Science.gov

Sample records for activation product release

  1. Effect of linoleic acid sustained-release microspheres on Microcystis aeruginosa antioxidant enzymes activity and microcystins production and release.

    PubMed

    Ni, Lixiao; Jie, Xiaoting; Wang, Peifang; Li, Shiyin; Wang, Guoxiang; Li, Yiping; Li, Yong; Acharya, Kumud

    2015-02-01

    The objective of this work was to identify the optimal dose range for good anti-algal effect of linoleic acid (LA) sustained-release microspheres and investigate their impact on the antioxidant enzymes (super oxide dismutase, Catalase and Peroxidase) activity changes of Microcystis aeruginosa, as well as the production and release of microcystins (MCs). Based on measured changes in algal cell density and inhibitory ratio (IR), the optimal dose of LA microspheres was 0.3 g L(-1) with over 90% of IR in this study. The Chlorophyll a content and antioxidant enzymes activity in the LA microspheres group decreased markedly until beyond the minimal detection limit after 16 d and 9 d, respectively. In addition, LA microspheres demonstrated no significant impact on the extracellular release of MCs during the culturing period. The amount of intracellular microcystin-LR (MC-LR) per 10(6) algal cells in LA microspheres group was highest among all groups during the whole experimental process. Under the sustained stress of LA released from LA microspheres, the LA microspheres could decrease the production and release of algal toxins. There was no increase in the total amount of MC-LR in the algal cell culture medium. These indicated that LA sustained-release microspheres represent a high degree of ecological safety and their practical applications for the treatment of water undergoing algal blooms need further study.

  2. Soil Moisture Active Passive Mission L4_C Data Product Assessment (Version 2 Validated Release)

    NASA Technical Reports Server (NTRS)

    Kimball, John S.; Jones, Lucas A.; Glassy, Joseph; Stavros, E. Natasha; Madani, Nima; Reichle, Rolf H.; Jackson, Thomas; Colliander, Andreas

    2016-01-01

    The SMAP satellite was successfully launched January 31st 2015, and began acquiring Earth observation data following in-orbit sensor calibration. Global data products derived from the SMAP L-band microwave measurements include Level 1 calibrated and geolocated radiometric brightness temperatures, Level 23 surface soil moisture and freezethaw geophysical retrievals mapped to a fixed Earth grid, and model enhanced Level 4 data products for surface to root zone soil moisture and terrestrial carbon (CO2) fluxes. The post-launch SMAP mission CalVal Phase had two primary objectives for each science product team: 1) calibrate, verify, and improve the performance of the science algorithms, and 2) validate accuracies of the science data products as specified in the L1 science requirements. This report provides analysis and assessment of the SMAP Level 4 Carbon (L4_C) product pertaining to the validated release. The L4_C validated product release effectively replaces an earlier L4_C beta-product release (Kimball et al. 2015). The validated release described in this report incorporates a longer data record and benefits from algorithm and CalVal refinements acquired during the SMAP post-launch CalVal intensive period. The SMAP L4_C algorithms utilize a terrestrial carbon flux model informed by SMAP soil moisture inputs along with optical remote sensing (e.g. MODIS) vegetation indices and other ancillary biophysical data to estimate global daily net ecosystem CO2 exchange (NEE) and component carbon fluxes for vegetation gross primary production (GPP) and ecosystem respiration (Reco). Other L4_C product elements include surface (10 cm depth) soil organic carbon (SOC) stocks and associated environmental constraints to these processes, including soil moisture and landscape freeze/thaw (FT) controls on GPP and respiration (Kimball et al. 2012). The L4_C product encapsulates SMAP carbon cycle science objectives by: 1) providing a direct link between terrestrial carbon fluxes and

  3. Soluble microbial products (SMPs) release in activated sludge systems: a review

    PubMed Central

    2012-01-01

    This review discusses the characterization, production and implications of soluble microbial products (SMPs) in biological wastewater treatment. The precise definition of SMPs is open to talk about, but is currently regarded as “the pool of organic compounds that are released into solution from substrate metabolism and biomass decay”'. Some of the SMPs have been identified as humic acids, polysaccharides, proteins, amino acids, antibiotics, extracellular enzymes and structural components of cells and products of energy metabolism. They adversely affect the kinetic activity, flocculating and settling properties of sludge. This review outlines some important findings with regard to biodegradability and treatability of SMPs and also the effect of process parameters on their production. As SMPs are produced during biological treatment process, their trace amounts normally remain in the effluent that defines the highest COD removal efficiency. Their presence in effluent represents a high potential risk of toxic by-product formation during chlorine disinfection. Studies have indicated that among all wastewater post-treatment processes, the adsorption by granular activated carbon combined with biologically induced degradation is the most effective method for removal of SMPs. However, it may be concludes that the knowledge regarding SMPs is still under progress and more work is required to fully understand their contribution to the treatment process. PMID:23369231

  4. TESTING PHARMACEUTICAL RELEASE OF ACTIVE SUBSTANCES FROM MEDICINAL PRODUCTS CONTAINING ST. JOHN'S WORT.

    PubMed

    Sakowska, Joanna; Anyzewska, Małgorzata; Łozak, Anna; Kowalczuk, Anna; Jabłczyńska, Renata

    2016-01-01

    The aim of this study was to determine the content of hypericins and flavonoids in tablets and capsules containing the extract or powdered herb of St. John's wort, in herbs for infusion and herbal infusions and to release of these compounds from tablets and capsules. HPLC method was used to determine the assay of hypericins and flavonoids in all tested products. The hypericins content was between 0.35 mg and 1.44 mg per tablet or capsule. The release of hypericins from these products in the phosphate buffer of pH 6.8 is between 30 and 60% of the determined content. The degree of hypericins release from herbs into infusions was 15% on average, which corresponds to 0.64 mg of hypericins per infusion of 4 g of herbs. The flavonoids content was between 8.79 and 36.3 mg per tablet or capsule. The release of flavonoids in the phosphate buffer of pH 6.8 is between 63 and 85% of the determined content. The degree of flavonoids release was 76% on average, which corresponds to 77.0 mg per infusion of 4 g of herbs. The test results confirmed that infusions from the St. John's wort constitute are a rich source of flavonoids. At the same time, the universally accepted opinion that aqueous infusions contain only trace amounts of hypericins was not confirmed. Infusions from Herba hyperici may also be a source of hypericins in amounts comparable with the minimum dose recommended for the treatment of mild to moderate depressive episodes. PMID:27180432

  5. TESTING PHARMACEUTICAL RELEASE OF ACTIVE SUBSTANCES FROM MEDICINAL PRODUCTS CONTAINING ST. JOHN'S WORT.

    PubMed

    Sakowska, Joanna; Anyzewska, Małgorzata; Łozak, Anna; Kowalczuk, Anna; Jabłczyńska, Renata

    2016-01-01

    The aim of this study was to determine the content of hypericins and flavonoids in tablets and capsules containing the extract or powdered herb of St. John's wort, in herbs for infusion and herbal infusions and to release of these compounds from tablets and capsules. HPLC method was used to determine the assay of hypericins and flavonoids in all tested products. The hypericins content was between 0.35 mg and 1.44 mg per tablet or capsule. The release of hypericins from these products in the phosphate buffer of pH 6.8 is between 30 and 60% of the determined content. The degree of hypericins release from herbs into infusions was 15% on average, which corresponds to 0.64 mg of hypericins per infusion of 4 g of herbs. The flavonoids content was between 8.79 and 36.3 mg per tablet or capsule. The release of flavonoids in the phosphate buffer of pH 6.8 is between 63 and 85% of the determined content. The degree of flavonoids release was 76% on average, which corresponds to 77.0 mg per infusion of 4 g of herbs. The test results confirmed that infusions from the St. John's wort constitute are a rich source of flavonoids. At the same time, the universally accepted opinion that aqueous infusions contain only trace amounts of hypericins was not confirmed. Infusions from Herba hyperici may also be a source of hypericins in amounts comparable with the minimum dose recommended for the treatment of mild to moderate depressive episodes.

