuximab-mediated activation of AMPK and subsequent phosphorylation and inhibition of ACC is followed by a compensatory increase in total ACC, which rewires cancer metabolism from glycolysis-dependent to lipogenesis-dependent. PMID:27693630

Carbon fate in a large temperate human-impacted river system: Focus on benthic dynamics

NASA Astrophysics Data System (ADS)

Vilmin, Lauriane; Flipo, Nicolas; Escoffier, Nicolas; Rocher, Vincent; Groleau, Alexis

2016-07-01

Fluvial networks play an important role in regional and global carbon (C) budgets. The Seine River, from the Paris urban area to the entrance of its estuary (220 km), is studied here as an example of a large human-impacted river system subject to temperate climatic conditions. We assess organic C (OC) budgets upstream and downstream from one of the world's largest wastewater treatment plants and for different hydrological conditions using a hydrobiogeochemical model. The fine representation of sediment accumulation on the river bed allows for the quantification of pelagic and benthic effects on OC export toward the estuary and on river metabolism (i.e., net CO2 production). OC export is significantly affected by benthic dynamics during the driest periods, when 25% of the inputs to the system is transformed or stored in the sediment layer. Benthic processes also substantially affect river metabolism under any hydrological condition. On average, benthic respiration accounts for one third of the total river respiration along the studied stretch (0.27 out of 0.86 g C m-2 d-1). Even though the importance of benthic processes was already acknowledged by the scientific community for headwater streams, these results stress the major influence of benthic dynamics, and thus of physical processes such as sedimentation and resuspension, on C cycling in downstream river systems. It opens the door to new developments in the quantification of C emissions by global models, whereby biogeochemical processing and benthic dynamics should be taken into account.

Phase I of the Kissimmee River restoration project, Florida, USA: impacts of construction on water quality.

PubMed

Colangelo, David J; Jones, Bradley L

2005-03-01

Phase I of the Kissimmee River restoration project included backfilling of 12 km of canal and restoring flow through 24 km of continuous river channel. We quantified the effects of construction activities on four water quality parameters (turbidity, total phosphorus flow-weighted concentration, total phosphorus load and dissolved oxygen concentration). Data were collected at stations upstream and downstream of the construction and at four stations within the construction zone to determine if canal backfilling and construction of 2.4 km of new river channel would negatively impact local and downstream water quality. Turbidity levels at the downstream station were elevated for approximately 2 weeks during the one and a half year construction period, but never exceeded the Florida Department of Environmental Protection construction permit criteria. Turbidity levels at stations within the construction zone were high at certain times. Flow-weighted concentration of total phosphorus at the downstream station was slightly higher than the upstream station during construction, but low discharge limited downstream transport of phosphorus. Total phosphorus loads at the upstream and downstream stations were similar and loading to Lake Okeechobee was not significantly affected by construction. Mean water column dissolved oxygen concentrations at all sampling stations were similar during construction.

Ganglioside GM2 mediates migration of tumor cells by interacting with integrin and modulating the downstream signaling pathway.

PubMed

Kundu, Manjari; Mahata, Barun; Banerjee, Avisek; Chakraborty, Sohini; Debnath, Shibjyoti; Ray, Sougata Sinha; Ghosh, Zhumur; Biswas, Kaushik

2016-07-01

The definitive role of ganglioside GM2 in mediating tumor-induced growth and progression is still unknown. Here we report a novel role of ganglioside GM2 in mediating tumor cell migration and uncovered its mechanism. Data shows differential expression levels of GM2-synthase as well as GM2 in different human cancer cells. siRNA mediated knockdown of GM2-synthase in CCF52, A549 and SK-RC-26B cells resulted in significant inhibition of tumor cell migration as well as invasion in vitro without affecting cellular proliferation. Over-expression of GM2-synthase in low-GM2 expressing SK-RC-45 cells resulted in a consequent increase in migration thus confirming the potential role GM2 and its downstream partners play in tumor cell migration and motility. Further, treatment of SK-RC-45 cells with exogenous GM2 resulted in a dramatic increase in migratory and invasive capacity with no change in proliferative capacity, thereby confirming the role of GM2 in tumorigenesis specifically by mediating tumor migration and invasion. Gene expression profiling of GM2-synthase silenced cells revealed altered expression of several genes involved in cell migration primarily those controlling the integrin mediated signaling. GM2-synthase knockdown resulted in decreased phosphorylation of FAK, Src as well as Erk, while over-expression and/or exogenous GM2 treatment caused increased FAK and Erk phosphorylation respectively. Again, GM2 mediated invasion and Erk phosphorylation is blocked in integrin knockdown SK-RC-45 cells, thus confirming that GM2 mediated migration and phosphorylation of Erk is integrin dependent. Finally, confocal microscopy suggested co-localization while co-immunoprecipitation and surface plasmon resonance (SPR) confirmed direct interaction of membrane bound ganglioside, GM2 with the integrin receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

Fuel combustion exhibiting low NO.sub.x and CO levels

DOEpatents

Keller, Jay O.; Bramlette, T. Tazwell; Barr, Pamela K.

1996-01-01

Method and apparatus for safely combusting a fuel in such manner that very low levels of NO.sub.x and CO are produced. The apparatus comprises an inlet line (12) containing a fuel and an inlet line (18) containing an oxidant. Coupled to the fuel line (12) and to the oxidant line (18) is a mixing means (11,29,33,40) for thoroughly mixing the fuel and the oxidant without combusting them. Coupled to the mixing means (11,29,33,40) is a means for injecting the mixed fuel and oxidant, in the form of a large-scale fluid dynamic structure (8), into a combustion region (2). Coupled to the combustion region (2) is a means (1,29,33) for producing a periodic flow field within the combustion region (2) to mix the fuel and the oxidant with ambient gases in order to lower the temperature of combustion. The means for producing a periodic flow field can be a pulse combustor (1), a rotating band (29), or a rotating cylinder (33) within an acoustic chamber (32) positioned upstream or downstream of the region (2) of combustion. The mixing means can be a one-way flapper valve (11); a rotating cylinder (33); a rotating band (29) having slots (31) that expose open ends (20,21) of said fuel inlet line (12) and said oxidant inlet line (18) simultaneously; or a set of coaxial fuel annuli (43) and oxidizer annuli (42,44). The means for producing a periodic flow field (1, 29, 33) may or may not be in communication with an acoustic resonance. When employed, the acoustic resonance may be upstream or downstream of the region of combustion (2).

Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression

PubMed Central

Cheng, Hsin-Lin; Hsieh, Ming-Ju; Yang, Jia-Sin; Lin, Chiao-Wen; Lue, Ko-Haung; Lu, Ko-Hsiu; Yang, Shun-Fa

2016-01-01

Nobiletin, a polymethoxyflavone, has a few pharmacological activities, including anti-inflammation and anti-cancer effects. However, its effect on human osteosarcoma progression remains uninvestigated. Therefore, we examined the effectiveness of nobiletin against cellular metastasis of human osteosarcoma and the underlying mechanisms. Nobiletin, up to 100 μM without cytotoxicity, significantly decreased motility, migration and invasion as well as enzymatic activities, protein levels and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in U2OS and HOS cells. In addition to inhibition of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), the inhibitory effect of nobiletin on the DNA-binding activity of the transcription factor nuclear factor-kappa B (NF-κB), cAMP response element-binding protein (CREB), and specificity protein 1 (SP-1) in U2OS and HOS cells. Co-treatment with ERK and JNK inhibitors and nobiletin further reduced U2OS cells migration and invasion. These results indicated that nobiletin inhibits human osteosarcoma U2OS and HOS cells motility, migration and invasion by down-regulating MMP-2 and MMP-9 expressions via ERK and JNK pathways and through the inactivation of downstream NF-κB, CREB, and SP-1. Nobiletin has the potential to serve as an anti-metastatic agent for treating osteosarcoma. PMID:27144433

Thailand's downstream projects proliferate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-06-03

Thailand continues to press expansion and modernization of its downstream sector. Among recent developments: Construction of an olefins unit at Thailand's second major petrochemical complex and a worldscale aromatics unit in Thailand is threatened by rising costs. Thailand's National Petrochemical Corp (NPC) let a 9 billion yen contract to Mitsui Engineering and Shipbuilding Co. and C. Itoh and Co. for a dual fuel cogeneration power plant at its Mab Ta Phud, Rayong province, petrochemical complex. Financing is in place to flash a green light for a $530 million Belgian-Thai joint venture sponsoring a worldscale polyvinyl chloride/vinyl chloride monomer plant inmore » Thailand. Work is more than 50% complete on the $345 million second phase expansion of Thai Oil's Sri Racha refinery in Chon Buri province. Petroleum Authority of Thailand (PTT) endorsed a plan to install two more natural gas processing plants in Thailand to meet rapidly growing domestic demand for petroleum gas.« less

Reduced AMPK-ACC and mTOR signaling in muscle from older men, and effect of resistance exercise

PubMed Central

Li, Mengyao; Verdijk, Lex B.; Sakamoto, Kei; Ely, Brian; van Loon, Luc J.C.; Musi, Nicolas

2012-01-01

AMP-activated protein kinase (AMPK) is a key energy-sensitive enzyme that controls numerous metabolic and cellular processes. Mammalian target of rapamycin (mTOR) is another energy/nutrient-sensitive kinase that controls protein synthesis and cell growth. In this study we determined whether older versus younger men have alterations in the AMPK and mTOR pathways in skeletal muscle, and examined the effect of a long term resistance type exercise training program on these signaling intermediaries. Older men had decreased AMPKα2 activity and lower phosphorylation of AMPK and its downstream signaling substrate acetyl-CoA carboxylase (ACC). mTOR phosphylation also was reduced in muscle from older men. Exercise training increased AMPKα1 activity in older men, however, AMPKα2 activity, and the phosphorylation of AMPK, ACC and mTOR, were not affected. In conclusion, older men have alterations in the AMPK-ACC and mTOR pathways in muscle. In addition, prolonged resistance type exercise training induces an isoform-selective up regulation of AMPK activity. PMID:23000302

Reduced AMPK-ACC and mTOR signaling in muscle from older men, and effect of resistance exercise.

PubMed

Li, Mengyao; Verdijk, Lex B; Sakamoto, Kei; Ely, Brian; van Loon, Luc J C; Musi, Nicolas

2012-01-01

AMP-activated protein kinase (AMPK) is a key energy-sensitive enzyme that controls numerous metabolic and cellular processes. Mammalian target of rapamycin (mTOR) is another energy/nutrient-sensitive kinase that controls protein synthesis and cell growth. In this study we determined whether older versus younger men have alterations in the AMPK and mTOR pathways in skeletal muscle, and examined the effect of a long term resistance type exercise training program on these signaling intermediaries. Older men had decreased AMPKα2 activity and lower phosphorylation of AMPK and its downstream signaling substrate acetyl-CoA carboxylase (ACC). mTOR phosphylation also was reduced in muscle from older men. Exercise training increased AMPKα1 activity in older men, however, AMPKα2 activity, and the phosphorylation of AMPK, ACC and mTOR, were not affected. In conclusion, older men have alterations in the AMPK-ACC and mTOR pathways in muscle. In addition, prolonged resistance type exercise training induces an isoform-selective up regulation of AMPK activity. Published by Elsevier Ireland Ltd.

Flow in a porous nozzle with massive wall injection

NASA Technical Reports Server (NTRS)

Kinney, R. B.

1973-01-01

An analytical and experimental investigation has been conducted to determine the effect of massive wall injection on the flow characteristics in a nozzle. The experiments were performed on a water table with a porous-nozzle test section. This had 45 deg and 15 deg half angles of convergence and divergence, respectively, throat radius of 2.5 inches, and throat width of 3 inches. The hydraulic analogy was employed to qualitatively extend the results to a compressible gas flow through the nozzle. An analysis of the water table flow was made using a one-dimensional flow assumption in the continuity and momentum equations. An analysis of a compressible flow in a nozzle was made in a manner analogous to that for the water flow. It is shown that the effect of blowing is to move the sonic position downstream of the geometric throat. Similar results were determined for the incompressible water table flow. Limited photographic results are presented for an injection of air, CO2, and Freon-12 into a main-stream air flow in a convergent-divergent nozzle. Schlieren photographs were used to visualize the flow.

Rapid establishment of the CO2 sink associated with Kerguelen's bloom observed during the KEOPS2/OISO20 cruise

NASA Astrophysics Data System (ADS)

Lo Monaco, C.; Metzl, N.; D'Ovidio, F.; Llort, J.; Ridame, C.

2014-12-01

Iron and light are the main factors limiting the biological pump of CO2 in the Southern Ocean. Iron fertilization experiments have demonstrated the potential for increased uptake of atmospheric CO2, but little is known about the evolution of fertilized environnements. This paper presents observations collected in one of the largest phytoplankton bloom of the Southern Ocean sustained by iron originating from the Kerguelen Plateau. We first complement previous studies by investigating the mechanisms that control air-sea CO2 fluxes over and downstream of the Kerguelen Plateau at the onset of the bloom based on measurements obtained in October-November 2011. These new observations show the rapid establishment of a strong CO2 sink in waters fertilized with iron as soon as vertical mixing is reduced. The magnitude of the CO2 sink was closely related to chlorophyll a and iron concentrations. Because iron concentration strongly depends on the distance from the iron source and the mode of delivery, we identified lateral advection as the main mechanism controlling air-sea CO2 fluxes downtream the Kerguelen Plateau during the growing season. In the southern part of the bloom, situated over the Plateau (iron source), the CO2 sink was stronger and spatially more homogeneous than in the plume offshore. However, we also witnessed a substantial reduction in the uptake of atmospheric CO2 over the Plateau following a strong winds event. Next, we used all the data available in this region in order to draw the seasonal evolution of air-sea CO2 fluxes. The CO2 sink is rapidly reduced during the course of the growing season, which we attribute to iron and silicic acid depletion. South of the Polar Front, where nutrients depletion is delayed, we suggest that the amplitude and duration of the CO2 sink is mainly controlled by vertical mixing. The impact of iron fertilization on air-sea CO2 fluxes is revealed by comparing the uptake of CO2 integrated over the productive season in the bloom, between 1 and 1.5 mol C m-2 yr-1, and in the iron-poor HNLC waters, where we found a typical value of 0.4 mol C m-2 yr-1. Extrapolating our results to the ice-free Southern Ocean (~50-60° S) suggests that iron fertilization of the whole area would increase the contemporay oceanic uptake of CO2 by less than 0.1 Pg C yr-1, i.e., less than 1% of the current anthropogenic CO2 emissions.

A Comprehensive Program for Measurement of Military Aircraft Emissions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Mengdawn

2009-11-01

Emissions of gases and particulate matter by military aircraft were characterized inplume by 'extractive' and 'optical remote-sensing (ORS)' technologies. Non-volatile particle size distribution, number and mass concentrations were measured with good precision and reproducibly. Time-integrated particulate filter samples were collected and analyzed for smoke number, elemental composition, carbon contents, and sulfate. Observed at EEP the geometric mean diameter (as measured by the mobility diameter) generally increased as the engine power setting increased, which is consistent with downstream observations. The modal diameters at the downstream locations are larger than that at EEP at the same engine power level. The results indicatemore » that engine particles were processed by condensation, for example, leading to particle growth in-plume. Elemental analysis indicated little metals were present in the exhaust, while most of the exhaust materials in the particulate phase were carbon and sulfate (in the JP-8 fuel). CO, CO{sub 2}, NO, NO{sub 2}, SO{sub 2}, HCHO, ethylene, acetylene, propylene, and alkanes were measured. The last five species were most noticeable under engine idle condition. The levels of hydrocarbons emitted at high engine power level were generally below the detection limits. ORS techniques yielded real-time gaseous measurement, but the same techniques could not be extended directly to ultrafine particles found in all engine exhausts. The results validated sampling methodology and measurement techniques used for non-volatile particulate aircraft emissions, which also highlighted the needs for further research on sampling and measurement for volatile particulate matter and semi-volatile species in the engine exhaust especially at the low engine power setting.« less

Atmospheric-pressure plasma jets: Effect of gas flow, active species, and snake-like bullet propagation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, S.; Wang, Z.; Huang, Q.

2013-02-15

Cold atmospheric-pressure plasma jets have recently attracted enormous interest owing to numerous applications in plasma biology, health care, medicine, and nanotechnology. A dedicated study of the interaction between the upstream and downstream plasma plumes revealed that the active species (electrons, ions, excited OH, metastable Ar, and nitrogen-related species) generated by the upstream plasma plume enhance the propagation of the downstream plasma plume. At gas flows exceeding 2 l/min, the downstream plasma plume is longer than the upstream plasma plume. Detailed plasma diagnostics and discharge species analysis suggest that this effect is due to the electrons and ions that are generatedmore » by the upstream plasma and flow into the downstream plume. This in turn leads to the relatively higher electron density in the downstream plasma. Moreover, high-speed photography reveals a highly unusual behavior of the plasma bullets, which propagate in snake-like motions, very differently from the previous reports. This behavior is related to the hydrodynamic instability of the gas flow, which results in non-uniform distributions of long-lifetime active species in the discharge tube and of surface charges on the inner surface of the tube.« less

Elevated YAP and its downstream targets CCN1 and CCN2 in basal cell carcinoma: impact on keratinocyte proliferation and stromal cell activation.

PubMed

Quan, Taihao; Xu, Yiru; Qin, Zhaoping; Robichaud, Patrick; Betcher, Stephanie; Calderone, Ken; He, Tianyuan; Johnson, Timothy M; Voorhees, John J; Fisher, Gary J

2014-04-01

Yes-associated protein (YAP) is a transcriptional co-activator of hippo signaling pathway, which plays an important role in organ size control and tumorigenesis. Here we report that YAP and its downstream transcriptional targets CCN1 and CCN2 are markedly elevated in keratinocytes in human skin basal cell carcinoma tumor islands. In human keratinocytes, knockdown of YAP significantly reduced expression of CCN1 and CCN2, and repressed proliferation and survival. This inhibition of proliferation and survival was rescued by restoration of CCN1 expression, but not by CCN2 expression. In basal cell carcinoma stroma, CCN2-regulated genes type I collagen, fibronectin, and α-smooth muscle actin were highly expressed. Furthermore, atomic force microscopy revealed increased tissue stiffness in basal cell carcinoma stroma compared to normal dermis. These data provide evidence that up-regulation of YAP in basal cell carcinoma impacts both aberrant keratinocyte proliferation, via CCN1, and tumor stroma cell activation and stroma remodeling, via CCN2. Targeting YAP and/or CCN1 and CCN2 may provide clinical benefit in basal cell carcinoma. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins*

PubMed Central

Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

2017-01-01

Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. PMID:27927989

Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins.

PubMed

Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

2017-01-20

Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Geomorphic responses to dam removal in the United States – a two-decade perspective

USGS Publications Warehouse

Major, Jon J.; East, Amy; O'Connor, Jim E.; Grant, Gordon E.; Wilcox, Andrew C.; Magirl, Christopher S.; Collins, Matthias J.; Tullos, Desiree D.; Tsutsumi, Daizo; Laronne, Jonathan B.

2017-01-01

Recent decades have seen a marked increase in the number of dams removed in the United States. Investigations following a number of removals are beginning to inform how, and how fast, rivers and their ecosystems respond to released sediment. Though only a few tens of studies detail physical responses to removals, common findings have begun to emerge. They include: (1) Rivers are resilient and respond quickly to dam removals, especially when removals are sudden rather than prolonged. Rivers can swiftly evacuate large fractions of reservoir sediment (≥50% within one year), especially when sediment is coarse grained (sand and gravel). The channel downstream typically takes months to years—not decades—to achieve a degree of stability within its range of natural variability. (2) Modest streamflows (<2-year return interval flows) can erode and transport large amounts of reservoir sediment. Greater streamflows commonly are needed to access remnant reservoir sediment and transport it downstream. (3) Dam height, sediment volume, and sediment caliber strongly influence downstream response to dam removal. Removals of large dams (≥10 m tall) have had longer-lasting and more widespread downstream effects than more common removals of small dams. (4) Downstream valley morphology and position of a dam within a watershed influence the distribution of released sediment. Valley confinement, downstream channel gradient, locations and depths of channel pools, locations and geometries of extant channel bars, and locations of other reservoirs all influence the downstream fate of released sediment.

Environmental signatures and effects of an oil and gas wastewater spill in the Williston Basin, North Dakota.

PubMed

Cozzarelli, I M; Skalak, K J; Kent, D B; Engle, M A; Benthem, A; Mumford, A C; Haase, K; Farag, A; Harper, D; Nagel, S C; Iwanowicz, L R; Orem, W H; Akob, D M; Jaeschke, J B; Galloway, J; Kohler, M; Stoliker, D L; Jolly, G D

2017-02-01

Wastewaters from oil and gas development pose largely unknown risks to environmental resources. In January 2015, 11.4ML (million liters) of wastewater (300g/L TDS) from oil production in the Williston Basin was reported to have leaked from a pipeline, spilling into Blacktail Creek, North Dakota. Geochemical and biological samples were collected in February and June 2015 to identify geochemical signatures of spilled wastewaters as well as biological responses along a 44-km river reach. February water samples had elevated chloride (1030mg/L) and bromide (7.8mg/L) downstream from the spill, compared to upstream levels (11mg/L and <0.4mg/L, respectively). Lithium (0.25mg/L), boron (1.75mg/L) and strontium (7.1mg/L) were present downstream at 5-10 times upstream concentrations. Light hydrocarbon measurements indicated a persistent thermogenic source of methane in the stream. Semi-volatile hydrocarbons indicative of oil were not detected in filtered samples but low levels, including tetramethylbenzenes and di-methylnaphthalenes, were detected in unfiltered water samples downstream from the spill. Labile sediment-bound barium and strontium concentrations (June 2015) were higher downstream from the Spill Site. Radium activities in sediment downstream from the Spill Site were up to 15 times the upstream activities and, combined with Sr isotope ratios, suggest contributions from the pipeline fluid and support the conclusion that elevated concentrations in Blacktail Creek water are from the leaking pipeline. Results from June 2015 demonstrate the persistence of wastewater effects in Blacktail Creek several months after remediation efforts started. Aquatic health effects were observed in June 2015; fish bioassays showed only 2.5% survival at 7.1km downstream from the spill compared to 89% at the upstream reference site. Additional potential biological impacts were indicated by estrogenic inhibition in downstream waters. Our findings demonstrate that environmental signatures from wastewater spills are persistent and create the potential for long-term environmental health effects. Published by Elsevier B.V.

Sediment Budgeting in Dam-Affected Rivers: Assessing the Influence of Damming, Tributaries, and Alluvial Valley Sediment Storage on Sediment Regimes

NASA Astrophysics Data System (ADS)

Wilcox, A. C.; Dekker, F. J.; Riebe, C. S.

2014-12-01

Although sediment supply is recognized as a fundamental driver of fluvial processes, measuring how dams affect sediment regimes and incorporating such knowledge into management strategies remains challenging. To determine the influences of damming, tributary supply, and valley morphology and sediment storage on downstream sediment supply in a dryland river, the Bill Williams River (BWR) in western Arizona, we measured basin erosion rates using cosmogenic nuclide analysis of beryllium-10 (10Be) at sites upstream and downstream of a dam along the BWR, as well as from tributaries downstream of the dam. Riverbed sediment mixing calculations were used to test if the dam, which blocks sediment supply from the upper 85% of the basin's drainage area, increases the proportion of tributary sediment to residual upstream sediment in mainstem samples downstream of the dam. Erosion rates in the BWR watershed are more than twice as large in the upper catchment (136 t km-2 yr-1) than in tributaries downstream of Alamo Dam (61 t km-2 yr-1). Tributaries downstream of the dam have little influence on mainstem sediment dynamics. The effect of the dam on reducing sediment supply is limited, however, because of the presence of large alluvial valleys along the mainstem BWR downstream of the dam that store substantial sediment and mitigate supply reductions from the upper watershed. These inferences, from our 10Be derived erosion rates and mixing calculations, are consistent with field observations of downstream changes in bed material size, which suggest that sediment-deficit conditions are restricted to a 10 km reach downstream of the dam, and limited reservoir bathymetry data. Many studies have suggested that tributary sediment inputs downstream of dams play a key role in mitigating dam-induced sediment deficits, but here we show that in a dryland river with ephemeral tributaries, sediment stored in alluvial valleys can also play a key role and in some cases trumps the role of tributaries.

Novel Paradigms for Dialysis Vascular Access: Downstream Vascular Biology–Is There a Final Common Pathway?

PubMed Central

2013-01-01

Summary Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development. PMID:23990166

ROLE OF SULFUR IN REDUCING PCDD AND PCDF FORMATION

EPA Science Inventory

Past research has suggested that the presence of sulfur (S) in municipal waste combustors (MWCs) can decrease downstream formation of chlorinated organic compounds, particularly polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Thus, co-firing a...

Effects of Whole-Ecosystem Warming on Porewater Chemistry and Hydrology in a Northern Peatland

NASA Astrophysics Data System (ADS)

Griffiths, N.; Sebestyen, S. D.

2016-12-01

Northern peatlands are carbon-rich ecosystems, and thus it is important to understand the effects of climate change on carbon cycle feedbacks in these vulnerable systems. An ecosystem-scale experiment is evaluating the effects of warming and elevated CO2 on an ombrotrophic bog in northern Minnesota, USA. Ten enclosures, each 12-m in diameter, were constructed in the peatland to allow for both above and belowground warming. Each enclosure receives one of five temperature treatments (+0 to +9°C), with half of the enclosures receiving elevated CO2 (+500ppm) and the other half ambient CO2. A belowground corral with a lateral drainage system surrounds each enclosure, and allows for measurements of lateral outflow volume and chemistry. Piezometers are used to sample porewater chemistry at different depths (0-3m) into the peat. We evaluated the effects of one year of whole-ecosystem warming on depth-specific porewater chemistry and outflow dynamics. Changes in porewater chemistry were observed upon initiation of whole-ecosystem warming. Total organic carbon (TOC) concentrations increased in near-surface porewater in the warmer enclosures, while concentrations were lower and similar to pre-treatment conditions in the ambient (+0°C) enclosures. The changes in TOC concentration measured in response to whole-ecosystem warming were initially limited to only the near-surface porewater (0 m); however, TOC concentrations began to increase at 0.3 m depth after several months of warming. These changes in TOC concentrations were also reflected in water draining from each enclosure, with generally higher TOC concentrations in water flowing from warmer enclosures. However, warmer treatments tended to have lower water outflow rates, possibly due to increased evapotranspiration, and thus TOC fluxes were generally lowest from the warmest enclosures. Overall, these initial results suggest that warming may increase porewater TOC concentrations, possibly due to increased mineralization rates of peat; however, due to the interaction with hydrology, export of this TOC to downstream ecosystems may be lower with warming. Continued measurements over the next 10 years will evaluate the long-term effects of warming on peatland chemistry and hydrology.

Effects of small impoundments on downstream crayfish assemblages

Treesearch

Susan B. Adams

2013-01-01

Dams and impoundments, both large and small, affect downstream physicochemical characteristics and up- and downstream biotic communities. I tested whether small dams and their impoundments altered downstream crayfish assemblages in northern Mississippi. I sampled crayfish and measured physicochemical variables at 4 sites downstream of impoundments (outlet sites) and 4...

The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling.

PubMed

Luo, K; Stroschein, S L; Wang, W; Chen, D; Martens, E; Zhou, S; Zhou, Q

1999-09-01

Smad proteins are critical signal transducers downstream of the receptors of the transforming growth factor-beta (TGFbeta) superfamily. On phosphorylation and activation by the active TGFbeta receptor complex, Smad2 and Smad3 form hetero-oligomers with Smad4 and translocate into the nucleus, where they interact with different cellular partners, bind to DNA, regulate transcription of various downstream response genes, and cross-talk with other signaling pathways. Here we show that a nuclear oncoprotein, Ski, can interact directly with Smad2, Smad3, and Smad4 on a TGFbeta-responsive promoter element and repress their abilities to activate transcription through recruitment of the nuclear transcriptional corepressor N-CoR and possibly its associated histone deacetylase complex. Overexpression of Ski in a TGFbeta-responsive cell line renders it resistant to TGFbeta-induced growth inhibition and defective in activation of JunB expression. This ability to overcome TGFbeta-induced growth arrest may be responsible for the transforming activity of Ski in human and avian cancer cells. Our studies suggest a new paradigm for inactivation of the Smad proteins by an oncoprotein through transcriptional repression.

The Ski oncoprotein interacts with the Smad proteins to repress TGFβ signaling

PubMed Central

Luo, Kunxin; Stroschein, Shannon L.; Wang, Wei; Chen, Dan; Martens, Eric; Zhou, Sharleen; Zhou, Qiang

1999-01-01

Smad proteins are critical signal transducers downstream of the receptors of the transforming growth factor-β (TGFβ) superfamily. On phosphorylation and activation by the active TGFβ receptor complex, Smad2 and Smad3 form hetero-oligomers with Smad4 and translocate into the nucleus, where they interact with different cellular partners, bind to DNA, regulate transcription of various downstream response genes, and cross-talk with other signaling pathways. Here we show that a nuclear oncoprotein, Ski, can interact directly with Smad2, Smad3, and Smad4 on a TGFβ-responsive promoter element and repress their abilities to activate transcription through recruitment of the nuclear transcriptional corepressor N-CoR and possibly its associated histone deacetylase complex. Overexpression of Ski in a TGFβ-responsive cell line renders it resistant to TGFβ-induced growth inhibition and defective in activation of JunB expression. This ability to overcome TGFβ-induced growth arrest may be responsible for the transforming activity of Ski in human and avian cancer cells. Our studies suggest a new paradigm for inactivation of the Smad proteins by an oncoprotein through transcriptional repression. PMID:10485843

Dual roles for coactivator activator and its counterbalancing isoform coactivator modulator in human kidney cell tumorigenesis.

PubMed

Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y; Tsai, Ming-Jer; O'Malley, Bert W

2008-10-01

Coactivator activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein, we show that CoAA is a dual-function coregulator that inhibits G(1)-S transition in human kidney cells and suppresses anchorage-independent growth and xenograft tumor formation. Suppression occurs in part by down-regulating c-myc and its downstream effectors ccnd1 and skp2 and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, coactivator modulator (CoAM), antagonizes CoAA-induced G(1)-S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma compared with normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice isoform. This is, thus far, the only example of a nuclear receptor coregulator involved in suppression of kidney cancer and suggests potentially significant new roles for coregulators in renal cancer biology.

Evasion of CO2 from streams - the dominant component of the carbon export through the aquatic conduit in a boreal landscape.

PubMed

Wallin, Marcus B; Grabs, Thomas; Buffam, Ishi; Laudon, Hjalmar; Agren, Ånneli; Öquist, Mats G; Bishop, Kevin

2013-03-01

Evasion of gaseous carbon (C) from streams is often poorly quantified in landscape C budgets. Even though the potential importance of the capillary network of streams as C conduits across the land-water-atmosphere interfaces is sometimes mentioned, low-order streams are often left out of budget estimates due to being poorly characterized in terms of gas exchange and even areal surface coverage. We show that evasion of C is greater than all the total dissolved C (both organic and inorganic) exported downstream in the waters of a boreal landscape. In this study evasion of carbon dioxide (CO2 ) from running waters within a 67 km(2) boreal catchment was studied. During a 4 year period (2006-2009) 13 streams were sampled on 104 different occasions for dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC). From a locally determined model of gas exchange properties, we estimated the daily CO2 evasion with a high-resolution (5 × 5 m) grid-based stream evasion model comprising the entire ~100 km stream network. Despite the low areal coverage of stream surface, the evasion of CO2 from the stream network constituted 53% (5.0 (±1.8) g C m(-2)  yr(-1) ) of the entire stream C flux (9.6 (±2.4) g C m(-2)  yr(-1) ) (lateral as DIC, DOC, and vertical as CO2 ). In addition, 72% of the total CO2 loss took place already in the first- and second-order streams. This study demonstrates the importance of including CO2 evasion from low-order boreal streams into landscape C budgets as it more than doubled the magnitude of the aquatic conduit for C from this landscape. Neglecting this term will consequently result in an overestimation of the terrestrial C sink strength in the boreal landscape. © 2012 Blackwell Publishing Ltd.

Soil greenhouse gas emissions and carbon budgeting in a short-hydroperiod floodplain wetland

NASA Astrophysics Data System (ADS)

Batson, Jackie; Noe, Gregory B.; Hupp, Cliff R.; Krauss, Ken W.; Rybicki, Nancy B.; Schenk, Edward R.

2015-01-01

Understanding the controls on floodplain carbon (C) cycling is important for assessing greenhouse gas emissions and the potential for C sequestration in river-floodplain ecosystems. We hypothesized that greater hydrologic connectivity would increase C inputs to floodplains that would not only stimulate soil C gas emissions but also sequester more C in soils. In an urban Piedmont river (151 km2 watershed) with a floodplain that is dry most of the year, we quantified soil CO2, CH4, and N2O net emissions along gradients of floodplain hydrologic connectivity, identified controls on soil aerobic and anaerobic respiration, and developed a floodplain soil C budget. Sites were chosen along a longitudinal river gradient and across lateral floodplain geomorphic units (levee, backswamp, and toe slope). CO2 emissions decreased downstream in backswamps and toe slopes and were high on the levees. CH4 and N2O fluxes were near zero; however, CH4 emissions were highest in the backswamp. Annual CO2 emissions correlated negatively with soil water-filled pore space and positively with variables related to drier, coarser soil. Conversely, annual CH4 emissions had the opposite pattern of CO2. Spatial variation in aerobic and anaerobic respiration was thus controlled by oxygen availability but was not related to C inputs from sedimentation or vegetation. The annual mean soil CO2 emission rate was 1091 g C m-2 yr-1, the net sedimentation rate was 111 g C m-2 yr-1, and the vegetation production rate was 240 g C m-2 yr-1, with a soil C balance (loss) of -338 g C m-2 yr-1. This floodplain is losing C likely due to long-term drying from watershed urbanization.

Simulating the Fate and Transport of an Acid Mine Drainage Release Using the WASP model

NASA Astrophysics Data System (ADS)

Knightes, C. D.; Kate, S.; Avant, B. K.; Cyterski, M.; Washington, J.; Prieto, L.

2016-12-01

On August 5, 2015, approximately 3 million gallons of acid mine drainage were released from the Gold King Mine into Cement Creek in the San Juan River watershed (CO, NM, UT). The release further mobilized additional metals, which resulted in a large mass of solids and dissolved metals entering Cement Creek. These metals were released into the Animas River. As the release acidity was neutralized, the metals precipitated and formed the visually noticeable "yellow boy," which flowed down the San Juan River. We applied the Water Quality Analysis Simulation Program (WASP) using empirically based parameterization to simulate and describe the movement of the plume and total and dissolved concentrations of all metals, including Arsenic, Copper, Lead, and Zinc. We estimated that the plume took between approximately 1 to 3 days to pass any given location. The peak concentration of the plume took about 2 hours to reach Silverton, CO (16 rkm), 1.5 days to reach Durango, CO (94 rkm), 2.9 days to reach Farmington, NM, (190 rkm) and 5.8 days to reach Mexican Hat, UT (422 km). Total metal concentration decreased rapidly going downstream, dropping 80% upon entering the Animas at Silverton, CO, and 99.5% entering the San Juan at Farmington. Metal concentrations decreased by dilution, settling, and dispersion. Modeling suggests that deposition occurred primarily in the upper Animas River near Silverton and near Durango, which was supported with empirical evidence. This work demonstrates the utility of a combined empirical and mechanistic modeling analysis. We additionally investigate long-term residual effects and potential exposure concentrations during storm and snowmelt high flow periods after the visible plume had traversed the system.

Fate of peat-derived carbon and associated CO2 and CO emissions from two Southeast Asian estuaries

NASA Astrophysics Data System (ADS)

Müller, D.; Warneke, T.; Rixen, T.; Müller, M.; Mujahid, A.; Bange, H. W.; Notholt, J.

2015-06-01

Coastal peatlands in Southeast Asia release large amounts of organic carbon to rivers, which transport it further to the adjacent estuaries. However, little is known about the fate of this terrestrial material in the coastal ocean. Although Southeast Asia is, by area, considered a hotspot of estuarine CO2 emissions, studies in this region are very scarce. We measured dissolved and particulate organic carbon, carbon dioxide (CO2) partial pressure and carbon monoxide (CO) concentrations in two tropical estuaries in Sarawak, Malaysia, whose coastal area is covered by peatlands. We surveyed the estuaries of the rivers Lupar and Saribas during the wet and dry season, respectively. The spatial distribution and the carbon-to-nitrogen ratios of dissolved organic matter (DOM) suggest that peat-draining rivers convey terrestrial organic carbon to the estuaries. We found evidence that a large fraction of this carbon is respired. The median pCO2 in the estuaries ranged between 618 and 5064 μatm with little seasonal variation. CO2 fluxes were determined with a floating chamber and estimated to amount to 14-272 mol m-2 yr-1, which is high compared to other studies from tropical and subtropical sites. In contrast, CO concentrations and fluxes were relatively moderate (0.3-1.4 nmol L-1 and 0.8-1.9 mmol m-2 yr-1) if compared to published data for oceanic or upwelling systems. We attributed this to the large amounts of suspended matter (4-5004 mg L-1), limiting the light penetration depth. However, the diurnal variation of CO suggests that it is photochemically produced, implying that photodegradation might play a role for the removal of DOM from the estuary as well. We concluded that unlike smaller peat-draining tributaries, which tend to transport most carbon downstream, estuaries in this region function as an efficient filter for organic carbon and release large amounts of CO2 to the atmosphere. The Lupar and Saribas mid-estuaries release 0.4 ± 0.2 Tg C yr-1, which corresponds to approximately 80% of the emissions from the aquatic systems in these two catchments.

Analysis of dissolved gas and fluid chemistry in mountainous region of Goaping river watershed in southern Taiwan

NASA Astrophysics Data System (ADS)

Tang, Kai-Wen; Chen, Cheng-Hong; Liu, Tsung-Kwei

2016-04-01

Annual rainfall in Taiwan is up to 2500 mm, about 2.5 times the average value of the world. However due to high topographic relief of the Central Mountain Range in Taiwan, groundwater storage is critical for water supply. Mountain region of the Goaping river watershed in southern Taiwan is one of the potential areas to develop groundwater recharge model. Therefore the target of this study is to understand sources of groundwater and surface water using dissolved gas and fluid chemistry. Four groundwater and 6 surface water samples were collected from watershed, 5 groundwater and 13 surface water samples were collected from downstream. All samples were analyzed for stable isotopes (hydrogen and oxygen), dissolved gases (including nitrogen, oxygen, argon, methane and carbon dioxide), noble gases (helium and radon) and major ions. Hydrogen and oxygen isotopic ratios of surface water and groundwater samples aligned along meteoric water line. For surface water, dissolved gases are abundant in N2 (>80%) and O2 (>10%); helium isotopic ratio is approximately equal to 1 RA (RA is 3He/4He ratio of air); radon-222 concentration is below the detection limit (<200 Bq/m3); and concentrations of major anions and cations are low (Na+ <20 ppm, Ca2+ < 60 ppm, Cl- <2 ppm). All these features indicate that surface waters are predominately recharged by precipitation. For groundwater, helium isotopic ratios (0.9˜0.23 RA) are lower and radon-222 concentrations (300˜6000 Bq/m3) are much higher than the surface water. Some samples have high amounts of dissolved gases, such as CH4 (>20%) or CO2 (>10%), most likely contributed by biogenic or geogenic sources. On the other hand, few samples that have temperature 5° higher than the average of other samples, show significantly high Na+ (>1000 ppm), Ca2+ (>150 ppm) and Cl- (>80 ppm) concentrations. An interaction between such groundwater and local hot springs is inferred. Watershed and downstream samples differ in dissolved gas species and fluid chemistry for groundwater and surface water. The higher hydrogen and oxygen isotopic ratios for surface water from downstream are most probably caused by evaporation. Low radon-222 concentrations of some groundwater from downstream may represent sources from different aquifers. Therefore, we conclude that surface water from downstream are recharged directly from its watershed, but groundwater are influenced by the local geological environment. Keywords: groundwater, dissolved gas, noble gas, radon in water, 3He/4He

THE RGM/DRAGON FAMILY OF BMP CO-RECEPTORS

PubMed Central

Corradini, Elena; Babitt, Jodie L.; Lin, Herbert Y.

2013-01-01

The BMP signaling pathway controls a number of cell processes during development and in adult tissues. At the cellular level, ligands of the BMP family act by binding a hetero-tetrameric signaling complex, composed of two type I and two type II receptors. BMP ligands make use of a limited number of receptors, which in turn activate a common signal transduction cascade at the intracellular level. A complex regulatory network is required in order to activate the signaling cascade at proper times and locations, and to generate specific downstream effects in the appropriate cellular context. One such regulatory mechanism is the repulsive guidance molecule (RGM) family of BMP co-receptors. This article reviews the current knowledge regarding the structure, regulation, and function of RGMs, focusing on known and potential roles of RGMs in physiology and pathophysiology. PMID:19897400

Quantification of mutation-derived bias for alternate mating functionalities of the Saccharomyces cerevisiae Ste2p pheromone receptor.

PubMed

Choudhary, Pooja; Loewen, Michele C

2016-01-01

Although well documented for mammalian G-protein-coupled receptors, alternate functionalities and associated alternate signalling remain to be unequivocally established for the Saccharomyces cerevisiae pheromone Ste2p receptor. Here, evidence supporting alternate functionalities for Ste2p is re-evaluated, extended and quantified. In particular, strong mating and constitutive signalling mutations, focusing on residues S254, P258 and S259 in TM6 of Ste2p, are stacked and investigated in terms of their effects on classical G-protein-mediated signal transduction associated with cell cycle arrest, and alternatively, their impact on downstream mating projection and zygote formation events. In relative dose response experiments, accounting for systemic and observational bias, mutational-derived functional differences were observed, validating the S254L-derived bias for downstream mating responses and highlighting complex relationships between TM6-mutation derived constitutive signalling and ligand-induced functionalities. Mechanistically, localization studies suggest that alterations to receptor trafficking may contribute to mutational bias, in addition to expected receptor conformational stabilization effects. Overall, these results extend previous observations and quantify the contributions of Ste2p variants to mediating cell cycle arrest versus downstream mating functionalities. © Crown copyright 2015.

Phosphorylation of the Nicotiana benthamiana WRKY8 Transcription Factor by MAPK Functions in the Defense Response[C][W][OA

PubMed Central

Ishihama, Nobuaki; Yamada, Reiko; Yoshioka, Miki; Katou, Shinpei; Yoshioka, Hirofumi

2011-01-01

Mitogen-activated protein kinase (MAPK) cascades have pivotal roles in plant innate immunity. However, downstream signaling of plant defense-related MAPKs is not well understood. Here, we provide evidence that the Nicotiana benthamiana WRKY8 transcription factor is a physiological substrate of SIPK, NTF4, and WIPK. Clustered Pro-directed Ser residues (SP cluster), which are conserved in group I WRKY proteins, in the N-terminal region of WRKY8 were phosphorylated by these MAPKs in vitro. Antiphosphopeptide antibodies indicated that Ser residues in the SP cluster of WRKY8 are phosphorylated by SIPK, NTF4, and WIPK in vivo. The interaction of WRKY8 with MAPKs depended on its D domain, which is a MAPK-interacting motif, and this interaction was required for effective phosphorylation of WRKY8 in plants. Phosphorylation of WRKY8 increased its DNA binding activity to the cognate W-box sequence. The phospho-mimicking mutant of WRKY8 showed higher transactivation activity, and its ectopic expression induced defense-related genes, such as 3-hydroxy-3-methylglutaryl CoA reductase 2 and NADP-malic enzyme. By contrast, silencing of WRKY8 decreased the expression of defense-related genes and increased disease susceptibility to the pathogens Phytophthora infestans and Colletotrichum orbiculare. Thus, MAPK-mediated phosphorylation of WRKY8 has an important role in the defense response through activation of downstream genes. PMID:21386030

An Experiment on the Near Flow Field of the GE/ARL Mixer Ejector Nozzle

NASA Technical Reports Server (NTRS)

Zaman, K. B. M. Q.

2004-01-01

This report is a documentation of the results on flowfield surveys for the GE/ARL mixer-ejector nozzle carried out in an open jet facility at NASA Glenn Research Center. The results reported are for cold (unheated) flow without any surrounding co-flowing stream. Distributions of streamwise vorticity as well as turbulent stresses, obtained by hot-wire anemometry, are presented for a low subsonic condition. Pitot probe survey results are presented for nozzle pressure ratios up to 3.5. Flowfields both inside and outside of the ejector are considered. Inside the ejector, the mean velocity distribution exhibits a cellular pattern on the cross sectional plane, originating from the flow through the primary and secondary chutes. With increasing downstream distance an interchange of low velocity regions with adjacent high velocity regions takes place due to the action of the streamwise vortices. At the ejector exit, the velocity distribution is nonuniform at low and high pressure ratios but reasonably uniform at intermediate pressure ratios. The effects of two chevron configurations and a tab configuration on the evolution of the downstream jet are also studied. Compared to the baseline case, minor but noticeable effects are observed on the flowfield.

A simple elution strategy for biotinylated proteins bound to streptavidin conjugated beads using excess biotin and heat.

PubMed

Cheah, Joleen S; Yamada, Soichiro

2017-12-02

Protein-protein interactions are the molecular basis of cell signaling. Recently, proximity based biotin identification (BioID) has emerged as an alternative approach to traditional co-immunoprecipitation. In this protocol, a mutant biotin ligase promiscuously labels proximal binding partners with biotin, and resulting biotinylated proteins are purified using streptavidin conjugated beads. This approach does not require preservation of protein complexes in vitro, making it an ideal approach to identify transient or weak protein complexes. However, due to the high affinity bond between streptavidin and biotin, elution of biotinylated proteins from streptavidin conjugated beads requires harsh denaturing conditions, which are often incompatible with downstream processing. To effectively release biotinylated proteins bound to streptavidin conjugated beads, we designed a series of experiments to determine optimal binding and elution conditions. Interestingly, the concentrations of SDS and IGEPAL-CA630 during the incubation with streptavidin conjugated beads were the key to effective elution of biotinylated proteins using excess biotin and heating. This protocol provides an alternative method to isolate biotinylated proteins from streptavidin conjugated beads that is suitable for further downstream analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Downstream reduction of rural channel size with contrasting urban effects in small coastal streams of southeastern Australia

NASA Astrophysics Data System (ADS)

Nanson, G. C.; Young, R. W.