  6. Soil Moisture Active Passive Mission L4_SM Data Product Assessment (Version 2 Validated Release)

    NASA Technical Reports Server (NTRS)

    Reichle, Rolf Helmut; De Lannoy, Gabrielle J. M.; Liu, Qing; Ardizzone, Joseph V.; Chen, Fan; Colliander, Andreas; Conaty, Austin; Crow, Wade; Jackson, Thomas; Kimball, John; Koster, Randal D.; Smith, E. Brent

    2016-01-01

    During the post-launch SMAP calibration and validation (Cal/Val) phase there are two objectives for each science data product team: 1) calibrate, verify, and improve the performance of the science algorithm, and 2) validate the accuracy of the science data product as specified in the science requirements and according to the Cal/Val schedule. This report provides an assessment of the SMAP Level 4 Surface and Root Zone Soil Moisture Passive (L4_SM) product specifically for the product's public Version 2 validated release scheduled for 29 April 2016. The assessment of the Version 2 L4_SM data product includes comparisons of SMAP L4_SM soil moisture estimates with in situ soil moisture observations from core validation sites and sparse networks. The assessment further includes a global evaluation of the internal diagnostics from the ensemble-based data assimilation system that is used to generate the L4_SM product. This evaluation focuses on the statistics of the observation-minus-forecast (O-F) residuals and the analysis increments. Together, the core validation site comparisons and the statistics of the assimilation diagnostics are considered primary validation methodologies for the L4_SM product. Comparisons against in situ measurements from regional-scale sparse networks are considered a secondary validation methodology because such in situ measurements are subject to up-scaling errors from the point-scale to the grid cell scale of the data product. Based on the limited set of core validation sites, the wide geographic range of the sparse network sites, and the global assessment of the assimilation diagnostics, the assessment presented here meets the criteria established by the Committee on Earth Observing Satellites for Stage 2 validation and supports the validated release of the data. An analysis of the time average surface and root zone soil moisture shows that the global pattern of arid and humid regions are captured by the L4_SM estimates. Results from the

  7. New Ru(II) Complex for Dual Activity: Photoinduced Ligand Release and (1)O2 Production.

    PubMed

    Loftus, Lauren M; White, Jessica K; Albani, Bryan A; Kohler, Lars; Kodanko, Jeremy J; Thummel, Randolph P; Dunbar, Kim R; Turro, Claudia

    2016-03-01

    The new complex [Ru(pydppn)(biq)(py)](2+) (1) undergoes both py photodissociation in CH3CN with Φ500 =0.0070(4) and (1)O2 production with ΦΔ =0.75(7) in CH3 OH from a long-lived (3) ππ* state centered on the pydppn ligand (pydppn=3-(pyrid-2-yl)benzo[i]dipyrido[3,2-a:2',3'-c]phenazine; biq = 2,2'-biquinoline; py=pyridine). This represents an order of magnitude decrease in the Φ500 compared to the previously reported model compound [Ru(tpy)(biq)(py)](2+) (3) (tpy=2,2':6',2''-terpyridine) that undergoes only ligand exchange. The effect on the quantum yields by the addition of a second deactivation pathway through the low-lying (3) ππ* state necessary for dual reactivity was investigated using ultrafast and nanosecond transient absorption spectroscopy, revealing a significantly shorter (3) MLCT lifetime in 1 relative to that of the model complex 3. Due to the structural similarities between the two compounds, the lower values of Φ500 and ΦΔ compared to that of [Ru(pydppn)(bpy)(py)](2+) (2) (bpy=2,2'-bipyridine) are attributed to a competitive excited state population between the (3) LF states involved in ligand dissociation and the long-lived (3) ππ* state in 1. Complex 1 represents a model compound for dual activity that may be applied to photochemotherapy. PMID:26715085

  8. New RuII Complex for Dual Activity: Photoinduced Ligand Release and 1O2 Production

    PubMed Central

    Loftus, Lauren M.; White, Jessica K.; Albani, Bryan A.; Kohler, Lars; Kodanko, Jeremy J.; Thummel, Randolph P.

    2016-01-01

    The new complex [Ru(pydppn)(biq)(py)]2+ (1) undergoes both py photodissociation in CH3CN with Φ500=0.0070(4) and 1O2 production with ΦΔ=0.75(7) in CH3OH from a long-lived 3ππ* state centered on the pydppn ligand (pydppn=3-(pyrid-2-yl)benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine; biq = 2,2′-biquinoline; py= pyridine). This represents an order of magnitude decrease in the Φ500 compared to the previously reported model compound [Ru(tpy)(biq)(py)]2+ (3) (tpy=2,2′:6′,2″-terpyridine) that undergoes only ligand exchange. The effect on the quantum yields by the addition of a second deactivation pathway through the low-lying 3ππ* state necessary for dual reactivity was investigated using ultrafast and nanosecond transient absorption spectroscopy, revealing a significantly shorter 3MLCT lifetime in 1 relative to that of the model complex 3. Due to the structural similarities between the two compounds, the lower values of Φ500 and ΦΔ compared to that of [Ru(pydppn)(bpy)(py)]2+ (2) (bpy=2,2′-bipyridine) are attributed to a competitive excited state population between the 3LF states involved in ligand dissociation and the long-lived 3ππ* state in 1. Complex 1 represents a model compound for dual activity that may be applied to photochemotherapy. PMID:26715085

  9. Crystal structures of Ophiostoma piceae sterol esterase: structural insights into activation mechanism and product release.

    PubMed

    Gutiérrez-Fernández, Javier; Vaquero, María Eugenia; Prieto, Alicia; Barriuso, Jorge; Martínez, María Jesús; Hermoso, Juan A

    2014-09-01

    Sterol esterases are able to efficiently hydrolyze both sterol esters and triglycerides and to carry out synthesis reactions in the presence of organic solvents. Their high versatility makes them excellent candidates for biotechnological purposes. Sterol esterase from fungus Ophiostoma piceae (OPE) belongs to the family abH03.01 of the Candida rugosa lipase-like proteins. Crystal structures of OPE were solved in this study for the closed and open conformations. Enzyme activation involves a large displacement of the conserved lid, structural rearrangements of loop α16-α17, and formation of a dimer with a large opening. Three PEG molecules are placed in the active site, mimicking chains of the triglyceride substrate, demonstrating the position of the oxyanion hole and the three pockets that accommodate the sn-1, sn-2 and sn-3 fatty acids chains. One of them is an internal tunnel, connecting the active center with the outer surface of the enzyme 30 Å far from the catalytic Ser220. Based on our structural and biochemical results we propose a mechanism by which a great variety of different substrates can be hydrolyzed in OPE paving the way for the construction of new variants to improve the catalytic properties of these enzymes and their biotechnological applications. PMID:25108239

  10. Crystal structures of Ophiostoma piceae sterol esterase: structural insights into activation mechanism and product release.

    PubMed

    Gutiérrez-Fernández, Javier; Vaquero, María Eugenia; Prieto, Alicia; Barriuso, Jorge; Martínez, María Jesús; Hermoso, Juan A

    2014-09-01

    Sterol esterases are able to efficiently hydrolyze both sterol esters and triglycerides and to carry out synthesis reactions in the presence of organic solvents. Their high versatility makes them excellent candidates for biotechnological purposes. Sterol esterase from fungus Ophiostoma piceae (OPE) belongs to the family abH03.01 of the Candida rugosa lipase-like proteins. Crystal structures of OPE were solved in this study for the closed and open conformations. Enzyme activation involves a large displacement of the conserved lid, structural rearrangements of loop α16-α17, and formation of a dimer with a large opening. Three PEG molecules are placed in the active site, mimicking chains of the triglyceride substrate, demonstrating the position of the oxyanion hole and the three pockets that accommodate the sn-1, sn-2 and sn-3 fatty acids chains. One of them is an internal tunnel, connecting the active center with the outer surface of the enzyme 30 Å far from the catalytic Ser220. Based on our structural and biochemical results we propose a mechanism by which a great variety of different substrates can be hydrolyzed in OPE paving the way for the construction of new variants to improve the catalytic properties of these enzymes and their biotechnological applications.

  11. Store-Operated Ca2+ Release-Activated Ca2+ Channels Regulate PAR2-Activated Ca2+ Signaling and Cytokine Production in Airway Epithelial Cells.

    PubMed

    Jairaman, Amit; Yamashita, Megumi; Schleimer, Robert P; Prakriya, Murali

    2015-09-01

    The G-protein-coupled protease-activated receptor 2 (PAR2) plays an important role in the pathogenesis of various inflammatory and auto-immune disorders. In airway epithelial cells (AECs), stimulation of PAR2 by allergens and proteases triggers the release of a host of inflammatory mediators to regulate bronchomotor tone and immune cell recruitment. Activation of PAR2 turns on several cell signaling pathways of which the mobilization of cytosolic Ca(2+) is likely a critical but poorly understood event. In this study, we show that Ca(2+) release-activated Ca(2+) (CRAC) channels encoded by stromal interaction molecule 1 and Orai1 are a major route of Ca(2+) entry in primary human AECs and drive the Ca(2+) elevations seen in response to PAR2 activation. Activation of CRAC channels induces the production of several key inflammatory mediators from AECs including thymic stromal lymphopoietin, IL-6, and PGE2, in part through stimulation of gene expression via nuclear factor of activated T cells (NFAT). Furthermore, PAR2 stimulation induces the production of many key inflammatory mediators including PGE2, IL-6, IL-8, and GM-CSF in a CRAC channel-dependent manner. These findings indicate that CRAC channels are the primary mechanism for Ca(2+) influx in AECs and a vital checkpoint for the induction of PAR2-induced proinflammatory cytokines.

  12. In vitro Effects of Selected Saponins on the Production and Release of Lysozyme Activity of Human Monocytic and Epithelial Cell Lines

    PubMed Central

    Helal, Racha; Melzig, Matthias F.

    2011-01-01

    Lysozyme is one of the most important factors of innate immunity and a unique enzybiotic in that it exerts not only antibacterial activity, but also antiviral, anti-inflammatory, anticancer and immunomodulatory activities. The purpose of the present study was to investigate whether in vitro exposure to saponins can affect the release and production of lysozyme activity in human monocytic cells THP-1, and in human epithelial cells HT-29. Lysozyme activity levels in cell culture fluids were measured using highly sensitive fluorescence-based lysozyme activity assay. Majority of the examined saponins were demonstrated to stimulate significantly the release of lysozyme activity of monocytes and epithelial cells after one hour treatment at non-toxic concentrations. On the contrary, cells treated with saponins for longer periods up to 72 hours showed tendency to decrease in the secretion and production of lysozyme activity. However, these inhibitory effects of saponins observed with long-term treatment periods were mostly associated with toxic effects of saponins to cells. The results suggested positive contribution of some saponins to lysozyme release of monocytes and epithelial cells upon short exposure. Furthermore, demonstrated ability of these saponins to enhance the release of lysozyme activity can present a new mechanism contribute to explaining important biological characteristics of saponins, including the antibacterial, antiviral, anti-inflammatory or immune-stimulating properties. PMID:21773070

  13. Production of hybrid lipid-based particles loaded with inorganic nanoparticles and active compounds for prolonged topical release.

    PubMed

    García-González, C A; Sampaio da Sousa, A R; Argemí, A; López Periago, A; Saurina, J; Duarte, C M M; Domingo, C

    2009-12-01

    The production of particulate hybrid carriers containing a glyceryl monostearate (Lumulse GMS-K), a waxy triglyceride (Cutina HR), silanized TiO(2) and caffeine were investigated with the aim of producing sunscreens with UV-radiation protection properties. Particles were obtained using the supercritical PGSS (Particles from Gas Saturated Solutions) technique. This method takes advantages of the lower melting temperatures of the lipids obtained from the dissolution of CO(2) in the bulk mixture. Experiments were performed at 13 MPa and 345 K, according to previous melting point measurements. Blends containing Lumulse GMS-K and Cutina HR lipids (50 wt%) were loaded with silanized TiO(2) and caffeine in percentile proportions of 6 and 4 wt%, respectively. The particles produced were characterized using several analytical techniques as follows: system crystallinity was checked by X-ray diffraction and differential scanning calorimetry, thermal stability by thermogravimetric analysis, and morphology by scanning and transmission electron microscopy. Further, the UV-shielding ability of TiO(2) after its dispersion in the lipidic matrix was assessed by solid UV-vis spectroscopy. Preliminary results indicated that caffeine-loaded solid lipid particles presented a two-step dissolution profile, with an initial burst of 60 wt% of the loaded active agent. Lipid blends loaded with TiO(2) and caffeine encompassed the UV-filter behavior of TiO(2) and the photoaging prevention properties of caffeine.

  14. Correlation of recent fission product release data

    SciTech Connect

    Kress, T.S.; Lorenz, R.A.; Nakamura, T.; Osborne, M.F.

    1989-01-01

    For the calculation of source terms associated with severe accidents, it is necessary to model the release of fission products from fuel as it heats and melts. Perhaps the most definitive model for fission product release is that of the FASTGRASS computer code developed at Argonne National Laboratory. There is persuasive evidence that these processes, as well as additional chemical and gas phase mass transport processes, are important in the release of fission products from fuel. Nevertheless, it has been found convenient to have simplified fission product release correlations that may not be as definitive as models like FASTGRASS but which attempt in some simple way to capture the essence of the mechanisms. One of the most widely used such correlation is called CORSOR-M which is the present fission product/aerosol release model used in the NRC Source Term Code Package. CORSOR has been criticized as having too much uncertainty in the calculated releases and as not accurately reproducing some experimental data. It is currently believed that these discrepancies between CORSOR and the more recent data have resulted because of the better time resolution of the more recent data compared to the data base that went into the CORSOR correlation. This document discusses a simple correlational model for use in connection with NUREG risk uncertainty exercises. 8 refs., 4 figs., 1 tab.

  15. Can erythrocytes release biologically active NO?

    PubMed

    Benz, Peter M; Fleming, Ingrid

    2016-01-01

    Under physiological conditions, endothelial cells and the endothelial nitric oxide (NO) synthase (eNOS) are the main source of NO in the cardiovascular system. However, several other cell types have also been implicated in the NO-dependent regulation of cell function, including erythrocytes. NO derived from red blood cells has been proposed to regulate erythrocyte membrane fluidity, inhibit platelet activation and induce vasodilation in hypoxic areas, but these proposals are highly controversial. In the current issue of Cell Communication and Signaling, an elegant study by Gambaryan et al., assayed NO production by erythrocytes by monitoring the activation of the platelet intracellular NO receptor, soluble guanylyl cyclase, and its downstream kinase protein kinase G. After systematically testing different combinations of erythrocyte/platelet suspensions, the authors found no evidence for platelet soluble guanylyl cyclase/protein kinase G activation by erythrocytes and conclude that erythrocytes do not release biologically active NO to inhibit platelet activation. PMID:27639852

  16. GENIE Production Release 2.10.0

    SciTech Connect

    Alam, M.; Andreopoulos, C.; Athar, M.; Bodek, A.; Christy, E.; Coopersmith, B.; Dennis, S.; Dytman, S.; Gallagher, H.; Geary, N.; Golan, T.; Hatcher, R.; Hoshina, K.; Liu, J.; Mahn, K.; Marshall, C.; Morrison, J.; Nirkko, M.; Nowak, J.; Perdue, G. N.; Yarba, J.

    2015-12-25

    GENIE is a neutrino Monte Carlo event generator that simulates the primary interaction of a neutrino with a nuclear target, along with the subsequent propagation of the reaction products through the nuclear medium. It additionally contains libraries for fully-featured detector geometries and for managing various types of neutrino flux. This note details recent updates to GENIE, in particular, changes introduced into the newest production release, version 2.10.0.

  17. Active Region Release Two CMEs

    NASA Video Gallery

    Solar material can be seen blowing off the sun in this video captured by NASA’s Solar Dynamics Observatory (SDO) on the night of Feb. 5, 2013. This active region on the sun sent out two coronal ...

  18. Analysis of a Nuclear Accident: Fission and Activation Product Releases from the Fukushima Daiichi Nuclear Facility as Remote Indicators of Source Identification, Extent of Release, and State of Damaged Spent Nuclear Fuel

    SciTech Connect

    Schwantes, Jon M.; Orton, Christopher R.; Clark, Richard A.

    2012-09-10

    Measurements of several radionuclides within environmental samples taken from the Fukushima Daiichi nuclear facility and reported on the Tokyo Electric Power Company website following the recent tsunami-initiated catastrophe were evaluated for the purpose of identifying the source term, reconstructing the release mechanisms, and estimating the extent of the release. 136Cs/137Cs and 134Cs/137Cs ratios identified Units 1-3 as the major source of radioactive contamination to the surface soil close to the facility. A trend was observed between the fraction of the total core inventory released for a number of fission product isotopes and their corresponding Gibbs Free Energy of formation for the primary oxide form of the isotope, suggesting that release was dictated primarily by chemical volatility driven by temperature and reduction potential within the primary containment vessels of the vented reactors. The absence of any major fractionation beyond volatilization suggested all coolant had evaporated by the time of venting. High estimates for the fraction of the total inventory released of more volatile species (Te, Cs, I) indicated the damage to fuel bundles was likely extensive, minimizing any potential containment due to physical migration of these species through the fuel matrix and across the cladding wall. 238Pu/239,240Pu ratios close-in and at 30 km from the facility indicated that the damaged reactors were the major contributor of Pu to surface soil at the source but that this contribution likely decreased rapidly with distance from the facility. The fraction of the total Pu inventory released to the environment from venting units 1 and 3 was estimated to be ~0.003% based upon Pu/Cs isotope ratios relative to the within-reactor modeled inventory prior to venting and was consistent with an independent model evaluation that considered chemical volatility based upon measured fission product release trends. Significant volatile radionuclides within the spent fuel

  19. Energy release, beam attenuation radiation damage, gas production and accumulation of long-lived activity in Pb, Pb-Bi and Hg targets

    SciTech Connect

    Shubin, Yu.N.