1981-07-01

Although most streams show a downstream increase in channel size corresponding to a downstream increase in flood discharges, those flowing off the Illawarra escarpment of New South Wales show a marked reduction of channel size, accompanied by a down-stream increase in flood frequency in their lower reaches. Within the confined and steeply sloping valleys of the escarpment foothills, bed and bank sediments are relatively coarse and uncohesive, and channels increase in size, corresponding to increasing discharge downstream. However, once these streams emerge into more open rural valleys at lower slopes and are accompanied by extensive floodplains formed of fine cohesive sediment, there is a dramatic reduction in channel size. This decrease in channel size apparently results from a sudden decline in channel slope and associated stream power, the cohesive nature of downstream alluvium, its retention on the channel banks by a dense cover of pasture grasses, and the availability of an extensive floodplain to carry displaced floodwater. Under these conditions floodwaters very frequently spill out over the floodplain and the downstream channel-flow becomes a relatively unimportant component of the total peak discharge. This emphasizes the importance of these floodplains as a part of the total channel system. In situations where urban development has increased peak runoff and reduced the available area of effective floodplain, stream channels formed in this fine alluvium rapidly entrench and increase in cross-sectional area by 2-3 times. Minor man-induced channel alteration and maintenance appears to trigger this enlargement.

Water quality effects of herded stream crossings by domestic sheep bands.

PubMed

Clark, Patrick E; Moffet, Corey A; Lewis, Gregory S; Seyfried, Mark S; Hardegree, Stuart P; Pierson, Fredrick B

2012-01-01

Livestock impacts on total suspended solids (TSS) and pathogen (e.g., ) levels in rangeland streams are a serious concern worldwide. Herded stream crossings by domestic sheep () are periodic, necessary managerial events on high-elevation rangelands, but their impacts on stream water quality are largely unknown. We evaluated the effects of herded, one-way crossings by sheep bands (about 2000 individuals) on TSS and concentration and load responses in downstream waters. Crossing trials were conducted during the summers of 2005 and 2006 on two reaches within each of three perennial streams in the Centennial Mountains of eastern Idaho and southwestern Montana. Water samples were collected at 2-min intervals at an upstream background station and at stations 25, 100, 500, and 1500 m downstream just before and during each crossing trial. Crossings produced substantial increases in TSS and concentrations and loads downstream, but these concentration increases were localized and short lived. Maximum TSS concentration was highest 25 m downstream, declined as a function of downstream distance, and at 500 m downstream was similar to background. Post-peak TSS concentrations at all downstream stations decreased to <25 mg L within 24 to 48 min after reaching their maxima. Findings for concentration and load responses were similar to that of TSS but less clear cut. Stream-crossing sheep do affect water quality; therefore, producers and resource managers should continue to evaluate the efficacy of herdsmanship techniques for reducing water quality impact. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

1. FORMER DENVER, SOUTH PARK AND PACIFIC RAILROAD BRIDGE OVER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. FORMER DENVER, SOUTH PARK AND PACIFIC RAILROAD BRIDGE OVER CHALK CREEK, NEAR MT. PRINCETON HOT SPRINGS. VIEW DOWNSTREAM - Denver South Park & Pacific Railroad Bridge, Spanning Chalk Creek, near Mount Princeton Hot Spring, Romley (historical), Chaffee County, CO

Plant responses to increasing CO 2 reduce estimates of climate impacts on drought severity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swann, Abigail L. S.; Hoffman, Forrest M.; Koven, Charles D.

Rising atmospheric CO 2 will make Earth warmer, and many studies have inferred that this warming will cause droughts to become more widespread and severe. However, rising atmospheric CO 2 also modifies stomatal conductance and plant water use, processes that are often are overlooked in impact analysis. We find that plant physiological responses to CO 2 reduce predictions of future drought stress, and that this reduction is captured by using plant-centric rather than atmosphere-centric metrics from Earth system models (ESMs). The atmosphere-centric Palmer Drought Severity Index predicts future increases in drought stress for more than 70% of global land area.more » This area drops to 37% with the use of precipitation minus evapo-transpiration (P-E), a measure that represents the water flux available to downstream ecosystems and humans. The two metrics yield consistent estimates of increasing stress in regions where precipitation decreases are more robust (southern North America, northeastern South America, and southern Europe). The metrics produce diverging estimates elsewhere, with P-E predicting decreasing stress across temperate Asia and central Africa. The differing sensitivity of drought metrics to radiative and physiological aspects of increasing CO 2 partly explains the divergent estimates of future drought reported in recent studies. Further, use of ESM output in offline models may double-count plant feedbacks on relative humidity and other surface variables, leading to overestimates of future stress. The use of drought metrics that account for the response of plant transpiration to changing CO 2, including direct use of P-E and soil moisture from ESMs, is needed to reduce uncertainties in future assessment.« less

Plant responses to increasing CO 2 reduce estimates of climate impacts on drought severity

DOE PAGES

Swann, Abigail L. S.; Hoffman, Forrest M.; Koven, Charles D.; ...

2016-08-29

Rising atmospheric CO 2 will make Earth warmer, and many studies have inferred that this warming will cause droughts to become more widespread and severe. However, rising atmospheric CO 2 also modifies stomatal conductance and plant water use, processes that are often are overlooked in impact analysis. We find that plant physiological responses to CO 2 reduce predictions of future drought stress, and that this reduction is captured by using plant-centric rather than atmosphere-centric metrics from Earth system models (ESMs). The atmosphere-centric Palmer Drought Severity Index predicts future increases in drought stress for more than 70% of global land area.more » This area drops to 37% with the use of precipitation minus evapo-transpiration (P-E), a measure that represents the water flux available to downstream ecosystems and humans. The two metrics yield consistent estimates of increasing stress in regions where precipitation decreases are more robust (southern North America, northeastern South America, and southern Europe). The metrics produce diverging estimates elsewhere, with P-E predicting decreasing stress across temperate Asia and central Africa. The differing sensitivity of drought metrics to radiative and physiological aspects of increasing CO 2 partly explains the divergent estimates of future drought reported in recent studies. Further, use of ESM output in offline models may double-count plant feedbacks on relative humidity and other surface variables, leading to overestimates of future stress. The use of drought metrics that account for the response of plant transpiration to changing CO 2, including direct use of P-E and soil moisture from ESMs, is needed to reduce uncertainties in future assessment.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Huijuan; Wang, Ke; Liu, Wenxin

Highlights: • Overexpression of PTEN enhanced the sensitivity of C13K cells to cisplatin. • KRT10 is a downstream molecule of PTEN involved in the resistance-reversing effect. • Overexpression of KRT10 enhanced the chemosensitivity of C13K cells to cisplatin. - Abstract: Multi-drug resistance (MDR) is a common cause of the failure of chemotherapy in ovarian cancer. PTEN, a tumor suppressor gene, has been demonstrated to be able to reverse cisplatin-resistance in ovarian cancer cell line C13K. However, the downstream molecules of PTEN involved in the resistance-reversing effect have not been completely clarified. Therefore, we screened the downstream molecules of PTEN andmore » studied their interactions in C13K ovarian cancer cells using a 3D culture model. Firstly, we constructed an ovarian cancer cell line stably expressing PTEN, C13K/PTEN. MTT assay showed that overexpression of PTEN enhanced the sensitivity of C13K cells to cisplatin, but not to paclitaxel. Then we examined the differently expressed proteins that interacted with PTEN in C13K/PTEN cells with or without cisplatin treatment by co-immunoprecipitation. KRT10 was identified as a differently expressed protein in cisplatin-treated C13K/PTEN cells. Further study confirmed that cisplatin could induce upregulation of KRT10 mRNA and protein in C13K/PTEN cells and there was a directly interaction between KRT10 and PTEN. Forced expression of KRT10 in C13K cells also enhanced cisplatin-induced proliferation inhibition and apoptosis of C13K cells. In addition, KRT10 siRNA blocked cisplatin-induced proliferation inhibition of C13K/PTEN cells. In conclusion, our data demonstrate that KRT10 is a downstream molecule of PTEN which improves cisplatin-resistance of ovarian cancer and forced KRT10 overexpression may also act as a therapeutic method for overcoming MDR in ovarian cancer.« less

Biodegradation of 17β-estradiol, estrone and testosterone in stream sediments

USGS Publications Warehouse

Bradley, Paul M.; Barber, Larry B.; Chapelle, Francis H.; Gray, James L.; Kolpin, Dana W.; McMahon, Peter B.

2009-01-01

Biodegradation of 17β-estradiol (E2), estrone (E1), and testosterone (T) was investigated in three wastewater treatment plant (WWTP) affected streams in the United States. Relative differences in the mineralization of [4-14C] substrates were assessed in oxic microcosms containing saturated sediment or water-only from locations upstream and downstream of the WWTP outfall in each system. Upstream sediment demonstrated significant mineralization of the “A” ring of E2, E1, and T, with biodegradation of T consistently greater than that of E2 and no systematic difference in E2 and E1 biodegradation. “A” ring mineralization also was observed in downstream sediment, with E1 and T mineralization being substantially depressed relative to upstream samples. In marked contrast, E2 mineralization in sediment immediately downstream from the WWTP outfalls was more than double that in upstream sediment. E2 mineralization was observed in water, albeit at insufficient rate to prevent substantial downstream transport. The results indicate that, in combination with sediment sorption processes which effectively scavenge hydrophobic contaminants from the water column and immobilize them in the vicinity of the WWTP outfall, aerobic biodegradation of reproductive hormones can be an environmentally important mechanism for nonconservative (destructive) attenuation of hormonal endocrine disruptors in effluent-affected streams.

Dana-Farber Cancer Institute: Identification of Therapeutic Targets in KRAS Driven Lung Cancer | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at Dana Farber Cancer Institute focuses on the use of high-throughput genetic and bioinformatic approaches to identify and credential oncogenes and co-dependencies in cancers. This Center aims to provide the cancer research community with information that will facilitate the prioritization of targets based on both genomic and functional evidence, inform the most appropriate genetic context for downstream mechanistic and validation studies, and enable the translation of this information into therapeutics and diagnostics.

Wogonin inhibits the proliferation and invasion, and induces the apoptosis of HepG2 and Bel7402 HCC cells through NF‑κB/Bcl-2, EGFR and EGFR downstream ERK/AKT signaling.

PubMed

Liu, Xiaodong; Tian, Shuo; Liu, Mei; Jian, Lingyan; Zhao, Limei

2016-10-01

The anticancer effects of the natural flavonoid, wogonin, have been reported. However, its molecular mechanisms of action have not yet been fully explored. In the present study, we aimed to examine the molecular mechanisms of action of wogonin and its effects on the biological behavior of the HepG2 and Bel7402 hepatocellular carcinoma (HCC) cell lines. We also examined the effects of wogonin on nuclear factor-κB (NF-κB)/Bcl-2 and epidermal growth factor receptor (EGFR) signaling, as well as on downstream pathways of EGFR, namely extracellular signal-regulated kinase (ERK)/AKT signaling. We found that treatment with wogonin inhibited the proliferation and invasion, and induced the apoptosis of the HepG2 and Bel7402 cells. In addition, treatment with wogonin decreased cyclin D1, cyclin E, CDK4/6, Bcl-2 and matrix metalloproteinase 2 (MMP2) expression, and promoted the cleavage of caspase-3 and caspase-9 in a concentration-dependent manner. Further experiments revealed that wogonin inhibited NF-κB/Bcl-2 signaling by decreasing the IκB and p65 phosphorylation levels. Wogonin also inhibited the activation of the EGFR (Tyr845) signaling pathway, and that of downstream pathways of EGFR, namely ERK/AKT/MMP2 signaling. The depletion of EGFR by siRNA partly abolished the inhibitory effects of wogonin on cyclin D1, MMP2 expression. On the whole, our our findings demonstrate that wogonin effectively suppresses the proliferation, invasion and survival of HCC cells through the modulation of the NF-κB and EGFR signaling pathways.

Comparative transcriptome analysis of the CO2 sensing pathway via differential expression of carbonic anhydrase in Cryptococcus neoformans.

PubMed

Kim, Min Su; Ko, Young-Joon; Maeng, Shinae; Floyd, Anna; Heitman, Joseph; Bahn, Yong-Sun

2010-08-01

Carbon dioxide (CO(2)) sensing and metabolism via carbonic anhydrases (CAs) play pivotal roles in survival and proliferation of pathogenic fungi infecting human hosts from natural environments due to the drastic difference in CO(2) levels. In Cryptococcus neoformans, which causes fatal fungal meningoencephalitis, the Can2 CA plays essential roles during both cellular growth in air and sexual differentiation of the pathogen. However the signaling networks downstream of Can2 are largely unknown. To address this question, the present study employed comparative transcriptome DNA microarray analysis of a C. neoformans strain in which CAN2 expression is artificially controlled by the CTR4 (copper transporter) promoter. The P(CTR4)CAN2 strain showed growth defects in a CO(2)-dependent manner when CAN2 was repressed but resumed normal growth when CAN2 was overexpressed. The Can2-dependent genes identified by the transcriptome analysis include FAS1 (fatty acid synthase 1) and GPB1 (G-protein beta subunit), supporting the roles of Can2 in fatty acid biosynthesis and sexual differentiation. Cas3, a capsular structure designer protein, was also discovered to be Can2-dependent and yet was not involved in CO(2)-mediated capsule induction. Most notably, a majority of Can2-dependent genes were environmental stress-regulated (ESR) genes. Supporting this, the CAN2 overexpression strain was hypersensitive to oxidative and genotoxic stress as well as antifungal drugs, such as polyene and azole drugs, potentially due to defective membrane integrity. Finally, an oxidative stress-responsive Atf1 transcription factor was also found to be Can2-dependent. Atf1 not only plays an important role in diverse stress responses, including thermotolerance and antifungal drug resistance, but also represses melanin and capsule production in C. neoformans. In conclusion, this study provides insights into the comprehensive signaling networks orchestrated by CA/CO(2)-sensing pathways in pathogenic fungi.

Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes.

PubMed

Wolters, Jarno E J; van Breda, Simone G J; Grossmann, Jonas; Fortes, Claudia; Caiment, Florian; Kleinjans, Jos C S

2018-06-01

We performed a multiple 'omics study by integrating data on epigenomic, transcriptomic, and proteomic perturbations associated with mitochondrial dysfunction in primary human hepatocytes caused by the liver toxicant valproic acid (VPA), to deeper understand downstream events following epigenetic alterations in the mitochondrial genome. Furthermore, we investigated persistence of cross-omics changes after terminating drug treatment. Upon transient methylation changes of mitochondrial genes during VPA-treatment, increasing complexities of gene-interaction networks across time were demonstrated, which normalized during washout. Furthermore, co-expression between genes and their corresponding proteins increased across time. Additionally, in relation to persistently decreased ATP production, we observed decreased expression of mitochondrial complex I and III-V genes. Persistent transcripts and proteins were related to citric acid cycle and β-oxidation. In particular, we identified a potential novel mitochondrial-nuclear signaling axis, MT-CO2-FN1-MYC-CPT1. In summary, this cross-omics study revealed dynamic responses of the mitochondrial epigenome to an impulse toxicant challenge resulting in persistent mitochondrial dysfunctioning. Moreover, this approach allowed for discriminating between the toxic effect of VPA and adaptation. Copyright © 2018 Elsevier B.V. All rights reserved.

Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tu, Yingfeng; Liu, Li; Zhao, Dongliang

Recent studies reported miR-497 exhibited inhibitory effects in various cancers. However, whether miR-497 is involved in inhibiting angiogenesis, which is critical for tumor growth and metastasis, is still unknown. The purpose of this study was to investigate the potential role of miR-497 in tumor angiogenesis. In this work, cell proliferation and apoptosis analyses were conducted to explore the potential function of miR-497 in HUVECs by using MTT and TUNEL assays. Western blotting (WB) was employed to validate the downstream targets of miR-497. Furthermore, in order to disclose the role of miR-497 on angiogenesis, VEGFR2-luc transgenic mice were treated with miR-497more » mimic and applied to monitor tumor angiogenesis and growth by in vivo bioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo. Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway. Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis. In summary, miR-497 inhibits tumor angiogenesis and growth via targeting VEGFR2, indicating miR-497 can be explored as a potential drug candidate for cancer therapy.« less

Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2

DOE PAGES

Tu, Yingfeng; Liu, Li; Zhao, Dongliang; ...

2015-09-08

Recent studies reported miR-497 exhibited inhibitory effects in various cancers. However, whether miR-497 is involved in inhibiting angiogenesis, which is critical for tumor growth and metastasis, is still unknown. The purpose of this study was to investigate the potential role of miR-497 in tumor angiogenesis. In this work, cell proliferation and apoptosis analyses were conducted to explore the potential function of miR-497 in HUVECs by using MTT and TUNEL assays. Western blotting (WB) was employed to validate the downstream targets of miR-497. Furthermore, in order to disclose the role of miR-497 on angiogenesis, VEGFR2-luc transgenic mice were treated with miR-497more » mimic and applied to monitor tumor angiogenesis and growth by in vivo bioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo. Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway. Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis. In summary, miR-497 inhibits tumor angiogenesis and growth via targeting VEGFR2, indicating miR-497 can be explored as a potential drug candidate for cancer therapy.« less

Comparative life cycle assessment and financial analysis of mixed culture polyhydroxyalkanoate production.

PubMed

Gurieff, Nicholas; Lant, Paul

2007-12-01

A life cycle assessment and financial analysis of mixed culture PHA (PHA(MC)) and biogas production was undertaken based on treating an industrial wastewater. Internal rate of return (IRR) and non-renewable CO(2)eq emissions were used to quantify financial viability and environmental impact. PHA(MC) was preferable to biogas production for treating the specified industrial effluent. PHA(MC) was also financially attractive in comparison to pure culture PHA production. Both PHA production processes had similar environmental impacts that were significantly lower than HDPE production. A large potential for optimisation exists for the PHA(MC) process as financial and environmental costs were primarily due to energy use for downstream processing. Under the conditions used in this work PHA(MC) was shown to be a viable biopolymer production process and an effective industrial wastewater treatment technology. This is the first study of its kind and provides valuable insight into the PHA(MC) process.

Process for injecting liquid in moving natural gas streams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivers, J.B. Jr.; Budke, H.T. Jr.

1979-01-02

Western Chemical Co.'s simplified, low-cost method of treating pressurized, moving natural gas streams in order to control problems created by entrained water facilitates the downstream treatment of the gas and increases product yields by lessening the formation of oil and water emulsions and hydrates that can coat and clog the processing equipment, while also minimizing equipment corrosion. The method involves introducing into the moving gas stream an agent that includes a polymer having recurring quaternized pyridinium groups for controlling the emulsion, hydrate, and corrosion problems. The method is especially effective when the entrained water contains surfactants, detergents, soaps, etc. Inmore » preferred forms, a low-molecular-weight copolymer of styrene and 2-vinyl pyridine dispersed in water is atomized into the gas stream adjacent to cooling and scrubbing stations. The method is particularly useful in connection with natural gas products plants.« less

The potential for catastrophic dam failure at Lake Nyos maar, Cameroon

USGS Publications Warehouse

Lockwood, J.P.; Costa, J.E.; Tuttle, M.L.; Nni, J.; Tebor, S.G.

1988-01-01

The upper 40 m of Lake Nyos is bounded on the north by a narrow dam of poorly consolidated pyroclastic rocks, emplaced during the eruptive formation of the Lake Nyos maar a few hundred years ago. This 50-m-wide natural dam is structurally weak and is being eroded at an uncertain, but geologically alarming, rate. The eventual failure of the dam could cause a major flood (estimated peak discharge, 17000 m3/s) that would have a tragic impact on downstream areas as far as Nigeria, 108 km away. This serious hazard could be eliminated by lowering the lake level, either by controlled removal of the dam or by construction of a 680-m-long drainage tunnel about 65 m below the present lake surface. Either strategy would also lessen the lethal effects of future massive CO2 gas releases, such as the one that occurred in August 1986. ?? 1988 Springer-Verlag.

Stabilization of benthic algal biomass in a temperate stream draining agroecosystems.

PubMed

Ford, William I; Fox, James F

2017-01-01

Results of the present study quantified carbon sequestration due to algal stabilization in low order streams, which has not been considered previously in carbon stream ecosystem studies. The authors used empirical mode decomposition of an 8-year carbon elemental and isotope dataset to quantify carbon accrual and fingerprint carbon derived from algal stabilization. The authors then applied a calibrated, process-based stream carbon model (ISOFLOC) that elicits further evidence of algal stabilization. Data and modeling results suggested that processes of shielding and burial during an extreme hydrologic event enhance algal stabilization. Given that previous studies assumed stream algae are turned over or sloughed downstream, the authors performed scenario simulations of the calibrated model in order to assess how changing environmental conditions might impact algae stabilization within the stream. Results from modeling scenarios showed an increase in algal stabilization as mean annual water temperature increases ranging from 0 to 0.04 tC km -2  °C -1 for the study watershed. The dependence of algal stabilization on temperature highlighted the importance of accounting for benthic fate of carbon in streams under projected warming scenarios. This finding contradicts the evolving paradigm that net efflux of CO 2 from streams increases with increasing temperatures. Results also quantified sloughed algae that is transported and potentially stabilized downstream and showed that benthos-derived sloughed algae was on the same order of magnitude, and at times greater, than phytoplankton within downstream water bodies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Integrating Waste Heat from CO 2 Removal and Coal-Fired Flue Gas to Increase Plant Efficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Irvin, Nick; Kowalczyk, Joseph

In project DE-FE0007525, Southern Company Services demonstrated heat integration methods for the capture and sequestration of carbon dioxide produced from pulverized coal combustion. A waste heat recovery technology (termed High Efficiency System) from Mitsubishi Heavy Industries America was integrated into an existing 25-MW amine-based CO 2 capture process (Kansai Mitsubishi Carbon Dioxide Recovery Process®1) at Southern Company’s Plant Barry to evaluate improvements in the energy performance of the pulverized coal plant and CO 2 capture process. The heat integration system consists of two primary pieces of equipment: (1) the CO 2 Cooler which uses product CO 2 gas from themore » capture process to heat boiler condensate, and (2) the Flue Gas Cooler which uses air heater outlet flue gas to further heat boiler condensate. Both pieces of equipment were included in the pilot system. The pilot CO 2 Cooler used waste heat from the 25-MW CO 2 capture plant (but not always from product CO 2 gas, as intended). The pilot Flue Gas Cooler used heat from a slipstream of flue gas taken from downstream of Plant Barry’s air heater. The pilot also included a 0.25-MW electrostatic precipitator. The 25-MW High Efficiency System operated for approximately six weeks over a four month time period in conjunction with the 25-MW CO 2 capture facility at Plant Barry. Results from the program were used to evaluate the technical and economic feasibility of full-scale implementation of this technology. The test program quantified energy efficiency improvements to a host power plant that could be realized due to the High Efficiency System. Through the execution of this project, the team verified the integrated operation of the High Efficiency System and Kansai Mitsubishi Carbon Dioxide Recovery Process®. The ancillary benefits of the High Efficiency System were also quantified, including reduced water consumption, a decrease in toxic air emissions, and better overall air quality control systems performance.« less

What Drives Carbon Isotope Fractionation by the Terrestrial Biosphere?

NASA Astrophysics Data System (ADS)

Still, Christopher; Rastogi, Bharat

2017-11-01

During photosynthesis, terrestrial plants preferentially assimilate the lighter and much more abundant form of carbon, 12C, which accounts for roughly 99% of naturally occurring forms of this element. This photosynthetic preference for lighter carbon is driven principally by differences in molecular diffusion of carbon dioxide with differing 13C/12C across stomatal pores on leaves, followed by differences in carboxylation rates by the Rubisco enzyme that is central to the process of photosynthesis. As a result of these slight preferences, which work out to about a 2% difference in the fixation rates of 12CO2 versus 13CO2 by C3 vegetation, plant tissues are depleted in the heavier form of carbon (13C) relative to atmospheric CO2. This difference has been exploited in a wide range of scientific applications, as the photosynthetic isotope signature is passed to ecosystem carbon pools and through ecological food webs. What is less appreciated is the signature that terrestrial carbon exchanges leave on atmospheric CO2, as the net uptake of carbon by land plants during their growing season not only draws down the local CO2 concentration, it also leaves behind relatively more CO2 molecules containing 13C. The converse happens outside the growing season, when autotrophic and heterotrophic respiration predominate. During these periods, atmospheric CO2 concentration increases and its corresponding carbon isotope composition becomes relatively depleted in 13C as the products of photosynthesis are respired, along with some small isotope fractionation that happen downstream of the initial photosynthetic assimilation. Similar phenomena were first observed at shorter time scales by the eminent carbon cycle scientist, Charles (Dave) Keeling. Keeling collected samples of air in glass flasks from sites along the Big Sur coast that he later measured for CO2 concentration and carbon isotope composition (δ13C) in his lab (Keeling, 1998). From these samples, Keeling observed increasing CO2 concentrations at night compared to the day, along with corresponding depletions in their δ13C. These phenomena were understood at the time to be driven by interactions between ecosystem carbon exchanges and vertical movements of the atmospheric boundary layer (Keeling, 1958).

TEAD1 mediates the oncogenic activities of Hippo-YAP1 signaling in osteosarcoma.

PubMed

Chai, Jiwei; Xu, Shijie; Guo, Fengbo

2017-06-24

Hippo signaling pathway is an evolutionarily conserved developmental network that governs the downstream transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs that responsible for cell proliferation, apoptosis, and stem cell self renewal. Emerging evidence has shown the tumor suppressor properties of Hippo signaling. However, limited knowledge is available concerning the downstream transcription factors of Hippo pathway in osteosarcoma (OS). In this study, we demonstrated that TEAD1 was the major transcription factor of Hippo signaling pathway in OS. Genetic silencing of TEAD1 suppressed multiple malignant phenotypes of OS cells including cell proliferation, apoptosis resistance, and invasive potential. Mechanistically, we showed that TEAD1 largely exerted its transcriptional control of its functional targets, PTGS2 and CYR61. Collectively, this work identifies the YAP1/TEAD1 complex as the representative dysregulated profile of Hippo signaling in OS and provides proof-of-principle that targeting TEAD1 may be a therapeutic strategy of osteosarcoma. Copyright © 2017. Published by Elsevier Inc.

Siphon flows in isolated magnetic flux tubes. V - Radiative flows with variable ionization

NASA Technical Reports Server (NTRS)

Montesinos, Benjamin; Thomas, John H.

1993-01-01

Steady siphon flows in arched isolated magnetic flux tubes in the solar atmosphere are calculated here including radiative transfer between the flux tube and its surrounding and variable ionization of the flowing gas. It is shown that the behavior of a siphon flow is strongly determined by the degree of radiative coupling between the flux tube and its surroundings in the superadiabatic layer just below the solar surface. Critical siphon flows with adiabatic tube shocks in the downstream leg are calculated, illustrating the radiative relaxation of the temperature jump downstream of the shock. For flows in arched flux tubes reaching up to the temperature minimum, where the opacity is low, the gas inside the flux tube is much cooler than the surrounding atmosphere at the top of the arch. It is suggested that gas cooled by siphon flows contribute to the cool component of the solar atmosphere at the height of the temperature minimum implied by observations of the infrared CO bands at 4.6 and 2.3 microns.

In situ impact assessment of wastewater effluents by integrating multi-level biomarker responses in the pale chub (Zacco platypus).

PubMed

Kim, Woo-Keun; Jung, Jinho

2016-06-01

The integration of biomarker responses ranging from the molecular to the individual level is of great interest for measuring the toxic effects of hazardous chemicals or effluent mixtures on aquatic organisms. This study evaluated the effects of wastewater treatment plant (WWTP) effluents on the freshwater pale chub Zacco platypus by using multi-level biomarker responses at molecular [mRNA expression of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and metallothionein (MT)], biochemical (enzyme activities of CAT, SOD, GST, and concentration of MT), and physiological [condition factor (CF) and liver somatic index (LSI)] levels. The mRNA expression levels of GST and MT in Z. platypus from a site downstream of a WWTP significantly increased by 2.2- and 4.5-fold (p<0.05) when compared with those from an upstream site. However, the enzyme activities of CAT, SOD, and GST in fish from the downstream site significantly decreased by 43%, 98%, and 13%, respectively (p<0.05), except for an increase in MT concentration (41%). In addition, a significant increase in LSI (46%) was observed in Z. platypus from the downstream site (p<0.05). Concentrations of Cu, Zn, Cd, and Pb in the liver of Z. platypus were higher (530%, 353%, 800%, and 2,200%, respectively) in fish from a downstream site than in fish from an upstream location, and several multi-level biomarker responses were significantly correlated with the accumulated metals in Z. platypus (p<0.05). Integrated biomarker responses at molecular, biochemical, and physiological levels (multi-level IBR) were much higher (about 4-fold) at the downstream site than at the upstream site. This study suggests that the multi-level IBR approach is very useful for quantifying in situ adverse effects of WWTP effluents. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of wastewater treatment facility closure on endocrine disrupting chemicals in a Coastal Plain stream

USGS Publications Warehouse

Bradley, Paul M.; Journey, Celeste A.; Clark, Jimmy M.

2016-01-01

Wastewater treatment facility (WWTF) closures are rare environmental remediation events; offering unique insight into contaminant persistence, long-term wastewater impacts, and ecosystem recovery processes. The U.S. Geological Survey assessed the fate of select endocrine disrupting chemicals (EDC) in surface water and streambed sediment one year before and one year after closure of a long-term WWTF located within the Spirit Creek watershed at Fort Gordon, Georgia. Sample sites included a WWTF-effluent control located upstream from the outfall, three downstream effluent-impacted sites located between the outfall and Spirit Lake, and one downstream from the lake's outfall. Prior to closure, the 2.2-km stream segment downstream from the WWTF outfall was characterized by EDC concentrations significantly higher (α = 0.05) than at the control site; indicating substantial downstream transport and limited in-stream attenuation of EDC, including pharmaceuticals, estrogens, alkylphenol ethoxylate (APE) metabolites, and organophosphate flame retardants (OPFR). Wastewater-derived pharmaceutical, APE metabolites, and OPFR compounds were also detected in the outflow of Spirit Lake, indicating the potential for EDC transport to aquatic ecosystems downstream of Fort Gordon under effluent discharge conditions. After the WWTF closure, no significant differences in concentrations or numbers of detected EDC compounds were observed between control and downstream locations. The results indicated EDC pseudo-persistence under preclosure, continuous supply conditions, with rapid attenuation following WWTF closure. Low concentrations of EDC at the control site throughout the study and comparable concentrations in downstream locations after WWTF closure indicated additional, continuing, upstream contaminant sources within the Spirit Creek watershed. 

Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway.

PubMed

Zhang, Zhiguo; Wang, Shudong; Zhou, Shanshan; Yan, Xiaoqing; Wang, Yonggang; Chen, Jing; Mellen, Nicholas; Kong, Maiying; Gu, Junlian; Tan, Yi; Zheng, Yang; Cai, Lu

2014-12-01

Type 2 diabetes mellitus (T2DM)-induced cardiomyopathy is associated with cardiac oxidative stress, inflammation, and remodeling. Sulforaphane (SFN), an isothiocyanate naturally presenting in widely consumed vegetables, particularly broccoli, plays an important role in cardiac protection from diabetes. We investigated the effect of SFN on T2DM-induced cardiac lipid accumulation and subsequent cardiomyopathy. Male C57BL/6J mice were fed a high-fat diet for 3months to induce insulin resistance, followed by a treatment with 100mg/kg body-weight streptozotocin to induce hyperglycemia; we referred to it as the T2DM mouse model. Other age-matched mice were fed a normal diet as control. T2DM and control mice were treated with or without 4-month SFN at 0.5mg/kg daily five days a week. At the study's end, cardiac function was assessed. SFN treatment significantly attenuated cardiac remodeling and dysfunction induced by T2DM. SFN treatment also significantly inhibited cardiac lipid accumulation, measured by Oil Red O staining, and improved cardiac inflammation oxidative stress and fibrosis, shown by down-regulating diabetes-induced PAI-1, TNF-α, CTGF, TGF-β, 3-NT, and 4-HNE expression. Elevated 4-HNE resulted in the increase of 4-HNE-LKB1 adducts that should inhibit LKB1 and subsequent AMPK activity. SFN upregulated the expression of Nrf2 and its downstream genes, NQO1 and HO-1, decreased 4-HNE-LKB1 adducts and then reversed diabetes-induced inhibition of LKB1/AMPK and its downstream targets, including sirtuin 1, PGC-1α, phosphorylated acetyl-CoA carboxylase, carnitine palmitoyl transferase-1, ULK1, and light chain-3 II. These results suggest that SFN treatment to T2DM mice may attenuate the cardiac oxidative stress-induced inhibition of LKB1/AMPK signaling pathway, thereby preventing T2DM-induced lipotoxicity and cardiomyopathy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cucurbitane Triterpenoids from the Fruits of Momordica Charantia Improve Insulin Sensitivity and Glucose Homeostasis in Streptozotocin-Induced Diabetic Mice.

PubMed

Han, Joo-Hui; Tuan, Nguyen Quoc; Park, Min-Ho; Quan, Khong Trong; Oh, Joonseok; Heo, Kyung-Sun; Na, MinKyun; Myung, Chang-Seon

2018-04-01

Momordica charantia (M. charantia) has antidiabetic effects, and cucurbitane-type triterpenoid is one of the compounds of M. charantia. This study aims to investigate whether the new cucurbitane-type triterpenoids affect insulin sensitivity both in vitro and in vivo, and the underlying mechanisms. Four compounds (C1-C4) isolated from the ethanol extract of M. charantia enhance glucose uptake in C2C12 myotubes via insulin receptor substrate-1 (IRS-1) rather than via adenosine monophosphate-activated protein kinase. The most potent, compound 2 (C2), significantly increases the activation of IRS-1 and downstream signaling pathways, resulting in glucose transporter 4 translocation. Furthermore, these C2-induced in vitro effects are blocked by specific signal inhibitors. We further evaluate the antidiabetic effect of C2 using a streptozotocin (STZ)-induced diabetic mouse model. Consistent with in vitro data, treatment with C2 (1.68 mg kg -1 ) significantly decreases blood glucose level and enhances glycogen storage in STZ-injected mice. These effects appear to be mediated by the IRS-1 signaling pathway in skeletal muscle, not in adipose and liver tissues, suggesting that C2 improves hyperglycemia by increasing glucose uptake into skeletal muscle. Our findings demonstrate that the new cucurbitane-type triterpenoids have potential for prevention and management of diabetes by improving insulin sensitivity and glucose homeostasis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantification of small GTPase glucosylation by clostridial glucosylating toxins using multiplexed MRM analysis.

PubMed

Junemann, Johannes; Lämmerhirt, Chantal M; Polten, Felix; Just, Ingo; Gerhard, Ralf; Genth, Harald; Pich, Andreas

2017-05-01

Large clostridial toxins mono-O-glucosylate small GTPases of the Rho and Ras subfamily. As a result of glucosylation, the GTPases are inhibited and thereby corresponding downstream signaling pathways are disturbed. Current methods for quantifying the extent of glucosylation include sequential [ 14 C]glucosylation, sequential [ 32 P]ADP-ribosylation, and Western Blot detection of nonglucosylated GTPases, with neither method allowing the quantification of the extent of glucosylation of an individual GTPase. Here, we describe a novel MS-based multiplexed MRM assay to specifically quantify the glucosylation degree of small GTPases. This targeted proteomics approach achieves a high selectivity and reproducibility, which allows determination of the in vivo substrate pattern of glucosylating toxins. As proof of principle, GTPase glucosylation was analyzed in CaCo-2 cells treated with TcdA, and glucosylation kinetics were determined for RhoA/B, RhoC, RhoG, Ral, Rap1, Rap2, (H/K/N)Ras, and R-Ras2. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biophotonics for Biofuel Upgradation

NASA Astrophysics Data System (ADS)

Rana, Gopinath; Mandal, Tanusri

2017-12-01

Experimental studies have been made to find out Cyanobacterias' biophotonical response in gaseous-fuelation and carbon dioxide fixation during photo-anaerobic digestion. A new horizontal type photo-bioreactor has been designed by using environment hazard plastic bottles and it works ideally for anoxygenic cyanobacterial growth. Through `V3-metagenomics' of 16S rRNA gene sequencing by paired-end Illumina MiSeq and downstream analysis by QIIME program, we have identified anaerobic cyanobacteria, represent the orders YS2 and Streptophyta. OTUs have been identified by aligning against Greengenes and Silva databases, separately. The flame temperature of the fuel gas is 860°C and the percent-content of carbon dioxide (CO2) is 17.6%.

Downstream Migration of Masu Salmon Smolt at a Diversion Facility of Dam

NASA Astrophysics Data System (ADS)

Hayashida, K.; Nii, H.; Kasuga, K.; Watanabe, K.

2014-12-01

A diversion facility was installed on the upstream of Pirika Dam in Northern Japan that produced a downstream flow into the fishway, thus allowing the fish to migrate to the sea. On the other hand, if the flow rate in the river was more than 7.00 m 3/s (design flow rate of diversion facility), masu salmon smolt were concerned about accessing the dam reservoir, because the smolt can't migrate to the sea through the diversion facility unfortunately. Therefore, the downstream migration of smolt was investigated around the diversion facility. The PIT tag system and radio transmitters as the biotelemetry were used to determine 1) whether masu salmon smolt were able to migrate downstream through the diversion facility and fishway at Pirika Dam, 2) when the smolt started to migrate downstream, 3) whether the downstream migration of smolt were affected by the flow increase in the river. It was clarified that 88% of the smolt were able to enter the diversion facility, and then 81% of the smolt were able to access the fishway. It was also clarified that smolt downstream migration had two peaks in a day (5:00 and 18:00). During the study period, although the flow rate was in the 2.21 m3/s to 30.44 m3/s range (average 6.70 m3/s), it was revealed that the diversion facility has a satisfactory function for the downstream migration of smolt as presented above. The survey clarified the downstream migration behavior of masu salmon by using two types of biotelemetry equipment. PIT tag and radio transmitter were found to be very effective in tracking the behavior of small fish such as smolt. PIT tags, in particular, require very little operating cost, because once they are inserted in the fish, they do not need human labor for tracking. It is desirable to actively introduce the biotelemetry as tracking equipment when surveying the fish migration in the river.

Rosuvastatin Treatment Affects Both Basal and Glucose-Induced Insulin Secretion in INS-1 832/13 Cells

PubMed Central

Salunkhe, Vishal A.; Elvstam, Olof; Eliasson, Lena; Wendt, Anna

2016-01-01

Rosuvastatin is a member of the statin family. Like the other statins it is prescribed to lower cholesterol levels and thereby reduce the risk of cardiovascular events. Rosuvastatin lowers the cholesterol levels by inhibiting the key enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) in the cholesterol producing mevalonate pathway. It has been recognized that apart from their beneficial lipid lowering effects, statins also exhibit diabetogenic properties. The molecular mechanisms behind these remain unresolved. To investigate the effects of rosuvastatin on insulin secretion, we treated INS-1 832/13 cells with varying doses (20 nM to 20 μM) of rosuvastatin for 48 h. At concentrations of 2 μM and above basal insulin secretion was significantly increased. Using diazoxide we could determine that rosuvastatin did not increase basal insulin secretion by corrupting the KATP channels. Glucose-induced insulin secretion on the other hand seemed to be affected differently at different rosuvastatin concentrations. Rosuvastatin treatment (20 μM) for 24–48 h inhibited voltage-gated Ca2+ channels, which lead to reduced depolarization-induced exocytosis of insulin-containing granules. At lower concentrations of rosuvastatin (≤ 2 μM) the stimulus-secretion coupling pathway was intact downstream of the KATP channels as assessed by the patch clamp technique. However, a reduction in glucose-induced insulin secretion could be observed with rosuvastatin concentrations as low as 200 nM. The inhibitory effects of rosuvastatin on glucose-induced insulin secretion could be reversed with mevalonate, but not squalene, indicating that rosuvastatin affects insulin secretion through its effects on the mevalonate pathway, but not through the reduction of cholesterol biosynthesis. Taken together, these data suggest that rosuvastatin has the potential to increase basal insulin secretion and reduce glucose-induced insulin secretion. The latter is possibly an unavoidable side effect of rosuvastatin treatment as it occurs through the same mechanisms as the lipid-lowering effects of the drug. PMID:26986474

5. Rockwork on the north bank of S. Platte River ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. Rockwork on the north bank of S. Platte River located approximately 5 of a mile downstream from Deansbury Bridge. View looking northwest from a distance of 50 feet. - Denver & Rio Grande Rockwork, East of South Platte, Waterton, Jefferson County, CO

7. Rockwork on north bank of S. Platte River located ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. Rockwork on north bank of S. Platte River located approximately .3 of a mile downstream from the Deansbury Bridge. View looking northwest from a distance of 30 feet. - Denver & Rio Grande Rockwork, East of South Platte, Waterton, Jefferson County, CO

Effect of multiphase radiation on coal combustion in a pulverized coal jet flame

NASA Astrophysics Data System (ADS)

Wu, Bifen; Roy, Somesh P.; Zhao, Xinyu; Modest, Michael F.

2017-08-01

The accurate modeling of coal combustion requires detailed radiative heat transfer models for both gaseous combustion products and solid coal particles. A multiphase Monte Carlo ray tracing (MCRT) radiation solver is developed in this work to simulate a laboratory-scale pulverized coal flame. The MCRT solver considers radiative interactions between coal particles and three major combustion products (CO2, H2O, and CO). A line-by-line spectral database for the gas phase and a size-dependent nongray correlation for the solid phase are employed to account for the nongray effects. The flame structure is significantly altered by considering nongray radiation and the lift-off height of the flame increases by approximately 35%, compared to the simulation without radiation. Radiation is also found to affect the evolution of coal particles considerably as it takes over as the dominant mode of heat transfer for medium-to-large coal particles downstream of the flame. To investigate the respective effects of spectral models for the gas and solid phases, a Planck-mean-based gray gas model and a size-independent gray particle model are applied in a frozen-field analysis of a steady-state snapshot of the flame. The gray gas approximation considerably underestimates the radiative source terms for both the gas phase and the solid phase. The gray coal approximation also leads to under-prediction of the particle emission and absorption. However, the level of under-prediction is not as significant as that resulting from the employment of the gray gas model. Finally, the effect of the spectral property of ash on radiation is also investigated and found to be insignificant for the present target flame.

Some design philosophy for reducing the community noise of advanced counter-rotation propellers

NASA Technical Reports Server (NTRS)

Dittmar, J. H.

1985-01-01

Advanced counter-rotation propellers have been indicated as possibly generating an unacceptable amount of noise for the people living near an airport. This report has explored ways to reduce this noise level, which is treated as being caused by the interaction of the upstream propeller wakes and vortices with the downstream propeller. The noise reduction techniques fall into two categories: (1) reducing the strength of the wakes and vortices, and (2) reducing the response of the downstream blades to them. The noise from the wake interaction was indicated as being reduced by increased propeller spacing and decreased blade drag coefficient. The vortex-interaction noise could be eliminated by having the vortex pass over the tips of the downstream blade, and it could be reduced by increased spacing or decreased initial circulation. The downstream blade response could be lessened by increasing the reduced frequency parameter omega or by phasing of the response from different sections to have a mutual cancellation effect. Uneven blade to blade spacing for the downstream blading was indicated as having a possible effect on the annoyance of counter-rotation propeller noise. Although there are undoubtedly additional methods of noise reduction not covered in this report, the inclusion of the design methods discussed would potentially result in a counter-rotation propeller that is acceptably quiet.

[Effects of Biejiajian Pills on Wnt signal pathway signal molecules β-catenin/TCF4 complex activities and downstream proteins cyclin D1 and MMP-2 in hepatocellular carcinoma cells].

PubMed

Wen, Bin; Sun, Haitao; He, Songqi; Cheng, Yang; Jia, Wenyan; Fan, Eryan; Pang, Jie

2014-12-01

To study the effect of Biejiajian Pills on Wnt signal pathway and the mechanisms underlying its action to suppress the invasiveness of hepatocellular carcinoma. HepG2 cells cultured in the serum of rats fed with Biejiajian Pills for 48 h were examined for β-catenin expression using immunofluorescence, β-catenin/TCF4 complex activity with luciferase, and expressions of the downstream proteins cyclin D1 and MMP-2 using qRT-PCR. Biejiajian Pills-treated sera significantly reduced the expressions of cytoplasmic and nuclear β-catenin protein, cyclin D1 and MMP-2 proteins and lowered the activities of β-catenin/TCF4 complex. Biejiajian Pills may serve as a potential anti-tumor agent, whose effect might be mediated by inhibiting the Wnt/β-catenin pathway.

Comparative studies on mitochondrial electron transport chain complexes of Sitophilus zeamais treated with allyl isothiocyanate and calcium phosphide.

PubMed

Zhang, Chao; Wu, Hua; Zhao, Yuan; Ma, Zhiqing; Zhang, Xing

2016-01-01

With Sitophilus zeamais as the target organism, the present study for the first time attempted to elucidate the comparative effects between allyl isothiocyanate (AITC) and calcium phosphide (Ca3P2), exposure on mitochondrial electron transport chain (ETC.) complex I & IV and their downstream effects on enzymes relevant to reactive oxygen species (ROS). In vivo, both AITC and Ca3P2 inhibited complex I and IV with similar downstream effects. In contrast with Ca3P2, the inhibition of complex I caused by AITC was dependent on time and dose. In vitro, AITC inhibited complex IV more significantly than complex I. These results indicate that mitochondrial complex IV is the primary target of AITC, and that complex I is another potential target. Copyright © 2015 Elsevier B.V. All rights reserved.

Downscaling catchment scale flood risk to contributing sub-catchments to determine the optimum location for flood management.