    1996-06-01

    The calculation and analysis of the nuclei concentrations and long-lived residual radioactivity accumulated in Pb, Pb-Bi and Hg targets irradiated by 800 MeV, 30 mA proton beam have been performed. The dominating components to the total radioactivity of radionuclides resulting from fission and spallation reactions and radiative capture by both target nuclei and accumulated radioactive nuclei for various irradiation and cooling times were analyzed. The estimations of spectral component contributions of neutron and proton fluxes to the accumulated activity were carried out. The contributions of fission products to the targets activity and partial activities of main long-lived fission products to the targets activity and partial activities of main long-lived fission products were evaluated. The accumulation of Po isotopes due to reactions induced by secondary alpha-particles were found to be important for the Pb target as compared with two-step radiative capture. The production of Tritium in the targets and its contribution to the total targets activity was considered in detail. It is found that total activities of both targets are close to one another.

  20. Light-Activated Content Release from Liposomes

    PubMed Central

    Leung, Sarah J.; Romanowski, Marek

    2012-01-01

    Successful integration of diagnostic and therapeutic actions at the level of individual cells requires new materials that combine biological compatibility with functional versatility. This review focuses on the development of liposome-based functional materials, where payload release is activated by light. Methods of sensitizing liposomes to light have progressed from the use of organic molecular moieties to the use of metallic plasmon resonant structures. This development has facilitated application of near infrared light for activation, which is preferred for its deep penetration and low phototoxicity in biological tissues. Presented mechanisms of light-activated liposomal content release enable precise in vitro manipulation of minute amounts of reagents, but their use in clinical diagnostic and therapeutic applications will require demonstration of safety and efficacy. PMID:23139729

  1. Recent Release of the ASTER Global DEM Product

    NASA Astrophysics Data System (ADS)

    Behnke, J.; Hall, A.; Meyer, D.; Sohre, T.; Doescher, C.

    2009-12-01

    On June 29th, the ASTER Global Digital Elevation Model (DEM) release was announced to the public and to a very eager audience. ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) is an imaging instrument flying on Terra, a satellite launched in December 1999 as part of NASA's Earth Observing System (EOS). ASTER is a cooperative effort between NASA, Japan's Ministry of Economy, Trade and Industry (METI) and Japan's Earth Remote Sensing Data Analysis Center (ERSDAC). On June 21, NASA Headquarters along with colleagues in Japan (METI) signed a plan for distribution of this product. The global digital elevation model of Earth is available online to users everywhere at no cost from NASA's Land Processes Distributed Active Archive Center (DAAC) located at Sioux Falls, SD. The DAAC is a joint project of NASA and the USGS and is a key component of NASA's EOSDIS. The new ASTER GDEM was created from nearly 1.3 million individual stereo-pair images acquired by the Japanese Advanced Spaceborne Thermal Emission and Reflection Radiometer (Aster) instrument aboard NASA’s Terra satellite. The ASTER elevation model was jointly developed by NASA and METI under contract to Sensor Information Laboratory Corp., Tsukuba, Japan. On June 29, the NASA press release was picked up quickly by numerous news organizations and online sites. Response to the product was incredible! The news of the release of the product was carried on websites across the globe, this fueled a tremendous response from users. Here are a few interesting metrics about the release: - over 41,000 unique visitors to website in first week following release - top countries in order were: US (approx. 20%), Germany, U.K., Brazil, Austria, Canada, Spain, Switzerland, Japan - approximately 29,000 visitors came to the news page in the first week and about 11,000 of these users downloaded the actual press release - by the end of August, over 2 Million ASTER GDEM files had been downloaded from the Land

  2. Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration.

    PubMed

    Rozenfeld, Claudia; Martinez, Rodrigo; Figueiredo, Rodrigo T; Bozza, Marcelo T; Lima, Flávia R S; Pires, Ana Lúcia; Silva, Patrícia M; Bonomo, Adriana; Lannes-Vieira, Joseli; De Souza, Wanderley; Moura-Neto, Vivaldo

    2003-04-01

    The maintenance of a benign chronic Toxoplasma gondii infection is mainly dependent on the persistent presence of gamma interferon (IFN-gamma) in the central nervous system (CNS). However, IFN-gamma-activated microglia are paradoxically involved in parasitism control and in tissue damage during a broad range of CNS pathologies. In this way, nitric oxide (NO), the main toxic metabolite produced by IFN-gamma-activated microglia, may cause neuronal injury during T. gondii infection. Despite the potential NO toxicity, neurodegeneration is not a common finding during chronic T. gondii infection. In this work, we describe a significant down-modulation of NO production by IFN-gamma-activated microglia in the presence of conditioned medium of T. gondii-infected astrocytes (CMi). The inhibition of NO production was paralleled with recovery of neurite outgrowth when neurons were cocultured with IFN-gamma-activated microglia in the presence of CMi. Moreover, the modulation of NO secretion and the neuroprotective effect were shown to be dependent on prostaglandin E(2) (PGE(2)) production by T. gondii-infected astrocytes and autocrine secretion of interleukin-10 (IL-10) by microglia. These events were partially eliminated when infected astrocytes were treated with aspirin and cocultures were treated with anti-IL-10 neutralizing antibodies and RP-8-Br cyclic AMP (cAMP), a protein kinase A inhibitor. Further, the modulatory effects of CMi were mimicked by the presence of exogenous PGE(2) and by forskolin, an adenylate cyclase activator. Altogether, these data point to a T. gondii-triggered regulatory mechanism involving PGE(2) secretion by astrocytes and cAMP-dependent IL-10 secretion by microglia. This may reduce host tissue inflammation, thus avoiding neuron damage during an established Th1 protective immune response. PMID:12654825

  3. Technical Report Series on Global Modeling and Data Assimilation. Volume 42; Soil Moisture Active Passive (SMAP) Project Calibration and Validation for the L4_C Beta-Release Data Product

    NASA Technical Reports Server (NTRS)

    Koster, Randal D. (Editor); Kimball, John S.; Jones, Lucas A.; Glassy, Joseph; Stavros, E. Natasha; Madani, Nima (Editor); Reichle, Rolf H.; Jackson, Thomas; Colliander, Andreas

    2015-01-01

    During the post-launch Cal/Val Phase of SMAP there are two objectives for each science product team: 1) calibrate, verify, and improve the performance of the science algorithms, and 2) validate accuracies of the science data products as specified in the L1 science requirements according to the Cal/Val timeline. This report provides analysis and assessment of the SMAP Level 4 Carbon (L4_C) product specifically for the beta release. The beta-release version of the SMAP L4_C algorithms utilizes a terrestrial carbon flux model informed by SMAP soil moisture inputs along with optical remote sensing (e.g. MODIS) vegetation indices and other ancillary biophysical data to estimate global daily NEE and component carbon fluxes, particularly vegetation gross primary production (GPP) and ecosystem respiration (Reco). Other L4_C product elements include surface (<10 cm depth) soil organic carbon (SOC) stocks and associated environmental constraints to these processes, including soil moisture and landscape FT controls on GPP and Reco (Kimball et al. 2012). The L4_C product encapsulates SMAP carbon cycle science objectives by: 1) providing a direct link between terrestrial carbon fluxes and underlying freeze/thaw and soil moisture constraints to these processes, 2) documenting primary connections between terrestrial water, energy and carbon cycles, and 3) improving understanding of terrestrial carbon sink activity in northern ecosystems.

  4. 14 CFR 1213.109 - News releases concerning international activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false News releases concerning international... RELEASE OF INFORMATION TO NEWS AND INFORMATION MEDIA § 1213.109 News releases concerning international activities. (a) Releases of information involving NASA activities, views, programs, or projects...

  5. 14 CFR 1213.109 - News releases concerning international activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true News releases concerning international... RELEASE OF INFORMATION TO NEWS AND INFORMATION MEDIA § 1213.109 News releases concerning international activities. (a) Releases of information involving NASA activities, views, programs, or projects...

  6. 14 CFR 1213.109 - News releases concerning international activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false News releases concerning international... RELEASE OF INFORMATION TO NEWS AND INFORMATION MEDIA § 1213.109 News releases concerning international activities. (a) Releases of information involving NASA activities, views, programs, or projects...

  7. Induction of apoptosis by Uncaria tomentosa through reactive oxygen species production, cytochrome c release, and caspases activation in human leukemia cells.

    PubMed

    Cheng, An-Chin; Jian, Cheng-Bang; Huang, Yu-Ting; Lai, Ching-Shu; Hsu, Ping-Chi; Pan, Min-Hsiung

    2007-11-01

    Uncaria tomentosa (Wild.) DC., found in the Amazon rain forest in South-America and known commonly as cat's claw, has been used in traditional medicine to prevent and treat inflammation and cancer. Recently, it has been found to possess potent anti-inflammation activities. In this study, we extracted cat's claw using four different solvents of different polarities and compared their relative influence on proliferation in human premyelocytic leukemia HL-60 cell lines. Cat's claw n-hexane extracts (CC-H), ethyl acetate extracts (CC-EA) and n-butanol extracts (CC-B) had a greater anti-cancer effect on HL-60 cells than those extracted with methanol (CC-M). Furthermore, CC-EA induced DNA fragmentation in HL-60 cells in a clearly more a concentration- and time-dependent manner than the other extracts. CC-EA-induced cell death was characterized by cell body shrinkage and chromatin condensation. Further investigating the molecular mechanism behind CC-EA-induced apoptosis, sells treated with CC-EA underwent a rapid loss of mitochondrial transmembrane (DeltaPsi(m)) potential, stimulation of phosphatidylserine flip-flop, release of mitochondrial cytochrome c into cytosol, induction of caspase-3 activity in a time-dependent manner, and induced the cleavage of DNA fragmentation factor (DFF-45) and PARP poly-(ADP-ribose) polymerase (PARP). CC-EA promoted the up-regulation of Fas before the processing and activation of procaspase-8 and cleavage of Bid. In addition, the apoptosis induced by CC-EA was accompanied by up-regulation of Bax, down-regulation of Bcl-X(L) and cleavage of Mcl-1, suggesting that CC-EA may have some compounds that have anti-cancer activities and that further studies using cat's claw extracts need to be pursued. Taken together, the results of our studies show clearly that CC-EA's induction of apoptosis in HL-60 cells may make it very important in the development of medicine that can trigger chemopreventive actions in the body.

  8. Release and activity of histone in diseases.

    PubMed

    Chen, R; Kang, R; Fan, X-G; Tang, D

    2014-01-01

    Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecular pattern molecules when they are released into the extracellular space. Administration of exogenous histones to animals leads to systemic inflammatory and toxic responses through activating Toll-like receptors and inflammasome pathways. Anti-histone treatment (e.g., neutralizing antibodies, activated protein C, recombinant thrombomodulin, and heparin) protect mice against lethal endotoxemia, sepsis, ischemia/reperfusion injury, trauma, pancreatitis, peritonitis, stroke, coagulation, and thrombosis. In addition, elevated serum histone and nucleosome levels have been implicated in multiple pathophysiological processes and progression of diseases including autoimmune diseases, inflammatory diseases, and cancer. Therefore, extracellular histones could serve as biomarkers and novel therapeutic targets in human diseases. PMID:25118930

  9. Fission product release from irradiated LWR fuel under accident conditions

    SciTech Connect

    Strain, R.V.; Sanecki, J.E.; Osborne, M.F.

    1984-01-01

    Fission product release from irradiated LWR fuel is being studied by heating fuel rod segments in flowing steam and an inert carrier gas to simulate accident conditions. Fuels with a range of irradiation histories are being subjected to several steam flow rates over a wide range of temperatures. Fission product release during each test is measured by gamma spectroscopy and by detailed examination of the collection apparatus after the test has been completed. These release results are complemented by a detailed posttest examination of samples of the fuel rod segment. Results of release measurements and fuel rod characterizations for tests at 1400 through 2000/sup 0/C are presented in this paper.

  10. The structure of Clostridium difficile toxin A glucosyltransferase domain bound to Mn2+ and UDP provides insights into glucosyltransferase activity and product release.

    PubMed

    D'Urzo, Nunzia; Malito, Enrico; Biancucci, Marco; Bottomley, Matthew J; Maione, Domenico; Scarselli, Maria; Martinelli, Manuele

    2012-09-01

    Clostridiumdifficile toxin A (TcdA) is a member of the large clostridial toxin family, and is responsible, together with C. difficile toxin B (TcdB), for many clinical symptoms d ring human infections. Like other large clostridial toxins, TcdA catalyzes the glucosylation of GTPases, and is able to inactivate small GTPases within the host cell. Here, we report the crystal structures of the TcdA glucosyltransferase domain (TcdA-GT) in the apo form and in the presence of Mn(2+) and hydrolyzed UDP-glucose. These structures, together with the recently reported crystal structure of TcdA-GT bound to UDP-glucose, provide a detailed understanding of the conformational changes of TcdA that occur during the catalytic cycle. Indeed, we present a new intermediate conformation of a so-called 'lid' loop (residues 510-522 in TcdA), concomitant with the absence of glucose in the catalytic domain. The recombinant TcdA was expressed in Brevibacillus in the inactive apo form. High thermal stability of wild-type TcdA was observed only after the addition of both Mn(2+) and UDP-glucose. The glucosylhydrolase activity, which is readily restored after reconstitution with both these cofactors, was similar to that reported for TcdB. Interestingly, we found that ammonium, like K(+) , is able to activate the UDP-glucose hydrolase activities of TcdA. Consequently, the presence of ammonium in the crystallization buffer enabled us to obtain the first crystal structure of TcdA-GT bound to the hydrolysis product UDP.

  11. USGS Releases New Digital Aerial Products

    USGS Publications Warehouse

    ,

    2005-01-01

    The U.S. Geological Survey (USGS) Center for Earth Resources Observation and Science (EROS) has initiated distribution of digital aerial photographic products produced by scanning or digitizing film from its historical aerial photography film archive. This archive, located in Sioux Falls, South Dakota, contains thousands of rolls of film that contain more than 8 million frames of historic aerial photographs. The largest portion of this archive consists of original film acquired by Federal agencies from the 1930s through the 1970s to produce 1:24,000-scale USGS topographic quadrangle maps. Most of this photography is reasonably large scale (USGS photography ranges from 1:8,000 to 1:80,000) to support the production of the maps. Two digital products are currently available for ordering: high-resolution scanned products and medium-resolution digitized products.

  12. Background and Derivation of ANS-5.4 Standard Fission Product Release Model

    SciTech Connect

    Beyer, Carl E.; Turnbull, Andrew J.

    2010-01-29

    This background report describes the technical basis for the newly proposed American Nuclear Society (ANS) 5.4 standard, Methods for Calculating the Fractional Release of Volatile Fission Products from Oxide Fuels. The proposed ANS 5.4 standard provides a methodology for determining the radioactive fission product releases from the fuel for use in assessing radiological consequences of postulated accidents that do not involve abrupt power transients. When coupled with isotopic yields, this method establishes the 'gap activity,' which is the inventory of volatile fission products that are released from the fuel rod if the cladding are breached.

  13. Analysis of a nuclear accident: fission and activation product releases from the Fukushima Daiichi nuclear facility as remote indicators of source identification, extent of release, and state of damaged spent nuclear fuel.

    PubMed

    Schwantes, Jon M; Orton, Christopher R; Clark, Richard A

    2012-08-21

    Researchers evaluated radionuclide measurements of environmental samples taken from the Fukushima Daiichi nuclear facility and reported on the Tokyo Electric Power Co. Website following the 2011 tsunami-initiated catastrophe. This effort identified Units 1 and 3 as the major source of radioactive contamination to the surface soil near the facility. Radionuclide trends identified in the soils suggested that: (1) chemical volatility driven by temperature and reduction potential within the vented reactors' primary containment vessels dictated the extent of release of radiation; (2) all coolant had likely evaporated by the time of venting; and (3) physical migration through the fuel matrix and across the cladding wall were minimally effective at containing volatile species, suggesting damage to fuel bundles was extensive. Plutonium isotopic ratios and their distance from the source indicated that the damaged reactors were the major contributor of plutonium to surface soil at the source, decreasing rapidly with distance from the facility. Two independent evaluations estimated the fraction of the total plutonium inventory released to the environment relative to cesium from venting Units 1 and 3 to be ∼0.002-0.004%. This study suggests significant volatile radionuclides within the spent fuel at the time of venting, but not as yet observed and reported within environmental samples, as potential analytes of concern for future environmental surveys around the site. The majority of the reactor inventories of isotopes of less volatile elements like Pu, Nb, and Sr were likely contained within the damaged reactors during venting.