NASA Astrophysics Data System (ADS)

Pattison, Ian; Lane, Stuart; Hardy, Richard; Reaney, Sim

2010-05-01

The recent increase in flood frequency and magnitude has been hypothesised to have been caused by either climate change or land management. Field scale studies have found that changing land management practices does affect local runoff and streamflow, but upscaling these effects to the catchment scale continues to be problematic, both conceptually and more importantly methodologically. The impact on downstream flood risk is highly dependent upon where the changes are in the catchment, indicating that some areas of the catchment are more important in determining downstream flood risk than others. This is a major flaw in the traditional approach to studying the effect of land use on downstream flood risk: catchment scale hydrological models, which treat every cell in the model equally. We are proposing an alternative ideological approach for doing flood management research, which is underpinned by downscaling the downstream effect (problem i.e. flooding) to the upstream causes (contributing sub-catchments). It is hoped that this approach could have several benefits over the traditional upscaling approach. Firstly, it provides an efficient method to prioritise areas for land use management changes to be implemented to reduce downstream flood risk. Secondly, targets for sub-catchment hydrograph change can be determined which will deliver the required downstream effect. Thirdly, it may be possible to detect the effect of land use changes in upstream areas on downstream flood risk, by weighting the areas of most importance in hydrological models. Two methods for doing this downscaling are proposed; 1) data-based statistical analysis; and 2) hydraulic modelling-based downscaling. These will be outlined using the case study of the River Eden, Cumbria, NW England. The data-based methodology uses the timing and magnitude of floods for each sub-catchment. Principal components analysis (PCA) is used to simplify sub-catchment interactions and optimising stepwise regression is used to predict downstream flood magnitude from the significant principal components. Two particular sub-catchments, the Eamont and the Upper Eden were highlighted as explaining the highest proportion of downstream flood risk, with 21.0% and 19.6% respectively. This approach uses the concept of data mining, whereby commonly available discharge data is used in an innovative way to learn about catchment behaviour. An alternative downscaling approach is hydraulic modelling whereby the input hydrographs from each tributary are changed in turn, both in terms of the magnitudes and the timing of the flows. This basic scenario testing approach can be used to assess the sensitivity of downstream flood risk to upstream contributing tributaries. This approach also highlighted the Upper Eden and Eamont as the most sensitive sub-catchments. A 25% reduction in the flows from these sub-catchments resulted in a 33.1cm and 21.9cm stage reduction downstream respectively, while an 8 hour delay of the peak flow caused a 32.3cm and 27.4cm decrease in downstream stage respectively. This alternative flood management approach is not a replacement to traditional hydrological modelling (upscaling), but a pre-step which allows for more focussed and informed investigation of land management scenarios, in the area where they are most likely to have beneficial impacts on downstream flooding.

Relation Between Flow and Dissolved Oxygen in the Roanoke River Between Roanoke Rapids and Jamesville, North Carolina, 1998-2005

USGS Publications Warehouse

Wehmeyer, Loren L.; Bales, Jerad D.

2009-01-01

Understanding the relation between dam release characteristics and downstream water quality in the lower Roanoke River, North Carolina, is important for natural-resource management and ecosystem protection. Data from four raingages, four water-quality monitoring sites, and one streamflow-measurement site were used to identify statistical relations and discernible quantitative or qualitative patterns linking Roanoke River instream dissolved-oxygen (DO) levels to releases at Roanoke Rapids Dam for the period 1998-2005. The time-series DO data, complicated by the occurrence of major hurricanes in the short period of hourly DO data collection at the dam, present a mixed picture of the effects of hydropower peaking (a technique used by hydropower dam operators to produce electricity when consumption is high by passing a large volume of water through the dam turbines, which dramatically increases the volume of flow below the dam) on downstream DO. Other than in 2003 when dissolved-oxygen concentrations in the Roanoke River were likely affected by runoff from Hurricane Isabel rains, there were not consistent, statistically significant differences detected in the annual medians of hourly and(or) daily DO values during peaking versus nonpeaking periods. Along the Roanoke River, downstream of Roanoke Rapids Dam at Oak City, North Carolina, using a 95-percent confidence interval, the median value of the May-November daily mean DO concentrations for each year was lower during peaking periods for 2 years, higher for 2 years, and not significantly different for 4 years. Downstream at Jamesville, North Carolina, also using a 95-percent confidence interval, the median value of the annual May-November daily mean DO concentrations during hydropower peaking was lower for 4 years, higher for 2 years, and not significantly different for 2 years. In summary, the effect of hydropower peaking on downstream DO was inconsistent. Conversely, large precipitation events downstream from the dam resulted in consistent, statistically significant decreases in DO in the mainstem of the Roanoke River at Oak City and Jamesville.

Experiments on tip vortices interacting with downstream wings

NASA Astrophysics Data System (ADS)

Chen, C.; Wang, Z.; Gursul, I.

2018-05-01

The interaction of meandering tip vortices shed from a leading wing with a downstream wing was investigated experimentally in a water tunnel using flow visualization, particle image velocimetry measurements, and volumetric velocity measurements. Counter-rotating upstream vortices may exhibit sudden variations of the vortex core location when the wing-tip separation is within approximately twice the vortex core radius. This is caused by the formation of vortex dipoles near the wing tip. In contrast, co-rotating upstream vortices do not exhibit such sensitivity. Large spanwise displacement of the trajectory due to the image vortex is possible when the incident vortex is further inboard. For both co-rotating and counter-rotating vortices, as long as there is no direct impingement upon the wing, there is a little change in the structure of the time-averaged vortex past the wing, even though the tip vortex shed from the downstream wing may be substantially weakened or strengthened. In the absence of the downstream wing, as well as for weak interactions, the most energetic unsteady modes represent the first helical mode | m| = 1, which is estimated from the three-dimensional Proper Orthogonal Decomposition modes and has a very large wavelength, on the order of 102 times the vortex core radius, λ/ a = O(102). Instantaneous vorticity measurements as well as flow visualization suggest the existence of a smaller wavelength, λ/ a = 5-6, which is not among the most energetic modes. These two-orders of magnitude different wavelengths are in agreement with the previous measurements of tip vortices and also exhibit qualitative agreement with the transient energy growth analysis. The very long wavelength mode in the upstream vortex may persist during the interaction, and reveal coupling with the trailing vortex as well as increased meandering.

The unliganded long isoform of estrogen receptor beta stimulates brain ryanodine receptor single channel activity alongside with cytosolic Ca2+

PubMed Central

Rybalchenko, Volodymyr; Grillo, Michael A.; Gastinger, Matthew J.; Rybalchenko, Nataliya; Payne, Andrew J.; Koulen, Peter

2010-01-01

Ca2+ release from intracellular stores mediated by endoplasmic reticulum membrane ryanodine receptors (RyR) plays a key role in activating and synchronizing downstream Ca2+-dependent mechanisms, in different cells varying from apoptosis to nuclear transcription and development of defensive responses. Recently discovered, atypical “non-genomic” effects mediated by estrogen receptors (ER) include rapid Ca2+ release upon estrogen exposure in conditions implicitly suggesting involvement of RyRs. In the present study, we report various levels of co-localization between RyR type 2 (RyR2) and ER type β (ERβ) in the neuronal cell line HT-22, indicating a possible functional interaction. Electrophysiological analyses revealed a significant increase in single channel ionic currents generated by mouse brain RyRs after application of the soluble monomer of the long form ERβ (ERβ1). The effect was due to a strong increase in open probability of RyR higher open channel sublevels at cytosolic [Ca2+] concentrations of 100 nM, suggesting a synergistic action of ERβ1 and Ca2+ in RyR activation, and a potential contribution to Ca2+-induced Ca2+ release rather than to basal intracellular Ca2+ concentration level at rest. This RyR/ERβ interaction has potential effects on cellular physiology, including roles of shorter ERβ isoforms and modulation of the RyR/ERβ complexes by exogenous estrogens. PMID:19899956

Effect of Wnt-1 inducible signaling pathway protein-2 (WISP-2/CCN5), a downstream protein of Wnt signaling, on adipocyte differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inadera, Hidekuni; Shimomura, Akiko; Tachibana, Shinjiro

2009-02-20

Wnt signaling negatively regulates adipocyte differentiation, and ectopic expression of Wnt-1 in 3T3-L1 cells induces several downstream molecules of Wnt signaling, including Wnt-1 inducible signaling pathway protein (WISP)-2. In this study, we examined the role of WISP-2 in the process of adipocyte differentiation using an in vitro cell culture system. In the differentiation of 3T3-L1 cells, WISP-2 expression was observed in growing cells and declined thereafter. In the mitotic clonal expansion phase of adipocyte differentiation, WISP-2 expression was transiently down-regulated concurrently with up-regulation of CCAAT/enhancer-binding protein {delta} expression. Treatment of 3T3-L1 cells in the differentiation medium with lithium, an activatormore » of Wnt signaling, inhibited the differentiation process with concomitant induction of WISP-2. Treatment of differentiated cells with lithium induced de-differentiation as evidenced by profound reduction of peroxisome proliferator-activator receptor {gamma} expression and concomitant induction of WISP-2. However, de-differentiation of differentiated cells induced by tumor necrosis factor-{alpha} did not induce WISP-2 expression. To directly examine the effect of WISP-2 on adipocyte differentiation, 3T3-L1 cells were infected with a retrovirus carrying WISP-2. Although forced expression of WISP-2 inhibited preadipocyte proliferation, it had no effect on adipocyte differentiation. Thus, although WISP-2 is a downstream protein of Wnt signaling, the role of WISP-2 on adipocyte differentiation may be marginal, at least in this in vitro culture model.« less

Inorganic and organic carbon spatial variability in the Congo River during high waters (December 2013)

NASA Astrophysics Data System (ADS)

Borges, Alberto V.; Bouillon, Steven; Teodoru, Cristian; Leporcq, Bruno; Descy, Jean-Pïerre; Darchambeau, François

2014-05-01

Rivers are important components of the global carbon cycle, as they transport terrestrial organic matter from the land to the sea, and emit CO2 to the atmosphere. In particular, tropical systems that account for 60% of global freshwater discharge to the oceans. In contrast with south American rivers, very little information is available for African rivers on their carbon flows and stocks, in particular the Congo river, the second largest river in the World in terms of freshwater discharge (1457 km3 yr-1) and in terms of drainage basin (3.75 106 km2) located the second largest tropical forest in the World. Here, we report a data-set of continuous (every minute) records of the partial pressure of CO2 (pCO2) (total of 10,000 records), and discrete samples of particulate (POC) and dissolved (DOC) organic carbon (total of 75 samples) in the mainstem and major tributaries of the Congo river, along the 1700 km stretch from Kisangani to Kinshasa (total river length = 4374 km), during the high water period (December 2013). The pCO2 dynamic range was high ranging from minimum values of 2000 ppm in white waters tributaries (higher turbidity, conductivity and O2, lower DOC), up to maximal values of 18,000 ppm in blackwaters tributaries (lower turbidity, conductivity and O2, higher DOC). In the mainstem, very strong horizontal (cross-section) gradients were imposed by the presence of blackwaters close to the riverbanks and the presence of whitewaters in the middle of the river. In the mainstem, a distinct horizontal (longitudinal) pattern was observed with pCO2 increasing, and conductivity and turbidity decreasing downstream.

Particulate Matter and Gaseous Pollutions in Three Metropolises along the Chinese Yangtze River: Situation and Implications.

PubMed

Mao, Mao; Zhang, Xiaolin; Yin, Yan

2018-05-28

The situation of criteria atmospheric pollutants, including particulate matter and trace gases (SO₂, NO₂, CO and O₃), over three metropolises (Chongqing, Wuhan, and Nanjing), representing the upstream, midstream and downstream portions of the Yangtze River Basin from September 2015 to August 2016 were analyzed. The maximum annual mean PM 2.5 and PM 10 concentrations were 61.3 and 102.7 μg/m³ in Wuhan, while highest annual average gaseous pollutions occurred in Nanjing, with 49.6 and 22.9 ppb for 8 h O₃ and NO₂, respectively. Compared to a few years ago, SO₂ and CO mass concentrations have dropped to well below the qualification standards, and the O₃ and NO₂ concentrations basically meet the requirements though occasionally is still high. In contrary, about 13%, 25%, 22% for PM 2.5 , and 4%, 17%, 15% for PM 10 exceed the Chinese Ambient Air Quality Standard (CAAQS) Grade II. Particulate matter, especially PM 2.5 , is the most frequent major pollutant to poor air quality with 73%, 64% and 88% accounting for substandard days. Mean PM 2.5 concentrations on PM 2.5 episode days are 2⁻3 times greater than non-episode days. On the basis of calculation of PM 2.5 /PM 10 and PM 2.5 /CO ratios, the enhanced particulate matter pollution on episode days is closely related to secondary aerosol production. Except for O₃, the remaining five pollutants exhibit analogous seasonal patterns, with the highest magnitude in winter and lowest in summer. The results of back trajectories show that air pollution displays synergistic effects on local emissions and long range transport. O₃ commonly demonstrated negative correlations with other pollutants, especially during winter, while moderate to strong positive correlation between particulate matter and NO₂, SO₂, CO were seen. Compared to pollutant substandard ratios over three megacities in eastern China (Beijing, Shanghai, and Guangzhou), the situation in our studied second-tier cities are also severe. The results in this paper provide basic knowledge for pollution status of three cities along Chinese Yangtze River and are conductive to mitigating future negative air quality levels.

Trans, trans-2,4-decadienal induced cell proliferation via p27 pathway in human bronchial epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Y.-C.; Lin Pinpin

2008-04-01

Lung cancer is the leading cause of cancer deaths worldwide. Epidemiological studies have shown that exposure to cooking oil fumes (COF) is a risk factor for lung cancer. Trans, trans-2,4-decadienal (tt-DDE), a dienaldehyde, is abundant in heated oils and COF. Previously, we found that long-term exposure (45 days) to a sub-lethal dose (1 {mu}M) of tt-DDE significantly increased growth of human bronchial epithelial cells (BEAS-2B). Aims of this study are to understand the mechanism of tt-DDE-induced cell proliferation and possible protective effects of antioxidant, vitamin C and N-acetylcysteine (NAC) in BEAS-2B cells. Utilizing the real-time RT-PCR and Western immunoblotting, wemore » found that p27 mRNA and protein levels were significantly increased by 1 {mu}M tt-DDE treatment. Co-treatment with vitamin C or NAC partially prevented tt-DDE-induced cell proliferation. In addition, the downstream targets of p27, including CDK4, cyclin D{sub 1} and phosphorylated-Rb proteins, increased in 1 {mu}M tt-DDE-treated cells and these changes were prevented by NAC co-treatment. Therefore, these results suggest that tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D{sub 1} protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis.« less

Identification of residues within the African swine fever virus DP71L protein required for dephosphorylation of translation initiation factor eIF2α and inhibiting activation of pro-apoptotic CHOP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barber, Claire; Netherton, Chris; Goatley, Lynnett

The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate the translation initiation factor 2α (eIF2α) and avoid shut-off of global protein synthesis and downstream activation of the pro-apoptotic factor CHOP. Residues V16 and F18A were critical for binding of DP71L to PP1. Mutation of this PP1 binding motif or deletion of residues between 52 and 66 reduced the ability of DP71L to cause dephosphorylation of eIF2α and inhibit CHOP induction. The residues LSAVL, between 57 and 61, were also required. PP1 was co-precipitated with wild type DP71L and the mutant lacking residues 52- 66 ormore » the LSAVL motif, but not with the PP1 binding motif mutant. The residues in the LSAVL motif play a critical role in DP71L function but do not interfere with binding to PP1. Instead we propose these residues are important for DP71L binding to eIF2α. - Highlights: •The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate translation initiation factor eIF2α (eIF2α). •The residues V{sup 16}, F{sup 18} of DP71L are required for binding to the α, β and γ isoforms of PP1 and for DP71L function. •The sequence LSAVL downstream from the PP1 binding site (residues 57–61) are also important for DP71L function. •DP71L mutants of the LSAVL sequence retain ability to co-precipitate with PP1 showing these sequences have a different role to PP1 binding.« less

Hydrological controls on riverine carbon export in a seasonally wet tropical catchment

NASA Astrophysics Data System (ADS)

Duvert, C.; Hutley, L. B.; Bossa, M.; Bird, M. I.; Munksgaard, N.; Wynn, J. G.; Setterfield, S. A.; Northwood, M.

2017-12-01

Understanding the movement of carbon (C) through the landscape is critical for accurate C accounting. Failure to account for the transport of terrestrially-derived C to aquifers and streams can result in a considerable over-estimation of the C sequestration by the biosphere. Here we report on the magnitude of C export via shallow groundwater and adjacent streams in a savanna-covered seasonally wet tropical catchment of northern Australia. Riverine fluxes of carbon dioxide (CO2), dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) were measured at a high resolution over a full year to gain insight into the drivers of C export in this system. Water and C stable isotopes were also measured in order to elucidate water sources and dominant flow pathways. Our results suggest that CO2 evasion was the major process contributing to riverine C loss in the catchment (111 kg C ha-1 yr-1). The downstream export of C was dominated by DOC (78 kg C ha-1 yr-1), while DIC accounted for 39 kg C ha-1 yr-1 of the annual export. The bulk of annual DOC export was flushed out during the very first high-flow events, with export decreasing throughout the wet season to pre-flood levels. In contrast, the DIC flux was more important during flow recession, upon activation of deeper flowpaths carrying geologically-derived C. Shallow groundwater measured in boreholes was supersaturated with CO2 (15,000 < pCO2 < 55,000 ppm), whereas in-stream concentrations were an order of magnitude lower, suggesting substantial outgassing of CO2. Our findings outline the key role of point-source groundwater discharge in riverine CO2 evasion, with C largely sourced from seasonally productive savanna vegetation. Given the complexity of this pathway and the magnitude of this flux, new methods are needed to more precisely quantify CO2 evasion.

Functional selectivity induced by mGlu₄ receptor positive allosteric modulation and concomitant activation of Gq coupled receptors.

PubMed

Yin, Shen; Zamorano, Rocio; Conn, P Jeffrey; Niswender, Colleen M

2013-03-01

Metabotropic glutamate receptors (mGlus) are a group of Family C Seven Transmembrane Spanning Receptors (7TMRs) that play important roles in modulating signaling transduction, particularly within the central nervous system. mGlu(4) belongs to a subfamily of mGlus that is predominantly coupled to G(i/o) G proteins. We now report that the ubiquitous autacoid and neuromodulator, histamine, induces substantial glutamate-activated calcium mobilization in mGlu(4)-expressing cells, an effect which is observed in the absence of co-expressed chimeric G proteins. This strong induction of calcium signaling downstream of glutamate activation of mGlu(4) depends upon the presence of H(1) histamine receptors. Interestingly, the potentiating effect of histamine activation does not extend to other mGlu(4)-mediated signaling events downstream of G(i/o) G proteins, such as cAMP inhibition, suggesting that the presence of G(q) coupled receptors such as H(1) may bias normal mGlu(4)-mediated G(i/o) signaling events. When the activity induced by small molecule positive allosteric modulators of mGlu(4) is assessed, the potentiated signaling of mGlu(4) is further biased by histamine toward calcium-dependent pathways. These results suggest that G(i/o)-coupled mGlus may induce substantial, and potentially unexpected, calcium-mediated signaling events if stimulation occurs concomitantly with activation of G(q) receptors. Additionally, our results suggest that signaling induced by small molecule positive allosteric modulators may be substantially biased when G(q) receptors are co-activated. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. Copyright © 2012 Elsevier Ltd. All rights reserved.

TAZ Expression as a Prognostic Indicator in Colorectal Cancer

PubMed Central

Tham, Jill M.; Zhang, Xiaoqian; Zeng, Qi; Zhang, Shu-Dong; Hong, WanJin

2013-01-01

The Hippo pathway restricts the activity of transcriptional coactivators TAZ (WWTR1) and YAP. TAZ and YAP are reported to be overexpressed in various cancers, however, their prognostic significance in colorectal cancers remains unstudied. The expression levels of TAZ and YAP, and their downstream transcriptional targets, AXL and CTGF, were extracted from two independent colon cancer patient datasets available in the Gene Expression Omnibus database, totaling 522 patients. We found that mRNA expressions of both TAZ and YAP were positively correlated with those of AXL and CTGF (p<0.05). High level mRNA expression of TAZ, AXL or CTGF significantly correlated with shorter survival. Importantly, patients co-overexpressing all 3 genes had a significantly shorter survival time, and combinatorial expression of these 3 genes was an independent predictor for survival. The downstream target genes for TAZ-AXL-CTGF overexpression were identified by Java application MyStats. Interestingly, genes that are associated with colon cancer progression (ANTXR1, EFEMP2, SULF1, TAGLN, VCAN, ZEB1 and ZEB2) were upregulated in patients co-overexpressing TAZ-AXL-CTGF. This TAZ-AXL-CTGF gene expression signature (GES) was then applied to Connectivity Map to identify small molecules that could potentially be utilized to reverse this GES. Of the top 20 small molecules identified by connectivity map, amiloride (a potassium sparing diuretic,) and tretinoin (all-trans retinoic acid) have shown therapeutic promise in inhibition of colon cancer cell growth. Using MyStats, we found that low level expression of either ANO1 or SQLE were associated with a better prognosis in patients who co-overexpressed TAZ-AXL-CTGF, and that ANO1 was an independent predictor of survival together with TAZ-AXL-CTGF. Finally, we confirmed that TAZ regulates Axl, and plays an important role in clonogenicity and non-adherent growth in vitro and tumor formation in vivo. These data suggest that TAZ could be a therapeutic target for the treatment of colon cancer. PMID:23372686

Radioactivity levels in major French rivers: summary of monitoring chronicles acquired over the past thirty years and current status.

PubMed

Eyrolle, Frédérique; Claval, David; Gontier, Gilles; Antonelli, Christelle

2008-07-01

Since the beginning of the 1990 s, liquid releases of gamma-emitting radionuclides from French nuclear facilities have generally fallen by almost 85%. Almost 65% of gamma-emitting liquid effluents released into freshwater rivers concerned the River Rhône (Southeast France), with around 85% of this originating from the Marcoule spent fuel reprocessing plant. Upstream of French nuclear plants, artificial radionuclides still detected by gamma spectrometry in 2006, include (137)Cs, (131)I as well as (60)Co, (58)Co and (54)Mn in the case of the Rhine (Switzerland nuclear industries). In the wake of the fallout from the Chernobyl accident, (103)Ru, (106)Rh-Ru, (110 m)Ag, (141)Ce and (129)Te were detected in rivers in the east of France. Some of these radionuclides were found in aquatic plants until 1989. In eastern France, (137)Cs activity in river sediments and mosses is still today two to three times greater than that observed in similar environments in western France. No (134)Cs has been detected upstream of nuclear plants in French rivers since 2001. Downstream of nuclear plants, the gamma emitters still detected regularly in rivers in 2006 are (137)Cs, (134)Cs, (60)Co, (58)Co, (110 m)Ag, (54)Mn, (131)I, together with (241)Am downstream of the Marcoule spent fuel reprocessing plant. Alpha and beta emitters such as plutonium isotopes and (90)Sr first entered freshwaters at the early 1950s due to the leaching of soils contaminated by atmospheric fallout from nuclear testing. These elements were also introduced, in the case of the Rhône River, via effluent from the Marcoule reprocessing plant. Until the mid 1990 s, plutonium isotope levels observed in the lower reaches of the Rhône were 10 to 1000 times higher than those observed in other French freshwaters. Data gathered over a period of almost thirty years of radioecological studies reveal that the only radionuclides detected in fish muscles are (137)Cs, (90)Sr, plutonium isotopes and (241)Am. At the scale of the French territory, there is no significant difference since the mid 1990 s between (137)Cs activity observed downstream of nuclear facilities and that observed upstream, whether in sediments, mosses and fish. Finally, this study highlights that the natural radioactivity of surface freshwaters are around 25 times greater than artificial radioactivity from gamma emitters. However, non gamma emitters released by nuclear industries, such as (3)H, may lead to artificial activity levels 2 to 20 times higher than natural levels.

A kinetic study of Ca-containing ions reacting with O, O2, CO2 and H2O: implications for calcium ion chemistry in the upper atmosphere.

PubMed

Broadley, Sarah; Vondrak, Tomas; Wright, Timothy G; Plane, John M C

2008-09-14

A series of gas-phase reactions involving molecular Ca-containing ions was studied by the pulsed laser ablation of a calcite target to produce Ca+ in a fast flow of He, followed by the addition of reagents downstream and detection of ions by quadrupole mass spectrometry. Most of the reactions that were studied are important for describing the chemistry of meteor-ablated calcium in the earth's upper atmosphere. The following rate coefficients were measured: k(CaO+ + O --> Ca+ + O2) = (4.2 +/- 2.8) x 10(-11) at 197 K and (6.3 +/- 3.0) x 10(-11) at 294 K; k(CaO+ + CO --> Ca+ + CO2, 294 K) = (2.8 +/- 1.5) x 10(-10); k(Ca+.CO2 + O2 --> CaO2+ + CO2, 294 K) = (1.2 +/- 0.5) x10(-10); k(Ca+.CO2 + H2O --> Ca+.H2O + CO2) = (13.0 +/- 4.0) x 10(-10); and k(Ca+.H2O + O2 --> CaO2+ + H2O, 294 K) = (4.0 +/- 2.5) x 10(-10) cm3 molecule(-1) s(-1). The quoted uncertainties are a combination of the 1 sigma standard errors in the kinetic data and the systematic errors in the models used to extract the rate coefficients. Rate coefficients were also obtained for the following recombination (also termed association) reactions in He bath gas: k(Ca+.CO2 + CO2 --> Ca+.(CO2)2, 294 K) = (2.6 +/- 1.0) x 10(-29); k(Ca+.H2O + H2O --> Ca+.(H2O)2) = (1.6 +/- 1.1) x 10(-27); and k(CaO2+ + O2 --> CaO2+.O2) < 1 x 10(-31) cm6 molecule(-2) s(-1). These recombination rate coefficients, as well as those for the ligand-switching reactions listed above, were then interpreted using a combination of high level quantum chemistry calculations and RRKM theory using an inverse Laplace transform solution of the master equation. The surprisingly slow reaction between CaO+ and O was explained using quantum chemistry calculations on the lowest 2A', 2A'' and 4A'' potential energy surfaces. These calculations indicate that reaction mostly occurs on the 2A' surface, leading to production of Ca+ (2S) + O2(1 Delta g). The importance of this reaction for controlling the lifetime of Ca+ in the upper mesosphere and lower thermosphere is then discussed.

Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab.

PubMed

Luo, Jingtao; Hong, Yun; Lu, Yang; Qiu, Songbo; Chaganty, Bharat K R; Zhang, Lun; Wang, Xudong; Li, Qiang; Fan, Zhen

2017-01-01

Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing the Warburg effect and leading to inhibition of cancer cell metabolism. AMP-activated protein kinase (AMPK) is activated after cetuximab treatment, and a sustained AMPK activity is a mechanism contributing to cetuximab resistance. Here, we investigated how acetyl-CoA carboxylase (ACC), a downstream target of AMPK, rewires cancer metabolism in response to cetuximab treatment. We found that introduction of experimental ACC mutants lacking the AMPK phosphorylation sites (ACC1_S79A and ACC2_S212A) into head and neck squamous cell carcinoma (HNSCC) cells protected HNSCC cells from cetuximab-induced growth inhibition. HNSCC cells with acquired cetuximab resistance contained not only high levels of T172-phosphorylated AMPK and S79-phosphorylated ACC1 but also an increased level of total ACC. These findings were corroborated in tumor specimens of HNSCC patients treated with cetuximab. Cetuximab plus TOFA (an allosteric inhibitor of ACC) achieved remarkable growth inhibition of cetuximab-resistant HNSCC xenografts. Our data suggest a novel paradigm in which cetuximab-mediated activation of AMPK and subsequent phosphorylation and inhibition of ACC is followed by a compensatory increase in total ACC, which rewires cancer metabolism from glycolysis-dependent to lipogenesis-dependent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Epistatic and Independent Effects on Schizophrenia-Related Phenotypes Following Co-disruption of the Risk Factors Neuregulin-1 × DISC1.

PubMed

O'Tuathaigh, Colm M P; Fumagalli, Fabio; Desbonnet, Lieve; Perez-Branguli, Francesc; Moloney, Gerard; Loftus, Samim; O'Leary, Claire; Petit, Emilie; Cox, Rachel; Tighe, Orna; Clarke, Gerard; Lai, Donna; Harvey, Richard P; Cryan, John F; Mitchell, Kevin J; Dinan, Timothy G; Riva, Marco A; Waddington, John L

2017-01-01

Few studies have addressed likely gene × gene (ie, epistatic) interactions in mediating risk for schizophrenia. Using a preclinical genetic approach, we investigated whether simultaneous disruption of the risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant phenotypic profile different from that observed following disruption to either gene alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse inhibition, both reversed by antipsychotic treatment, and accompanied by reduced striatal dopamine D2 receptor protein expression, impaired social cognition, and altered glutamatergic synaptic protein expression in selected brain areas. Single gene DISC1 mutants demonstrated a disruption in social cognition and nest-building, altered brain 5-hydroxytryptamine levels and hippocampal ErbB4 expression, and decreased cortical expression of the schizophrenia-associated microRNA miR-29b. Co-disruption of DISC1 and NRG1, indicative of epistasis, evoked an impairment in sociability and enhanced self-grooming, accompanied by changes in hypothalamic oxytocin/vasopressin gene expression. The findings indicate specific behavioral correlates and underlying cellular pathways downstream of main effects of DNA variation in the schizophrenia-associated genes NRG1 and DISC1. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Patterns in stream greenhouse gas dynamics from mountains to plains in northcentral Wyoming

NASA Astrophysics Data System (ADS)

Kuhn, C.; Bettigole, C.; Glick, H. B.; Seegmiller, L.; Oliver, C. D.; Raymond, P.

2017-09-01

Quantification of small stream contributions to global carbon cycling is key to understanding how freshwater systems transmit and transform carbon between terrestrial and atmospheric pools. To date, greenhouse gas emissions of carbon dioxide and methane from freshwaters, particularly in mountainous regions, remain poorly characterized due to a lack of direct field observations. Using a unique longitudinal approach, we conducted field surveys across two ecoregions (Middle Rockies and Great Plains) in the Clear Creek watershed, a subwatershed of Wyoming's Powder River Basin. We took direct measurements of stream gases using headspace sampling at 30 sites (8 June to 23 October). We observed the lowest and most variable concentrations in headwaters, which flow through a federally designated alpine wilderness area. By contrast, the Great Plains exhibited 1.45 and 4 times higher pCO2 and pCH4 concentrations and the relative contributions of methane increased downstream. Fluxes during snowmelt were 45% and 58% higher for CO2 and CH4 than during base flow but overall were lower than estimates for other systems. Variability for pCO2 was highest during late summer and in the uppermost sections of the headwaters. The high heterogeneity and common undersaturation observed through space and time, especially in the mountains, suggest that downscaled regional estimates may fail to capture variability in fluxes observed at these smaller scales. Based on these results, we strongly recommend higher resolution time series studies and increased scrutiny of systems at near equilibrium, inclusive of winter storage and ice-off events, to improve our understanding of the effects of seasonal dynamics on these processes.

Mitochondrial control by DRP1 in brain tumor initiating cells.

PubMed

Xie, Qi; Wu, Qiulian; Horbinski, Craig M; Flavahan, William A; Yang, Kailin; Zhou, Wenchao; Dombrowski, Stephen M; Huang, Zhi; Fang, Xiaoguang; Shi, Yu; Ferguson, Ashley N; Kashatus, David F; Bao, Shideng; Rich, Jeremy N

2015-04-01

Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), showed activating phosphorylation in BTICs and inhibitory phosphorylation in non-BTIC tumor cells. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and targeting AMPK rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca(2+)-calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTIC tumor cells, suggesting that tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlated with poor prognosis in glioblastoma, suggesting that mitochondrial dynamics may represent a therapeutic target for BTICs.

CO2 and CH4 emissions from streams in a lake-rich landscape: Patterns, controls, and regional significance

USGS Publications Warehouse

Crawford, John T.; Lottig, Noah R.; Stanley, Emily H.; Walker, John F.; Hanson, Paul C.; Finlay, Jacques C.; Striegl, Robert G.

2014-01-01

Aquatic ecosystems are important components of landscape carbon budgets. In lake-rich landscapes, both lakes and streams may be important sources of carbon gases (CO2 and CH4) to the atmosphere, but the processes that control gas concentrations and emissions in these interconnected landscapes have not been adequately addressed. We use multiple data sets that vary in their spatial and temporal extent during 2001–2012 to investigate the carbon gas source strength of streams in a lake-rich landscape and to determine the contribution of lakes, metabolism, and groundwater to stream CO2 and CH4. We show that streams emit roughly the same mass of CO2 (23.4 Gg C yr−1; 0.49 mol CO2 m−2 d−1) as lakes at a regional scale (27 Gg C yr−1) and that stream CH4 emissions (189 Mg C yr−1; 8.46 mmol CH4 m−2 d−1) are an important component of the regional greenhouse gas balance. Gas transfer velocity variability (range = 0.34 to 13.5 m d−1) contributed to the variability of gas flux in this landscape. Groundwater inputs and in-stream metabolism control stream gas supersaturation at the landscape scale, while carbon cycling in lakes and deep groundwaters does not control downstream gas emissions. Our results indicate the need to consider connectivity of all aquatic ecosystems (lakes, streams, wetlands, and groundwater) in lake-rich landscapes and their connections with the terrestrial environment in order to understand the full nature of the carbon cycle.

Environmental signatures and effects of an oil and gas wastewater spill in the Williston Basin, North Dakota

USGS Publications Warehouse

Cozzarelli, Isabelle M.; Skalak, Katherine; Kent, D.B.; Engle, Mark A.; Benthem, Adam J.; Mumford, Adam; Haase, Karl B.; Farag, Aïda M.; Harper, David; Nagel, S. C.; Iwanowicz, Luke R.; Orem, William H.; Akob, Denise M.; Jaeschke, Jeanne B.; Galloway, Joel M.; Kohler, Matthias; Stoliker, Deborah L.; Jolly, Glenn D.

2017-01-01

Wastewaters from oil and gas development pose largely unknown risks to environmental resources. In January 2015, 11.4 M L (million liters) of wastewater (300 g/L TDS) from oil production in the Williston Basin was reported to have leaked from a pipeline, spilling into Blacktail Creek, North Dakota. Geochemical and biological samples were collected in February and June 2015 to identify geochemical signatures of spilled wastewaters as well as biological responses along a 44-km river reach. February water samples had elevated chloride (1030 mg/L) and bromide (7.8 mg/L) downstream from the spill, compared to upstream levels (11 mg/L and < 0.4 mg/L, respectively). Lithium (0.25 mg/L), boron (1.75 mg/L) and strontium (7.1 mg/L) were present downstream at 5–10 times upstream concentrations. Light hydrocarbon measurements indicated a persistent thermogenic source of methane in the stream. Semi-volatile hydrocarbons indicative of oil were not detected in filtered samples but low levels, including tetramethylbenzenes and di-methylnaphthalenes, were detected in unfiltered water samples downstream from the spill. Labile sediment-bound barium and strontium concentrations (June 2015) were higher downstream from the Spill Site. Radium activities in sediment downstream from the Spill Site were up to 15 times the upstream activities and, combined with Sr isotope ratios, suggest contributions from the pipeline fluid and support the conclusion that elevated concentrations in Blacktail Creek water are from the leaking pipeline. Results from June 2015 demonstrate the persistence of wastewater effects in Blacktail Creek several months after remediation efforts started. Aquatic health effects were observed in June 2015; fish bioassays showed only 2.5% survival at 7.1 km downstream from the spill compared to 89% at the upstream reference site. Additional potential biological impacts were indicated by estrogenic inhibition in downstream waters. Our findings demonstrate that environmental signatures from wastewater spills are persistent and create the potential for long-term environmental health effects.

Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

PubMed Central

Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

2016-01-01

Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells

PubMed Central

Smith, Stephen P.; Scarpini, Cinzia G.; Groves, Ian J.; Odle, Richard I.; Coleman, Nicholas

2016-01-01

Development of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of ‘master regulators’ for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n = 7) or HPV16 E7 (n = 5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes in vitro. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins. PMID:27457222

Prospects and challenges for the recovery of 2-butanol produced by vacuum fermentation - a techno-economic analysis.

PubMed

Pereira, Joana P C; Lopez-Gomez, Gustavo; Reyes, Noelia G; van der Wielen, Luuk A M; Straathof, Adrie J J

2017-07-01

The conceptual design of a bio-based process for 2-butanol production is presented for the first time. Considering a hypothetical efficient producing strain, a vacuum fermentation is proposed to alleviate product toxicity, but the main challenge is the energy-efficient product recovery from the vapor. Three downstream scenarios were examined for this purpose: 1) multi-stage vapor recompression; 2) temperature swing adsorption; and 3) vapor absorption. The processes were simulated using Aspen Plus, considering a production capacity of 101 kton/yr. Process optimization was performed targeting the minimum selling price of 2-butanol. The feasibility of the different configurations was analyzed based on the global energy requirements and capital expenditure. The use of integrated adsorption and absorption minimized the energy duty required for azeotrope purification, which represents 11% of the total operational expenditure in Scenario 1. The minimum selling price of 2-butanol as commodity chemical was estimated as 1.05 $/kg, 1.21 $/kg, and 1.03 $/kg regarding the fermentation integrated with downstream scenarios 1), 2), and 3), respectively. Significant savings in 2-butanol production could be achieved in the suggested integrated configurations if more efficient microbial strains were engineered, and more selective adsorption and absorption materials were found for product recovery. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gas-phase reactions of carbon dioxide with atomic transition-metal and main-group cations: room-temperature kinetics and periodicities in reactivity.

PubMed

Koyanagi, Gregory K; Bohme, Diethard K

2006-02-02

The chemistry of carbon dioxide has been surveyed systematically with 46 atomic cations at room temperature using an inductively-coupled plasma/selected-ion flow tube (ICP/SIFT) tandem mass spectrometer. The atomic cations were produced at ca. 5500 K in an ICP source and allowed to cool radiatively and to thermalize by collisions with Ar and He atoms prior to reaction downstream in a flow tube in helium buffer gas at 0.35 +/- 0.01 Torr and 295 +/- 2 K. Rate coefficients and products were measured for the reactions of first-row atomic ions from K(+) to Se(+), of second-row atomic ions from Rb(+) to Te(+) (excluding Tc(+)), and of third-row atomic ions from Cs(+) to Bi(+). CO(2) was found to react in a bimolecular fashion by O atom transfer only with 9 early transition-metal cations: the group 3 cations Sc(+), Y(+), and La(+), the group 4 cations Ti(+), Zr(+), and Hf(+), the group 5 cations Nb(+) and Ta(+), and the group 6 cation W(+). Electron spin conservation was observed to control the kinetics of O atom transfer. Addition of CO(2) was observed for the remaining 37 cations. While the rate of addition was not measurable some insight was obtained into the standard free energy change, DeltaG(o), for CO(2) ligation from equilibrium constant measurements. A periodic variation in DeltaG(o) was observed for first row cations that is consistent with previous calculations of bond energies D(0)(M(+)-CO(2)). The observed trends in D(0) and DeltaG(o) are expected from the variation in electrostatic attraction between M(+) and CO(2) which follows the trend in atomic-ion size and the trend in repulsion between the orbitals of the atomic cations and the occupied orbitals of CO(2). Higher-order CO(2) cluster ions with up to four CO(2) ligands also were observed for 24 of the atomic cations while MO(2)(+) dioxide formation by sequential O atom transfer was seen only with Hf(+), Nb(+), Ta(+), and W(+).

Optical emission spectroscopic studies and comparisons of CH{sub 3}F/CO{sub 2} and CH{sub 3}F/O{sub 2} inductively coupled plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lou, Qiaowei; Kaler, Sanbir; Donnelly, Vincent M., E-mail: vmdonnelly@uh.edu

2015-03-15

A CH{sub 3}F/CO{sub 2} inductively coupled plasma (ICP), sustained in a compact plasma reactor, was investigated as a function of power (5–400 W) and feed gas composition, at a pressure of 10 mTorr, using optical emission spectroscopy and rare gas actinometry. Number densities of H, F, and O increased rapidly between 74% and 80% CO{sub 2}, ascribed to the transition from polymer-covered to polymer-free reactor walls, similar to that found previously in CH{sub 3}F/O{sub 2} ICPs at 48% O{sub 2}. Below 40% O{sub 2} or CO{sub 2}, relative emission intensity ratios were almost identical for most key species in CH{sub 3}F/O{submore » 2} and CH{sub 3}F/CO{sub 2} ICPs except for higher OH/Xe (a qualitative measure of OH and H{sub 2}O densities) over the full range of CH{sub 3}F/O{sub 2} composition. The number density of H, F, and O increased with power in CH{sub 3}F/CO{sub 2} (20%/80%) plasmas (polymer-free walls), reaching 4.0, 0.34, and 1.6 × 10{sup 13}/cm{sup 3}, respectively, at 300 W. The CO number density increased with power and was estimated, based on self-actinometry, to be 8.8 × 10{sup 13}/cm{sup 3} at 300 W. The CO{sub 2} number density was independent of power below 40 W (where very little decomposition occurred), and then decreased rapidly with increasing power, reaching 2.8 × 10{sup 13}/cm{sup 3} at 300 W, corresponding to 83% dissociation. Films deposited on p-Si, 10 cm from the open, downstream end of the plasma reactor, were analyzed by x-ray photoelectron spectroscopy. Between 10% and 40% CO{sub 2} or O{sub 2} addition to CH{sub 3}F, film deposition rates fell and O content in the films increased. Faster deposition rates in CH{sub 3}F/CO{sub 2} plasmas were ascribed mainly to a larger thermodynamic driving force to form solid carbon, compared with CH{sub 3}F/O{sub 2} plasmas. Oxygen content in the films increased with increasing CO{sub 2} or O{sub 2} addition, but for the same deposition rate, no substantial differences were observed in the composition of the films.« less

Downstream boundary effects on the frequency of self-excited oscillations in transonic diffuser flows

NASA Astrophysics Data System (ADS)

Hsieh, T.

1986-10-01

Investigation of downstream boundary effects on the frequency of self-excited oscillations in two-dimensional, separated transonic diffuser flows were conducted numerically by solving the compressible, Reynolds-averaged, thin-layer Navier-Stokes equation with two equation turbulence models. It was found that the flow fields are very sensitive to the location of the downstream boundary. Extension of the diffuser downstream boundary significantly reduces the frequency and amplitude of oscillations for pressure, velocity, and shock. The existence of a suction slot in the experimental setpup obscures the physical downstream boundary and therefore presents a difficulty for quantitative comparisons between computation and experiment.

Effect of the selective pressure of sub-lethal level of heavy metals on the fate and distribution of ARGs in the catchment scale.

PubMed

Xu, Yan; Xu, Jian; Mao, Daqing; Luo, Yi

2017-01-01

Our previous study demonstrated that high levels of antibiotic resistance genes (ARGs) in the Haihe River were directly attributed to the excessive use of antibiotics in animal agriculture. The antibiotic residues of the Xiangjiang River determined in this study were much lower than those of the Haihe River, but the relative abundance of 16 detected ARGs (sul1, sul2 and sul3, qepA, qnrA, qnrB, qnrD and qnrS, tetA, tetB, tetW, tetM, tetQ and tetO, ermB and ermC), were as high as the Haihe River particularly in the downstream of the Xiangjiang River which is close to the extensive metal mining. The ARGs discharged from the pharmaceutical wastewater treatment plant (PWWTP) are a major source of ARGs in the upstream of the Xiangjiang River. In the downstream, selective stress of heavy metals rather than source release had a significant influence on the distinct distribution pattern of ARGs. Some heavy metals showed a positive correlation with certain ARG subtypes. Additionally, there is a positive correlation between individual ARG subtypes and heavy metal resistance genes, suggesting that heavy metals may co select the ARGs on the same plasmid of antibiotic resistant bacteria. The co-selection mechanism between specific metal and antibiotic resistance was further confirmed by these isolations encoding the resistance genotypes to antibiotics and metals. To our knowledge, this is the first study on the fate and distribution of ARGs under the selective pressure exerted by heavy metals in the catchment scale. These results are beneficial to understand the fate, and to discern the contributors of ARGs from either the source release or the selective pressure by sub-lethal levels of environmental stressors during their transport on a river catchment scale. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative Infrared Image Analysis Of Simultaneous Upstream and Downstream Microgravity Flame Spread over Thermally-Thin Cellulose in Low Speed Forced Flow

NASA Technical Reports Server (NTRS)

Olson, S. L.; Lee, J. R.; Fujita, O.; Kikuchi, M.; Kashiwagi, T.

2013-01-01

The effect of low velocity forced flow on microgravity flame spread is examined using quantitative analysis of infrared video imaging. The objective of the quantitative analysis is to provide insight into the mechanisms of flame spread in microgravity where the flame is able to spread from a central location on the fuel surface, rather than from an edge. Surface view calibrated infrared images of ignition and flame spread over a thin cellulose fuel were obtained along with a color video of the surface view and color images of the edge view using 35 mm color film at 2 Hz. The cellulose fuel samples were mounted in the center of a 12 cm wide by 16 cm tall flow duct and were ignited in microgravity using a straight hot wire across the center of the 7.5 cm wide by 14 cm long samples. Four cases, at 1 atm. 35%O2 in N2, at forced flows from 2 cm/s to 20 cm/s are presented here. This flow range captures flame spread from strictly upstream spread at low flows, to predominantly downstream spread at high flow. Surface temperature profiles are evaluated as a function of time, and temperature gradients for upstream and downstream flame spread are measured. Flame spread rates from IR image data are compared to visible image spread rate data. IR blackbody temperatures are compared to surface thermocouple readings to evaluate the effective emissivity of the pyrolyzing surface. Preheat lengths and pyrolysis lengths are evaluated both upstream and downstream of the central ignition point. A surface energy balance estimates the net heat flux from the flame to the fuel surface along the length of the fuel. Surface radiative loss and gas-phase radiation from soot are measured relative to the net heat feedback from the flame. At high surface heat loss relative to heat feedback, the downstream flame spread does not occur.

STAT3 Target Genes Relevant to Human Cancers

PubMed Central

Carpenter, Richard L.; Lo, Hui-Wen

2014-01-01

Since its discovery, the STAT3 transcription factor has been extensively studied for its function as a transcriptional regulator and its role as a mediator of development, normal physiology, and pathology of many diseases, including cancers. These efforts have uncovered an array of genes that can be positively and negatively regulated by STAT3, alone and in cooperation with other transcription factors. Through regulating gene expression, STAT3 has been demonstrated to play a pivotal role in many cellular processes including oncogenesis, tumor growth and progression, and stemness. Interestingly, recent studies suggest that STAT3 may behave as a tumor suppressor by activating expression of genes known to inhibit tumorigenesis. Additional evidence suggested that STAT3 may elicit opposing effects depending on cellular context and tumor types. These mixed results signify the need for a deeper understanding of STAT3, including its upstream regulators, parallel transcription co-regulators, and downstream target genes. To help facilitate fulfilling this unmet need, this review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers. PMID:24743777

Export of Dissolved Methane and Carbon Dioxide with Effluents from Municipal Wastewater Treatment Plants.