  14. Analysis of a nuclear accident: fission and activation product releases from the Fukushima Daiichi nuclear facility as remote indicators of source identification, extent of release, and state of damaged spent nuclear fuel.

    PubMed

    Schwantes, Jon M; Orton, Christopher R; Clark, Richard A

    2012-08-21

    Researchers evaluated radionuclide measurements of environmental samples taken from the Fukushima Daiichi nuclear facility and reported on the Tokyo Electric Power Co. Website following the 2011 tsunami-initiated catastrophe. This effort identified Units 1 and 3 as the major source of radioactive contamination to the surface soil near the facility. Radionuclide trends identified in the soils suggested that: (1) chemical volatility driven by temperature and reduction potential within the vented reactors' primary containment vessels dictated the extent of release of radiation; (2) all coolant had likely evaporated by the time of venting; and (3) physical migration through the fuel matrix and across the cladding wall were minimally effective at containing volatile species, suggesting damage to fuel bundles was extensive. Plutonium isotopic ratios and their distance from the source indicated that the damaged reactors were the major contributor of plutonium to surface soil at the source, decreasing rapidly with distance from the facility. Two independent evaluations estimated the fraction of the total plutonium inventory released to the environment relative to cesium from venting Units 1 and 3 to be ∼0.002-0.004%. This study suggests significant volatile radionuclides within the spent fuel at the time of venting, but not as yet observed and reported within environmental samples, as potential analytes of concern for future environmental surveys around the site. The majority of the reactor inventories of isotopes of less volatile elements like Pu, Nb, and Sr were likely contained within the damaged reactors during venting. PMID:22680069

  15. Thermal-induced conformational changes in the product release area drive the enzymatic activity of xylanases 10B: Crystal structure, conformational stability and functional characterization of the xylanase 10B from Thermotoga petrophila RKU-1

    SciTech Connect

    Santos, Camila Ramos; Meza, Andreia Navarro; Hoffmam, Zaira Bruna; Silva, Junio Cota; Alvarez, Thabata Maria; Ruller, Roberto; Giesel, Guilherme Menegon; Verli, Hugo; Squina, Fabio Marcio; Prade, Rolf Alexander; Murakami, Mario Tyago

    2010-12-10

    Research highlights: {yields} The hyperthermostable xylanase 10B from Thermotoga petrophila RKU-1 produces exclusively xylobiose at the optimum temperature. {yields} Circular dichroism spectroscopy suggests a coupling effect of temperature-induced structural changes with its enzymatic behavior. {yields} Crystallographic and molecular dynamics studies indicate that conformational changes in the product release area modulate the enzyme action mode. -- Abstract: Endo-xylanases play a key role in the depolymerization of xylan and recently, they have attracted much attention owing to their potential applications on biofuels and paper industries. In this work, we have investigated the molecular basis for the action mode of xylanases 10B at high temperatures using biochemical, biophysical and crystallographic methods. The crystal structure of xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1 (TpXyl10B) has been solved in the native state and in complex with xylobiose. The complex crystal structure showed a classical binding mode shared among other xylanases, which encompasses the -1 and -2 subsites. Interestingly, TpXyl10B displayed a temperature-dependent action mode producing xylobiose and xylotriose at 20 {sup o}C, and exclusively xylobiose at 90 {sup o}C as assessed by capillary zone electrophoresis. Moreover, circular dichroism spectroscopy suggested a coupling effect of temperature-induced structural changes with this particular enzymatic behavior. Molecular dynamics simulations supported the CD analysis suggesting that an open conformational state adopted by the catalytic loop (Trp297-Lys326) provokes significant modifications in the product release area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific release of xylobiose at high temperatures.

  16. Coalition releases declaration for healthy and productive oceans

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2012-06-01

    Coalition releases declaration for healthy and productive oceans A coalition of 13 countries or federal agencies participating in a new Global Partnership for Oceans (GPO) indicated its support for a “Declaration for Healthy and Productive Oceans to Help Reduce Poverty” on 16 June, just prior to the Rio+20 conference in Rio de Janeiro, Brazil.

  17. ALKALINITY, PH, AND COPPER CORROSION BY-PRODUCT RELEASE

    EPA Science Inventory

    Contrary to expectations, higher bicarbonate concentrations exacerbate copper corrosion rates and by-product release. In fact, as illustrated by monitoring experiences of large utilities and by laboratory data, the concentration of copper corrosion by-products in drinking water i...

  18. Explanatory Supplement to the WISE Preliminary Data Release Products

    NASA Astrophysics Data System (ADS)

    Cutri, R. M.; Wright, E. L.; Conrow, T.; Bauer, J.; Benford, D.; Brandenburg, H.; Dailey, J.; Eisenhardt, P. R. M.; Evans, T.; Fajardo-Acosta, S.; Fowler, J.; Gelino, C.; Grillmair, C.; Harbut, M.; Hoffman, D.; Jarrett, T.; Kirkpatrick, J. D.; Liu, W.; Mainzer, A.; Marsh, K.; Masci, F.; McCallon, H.; Padgett, D.; Ressler, M. E.; Royer, D.; Skrutskie, M. F.; Stanford, S. A.; Wyatt, P. L.; Tholen, D.; Tsai, C. W.; Wachter, S.; Wheelock, S. L.; Yan, L.; Alles, R.; Beck, R.; Grav, T.; Masiero, J.; McCollum, B.; McGehee, P.; Wittman, M.

    2011-04-01

    The Wide-field Infrared Survey Explorer (WISE; Wright et al. 2010) surveyed the entire sky at 3.4, 4.6, 12 and 22 microns in 2010, achieving 5-sigma point source sensitivities per band better than 0.08, 0.11, 1 and 6 mJy in unconfused regions on the ecliptic. The WISE Preliminary Data Release, conducted on April 14, 2011, incorporates data covering the first ~57% of the sky surveyed that were processed with initial calibrations and reduction algorithms. Release data products include: (1) an Atlas of 10,464 sets of calibrated, coadded images, depth-of-coverage and uncertainty maps in the four WISE bands, (2) a Source Catalog containing positions and four-band photometry for 257 million objects, and (3) an Explanatory Supplement. Ancillary products include an archive of 754,000 sets of calibrated WISE single-exposure images, uncertainty and bit-mask maps, and a database of 2.2 billion source extractions made from the single-exposure images, and moving object tracklets identified by the NEOWISE program (Mainzer et al. 2011). The Explanatory Supplement to the WISE Preliminary Data Release Products is a general guide for users of the WISE data. The Supplement contains an overview of the WISE mission, facilities, and operations, a description of the contents and formats of the WISE image and tabular data products, and cautionary notes that describe known limitations of the Preliminary Release products. Instructions for accessing the WISE data products via the services of the NASA/IPAC Infrared Science Archive are provided. Detailed descriptions of the data processing system and algorithms used to ingest and convert raw WISE data to the calibrated data products are presented, along with assessments of the achieved sky coverage, photometric and astrometric characteristics and completeness and reliability of the Preliminary Release data products. The WISE Preliminary Release Explanatory Supplement is an on-line document that is updated frequently to provide the most current

  19. Production Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Gallaway, Ann, Ed.

    This production systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, domains and objectives, a course description, and a content outline. The guide contains 30 modules on the following topics: production…

  20. Histamine release inhibition activity of bisbenzylisoquinoline alkaloids.

    PubMed

    Nakamura, K; Tsuchiya, S; Sugimoto, Y; Sugimura, Y; Yamada, Y

    1992-12-01

    Eleven examples of bisbenzylisoquinoline alkaloids (head-to-head; 10, head-to-tail; 1) and one half molecule type (N-methylcoclaurine), were tested by in vitro histamine release inhibition assay. The order of the potency of the inhibitory effect was ranked thus: homoaromoline, aromoline, isotetrandrine, cepharanthine, fangchinoline, obaberine, and tetrandrine. The following substances, cepharanoline, berbamine, oxyacanthine, and cycleanine (head-to-tail structure) had no inhibitory effect. N-Methylcoclaurine showed an inhibitory effect comparable to that of fangchinoline. PMID:1484888

  1. Data summary report for fission product release test VI-6

    SciTech Connect

    Osborne, M.F.; Lorenz, R.A.; Travis, J.R.; Webster, C.S.; Collins, J.L.