PubMed

Alshboul, Zeyad; Encinas-Fernández, Jorge; Hofmann, Hilmar; Lorke, Andreas

2016-06-07

Inland waters play an important role for regional and global scale carbon cycling and are significant sources of the atmospheric greenhouse gases methane (CH4) and carbon dioxide (CO2). Although most studies considered the input of terrestrially derived organic and inorganic carbon as the main sources for these emissions, anthropogenic sources have rarely been investigated. Municipal wastewater treatment plants (WWTPs) could be additional sources of carbon by discharging the treated wastewater into the surrounding aquatic ecosystems. Here we analyze seasonally resolved measurements of dissolved CH4 and CO2 concentrations in effluents and receiving streams at nine WWTPs in Germany. We found that effluent addition significantly altered the physicochemical properties of the streamwater. Downstream of the WWTPs, the concentrations of dissolved CH4 and CO2 were enhanced and the atmospheric fluxes of both gases increased by a factor of 1.2 and 8.6, respectively. The CH4 exported with discharged effluent, however, accounted for only a negligible fraction (0.02%) of the estimated total CH4 emissions during the treatment process. The CH4 concentration in the effluent water was linearly related to the organic load of the wastewater, which can provide an empirical basis for future attempts to add WWTPs inputs to regional-scale models for inland water-carbon fluxes.

Contribution of G protein-coupled estrogen receptor 1 (GPER) to 17β-estradiol-induced developmental toxicity in zebrafish.

PubMed

Diamante, Graciel; Menjivar-Cervantes, Norma; Leung, Man Sin; Volz, David C; Schlenk, Daniel

2017-05-01

Exposure to 17β-estradiol (E2) influences the regulation of multiple signaling pathways, and E2-mediated disruption of signaling events during early development can lead to malformations such as cardiac defects. In this study, we investigated the potential role of the G-protein estrogen receptor 1 (GPER) in E2-induced developmental toxicity. Zebrafish embryos were exposed to E2 from 2h post fertilization (hpf) to 76 hpf with subsequent transcriptional measurements of heart and neural crest derivatives expressed 2 (hand2), leucine rich repeat containing 10 (lrrc10), and gper at 12, 28 and 76 hpf. Alteration in the expression of lrrc10, hand2 and gper was observed at 12 hpf and 76 hpf, but not at 28 hpf. Expression of these genes was also altered after exposure to G1 (a GPER agonist) at 76 hpf. Expression of lrrc10, hand2 and gper all coincided with the formation of cardiac edema at 76 hpf as well as other developmental abnormalities. While co-exposure of G1 with G36 (a GPER antagonist) rescued G1-induced abnormalities and altered gene expression, co-exposure of E2 with G36, or ICI 182,780 (an estrogen receptor antagonist) did not rescue E2-induced cardiac deformities or gene expression. In addition, no effects on the concentrations of downstream ER and GPER signaling molecules (cAMP or calcium) were observed in embryo homogenates after E2 treatment. These data suggest that the impacts of E2 on embryonic development at this stage are complex and may involve multiple receptor and/or signaling pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

[Characteristics of heavy metal elements and their relationship with magnetic properties of river sediment from urban area in Lanzhou].

PubMed

Wang, Bo; Zhao, Shuang; Xia, Dun-sheng; Yu, Ye; Tian, Shi-li; Jia, Jia; Jiang, Xiao-rong

2011-05-01

The contents of As, Co, Cr, Cu, Ni, Pb, V and Zn in the surface sediments from 8 rivers in urban area in Lanzhou were monitored by ecological risk which was assessed by the potential ecological Håkanson index, and the index of geoaccumulation (Igeo), sediment enrichment factor (R), and environmental magnetism. The results showed that: (1) the potential ecological risk of heavy metals of As, Co, Ni, V in surface sediments from 8 rivers were low, which belonged to low ecological risk. But the risk of heave metals Cr, Pb, Zn in surface sediments from Yuer river was high, which belonged to middle ecological risk, and in downstream of Yuer river, the element of Cu belonged to high ecological risk. (2) The rivers in Lanzhou could be divided into four groups according to the heavy mental pollution degree: first type, such as Paihong river, Shier river, Yuer river and Shuimo river, called downstream concentrate type; second type, such as Qili river, called upstream concentrate type; third type, such as Luoguo river and Dasha river, called less affected type; fourth type, Lanni river, which polluted heavily in up and downstream; (3) The correlation analysis between magnetic parameters and element contents show that the parameters which mainly reflect the concentration of the magnetic minerals (X, SIRM, Ms) have close association with Cr, Ni, Pb, Zn, Cu, So we can infer that the magnetic minerals in deposits samples mainly came from electroplating effluent, motor vehicle emission, and domestic sewage. SIRM/X shows a strong correlation with Cr, Ni, Pb, Zn, indicating the distribution of anthropogenic particulates. (4) The magnetic minerals(X, SIRM, Ms) have a strong correlation with the geoaccumulation (Igeo) than potential ecological risk index and enrichment factor (R). These results suggest a possible approach for source identification of magnetic material in pollution studies and the validity of using magnetic measurements to mapping the polluted area.

An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks.

PubMed

Botía, Juan A; Vandrovcova, Jana; Forabosco, Paola; Guelfi, Sebastian; D'Sa, Karishma; Hardy, John; Lewis, Cathryn M; Ryten, Mina; Weale, Michael E

2017-04-12

Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used R software package for the generation of gene co-expression networks (GCN). WGCNA generates both a GCN and a derived partitioning of clusters of genes (modules). We propose k-means clustering as an additional processing step to conventional WGCNA, which we have implemented in the R package km2gcn (k-means to gene co-expression network, https://github.com/juanbot/km2gcn ). We assessed our method on networks created from UKBEC data (10 different human brain tissues), on networks created from GTEx data (42 human tissues, including 13 brain tissues), and on simulated networks derived from GTEx data. We observed substantially improved module properties, including: (1) few or zero misplaced genes; (2) increased counts of replicable clusters in alternate tissues (x3.1 on average); (3) improved enrichment of Gene Ontology terms (seen in 48/52 GCNs) (4) improved cell type enrichment signals (seen in 21/23 brain GCNs); and (5) more accurate partitions in simulated data according to a range of similarity indices. The results obtained from our investigations indicate that our k-means method, applied as an adjunct to standard WGCNA, results in better network partitions. These improved partitions enable more fruitful downstream analyses, as gene modules are more biologically meaningful.

Biodegradation of 17β-Estradiol, Estrone and Testosterone in Stream Sediments

NASA Astrophysics Data System (ADS)

Bradley, P. M.; Chapelle, F. H.; Barber, L. B.; McMahon, P. B.; Gray, J. L.; Kolpin, D. W.

2009-12-01

The potentials for in situ biodegradation of 17β-estradiol (E2), estrone (E1), and testosterone (T) were investigated in three, hydrologically-distinct, WWTP-impacted streams in the United States. Relative differences in the mineralization of [4-14C] substrates were assessed in oxic microcosms containing sediment or water-only from locations upstream and downstream of the WWTP outfall in each system. Upstream samples provided insight into the biodegradative potential of sediment microbial communities that were not under the immediate impact of WWTP effluent. Upstream sediment from all three systems demonstrated significant mineralization of the “A” ring of E2, E1 and T, with the potential of T biodegradation consistently greater than of E2 and no systematic difference in the potentials of E2 and E1. Downstream samples provided insight into the impacts of effluent on reproductive hormone biodegradation. Significant “A” ring mineralization was also observed in downstream sediment, with the potentials for E1 and T mineralization being substantially depressed relative to upstream samples. In marked contrast, the potentials for E2 mineralization immediately downstream of the WWTP outfalls were more than double that of upstream samples. E2 mineralization was also observed in water, albeit at insufficient rate to prevent substantial downstream transport in the water column. The results of this study indicate that, in combination with sediment sorption processes which effectively scavenge hydrophobic contaminants from the water column and immobilize them in the vicinity of the WWTP outfall, aerobic biodegradation of reproductive hormones can be an environmentally important mechanism for non-conservative (destructive) attenuation of hormonal endocrine disruptors in effluent-impacted streams.

Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

PubMed Central

Deffains, Marc; Iskhakova, Liliya; Katabi, Shiran; Haber, Suzanne N; Israel, Zvi; Bergman, Hagai

2016-01-01

The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson's disease and other BG-related disorders. DOI: http://dx.doi.org/10.7554/eLife.16443.001 PMID:27552049

Unit 2, downstream from Coppersdale Bridge Johnstown Local Flood ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Unit 2, downstream from Coppersdale Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

Effects of historical coal mining and drainage from abandoned mines on streamflow and water quality in Bear Creek, Dauphin County, Pennsylvania-March 1999-December 2002

USGS Publications Warehouse

Chaplin, Jeffrey J.

2005-01-01

More than 100 years of anthracite coal mining has changed surface- and ground-water hydrology and contaminated streams draining the Southern Anthracite Coal Field in east-central Pennsylvania. Bear Creek drains the western prong of the Southern Anthracite Coal Field and is affected by metals in drainage from abandoned mines and streamwater losses. Total Maximum Daily Loads (TMDL) developed for dissolved iron of about 5 lb/d (pounds per day) commonly are exceeded in the reach downstream of mine discharges. Restoration of Bear Creek using aerobic ponds to passively remove iron in abandoned mine drainage is under consideration (2004) by the Dauphin County Conservation District. This report, prepared in cooperation with the Dauphin County Conservation District, evaluates chemical and hydrologic data collected in Bear Creek and its receiving waters prior to implementation of mine-drainage treatment. The data collected represent the type of baseline information needed for documentation of water-quality changes following passive treatment of mine drainage in Pennsylvania and in other similar hydrogeologic settings. Seven surface-water sites on Bear Creek and two mine discharges were monitored for nearly three years to characterize the chemistry and hydrology of the following: (1) Bear Creek upstream of the mine discharges (BC-UMD), (2) water draining from the Lykens-Williamstown Mine Pool at the Lykens Water-Level Tunnel (LWLT) and Lykens Drift (LD) discharges, (3) Bear Creek after mixing with the mine discharges (BC-DMD), and (4) Bear Creek prior to mixing with Wiconisco Creek (BCM). Two sites on Wiconisco Creek, upstream and downstream of Bear Creek (WC-UBC and WC-DBC, respectively), were selected to evaluate changes in streamflow and water quality upon mixing with Bear Creek. During periods of below-normal precipitation, streamwater loss was commonly 100 percent upstream of site BC-UMD (streamflow range = 0 to 9.7 ft3/s (cubic feet per second)) but no loss was detected downstream owing to sustained mine water drainage from the Lykens Water-Level Tunnel (range = 0.41 to 3.7 ft3/s), Lykens Drift (range = 0.40 to 6.1 ft3/s), and diffuse zones of seepage. Collectively, mine water inputs contributed about 84 percent of base flow and 53 percent of stormflow measured in the downstream reach. An option under consideration by the Dauphin County Conservation District for treatment of the discharge from the LWLT requires the source of the discharge to be captured and rerouted downstream, bypassing approximately 1,000 feet of stream channel. Because streamwater loss upstream of the tunnel was commonly 100 percent, rerouting the discharge from the LWLT may extend the reach of Bear Creek that is subject to dryness. Differences in the chemistry of water discharging from the LWLT compared to the LD suggest that the flow path through the Lykens-Williamstown Mine Pool to each mine discharge is unique. The LWLT is marginally alkaline (median net acid neutralizing capacity (ANC) = 9 mg/L (milligrams per liter) as CaCO3; median pH = 5.9), commonly becomes acidic (minimum net ANC = -74 mg/L as CaCO3) at low flow, and may benefit from alkaline amendments prior to passive treatment. Water discharging from the LD provides excess ANC (median net ANC = 123 mg/L as CaCO3; median pH = 6.5) to the downstream reach and is nearly anoxic at its source (median dissolved oxygen = 0.5 mg/L). Low dissolved oxygen water with relatively high ANC and metals concentrations discharging from the LD is characteristic of a deeper flow path and longer residence time within the mine pool than the more acidic, oxygenated water discharging from the LWLT. TMDLs for iron have been developed for dissolved species only. Consequently, distinguishing between dissolved and suspended iron in Bear Creek is important for evaluating water-quality improvement through TMDL attainment. Median total iron concentration increased from 550 mg/L (micrograms per liter) at site BC-UM

Economic Analysis of an Integrated Annatto Seeds-Sugarcane Biorefinery Using Supercritical CO2 Extraction as a First Step

PubMed Central

Albarelli, Juliana Q.; Santos, Diego T.; Cocero, María José; Meireles, M. Angela A.

2016-01-01

Recently, supercritical fluid extraction (SFE) has been indicated to be utilized as part of a biorefinery, rather than as a stand-alone technology, since besides extracting added value compounds selectively it has been shown to have a positive effect on the downstream processing of biomass. To this extent, this work evaluates economically the encouraging experimental results regarding the use of SFE during annatto seeds valorization. Additionally, other features were discussed such as the benefits of enhancing the bioactive compounds concentration through physical processes and of integrating the proposed annatto seeds biorefinery to a hypothetical sugarcane biorefinery, which produces its essential inputs, e.g., CO2, ethanol, heat and electricity. For this, first, different configurations were modeled and simulated using the commercial simulator Aspen Plus® to determine the mass and energy balances. Next, each configuration was economically assessed using MATLAB. SFE proved to be decisive to the economic feasibility of the proposed annatto seeds-sugarcane biorefinery concept. SFE pretreatment associated with sequential fine particles separation process enabled higher bixin-rich extract production using low-pressure solvent extraction method employing ethanol, meanwhile tocotrienols-rich extract is obtained as a first product. Nevertheless, the economic evaluation showed that increasing tocotrienols-rich extract production has a more pronounced positive impact on the economic viability of the concept. PMID:28773616

Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

PubMed

Mera, Paula; Mir, Joan Francesc; Fabriàs, Gemma; Casas, Josefina; Costa, Ana S H; Malandrino, Maria Ida; Fernández-López, José-Antonio; Remesar, Xavier; Gao, Su; Chohnan, Shigeru; Rodríguez-Peña, Maria Sol; Petry, Harald; Asins, Guillermina; Hegardt, Fausto G; Herrero, Laura; Serra, Dolors

2014-01-01

Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.

Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile

PubMed Central

Fabriàs, Gemma; Casas, Josefina; Costa, Ana S. H.; Malandrino, Maria Ida; Fernández-López, José-Antonio; Remesar, Xavier; Gao, Su; Chohnan, Shigeru; Rodríguez-Peña, Maria Sol; Petry, Harald; Asins, Guillermina; Hegardt, Fausto G.; Herrero, Laura; Serra, Dolors

2014-01-01

Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH. PMID:24819600

Carbon Dioxide Dispersion in the Combustion Integrated Rack Simulated Numerically

NASA Technical Reports Server (NTRS)

Wu, Ming-Shin; Ruff, Gary A.

2004-01-01

When discharged into an International Space Station (ISS) payload rack, a carbon dioxide (CO2) portable fire extinguisher (PFE) must extinguish a fire by decreasing the oxygen in the rack by 50 percent within 60 sec. The length of time needed for this oxygen reduction throughout the rack and the length of time that the CO2 concentration remains high enough to prevent the fire from reigniting is important when determining the effectiveness of the response and postfire procedures. Furthermore, in the absence of gravity, the local flow velocity can make the difference between a fire that spreads rapidly and one that self-extinguishes after ignition. A numerical simulation of the discharge of CO2 from PFE into the Combustion Integrated Rack (CIR) in microgravity was performed to obtain the local velocity and CO2 concentration. The complicated flow field around the PFE nozzle exits was modeled by sources of equivalent mass and momentum flux at a location downstream of the nozzle. The time for the concentration of CO2 to reach a level that would extinguish a fire anywhere in the rack was determined using the Fire Dynamics Simulator (FDS), a computational fluid dynamics code developed by the National Institute of Standards and Technology specifically to evaluate the development of a fire and smoke transport. The simulation shows that CO2, as well as any smoke and combustion gases produced by a fire, would be discharged into the ISS cabin through the resource utility panel at the bottom of the rack. These simulations will be validated by comparing the results with velocity and CO2 concentration measurements obtained during the fire suppression system verification tests conducted on the CIR in March 2003. Once these numerical simulations are validated, portions of the ISS labs and living areas will be modeled to determine the local flow conditions before, during, and after a fire event. These simulations can yield specific information about how long it takes for smoke and combustion gases produced by a fire to reach a detector location, how large the fire would be when the detector alarms, and the behavior of the fire until it has been extinguished. This new capability could then be used to optimize the location of fire detectors and fire-suppression ports as well as to evaluate the effectiveness of fire suppressants and response strategies. Numerical data collected from these simulations could also be used to develop a virtual reality fire event for crew training and fire safety awareness. This work is funded by NASA's Bioastronautics Initiative, which has the objective of ensuring and enhancing the health, safety, and performance of humans in space. As part of this initiative, the Microgravity Combustion Science Branch at the NASA Glenn Research Center is conducting spacecraft fire safety research to significantly improve fire safety on inhabited spacecraft.

Modulation of human extrastriate visual processing by selective attention to colours and words.

PubMed

Nobre, A C; Allison, T; McCarthy, G

1998-07-01

The present study investigated the effect of visual selective attention upon neural processing within functionally specialized regions of the human extrastriate visual cortex. Field potentials were recorded directly from the inferior surface of the temporal lobes in subjects with epilepsy. The experimental task required subjects to focus attention on words from one of two competing texts. Words were presented individually and foveally. Texts were interleaved randomly and were distinguishable on the basis of word colour. Focal field potentials were evoked by words in the posterior part of the fusiform gyrus. Selective attention strongly modulated long-latency potentials evoked by words. The attention effect co-localized with word-related potentials in the posterior fusiform gyrus, and was independent of stimulus colour. The results demonstrated that stimuli receive differential processing within specialized regions of the extrastriate cortex as a function of attention. The late onset of the attention effect and its co-localization with letter string-related potentials but not with colour-related potentials recorded from nearby regions of the fusiform gyrus suggest that the attention effect is due to top-down influences from downstream regions involved in word processing.

Watershed sustainability: Downstream effects of timber harvest in the Ozarks of Missouri

USGS Publications Warehouse

Jacobson, Robert B.

2004-01-01

The downstream effects of timber harvest in the Ozarks of Missouri can be evaluated by analogy to other geographic areas and by historical analysis of responses to past land use activities. Based on research from other geographic regions, timber harvest in the Ozarks would be expected to have minor effects on annual water yield and dissolved-phase water quality. The potential exists for haul roads to increase stormflow discharges and sediment yields. Of the possible downstream effects, sediment yield is potentially the most severe and difficult to predict; siting and design of roads are probably the most critical management concerns for minimizing downstream effects. Historical analysis shows that Ozark streams have been destabilized by past land use practices, primarily in the riparian zone. Therefore, present-day timber harvest takes place in a landscape where streams have lowered resilience to disturbance. Predictions of future downstream effects of timber harvest in the Ozarks are complicated by the inherent complexity of cumulative watershed effects and the lack of detailed, long-term instrumental records at appropriate scales.

Proliferation of murine c-kit(pos) cardiac stem cells stimulated with IGF-1 is associated with Akt-1 mediated phosphorylation and nuclear export of FoxO3a and its effect on downstream cell cycle regulators.

PubMed

Johnson, Ann Mary; Kartha, C C

2014-04-01

Insulin-like growth factor-1 (IGF-1) is known to promote proliferation in many cell types including c-kit(pos) cardiac stem cells (CSCs). Downstream signaling pathways of IGF-1 induced CSC proliferation have not been investigated. An important downstream target of IGF-1/Akt-1 signaling is FoxO3a, a key negative regulator of cell-cycle progression. We studied the effect of IGF-1 on proliferation of c-kit(pos) murine CSCs and found that IGF-1-mediated cell proliferation is associated with FoxO3a phosphorylation and inactivation of its transcriptional activity. PI3 inhibitors LY294002 and Wortmannin abolished the effect of IGF-1 on FoxO3a phosphorylation indicating that FoxO3a phosphorylation is mediated by PI3/Akt-1 pathway. In cells with FoxO3a translocation to the cytoplasm, there is decreased expression of cell-cycle inhibitors such as p27(kip1) and p57(kip2) and increased expression of CyclinD1. Our study provides evidence that IGF-1 induced CSC proliferation could be the result of FoxO3a inactivation and its downstream effect on cell-cycle regulators.

WEREWOLF and ENHANCER of GLABRA3 are interdependent regulators of the spatial expression pattern of GLABRA2 in Arabidopsis.

PubMed

Song, Sang-Kee; Kwak, Su-Hwan; Chang, Soo Chul; Schiefelbein, John; Lee, Myeong Min

2015-11-06

In multicellular organisms, cell fates are specified through differential regulation of transcription. Epidermal cell fates in the Arabidopsis thaliana root are precisely specified by several transcription factors, with the GLABRA2 (GL2) homeodomain protein acting at the farthest downstream in this process. To better understand the regulation of GL2 expression, we ectopically expressed WEREWOLF (WER) and ENHANCER OF GLABRA3 (EGL3) in various tissues and examined GL2 expression. Here we show that WER expressed ubiquitously in the root induced GL2 expression only in the root epidermis, whereas co-expression of WER and EGL3 induced GL2 expression in the corresponding tissues. We also found that GL3 accumulated in the nucleus at the early meristematic region and EGL3 accumulated later in the nucleus of epidermal cells. We further found that ectopic expression of WER and EGL3 in ground tissues inhibited GL2 expression in the epidermis. Our results suggest that the co-expression of WER and EGL3 is sufficient for driving GL2 and CPC expression. Copyright © 2015 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ploskey, Gene R.; Weiland, Mark A.; Carlson, Thomas J.

The purpose of this study was to estimate dam passage and route specific survival rates for subyearling Chinook salmon smolts to a primary survival-detection array located 81 km downstream of the dam, evaluate a BGS located in the B2 forebay, and evaluate effects of two spill treatments. The 2010 study also provided estimates of forebay residence time, tailrace egress time, spill passage efficiency (SPE), and spill + B2 Corner Collector (B2CC) efficiency, as required in the Columbia Basin Fish Accords. In addition, the study estimated forebay passage survival and survival of fish traveling from the forebay entrance array, through themore » dam and downstream through 81 km of tailwater.« less

Suppression Characteristics of Cup-Burner Flames in Low Gravity

NASA Technical Reports Server (NTRS)

Takahashi, Fumiaki; Linteris, Gregory T.; Katta, Viswanath R.

2004-01-01

The structure and suppression of laminar methane-air co-flow diffusion flames formed on a cup burner have been studied experimentally and numerically using physically acting fire-extinguishing agents (CO2, N2, He, and Ar) in normal earth (lg) and zero gravity (0g). The computation uses a direct numerical simulation with detailed chemistry and radiative heat-loss models. An initial observation of the flame without agent was also made at the NASA Glenn 2.2-Second Drop Tower. An agent was introduced into a low-speed coflowing oxidizing stream by gradually replacing the air until extinguishment occurred under a fixed minimal fuel velocity. The suppression of cup-burner flames, which resemble real fires, occurred via a blowoff process (in which the flame base drifted downstream) rather than the global extinction phenomenon typical of counterflow diffusion flames. The computation revealed that the peak reactivity spot (the reaction kernel) formed in the flame base was responsible for attachment and blowoff phenomena of the trailing diffusion flame. The thermal and transport properties of the agents affected the flame extinguishment limits.

Rotor Aerodynamics in Ground Effect at Low Advance Ratios.

DTIC Science & Technology

1982-07-27

the rotor wake flows entirely downstream. At test conditions were the recirculating flow or ground vortex is present there are marked departures...ILLUSTRATIONS Figure Page 1 Cross Section of Test Facilty 12 2 Overall View of Test Facility and Rotor Model 13 3 Flow Pattern in Ground Vortex Regime, (v...entirely flowing downstream splits and a portion of the rotor wake flows forward (upstream) and then recirculates through the rotor or forms a vortex or

Hydrologic connectivity of floodplains, northern Missouri: implications for management and restoration of floodplain forest communities in disturbed landscapes

USGS Publications Warehouse

Jacobson, R.; Faust, T.

2014-01-01

Hydrologic connectivity between the channel and floodplain is thought to be a dominant factor determining floodplain processes and characteristics of floodplain forests. We explored the role of hydrologic connectivity in explaining floodplain forest community composition along streams in northern Missouri, USA. Hydrologic analyses at 20 streamgages (207–5827 km2 area) document that magnitudes of 2-year return floods increase systematically with increasing drainage area whereas the average annual number and durations of floodplain-connecting events decrease. Flow durations above the active-channel shelf vary little with increasing drainage area, indicating that the active-channel shelf is in quasi-equilibrium with prevailing conditions. The downstream decrease in connectivity is associated with downstream increase in channel incision. These relations at streamflow gaging stations are consistent with regional channel disturbance patterns: channel incision increases downstream, whereas upstream reaches have either not incised or adjusted to incision by forming new equilibrium floodplains. These results provide a framework to explain landscape-scale variations in composition of floodplain forest communities in northern Missouri. Faust (2006) had tentatively explained increases of flood-dependent tree species, and decreases of species diversity, with a downstream increase in flood magnitude and duration. Because frequency and duration of floodplain-connecting events do not increase downstream, we hypothesize instead that increases in relative abundance of flood-dependent trees at larger drainage area result from increasing size of disturbance patches. Bank-overtopping floods at larger drainage area create large, open, depositional landforms that promoted the regeneration of shade-intolerant species. Higher tree species diversity in floodplains with small drainage areas is associated with non-incised floodplains that are frequently connected to their channels and therefore subject to greater effective hydrologic variability compared with downstream floodplains. Understanding the landscape-scale geomorphic and hydrologic controls on floodplain connectivity provides a basis for more effective management and restoration of floodplain forest communities.

Satellite-based Analysis of CO Variability over the Amazon Basin

NASA Astrophysics Data System (ADS)

Deeter, M. N.; Emmons, L. K.; Martinez-Alonso, S.; Tilmes, S.; Wiedinmyer, C.

2017-12-01

Pyrogenic emissions from the Amazon Basin exert significant influence on both climate and air quality but are highly variable from year to year. The ability of models to simulate the impact of biomass burning emissions on downstream atmospheric concentrations depends on (1) the quality of surface flux estimates (i.e., emissions inventories), (2) model dynamics (e.g., horizontal winds, large-scale convection and mixing) and (3) the representation of atmospheric chemical processes. With an atmospheric lifetime of a few months, carbon monoxide (CO) is a commonly used diagnostic for biomass burning. CO products are available from several satellite instruments and allow analyses of CO variability over extended regions such as the Amazon Basin with useful spatial and temporal sampling characteristics. The MOPITT ('Measurements of Pollution in the Troposphere') instrument was launched on the NASA Terra platform near the end of 1999 and is still operational. MOPITT is uniquely capable of measuring tropospheric CO concentrations using both thermal-infrared and near-infrared observations, resulting in the ability to independently retrieve lower- and upper-troposphere CO concentrations. We exploit the 18-year MOPITT record and related datasets to analyze the variability of CO over the Amazon Basin and evaluate simulations performed with the CAM-chem chemical transport model. We demonstrate that observed differences between MOPITT observations and model simulations provide important clues regarding emissions inventories, convective mixing and long-range transport.

DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals.

PubMed

Li, Jinyao; Geng, Shuang; Liu, Xiuping; Liu, Hu; Jin, Huali; Liu, Chang-Gong; Wang, Bin

2013-10-01

We previously demonstrated that DNA and protein co-administration induced differentiation of immature dendritic cells (iDCs) into CD11c(+)CD40(low)IL-10(+) regulatory DCs (DCregs) via the caveolin-1 (Cav-1) -mediated signal pathway. Here, we demonstrate that production of IL-10 and the low expression of CD40 play a critical role in the subsequent induction of regulatory T cells (Tregs) by the DCregs. We observed that DNA and protein were co-localized with DC-SIGN in caveolae and early lysosomes in the treated DCs, as indicated by co-localization with Cav-1 and EEA-1 compartment markers. DNA and protein also co-localized with LAMP-2. Gene-array analysis of gene expression showed that more than a thousand genes were significantly changed by the DC co-treatment with DNA + protein compared with controls. Notably, the level of DC-SIGN expression was dramatically upregulated in pOVA + OVA co-treated DCs. The expression levels of Rho and Rho GNEF, the down-stream molecules of DC-SIGN mediated signal pathway, were also greatly upregulated. Further, the level of TLR9, the traditional DNA receptor, was significantly downregulated. These results suggest that DC-SIGN as the potential receptor for DNA and protein might trigger the negative pathway to contribute the induction of DCreg combining with Cav-1 mediated negative signal pathway.

DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals

PubMed Central

Li, Jinyao; Geng, Shuang; Liu, Xiuping; Liu, Hu; Jin, Huali; Liu, Chang-Gong; Wang, Bin

2013-01-01

We previously demonstrated that DNA and protein co-administration induced differentiation of immature dendritic cells (iDCs) into CD11c+CD40lowIL-10+ regulatory DCs (DCregs) via the caveolin-1 (Cav-1) -mediated signal pathway. Here, we demonstrate that production of IL-10 and the low expression of CD40 play a critical role in the subsequent induction of regulatory T cells (Tregs) by the DCregs. We observed that DNA and protein were co-localized with DC-SIGN in caveolae and early lysosomes in the treated DCs, as indicated by co-localization with Cav-1 and EEA-1 compartment markers. DNA and protein also co-localized with LAMP-2. Gene-array analysis of gene expression showed that more than a thousand genes were significantly changed by the DC co-treatment with DNA + protein compared with controls. Notably, the level of DC-SIGN expression was dramatically upregulated in pOVA + OVA co-treated DCs. The expression levels of Rho and Rho GNEF, the down-stream molecules of DC-SIGN mediated signal pathway, were also greatly upregulated. Further, the level of TLR9, the traditional DNA receptor, was significantly downregulated. These results suggest that DC-SIGN as the potential receptor for DNA and protein might trigger the negative pathway to contribute the induction of DCreg combining with Cav-1 mediated negative signal pathway. PMID:24051433

Effects of stream-adjacent logging in fishless headwaters on downstream coastal cutthroat trout

USGS Publications Warehouse

Bateman, Douglas S.; Sloat, Matthew R.; Gresswell, Robert E.; Berger, Aaron M.; Hockman-Wert, David; Leer, David W.; Skaugset, Arne E.

2016-01-01

To investigate effects of headwater logging on downstream coastal cutthroat trout (Oncorhynchus clarkii clarkii) populations, we monitored stream habitat and biotic indicators including biomass, abundance, growth, movement, and survival over 8 years using a paired-watershed approach. Reference and logged catchments were located on private industrial forestland on ∼60-year harvest rotation. Five clearcuts (14% of the logged catchment area) were adjacent to fishless portions of the headwater streams, and contemporary regulations did not require riparian forest buffers in the treatment catchment. Logging did not have significant negative effects on downstream coastal cutthroat trout populations for the duration of the sample period. Indeed, the only statistically significant response of fish populations following logging in fishless headwaters was an increase in late-summer biomass (g·m−2) of age-1+ coastal cutthroat trout in tributaries. Ultimately, the ability to make broad generalizations concerning effects of timber harvest is difficult because response to disturbance (anthropogenically influenced or not) in aquatic systems is complex and context-dependent, but our findings provide one example of environmentally compatible commercial logging in a regenerated forest setting.

Hydrogeological properties of bank storage area in Changwon city, Korea

NASA Astrophysics Data System (ADS)

Hamm, S.-Y.; Kim, H.-S.; Cheong, J.-Y.; Ryu, S. M.; Kim, M. J.

2003-04-01

Bank filtrated water has been used in developed countries such as United States, France, Germany, Austria, Nederland and so on. In Korea, most of the drinking water is provided from the surface water. However, drinking water acquisition is becoming difficult due to the degradation of surface water quality. In special, the quality of drinking water source is much lower in downstream area than in upstream area. Thus, the use of bank filtrated water is getting attracted by central and local governments in Korea. The bank filtrated water was surveyed in the areas of Yeongsan river, Nakdong river, Geum river and Han river. Up to present, however, the downstream areas of Nakdong river are most suitable places to apply the bank filtration system. This study investigates hydrogeological characteristics of bank-storage area located in Daesan- Myeon, Changwon city, adjacent the downstream of Nakdong river. Changwon city is the capital city of Gyeongsangnam-Do province. Changwon city uses water derived from Nakdong river as municipal water. However, the quantity and quality of the river water are gradually decreased. Thus, Changwon city developed two sites of bank filtration system in Daesan-myeon and Buk-myeon. Pumping rate is 2,000m3/day at present and will be increased to 60,000m3/day in Daesan-myeon site at the end of the first stage of the project. For the study, we conducted pumping tests four times on seven pumping wells (PW1, PW2, PW3, PW4, PW5, PW6, and PW7) and twelve drill holes (BH-2, OW2-OW12) in the area of 370 m x 100 m. Pumping wells PW1 and PW2 were drilled in 1999 by Samjung Engineering Co. and pumping wells PW3, PW4, PW5, PW6 and PW7 were drilled in 2000 by Donga Construction Co. and Daeduk Gongyeong Co. The pumping wells are located at 45-110 meters from Nakdong riverside. The geology of the study area is composed of volcanic rocks (Palryeongsan tuff and Jusasan andesitic rock) and alluvium. Palryeongsan tuff consists of mostly green tuff with partly tuffaceous sandstone, shale, mudstone and sandstone. Thick alluvium is overlain on Palryeongsan tuff (Samjung Engineering Co., 1999; Donga Construction Co. and Daeduk Gongyeong Co., 2000; Kim and Lee, 1964). The alluvium is composed of sand, sandy gravel and weathered zone from the surface (Table 1, Fig. 3). The aquifer is sandy gravel layer (Samjung Engineering Co., 1999). The gravel layer is thicker near the wells of PW1, PW2, PW3, and PW4 (13.5-17.5m), whereas is thinner near the wells of PW5, PW6, and PW7 (6.3-10.5m). The pumping data obtained were analyzed to determine hydraulic parameters (transmissivity and storativity) using various models of pumping test analysis. The appropriate models for the study area were found from several models. The selected model for observation well is Theis model using corrected drawdown and the selected model for pumped well is Papadopulos-Cooper model using corrected drawdown. As a result, alluvial aquifer in the study area behaviors as confined aquifer rather than phreatic aquifer. Thus, infiltration amount from the river to the aquifer in the study area is lower than that from river to phreatic aquifer for the same water level change. And also storativity of the aquifer is represented by elastic storativity rather than specific yield. Transmissivity obtained by the models ranges from 4.54x10-4 to 1.79x10-1 m2/s with arithmetic mean 2.92x10-2 m2/s. Storativity ranges from 2.59x10-4-5.54x10-1 with arithmetic mean 6.36x10-2. Frequency distribution of hydraulic parameters was determined from statistical analyses. The distribution of transmissivity values does not follow normal distribution showing skewness 2.36 and kurtosis 5.085. Aquifer heterogeneity was found by hydraulic parameters and subsurface geology data in the study area. Furthermore, hydraulic parameters obtained at a well that serves as both pumping well and observation well were compared, and the correlation equation was determined to evaluate hydraulic parameters considering aquifer loss. Transmissivity values obtained by the two cases do not show distinct correlation. However, storativity values obtained by the two cases show distinct negative correlation. ACKNOWLEDGEMENT The authors wish to acknowledge the financial support of the Sustainable Water Resources Research Center under the program of the 21st Century Frontier R&D Program by the Korean government (project no: 3-4-1).

Establishment of turbidity forecasting model and early-warning system for source water turbidity management using back-propagation artificial neural network algorithm and probability analysis.

PubMed

Yang, Tsung-Ming; Fan, Shu-Kai; Fan, Chihhao; Hsu, Nien-Sheng

2014-08-01

The purpose of this study is to establish a turbidity forecasting model as well as an early-warning system for turbidity management using rainfall records as the input variables. The Taipei Water Source Domain was employed as the study area, and ANOVA analysis showed that the accumulative rainfall records of 1-day Ping-lin, 2-day Ping-lin, 2-day Fei-tsui, 2-day Shi-san-gu, 2-day Tai-pin and 2-day Tong-hou were the six most significant parameters for downstream turbidity development. The artificial neural network model was developed and proven capable of predicting the turbidity concentration in the investigated catchment downstream area. The observed and model-calculated turbidity data were applied to developing the turbidity early-warning system. Using a previously determined turbidity as the threshold, the rainfall criterion, above which the downstream turbidity would possibly exceed this respective threshold turbidity, for the investigated rain gauge stations was determined. An exemplary illustration demonstrated the effectiveness of the proposed turbidity early-warning system as a precautionary alarm of possible significant increase of downstream turbidity. This study is the first report of the establishment of the turbidity early-warning system. Hopefully, this system can be applied to source water turbidity forecasting during storm events and provide a useful reference for subsequent adjustment of drinking water treatment operation.

Co-expression of interleukin 12 enhances antitumor effects of a novel chimeric promoter-mediated suicide gene therapy in an immunocompetent mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Yu, E-mail: xuyu1001@gmail.com; Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071; Liu, Zhengchun, E-mail: l135027@126.com

Highlights: {yields} A novel chimeric promoter consisting of CArG element and hTERT promoter was developed. {yields} The promoter was characterized with radiation-inducibility and tumor-specificity. {yields} Suicide gene system driven by the promoter showed remarkable cytotoxicity in vitro. {yields} Co-expression of IL12 enhanced the promoter mediated suicide gene therapy in vivo. -- Abstract: The human telomerase reverse transcriptase (hTERT) promoter has been widely used in target gene therapy of cancer. However, low transcriptional activity limited its clinical application. Here, we designed a novel dual radiation-inducible and tumor-specific promoter system consisting of CArG elements and the hTERT promoter, resulting in increased expressionmore » of reporter genes after gamma-irradiation. Therapeutic and side effects of adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic (IAA) system downstream of the chimeric promoter were evaluated in mice bearing Lewis lung carcinoma, combining with or without adenovirus-mediated interleukin 12 (IL12) gene driven by the cytomegalovirus promoter. The combination treatment showed more effective suppression of tumor growth than those with single agent alone, being associated with pronounced intratumoral T-lymphocyte infiltration and minor side effects. Our results suggest that the combination treatment with HRP/IAA system driven by the novel chimeric promoter and the co-expression of IL12 might be an effective and safe target gene therapy strategy of cancer.« less

Characterization of an Aldolase Involved in Cholesterol Side Chain Degradation in Mycobacterium tuberculosis.

PubMed

Gilbert, Stephanie; Hood, LaChae; Seah, Stephen Y K

2018-01-15

The heteromeric acyl coenzyme A (acyl-CoA) dehydrogenase FadE28-FadE29 and the enoyl-CoA hydratase ChsH1-ChsH2, encoded by genes within the intracellular growth ( igr ) operon of Mycobacterium tuberculosis , catalyze the dehydrogenation of the cholesterol metabolite 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA), with a 3-carbon side chain, and subsequent hydration of the product 3-oxo-4,17-pregnadiene-20-carboxyl-CoA (3-OPDC-CoA) to form 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA (17-HOPC-CoA). The gene downstream of chsH2 , i.e., ltp2 , was expressed in recombinant Rhodococcus jostii RHA1 in combination with other genes within the igr operon. His-tagged Ltp2 copurified with untagged ChsH1-ChsH2, ChsH2, or the C-terminal domain of ChsH2, which contains a domain of unknown function (DUF35). Ltp2 in association with ChsH1-ChsH2 or just the DUF35 domain of ChsH2 was shown to catalyze the retroaldol cleavage of 17-HOPC-CoA to form androst-4-ene-3,17-dione and propionyl-CoA. Steady-state kinetic analysis using the Ltp2-DUF35 complex showed that the aldolase had optimal activity at pH 7.5, with a K m of 6.54 ± 0.90 μM and a k cat of 159 ± 8.50 s -1 ChsH1-ChsH2 could hydrate only about 30% of 3-OPDC-CoA, but this unfavorable equilibrium could be overcome when the aldolase was present to remove the hydrated product, providing a rationale for the close association of the aldolase with the hydratase. Homologs of ChsH1, ChsH2, and Ltp2 are found in steroid-degrading Gram-positive and Gram-negative bacteria, suggesting that side chains of diverse steroids may be cleaved by aldolases in the bacteria. IMPORTANCE The C-C bond cleavage of the D-ring side chain of cholesterol was shown to be catalyzed by an aldolase. The aldolase associates with the hydratase that catalyzes the preceding reaction in the cholesterol side chain degradation pathway. These enzymes are encoded by genes within the intracellular growth ( igr ) operon of M. tuberculosis , and the operon was demonstrated previously to be linked to the pathogenicity and persistence of the bacteria in macrophages and in mice. Copyright © 2017 American Society for Microbiology.

Joule heating effects on electroosmotic flow in insulator-based dielectrophoresis.

PubMed

Sridharan, Sriram; Zhu, Junjie; Hu, Guoqing; Xuan, Xiangchun

2011-09-01

Insulator-based dielectrophoresis (iDEP) is an emerging technology that has been successfully used to manipulate a variety of particles in microfluidic devices. However, due to the locally amplified electric field around the in-channel insulator, Joule heating often becomes an unavoidable issue that may disturb the electroosmotic flow and affect the particle motion. This work presents the first experimental study of Joule heating effects on electroosmotic flow in a typical iDEP device, e.g., a constriction microchannel, under DC-biased AC voltages. A numerical model is also developed to simulate the observed flow pattern by solving the coupled electric, energy, and fluid equations in a simplified two-dimensional geometry. It is observed that depending on the magnitude of the DC voltage, a pair of counter-rotating fluid circulations can occur at either the downstream end alone or each end of the channel constriction. Moreover, the pair at the downstream end appears larger in size than that at the upstream end due to DC electroosmotic flow. These fluid circulations, which are reasonably simulated by the numerical model, form as a result of the action of the electric field on Joule heating-induced fluid inhomogeneities in the constriction region. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

O-Hexadecyl-Dextran Entrapped Berberine Nanoparticles Abrogate High Glucose Stress Induced Apoptosis in Primary Rat Hepatocytes

PubMed Central

Tripathi, Madhulika; Bhatnagar, Priyanka; Kakkar, Poonam; Gupta, Kailash Chand

2014-01-01

Nanotized phytochemicals are being explored by researchers for promoting their uptake and effectiveness at lower concentrations. In this study, O-hexadecyl-dextran entrapped berberine chloride nanoparticles (BC-HDD NPs) were prepared, and evaluated for their cytoprotective efficacy in high glucose stressed primary hepatocytes and the results obtained compared with bulk berberine chloride (BBR) treatment. The nanotized formulation treated primary hepatocytes that were exposed to high glucose (40 mM), showed increased viability compared to the bulk BBR treated cells. BC-HDD NPs reduced the ROS generation by ∼3.5 fold during co-treatment, prevented GSH depletion by ∼1.6 fold, reduced NO formation by ∼5 fold and significantly prevented decline in SOD activity in stressed cells. Lipid peroxidation was also prevented by ∼1.9 fold in the presence of these NPs confirming the antioxidant capacity of the formulation. High glucose stress increased Bax/Bcl2 ratio followed by mitochondrial depolarization and activation of caspase-9/−3 confirming involvement of mitochondrial pathway of apoptosis in the exposed cells. Co- and post-treatment of BC-HDD NPs prevented depolarization of mitochondrial membrane, reduced Bax/Bcl2 ratio and prevented externalization of phosphatidyl-serine confirming their anti-apoptotic capacity in those cells. Sub-G1 phase apparent in high glucose stressed cells was not seen in BC-HDD NPs treated cells. The present study reveals that BC-HDD NPs at ∼20 fold lower concentration are as effective as BBR in preventing high glucose induced oxidative stress, mitochondrial depolarization and downstream events of apoptotic cell death. PMID:24586539

Transesterification of diethyl oxalate with phenol over sol-gel MoO(3)/TiO(2) catalysts.

PubMed

Kotbagi, Trupti; Nguyen, Duy Luan; Lancelot, Christine; Lamonier, Carole; Thavornprasert, Kaew-Arpha; Wenli, Zhu; Capron, Mickaël; Jalowiecki-Duhamel, Louise; Umbarkar, Shubhangi; Dongare, Mohan; Dumeignil, Franck

2012-08-01

The transesterification of diethyl oxalate (DEO) with phenol to form diphenyl oxalate (DPO) has been carried out in the liquid phase over very efficient MoO(3)/TiO(2) solid-acid sol-gel catalysts. A selectivity of 100 % with a remarkable maximum yield of 88 % were obtained, which opens the route to downstream phosgene-free processes for the synthesis of polycarbonates. Interpretation of the results of various acidity measurements (NH(3) and pyridine desorption, methanol oxidation as a probe reaction) allowed us to identify the catalytic sites as Lewis acid sites. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of water use strategies of the desert riparian forest plant community in inland rivers of two arid regions in northwestern China

NASA Astrophysics Data System (ADS)

Chen, Y. N.; Li, W. H.; Zhou, H. H.; Chen, Y. P.; Hao, X. M.; Fu, A. H.; Ma, J. X.

2014-10-01

Studies of the water use of the desert riparian forest plant community in arid regions and analyses of the response and adaptive strategies of plants to environmental stress are of great significance to the formulation of effective ecological conservation and restoration strategies. Taking two inland rivers in the arid regions of northwestern China, downstream of the Tarim River and Heihe River Basin as the research target regions, this paper explored the stem water potential, sap flow, root hydraulic lift, and characteristics of plant water sources of the major constructive species in the desert riparian forest, Populus euphratica and Tamarix ramosissima. Specifically, this was accomplished by combining the monitoring of field physiological and ecological indicators, and the analysis of laboratory tests. Then, the water use differences of species in different ecological environments and their ecological significance were analyzed. This study indicated that: (1) in terms of water sources, Populus euphratica and Tamarix ramosissima mainly used deep subsoil water and underground water, but the plant root system in the downstream of the Tarim River was more diversified than that in the downstream of the Heihe River in water absorption, (2) in terms of water distribution, Populus euphratica root possessed hydraulic lift capacity, but Populus euphratica root in the downstream of the Tarim River presented stronger hydraulic lift capacity and more significant ecological effect of water redistribution, (3) in terms of water transport, the plants in the downstream of the Heihe River can adapt to the environment through the current limiting of branch xylem, while plants in the downstream of the Tarim River substantially increased the survival probability of the whole plant by sacrificing weak branches and improving the water acquisition capacity of dominant branches; and (4) in terms of water dissipation, the water use and consumption of Populus euphratica at night exhibited no significant difference, but the water use and consumption of Populus euphratica in the downstream of the Tarim River in the day was significantly higher than that in the downstream of the Heihe River, and the essential reason for this is the groundwater depth. The ecology in the downstream of the Heihe River has been in balance in the maintenance and development stage, while desert riparian forest plants in the downstream of the Tarim River are still in severe arid stress.

Modification of a three-way catalyst washcoat by aging: A study along the longitudinal axis

NASA Astrophysics Data System (ADS)

Granados, M. López; Galisteo, F. Cabello; Mariscal, R.; Alifanti, M.; Gurbani, A.; Fierro, J. L. G.; Fernández-Ruíz, R.

2006-10-01

This work reports the research carried out by studying aliquots extracted at different axial coordinates from Three Way Catalyst (TWC) monoliths aged under real traffic conditions. Our study focused on the catalytic properties and on several chemical and physical effects caused in the Front and Rear monolith washcoat surfaces by vehicle aging after 60,000 km. Regarding the catalytic properties, all the used aliquots showed poorer activity than their corresponding fresh counterparts. The strongest deactivation was detected for NO and hydrocarbon conversion. CO conversion was less affected and the Rear monolith was as deactivated as the Front one. The characterisation techniques (TXRF, N 2 adsorption-desorption isotherms, XRD and H 2-TPR) detected - (i) the deposition of P, Zn and Pb; (ii) the formation of CePO 4 on account of the Ce from the washcoat; (iii) thermal sintering; (iv) inhibition of the reducibility of Ce oxides - as the main effects brought about by vehicle aging conditions. The deactivation observed at the beginning of the Front monolith was the result of a combination of the former effects. When moving downstream to higher axial coordinates, Pb accumulation and the loss of specific area appeared to be the only probable sources of deactivation.

AT-rich sequence elements promote nascent transcript cleavage leading to RNA polymerase II termination

PubMed Central

White, Eleanor; Kamieniarz-Gdula, Kinga; Dye, Michael J.; Proudfoot, Nick J.

2013-01-01

RNA Polymerase II (Pol II) termination is dependent on RNA processing signals as well as specific terminator elements located downstream of the poly(A) site. One of the two major terminator classes described so far is the Co-Transcriptional Cleavage (CoTC) element. We show that homopolymer A/T tracts within the human β-globin CoTC-mediated terminator element play a critical role in Pol II termination. These short A/T tracts, dispersed within seemingly random sequences, are strong terminator elements, and bioinformatics analysis confirms the presence of such sequences in 70% of the putative terminator regions (PTRs) genome-wide. PMID:23258704

The role of the rectum in osmoregulation and the potential effect of renoguanylin on SLC26a6 transport activity in the Gulf toadfish (Opsanus beta)

PubMed Central

Takei, Yoshio; Grosell, Martin

2016-01-01

Teleosts living in seawater continually absorb water across the intestine to compensate for branchial water loss to the environment. The present study reveals that the Gulf toadfish (Opsanus beta) rectum plays a comparable role to the posterior intestine in ion and water absorption. However, the posterior intestine appears to rely more on SLC26a6 (a HCO3−/Cl− antiporter) and the rectum appears to rely on NKCC2 (SLC12a1) for the purposes of solute-coupled water absorption. The present study also demonstrates that the rectum responds to renoguanylin (RGN), a member of the guanylin family of peptides that alters the normal osmoregulatory processes of the distal intestine, by inhibited water absorption. RGN decreases rectal water absorption more greatly than in the posterior intestine and leads to net Na+ and Cl− secretion, and a reversal of the absorptive short-circuit current (ISC). It is hypothesized that maintaining a larger fluid volume within the distal segments of intestinal tract facilitates the removal of CaCO3 precipitates and other solids from the intestine. Indeed, the expression of the components of the Cl−-secretory response, apical CFTR, and basolateral NKCC1 (SLC12a2), are upregulated in the rectum of the Gulf toadfish after 96 h in 60 ppt, an exposure that increases CaCO3 precipitate formation relative to 35 ppt. Moreover, the downstream intracellular effects of RGN appear to directly inhibit ion absorption by NKCC2 and anion exchange by SLC26a6. Overall, the present findings elucidate key electrophysiological differences between the posterior intestine and rectum of Gulf toadfish and the potent regulatory role renoguanylin plays in osmoregulation. PMID:27030664

An LCA model for waste incineration enhanced with new technologies for metal recovery and application to the case of Switzerland.

PubMed

Boesch, Michael E; Vadenbo, Carl; Saner, Dominik; Huter, Christoph; Hellweg, Stefanie

2014-02-01

A process model of municipal solid waste incinerators (MSWIs) and new technologies for metal recovery from combustion residues was developed. The environmental impact is modeled as a function of waste composition as well as waste treatment and material recovery technologies. The model includes combustion with a grate incinerator, several flue gas treatment technologies, electricity and steam production from waste heat recovery, metal recovery from slag and fly ash, and landfilling of residues and can be tailored to specific plants and sites (software tools can be downloaded free of charge). Application of the model to Switzerland shows that the treatment of one tonne of municipal solid waste results on average in 425 kg CO2-eq. generated in the incineration process, and 54 kg CO2-eq. accrue in upstream processes such as waste transport and the production of operating materials. Downstream processes, i.e. residue disposal, generates 5 kg CO2-eq. Savings from energy recovery are in the range of 67 to 752 kg CO2-eq. depending on the assumptions regarding the substituted energy production, while the recovery of metals from slag and fly ash currently results in a net saving of approximately 35 kg CO2-eq. A similar impact pattern is observed when assessing the MSWI model for aggregated environmental impacts (ReCiPe) and for non-renewable resource consumption (cumulative exergy demand), except that direct emissions have less and no relevance, respectively, on the total score. The study illustrates that MSWI plants can be an important element of industrial ecology as they provide waste disposal services and can help to close material and energetic cycles. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of backpacker use, pack stock trail use, and pack stock grazing on water-quality indicators, including nutrients, E. coli, hormones, and pharmaceuticals, in Yosemite National Park, USA

USGS Publications Warehouse

Forrester, Harrison; Clow, David W.; Roche, James W.; Heyvaert, Alan C.; Battaglin, William A.

2017-01-01

We investigated how visitor-use affects water quality in wilderness in Yosemite National Park. During the summers of 2012–2014, we collected and analyzed surface-water samples for water-quality indicators, including fecal indicator bacteria Escherichia coli, nutrients (nitrogen, phosphorus, carbon), suspended sediment concentration, pharmaceuticals, and hormones. Samples were collected upstream and downstream from different types of visitor use at weekly to biweekly intervals and during summer storms. We conducted a park-wide synoptic sampling campaign during summer 2014, and sampled upstream and downstream from meadows to evaluate the mitigating effect of meadows on water quality. At pack stock stream crossings, Escherichia coli concentrations were greater downstream from crossings than upstream (median downstream increase in Escherichia coli of three colony forming units 100 mL−1), with the greatest increases occurring during storms (median downstream increase in Escherichia coli of 32 CFU 100 mL−1). At backpacker use sites, hormones, and pharmaceuticals (e.g., insect repellent) were detected at downstream sites, and Escherichia coli concentrations were greater at downstream sites (median downstream increase in Escherichia coli of 1 CFU 100 mL−1). Differences in water quality downstream vs. upstream from meadows grazed by pack stock were not detectable for most water-quality indicators, however, Escherichia coli concentrations decreased downstream, suggesting entrapment and die-off of fecal indicator bacteria in meadows. Our results indicate that under current-use levels pack stock trail use and backpacker use are associated with detectable, but relatively minor, effects on water quality, which are most pronounced during storms.

Effects of Backpacker Use, Pack Stock Trail Use, and Pack Stock Grazing on Water-Quality Indicators, Including Nutrients, E. coli, Hormones, and Pharmaceuticals, in Yosemite National Park, USA

NASA Astrophysics Data System (ADS)

Forrester, Harrison; Clow, David; Roche, James; Heyvaert, Alan; Battaglin, William

2017-09-01

We investigated how visitor-use affects water quality in wilderness in Yosemite National Park. During the summers of 2012-2014, we collected and analyzed surface-water samples for water-quality indicators, including fecal indicator bacteria Escherichia coli, nutrients (nitrogen, phosphorus, carbon), suspended sediment concentration, pharmaceuticals, and hormones. Samples were collected upstream and downstream from different types of visitor use at weekly to biweekly intervals and during summer storms. We conducted a park-wide synoptic sampling campaign during summer 2014, and sampled upstream and downstream from meadows to evaluate the mitigating effect of meadows on water quality. At pack stock stream crossings, Escherichia coli concentrations were greater downstream from crossings than upstream (median downstream increase in Escherichia coli of three colony forming units 100 mL-1), with the greatest increases occurring during storms (median downstream increase in Escherichia coli of 32 CFU 100 mL-1). At backpacker use sites, hormones, and pharmaceuticals (e.g., insect repellent) were detected at downstream sites, and Escherichia coli concentrations were greater at downstream sites (median downstream increase in Escherichia coli of 1 CFU 100 mL-1). Differences in water quality downstream vs. upstream from meadows grazed by pack stock were not detectable for most water-quality indicators, however, Escherichia coli concentrations decreased downstream, suggesting entrapment and die-off of fecal indicator bacteria in meadows. Our results indicate that under current-use levels pack stock trail use and backpacker use are associated with detectable, but relatively minor, effects on water quality, which are most pronounced during storms.

Four MicroRNAs Promote Prostate Cell Proliferation with Regulation of PTEN and Its Downstream Signals In Vitro

PubMed Central

Xue, Jing-lun; Chen, Jin-zhong

2013-01-01

Background Phosphatase and tensin homologue (PTEN), as a tumor suppressor, plays vital roles in tumorigenesis and progression of prostate cancer. However, the mechanisms of PTEN regulation still need further investigation. We here report that a combination of four microRNAs (miR-19b, miR-23b, miR-26a and miR-92a) promotes prostate cell proliferation by regulating PTEN and its downstream signals in vitro. Methodology/Principal Findings We found that the four microRNAs (miRNAs) could effectively suppress PTEN expression by directly interacting with its 3’ UTR in prostate epithelial and cancer cells. Under-expression of the four miRNAs by antisense neutralization up-regulates PTEN expression, while overexpression of the four miRNAs accelerates epithelial and prostate cancer cell proliferation. Furthermore, the expression of the four miRNAs could, singly or jointly, alter the expression of the key components in the phosphoinositide 3-kinase (PI3K)/Akt pathway, including PIK3CA, PIK3CD, PIK3R1 and Akt, along with their downstream signal, cyclin D1. Conclusions These results suggested that the four miRNAs could promote prostate cancer cell proliferation by co-regulating the expression of PTEN, PI3K/Akt pathway and cyclin D1 in vitro. These findings increase understanding of the molecular mechanisms of prostate carcinogenesis and progression, even provide valuable insights into the diagnosis, prognosis, and rational design of novel therapeutics for prostate cancer. PMID:24098737

WNT16 antagonises excessive canonical WNT activation and protects cartilage in osteoarthritis.

PubMed

Nalesso, Giovanna; Thomas, Bethan Lynne; Sherwood, Joanna Claire; Yu, Jing; Addimanda, Olga; Eldridge, Suzanne Elizabeth; Thorup, Anne-Sophie; Dale, Leslie; Schett, Georg; Zwerina, Jochen; Eltawil, Noha; Pitzalis, Costantino; Dell'Accio, Francesco

2017-01-01

Both excessive and insufficient activation of WNT signalling results in cartilage breakdown and osteoarthritis. WNT16 is upregulated in the articular cartilage following injury and in osteoarthritis. Here, we investigate the function of WNT16 in osteoarthritis and the downstream molecular mechanisms. Osteoarthritis was induced by destabilisation of the medial meniscus in wild-type and WNT16-deficient mice. Molecular mechanisms and downstream effects were studied in vitro and in vivo in primary cartilage progenitor cells and primary chondrocytes. The pathway downstream of WNT16 was studied in primary chondrocytes and using the axis duplication assay in Xenopus. WNT16-deficient mice developed more severe osteoarthritis with reduced expression of lubricin and increased chondrocyte apoptosis. WNT16 supported the phenotype of cartilage superficial-zone progenitor cells and lubricin expression. Increased osteoarthritis in WNT16-deficient mice was associated with excessive activation of canonical WNT signalling. In vitro, high doses of WNT16 weakly activated canonical WNT signalling, but, in co-stimulation experiments, WNT16 reduced the capacity of WNT3a to activate the canonical WNT pathway. In vivo, WNT16 rescued the WNT8-induced primary axis duplication in Xenopus embryos. In osteoarthritis, WNT16 maintains a balanced canonical WNT signalling and prevents detrimental excessive activation, thereby supporting the homeostasis of progenitor cells. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Network-directed cis-mediator analysis of normal prostate tissue expression profiles reveals downstream regulatory associations of prostate cancer susceptibility loci.

PubMed

Larson, Nicholas B; McDonnell, Shannon K; Fogarty, Zach; Larson, Melissa C; Cheville, John; Riska, Shaun; Baheti, Saurabh; Weber, Alexandra M; Nair, Asha A; Wang, Liang; O'Brien, Daniel; Davila, Jaime; Schaid, Daniel J; Thibodeau, Stephen N

2017-10-17

Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis -acting associations due to study limitations. While trans -eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans -eQTL associations are mediated by cis -regulated genes, such as transcription factors. Leveraging a data-driven gene co-expression network, we conducted a comprehensive cis -mediator analysis using RNA-Seq data from 471 normal prostate tissue samples to identify downstream regulatory associations of previously identified prostate cancer risk variants. We discovered multiple trans -eQTL associations that were significantly mediated by cis -regulated transcripts, four of which involved risk locus 17q12, proximal transcription factor HNF1B , and target trans -genes with known HNF response elements ( MIA2 , SRC , SEMA6A , KIF12 ). We additionally identified evidence of cis -acting down-regulation of MSMB via rs10993994 corresponding to reduced co-expression of NDRG1 . The majority of these cis -mediator relationships demonstrated trans -eQTL replicability in 87 prostate tissue samples from the Gene-Tissue Expression Project. These findings provide further biological context to known risk loci and outline new hypotheses for investigation into the etiology of prostate cancer.

Geomorphic response of the North Fork Stillaguamish River to the State Route 530 landslide near Oso, Washington

USGS Publications Warehouse

Anderson, Scott W.; Keith, Mackenzie K.; Magirl, Christopher S.; Wallick, J. Rose; Mastin, Mark C.; Foreman, James R.

2017-08-03

On March 22, 2014, the State Route 530 Landslide near Oso, Washington mobilized 8 million cubic meters of unconsolidated Pleistocene material, creating a valley‑spanning deposit that fully impounded the North Fork Stillaguamish River. The river overtopped the 8-meter high debris impoundment within 25 hours and began steadily incising a new channel through the center of the deposit. Repeat topographic surveys, sediment transport measurements, bedload transport models, and observations of downstream channel change were used to document the establishment of that new channel through the landslide and assess the potential for downstream aggradation or channel change that might increase downstream flood hazards.Efficient erosion of the landslide deposit, associated with the steep knickzone formed by the downstream edge of the deposit, resulted in the re-establishment of a 20–40 meters wide, deeply inset channel through the entire deposit by May 2014, 2 months after the landslide. The mean water-surface elevation of the channel through the landslide decreased 7 meters during that 2-month period, and was about 1 meter above the pre-landslide profile in July 2014. The 2014–15 flood season, which included flows near the 0.5 annual exceedance probability discharge (2-year flood), widened the channel tens of meters, and further lowered the water-surface profile 0.5 meter. The planform position evolved slowly as a result of 5–20-meter high banks predominantly composed of clay-rich, cohesive lacustrine material. Erosion of the landslide deposit delivered a total of 820 thousand metric tons of sediment to the North Fork Stillaguamish River over the 18 months following the landslide. The sediment delivery from the deposit was predominantly fine grained: 77 percent (by mass) of the eroded material was silt or clay (less than 0.063 millimeter [mm]), 19 percent sand (0.063–2 mm), and 4 percent pebbles and cobbles (greater than 2 mm).Over the 18 months following the landslide, the bedload at a site 5 kilometers downstream of the landslide was estimated to be 310±65 thousand metric tons, and the suspended load at that same site was estimated to be 990±110 thousand metric tons. These loads represent the combined input from the landslide and ambient upstream sources; over the study interval, landslide sediment made up about 20–40 percent of the bedload, and 65–85 percent of the suspended-sediment load at this site. At a site 70 kilometers downstream of the landslide, near the mouth of the main‑stem Stillaguamish River, suspended sediment loads were estimated to be about 1,440 thousand metric tons, of which about 600 thousand metric tons, or 30 percent, likely was derived from the landslide. The mass of landslide sediment in suspension at the mouth of the river, and the timing of arrival of that sediment, indicates that about 70 percent of the landslide sediment eroded during the study period was quickly transported through the entire basin, exiting into Puget Sound within weeks of initial entrainment.Empirical bedload transport equations, in conjunction with surficial grain-size data and output from a one‑dimensional hydraulic model, were used to estimate spatial trends in bedload transport capacity, highlighting areas where reach-scale conditions would be most likely to promote deposition of coarse landslide sediment. Transport capacities decreased sharply over a reach about 5 kilometers downstream of the landslide and remained relatively low over the next 10 kilometers downstream. However, the magnitude of calculated transport capacities are large relative to the coarse sediment input from the landslide, suggesting that substantial deposition of landslide sediment was not likely to occur. These assessments were corroborated by observations of channel change, which indicated that the downstream channel response to the landslide was modest and short-lived. The most pronounced downstream effects included a wedge of aggradation just downstream of the landslide, about 1 meter high and extending a kilometer downstream, and a 0.3-meter pulse of aggradation observed 5 kilometers downstream of the landslide. In both locations, peak aggradation and channel response occurred within about a month of the landslide, and both sites had largely recovered to pre-landslide conditions by July 2014. No substantial channel change clearly linked to the landslide was observed after July 2014 except for a modest fining of surficial gravel size distributions and continued recovery and incision of the reach just downstream of the landslide.The muted downstream response of the North Fork Stillaguamish River to the State Route 530 Landslide primarily can be attributed to the cohesive, silt- and clay-rich material that bounded most of the new channel. Although the river efficiently incised a new channel through the deposit, subsequent rates of lateral erosion were slowed by the tall, cohesive banks, limiting the total volume of sediment delivery. Once entrained, however, most landslide material was rapidly transported downstream in suspension with little geomorphic effect. Landslide material coarse enough to travel as bedload was predominantly sand and fine gravel, and sediment transport models and observations of downstream change indicated that the rate of coarse sediment delivery from the landslide did not exceed the rivers ability to transport that material. The generally muted downstream response to sediment delivery from the State Route 530 Landslide, as well as the mechanics of that delivery and response, were generally consistent with observations made following the intentional removal of constructed dams.The rate and efficiency of erosion from the landslide decreased over the period of analysis, as the new channel approached a quasi-equilibrium form. In the absence of additional hillslope activity, rates of erosion from the landslide are likely to be small compared to those over the first 18 months after the landslide. The modest channel response to the highest rates of sediment delivery, and rapid recovery thereafter, indicate that the river should be able to convey the continued supply of landslide-derived sediment effectively with little effect on the downstream morphology and flood risks.

Performance of Ni/dolomite pellet catalyst on gas distribution from cassava rhizome gasification with a modular fixed-bed gasifier.

PubMed

Sricharoenchaikul, V; Atong, D; Sornkade, P; Nisamaneenate, J

2017-05-01

Thermal conversion of cassava rhizome was performed using a modular downdraft gasifier with the addition of Ni-based catalysts as promising tar eliminating and produced gas upgrading techniques. The activities of a synthesized 5% Ni/dolomite pellet catalyst prepared by impregnation method were investigated in a secondary reactor downstream of the gasifier. High reforming activity of the Ni/dolomite pellet catalyst on tar reduction was achieved. The conversion to H 2 and CO was improved via steam reforming of methane and char reaction with CO 2 . Moreover, the formation of CH 4 and C x H y was diminished through the tar or condensable hydrocarbon reformed on the catalyst surface. The carbon and hydrogen conversions of cassava rhizome with prepared catalyst were 83.79% and 61.78%, respectively, at an air flow rate of 1.98 m 3 /hr. At this condition, tar formation was low, while the lower heating value was 4.39 MJ/m 3 and H 2 to CO molar ratio was 1.22. Generally, the addition of a catalyst not only enhanced gas production, but also reduced tar and particulate matter generation; thus, its implementation should help lessen the pollution control requirement and cost of operation, while allowing higher quality fuel gas production.

Soil greenhouse gas emissions and carbon budgeting in a short-hydroperiod floodplain wetland

USGS Publications Warehouse

Batson, Jackie; Noe, Gregory B.; Hupp, Cliff R.; Krauss, Ken W.; Rybicki, Nancy B.; Schenk, Edward R.

2015-01-01

Understanding the controls on floodplain carbon (C) cycling is important for assessing greenhouse gas emissions and the potential for C sequestration in river-floodplain ecosystems. We hypothesized that greater hydrologic connectivity would increase C inputs to floodplains that would not only stimulate soil C gas emissions but also sequester more C in soils. In an urban Piedmont river (151 km2 watershed) with a floodplain that is dry most of the year, we quantified soil CO2, CH4, and N2O net emissions along gradients of floodplain hydrologic connectivity, identified controls on soil aerobic and anaerobic respiration, and developed a floodplain soil C budget. Sites were chosen along a longitudinal river gradient and across lateral floodplain geomorphic units (levee, backswamp, and toe slope). CO2 emissions decreased downstream in backswamps and toe slopes and were high on the levees. CH4 and N2O fluxes were near zero; however, CH4emissions were highest in the backswamp. Annual CO2 emissions correlated negatively with soil water-filled pore space and positively with variables related to drier, coarser soil. Conversely, annual CH4 emissions had the opposite pattern of CO2. Spatial variation in aerobic and anaerobic respiration was thus controlled by oxygen availability but was not related to C inputs from sedimentation or vegetation. The annual mean soil CO2 emission rate was 1091 g C m−2 yr−1, the net sedimentation rate was 111 g C m−2 yr−1, and the vegetation production rate was 240 g C m−2 yr−1, with a soil C balance (loss) of −338 g C m−2 yr−1. This floodplain is losing C likely due to long-term drying from watershed urbanization.

Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.

PubMed

Desale, Swapnil S; Raja, Srikumar M; Kim, Jong Oh; Mohapatra, Bhopal; Soni, Kruti S; Luan, Haitao; Williams, Stetson H; Bielecki, Timothy A; Feng, Dan; Storck, Matthew; Band, Vimla; Cohen, Samuel M; Band, Hamid; Bronich, Tatiana K

2015-06-28

ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full potential as an anti-cancer agent. Copyright © 2015 Elsevier B.V. All rights reserved.

Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.

PubMed

Botta, Amy; Laher, Ismail; Beam, Julianne; Decoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L; Ghosh, Sanjoy

2013-01-01

PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.

A Single Acyl-CoA Dehydrogenase Is Required For Catabolism Of Isoleucine, Valine And Short-Chain Fatty Acids In Aspergillus nidulans

PubMed Central

Maggio-Hall, Lori A.; Lyne, Paul; Wolff, Jon A.; Keller, Nancy P.

2010-01-01

An acyl-CoA dehydrogenase has been identified as part of the mitochondrial β-oxidation pathway in the ascomycete fungus Aspergillus nidulans. Disruption of the scdA gene prevented use of butyric acid (C4) and hexanoic acid (C6) as carbon sources and reduced cellular butyryl-CoA dehydrogenase activity by 7.5-fold. While the mutant strain exhibited wild-type levels of growth on erucic acid (C22:1) and oleic acid (C18:1), some reduction in growth was observed with myristic acid (C14). The ΔscdA mutation was found to be epistatic to a mutation downstream in the β-oxidation pathway (disruption of enoyl-CoA hydratase). The ΔscdA mutant was also unable to use isoleucine or valine as a carbon source. Transcription of scdA was observed in the presence of either fatty acids or amino acids. When the mutant was grown in medium containing either isoleucine or valine, organic acid analysis of culture supernatants showed accumulation of 2-oxo acid intermediates of branched chain amino acid catabolism, suggesting feedback inhibition of the upstream branched-chain α-keto acid dehydrogenase. PMID:17656140

Co-regulation of nuclear respiratory factor-1 by NFκB and CREB links LPS-induced inflammation to mitochondrial biogenesis

PubMed Central

Suliman, Hagir B.; Sweeney, Timothy E.; Withers, Crystal M.; Piantadosi, Claude A.

2010-01-01

The nuclear respiratory factor-1 (NRF1) gene is activated by lipopolysaccharide (LPS), which might reflect TLR4-mediated mitigation of cellular inflammatory damage via initiation of mitochondrial biogenesis. To test this hypothesis, we examined NRF1 promoter regulation by NFκB, and identified interspecies-conserved κB-responsive promoter and intronic elements in the NRF1 locus. In mice, activation of Nrf1 and its downstream target, Tfam, by Escherichia coli was contingent on NFκB, and in LPS-treated hepatocytes, NFκB served as an NRF1 enhancer element in conjunction with NFκB promoter binding. Unexpectedly, optimal NRF1 promoter activity after LPS also required binding by the energy-state-dependent transcription factor CREB. EMSA and ChIP assays confirmed p65 and CREB binding to the NRF1 promoter and p65 binding to intron 1. Functionality for both transcription factors was validated by gene-knockdown studies. LPS regulation of NRF1 led to mtDNA-encoded gene expression and expansion of mtDNA copy number. In cells expressing plasmid constructs containing the NRF-1 promoter and GFP, LPS-dependent reporter activity was abolished by cis-acting κB-element mutations, and nuclear accumulation of NFκB and CREB demonstrated dependence on mitochondrial H2O2. These findings indicate that TLR4-dependent NFκB and CREB activation co-regulate the NRF1 promoter with NFκB intronic enhancement and redox-regulated nuclear translocation, leading to downstream target-gene expression, and identify NRF-1 as an early-phase component of the host antibacterial defenses. PMID:20587593

Landfilling of waste: accounting of greenhouse gases and global warming contributions.

PubMed

Manfredi, Simone; Tonini, Davide; Christensen, Thomas H; Scharff, Heijo

2009-11-01

Accounting of greenhouse gas (GHG) emissions from waste landfilling is summarized with the focus on processes and technical data for a number of different landfilling technologies: open dump (which was included as the worst-case-scenario), conventional landfills with flares and with energy recovery, and landfills receiving low-organic-carbon waste. The results showed that direct emissions of GHG from the landfill systems (primarily dispersive release of methane) are the major contributions to the GHG accounting, up to about 1000 kg CO(2)-eq. tonne( -1) for the open dump, 300 kg CO(2)-eq. tonne( -1) for conventional landfilling of mixed waste and 70 kg CO(2)-eq. tonne(-1) for low-organic-carbon waste landfills. The load caused by indirect, upstream emissions from provision of energy and materials to the landfill was low, here estimated to be up to 16 kg CO(2)-eq. tonne(-1). On the other hand, utilization of landfill gas for electricity generation contributed to major savings, in most cases, corresponding to about half of the load caused by direct GHG emission from the landfill. However, this saving can vary significantly depending on what the generated electricity substitutes for. Significant amounts of biogenic carbon may still be stored within the landfill body after 100 years, which here is counted as a saved GHG emission. With respect to landfilling of mixed waste with energy recovery, the net, average GHG accounting ranged from about -70 to 30 kg CO(2)-eq. tonne(- 1), obtained by summing the direct and indirect (upstream and downstream) emissions and accounting for stored biogenic carbon as a saving. However, if binding of biogenic carbon was not accounted for, the overall GHG load would be in the range of 60 to 300 kg CO(2)-eq. tonne( -1). This paper clearly shows that electricity generation as well as accounting of stored biogenic carbon are crucial to the accounting of GHG of waste landfilling.

Quantification of Greenhouse Gas Emission Rates from strong Point Sources by Space-borne IPDA Lidar Measurements: Results from a Sensitivity Analysis Study

NASA Astrophysics Data System (ADS)

Ehret, G.; Kiemle, C.; Rapp, M.

2017-12-01

The practical implementation of the Paris Agreement (COP21) vastly profit from an independent, reliable and global measurement system of greenhouse gas emissions, in particular of CO2, in order to complement and cross-check national efforts. Most fossil-fuel CO2 emitters emanate from large sources such as cities and power plants. These emissions increase the local CO2 abundance in the atmosphere by 1-10 parts per million (ppm) which is a signal that is significantly larger than the variability from natural sources and sinks over the local source domain. Despite these large signals, they are only sparsely sampled by the ground-based network which calls for satellite measurements. However, none of the existing and forthcoming passive satellite instruments, operating in the NIR spectral domain, can measure CO2 emissions at night time or in low sunlight conditions and in high latitude regions in winter times. The resulting sparse coverage of passive spectrometers is a serious limitation, particularly for the Northern Hemisphere, since these regions exhibit substantial emissions during the winter as well as other times of the year. In contrast, CO2 measurements by an Integrated Path Differential Absorption (IPDA) Lidar are largely immune to these limitations and initial results from airborne application look promising. In this study, we discuss the implication for a space-borne IPDA Lidar system. A Gaussian plume model will be used to simulate the CO2-distribution of large power plants downstream to the source. The space-borne measurements are simulated by applying a simple forward model based on Gaussian error distribution. Besides the sampling frequency, the sampling geometry (e.g. measurement distance to the emitting source) and the error of the measurement itself vastly impact on the flux inversion performance. We will discuss the results by incorporating Gaussian plume and mass budget approaches to quantify the emission rates.

Power Plant Bromide Discharges and Downstream Drinking Water Systems in Pennsylvania.

PubMed

Good, Kelly D; VanBriesen, Jeanne M

2017-10-17

Coal-fired power plants equipped with wet flue gas desulfurization (FGD) systems have been implicated in increasing bromide levels and subsequent increases in disinfection byproducts at downstream drinking water plants. Bromide was not included as a regulated constituent in the recent steam electric effluent limitations guidelines and standards (ELGs) since the U.S. EPA analysis suggested few drinking water facilities would be affected by bromide discharges from power plants. The present analysis uses a watershed approach to identify Pennsylvania drinking water intakes downstream of wet FGD discharges and to assess the potential for bromide discharge effects. Twenty-two (22) public drinking water systems serving 2.5 million people were identified as being downstream of at least one wet FGD discharge. During mean August conditions (generally low-flow, minimal dilution) in receiving rivers, the median predicted bromide concentrations contributed by wet FGD at Pennsylvania intake locations ranged from 5.2 to 62 μg/L for the Base scenario (including only natural bromide in coal) and from 16 to 190 μg/L for the Bromide Addition scenario (natural plus added bromide for mercury control); ranges depend on bromide loads and receiving stream dilution capacity.

The impact of urban open space and 'lift-up' building design on building intake fraction and daily pollutant exposure in idealized urban models.

PubMed

Sha, Chenyuan; Wang, Xuemei; Lin, Yuanyuan; Fan, Yifan; Chen, Xi; Hang, Jian

2018-08-15

Sustainable urban design is an effective way to improve urban ventilation and reduce vehicular pollutant exposure to urban residents. This paper investigated the impacts of urban open space and 'lift-up' building design on vehicular CO (carbon monoxide) exposure in typical three-dimensional (3D) urban canopy layer (UCL) models under neutral atmospheric conditions. The building intake fraction (IF) represents the fraction of total vehicular pollutant emissions inhaled by residents when they stay at home. The building daily CO exposure (E t ) means the extent of human beings' contact with CO within one day indoor at home. Computational fluid dynamics (CFD) simulations integrating with these two concepts were performed to solve turbulent flow and assess vehicular CO exposure to urban residents. CFD technique with the standard k-ε model was successfully validated by wind tunnel data. The initial numerical UCL model consists of 5-row and 5-column (5×5) cubic buildings (building height H=street width W=30m) with four approaching wind directions (θ=0°, 15°, 30°, 45°). In Group I, one of the 25 building models is removed to attain urban open space settings. In Group II, the first floor (Lift-up1), or second floor (Lift-up2), or third floor (Lift-up3) of all buildings is elevated respectively to create wind pathways through buildings. Compared to the initial case, urban open space can slightly or significantly reduce pollutant exposure for urban residents. As θ=30° and 45°, open space settings are more effective to reduce pollutant exposure than θ=0° and 15°.The pollutant dilution near or surrounding open space and in its adjacent downstream regions is usually enhanced. Lift-up1 and Lift-up2 experience much greater pollutant exposure reduction in all wind directions than Lift-up3 and open space. Although further investigations are still required to provide practical guidelines, this study is one of the first attempts for reducing urban pollutant exposure by improving urban design. Copyright © 2018. Published by Elsevier B.V.

Diatom Milking: A Review and New Approaches

PubMed Central

Vinayak, Vandana; Manoylov, Kalina M.; Gateau, Hélène; Blanckaert, Vincent; Hérault, Josiane; Pencréac’h, Gaëlle; Marchand, Justine; Gordon, Richard; Schoefs, Benoît

2015-01-01

The rise of human populations and the growth of cities contribute to the depletion of natural resources, increase their cost, and create potential climatic changes. To overcome difficulties in supplying populations and reducing the resource cost, a search for alternative pharmaceutical, nanotechnology, and energy sources has begun. Among the alternative sources, microalgae are the most promising because they use carbon dioxide (CO2) to produce biomass and/or valuable compounds. Once produced, the biomass is ordinarily harvested and processed (downstream program). Drying, grinding, and extraction steps are destructive to the microalgal biomass that then needs to be renewed. The extraction and purification processes generate organic wastes and require substantial energy inputs. Altogether, it is urgent to develop alternative downstream processes. Among the possibilities, milking invokes the concept that the extraction should not kill the algal cells. Therefore, it does not require growing the algae anew. In this review, we discuss research on milking of diatoms. The main themes are (a) development of alternative methods to extract and harvest high added value compounds; (b) design of photobioreactors; (c) biodiversity and (d) stress physiology, illustrated with original results dealing with oleaginous diatoms. PMID:25939034

Biodegradation of 17β-estradiol, estrone, and testosterone in stream sediments

USGS Publications Warehouse

Bradley, P.M.; Chapelle, F.H.; Barber, L.B.; McMahon, P.B.; Gray, J.L.; Kolpin, D.W.

2009-01-01

The release of endocrine-disrupting chemicals (EDCs) in wastewater treatment plant (WWTP) effluent poses a significant threat to the ecology of surface water receptors, due to impacts on the hormonal control, sexual development, reproductive success and community structure of the indigenous aquatic organisms and associated wildlife. Among the EDCs commonly observed in WWTP effluent, the natural [e.g., 17??-estradiol (E2) and estrone (E1)] and synthetic [e.g., ethynylestradiol (EE2)] estrogens are particular concerns owing to their high endocrine reactivity in both in vitro and in vivo laboratory models. These reproductive hormones have been identified as the primary cause of estrogenic effects in wastewater effluent, with greater than 95% of the estrogen receptor agonist activity in effluent attributed to this contaminant group. The potentials for in situ biodegradation of 17??-estradiol (E2), estrone (E1), and testosterone (T) were investigated in three, hydrologically-distinct, WWTP-impacted streams in the United States. Relative differences in the mineralization of [4-14C] substrates were assessed in oxic microcosms containing sediment or water-only from locations upstream and downstream of the WWTP outfall in each system. Upstream samples provided insight into the biodegradative potential of sediment microbial communities that were not under the immediate impact of WWTP effluent. Upstream sediment from all three systems demonstrated significant mineralization of the "A" ring of E2, E1 and T, with the potential of T biodegradation consistently greater than of E2 and no systematic difference in the potentials of E2 and E1. Downstream samples provided insight into the impacts of effluent on reproductive hormone biodegradation. Significant "A" ring mineralization was also observed in downstream sediment, with the potentials for E1 and T mineralization being substantially depressed relative to upstream samples. In marked contrast, the potentials for E2 mineralization immediately downstream of the WWTP outfalls were more than double that of upstream samples. E2 mineralization was also observed in water, albeit at insufficient rate to prevent substantial downstream transport in the water column. The results of this study indicate that, in combination with sediment sorption processes which effectively scavenge hydrophobic contaminants from the water column and immobilize them in the vicinity of the WWTP outfall, aerobic biodegradation of reproductive hormones can be an environmentally important mechanism for nonconservative (destructive) attenuation of hormonal endocrine disruptors in effluent-impacted streams.

Hydrochemical study of an arsenic-contaminated plain in Guandu, north Taiwan

NASA Astrophysics Data System (ADS)

Hsiao, Yu-Hsiang

2015-04-01

Arsenic pollution in Guandu Plain, north Taiwan is a critical issue due to highly developed anthropogenic activities. It was considered that arsenic was carried in by surface water system. Two major rivers, Huanggang Creek and South Huang Greek, flow through Guandu Plain. Both creeks originate from Tatung Volcano Group, which is extensively active in post-volcanic activities. In this study, the hydrochemistry along the two major rivers was studied for tracing the source of arsenic pollution in Guandu Plain. The pH values in the upstream water are in the range from 6 to 8 but dramatically decrease down to 2-4.5 in the downstream area. It can be concluded that the creeks are recharged with very low pH geothermal water. In addition, arsenic shows a different spatial distribution. In Huanggang Creek, arsenic concentration is much higher, about 200 ppb to 500 ppb, in the downstream than in the upstream while arsenic concentration is extremely low, below 1 ppb, in the downstream of South Huang Greek. The geochemical results show that rare earth elements (REEs) are depleted in the upstream both in Huanggang creek and South Huang creek, and the NASC-normalized ratios of heavy to light REE (Lu/La) in the upstream are very close to 1. This demonstrates that the upstream water is geochemically dominated by the interaction between water and sedimentary rock. In the downstream, the NASC-normalized REE pattern shows a quit different type which is depleted in light REEs (much higher Lu/La ratio). It is well known that igneous rock is depleted in light REEs; therefore, arsenic is possibly volcanic origin. In this study, PHREEQC, a thermodynamic modeling program, was also utilized to calculate the saturation index (SI) of hydrous ferric oxide (HFO), which can effectively scavenge arsenic in water. The results demonstrate that SI of HFO is mainly controlled by pH in this study. When pH is greater than 3.5, HFO start to precipitate and remove arsenic from water. Therefore, it is believed that the arsenic pollution in Guandu Plain could result from HFO co-precipitation due to the increase of pH when Huanggang creek and South Huang creek flow through the land.

Interleukin 1 β-induced SMAD2/3 linker modifications are TAK1 dependent and delay TGFβ signaling in primary human mesenchymal stem cells.

PubMed

van den Akker, Guus G; van Beuningen, Henk M; Vitters, Elly L; Koenders, Marije I; van de Loo, Fons A; van Lent, Peter L; Blaney Davidson, Esmeralda N; van der Kraan, Peter M

2017-12-01

Chondrogenic differentiation of mesenchymal stem cells (MSC) requires transforming growth factor beta (TGFβ) signaling. TGFβ binds to the type I receptor activin-like kinase (ALK)5 and results in C-terminal SMAD2/3 phosphorylation (pSMAD2/3C). In turn pSMAD2/3C translocates to the nucleus and regulates target gene expression. Inflammatory mediators are known to exert an inhibitory effect on MSC differentiation. In this study we investigated the effect of interleukin 1 β (IL1β) on SMAD2/3 signaling dynamics and post-translational modifications. Co-stimulation of MSC with TGFβ and IL1β did not affect peak pSMAD2C levels at 1h post-stimulation. Surprisingly, SMAD3 transcriptional activity, as determined by the CAGA 12 -luciferase reporter construct, was enhanced by co-stimulation of TGFβ and IL1β compared to TGFβ alone. Furthermore, IL1β stimulation induced CAGA 12 -luciferase activity in a SMAD dependent way. As SMAD function can be modulated independent of canonical TGFβ signaling through the SMAD linker domain, we studied SMAD2 linker phosphorylation at specific threonine and serine residues. SMAD2 linker threonine and serine modifications were observed within 1h following TGFβ, IL1β or TGFβ and IL1β stimulation. Upon co-stimulation linker modified SMAD2 accumulated in the cytoplasm and SMAD2/3 target gene transcription (ID1, JUNB) at 2-4h was inhibited. A detailed time course analysis of IL1β-induced SMAD2 linker modifications revealed a distinct temperospatial pattern compared to TGFβ. Co-stimulation with both factors resulted in a similar kinetic profile as TGFβ alone. Nevertheless, IL1β did subtly alter TGFβ-induced pSMAD2C levels between 8 and 24h post-stimulation, which was reflected by TGFβ target gene expression (PAI1, JUNB). Direct evidence for the importance of SMAD3 linker modifications for the effect of IL1β on TGFβ signaling was obtained by over-expression of SMAD3 or a SMAD3 linker phospho-mutant. Finally, an inhibitor screening was performed to identify kinases involved in SMAD2/3 linker modifications. We identified TAK1 kinase activity as crucial for IL1β-induced SMAD2 linker modifications and CAGA 12 -luciferase activity. TGFβ and IL1β signaling interact at the SMAD2/3 level in human primary MSC. Down-stream TGFβ target genes were repressed by IL1β independent of C-terminal SMAD2 phosphorylation. We demonstrate that SMAD2/3 linker modifications are required for this interplay and identified TAK1 as a crucial mediator of IL1β-induced TGFβ signal modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Disturbed adiponectin – AMPK system in skeletal muscle of patients with metabolic syndrome.

PubMed

Van Berendoncks, An M; Stensvold, Dorthe; Garnier, Anne; Fortin, Dominique; Sente, Tahnee; Vrints, Christiaan J; Arild, Slørdahl Stig; Ventura-Clapier, Renee; Wisløff, Ulrik; Conraads, Viviane M

2015-02-01

Patients with metabolic syndrome are characterized by low circulating adiponectin levels and reduced adiponectin sensitivity in skeletal muscles. Through binding on its main skeletal muscle receptor AdipoR1, adiponectin activates AMP-activated protein kinase (AMPK), a key player in energy homeostasis. Fourteen metabolic syndrome patients and seven healthy control subjects were included. Blood samples were taken to determine insulin resistance, adiponectin, lipoproteins, and C-reactive protein. Muscle biopsies (m. vastus lateralis) were obtained to assess mRNA expression of AdipoR1 and both AMPKα1 and AMPKα2 subunits, as well as downstream targets in lipid and glucose metabolism. Skeletal muscle mRNA expression of AMPKα1 and AMPKα2 was lower in metabolic syndrome patients (100 ± 6 vs. 122 ± 8 AU, p = 0.030 and 64 ± 4 vs. 85 ± 9 AU, p = 0.044, respectively), whereas the expression of AdipoR1 was upregulated (138 ± 9 vs. 105 ± 7, p = 0.012). AMPKα1 and AdipoR1 correlated positively in both the control (r = 0.964, p < 0.001) and the metabolic syndrome group (r = 0.600, p = 0.023). However, this relation was shifted upwards in metabolic syndrome patients, indicating increased AdipoR1mRNA expression for a similar AMPKα1 expression. Previously, a blunted stimulatory effect of adiponectin on AMPK activation has been shown in metabolic syndrome patients. The present data suggest that the disturbed interaction of adiponectin with AMPK is located downstream of the AdipoR1 receptor. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

KCNQ channels determine serotonergic modulation of ventral surface chemoreceptors and respiratory drive

PubMed Central

Hawryluk, Joanna M.; Moreira, Thiago S.; Takakura, Ana C.; Wenker, Ian C.; Tzingounis, Anastasios V.; Mulkey, Daniel K.

2012-01-01

Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+ changes. Their activity is also sensitive to neuromodulatory inputs from multiple respiratory centers, and thus they serve as a key nexus of respiratory control. However, molecular mechanisms that control their activity and susceptibility to neuromodulation are unknown. Here, we show in vitro and in vivo that KCNQ channels are critical determinants of RTN neural activity. In particular, we find that pharmacological block of KCNQ channels (XE991, 10 μM) increased basal activity and CO2-responsivness of RTN neurons in rat brain slices; whereas KCNQ channel activation (retigabine 2–40 μM) silenced these neurons. Interestingly, we also find that KCNQ and apamin sensitive SK channels act synergistically to regulate firing rate of RTN chemoreceptors; simultaneous blockade of both channels led to a increase in CO2-responsivness. Furthermore, we also show that KCNQ channels but not SK channels are downstream effectors of serotonin modulation of RTN activity in vitro. In contrast, inhibition of KCNQ channel did not prevent modulation of RTN activity by Substance P or TRH; previously identified neuromodulators of RTN chemoreception. Importantly, we also show that KCNQ channels are critical for RTN activity in vivo. Inhibition of KCNQ channels lowered the CO2 threshold for phrenic nerve discharge in anesthetized rats and decreased the ventilatory response to serotonin in awake and anesthetized animals. Given that serotonergic dysfunction may contribute to respiratory failure, our findings suggest KCNQ channels as a new therapeutic avenue for respiratory complications associated with multiple neurological disorders. PMID:23175845

Estrogen attenuates glutamate-induced cell death by inhibiting Ca2+ influx through L-type voltage-gated Ca2+ channels

PubMed Central

Sribnick, Eric A.; Del Re, Angelo M.; Ray, Swapan K.; Woodward, John J.; Banik, Naren L.

2009-01-01

Estrogen-mediated neuroprotection is observed in neurodegenerative disease and neurotrauama models; however, determining a mechanism for these effects has been difficult. We propose that estrogen may limit cell death in the nervous system tissue by inhibiting increases in intracellular free Ca2+. Here, we present data using VSC 4.1 cell line, a ventral spinal motoneuron and neuroblastoma hybrid cell line. Treatment with 1 mM glutamate for 24 h induced apoptosis. When cells were pre-treated with 100 nM 17β-estradiol (estrogen) for 1 h and then co-treated with glutamate, apoptotic death was significantly attenuated. Estrogen also prevented glutamate-mediated changes in resting membrane potential and membrane capacitance. Treatment with either 17α-estradiol or cell impermeable estrogen did not mimic the findings seen with estrogen. Glutamate treatment significantly increased both intracellular free Ca2+ and the activities of downstream proteases such as calpain and caspase-3. Estrogen attenuated both the increases in intracellular free Ca2+ and protease activities. In order to determine the pathway responsible for estrogen-mediated inhibition of these increases in intracellular free Ca2+, cells were treated with several Ca2+ entry inhibitors, but only the L-type Ca2+ channel blocker nifedipine demonstrated cytoprotective effects comparable to estrogen. To expand these findings, cells were treated with the L-type Ca2+ channel agonist FPL 64176, which increased both cell death and intracellular free Ca2+, and estrogen inhibited both effects. From these observations, we conclude that estrogen limits glutamate-induced cell death in VSC 4.1 cells through effects on L-type Ca2+ channels, inhibiting Ca2+ influx as well as activation of the pro-apoptotic proteases calpain and caspase-3. PMID:19389388

Comparison of anti-inflammatory mechanisms of mango (Mangifera Indica L.) and pomegranate (Punica Granatum L.) in a preclinical model of colitis.