    1994-03-01

    Test VI-6 was the sixth test in the VI series conducted in the vertical furnace. The fuel specimen was a 15.2-cm-long section of a fuel rod from the BR3 reactor in Belgium. The fuel had experienced a burnup of {approximately}42 MWd/kg, with inert gas release during irradiation of {approximately}2%. The fuel specimen was heated in an induction furnace at 2300 K for 60 min, initially in hydrogen, then in a steam atmosphere. The released fission products were collected in three sequentially operated collection trains designed to facilitate sampling and analysis. The fission product inventories in the fuel were measured directly by gamma-ray spectrometry, where possible, and were calculated by ORIGEN2. Integral releases were 75% for {sup 85}Kr, 67% for {sup 129}I, 64% for {sup 125}Sb, 80% for both {sup 134}Cs and {sup 137}Cs, 14% for {sup 154}Eu, 63% for Te, 32% for Ba, 13% for Mo, and 5.8% for Sr. Of the totals released from the fuel, 43% of the Cs, 32% of the Sb, and 98% of the Eu were deposited in the outlet end of the furnace. During the heatup in hydrogen, the Zircaloy cladding melted, ran down, and reacted with some of the UO{sub 2} and fission products, especially Te and Sb. The total mass released from the furnace to the collection system, including fission products, fuel, and structural materials, was 0.57 g, almost equally divided between thermal gradient tubes and filters. The release behaviors for the most volatile elements, Kr and Cs, were in good agreement with the ORNL Diffusion Model.

  2. Controlled release of biologically active silver from nanosilver surfaces.

    PubMed

    Liu, Jingyu; Sonshine, David A; Shervani, Saira; Hurt, Robert H

    2010-11-23

    Major pathways in the antibacterial activity and eukaryotic toxicity of nanosilver involve the silver cation and its soluble complexes, which are well established thiol toxicants. Through these pathways, nanosilver behaves in analogy to a drug delivery system, in which the particle contains a concentrated inventory of an active species, the ion, which is transported to and released near biological target sites. Although the importance of silver ion in the biological response to nanosilver is widely recognized, the drug delivery paradigm has not been well developed for this system, and there is significant potential to improve nanosilver technologies through controlled release formulations. This article applies elements of the drug delivery paradigm to nanosilver dissolution and presents a systematic study of chemical concepts for controlled release. After presenting thermodynamic calculations of silver species partitioning in biological media, the rates of oxidative silver dissolution are measured for nanoparticles and macroscopic foils and used to derive unified area-based release kinetics. A variety of competing chemical approaches are demonstrated for controlling the ion release rate over 4 orders of magnitude. Release can be systematically slowed by thiol and citrate ligand binding, formation of sulfidic coatings, or the scavenging of peroxy-intermediates. Release can be accelerated by preoxidation or particle size reduction, while polymer coatings with complexation sites alter the release profile by storing and releasing inventories of surface-bound silver. Finally, the ability to tune biological activity is demonstrated through a bacterial inhibition zone assay carried out on selected formulations of controlled release nanosilver.

  3. Data summary report for fission product release test VI-5

    SciTech Connect

    Osborne, M.F.; Lorenz, R.A.; Travis, J.R.; Webster, C.S.; Collins, J.L. )

    1991-10-01

    Test VI-5, the fifth in a series of high-temperature fission product release tests in a vertical test apparatus, was conducted in a flowing mixture of hydrogen and helium. The test specimen was a 15.2-cm-long section of a fuel rod from the BR3 reactor in Belgium which had been irradiated to a burnup of {approximately}42 MWd/kg. Using a hot cell-mounted test apparatus, the fuel rod was heated in an induction furnace under simulated LWR accident conditions to two test temperatures, 2000 K for 20 min and then 2700 K for an additional 20 min. The released fission products were collected in three sequentially operated collection trains on components designed to measure fission product transport characteristics and facilitate sampling and analysis. The results from this test were compared with those obtained in previous tests in this series and with the CORSOR-M and ORNL diffusion release models for fission product release. 21 refs., 19 figs., 12 tabs.

  4. Kinetic release of hydrogen peroxide from different whitening products.

    PubMed

    da Silva Marques, Duarte Nuno; Silveira, Joao Miguel; Marques, Joana Rita; Amaral, Joao Almeida; Guilherme, Nuno Marques; da Mata, António Duarte

    2012-01-01

    The objective of this in vitro study was to evaluate the kinetics of hydrogen peroxide (HP) release from five different bleaching products: VivaStyle® 10% fitted tray gel, VivaStyle® 30% in-office bleaching gel, VivaStyle® Paint-On Plus paint-on bleaching varnish, Opalescence PF® 10% carbamide peroxide gel and Trèswhite Supreme™ 10% HP gel. Each product was firstly titrated for its HP content by a described method. HP release kinetics was assessed by a modified spectrophotometric technique. One sample t test was performed to test for differences between the manufacturers' claimed HP concentrations and the titrated HP content in the whitening products. Analysis of variance plus Tamhane's post hoc tests and Pearson correlation analysis were used as appropriate. Values of P < 0.05 were taken as significant. Titrated HP revealed an increased content when compared to the manufacturer's specifications for all the products tested (P < 0.05), although only products from one manufacturer produced significantly higher results. All products presented a significant (P < 0.05) and sustained release of HP. However, the product with paint-on cellulose-based matrix resulted in significantly (P < 0.05) faster kinetics when compared to other products tested. These results are consistent with manufacturers' reduced recommended application times. The results of this study suggest that modifying the matrix composition may be a viable alternative to HP concentration increase, since this may result in faster release kinetics without exposure to high HP concentrations. PMID:22908081

  5. Presence in, and release of, nanomaterials from consumer products.

    PubMed

    Yang, Yu; Westerhoff, Paul

    2014-01-01

    Widespread use of engineered nanomaterials (ENMs) in consumer products has led to concerns about their potential impact on humans and the environment. In order to fully assess the impacts and release of ENMs from consumer products, this chapter provides an overview of the types of consumer products that contain nanomaterials, the potential release mechanisms of these ENMs from consumer products, and the associated human exposure. Information from two large datasets on consumer goods associated with ENMs, namely, the U.S.-based Project for Emerging Nanotechnologies from the Woodrow Wilson International Center, and the European-based National Institute for Public Health and the Environment of Netherlands, have been summarized. These databases reveal that silver, titanium, carbon-based ENMs are the major nanomaterials associated with consumer products. The presence and potential release of silver, titanium, carbon-based, and other nanomaterials from consumer goods available in published literature are also summarized, as well as the potential human exposure scenarios of inhalation, ingestion, dermal, and combination of all means. The prospecting of nanomaterial in water and biosolids provides further evidence of ENM occurrence, which could be linked to the use of nanomaterials containing consumer goods. Finally, this overview provides guidelines on toxicity studies, which calls for further efforts to analyze the biological effects of ENMs on human beings and their exposure pathways in consumer products.

  6. Presence in, and release of, nanomaterials from consumer products.

    PubMed

    Yang, Yu; Westerhoff, Paul

    2014-01-01

    Widespread use of engineered nanomaterials (ENMs) in consumer products has led to concerns about their potential impact on humans and the environment. In order to fully assess the impacts and release of ENMs from consumer products, this chapter provides an overview of the types of consumer products that contain nanomaterials, the potential release mechanisms of these ENMs from consumer products, and the associated human exposure. Information from two large datasets on consumer goods associated with ENMs, namely, the U.S.-based Project for Emerging Nanotechnologies from the Woodrow Wilson International Center, and the European-based National Institute for Public Health and the Environment of Netherlands, have been summarized. These databases reveal that silver, titanium, carbon-based ENMs are the major nanomaterials associated with consumer products. The presence and potential release of silver, titanium, carbon-based, and other nanomaterials from consumer goods available in published literature are also summarized, as well as the potential human exposure scenarios of inhalation, ingestion, dermal, and combination of all means. The prospecting of nanomaterial in water and biosolids provides further evidence of ENM occurrence, which could be linked to the use of nanomaterials containing consumer goods. Finally, this overview provides guidelines on toxicity studies, which calls for further efforts to analyze the biological effects of ENMs on human beings and their exposure pathways in consumer products. PMID:24683024

  7. Explanatory Supplement to the WISE All-Sky Release Products

    NASA Technical Reports Server (NTRS)