PubMed

Kim, Hyemee; Banerjee, Nivedita; Ivanov, Ivan; Pfent, Catherine M; Prudhomme, Kalan R; Bisson, William H; Dashwood, Roderick H; Talcott, Stephen T; Mertens-Talcott, Susanne U

2016-09-01

Tannin-rich fruits have been evaluated as alternative prevention strategies for colorectal cancer based on their anti-inflammatory properties. This study compared tannin-rich preparations from mango (rich in gallotannins) and pomegranate (rich in ellagitannins) in the dextran sodium sulfate-induced colitis model. In rats, mango and pomegranate beverages decreased intestinal inflammation and the levels of pro-inflammatory cytokines in mucosa and serum. The mango beverage suppressed the ratio of phosphorylated/total protein expression of the IGF-1R-AKT/mTOR axis and downregulated mRNA expression of Igf1, Insr, and pik3cv. Pomegranate decreased p70S6K and RPS6, as well as Rps6ka2, Map2k2, and Mapk1 mRNA. In silico modeling indicated a high binding of docked of gallic acid to the catalytic domain of IGF-1R, which may suppress the activity of the enzyme. Ellagic acid docked effectively into the catalytic domains of both IGF-1R and EGFR. In vitro assays with lipopolysaccharide-treated CCD-18Co cells using polyphenolic extracts from each beverage, as well as pure compounds, corroborated the predictions made in silico. Mango polyphenols inhibited the IGF-1R- AKT/mTOR axis, and pomegranate polyphenols downregulate the mTOR downstream pathway through reductions in ERK1/2. These results suggest that extracts rich in gallo- and ellagitannins act on different molecular targets in the protection against ulcerative colitis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Testing REACH draft technical guidance notes for conducting chemical safety assessments-the experience of a downstream user of a preparation.

PubMed

Gade, Anne Lill; Ovrebø, Steinar; Hylland, Ketil

2008-07-01

The goal of REACH is the safe use of chemicals. This study examines the efficiency and usefulness of two draft technical guidance notes in the REACH Interim Project 3.2-2 for the development of the chemical safety report and exposure scenarios. A case study was carried out for a paint system for protection of structural steel. The focuses of the study were risk assessment of preparations based on Derived No Effect Level (DNEL) and Predicted No Effect Concentrations (PNEC) and on effective and accurate communication in the supply chain. Exposure scenarios and generic descriptions of uses, risk management measures, and exposure determinants were developed. The study showed that communication formats, software tools, and guidelines for chemical risk assessment need further adjustment to preparations and real-life situations. Web platforms may simplify such communication. The downstream formulator needs basic substance data from the substance manufacturer during the pre-registration phase to develop exposure scenarios for preparations. Default values need to be communicated in the supply chain because these were critical for the derivation of applicable risk management demands. The current guidelines which rely on the available toxicological knowledge are insufficient to advise downstream users on how to develop exposure scenarios for preparations.

Effects of high salinity wastewater discharges on unionid mussels in the Allegheny River, Pennsylvania

USGS Publications Warehouse

Kathleen Patnode,; Hittle, Elizabeth A.; Robert Anderson,; Lora Zimmerman,; Fulton, John W.

2015-01-01

We examined the effect of high salinity wastewater (brine) from oil and natural gas drilling on freshwater mussels in the Allegheny River, Pennsylvania, during 2012. Mussel cages (N = 5 per site) were deployed at two sites upstream and four sites downstream of a brine treatment facility on the Allegheny River. Each cage contained 20 juvenile northern riffleshell mussels Epioblasma torulosa rangiana). Continuous specific conductance and temperature data were recorded by water quality probes deployed at each site. To measure the amount of mixing throughout the entire study area, specific conductance surveys were completed two times during low-flow conditions along transects from bank to bank that targeted upstream (reference) reaches, a municipal wastewater treatment plant discharge upstream of the brine-facility discharge, the brine facility, and downstream reaches. Specific conductance data indicated that high specific conductance water from the brine facility (4,000–12,000 µS/cm; mean 7,846) compared to the reference reach (103–188 µS/cm; mean 151) is carried along the left descending bank of the river and that dilution of the discharge via mixing does not occur until 0.5 mi (805 m) downstream. Juvenile northern riffleshell mussel survival was severely impaired within the high specific conductance zone (2 and 34% at and downstream of the brine facility, respectively) and at the municipal wastewater treatment plant (21%) compared to background (84%). We surveyed native mussels (family Unionidae) at 10 transects: 3 upstream, 3 within, and 4 downstream of the high specific conductance zone. Unionid mussel abundance and diversity were lower for all transects within and downstream of the high conductivity zone compared to upstream. The results of this study clearly demonstrate in situ toxicity to juvenile northern riffleshell mussels, a federally endangered species, and to the native unionid mussel assemblage located downstream of a brine discharge to the Allegheny River.

Linking pyrolysis and anaerobic digestion (Py-AD) for the conversion of lignocellulosic biomass.

PubMed

Fabbri, Daniele; Torri, Cristian

2016-04-01

Biogas is a mixture of CO2 and CH4 produced by a consortia of Bacteria and Archeae operating in anaerobic digestion (AD) plants. Biogas can be burnt as such in engines to produce electricity and heat or upgraded into biomethane. Biomethane is a drop-in fuel that can be injected in the natural gas grid or utilised as a transport fuel. While a wide array of biomass feedstock can be degraded into biogas, unconverted lignin, hemicellulose and cellulose end up in the co-product digestate leaving a large portion of chemical energy unutilised. Pyrolysis (Py) transforms in a single step and without chemical reagents the lignocellulose matrix into gaseous (syngas), liquid (bio-oil, pyrolysis oil) and solid (biochar) fractions for the development of renewable fuels and materials. The Py route applied downstream to AD is actively investigated in order to valorise the solid digestate presently destined only for soil applications. Coupling Py upstream to AD is an emerging field of research aimed at expanding the feedstock towards biologically recalcitrant substrates (wood, paper, sludge). The biomethanation potential was demonstrated for gaseous (H2/CO) and water soluble pyrolysis products, while the influence of insoluble pyrolytic lignin remains fairly unexplored. Biochar can promote the production of biomethane by acting as a support for microorganism colonisation, conductor for direct interspecies electron transfer, sorbent for hydrophobic inhibitors, and reactant for in situ biogas upgrading. Enhancing the advantages (carbon source) over the side effects (toxicity) of Py fractions represents the main challenge of Py-AD. This can be addressed by increasing the selectivity of the thermochemical process or improving the ecological flexibility of mixed bacterial consortia towards chemically complex environments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nutrient Chemistry and Microbial Activity in the Upper Mississippi River Basin: Stoichiometry and Downstream Patterns

EPA Science Inventory

Nutrients, carbon, and silica have been used to track changes in water quality in the major rivers of the world. Most studies focus on the mouths of rivers and adjacent coastal waters. Studies on the Mississippi River have concluded that N enrichment and stable or declining Si co...

Barrage fishponds: Reduction of pesticide concentration peaks and associated risk of adverse ecological effects in headwater streams.

PubMed

Gaillard, Juliette; Thomas, Marielle; Iuretig, Alain; Pallez, Christelle; Feidt, Cyril; Dauchy, Xavier; Banas, Damien

2016-03-15

Constructed wetlands have been suggested as pesticide risk mitigation measures. Yet, in many agricultural areas, ponds or shallow lakes are already present and may contribute to the control of non-point source contamination by pesticides. In order to test this hypothesis, we investigated the influence of extensively managed barrage fishponds (n = 3) on the dissolved concentrations of 100 pesticides in headwater streams over the course of a year. Among the 100 pesticides, 50 different substances were detected upstream and 48 downstream. Highest measured concentration upstream was 26.5 μg/L (2-methyl-4-chlorophenoxyacetic acid, MCPA) and 5.19 μg/L (isoproturon) downstream. Fishponds were found to reduce peak exposure levels as high pesticide concentrations (defined here as ≥ 1 μg/L) generally decreased by more than 90% between upstream and downstream sampling sites. The measured concentrations in the investigated streams were compared to laboratory toxicity data for standard test organisms (algae, invertebrates and fish) using the toxic unit approach. When considering the threshold levels set by the European Union within the first tier risk assessment procedure for pesticide registration (commission regulation (EU) N° 546/2011), regulatory threshold exceedances were observed for 22 pesticides upstream from fishponds and for 9 pesticides downstream. Therefore, the investigated barrage fishponds contributed to the reduction of pesticide peak concentrations and potential risk of adverse effects for downstream ecosystems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of Pulsed Plasma Jets on the Recovering Boundary Layer Downstream of a Reflected Shock Interaction

NASA Astrophysics Data System (ADS)

Greene, Benton; Clemens, Noel; Magari, Patrick; Micka, Daniel; Ueckermann, Mattheus

2015-11-01

Shock-induced turbulent boundary layer separation can have many detrimental effects in supersonic inlets including flow distortion and instability, structural fatigue, poor pressure recovery, and unstart. The current study investigates the effect of pulsed plasma jets on the recovering boundary layer downstream of a reflected shock wave-boundary layer interaction. The effects of pitch and skew angle of the jet as well as the heating parameter and discharge time scale are tested using several pulsing frequencies. In addition, the effect of the plasma jets on the undisturbed boundary layer at 6 mm and 11 mm downstream of the jets is measured. A pitot-static pressure probe is used to measure the velocity profile of the boundary layer 35 mm downstream of the plasma jets, and the degree of boundary layer distortion is compared between the different models and run conditions. Additionally, the effect of each actuator configuration on the shape of the mean separated region is investigated using surface oil flow visualization. Previous studies with lower energy showed a weak effect on the downstream boundary layer. The current investigation will attempt to increase this effect using a higher-energy discharge. Funded by AFRL through and SBIR in collaboration with Creare, LLC.

Application of a Depositional Facies Model to an Acid Mine Drainage Site▿ †

PubMed Central

Brown, Juliana F.; Jones, Daniel S.; Mills, Daniel B.; Macalady, Jennifer L.; Burgos, William D.

2011-01-01

Lower Red Eyes is an acid mine drainage site in Pennsylvania where low-pH Fe(II) oxidation has created a large, terraced iron mound downstream of an anoxic, acidic, metal-rich spring. Aqueous chemistry, mineral precipitates, microbial communities, and laboratory-based Fe(II) oxidation rates for this site were analyzed in the context of a depositional facies model. Depositional facies were defined as pools, terraces, or microterracettes based on cm-scale sediment morphology, irrespective of the distance downstream from the spring. The sediments were composed entirely of Fe precipitates and cemented organic matter. The Fe precipitates were identified as schwertmannite at all locations, regardless of facies. Microbial composition was studied with fluorescence in situ hybridization (FISH) and transitioned from a microaerophilic, Euglena-dominated community at the spring, to a Betaproteobacteria (primarily Ferrovum spp.)-dominated community at the upstream end of the iron mound, to a Gammaproteobacteria (primarily Acidithiobacillus)-dominated community at the downstream end of the iron mound. Microbial community structure was more strongly correlated with pH and geochemical conditions than depositional facies. Intact pieces of terrace and pool sediments from upstream and downstream locations were used in flowthrough laboratory reactors to measure the rate and extent of low-pH Fe(II) oxidation. No change in Fe(II) concentration was observed with 60Co-irradiated sediments or with no-sediment controls, indicating that abiotic Fe(II) oxidation was negligible. Upstream sediments attained lower effluent Fe(II) concentrations compared to downstream sediments, regardless of depositional facies. PMID:21097582

Development, Optimization and Structure-Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4-d]pyrrolo[2,3-b]pyridine Scaffold.

PubMed

Forster, Michael; Chaikuad, Apirat; Dimitrov, Teodor; Döring, Eva; Holstein, Julia; Berger, Benedict-Tilman; Gehringer, Matthias; Ghoreschi, Kamran; Müller, Susanne; Knapp, Stefan; Laufer, Stefan A

2018-05-31

Janus kinases are major drivers of immune signaling and have been the focus of anti-inflammatory drug discovery for more than a decade. Because of the invariable co-localization of JAK1 and JAK3 at cytokine receptors, the question if selective JAK3 inhibition is sufficient to effectively block downstream signaling has been highly controversial. Recently, we discovered the covalent-reversible JAK3 inhibitor FM-381 (23) featuring high isoform and kinome selectivity. Crystallography revealed that this inhibitor induces an unprecedented binding pocket by interactions of a nitrile substituent with arginine residues in JAK3. Herein we describe detailed structure activity relationships necessary for induction of the arginine pocket and the impact of this structural change on potency, isoform selectivity and efficacy in cellular models. Furthermore, we evaluated the stability of this novel inhibitor class in in vitro metabolic assays and were able to demonstrate an adequate stability of key compound 23 for in vivo use.

Cost-effective WDM-PON Delivering Up/Down-stream Data on a Single Wavelength Using Soliton Pulse

NASA Astrophysics Data System (ADS)

Tawade, Laxman

2013-06-01

This paper presents wavelength division multiplexing passive optical network (WDM-PON) system delivering downstream 2.5 Gbit/s data and upstream 1 Gbit/s data on a single wavelength using pulse source is mode locked laser which generating a single pulse of "sech" shape with specified power and width i.e. soliton pulse. The optical source for downstream data and upstream data is sech pulse generator at central office and reflective semiconductor optical amplifier (RSOA) at each optical network unit. We also investigate analysis of backscattered optical signal for upstream data and downstream data simultaneously. Bit error rate, Q-Factor were measured to demonstrate the proposed scheme. In this paper Long reach aspects of an access network is investigated using single channel scenario.

Occurrence of turbulent flow conditions in supercritical fluid chromatography.

PubMed

De Pauw, Ruben; Choikhet, Konstantin; Desmet, Gert; Broeckhoven, Ken

2014-09-26

Having similar densities as liquids but with viscosities up to 20 times lower (higher diffusion coefficients), supercritical CO2 is the ideal (co-)solvent for fast and/or highly efficient separations without mass-transfer limitations or excessive column pressure drops. Whereas in liquid chromatography the flow remains laminar in both the packed bed and tubing, except in extreme cases (e.g. in a 75 μm tubing, pure acetonitrile at 5 ml/min), a supercritical fluid can experience a transition from laminar to turbulent flow in more typical operation modes. Due to the significant lower viscosity, this transition for example already occurs at 1.3 ml/min for neat CO2 when using connection tubing with an ID of 127 μm. By calculating the Darcy friction factor, which can be plotted versus the Reynolds number in a so-called Moody chart, typically used in fluid dynamics, higher values are found for stainless steel than PEEK tubing, in agreement with their expected higher surface roughness. As a result turbulent effects are more pronounced when using stainless steel tubing. The higher than expected extra-column pressure drop limits the kinetic performance of supercritical fluid chromatography and complicates the optimization of tubing ID, which is based on a trade-off between extra-column band broadening and pressure drop. One of the most important practical consequences is the non-linear increase in extra-column pressure drop over the tubing downstream of the column which leads to an unexpected increase in average column pressure and mobile phase density, and thus decrease in retention. For close eluting components with a significantly different dependence of retention on density, the selectivity can significantly be affected by this increase in average pressure. In addition, the occurrence of turbulent flow is also observed in the detector cell and connection tubing. This results in a noise-increase by a factor of four when going from laminar to turbulent flow (e.g. going from 0.5 to 2.5 ml/min for neat CO2). Copyright © 2014 Elsevier B.V. All rights reserved.

O2 and CO2 glow-discharge-assisted oxygen transport through Ag

NASA Astrophysics Data System (ADS)

Outlaw, R. A.

1990-08-01

The permeation of oxygen through Ag normally occurs by a sequence of steps which include the initial dissociative adsorption of molecular oxygen at the upstream surface, the dissolution of the atoms into the bulk, and the subsequent migration of the atoms between octahedral sites of the lattice until they arrive at the vacuum interface downstream. The dissociative adsorption step, however, proceeds slowly, as indicated by the low sticking coefficient of O2 on Ag(10-6-10-3). The application of a dc field in 0.5 Torr of O2 (E/n˜10-14 V cm2) on the upstream side of a Ag membrane generated gas phase atomic oxygen that substantially enhanced the transport. The transport flux was observed to increase from a value of 4.4×1013 cm-2 s-1 to a glow discharge value of 2.83×1014 cm-2 s-1 at a membrane temperature of 650 °C. This suggests that the dissociative adsorption step limits the supply of oxygen atoms to the upstream side of the membrane. When the upstream O2 was replaced by an equal pressure of CO2, only a small permeation signal was observed, but the application of the glow discharge substantially increased the transport flux from 3.25×1012 cm-2 s-1 to 1.74×1014 cm-2 s-1. This method of separating O2 from a CO2 environment may be a possible mechanism for providing a supply of oxygen for astronauts in a manned mission to Mars.

Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, Yong Pil; Department of Pharmaceutical Engineering, International University of Korea, Jinju; Choi, Jae Ho

AMP-activated protein kinase (AMPK) plays a central role in controlling hepatic lipid metabolism through modulating the downstream acetyl CoA carboxylase (ACC) and sterol regulatory element-binding protein-1c (SREBP-1c) pathway. Saponins, particularly platycodin D, from the roots of Platycodon grandiflorum (Changkil saponins, CKS) have a variety of pharmacological properties, including antioxidant and hepatoprotective properties. The aim of this study was to investigate the effects of CKS on hepatic lipogenesis and on the expression of genes involved in lipogenesis, and the mechanisms involved. CKS attenuated fat accumulation and the induction of the lipogenic genes encoding SREBP-1c and fatty acid synthase in the liversmore » of HFD-fed rats and in steatotic HepG2 cells. Blood biochemical analyses and histopathological examinations showed that CKS prevented liver injury. CKS and platycodin D each increased the phosphorylation of AMPK and acetyl-CoA carboxylase in HFD-fed rats and HepG2 cells. The use of specific inhibitors showed that platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells. This study demonstrates that CKS or platycodin D alone can regulate hepatic lipogenesis via an AMPK-dependent signalling pathway. - Highlights: ► CKS attenuated fat accumulation in HFD-fed rats and in steatotic HepG2 cells. ► CKS and its major component, platycodin D, inhibited the levels of SREBP-1 and FAS. ► CKS and platycodin D increased the phosphorylation of AMPK and ACC. ► Platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells.« less

West Closure Complex Pump Intake Model, New Orleans, Louisiana

DTIC Science & Technology

2013-02-01

72  Figure 71. Velocities in Pump 12 intake, intake level = 2.0, only Pump 12 operating. Cross section looking downstream...intake level = 2.0, Pumps 11-13 operating. Cross -section looking downstream. Discharge = 1,740 cfs...73  Figure 73. Velocities in Pump 12 intake, intake level = 2.0, all 11 pumps operating. Cross - section looking downstream. Discharge

Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.

PubMed

Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

2010-07-16

Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1alpha and HIF-2alpha immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1alpha-positive, 15 HIF-2alpha-positive and 10 positive for HIF-1alpha and HIF-2alpha. Expression of HIF-1alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1alpha and HIF-2alpha in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2alpha in Ewing's. Downstream transcription was HIF-1alpha-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by >or= 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1alpha and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1α expression.

PubMed

Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Kandimalla, Ramesh J L; Bal, Amanjit; Gill, Kiran Dip

2013-12-01

The present investigation was carried out to elucidate a possible molecular mechanism related to the effects of aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of Peroxisome proliferator activated receptor gamma co-activator 1α (PGC-1α) and its downstream targets i.e. Nuclear respiratory factor-1(NRF-1), Nuclear respiratory factor-2(NRF-2) and Mitochondrial transcription factor A (Tfam) in mitochondrial biogenesis. Aluminium lactate (10mg/kgb.wt./day) was administered intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an increase in ROS levels, mitochondrial DNA oxidation and decrease in citrate synthase activity in the Hippocampus (HC) and Corpus striatum (CS) regions of rat brain. On the other hand, there was a decrease in the mRNA levels of the mitochondrial encoded subunits-NADH dehydrogenase (ND) subunits i.e. ND1, ND2, ND3, Cytochrome b (Cytb), Cytochrome oxidase (COX) subunits i.e. COX1, COX3, ATP synthase (ATPase) subunit 6 along with reduced expression of nuclear encoded subunits COX4, COX5A, COX5B of Electron transport chain (ETC). Besides, a decrease in mitochondrial DNA copy number and mitochondrial content in both regions of rat brain was observed. The PGC-1α was down-regulated in aluminium treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1α in aluminium treated rats. Electron microscopy results revealed a significant increase in the mitochondrial swelling, loss of cristae, chromatin condensation and decreases in mitochondrial number in case of aluminium treated rats as compared to control. So, PGC-1α seems to be a potent target for aluminium neurotoxicity, which makes it an almost ideal target to control or limit the damage that has been associated with the defective mitochondrial function seen in neurodegenerative diseases. © 2013.

Effect of Krueger nose flaps on the experimental force and moment characteristics of an oblique wing

NASA Technical Reports Server (NTRS)

Hopkins, E. J.; Lovette, G. H.

1976-01-01

Experimental force and moment data are presented for an oblique wing mounted on a body of revolution and equipped with Krueger type nose flaps. The effectiveness of these flaps in making the moment curves more linear by controlling the flow separation on the downstream wing panel at high lift coefficients was determined. The investigation of the effects of the Krueger flaps covered two cases: (1) use of the flaps on the downstream wing panel only and (2) use of the flaps on both wing panels. For part of the tests, the Krueger flaps were mounted on nose flaps that were drooped either 5 deg or 10 deg. The wing was elliptical in planform, had an aspect ratio of 6.0 (based on the unswept span) and was tested at sweep angles of 0, 45 deg, and 50 deg. The Mach-number range covered was from 0.25 to 0.95. It was found that the most effective arrangement of the Krueger flaps for making the pitching-, rolling-, and yawing-moment curves more linear at high lift coefficients was having the Krueger flaps mounted on the nose flaps drooped 5 deg and only on the downstream wing panel.

Effect of Dam operation on monthly and annual trends of flow discharge in the Qom Rood Watershed, Iran

NASA Astrophysics Data System (ADS)

Yaghmaei, Hiva; Sadeghi, Seyed Hamidreza; Moradi, Hamidreza; Gholamalifard, Mehdi

2018-02-01

Trends in flow discharge, temperature and rainfall from the Qom Rood Watershed, Iran, for a period of 1979-2016 were analyzed at monthly and annual time scales. Trend analyses were conducted using the Mann-Kendall test, the double-mass curve of mean annual discharge versus rainfall, and rainfall-runoff relationship before and after the 15 Khordad Dam operation. Multiple regression of flow discharge against rainfall and temperature was used to determine the residual trend at four meteorological and hydrological stations located upstream and downstream of the Qom Rood Watershed. Results showed that the temperature at the upstream and downstream stations did not have any significant trend, but a significant decreasing trend (P < .05) in rainfall was detected only in May (z = -1.66) at the downstream stations. There was a significant positive trend (P < .05) in rainfall in February (z = 2.22) and July (z = 2.15) at the upstream stations, and in October (z = 2.3) and November (z = 1.8) at the downstream stations. However, there was a noticeable decrease in monthly and annual flow discharge, and residual trend at 99% significance level at the downstream stations. At the upstream stations, the flow discharges had significant (P < .05) declining trend in all months, but annual flow discharge did not change significantly. Analysis of double mass curve between runoff and rainfall at the downstream stations showed an inconsistency in the line slope concordant with the time of 15 Khordad Dam operation. Annual mean discharge at the upstream stations did not show a significant change before and after 15 Khordad Dam operation. However, annual flow magnitude decreased significantly by 87.5 and 81.7% in Shad Abad and KoohSefid, respectively. These results confirmed that natural driving forces did not affect flow discharge changes and the observed decreasing tendency in flow discharge at the downstream stations was due to 15 Khordad Dam, and at the upstream stations due to diversion/storage dams. These findings highlighted the role of human interference in changing the hydrologic regime in the study area based on which appropriate adaptive decisions can be made.

A Chemokine Receptor CXCR2 Macromolecular Complex Regulates Neutrophil Functions in Inflammatory Diseases*

PubMed Central

Wu, Yanning; Wang, Shuo; Farooq, Shukkur M.; Castelvetere, Marcello P.; Hou, Yuning; Gao, Ji-Liang; Navarro, Javier V.; Oupicky, David; Sun, Fei; Li, Chunying

2012-01-01

Inflammation plays an important role in a wide range of human diseases such as ischemia-reperfusion injury, arteriosclerosis, cystic fibrosis, inflammatory bowel disease, etc. Neutrophilic accumulation in the inflamed tissues is an essential component of normal host defense against infection, but uncontrolled neutrophilic infiltration can cause progressive damage to the tissue epithelium. The CXC chemokine receptor CXCR2 and its specific ligands have been reported to play critical roles in the pathophysiology of various inflammatory diseases. However, it is unclear how CXCR2 is coupled specifically to its downstream signaling molecules and modulates cellular functions of neutrophils. Here we show that the PDZ scaffold protein NHERF1 couples CXCR2 to its downstream effector phospholipase C (PLC)-β2, forming a macromolecular complex, through a PDZ-based interaction. We assembled a macromolecular complex of CXCR2·NHERF1·PLC-β2 in vitro, and we also detected such a complex in neutrophils by co-immunoprecipitation. We further observed that the CXCR2-containing macromolecular complex is critical for the CXCR2-mediated intracellular calcium mobilization and the resultant migration and infiltration of neutrophils, as disrupting the complex with a cell permeant CXCR2-specific peptide (containing the PDZ motif) inhibited intracellular calcium mobilization, chemotaxis, and transepithelial migration of neutrophils. Taken together, our data demonstrate a critical role of the PDZ-dependent CXCR2 macromolecular signaling complex in regulating neutrophil functions and suggest that targeting the CXCR2 multiprotein complex may represent a novel therapeutic strategy for certain inflammatory diseases. PMID:22203670

Magnetic chicane for terahertz management

DOEpatents

Benson, Stephen; Biallas, George Herman; Douglas, David; Jordan, Kevin Carl; Neil, George R.; Michelle D. Shinn; Willams, Gwyn P.

2010-12-28

The introduction of a magnetic electron beam orbit chicane between the wiggler and the downstream initial bending dipole in an energy recovering Linac alleviates the effects of radiation propagated from the downstream bending dipole that tend to distort the proximate downstream mirror of the optical cavity resonator.

Effects of Timber Harvest on River Food Webs: Physical, Chemical and Biological Responses

PubMed Central

Wootton, J. Timothy

2012-01-01

I compared physical, chemical and biological characteristics of nine rivers running through three timber harvest regimes to investigate the effects of land use on river ecosystems, to determine whether these corresponded to changes linked with downstream location, and to compare the response of different types of indicator variables. Physical variables changed with downstream location, but varied little with timber harvest. Most chemical variables increased strongly with timber harvest, but not with downstream location. Most biological variables did not vary systematically with either timber harvst or downstream location. Dissolved organic carbon did not vary with timber harvest or downstream location, but correlated positively with salmonid abundance. Nutrient manipulations revealed no general pattern of nutrient limitation with timber harvest or downstream location. The results suggest that chemical variables most reliably indicate timber harvest impact in these systems. The biological variables most relevant to human stakeholders were surprisingly insensitive to timber harvest, however, apparently because of decoupling from nutrient responses and unexpectedly weak responses by physical variables. PMID:22957030

Species and temperature measurements of methane oxidation in a nanosecond repetitively pulsed discharge

PubMed Central

Lefkowitz, Joseph K; Guo, Peng; Rousso, Aric; Ju, Yiguang

2015-01-01

Speciation and temperature measurements of methane oxidation during a nanosecond repetitively pulsed discharge in a low-temperature flow reactor have been performed. Measurements of temperature and formaldehyde during a burst of pulses were made on a time-dependent basis using tunable diode laser absorption spectroscopy, and measurements of all other major stable species were made downstream of a continuously pulsed discharge using gas chromatography. The major species for a stoichiometric methane/oxygen/helium mixture with 75% dilution are H2O, CO, CO2, H2, CH2O, CH3OH, C2H6, C2H4 and C2H2. A modelling tool to simulate homogeneous plasma combustion kinetics is assembled by combining the ZDPlasKin and CHEMKIN codes. In addition, a kinetic model for plasma-assisted combustion (HP-Mech/plasma) of methane, oxygen and helium mixtures has been assembled to simulate the measurements. Predictions can accurately capture reactant consumption as well as production of the major product species. However, significant disagreement is found for minor species, particularly CH2O and CH3OH. Further analysis revealed that the plasma-activated low-temperature oxidation pathways, particularly those involving CH3O2 radical reactions and methane reactions with O(1D), are responsible for this disagreement. PMID:26170433

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis

PubMed Central

Kernbauer, Elisabeth; Hölzl, Markus A.; Hofer, Johannes; Gualdoni, Guido A.; Schmetterer, Klaus G.; Miftari, Fitore; Sobanov, Yury; Meshcheryakova, Anastasia; Mechtcheriakova, Diana; Witzeneder, Nadine; Greiner, Georg; Ohradanova-Repic, Anna; Waidhofer-Söllner, Petra; Säemann, Marcus D.; Decker, Thomas

2017-01-01

A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation. PMID:28742108

Protection against acetaminophen-induced acute liver failure by omentum adipose tissue derived stem cells through the mediation of Nrf2 and cytochrome P450 expression.

PubMed

Huang, Yu-Jen; Chen, Poda; Lee, Chih-Yuan; Yang, Sin-Yu; Lin, Ming-Tsan; Lee, Hsuan-Shu; Wu, Yao-Ming

2016-01-19

Acetaminophen (APAP) overdose causes acute liver failure (ALF) in animals and humans via the rapid depletion of intracellular glutathione (GSH) and the generation of excess reactive oxygen species (ROS) that damage hepatocytes. Stem cell therapy is a potential treatment strategy for ALF. We isolated mesenchymal stem cells (MSCs) from mice omentum adipose tissue-derived stem cells (ASCs) and transplanted them into a mouse model of APAP-induced ALF to explore their therapeutic potential. In addition, we performed in vitro co-culture studies with omentum-derived ASCs and primary isolated hepatocytes to demonstrate the hepatoprotective effect of omentum-derived ASCs on hepatocytes that were subjected to APAP-induced damage. ASC transplantation significantly improved the survival rate of mice with ALF and attenuated the severity of APAP-induced liver damage by suppressing cytochrome P450 activity to reduce the accumulation of toxic nitrotyrosine and the upregulation of NF-E2-related factor 2 (Nrf2) expression, resulting in an increase in the subsequent antioxidant activity. These effects protected the hepatocytes from APAP-induced damage through the suppression of downstream MAPK signal activation and inflammatory cytokine production. our results demonstrate that omentum-derived ASCs are an alternative source of ASCs that regulate the antioxidant response and may represent a beneficial therapeutic strategy for ALF.

Triazole-linked DNA as a primer surrogate in the synthesis of first-strand cDNA.

PubMed

Fujino, Tomoko; Yasumoto, Ken-ichi; Yamazaki, Naomi; Hasome, Ai; Sogawa, Kazuhiro; Isobe, Hiroyuki

2011-11-04

A phosphate-eliminated nonnatural oligonucleotide serves as a primer surrogate in reverse transcription reaction of mRNA. Despite of the nonnatural triazole linkages in the surrogate, the reverse transcriptase effectively elongated cDNA sequences on the 3'-downstream of the primer by transcription of the complementary sequence of mRNA. A structure-activity comparison with the reference natural oligonucleotides shows the superior priming activity of the surrogate containing triazole-linkages. The nonnatural linkages also protect the transcribed cDNA from digestion reactions with 5'-exonuclease and enable us to remove noise transcripts of unknown origins. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

National Dam Inspection Program. Canonsburg Dam Number 2 (Johnsons Run Dam) (NDI Number PA 00506, PennDER Number 63-41), Ohio River Basin, Johnsons Run, Washington County, Pennsylvania. Phase I Inspection Report,

DTIC Science & Technology

1980-02-01

00W> 0 a*a) 9C ’~ 1 )0 MV U) CO 4 0 2, ) P4 w 4) aj 41 0 qVa 0-q40 0.4)r- ( 0 Do44 4-4 nu 00 rA ~UW 4 4 % 1 -2-i I4j V 0 > C V -4 (a 0) 41 Z -,4 4 fO 4...life or property. The assessment of the general condition ~ 1 of the dam isbased upon available data and visual inspections. Detailed investigation, and...should include items 1 through 3 below. 1 ) Detailed investigation of the structural stability of the dam. Information concerning the downstream slope has

Particulate Organic Matter Distribution along the Lower Amazon River: Addressing Aquatic Ecology Concepts Using Fatty Acids

PubMed Central

Mortillaro, Jean-Michel; Rigal, François; Rybarczyk, Hervé; Bernardes, Marcelo; Abril, Gwenaël; Meziane, Tarik

2012-01-01

One of the greatest challenges in understanding the Amazon basin functioning is to ascertain the role played by floodplains in the organic matter (OM) cycle, crucial for a large spectrum of ecological mechanisms. Fatty acids (FAs) were combined with environmental descriptors and analyzed through multivariate and spatial tools (asymmetric eigenvector maps, AEM and principal coordinates of neighbor matrices, PCNM). This challenge allowed investigating the distribution of suspended particulate organic matter (SPOM), in order to trace its seasonal origin and quality, along a 800 km section of the Amazon river-floodplain system. Statistical analysis confirmed that large amounts of saturated FAs (15:0, 18:0, 24:0, 25:0 and 26:0), an indication of refractory OM, were concomitantly recorded with high pCO2 in rivers, during the high water season (HW). Contrastingly, FAs marker which may be attributed in this ecosystem to aquatic plants (18:2ω6 and 18:3ω3) and cyanobacteria (16:1ω7), were correlated with higher O2, chlorophyll a and pheopigments in floodplains, due to a high primary production during low waters (LW). Decreasing concentrations of unsaturated FAs, that characterize labile OM, were recorded during HW, from upstream to downstream. Furthermore, using PCNM and AEM spatial methods, FAs compositions of SPOM displayed an upstream-downstream gradient during HW, which was attributed to OM retention and the extent of flooded forest in floodplains. Discrimination of OM quality between the Amazon River and floodplains corroborate higher autotrophic production in the latter and transfer of OM to rivers at LW season. Together, these gradients demonstrate the validity of FAs as predictors of spatial and temporal changes in OM quality. These spatial and temporal trends are explained by 1) downstream change in landscape morphology as predicted by the River Continuum Concept; 2) enhanced primary production during LW when the water level decreased and its residence time increased as predicted by the Flood Pulse Concept. PMID:23029412

Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 During Fear Conditioning

PubMed Central

Sindreu, Carlos Balet; Scheiner, Zachary S.; Storm, Daniel R.

2007-01-01

The cAMP and ERK/MAP kinase (MAPK) signal transduction pathways are critical for hippocampus-dependent memory, a process that depends on CREB-mediated transcription. However, the extent of crosstalk between these pathways and the downstream CREB kinase activated during memory formation have not been elucidated. Here we report that PKA, MAPK, and MSK1, a CREB kinase, are co-activated in a subset of hippocampal CA1 pyramidal neurons following contextual fear conditioning. Activation of PKA, MAPK, MSK1, and CREB is absolutely dependent on Ca2+-stimulated adenylyl cyclase activity. We conclude that adenylyl cyclase activity supports the activation of MAPK, and that MSK1 is the major CREB kinase activated during training for contextual memory. PMID:17196532

Spatial gradients in stream power and the implications for lateral and downstream transport of material during the 2013 Floods in Colorado and 2011 Irene Floods in Vermont, USA

NASA Astrophysics Data System (ADS)

Gartner, J. D.; Renshaw, C. E.; Magilligan, F. J.; Buraas, E. M.; Dethier, E.; Dade, W. B.

2014-12-01

Classic approaches to understand sediment transport and channel-hillslope coupling focus on magnitudes of forces at a point location or reach. Yet often overlooked are downstream gradients in forces along a river. Here we show a physical rationale supported by field evidence that downstream spatial gradients in sediment transport capacity affect lateral exchange of material in the form of landslides, bank failures and floodplain deposition. Taking advantage of the strong signals of near-channel deposition and erosion during the record-high 2011 Irene floods in Vermont and 2013 floods in Colorado, USA, we test if these spatial gradients can predict geomorphic response in flood events. Total stream power, an indicator of total sediment transport capacity, was mapped using GIS analysis along the Saxtons River (190 km2) and West Branch of White River (112 km2) in Vermont and Fourmile Creek (20 km2) and an unnamed creek on Mt Sanitas (7 km2) in Boulder, CO. These mountainous streams exhibit reach slopes of 0.5 to > 10%, with less steep reaches interspersed among steeper reaches. Near-channel erosion and deposition were quantified along 52 river km by pre/post satellite imagery, field surveys, and, when available, differencing of pre/post topography measured by aerial LiDAR. Zones of abundant mass wasting inputs—up to 11,000 m3 per km—were generally distinct from zones of abundant floodplain deposition—up to 30,000 m3 per km. Spatial patterns indicate that zones of abundant mass wasting into the channels align approximately with zones of down-flow increasing stream power. These reaches can convey material delivered from upstream plus additional lateral inputs of sediment. Conversely, reaches of abundant lateral flux out of the channel via near-channel deposition occur predominantly where mapped total stream power declines in the down-flow direction. These reaches appear unable to convey material supplied from upstream, which induces lateral deposition. The demonstrated interaction between downstream and lateral fluxes of material provides insight on physical controls on broad-scale geomorphic processes at channel margins as well as the sources and fates of matter transported by rivers, with implications for flood recovery and long-term river management.

Endocrine disruption and differential gene expression in sentinel fish on St. Lawrence Island, Alaska: Health implications for indigenous residents.

PubMed

von Hippel, Frank A; Miller, Pamela K; Carpenter, David O; Dillon, Danielle; Smayda, Lauren; Katsiadaki, Ioanna; Titus, Tom A; Batzel, Peter; Postlethwait, John H; Buck, C Loren

2018-03-01

People living a subsistence lifestyle in the Arctic are highly exposed to persistent organic pollutants, including polychlorinated biphenyls (PCBs). Formerly Used Defense (FUD) sites are point sources of PCB pollution; the Arctic contains thousands of FUD sites, many co-located with indigenous villages. We investigated PCB profiles and biological effects in freshwater fish (Alaska blackfish [Dallia pectoralis] and ninespine stickleback [Pungitius pungitius]) living upstream and downstream of the Northeast Cape FUD site on St. Lawrence Island in the Bering Sea. Despite extensive site remediation, fish remained contaminated with PCBs. Vitellogenin concentrations in males indicated exposure to estrogenic contaminants, and some fish were hypothyroid. Downstream fish showed altered DNA methylation in gonads and altered gene expression related to DNA replication, response to DNA damage, and cell signaling. This study demonstrates that, even after site remediation, contaminants from Cold War FUD sites in remote regions of the Arctic remain a potential health threat to local residents - in this case, Yupik people who had no influence over site selection and use by the United States military. Copyright © 2017 Elsevier Ltd. All rights reserved.

Kinetics of Hydrogen Oxidation Downstream of Lean Propane and Hydrogen Flames

NASA Technical Reports Server (NTRS)

Fine, Burton

1961-01-01

The decay of hydrogen was measured downstream of lean, flat, premixed hydrogen and propane-air flames seated on cooled porous burners. Experimental variables included temperature, pressure, initial equivalence ratio and diluent. Sampling of burned gas was done through uncooled quartz orifice probes, and the analysis was based on gas chromatography. An approximate treatment of the data in which diffusion was neglected led to the following rate expression for the zone downstream of hydrogen flames d[H (sub 2)] divided by (d times t) equals 1.7 times 10 (sup 10) [H (sub 2)] (sup 3) divided by (sub 2) [O (sub 2)]e (sup (-8100 divided by RT)) moles per liters per second. On the basis of a rate expression of this form, the specific rate constant for the reaction downstream of hydrogen flames was about three times as great as that determined downstream of propane flames. This result was explained on the basis of the existence of a steady state between hydrogen and carbon monoxide in the burned gas downstream of propane flames.

Greenhouse gas emissions from reservoir water surfaces: A ...

EPA Pesticide Factsheets

Collectively, reservoirs created by dams are thought to be an important source ofgreenhouse gases (GHGs) to the atmosphere. So far, efforts to quantify, model, andmanage these emissions have been limited by data availability and inconsistenciesin methodological approach. Here we synthesize worldwide reservoir methane,carbon dioxide, and nitrous oxide emission data with three main objectives: (1) togenerate a global estimate of GHG emissions from reservoirs, (2) to identify the bestpredictors of these emissions, and (3) to consider the effect of methodology onemission estimates. We estimate that GHG emission from reservoir water surfacesaccount for 0.8 (0.5-1.2) Pg CO2-equivalents per year, equal to ~1.3 % of allanthropogenic GHG emissions, with the majority (79%) of this forcing due tomethane. We also discuss the potential for several alternative pathways such as damdegassing and downstream emissions to contribute significantly to overall GHGemissions. Although prior studies have linked reservoir GHG emissions to systemage and latitude, we find that factors related to reservoir productivity are betterpredictors of emission. Finally, as methane contributed the most to total reservoirGHG emissions, it is important that future monitoring campaigns incorporatemethane emission pathways, especially ebullition. To inform the public.

A long-reach WDM passive optical network enabling broadcasting service with centralized light source

NASA Astrophysics Data System (ADS)

Liu, D.; Tang, M.; Fu, S.; Liu, D.; Shum, P.

2012-02-01

We propose a long-reach wavelength-division-multiplexed (WDM) passive optical network (PON) to provide conventional point-to-point (P2P) data and downstream broadcasting service simultaneously by superimposing, for each WDM channel, the differential-phase-shift-keying (DPSK) broadcasting signal with the subcarrier multiplexing (SCM) modulated downstream P2P signal, at the optical line terminal (OLT). In the optical network units (ONUs), by re-modulating part of the downstream signal with a reflective semiconductor optical amplifier (RSOA), we realize color-less ONUs for upstream data transmission. The proposed scheme is numerically verified with a 5 Gb/s downstream P2P signal and broadcasting services, as well as 2.5 Gb/s upstream data through a 60 km bidirectional fiber link. In particular, the influence of the downstream lightwave's optical carrier-subcarrier ratio (OCSR) on the system performance is also investigated.

The weathering of organic carbon and pyrite sulfur in Earth's crust and its importance for regulating atmospheric composition, seawater chemistry, and stable isotope records

NASA Astrophysics Data System (ADS)

Reinhard, C. T.; Planavsky, N.; Bolton, E. W.

2016-12-01

Earth's crust stores extremely large reservoirs of organic carbon and pyrite sulfur, and transient or secular changes in the sizes of these reservoirs have the capacity to dramatically alter atmospheric composition, climate, seawater acid-base chemistry, and the propagation of isotopic signals into the geologic record. This talk will present and discuss new quantitative approaches toward better understanding the factors that control organic carbon and pyrite sulfur weathering under a wide range of Earth surface conditions, as well as their downstream effects on seawater chemistry, stability of atmospheric pO2, and conventional interpretations of stable carbon isotope mass balance during pivotal events in Earth's biogeochemical evolution. In particular, we will focus on (1) development of a weathering-driven scaling between atmospheric pO2 and geologic carbon isotope signals that explains the relative stability of marine δ13C through time and provides a mechanism for protracted negative δ13C excursions during transient increases in atmospheric pO2; (2) experimental and theoretical approaches aimed at better understanding the role of pyrite sulfur weathering in stabilizing atmospheric pO2; and (3) the importance of redox balance in the sedimentary rock cycle for controlling the marine carbonate system and atmospheric pCO2.

Pharmacological AMP-kinase activators have compartment-specific effects on cell physiology.

PubMed

Kodiha, Mohamed; Ho-Wo-Cheong, Dennis; Stochaj, Ursula

2011-12-01

5'-AMP-activated kinase (AMPK) regulates numerous biological events and is an essential target for the treatment of type 2 diabetes. The objectives of the present study were first to determine the compartment-specific effects of three established AMPK activators on Thr172 phosphorylation of the α-subunit, an indicator of AMPK activation. Second, we examined how cytoplasmic and nuclear processes are modulated by pharmacological AMPK activators. Specifically, the impact of phenformin, resveratrol, and 5-aminoimidazole-4-carboxamide riboside (AICAR) on Thr172 phosphorylation in the cytoplasm and nucleus was quantified by different methods. To analyze how these activators change cell physiology, we measured the inactivation of acetyl-CoA-carboxylase 1, a predominantly cytoplasmic enzyme that is crucial for lipid metabolism. As a criterion for activities associated with the nucleus, de novo RNA synthesis in nucleoli was quantified. Our studies demonstrate that pharmacological activators of AMPK can alter the balance between nuclear and cytoplasmic AMPK pools. Thus, phenformin and resveratrol caused a strong activation of AMPK in the cytoplasm, whereas the effect was less pronounced in nuclei. By contrast, AICAR elicited a comparable rise in Thr172 phosphorylation in both compartments. Notably, these activators differed drastically in their effects on physiological processes that are located in distinct subcellular compartments. All compounds led to a substantial inactivation of acetyl-CoA-carboxylase 1 in the cytoplasm, with only minor changes to the nuclear enzyme. In the nucleolus, transcription was strongly inhibited by resveratrol, while a moderate inhibition was observed with phenformin and AICAR. Taken together, the compartment-specific phosphorylation of AMPK and downstream events are determined by the activator.

Mercury biogeochemistry in the Idrija River, Slovenia, from above the mine into the Gulf of Trieste

USGS Publications Warehouse

Hines, M.E.; Horvat, M.; Faganeli, J.; Bonzongo, J.-C.J.; Barkay, T.; Major, E.B.; Scott, K.J.; Bailey, E.A.; Warwick, J.J.; Lyons, W.B.

2000-01-01

The Idrija Mine is the second largest Hg mine in the world which operated for 500 years. Mercury (Hg)-laden tailings still line the banks, and the system is a threat to the Idrija River and water bodies downstream including the Soca/Isonzo River and the Gulf of Trieste in the northern Adriatic Sea. A multidisciplinary study was conducted in June 1998 on water samples collected throughout the Idrija and Soca River systems and waters and sediments in the Gulf. Total Hg in the Idrija River increased >20-fold downstream of the mine from 60 ng liter-1 with methyl mercury (MeHg) accounting for ~0.5%. Concentrations increased again downstream and into the estuary with MeHg accounting for nearly 1.5% of the total. While bacteria upstream of the mine did not contain mercury detoxification genes (mer), such genes were detected in bacteria collected downstream. Benthic macroinvertebrate diversity decreased downstream of the mine. Gulf waters near the river mouth contained up to 65 ng liter-1 total Hg with ~0.05 ng liter-1 MeHg. Gulf sediments near the river mouth contained 40 ??g g-1 total Hg with MeHg concentrations of about 3 ng g-1. Hg in sediment pore waters varied between 1 and 8 ng liter-1, with MeHg accounting for up to 85%. Hg methylation and MeHg demethylation were active in Gulf sediments with highest activities near the surface. MeHg was degraded by an oxidative pathway with >97% C released from MeHg as CO2. Hg methylation depth profiles resembled profiles of dissolved MeHg. Hg-laden waters still strongly impact the riverine, estuarine, and marine systems. Macroinvertebrates and bacteria in the Idrija River responded to Hg stress, and high Hg levels persist into the Gulf. Increases in total Hg and MeHg in the estuary demonstrate the remobilization of Hg, presumably as HgS dissolution and recycling. Gulf sediments actively produce MeHg, which enters bottom waters and presumably the marine food chain. (C) 2000 Academic Press.

Film-Cooling Heat-Transfer Measurements Using Liquid Crystals

NASA Technical Reports Server (NTRS)

Hippensteele, Steven A.

1997-01-01

The following topics are discussed: (1) The Transient Liquid-Crystal Heat-Transfer Technique; (2) 2-D Film-Cooling Heat-Transfer on an AlliedSignal Vane; and (3) Effects of Tab Vortex Generators on Surface Heat Transfer. Downstream of a Jet in Crossflow.

Cytotoxic 1-deoxysphingolipids are metabolized by a cytochrome P450-dependent pathway[S

PubMed Central

Alecu, Irina; Othman, Alaa; Penno, Anke; Saied, Essa M.; Arenz, Christoph; von Eckardstein, Arnold; Hornemann, Thorsten

2017-01-01

The 1-deoxysphingolipids (1-deoxySLs) are atypical sphingolipids (SLs) that are formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during SL synthesis. The 1-deoxySLs are toxic to neurons and pancreatic β-cells. Pathologically elevated 1-deoxySLs cause the inherited neuropathy, hereditary sensory autonomic neuropathy type 1 (HSAN1), and are also found in T2D. Diabetic sensory polyneuropathy (DSN) and HSAN1 are clinically very similar, suggesting that 1-deoxySLs may be implicated in both pathologies. The 1-deoxySLs are considered to be dead-end metabolites, as they lack the C1-hydroxyl group, which is essential for the canonical degradation of SLs. Here, we report a previously unknown metabolic pathway, which is capable of degrading 1-deoxySLs. Using a variety of metabolic labeling approaches and high-resolution high-accuracy MS, we identified eight 1-deoxySL downstream metabolites, which appear to be formed by cytochrome P450 (CYP)4F enzymes. Comprehensive inhibition and induction of CYP4F enzymes blocked and stimulated, respectively, the formation of the downstream metabolites. Consequently, CYP4F enzymes might be novel therapeutic targets for the treatment of HSAN1 and DSN, as well as for the prevention of T2D. PMID:27872144

Experimental study of the effects of flameholder geometry on emissions and performance of lean premixed combustors

NASA Technical Reports Server (NTRS)

Roffe, G.; Venkataramani, K. S.

1978-01-01

Emissions of NOx, CO, and unburned hydrocarbons (UHC) are reported for a lean premixed propane-air system at inlet conditions of 800K and 1MPa using twelve flameholder designs. The flameholders tested represent six design concepts with two values of blockage for each concept. Data were obtained at reference velocities of 35 m/s, 25 m/s and 20 m/s at combustor stations 10 cm and 30 cm downstream of the flameholders. Flameholder pressure drop was found to be a principal determinant of emissions performance. Designs producing larger pressure drops also produced less NOx, CO, and UHC emissions. The lean stability limit equivalence ratio was found to be approximately 0.35 for all designs. Flashback velocities (axial components in the flameholder passages) varied between 30 m/s and 40 m/s. A perforated plate flameholder was operated with a velocity as low as 23 m/s through the perforations at equivalence ratio 0.7 without producing flashback.

Performance evaluation of a biodiesel fuelled transportation engine retrofitted with a non-noble metal catalysed diesel oxidation catalyst for controlling unregulated emissions.

PubMed

Shukla, Pravesh Chandra; Gupta, Tarun; Agarwal, Avinash Kumar

2018-02-15

In present study, engine exhaust was sampled for measurement and analysis of unregulated emissions from a four cylinder transportation diesel engine using a state-of-the-art FTIR (Fourier transform infrared spectroscopy) emission analyzer. Test fuels used were Karanja biodiesel blend (B20) and baseline mineral diesel. Real-time emission measurements were performed for raw exhaust as well as exhaust sampled downstream of the two in-house prepared non-noble metal based diesel oxidation catalysts (DOCs) and a baseline commercial DOC based on noble metals. Two prepared non-noble metal based DOCs were based on Co-Ce mixed oxide and Lanthanum based perovskite catalysts. Perovskite based DOC performed superior compared to Co-Ce mixed oxide catalyst based DOC. Commercial noble metal based DOC was found to be the most effective in reducing unregulated hydrocarbon emissions in the engine exhaust, followed by the two in-house prepared non-noble metal based DOCs. Copyright © 2017 Elsevier B.V. All rights reserved.

A direct numerical simulation study of flame structure and stabilization of an experimental high Ka CH 4/air premixed jet flame

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Haiou; Hawkes, Evatt R.; Chen, Jacqueline H.

In the present work, a direct numerical simulation (DNS) of an experimental high Karlovitz number (Ka) CH 4/air piloted premixed flame was analyzed to study the inner structure and the stabilization mechanism of the turbulent flame. A reduced chemical mechanism for premixed CH 4/air combustion with NO x based on GRI-Mech3.0 was used, including 268 elementary reactions and 28 transported species. The evolution of the stretch factor, I0, indicates that the burning rate per unit flame surface area is considerably reduced in the near field and exhibits a minimum at x/D = 8. Downstream, the burning rate gradually increases. Themore » stretch factor is different between different species, suggesting the quenching of some reactions but not others. Comparison between the turbulent flame and strained laminar flames indicates that certain aspects of the mean flame structure can be represented surprisingly well by flamelets if changes in boundary conditions are accounted for and the strain rate of the mean flow is employed; however, the thickening of the flame due to turbulence is not captured. The spatial development of displacement speeds is studied at higher Ka than previous DNS. In contrast to almost all previous studies, the mean displacement speed conditioned on the flame front is negative in the near field, and the dominant contribution to the displacement speed is normal diffusion with the reaction contribution being secondary. Further downstream, reaction overtakes normal diffusion, contributing to a positive displacement speed. The negative displacement speed in the near field implies that the flame front situates itself in the pilot region where the inner structure of the turbulent flame is affected significantly, and the flame stabilizes in balance with the inward flow. Notably, in the upstream region of the turbulent flame, the main reaction contributing to the production of OH, H+O 2⇌O+OH (R35), is weak. Moreover, oxidation reactions, H 2+OH⇌H+H 2O (R79) and CO+OH⇌CO 2+H (R94), are influenced by H 2O and CO 2 from the pilot and are completely quenched. Hence, the entire radical pool of OH, H and O is affected. Furthermore, the fuel consumption layer remains comparably active and generates heat, mainly via the reaction CH 4+OH⇌CH 3+H 2O (R93).« less

A direct numerical simulation study of flame structure and stabilization of an experimental high Ka CH 4/air premixed jet flame

DOE PAGES

Wang, Haiou; Hawkes, Evatt R.; Chen, Jacqueline H.

2017-03-17

In the present work, a direct numerical simulation (DNS) of an experimental high Karlovitz number (Ka) CH 4/air piloted premixed flame was analyzed to study the inner structure and the stabilization mechanism of the turbulent flame. A reduced chemical mechanism for premixed CH 4/air combustion with NO x based on GRI-Mech3.0 was used, including 268 elementary reactions and 28 transported species. The evolution of the stretch factor, I0, indicates that the burning rate per unit flame surface area is considerably reduced in the near field and exhibits a minimum at x/D = 8. Downstream, the burning rate gradually increases. Themore » stretch factor is different between different species, suggesting the quenching of some reactions but not others. Comparison between the turbulent flame and strained laminar flames indicates that certain aspects of the mean flame structure can be represented surprisingly well by flamelets if changes in boundary conditions are accounted for and the strain rate of the mean flow is employed; however, the thickening of the flame due to turbulence is not captured. The spatial development of displacement speeds is studied at higher Ka than previous DNS. In contrast to almost all previous studies, the mean displacement speed conditioned on the flame front is negative in the near field, and the dominant contribution to the displacement speed is normal diffusion with the reaction contribution being secondary. Further downstream, reaction overtakes normal diffusion, contributing to a positive displacement speed. The negative displacement speed in the near field implies that the flame front situates itself in the pilot region where the inner structure of the turbulent flame is affected significantly, and the flame stabilizes in balance with the inward flow. Notably, in the upstream region of the turbulent flame, the main reaction contributing to the production of OH, H+O 2⇌O+OH (R35), is weak. Moreover, oxidation reactions, H 2+OH⇌H+H 2O (R79) and CO+OH⇌CO 2+H (R94), are influenced by H 2O and CO 2 from the pilot and are completely quenched. Hence, the entire radical pool of OH, H and O is affected. Furthermore, the fuel consumption layer remains comparably active and generates heat, mainly via the reaction CH 4+OH⇌CH 3+H 2O (R93).« less

Plume flowfield analysis of the shuttle primary Reaction Control System (RCS) rocket engine

NASA Technical Reports Server (NTRS)

Hueser, J. E.; Brock, F. J.

1990-01-01

A solution was generated for the physical properties of the Shuttle RCS 4000 N (900 lb) rocket engine exhaust plume flowfield. The modeled exhaust gas consists of the five most abundant molecular species, H2, N2, H2O, CO, and CO2. The solution is for a bare RCS engine firing into a vacuum; the only additional hardware surface in the flowfield is a cylinder (=engine mount) which coincides with the nozzle lip outer corner at X = 0, extends to the flowfield outer boundary at X = -137 m and is coaxial with the negative symmetry axis. Continuum gas dynamic methods and the Direct Simulation Monte Carlo (DSMC) method were combined in an iterative procedure to produce a selfconsistent solution. Continuum methods were used in the RCS nozzle and in the plume as far as the P = 0.03 breakdown contour; the DSMC method was used downstream of this continuum flow boundary. The DSMC flowfield extends beyond 100 m from the nozzle exit and thus the solution includes the farfield flow properties, but substantial information is developed on lip flow dynamics and thus results are also presented for the flow properties in the vicinity of the nozzle lip.

Activated platelet-derived growth factor β receptor and Ras-mitogen-activated protein kinase pathway in natural bovine urinary bladder carcinomas.

PubMed

Corteggio, Annunziata; Di Geronimo, Ornella; Roperto, Sante; Roperto, Franco; Borzacchiello, Giuseppe

2012-03-01

Bovine papillomavirus types 1 or 2 (BPV-1/2) are involved in the aetiopathogenesis of bovine urinary bladder cancer. BPV-1/2 E5 activates the platelet-derived growth factor β receptor (PDGFβR). The aim of this study was to analyse the Ras/mitogen-activated protein kinase (MAPK) pathway in relation to activation of PDGFβR in natural bovine urinary bladder carcinomas. Co-immunoprecipitation and Western blot analysis demonstrated that recruitment of growth factor receptor bound protein 2 (GRB-2) and Sos-1 to the activated PDGFβR was increased in carcinomas compared to normal tissues. Higher grade bovine urinary bladder carcinomas were associated with activation of Ras, but not with activation of downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (Mek 1/2) or extracellular signal-regulated kinase (Erk 1/2). Copyright © 2011 Elsevier Ltd. All rights reserved.

Mechanisms of carbon storage in mountainous headwater rivers

Treesearch

Ellen Wohl; Kathleen Dwire; Nicholas Sutfin; Lina Polvi; Roberto Bazan

2012-01-01

Published research emphasizes rapid downstream export of terrestrial carbon from mountainous headwater rivers, but little work focuses on mechanisms that create carbon storage along these rivers, or on the volume of carbon storage. Here we estimate organic carbon stored in diverse valley types of headwater rivers in Rocky Mountain National Park, CO, USA. We show that...

Impact of surfactants on the target recognition of Fab-conjugated PLGA nanoparticles.

PubMed

Kennedy, Patrick J; Perreira, Ines; Ferreira, Daniel; Nestor, Marika; Oliveira, Carla; Granja, Pedro L; Sarmento, Bruno

2018-06-01

Targeted drug delivery with nanoparticles (NPs) requires proper surface ligand presentation and availability. Surfactants are often used as stabilizers in the production of targeted NPs. Here, we evaluated the impact of surfactants on ligand functionalization and downstream molecular recognition. Our model system consisted of fluorescent poly(lactic-co-glycolic acid) (PLGA) NPs that were nanoprecipitated in one of a small panel of commonly-used surfactants followed by equivalent washes and conjugation of an engineered Fab antibody fragment. Size, polydispersity index and zeta potential were determined by dynamic light scattering and laser Doppler anemometry, and Fab presence on the NPs was assessed by enzyme-linked immunosorbent assay. Most importantly, Fab-decorated NP binding to the cell surface receptor was monitored by fluorescence-activated cell sorting. 2% polyvinyl alcohol, 1% sodium cholate, 0.5% Pluronic F127 (F127) and 2% Tween-80 were initially tested. Of the four surfactants tested, PLGA NPs in 0.5% F127 and 2% Tween-80 had the highest cell binding. These two surfactants were then retested in two different concentrations, 0.5% and 2%. The Fab-decorated PLGA NPs in 2% F127 had the highest cell binding. This study highlights the impact of common surfactants and their concentrations on the downstream targeting of ligand-decorated NPs. Similar principles should be applied in the development of future targeted nanosystems where surfactants are employed. Copyright © 2018 Elsevier B.V. All rights reserved.

The optimal atmospheric CO2 concentration for the growth of winter wheat (Triticum aestivum).

PubMed

Xu, Ming

2015-07-20

This study examined the optimal atmospheric CO2 concentration of the CO2 fertilization effect on the growth of winter wheat with growth chambers where the CO2 concentration was controlled at 400, 600, 800, 1000, and 1200 ppm respectively. I found that initial increase in atmospheric CO2 concentration dramatically enhanced winter wheat growth through the CO2 fertilization effect. However, this CO2 fertilization effect was substantially compromised with further increase in CO2 concentration, demonstrating an optimal CO2 concentration of 889.6, 909.4, and 894.2 ppm for aboveground, belowground, and total biomass, respectively, and 967.8 ppm for leaf photosynthesis. Also, high CO2 concentrations exceeding the optima not only reduced leaf stomatal density, length and conductance, but also changed the spatial distribution pattern of stomata on leaves. In addition, high CO2 concentration also decreased the maximum carboxylation rate (Vc(max)) and the maximum electron transport rate (J(max)) of leaf photosynthesis. However, the high CO2 concentration had little effect on leaf length and plant height. The optimal CO2 fertilization effect found in this study can be used as an indicator in selecting and breeding new wheat strains in adapting to future high atmospheric CO2 concentrations and climate change. Copyright © 2015. Published by Elsevier GmbH.

Simultaneous targeting of insulin-like growth factor-1 receptor and anaplastic lymphoma kinase in embryonal and alveolar rhabdomyosarcoma: a rational choice.

PubMed

van Gaal, J Carlijn; Roeffen, Melissa H S; Flucke, Uta E; van der Laak, Jeroen A W M; van der Heijden, Gwen; de Bont, Eveline S J M; Suurmeijer, Albert J H; Versleijen-Jonkers, Yvonne M H; van der Graaf, Winette T A

2013-11-01

Rhabdomyosarcoma (RMS) is an aggressive soft tissue tumour mainly affecting children and adolescents. Since survival of high-risk patients remains poor, new treatment options are awaited. The aim of this study is to investigate anaplastic lymphoma kinase (ALK) and insulin-like growth factor-1 receptor (IGF-1R) as potential therapeutic targets in RMS. One-hundred-and-twelve primary tumours (embryonal RMS (eRMS)86; alveolar RMS (aRMS)26) were collected. Expression of IGF-1R, ALK and downstream pathway proteins was evaluated by immunohistochemistry. The effect of ALK inhibitor NVP-TAE684 (Novartis), IGF-1R antibody R1507 (Roche) and combined treatment was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in cell lines (aRMS Rh30, Rh41; eRMS Rh18, RD). IGF-1R and ALK expression was observed in 72% and 92% of aRMS and 61% and 39% of eRMS, respectively. Co-expression was observed in 68% of aRMS and 32% of eRMS. Nuclear IGF-1R expression was an adverse prognostic factor in eRMS (5-year survival 46.9 ± 18.7% versus 84.4 ± 5.9%, p=0.006). In vitro, R1507 showed diminished viability predominantly in Rh41. NVP-TAE684 showed diminished viability in Rh41 and Rh30, and to a lesser extent in Rh18 and RD. Simultaneous treatment revealed synergistic activity against Rh41 and Rh30. Co-expression of IGF-1R and ALK is detected in eRMS and particularly in aRMS. As combined inhibition reveals synergistic cytotoxic effects, this combination seems promising and needs further investigation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Expression of a putative dioxygenase gene adjacent to an insertion mutation is involved in the short internodes of columnar apples (Malus × domestica).

PubMed

Okada, Kazuma; Wada, Masato; Moriya, Shigeki; Katayose, Yuichi; Fujisawa, Hiroko; Wu, Jianzhong; Kanamori, Hiroyuki; Kurita, Kanako; Sasaki, Harumi; Fujii, Hiroshi; Terakami, Shingo; Iwanami, Hiroshi; Yamamoto, Toshiya; Abe, Kazuyuki

2016-11-01

Determining the molecular mechanism of fruit tree architecture is important for tree management and fruit production. An apple mutant 'McIntosh Wijcik', which was discovered as a bud mutation from 'McIntosh', exhibits a columnar growth phenotype that is controlled by a single dominant gene, Co. In this study, the mutation and the Co gene were analyzed. Fine mapping narrowed the Co region to a 101 kb region. Sequence analysis of the Co region and the original wild-type co region identified an insertion mutation of an 8202 bp long terminal repeat (LTR) retroposon in the Co region. Segregation analysis using a DNA marker based on the insertion polymorphism showed that the LTR retroposon was closely associated with the columnar growth phenotype. RNA-seq and RT-PCR analysis identified a promising Co candidate gene (91071-gene) within the Co region that is specifically expressed in 'McIntosh Wijcik' but not in 'McIntosh'. The 91071-gene was located approximately 16 kb downstream of the insertion mutation and is predicted to encode a 2-oxoglutarate-dependent dioxygenase involved in an unknown reaction. Overexpression of the 91071-gene in transgenic tobaccos and apples resulted in phenotypes with short internodes, like columnar apples. These data suggested that the 8202 bp retroposon insertion in 'McIntosh Wijcik' is associated with the short internodes of the columnar growth phenotype via upregulated expression of the adjacent 91071-gene. Furthermore, the DNA marker based on the insertion polymorphism could be useful for the marker-assisted selection of columnar apples.

Improvement of film cooling effectiveness with a small downstream block body

NASA Astrophysics Data System (ADS)

Khorsi, A.; Guelailia, A.; Hamidou, M. K.

2016-07-01

The aim of this study is to predict the improvement in film cooling performance over a flat plate through a single row of cylindrical holes with different streamwise angles by using the Ansys CFX software package. In order to improve the film cooling effectiveness, a short crescent-shaped block is placed downstream of a cylindrical cooling hole. The numerical results of the cylindrical hole without the downstream short crescent-shaped block are compared with experimental data.

Quantitative Infrared Image Analysis Of Thermally-Thin Cellulose Surface Temperatures During Upstream and Downstream Microgravity Flame Spread from A Central Ignition Line

NASA Technical Reports Server (NTRS)

Olson, Sandra L.; Lee, J. R.; Fujita, O.; Kikuchi, M.; Kashiwagi, T.

2012-01-01

Surface view calibrated infrared images of ignition and flame spread over a thin cellulose fuel were obtained at 30 Hz during microgravity flame spread tests in the 10 second Japan Microgravity Center (JAMIC). The tests also used a color video of the surface view and color images of the edge view using 35 millimeter 1600 Kodak Ektapress film at 2 Hz. The cellulose fuel samples (50% long fibers from lumi pine and 50% short fibers from birch) were made with an area density of 60 grams per square meters. The samples were mounted in the center of a 12 centimeter wide by 16 centimeter tall flow duct that uses a downstream fan to draw the air through the flow duct. Samples were ignited after the experiment package was released using a straight hot wire across the center of the 7.5 centimeter wide by 14 centimeter long samples. One case, at 1 atmosphere 35%O2 in N2, at a forced flow of 10 centimeters per second, is presented here. In this case, as the test progresses, the single flame begins to separate into simultaneous upstream and downstream flames. Surface temperature profiles are evaluated as a function of time, and temperature gradients for upstream and downstream flame spread are measured. Flame spread rates from IR image data are compared to visible image spread rate data. IR blackbody temperatures are compared to surface thermocouple readings to evaluate the effective emissivity of the pyrolyzing surface. Preheat lengths are evaluated both upstream and downstream of the central ignition point. A surface energy balance estimates the net heat flux from the flame to the fuel surface along the length of the fuel.

Oleuropein and hydroxytyrosol activate GPER/ GPR30-dependent pathways leading to apoptosis of ER-negative SKBR3 breast cancer cells.

PubMed

Chimento, Adele; Casaburi, Ivan; Rosano, Camillo; Avena, Paola; De Luca, Arianna; Campana, Carmela; Martire, Emilia; Santolla, Maria Francesca; Maggiolini, Marcello; Pezzi, Vincenzo; Sirianni, Rosa

2014-03-01

We have previously demonstrated that oleuropein (OL) and hydroxytyrosol (HT) reduce 17β-estradiol-mediated proliferation in MCF-7 breast cancer (BC) cells without affecting the classical genomic action of estrogen receptor (ER), but activating instead the ERK1/2 pathway. Here, we hypothesized that this inhibition could be mediated by a G-protein-coupled receptor named GPER/GPR30. Using the ER-negative and GPER-positive SKBR3 BC cells as experimental model, we investigated the effects of OL and HT on GPER-mediated activation of downstream pathways. Docking simulations and ligand-binding studies evidenced that OL and HT are able to bind GPER. MTT cell proliferation assays revealed that both phenols reduced SKBR3 cell growth; this effect was abolished silencing GPER. Focusing on OL and HT GPER-mediated pathways, using Western blot analysis we showed a sustained ERK1/2 activation triggering an intrinsic apoptotic pathway. Showing that OL and HT work as GPER inverse agonists in ER-negative and GPER-positive SKBR3 BC cells, we provide novel insights into the potential of these two molecules as tools in the therapy of this subtype of BC. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, Tyler F; Jett, Robert Trent; Smith, John G.

A dike failure at the Tennessee Valley Authority Kingston Fossil Plant in East Tennessee, United States, in December 2008, released approximately 4.1 million m3 of coal ash into the Emory River. From 2009 through 2012, samples of mayfly nymphs ( Hexagenia bilineata) were collected each spring from sites in the Emory, Clinch, and Tennessee Rivers upstream and downstream of the spill. Samples were analyzed for 17 metals. Concentrations of metals were generally highest the first 2 miles downstream of the spill, and then decreased with increasing distance from the spill. Arsenic, B, Ba, Be, Mo, Sb, Se, Sr, and Vmore » appeared to have strong ash signatures, whereas Co, Cr, Cu, Ni, and Pb appeared to be associated with ash and other sources. Furthermore, the concentrations for most of these contaminants were modest and are unlikely to cause widespread negative ecological effects. Trends in Hg, Cd, and Zn suggested little (Hg) or no (Cd, Zn) association with ash. Temporal trends suggested that concentrations of ash-related contaminants began to subside after 2010, but because of the limited time period of that analysis (4 yr), further monitoring is needed to verify this trend. The present study provides important information on the magnitude of contaminant exposure to aquatic receptors from a major coal ash spill, as well as spatial and temporal trends for transport of the associated contaminants in a large open watershed. Environ Toxicol Chem 2016;35:1159 1171. Published 2015 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.« less

Transcriptome and metabolome analysis of plant sulfate starvation and resupply provides novel information on transcriptional regulation of metabolism associated with sulfur, nitrogen and phosphorus nutritional responses in Arabidopsis

PubMed Central

Bielecka, Monika; Watanabe, Mutsumi; Morcuende, Rosa; Scheible, Wolf-Rüdiger; Hawkesford, Malcolm J.; Hesse, Holger; Hoefgen, Rainer

2015-01-01

Sulfur is an essential macronutrient for plant growth and development. Reaching a thorough understanding of the molecular basis for changes in plant metabolism depending on the sulfur-nutritional status at the systems level will advance our basic knowledge and help target future crop improvement. Although the transcriptional responses induced by sulfate starvation have been studied in the past, knowledge of the regulation of sulfur metabolism is still fragmentary. This work focuses on the discovery of candidates for regulatory genes such as transcription factors (TFs) using ‘omics technologies. For this purpose a short term sulfate-starvation/re-supply approach was used. ATH1 microarray studies and metabolite determinations yielded 21 TFs which responded more than 2-fold at the transcriptional level to sulfate starvation. Categorization by response behaviors under sulfate-starvation/re-supply and other nutrient starvations such as nitrate and phosphate allowed determination of whether the TF genes are specific for or common between distinct mineral nutrient depletions. Extending this co-behavior analysis to the whole transcriptome data set enabled prediction of putative downstream genes. Additionally, combinations of transcriptome and metabolome data allowed identification of relationships between TFs and downstream responses, namely, expression changes in biosynthetic genes and subsequent metabolic responses. Effect chains on glucosinolate and polyamine biosynthesis are discussed in detail. The knowledge gained from this study provides a blueprint for an integrated analysis of transcriptomics and metabolomics and application for the identification of uncharacterized genes. PMID:25674096

N2 and CO2 capillary breakthrough experiments on Opalinus Clay

NASA Astrophysics Data System (ADS)

Amann, Alexandra; Busch, Andreas; Krooss, Bernhard M.

2013-04-01

The aim of this project was to identify the critical capillary pressures on the drainage and the imbibition path for clay-rich rocks, at a burial depth of 1500 m (30 MPa confining pressure, 45°C). The experiments were performed on fully water-saturated sample plugs of 38 mm diameter and 5 to 20 mm length. The capillary breakthrough pressure was determined by step-wise increase of the differential pressure (drainage), the capillary snap-off pressure was determined from the final pressure difference at the end of a spontaneous imbibition phase. The confining pressure was kept constant throughout the experiment, which resulted in a continuous change of effective stress. The measurements were performed in a closed system and the pressure response was interpreted in terms of different flow mechanisms (diffusion-controlled vs. viscous flow). In total, four breakthrough experiments with N2 and five experiments with CO2 were conducted. Because of very low flow rates and high critical capillary pressures the experiments took rather long. In some cases the experiments were allowed to run for half a year (drainage experiments). Substantial differences were observed between gas breakthrough (drainage) and snap-off (imbibition) pressures. As expected, breakthrough pressures were always higher than the snap-off pressures. For three samples a pbreakthrough/psnap-off ratio of 1.6 to 1.9 was observed, for one sample a ratio of 4. A clear permeability-capillary pressure relationship could not be identified. Based on (omnidirectional) Hg-injection porosimetry results, and assuming perfectly water wet mineral surfaces, gas breakthrough pressures were predicted to occur at approximately 16 MPa for N2 and 5.7 MPa for CO2. The gas breakthrough experiments, however, produced different results. Even though a relatively homogeneous sample set was chosen, with permeability coefficients ranging between 1E-21 and 6E-21 m², the critical capillary breakthrough pressures for nitrogen ranged between 3.4 and 12.3 MPa and snap-off pressures from 0.5 to 6.4 MPa. The CO2 experiments yielded breakthrough pressures of 14.0 to 17.5 MPa and snap-off pressures of 3.5 to 10 MPa. No significant changes in single-phase water permeability coefficients before and after the gas breakthrough experiments were observed. In our contribution we will discuss the following points: 1. Gas fluxes occurring during gas breakthrough experiments may be extremely low. Therefore an unambigous identification of gas breakthrough is not always possible. Besides viscous or diffusive transport, dissolution of CO2 in the pore water may affect the observed pressure changes in the upstream and downstream compartments. All of these processes occur simultaneously and can only be partly discriminated. Gas fluxes detected during the diffusion-controlled flow regimes result in nominal effective gas permeability coefficients as low as 6E-25 m² to 7E-24m². 2. The application of purely capillary-controlled flow models may not be justified. o Gas breakthrough is controlled by effective stress, i.e. the opening of pores or small fissures. o Assumptions about wettability (completely water-wet mineral surfaces) may be incorrect.

Treatment of rats with Jiangzhi Capsule improves liquid fructose-induced fatty liver: modulation of hepatic expression of SREBP-1c and DGAT-2.

PubMed

Zhao, Yuanyang; Pan, Yongquan; Yang, Yifan; Batey, Robert; Wang, Jianwei; Li, Yuhao

2015-06-02

Jiangzhi Capsule is an Australian listed patented traditional Chinese medicine and has been used for management of lipid abnormalities over the past 10 years. To obtain a better understanding regarding Jiangzhi Capsule, the present study investigated the effects and underlying mechanisms of Jiangzhi Capsule on chronic fructose overconsumption-induced lipid abnormalities. Male rats were treated with liquid fructose in their drinking water over 14 weeks. Jiangzhi Capsule was co-administered (once daily, by oral gavage) during the last 7 weeks. Indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by real-time PCR, Western blot and/or immunohistochemistry. Treatment with Jiangzhi Capsule (100 mg/kg) attenuated fructose-induced excessive triglyceride accumulation and Oil Red O-stained area in the liver. This effect was accompanied by amelioration of hyperinsulinemia. There was no significant difference in intakes of fructose and chow, and body weight between fructose control and fructose Jiangzhi Capsule-treated groups. Mechanistically, Jiangzhi Capsule downregulated fructose-stimulated hepatic overexpression of sterol regulatory element binding protein (SREBP)-1/1c at the mRNA and protein levels. Accordingly, the SREBP-1c downstream genes, acetyl-CoA carboxylase-1 and stearoyl-CoA desaturase-1, were also inhibited. In addition, acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver was also inhibited after Jiangzhi Capsule treatment. In contrast, Jiangzhi Capsule affected neither carbohydrate response element binding protein, peroxisome proliferator-activated receptor (PPAR)-gamma and DGAT-1, nor PPAR-alpha and its target genes. These findings demonstrate the anti-steatotic action of Jiangzhi Capsule in fructose-fed rats, and modulation of hepatic SREBP-1c and DGAT-2 involved in hepatic de novo synthesis of fatty acids and triglyceride, respectively. Our findings provide an evidence-based and mechanistic understanding of Jiangzhi Capsule supporting its application for the prevention and/or treatment of fatty liver and its associated disorders in clinical practice.

Methylation of Hg downstream from the Bonanza Hg mine, Oregon

USGS Publications Warehouse

Gray, John E.; Hines, Mark E.; Krabbenhoft, David P.; Thoms, Bryn

2012-01-01

Speciation of Hg and conversion to methyl-Hg were evaluated in stream sediment, stream water, and aquatic snails collected downstream from the Bonanza Hg mine, Oregon. Total production from the Bonanza mine was >1360t of Hg, during mining from the late 1800s to 1960, ranking it as an intermediate sized Hg mine on an international scale. The primary objective of this study was to evaluate the distribution, transport, and methylation of Hg downstream from a Hg mine in a coastal temperate climatic zone. Data shown here for methyl-Hg, a neurotoxin hazardous to humans, are the first reported for sediment and water from this area. Stream sediment collected from Foster Creek flowing downstream from the Bonanza mine contained elevated Hg concentrations that ranged from 590 to 71,000ng/g, all of which (except the most distal sample) exceeded the probable effect concentration (PEC) of 1060ng/g, the Hg concentration above which harmful effects are likely to be observed in sediment-dwelling organisms. Concentrations of methyl-Hg in stream sediment collected from Foster Creek varied from 11 to 62ng/g and were highly elevated compared to regional baseline concentrations (0.11-0.82ng/g) established in this study. Methyl-Hg concentrations in stream sediment collected in this study showed a significant correlation with total organic C (TOC, R2=0.62), generally indicating increased methyl-Hg formation with increasing TOC in sediment. Isotopic-tracer methods indicated that several samples of Foster Creek sediment exhibited high rates of Hg-methylation. Concentrations of Hg in water collected downstream from the mine varied from 17 to 270ng/L and were also elevated compared to baselines, but all were below the 770ng/L Hg standard recommended by the USEPA to protect against chronic effects to aquatic wildlife. Concentrations of methyl-Hg in the water collected from Foster Creek ranged from 0.17 to 1.8ng/L, which were elevated compared to regional baseline sites upstream and downstream from the mine that varied from <0.02 to 0.22ng/L. Aquatic snails collected downstream from the mine were elevated in Hg indicating significant bioavailability and uptake of Hg by these snails. Results for sediment and water indicated significant methyl-Hg formation in the ecosystem downstream from the Bonanza mine, which is enhanced by the temperate climate, high precipitation in the area, and high organic matter.

Unveiling the biotransformation mechanism of indole in a Cupriavidus sp. strain.

PubMed

Qu, Yuanyuan; Ma, Qiao; Liu, Ziyan; Wang, Weiwei; Tang, Hongzhi; Zhou, Jiti; Xu, Ping

2017-12-01

Indole, an important signaling molecule as well as a typical N-heterocyclic aromatic pollutant, is widespread in nature. However, the biotransformation mechanisms of indole are still poorly studied. Here, we sought to unlock the genetic determinants of indole biotransformation in strain Cupriavidus sp. SHE based on genomics, proteomics and functional studies. A total of 177 proteins were notably altered (118 up- and 59 downregulated) in cells grown in indole mineral salt medium when compared with that in sodium citrate medium. RT-qPCR and gene knockout assays demonstrated that an indole oxygenase gene cluster was responsible for the indole upstream metabolism. A functional indole oxygenase, termed IndA, was identified in the cluster, and its catalytic efficiency was higher than those of previously reported indole oxidation enzymes. Furthermore, the indole downstream metabolism was found to proceed via the atypical CoA-thioester pathway rather than conventional gentisate and salicylate pathways. This unusual pathway was catalyzed by a conserved 2-aminobenzoyl-CoA gene cluster, among which the 2-aminobenzoyl-CoA ligase initiated anthranilate transformation. This study unveils the genetic determinants of indole biotransformation and will provide new insights into our understanding of indole biodegradation in natural environments and its functional studies. © 2017 John Wiley & Sons Ltd.

Effects of Deposition Parameters on Thin Film Properties of Silicon-Based Electronic Materials Deposited by Remote Plasma-Enhanced Chemical-Vapor Deposition

NASA Astrophysics Data System (ADS)

Theil, Jeremy Alfred

The motivation of this thesis is to discuss the major issues of remote plasma enhanced chemical vapor deposition (remote PECVD) that affect the properties Si-based thin films. In order to define the issues required for process optimization, the behavior of remote PECVD process must be understood. The remote PECVD process is defined as having four segments: (1) plasma generation, (2) excited species extraction, (3) excited species/downstream gas mixing, and (4) surface reaction. The double Langmuir probe technique is employed to examine plasma parameters under 13.56 MHz and 2.54 GHz excitation. Optical emission spectroscopy is used to determine changes in the excited states of radiating species in the plasma afterglow. Mass spectrometry is used to determine the excitation and consumption of process gases within the reactor during film growth. Various analytical techniques such as infrared absorption spectroscopy, (ir), high resolution transmission electron microscopy, (HRTEM), and reflected high energy electron diffraction, (RHEED), are used to ascertain film properties. The results of the Langmuir probe show that plasma coupling is frequency dependent and that the capacitive coupling mode is characterized by orders of magnitude higher electron densities in the reactor than inductive coupling. These differences can be manifested in the degree to which a hydrogenated amorphous silicon, a-Si:H, component co-deposition reaction affects film stoichiometry. Mass spectrometry shows that there is an additional excitation source in the downstream glow. In addition the growth of microcrystalline silicon, muc-Si, is correlated with the decrease in the production of disilane and heavier Si-containing species. Chloronium, H_2 Cl^{+}, a super acid ion is identified for the first time in a CVD reactor. It forms from plasma fragmentation of SiH_2 Cl_2, and H_2 . Addition of impurity gases was shown not to affect the electron temperature of the plasma. By products of deposition reactions can affect film properties by post -deposition reactions with the film. In the case of SiO _2 film growth, residual H _2O is shown to create OH groups within the film by reacting with distorted Si-O-Si bonding groups.

The Effect of Sedimentary Basins on Through-Passing Short-Period Surface Waves

NASA Astrophysics Data System (ADS)

Feng, L.; Ritzwoller, M. H.

2017-12-01

Surface waves propagating through sedimentary basins undergo elastic wave field complications that include multiple scattering, amplification, the formation of secondary wave fronts, and subsequent wave front healing. Unless these effects are accounted for accurately, they may introduce systematic bias to estimates of source characteristics, the inference of the anelastic structure of the Earth, and ground motion predictions for hazard assessment. Most studies of the effects of basins on surface waves have centered on waves inside the basins. In contrast, we investigate wave field effects downstream from sedimentary basins, with particular emphasis on continental basins and propagation paths, elastic structural heterogeneity, and Rayleigh waves at 10 s period. Based on wave field simulations through a recent 3D crustal and upper mantle model of East Asia, we demonstrate significant Rayleigh wave amplification downstream from sedimentary basins in eastern China such that Ms measurements obtained on the simulated wave field vary by more than a magnitude unit. We show that surface wave amplification caused by basins results predominantly from elastic focusing and that amplification effects produced through 3D basin models are reproduced using 2D membrane wave simulations through an appropriately defined phase velocity map. The principal characteristics of elastic focusing in both 2D and 3D simulations include (1) retardation of the wave front inside the basins; (2) deflection of the wave propagation direction; (3) formation of a high amplitude lineation directly downstream from the basin bracketed by two low amplitude zones; and (4) formation of a secondary wave front. Finally, by comparing the impact of elastic focusing with anelastic attenuation, we argue that on-continent sedimentary basins are expected to affect surface wave amplitudes more strongly through elastic focusing than through the anelastic attenuation.

Influence of deoxynivalenol on NF-kappaB activation and IL-8 secretion in human intestinal Caco-2 cells.

PubMed

Van De Walle, Jacqueline; Romier, Béatrice; Larondelle, Yvan; Schneider, Yves-Jacques

2008-04-01

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. In human intestinal Caco-2 cells, DON activates the mitogen-activated protein kinases (MAPKs). We hypothesized a link between DON ingestion and intestinal inflammation, and used Caco-2 cells to assess the effects of DON, at plausible intestinal concentrations (250-10,000 ng/ml), on inflammatory mediators acting downstream the MAPKs cascade i.e. activation of nuclear factor-kappaB (NF-kappaB) and interleukin-8 (IL-8) secretion. In addition, Caco-2 cells were co-exposed to pro-inflammatory stimuli in order to mimic an inflamed intestinal epithelium. Dose-dependent increases in NF-kappaB activity and IL-8 secretion were observed, reaching 1.4- and 7.6-fold, respectively using DON at 10 microg/ml. Phosphorylation of inhibitor-kappaB (IkappaB) increased (1.6-fold) at DON levels <0.5 microg/ml. Exposure of Caco-2 cells to pro-inflammatory agents, i.e. 25 ng/ml interleukin-1beta, 100 ng/ml tumor necrosis factor-alpha or 10 microg/ml lipopolysaccharides, activated NF-kappaB and increased IL-8 secretion. Synergistic interactions between these stimuli and DON were observed. These data show that DON induces NF-kappaB activation and IL-8 secretion dose-dependently in Caco-2 cells, and this effect was accentuated upon pro-inflammatory stimulation, suggesting DON exposure could cause or exacerbate intestinal inflammation.

Icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone.

PubMed

Liu, Weidong; Mao, Li; Ji, Feng; Chen, Fengli; Wang, Shouguo; Xie, Yue

2017-01-10

The potential effect of icariside II on dexamethasone-induced osteoblast cell damages was evaluated here. In MC3T3-E1 osteoblastic cells and the primary murine osteoblasts, co-treatment with icariside II dramatically attenuated dexamethasone- induced cell death and apoptosis. Icariside II activated Akt signaling, which is required for its actions in osteoblasts. Akt inhibitors (LY294002, perifosine and MK-2206) almost abolished icariside II-induced osteoblast cytoprotection against dexamethasone. Further studies showed that icariside II activated Nrf2 signaling, downstream of Akt, to inhibit dexamethasone-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary osteoblasts. On the other hand, Nrf2 shRNA knockdown inhibited icariside II-induced anti-dexamethasone cytoprotection in MC3T3-E1 cells. Finally, we showed that icariside II induced heparin-binding EGF (HB-EGF) production and EGFR trans-activation in MC3T3-E1 cells. EGFR inhibition, via anti-HB-EGF antibody, EGFR inhibitor AG1478 or EGFR shRNA knockdown, almost blocked icariside II-induced Akt-Nrf2 activation in MC3T3-E1 cells. Collectively, we conclude that icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone. Icariside II might have translational value for the treatment of dexamethasone-associated osteoporosis/osteonecrosis.

Proteasomal Ubiquitin Receptor RPN-10 Controls Sex Determination in Caenorhabditis elegans

PubMed Central

Shimada, Masumi; Kanematsu, Kenji; Tanaka, Keiji; Yokosawa, Hideyoshi

2006-01-01

The ubiquitin-binding RPN-10 protein serves as a ubiquitin receptor that delivers client proteins to the 26S proteasome. Although ubiquitin recognition is an essential step for proteasomal destruction, deletion of the rpn-10 gene in yeast does not influence viability, indicating redundancy of the substrate delivery pathway. However, their specificity and biological relevance in higher eukaryotes is still enigmatic. We report herein that knockdown of the rpn-10 gene, but not any other proteasome subunit genes, sexually transforms hermaphrodites to females by eliminating hermaphrodite spermatogenesis in Caenorhabditis elegans. The feminization phenotype induced by deletion of the rpn-10 gene was rescued by knockdown of tra-2, one of sexual fate decision genes promoting female development, and its downstream target tra-1, indicating that the TRA-2–mediated sex determination pathway is crucial for the Δrpn-10–induced sterile phenotype. Intriguingly, we found that co-knockdown of rpn-10 and functionally related ubiquitin ligase ufd-2 overcomes the germline-musculinizing effect of fem-3(gf). Furthermore, TRA-2 proteins accumulated in rpn-10-defective worms. Our results show that the RPN-10–mediated ubiquitin pathway is indispensable for control of the TRA-2–mediated sex-determining pathway. PMID:17050737

Genetic Ablation of Calcium-independent Phospholipase A2γ (iPLA2γ) Attenuates Calcium-induced Opening of the Mitochondrial Permeability Transition Pore and Resultant Cytochrome c Release*

PubMed Central

Moon, Sung Ho; Jenkins, Christopher M.; Kiebish, Michael A.; Sims, Harold F.; Mancuso, David J.; Gross, Richard W.

2012-01-01

Herein, we demonstrate that calcium-independent phospholipase A2γ (iPLA2γ) is a critical mechanistic participant in the calcium-induced opening of the mitochondrial permeability transition pore (mPTP). Liver mitochondria from iPLA2γ−/− mice were markedly resistant to calcium-induced swelling in the presence or absence of phosphate in comparison with wild-type littermates. Furthermore, the iPLA2γ enantioselective inhibitor (R)-(E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one ((R)-BEL) was markedly more potent than (S)-BEL in inhibiting mPTP opening in mitochondria from wild-type liver in comparison with hepatic mitochondria from iPLA2γ−/− mice. Intriguingly, low micromolar concentrations of long chain fatty acyl-CoAs and the non-hydrolyzable thioether analog of palmitoyl-CoA markedly accelerated Ca2+-induced mPTP opening in liver mitochondria from wild-type mice. The addition of l-carnitine enabled the metabolic channeling of acyl-CoA through carnitine palmitoyltransferases (CPT-1/2) and attenuated the palmitoyl-CoA-mediated amplification of calcium-induced mPTP opening. In contrast, mitochondria from iPLA2γ−/− mice were insensitive to fatty acyl-CoA-mediated augmentation of calcium-induced mPTP opening. Moreover, mitochondria from iPLA2γ−/− mouse liver were resistant to Ca2+/t-butyl hydroperoxide-induced mPTP opening in comparison with wild-type littermates. In support of these findings, cytochrome c release from iPLA2γ−/− mitochondria was dramatically decreased in response to calcium in the presence or absence of either t-butyl hydroperoxide or phenylarsine oxide in comparison with wild-type littermates. Collectively, these results identify iPLA2γ as an important mechanistic component of the mPTP, define its downstream products as potent regulators of mPTP opening, and demonstrate the integrated roles of mitochondrial bioenergetics and lipidomic flux in modulating mPTP opening promoting the activation of necrotic and necroapoptotic pathways of cell death. PMID:22778252

Effectiveness of carbon dioxide removal in lowering atmospheric CO2 and reversing global warming in the context of 1.5 degrees

NASA Astrophysics Data System (ADS)

Zickfeld, K.; Azevedo, D.

2017-12-01

The majority of emissions scenarios that limit warming to 2°C, and nearly all emission scenarios that do not exceed 1.5°C warming by the year 2100 require artificial removal of CO2 from the atmosphere. Carbon dioxide removal (CDR) technologies in these scenarios are required to offset emissions from sectors that are difficult or costly to decarbonize and to generate global `net negative' emissions, allowing to compensate for earlier emissions and to meet long-term climate stabilization targets after overshoot. Only a few studies have explored the Earth system response to CDR and large uncertainties exist regarding the effect of CDR on the carbon cycle and its effectiveness in reversing climate impacts after overshoot. Here we explore the effectiveness of CDR in lowering atmospheric CO2 ("carbon cycle effectiveness") and cool global climate ("cooling effectiveness"). We force the University of Victoria Earth System Climate Model, a model of intermediate complexity, with a set of negative CO2 emissions pulses of different magnitude and applied from different background atmospheric CO2 concentrations. We find the carbon cycle effectiveness of CDR - defined as the change in atmospheric CO2 per unit CO2 removed - decreases with the amount of CO2 removed from the atmosphere and increases at higher background CO2 concentrations from which CDR is applied due to nonlinear responses of carbon sinks to CO2 and climate. The cooling effectiveness - defined as the change in global mean surface air temperature per unit CO2 removed - on the other hand, is largely insensitive to the amount of CO2 removed, but decreases if CDR is applied at higher atmospheric CO2 concentrations, due to the logarithmic relationship between atmospheric CO2 and radiative forcing. Based on our results we conclude that CDR is more effective in restoring a lower atmospheric CO2 concentration and reversing impacts directly linked to CO2 at lower levels of overshoot. CDR's effectiveness in restoring a cooler climate, on the other hand, is largely insensitive to the level of overshoot.

Caspar Creek experimental watersheds: cumulative effects of forest practices on downstream resources

Treesearch

Anne M. Rosenthal; Thomas E. Featured: Lisle

2005-01-01

Research at Caspar Creek provides information that helps forest managers assess and predict the environmental effects of forest practices and natural disturbances on downstream resources. Monitoring long-term effects and adapting practices can help protect and restore water quality and fish habitat in Northern California.

RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation.

PubMed

Wu, Xiangbing; Walker, Chandler L; Lu, Qingbo; Wu, Wei; Eddelman, Daniel B; Parish, Jonathan M; Xu, Xiao-Ming

2017-11-01

Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A 2 (cPLA 2 ), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10th thoracic (T10) vertebral level. We found that co-administration of TNF-α and glutamate induced spinal neuron death, and activation of RhoA, Rho kinase and cPLA 2 . Inhibition of RhoA, Rho kinase and cPLA 2 significantly reduced TNF-α/glutamate-induced cell death by 33, 52 and 43 %, respectively (p < 0.001). Inhibition of RhoA and Rho kinase also significantly downregulated cPLA 2 activation by 66 and 60 %, respectively (p < 0.01). Furthermore, inhibition of RhoA and Rho kinase reduced the release of arachidonic acid, a downstream substrate of cPLA 2 . The immunofluorescence staining showed that ROCK 1 or ROCK 2 , two isoforms of Rho kinase, was co-localized with cPLA 2 in neuronal cytoplasm. Interestingly, co-immunoprecipitation (Co-IP) assay showed that ROCK 1 or ROCK 2 bonded directly with cPLA 2 and phospho-cPLA 2 . When the Rho kinase inhibitor Y27632 was applied in mice with T10 contusion injury, it significantly decreased cPLA 2 activation and expression and reduced injury-induced apoptosis at and close to the lesion site. Taken together, our results reveal a novel mechanism of RhoA/Rho kinase-mediated neuronal death through regulating cPLA 2 activation.

Downstream movement of mature eels in a hydroelectric reservoir in New Zealand

USGS Publications Warehouse

Watene, E.M.; Boubee, J.A.T.; Haro, A.

2003-01-01

This study investigates the behavior of migrant eels as they approached the Patea hydroelectric dam on the West Coast of the North Island, New Zealand. Seventeen mature migrant eels (870-1,240 mm; 2,000-6,380 g) were implanted with coded acoustic transmitters and released. Their movements in the reservoir were monitored for 14 months with stationary data logging and manual tracking receivers. The downstream migration of sexually maturing eels was found to occur mainly at night, usually during, or immediately after, rainfall events. Eels tended to travel at the surface, within the upper 4 m of the water column, at speeds ranging from 16 to 89 cm/s. Upon reaching the headrace, eels typically spent time searching, presumably for an unobstructed downstream route. In order to aid downstream passage of eels at the Patea Dam, power station operators began spillway opening trials during peak migration periods. Although this allowed some migrant eels to safely pass over the dam, information on the relative effectiveness and cost of this method over other possible mitigation methods is still required. ?? Copyright by the American Fisheries Society 2003.

Quantifying spatially and temporally explicit CO 2 fertilization effects on global terrestrial ecosystem carbon dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Shaoqing; Zhuang, Qianlai; Chen, Min

Current terrestrial ecosystem models are usually driven with global average annual atmospheric carbon dioxide (CO 2) concentration data at the global scale. However, high-precision CO 2 measurement from eddy flux towers showed that seasonal, spatial surface atmospheric CO 2 concentration differences were as large as 35 ppmv and the site-level tests indicated that the CO 2 variation exhibited different effects on plant photosynthesis. Here we used a process-based ecosystem model driven with two spatially and temporally explicit CO 2 data sets to analyze the atmospheric CO 2 fertilization effects on the global carbon dynamics of terrestrial ecosystems from 2003 tomore » 2010. Our results demonstrated that CO 2 seasonal variation had a negative effect on plant carbon assimilation, while CO2 spatial variation exhibited a positive impact. When both CO 2 seasonal and spatial effects were considered, global gross primary production and net ecosystem production were 1.7 Pg C•yr –1 and 0.08 Pg C•yr –1 higher than the simulation using uniformly distributed CO 2 data set and the difference was significant in tropical and temperate evergreen broadleaf forest regions. Moreover, this study suggests that the CO 2 observation network should be expanded so that the realistic CO 2 variation can be incorporated into the land surface models to adequately account for CO 2 fertilization effects on global terrestrial ecosystem carbon dynamics.« less

Quantifying spatially and temporally explicit CO 2 fertilization effects on global terrestrial ecosystem carbon dynamics

DOE PAGES

Liu, Shaoqing; Zhuang, Qianlai; Chen, Min; ...

2016-07-25

Current terrestrial ecosystem models are usually driven with global average annual atmospheric carbon dioxide (CO 2) concentration data at the global scale. However, high-precision CO 2 measurement from eddy flux towers showed that seasonal, spatial surface atmospheric CO 2 concentration differences were as large as 35 ppmv and the site-level tests indicated that the CO 2 variation exhibited different effects on plant photosynthesis. Here we used a process-based ecosystem model driven with two spatially and temporally explicit CO 2 data sets to analyze the atmospheric CO 2 fertilization effects on the global carbon dynamics of terrestrial ecosystems from 2003 tomore » 2010. Our results demonstrated that CO 2 seasonal variation had a negative effect on plant carbon assimilation, while CO2 spatial variation exhibited a positive impact. When both CO 2 seasonal and spatial effects were considered, global gross primary production and net ecosystem production were 1.7 Pg C•yr –1 and 0.08 Pg C•yr –1 higher than the simulation using uniformly distributed CO 2 data set and the difference was significant in tropical and temperate evergreen broadleaf forest regions. Moreover, this study suggests that the CO 2 observation network should be expanded so that the realistic CO 2 variation can be incorporated into the land surface models to adequately account for CO 2 fertilization effects on global terrestrial ecosystem carbon dynamics.« less

Mixing Enhancement in a Lobed Injector

NASA Technical Reports Server (NTRS)

Smith, L. L.; Majamaki, A. J.; Lam, I. T.; Delabroy, O.; Karagozian, A. R.; Marble, F. E.; Smith, O. I.

1997-01-01

An experimental investigation of the non-reactive mixing processes associated with a lobed fuel injector in a coflowing air stream is presented. The lobed fuel injector is a device which generates streamwise vorticity, producing high strain rates which can enhance the mixing of reactants while delaying ignition in a controlled manner. The lobed injectors examined in the present study consist of two corrugated plates between which a fuel surrogate, CO2, is injected into coflowing air. Acetone is seeded in the CO2 supply as a fuel marker. Comparison of two alternative lobed injector geometries is made with a straight fuel injector to determine net differences in mixing and strain fields due to streamwise vorticity generation. Planar laser-induced fluorescence (PLIF) of the seeded acetone yields two-dimensional images of the scalar concentration field at various downstream locations, from which local mixing and scalar dissipation rates are computed. It is found that the lobed injector geometry can enhance molecular mixing and create a highly strained flowfield, and that the strain rates generated by scalar energy dissipation can potentially delay ignition in a reacting flowfield.

The Effects of Dams on Downstream Channel Characteristics in Pennsylvania and Maryland: Assessing the Potential Consequences of Dam Removal

NASA Astrophysics Data System (ADS)

Skalak, K. J.; Pizzuto, J. E.; Jenkins, P.

2003-12-01

The potential downstream effects of dam removal were assessed on fifteen sites of varying dam size and characteristics in Pennsylvania and Maryland. The dams ranged in size from a 30 cm high fish weir to a water supply dam 57 m high. Stream order ranged from 1 to 4. The dams are located in watersheds with varying degrees of human disturbance and urbanization. The dams are also operated differently, with significant consequences for hydraulic residence time and downstream flow variability. Most streams were alluvial, but 6 of the reaches were clearly bedrock channels. We hypothesize that the channel upstream, which is unaffected by the dam, will provide an accurate model for the channel downstream of the dam long after dam removal. Therefore, reaches upstream and downstream of the dam were compared to determine the effects of the dam as well as the condition of the stream that will ultimately develop decades after dam removal. Surprisingly, the dams had no consistent influence on channel morphology. However, the percentage of sand is significantly lower downstream than upstream: the mean % sand downstream is 11.47%, while the mean % sand upstream is 21.39%. The coarser fractions of the bed, as represented by the 84th percentile grain diameter, are unaffected by the presence of the dam. These results imply that decades after dam removal, the percentage of sand on the bed will increase, but the coarse fraction of the bed will remain relatively unchanged.

Finite-rate chemistry effects in a Mach 2 reacting flow

NASA Technical Reports Server (NTRS)

Cheng, T. S.; Wehrmeyer, J. A.; Pitz, R. W.; Jarrett, O., Jr.; Northam, G. B.

1991-01-01

UV spontaneous vibrational Raman scattering and laser-induced predissociative fluorescence (LIPF) are combined and applied to a supersonic flame. For the first time, simultaneous measurements of temperature, major species (H2, O2, N2, H2O), and minor species (OH) concentrations are obtained with a 'single' excimer laser in a supersonic-lifted hydrogen-air diffusion flame. In the supersonic flame, a small amount of reaction occurs upstream of the lifted flame base, due to shock wave interactions and mixing with hot vitiated air. The strong turbulent mixing and high total enthalpy fluctuations lead to nonequilibrium values of temperature, and major and minor species concentrations. Combustion occurs farther downstream of the lifted region where slow three-body recombination reactions result in superequilibrium OH concentrations that depress the temperatures below their equilibrium values. Farther downstream, ambient air entrainment contaminates flame properties.

17beta-estradiol potently suppresses cAMP-induced insulin-like growth factor-I gene activation in primary rat osteoblast cultures

NASA Technical Reports Server (NTRS)

McCarthy, T. L.; Ji, C.; Shu, H.; Casinghino, S.; Crothers, K.; Rotwein, P.; Centrella, M.

1997-01-01

Insulin-like growth factor-I (IGF-I) is a key factor in bone remodeling. In osteoblasts, IGF-I synthesis is enhanced by parathyroid hormone and prostaglandin E2 (PGE2) through cAMP-activated protein kinase. In rats, estrogen loss after ovariectomy leads to a rise in serum IGF-I and an increase in bone remodeling, both of which are reversed by estrogen treatment. To examine estrogen-dependent regulation of IGF-I expression at the molecular level, primary fetal rat osteoblasts were co-transfected with the estrogen receptor (hER, to ensure active ER expression), and luciferase reporter plasmids controlled by promoter 1 of the rat IGF-I gene (IGF-I P1), used exclusively in these cells. As reported, 1 microM PGE2 increased IGF-I P1 activity by 5-fold. 17beta-Estradiol alone had no effect, but dose-dependently suppressed the stimulatory effect of PGE2 by up to 90% (ED50 approximately 0.1 nM). This occurred within 3 h, persisted for at least 16 h, required ER, and appeared specific, since 17alpha-estradiol was 100-300-fold less effective. By contrast, 17beta-estradiol stimulated estrogen response element (ERE)-dependent reporter expression by up to 10-fold. 17beta-Estradiol also suppressed an IGF-I P1 construct retaining only minimal promoter sequence required for cAMP-dependent gene activation, but did not affect the 60-fold increase in cAMP induced by PGE2. There is no consensus ERE in rat IGF-I P1, suggesting novel downstream interactions in the cAMP pathway that normally enhances IGF-I expression in skeletal cells. To explore this, nuclear extract from osteoblasts expressing hER were examined by electrophoretic mobility shift assay using the atypical cAMP response element in IGF-I P1. Estrogen alone did not cause DNA-protein binding, while PGE2 induced a characteristic gel shift complex. Co-treatment with both hormones caused a gel shift greatly diminished in intensity, consistent with their combined effects on IGF-I promoter activity. Nonetheless, hER did not bind IGF-I cAMP response element or any adjacent sequences. These results provide new molecular evidence that estrogen may temper the biological effects of hormones acting through cAMP to regulate skeletal IGF-I expression and activity.

Coal-Derived Warm Syngas Purification and CO 2 Capture-Assisted Methane Production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dagle, Robert A.; King, David L.; Li, Xiaohong S.

2014-10-01

Gasifier-derived syngas from coal has many applications in the area of catalytic transformation to fuels and chemicals. Raw syngas must be treated to remove a number of impurities that would otherwise poison the synthesis catalysts. Inorganic impurities include alkali salts, chloride, sulfur compounds, heavy metals, ammonia, and various P, As, Sb, and Se- containing compounds. Systems comprising multiple sorbent and catalytic beds have been developed for the removal of impurities from gasified coal using a warm cleanup approach. This approach has the potential to be more economic than the currently available acid gas removal (AGR) approaches and improves upon currentlymore » available processes that do not provide the level of impurity removal that is required for catalytic synthesis application. Gasification also lends itself much more readily to the capture of CO 2, important in the regulation and control of greenhouse gas emissions. CO 2 capture material was developed and in this study was demonstrated to assist in methane production from the purified syngas. Simultaneous CO 2 sorption enhances the CO methanation reaction through relaxation of thermodynamic constraint, thus providing economic benefit rather than simply consisting of an add-on cost for carbon capture and release. Molten and pre-molten LiNaKCO 3 can promote MgO and MgO-based double salts to capture CO 2 with high cycling capacity. A stable cycling CO 2 capacity up to 13 mmol/g was demonstrated. This capture material was specifically developed in this study to operate in the same temperature range and therefore integrate effectively with warm gas cleanup and methane synthesis. By combining syngas methanation, water-gas-shift, and CO 2 sorption in a single reactor, single pass yield to methane of 99% was demonstrated at 10 bar and 330°C when using a 20 wt% Ni/MgAl 2O 4 catalyst and a molten-phase promoted MgO-based sorbent. Under model feed conditions both the sorbent and catalyst exhibited favorable stability after multiple test cycles. The cleanup for warm gas cleanup of inorganics was broken down into three major steps: chloride removal, sulfur removal, and the removal for a multitude of trace metal contaminants. Na 2CO 3 was found to optimally remove chlorides at an operating temperature of 450ºC. For sulfur removal two regenerable ZnO beds are used for bulk H 2S removal at 450ºC (<5 ppm S) and a non-regenerable ZnO bed for H 2S polishing at 300ºC (<40 ppb S). It was also found that sulfur from COS could be adsorbed (to levels below our detection limit of 40 ppb) in the presence of water that leads to no detectable slip of H 2S. Finally, a sorbent material comprising of Cu and Ni was found to be effective in removing trace metal impurities such as AsH 3 and PH 3 when operating at 300ºC. Proof-of-concept of the integrated cleanup process was demonstrated with gasifier-generated syngas produced at the Western Research Institute using Wyoming Decker Coal. When operating with a ~1 SLPM feed, multiple inorganic contaminant removal sorbents and a tar-reforming bed was able to remove the vast majority of contaminants from the raw syngas. A tar-reforming catalyst was employed due to the production of tars generated from the gasifier used in this particular study. It is envisioned that in a real application a commercial scale gasifier operating at a higher temperature would produce lesser amount of tar. Continuous operation of a poison-sensitive copper-based WGS catalyst located downstream from the cleanup steps resulted in successful demonstration.« less

Co-clustering of Fcgamma and B cell receptors induces dephosphorylation of the Grb2-associated binder 1 docking protein.

PubMed

Koncz, G; Tóth, G K; Bökönyi, G; Kéri, G; Pecht, I; Medgyesi, D; Gergely, J; Sármay, G

2001-07-01

The immunoreceptor tyrosine-based inhibitory motif (ITIM) of human type IIb Fcgamma receptor (FcgammaRIIb) is phosphorylated on its tyrosine upon co-clustering with the B cell receptor (BCR). The phosphorylated ITIM (p-ITIM) binds to the SH2 domains of polyphosphoinositol 5-phosphatase (SHIP) and the tyrosine phosphatase, SHP-2. We investigated the involvement of the molecular complex composed of the phosphorylated SHIP and FcgammaRIIb in the activation of SHP-2. As a model compound, we synthesized a bisphosphopeptide, combining the sequences of p-ITIM and the N-terminal tyrosine phosphorylated motif of SHIP with a flexible spacer. This compound bound to the recombinant SH2 domains of SHP-2 with high affinity and activated the phosphatase in an in vitro assay. These data suggest that the phosphorylated FcgammaRII-SHIP complexes formed in the intact cells may also activate SHP-2. Grb2-associated binder 1 (Gab1) is a multisite docking protein, which becomes tyrosine-phosphorylated in response to various types of signaling, including BCR. In turn it binds to the SH2 domains of SHP-2, SHIP and the p85 subunit of phosphatidyl inositol 3-kinase (PtdIns3-K) and may regulate their activity. Gab1 is a potential substrate of SHP-2, thus its binding to FcgammaRIIb may modify the Gab1-bound signaling complex. We show here that Gab1 is part of the multiprotein complex assembled by FcgammaRIIb upon its co-clustering with BCR. Gab1 may recruit SH2 domain-containing molecules to the phosphorylated FcgammaRIIb. SHP-2, activated upon the binding to FcgammaRIIb-SHIP complex, partially dephosphorylates Gab1, resulting in the release of PtdIns3-K and ultimately in the inhibition of downstream activation pathways in BCR/FcgammaRIIb co-aggregated cells.

Beta-arrestin inhibits CAMKKbeta-dependent AMPK activation downstream of protease-activated-receptor-2.

PubMed

Wang, Ping; Jiang, Yong; Wang, Yinsheng; Shyy, John Y; DeFea, Kathryn A

2010-09-21

Proteinase-activated-receptor-2 (PAR2) is a seven transmembrane receptor that can activate two separate signaling arms: one through Gαq and Ca2+ mobilization, and a second through recruitment of β-arrestin scaffolds. In some cases downstream targets of the Gαq/Ca2+ signaling arm are directly inhibited by β-arrestins, while in other cases the two pathways are synergistic; thus β-arrestins act as molecular switches capable of modifying the signal generated by the receptor. Here we demonstrate that PAR2 can activate adenosine monophosphate-activated protein kinase (AMPK), a key regulator of cellular energy balance, through Ca2+-dependent Kinase Kinase β (CAMKKβ), while inhibiting AMPK through interaction with β-arrestins. The ultimate outcome of PAR2 activation depended on the cell type studied; in cultured fibroblasts with low endogenous β-arrestins, PAR2 activated AMPK; however, in primary fat and liver, PAR2 only activated AMPK in β-arrestin-2-/- mice. β-arrestin-2 could be co-immunoprecipitated with AMPK and CAMKKβ under baseline conditions from both cultured fibroblasts and primary fat, and its association with both proteins was increased by PAR2 activation. Addition of recombinant β-arrestin-2 to in vitro kinase assays directly inhibited phosphorylation of AMPK by CAMKKβ on Thr172. Studies have shown that decreased AMPK activity is associated with obesity and Type II Diabetes, while AMPK activity is increased with metabolically favorable conditions and cholesterol lowering drugs. These results suggest a role for β-arrestin in the inhibition of AMPK signaling, raising the possibility that β-arrestin-dependent PAR2 signaling may act as a molecular switch turning a positive signal to AMPK into an inhibitory one.

PIK3CA-mutated melanoma cells rely on cooperative signaling through mTORC1/2 for sustained proliferation.

PubMed

Silva, Jillian M; Deuker, Marian M; Baguley, Bruce C; McMahon, Martin

2017-05-01

Malignant conversion of BRAF- or NRAS-mutated melanocytes into melanoma cells can be promoted by PI3'-lipid signaling. However, the mechanism by which PI3'-lipid signaling cooperates with mutationally activated BRAF or NRAS has not been adequately explored. Using human NRAS- or BRAF-mutated melanoma cells that co-express mutationally activated PIK3CA, we explored the contribution of PI3'-lipid signaling to cell proliferation. Despite mutational activation of PIK3CA, melanoma cells were more sensitive to the biochemical and antiproliferative effects of broader spectrum PI3K inhibitors than to an α-selective PI3K inhibitor. Combined pharmacological inhibition of MEK1/2 and PI3K signaling elicited more potent antiproliferative effects and greater inhibition of the cell division cycle compared to single-agent inhibition of either pathway alone. Analysis of signaling downstream of MEK1/2 or PI3K revealed that these pathways cooperate to regulate cell proliferation through mTORC1-mediated effects on ribosomal protein S6 and 4E-BP1 phosphorylation in an AKT-dependent manner. Although PI3K inhibition resulted in cytostatic effects on xenografted NRAS Q61H /PIK3CA H1047R melanoma, combined inhibition of MEK1/2 plus PI3K elicited significant melanoma regression. This study provides insights as to how mutationally activated PIK3CA acts in concert with MEK1/2 signaling to cooperatively regulate mTORC1/2 to sustain PIK3CA-mutated melanoma proliferation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

True-lumen and false-lumen diameter changes in the downstream aorta after frozen elephant trunk implantation.

PubMed

Berger, Tim; Kreibich, Maximilian; Morlock, Julia; Kondov, Stoyan; Scheumann, Johannes; Kari, Fabian A; Rylski, Bartosz; Siepe, Matthias; Beyersdorf, Friedhelm; Czerny, Martin

2018-02-19

To evaluate early and mid-term clinical outcomes and to assess the potential of the frozen elephant trunk technique to induce remodelling of downstream aortic segments in acute and chronic thoracic aortic dissections. Over a 4-year period, 65 patients (48 men, aged 61 ± 12 years) underwent total aortic arch replacement using the frozen elephant trunk technique for acute (n = 31) and chronic (n = 34) thoracic aortic dissections at our institution. We assessed diameter changes at 3 levels: the L1 segment at the stent graft level; the L2 segment at the thoraco-abdominal transition level and the L3 segment at the coeliac trunk level. True-lumen (TL) and false-lumen (FL) diameter changes were assessed at each level. Fifty-six percent of patients had already undergone previous aortic or cardiac surgery. In-hospital mortality was 6%. Symptomatic spinal cord injury was not observed in this series. During a mean follow-up of 12 ± 12 months, late death was observed in 6% of patients. Aortic reinterventions in downstream aortic segments were performed in 28% at a mean of 394 ± 385 days. TL expansion and FL shrinkage were measured in all segments and were observed at each level. This effect was the most pronounced at the level of the stent graft in patients with chronic aortic dissection, TL diameter increased from 15 ± 17 mm before surgery to 28 ± 2 mm (P = 0.001) after 2 years, and the FL diameter decreased from 40 ± 11 mm before surgery to 32 ± 17 mm (P = 0.026). The frozen elephant trunk technique is associated with an excellent clinical outcome in a complex cohort of patients, and also effectively induces remodelling in downstream aortic segments in acute and chronic thoracic aortic dissections. The need for secondary interventions in downstream segments, which mainly depends on the extent of the underlying disease process, remains substantial. Further studies are required to assess the long-term outcome of this approach.

Acetyl L-carnitine targets adenosine triphosphate synthase in protecting zebrafish embryos from toxicities induced by verapamil and ketamine: An in vivo assessment.

PubMed

Guo, Xiaoqing; Dumas, Melanie; Robinson, Bonnie L; Ali, Syed F; Paule, Merle G; Gu, Qiang; Kanungo, Jyotshna

2017-02-01

Verapamil is a Ca 2 + channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug. Ketamine, an antagonist of the Ca 2 + -permeable N-methyl-d-aspartate-type glutamate receptors, is a pediatric anesthetic. Previously we have shown that acetyl l-carnitine (ALCAR) reverses ketamine-induced attenuation of heart rate and neurotoxicity in zebrafish embryos. Here, we used 48 h post-fertilization zebrafish embryos that were exposed to relevant drugs for 2 or 4 h. Heart beat and overall development were monitored in vivo. In 48 h post-fertilization embryos, 2 mm ketamine reduced heart rate in a 2 or 4 h exposure and 0.5 mm ALCAR neutralized this effect. ALCAR could reverse ketamine's effect, possibly through a compensatory mechanism involving extracellular Ca 2 + entry through L-type Ca 2 + channels that ALCAR is known to activate. Hence, we used verapamil to block the L-type Ca 2 + channels. Verapamil was more potent in attenuating heart rate and inducing morphological defects in the embryos compared to ketamine at specific times of exposure. ALCAR reversed cardiotoxicity and developmental toxicity in the embryos exposed to verapamil or verapamil plus ketamine, even in the presence of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, an inhibitor of intracellular Ca 2 + release suggesting that ALCAR acts via effectors downstream of Ca 2 + . In fact, ALCAR's protective effect was blunted by oligomycin A, an inhibitor of adenosine triphosphate synthase that acts downstream of Ca 2 + during adenosine triphosphate generation. We have identified, for the first time, using in vivo studies, a downstream effector of ALCAR that is critical in abrogating ketamine- and verapamil-induced developmental toxicities. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Feeding by whiteflies suppresses downstream jasmonic acid signaling by eliciting salicylic acid signaling.

PubMed

Zhang, Peng-Jun; Li, Wei-Di; Huang, Fang; Zhang, Jin-Ming; Xu, Fang-Cheng; Lu, Yao-Bin

2013-05-01

Phloem-feeding whiteflies in the species complex Bemisia tabaci cause extensive crop damage worldwide. One of the reasons for their "success" is their ability to suppress the effectual jasmonic acid (JA) defenses of the host plant. However, little is understood about the mechanisms underlying whitefly suppression of JA-regulated defenses. Here, we showed that the expression of salicylic acid (SA)-responsive genes (EDS1 and PR1) in Arabidopsis thaliana was significantly enhanced during feeding by whitefly nymphs. Whereas upstream JA-responsive genes (LOX2 and OPR3) also were induced, the downstream JA-responsive gene (VSP1) was repressed, i.e., whiteflies only suppressed downstream JA signaling. Gene-expression analyses with various Arabidopsis mutants, including NahG, npr-1, ein2-1, and dde2-2, revealed that SA signaling plays a key role in the suppression of downstream JA defenses by whitefly feeding. Assays confirmed that SA activation enhanced whitefly performance by suppressing downstream JA defenses.

Simulated effect of calcification feedback on atmospheric CO2 and ocean acidification

PubMed Central

Zhang, Han; Cao, Long

2016-01-01

Ocean uptake of anthropogenic CO2 reduces pH and saturation state of calcium carbonate materials of seawater, which could reduce the calcification rate of some marine organisms, triggering a negative feedback on the growth of atmospheric CO2. We quantify the effect of this CO2-calcification feedback by conducting a series of Earth system model simulations that incorporate different parameterization schemes describing the dependence of calcification rate on saturation state of CaCO3. In a scenario with SRES A2 CO2 emission until 2100 and zero emission afterwards, by year 3500, in the simulation without CO2-calcification feedback, model projects an accumulated ocean CO2 uptake of 1462 PgC, atmospheric CO2 of 612 ppm, and surface pH of 7.9. Inclusion of CO2-calcification feedback increases ocean CO2 uptake by 9 to 285 PgC, reduces atmospheric CO2 by 4 to 70 ppm, and mitigates the reduction in surface pH by 0.003 to 0.06, depending on the form of parameterization scheme used. It is also found that the effect of CO2-calcification feedback on ocean carbon uptake is comparable and could be much larger than the effect from CO2-induced warming. Our results highlight the potentially important role CO2-calcification feedback plays in ocean carbon cycle and projections of future atmospheric CO2 concentrations. PMID:26838480

Warm Cleanup of Coal-Derived Syngas: Multicontaminant Removal Process Demonstration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spies, Kurt A.; Rainbolt, James E.; Li, Xiaohong S.

Warm cleanup of coal- or biomass-derived syngas requires sorbent and catalytic beds to protect downstream processes and catalysts from fouling. Sulfur is particularly harmful because even parts-per-million amounts are sufficient to poison downstream synthesis catalysts. Zinc oxide (ZnO) is a conventional sorbent for sulfur removal; however, its operational performance using real gasifier-derived syngas and in an integrated warm cleanup process is not well reported. In this paper, we report the optimal temperature for bulk desulfurization to be 450oC, while removal of sulfur to parts-per-billion levels requires a lower temperature of approximately 350oC. Under these conditions, we found that sulfur inmore » the form of both hydrogen sulfide and carbonyl sulfide could be absorbed equally well using ZnO. For long-term operation, sorbent regeneration is desirable to minimize process costs. Over the course of five sulfidation and regeneration cycles, a ZnO bed lost about a third of its initial sulfur capacity, however sorbent capacity stabilized. Here, we also demonstrate, at the bench-scale, a process and materials used for warm cleanup of coal-derived syngas using five operations: 1) Na2CO3 for HCl removal, 2) regenerable ZnO beds for bulk sulfur removal, 3) a second ZnO bed for trace sulfur removal, 4) a Ni-Cu/C sorbent for multi-contaminant inorganic removal, and 5) a Ir-Ni/MgAl2O4 catalyst employed for ammonia decomposition and tar and light hydrocarbon steam reforming. Syngas cleanup was demonstrated through successful long-term performance of a poison-sensitive, Cu-based, water-gas-shift catalyst placed downstream of the cleanup process train. The tar reformer is an important and necessary operation with this particular gasification system; its inclusion was the difference between deactivating the water-gas catalyst with carbon deposition and successful 100-hour testing using 1 LPM of coal-derived syngas.« less

Regional acidosis locally inhibits but remotely stimulates Ca2+ waves in ventricular myocytes

PubMed Central

Ford, Kerrie L.; Moorhouse, Emma L.; Bortolozzi, Mario; Richards, Mark A.; Swietach, Pawel; Vaughan-Jones, Richard D.

2017-01-01

Abstract Aims Spontaneous Ca2+ waves in cardiomyocytes are potentially arrhythmogenic. A powerful controller of Ca2+ waves is the cytoplasmic H+ concentration ([H+]i), which fluctuates spatially and temporally in conditions such as myocardial ischaemia/reperfusion. H+-control of Ca2+ waves is poorly understood. We have therefore investigated how [H+]i co-ordinates their initiation and frequency. Methods and results Spontaneous Ca2+ waves were imaged (fluo-3) in rat isolated ventricular myocytes, subjected to modest Ca2+-overload. Whole-cell intracellular acidosis (induced by acetate-superfusion) stimulated wave frequency. Pharmacologically blocking sarcolemmal Na+/H+ exchange (NHE1) prevented this stimulation, unveiling inhibition by H+. Acidosis also increased Ca2+ wave velocity. Restricting acidosis to one end of a myocyte, using a microfluidic device, inhibited Ca2+ waves in the acidic zone (consistent with ryanodine receptor inhibition), but stimulated wave emergence elsewhere in the cell. This remote stimulation was absent when NHE1 was selectively inhibited in the acidic zone. Remote stimulation depended on a locally evoked, NHE1-driven rise of [Na+]i that spread rapidly downstream. Conclusion Acidosis influences Ca2+ waves via inhibitory Hi+ and stimulatory Nai+ signals (the latter facilitating intracellular Ca2+-loading through modulation of sarcolemmal Na+/Ca2+ exchange activity). During spatial [H+]i-heterogeneity, Hi+-inhibition dominates in acidic regions, while rapid Nai+ diffusion stimulates waves in downstream, non-acidic regions. Local acidosis thus simultaneously inhibits and stimulates arrhythmogenic Ca2+-signalling in the same myocyte. If the principle of remote H+-stimulation of Ca2+ waves also applies in multicellular myocardium, it raises the possibility of electrical disturbances being driven remotely by adjacent ischaemic areas, which are known to be intensely acidic. PMID:28339694

Regional acidosis locally inhibits but remotely stimulates Ca2+ waves in ventricular myocytes.

PubMed

Ford, Kerrie L; Moorhouse, Emma L; Bortolozzi, Mario; Richards, Mark A; Swietach, Pawel; Vaughan-Jones, Richard D

2017-07-01

Spontaneous Ca2+ waves in cardiomyocytes are potentially arrhythmogenic. A powerful controller of Ca2+ waves is the cytoplasmic H+ concentration ([H+]i), which fluctuates spatially and temporally in conditions such as myocardial ischaemia/reperfusion. H+-control of Ca2+ waves is poorly understood. We have therefore investigated how [H+]i co-ordinates their initiation and frequency. Spontaneous Ca2+ waves were imaged (fluo-3) in rat isolated ventricular myocytes, subjected to modest Ca2+-overload. Whole-cell intracellular acidosis (induced by acetate-superfusion) stimulated wave frequency. Pharmacologically blocking sarcolemmal Na+/H+ exchange (NHE1) prevented this stimulation, unveiling inhibition by H+. Acidosis also increased Ca2+ wave velocity. Restricting acidosis to one end of a myocyte, using a microfluidic device, inhibited Ca2+ waves in the acidic zone (consistent with ryanodine receptor inhibition), but stimulated wave emergence elsewhere in the cell. This remote stimulation was absent when NHE1 was selectively inhibited in the acidic zone. Remote stimulation depended on a locally evoked, NHE1-driven rise of [Na+]i that spread rapidly downstream. Acidosis influences Ca2+ waves via inhibitory Hi+ and stimulatory Nai+ signals (the latter facilitating intracellular Ca2+-loading through modulation of sarcolemmal Na+/Ca2+ exchange activity). During spatial [H+]i-heterogeneity, Hi+-inhibition dominates in acidic regions, while rapid Nai+ diffusion stimulates waves in downstream, non-acidic regions. Local acidosis thus simultaneously inhibits and stimulates arrhythmogenic Ca2+-signalling in the same myocyte. If the principle of remote H+-stimulation of Ca2+ waves also applies in multicellular myocardium, it raises the possibility of electrical disturbances being driven remotely by adjacent ischaemic areas, which are known to be intensely acidic. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.

Molecular and functional interactions between AKT and SOX2 in breast carcinoma

PubMed Central

Mir, Perihan; Konantz, Martina; Pereboom, Tamara C.; Paczulla, Anna M.; Merz, Britta; Fehm, Tanja; Perner, Sven; Rothfuss, Oliver C.; Kanz, Lothar; Schulze-Osthoff, Klaus; Lengerke, Claudia

2015-01-01

The transcription factor SOX2 is a key regulator of pluripotency in embryonic stem cells and plays important roles in early organogenesis. Recently, SOX2 expression was documented in various cancers and suggested as a cancer stem cell (CSC) marker. Here we identify the Ser/Thr-kinase AKT as an upstream regulator of SOX2 protein turnover in breast carcinoma (BC). SOX2 and pAKT are co-expressed and co-regulated in breast CSCs and depletion of either reduces clonogenicity. Ectopic SOX2 expression restores clonogenicity and in vivo tumorigenicity of AKT-inhibited cells, suggesting that SOX2 acts as a functional downstream AKT target. Mechanistically, we show that AKT physically interacts with the SOX2 protein to modulate its subcellular distribution. AKT kinase inhibition results in enhanced cytoplasmic retention of SOX2, presumably via impaired nuclear import, and in successive cytoplasmic proteasomal degradation of the protein. In line, blockade of either nuclear transport or proteasomal degradation rescues SOX2 expression in AKT-inhibited BC cells. Finally, AKT inhibitors efficiently suppress the growth of SOX2-expressing putative cancer stem cells, whereas conventional chemotherapeutics select for this population. Together, our results suggest the AKT/SOX2 molecular axis as a regulator of BC clonogenicity and AKT inhibitors as promising drugs for the treatment of SOX2-positive BC. PMID:26498353

Analysis of exosome purification methods using a model liposome system and tunable-resistive pulse sensing

NASA Astrophysics Data System (ADS)

Lane, Rebecca E.; Korbie, Darren; Anderson, Will; Vaidyanathan, Ramanathan; Trau, Matt

2015-01-01

Exosomes are vesicles which have garnered interest due to their diagnostic and therapeutic potential. Isolation of pure yields of exosomes from complex biological fluids whilst preserving their physical characteristics is critical for downstream applications. In this study, we use 100 nm-liposomes from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and cholesterol as a model system as a model system to assess the effect of exosome isolation protocols on vesicle recovery and size distribution using a single-particle analysis method. We demonstrate that liposome size distribution and ζ-potential are comparable to extracted exosomes, making them an ideal model for comparison studies. Four different purification protocols were evaluated, with liposomes robustly isolated by three of them. Recovered yields varied and liposome size distribution was unaltered during processing, suggesting that these protocols do not induce particle aggregation. This leads us to conclude that the size distribution profile and characteristics of vesicles are stably maintained during processing and purification, suggesting that reports detailing how exosomes derived from tumour cells differ in size to those from normal cells are reporting a real phenomenon. However, we hypothesize that larger particles present in most purified exosome samples represent co-purified contaminating non-exosome debris. These isolation techniques are therefore likely nonspecific and may co-isolate non-exosome material of similar physical properties.

Combinatorial pathway optimization in Escherichia coli by directed co-evolution of rate-limiting enzymes and modular pathway engineering.

PubMed

Lv, Xiaomei; Gu, Jiali; Wang, Fan; Xie, Wenping; Liu, Min; Ye, Lidan; Yu, Hongwei

2016-12-01

Metabolic engineering of microorganisms for heterologous biosynthesis is a promising route to sustainable chemical production which attracts increasing research and industrial interest. However, the efficiency of microbial biosynthesis is often restricted by insufficient activity of pathway enzymes and unbalanced utilization of metabolic intermediates. This work presents a combinatorial strategy integrating modification of multiple rate-limiting enzymes and modular pathway engineering to simultaneously improve intra- and inter-pathway balance, which might be applicable for a range of products, using isoprene as an example product. For intra-module engineering within the methylerythritol-phosphate (MEP) pathway, directed co-evolution of DXS/DXR/IDI was performed adopting a lycopene-indicated high-throughput screening method developed herein, leading to 60% improvement of isoprene production. In addition, inter-module engineering between the upstream MEP pathway and the downstream isoprene-forming pathway was conducted via promoter manipulation, which further increased isoprene production by 2.94-fold compared to the recombinant strain with solely protein engineering and 4.7-fold compared to the control strain containing wild-type enzymes. These results demonstrated the potential of pathway optimization in isoprene overproduction as well as the effectiveness of combining metabolic regulation and protein engineering in improvement of microbial biosynthesis. Biotechnol. Bioeng. 2016;113: 2661-2669. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Gene Co-Expression Analysis Inferring the Crosstalk of Ethylene and Gibberellin in Modulating the Transcriptional Acclimation of Cassava Root Growth in Different Seasons

PubMed Central

Saithong, Treenut; Saerue, Samorn; Kalapanulak, Saowalak; Sojikul, Punchapat; Narangajavana, Jarunya; Bhumiratana, Sakarindr

2015-01-01

Cassava is a crop of hope for the 21st century. Great advantages of cassava over other crops are not only the capacity of carbohydrates, but it is also an easily grown crop with fast development. As a plant which is highly tolerant to a poor environment, cassava has been believed to own an effective acclimation process, an intelligent mechanism behind its survival and sustainability in a wide range of climates. Herein, we aimed to investigate the transcriptional regulation underlying the adaptive development of a cassava root to different seasonal cultivation climates. Gene co-expression analysis suggests that AP2-EREBP transcription factor (ERF1) orthologue (D142) played a pivotal role in regulating the cellular response to exposing to wet and dry seasons. The ERF shows crosstalk with gibberellin, via ent-Kaurene synthase (D106), in the transcriptional regulatory network that was proposed to modulate the downstream regulatory system through a distinct signaling mechanism. While sulfur assimilation is likely to be a signaling regulation for dry crop growth response, calmodulin-binding protein is responsible for regulation in the wet crop. With our initiative study, we hope that our findings will pave the way towards sustainability of cassava production under various kinds of stress considering the future global climate change. PMID:26366737

Gene Co-Expression Analysis Inferring the Crosstalk of Ethylene and Gibberellin in Modulating the Transcriptional Acclimation of Cassava Root Growth in Different Seasons.

PubMed

Saithong, Treenut; Saerue, Samorn; Kalapanulak, Saowalak; Sojikul, Punchapat; Narangajavana, Jarunya; Bhumiratana, Sakarindr

2015-01-01

Cassava is a crop of hope for the 21st century. Great advantages of cassava over other crops are not only the capacity of carbohydrates, but it is also an easily grown crop with fast development. As a plant which is highly tolerant to a poor environment, cassava has been believed to own an effective acclimation process, an intelligent mechanism behind its survival and sustainability in a wide range of climates. Herein, we aimed to investigate the transcriptional regulation underlying the adaptive development of a cassava root to different seasonal cultivation climates. Gene co-expression analysis suggests that AP2-EREBP transcription factor (ERF1) orthologue (D142) played a pivotal role in regulating the cellular response to exposing to wet and dry seasons. The ERF shows crosstalk with gibberellin, via ent-Kaurene synthase (D106), in the transcriptional regulatory network that was proposed to modulate the downstream regulatory system through a distinct signaling mechanism. While sulfur assimilation is likely to be a signaling regulation for dry crop growth response, calmodulin-binding protein is responsible for regulation in the wet crop. With our initiative study, we hope that our findings will pave the way towards sustainability of cassava production under various kinds of stress considering the future global climate change.

Downstream on the Mekong: Contrasting Cambodian and Vietnamese Responses to Chinese Water Control

DTIC Science & Technology

2017-06-01

Barma Co-Advisor: Michael Malley THIS PAGE INTENTIONALLY LEFT BLANK i REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public...Unclassified 19. SECURITY CLASSIFICATION OF ABSTRACT Unclassified 20. LIMITATION OF ABSTRACT UU NSN 7540-01-280-5500 Standard Form 298 (Rev... form balancing coalitions against their stronger competitors.37 34 Alexander L. Vuving, “Vietnam in

Plant cell surface receptor-mediated signaling - a common theme amid diversity.

PubMed

He, Yunxia; Zhou, Jinggeng; Shan, Libo; Meng, Xiangzong

2018-01-29

Sessile plants employ a diverse array of plasma membrane-bound receptors to perceive endogenous and exogenous signals for regulation of plant growth, development and immunity. These cell surface receptors include receptor-like kinases (RLKs) and receptor-like proteins (RLPs) that harbor different extracellular domains for perception of distinct ligands. Several RLK and RLP signaling pathways converge at the somatic embryogenesis receptor kinases (SERKs), which function as shared co-receptors. A repertoire of receptor-like cytoplasmic kinases (RLCKs) associate with the receptor complexes to relay intracellular signaling. Downstream of the receptor complexes, mitogen-activated protein kinase (MAPK) cascades are among the key signaling modules at which the signals converge, and these cascades regulate diverse cellular and physiological responses through phosphorylation of different downstream substrates. In this Review, we summarize the emerging common theme that underlies cell surface receptor-mediated signaling pathways in Arabidopsis thaliana : the dynamic association of RLKs and RLPs with specific co-receptors and RLCKs for signal transduction. We further discuss how signaling specificities are maintained through modules at which signals converge, with a focus on SERK-mediated receptor signaling. © 2018. Published by The Company of Biologists Ltd.

Spatial organization of the gastrointestinal microbiota in urban Canada geese

USGS Publications Warehouse

Drovetski, Sergei V.; O'Mahoney, Michael; Ransome, Emma J.; Matterson, Kenan O.; Lim, Haw Chuan; Chesser, Terry; Graves, Gary R.

2018-01-01

Recent reviews identified the reliance on fecal or cloacal samples as a significant limitation hindering our understanding of the avian gastrointestinal (gut) microbiota and its function. We investigated the microbiota of the esophagus, duodenum, cecum, and colon of a wild urban population of Canada goose (Branta canadensis). From a population sample of 30 individuals, we sequenced the V4 region of the 16S SSU rRNA on an Illumina MiSeq and obtained 8,628,751 sequences with a median of 76,529 per sample. These sequences were assigned to 420 bacterial OTUs and a single archaeon. Firmicutes, Proteobacteria, and Bacteroidetes accounted for 90% of all sequences. Microbiotas from the four gut regions differed significantly in their richness, composition, and variability among individuals. Microbial communities of the esophagus were the most distinctive whereas those of the colon were the least distinctive, reflecting the physical downstream mixing of regional microbiotas. The downstream mixing of regional microbiotas was also responsible for the majority of observed co-occurrence patterns among microbial families. Our results indicate that fecal and cloacal samples inadequately represent the complex patterns of richness, composition, and variability of the gut microbiota and obscure patterns of co-occurrence of microbial lineages.

Altered protein expression profile associated with phenotypic changes in lung fibroblasts co-cultured with gold nanoparticle-treated small airway epithelial cells.

PubMed

Ng, Cheng-Teng; Yung, Lin-Yue Lanry; Swa, Hannah Lee-Foon; Poh, Rebecca Wan-Yan; Gunaratne, Jayantha; Bay, Boon-Huat

2015-01-01

Despite the availability of toxicity studies on cellular exposure to gold nanoparticles (AuNPs), there is scarcity of information with regard to the bystander effects induced by AuNPs on neighboring cells not exposed to the NPs. In this study, we showed that exposure of small airway epithelial cells (SAECs) to AuNPs induced changes in protein expression associated with functional effects in neighboring MRC5 lung fibroblasts in a co-culture system. Uptake of 20 nm size AuNPs by SAECs was first verified by focused ion beam scanning electron microscopy. Subsequently, pretreated SAECs were co-cultured with unexposed MRC5 lung fibroblasts, which then underwent proteome profiling using a quantitative proteomic approach. Stable-isotope labeling by amino acids in cell culture (SILAC)-based mass spectrometry identified 109 proteins (which included 47 up-regulated and 62 down-regulated proteins) that were differentially expressed in the lung fibroblasts co-cultured with AuNP pretreated SAECs. There was altered expression of proteins such as Paxillin, breast cancer anti-estrogen resistance 1 and Caveolin-1, which are known to be involved in the cell adhesion process. Morphological studies revealed that there was a concomitant increase in cell adhesion and altered F-actin stress fiber arrangement involving vinculin in the lung fibroblasts. It is likely that phenotypic changes observed in the underlying lung fibroblasts were mediated by AuNP-induced downstream signals in the pretreated SAECs and cell-cell cross talk. Copyright © 2014 Elsevier Ltd. All rights reserved.