    2012-01-01

    The Wide-field Infrared Survey Explorer (WISE; Wright et al. 2010) surveyed the entire sky at 3.4, 4.6, 12 and 22 microns in 2010, achieving 5-sigma point source sensitivities per band better than 0.08, 0.11, 1 and 6 mJy in unconfused regions on the ecliptic. The WISE All-Sky Data Release, conducted on March 14, 2012, incorporates all data taken during the full cryogenic mission phase, 7 January 2010 to 6 August 20l0,that were processed with improved calibrations and reduction algorithms. Release data products include: (1) an Atlas of 18,240 match-filtered, calibrated and coadded image sets; (2) a Source Catalog containing positions and four-band photometry for over 563 million objects, and (3) an Explanatory Supplement. Ancillary products include a Reject Table that contains 284 million detections that were not selected for the Source Catalog because they are low signal-to-noise ratio or spurious detections of image artifacts, an archive of over 1.5 million sets of calibrated WISE Single-exposure images, and a database of 9.4 billion source extractions from those single images, and moving object tracklets identified by the NEOWISE program (Mainzer et aI. 2011). The WISE All-Sky Data Release products supersede those from the WISE Preliminary Data Release (Cutri et al. 2011). The Explanatory Supplement to the WISE All-Sky Data Release Products is a general guide for users of the WISE data. The Supplement contains an overview of the WISE mission, facilities, and operations, a detailed description of WISE data processing algorithms, a guide to the content and formals of the image and tabular data products, and cautionary notes that describe known limitations of the All-Sky Release products. Instructions for accessing the WISE data products via the services of the NASA/IPAC Infrared Science Archive are provided. The Supplement also provides analyses of the achieved sky coverage, photometric and astrometric characteristics and completeness and reliability of the All

  8. Stagnation pressure activated fuel release mechanism for hypersonic projectiles

    DOEpatents

    Cartland, Harry E.; Hunter, John W.

    2003-01-01

    A propulsion-assisted projectile has a body, a cowl forming a combustion section and a nozzle section. The body has a fuel reservoir within a central portion of the body, and a fuel activation system located along the central axis of the body and having a portion of the fuel activation system within the fuel reservoir. The fuel activation system has a fuel release piston with a forward sealing member where the fuel release piston is adapted to be moved when the forward sealing member is impacted with an air flow, and an air-flow channel adapted to conduct ambient air during flight to the fuel release piston.

  9. Assessment of activation products in the Savannah River Site environment

    SciTech Connect

    Carlton, W.H.; Denham, M.

    1996-07-01

    This document assesses the impact of radioactive activation products released from SRS facilities since the first reactor became operational late in 1953. The isotopes reported here are those whose release resulted in the highest dose to people living near SRS: {sup 32}P, {sup 51}Cr, {sup 60}C, and {sup 65}Zn. Release pathways, emission control features, and annual releases to the aqueous and atmospheric environments are discussed. No single incident has resulted in a major acute release of activation products to the environment. The releases were the result of normal operations of the reactors and separations facilities. Releases declined over the years as better controls were established and production was reduced. The overall radiological impact of SRS activation product atmospheric releases from 1954 through 1994 on the offsite maximally exposed individual can be characterized by a total dose of 0.76 mrem. During the same period, such an individual received a total dose of 14,400 mrem from non-SRS sources of ionizing radiation present in the environment. SRS activation product aqueous releases between 1954 and 1994 resulted in a total dose of 54 mrem to the offsite maximally exposed individual. The impact of SRS activation product releases on offsite populations also has been evaluated.

  10. Formaldehyde release from selected consumer products: influence of chamber loading, multiple products, relative humidity, and temperature

    SciTech Connect

    Pickrell, J.A.; Griffis, L.C.; Mokler, B.V.; Kanapilly, G.M.; Hobbs, C.H.

    1984-09-01

    Formaldehyde release rates were measured for one sample each of a variety of consumer products under various conditions of temperature, humidity, and mass loading in a ventilated chamber. The rate of formaldehyde released from pressed wood products was much greater than from insulation material or carpeting, whether measured in a dynamic (ventilated) or static (nonventilated) chamber. Formaldehyde was released from wood products at a more rapid rate when chamber loadings (product surface area/chamber volume) and chamber concentrations of formaldehyde were reduced. Formaldehyde release from particle board and plywood was not substantially affected by the different temperatures (25-35/sup 0/C) and humidities (40-90%) tested. When particle board was paired with plywood, insulation, or carpet, the formaldehyde released was less than the sum of that released when each product was tested alone. These data suggest that these samples of plywood, insulation, or carpet (slow releasers of formaldehyde) absorbed formaldehyde released from the higher emitting particle board. Consequently, the surface area of carpet, insulation, and/or wood in a ventilated room relative to that of pressed wood products may be an important determinant of formaldehyde concentrations in the air of that room.

  11. Alkali activation of halloysite for adsorption and release of ofloxacin

    NASA Astrophysics Data System (ADS)

    Wang, Qin; Zhang, Junping; Wang, Aiqin

    2013-12-01

    Halloysite nanotubes are promising vehicles for the controlled release of drug molecules. Here, we systematically investigated the effects of alkali activation on the physicochemical properties, structure and morphology of halloysite nanotubes by XRD, FTIR, SEM and TEM, etc. Afterwards, the adsorption and in vitro release properties of halloysite for cationic ofloxacin (OFL) were evaluated. The results indicate that alkali activation dissolves amorphous aluminosilicate, free silica and alumina, which results in the increase in pore volume and pore size. OFL is adsorbed onto halloysite via electrostatic interaction and complexation. Alkali activation could increase the adsorption capacity of halloysite for OFL and prolong release of the adsorbed OFL compared with the natural halloysite. Thus, alkali activation of halloysite is an effective protocol to improve the adsorption and prolong release for cationic drug molecules.

  12. Development of Active Control Method for Supercooling Releasing of Water

    NASA Astrophysics Data System (ADS)

    Mito, Daisuke; Kozawa, Yoshiyuki; Tanino, Masayuki; Inada, Takaaki

    We have tested the prototype ice-slurry generator that enables both production of supercooled water (-2°C) and releasing of its supercooling simultaneously and continuously in a closed piping system. In the experiment, we adopted the irradiation of ultrasonic wave as an active control method of triggering for supercooling releasing, and evaluated the reliability for a practical use compared with the seed ice-crystal trigger. As the results, it has been confirmed that the ultrasonic wave trigger acts assuredly at the same level of degree of supercooling as that by using the seed ice-crystal Trigger. Moreover, it can be found that the ultrasonic wave trigger has the advantage of removing the growing ice-crystals on the pipe wall at the same time. Finally, we have specified the bombardment condition of ultrasonic wave enough to make continuously the ice-slurry in a closed system as the output surface power density > 31.4kW/m2 and the superficial bombardment time > 4.1sec. We have also demonstrated the continuous ice-slurry making for more than 6hours by using the refrigerator system with the practical scale of 88kW.

  13. The search for active release of volcanic gases on Mars

    NASA Astrophysics Data System (ADS)

    Khayat, Alain; Villanueva, Geronimo; Mumma, Michael; Tokunaga, Alan

    2015-11-01

    The study of planetary atmospheres by means of spectroscopy is important for understanding their origin and evolution. The presence of short-lived trace gases in the martian atmosphere would imply recent production, for example, by ongoing geologic activity. On Earth, sulfur dioxide (SO2), sulfur monoxide (SO) and hydrogen sulfide (H2S) are the main sulfur-bearing gases released during volcanic outgassing. Carbonyl sulfide (OCS), also released from some volcanoes on Earth (e.g., Erebus and Nyiragongo), could be formed by reactions involving SO2 or H2S inside magma chambers. We carried out the first ground-based, semi-simultaneous, multi-band and multi-species search for such gases above the Tharsis and Syrtis volcanic regions on Mars. The submillimeter search extended between 23 November 2011 and 13 May 2012 which corresponded to Mars’ mid Northern Spring and early Northern Summer seasons (Ls = 34-110°). The strong submillimeter rotational transitions of SO2, SO and H2S were targeted using the high-resolution heterodyne receiver (aka Barney) on the Caltech Submillimeter Observatory. We reached sensitivities sufficient to detect a volcanic release on Mars that is 4% of the SO2 released continuously from Kilauea volcano in Hawaii, or 5% that of the Masaya volcano in Nicaragua. The infrared search covered OCS in its combination band (ν2+ν3) at 3.42 μm at two successive Mars years, during Mars’ late Northern Spring and mid Northern Summer seasons, spanning Ls= 43º and Ls= 147º. The targeted volcanic districts were observed during the two intervals, 14 Dec. 2011 to 6 Jan. 2012 in the first year, and 30 May 2014 to 16 June 2014 in the second year, using the high resolution infrared spectrometer (CSHELL) on NASA’s Infrared Telescope Facility (NASA/IRTF). We will present our results and discuss their implications for current volcanic outgassing activity on the red planet. We gratefully acknowledge support from the NASA Planetary Astronomy Program under NASA

  14. Product Release Rather than Chelation Determines Metal Specificity for Ferrochelatase

    SciTech Connect

    Medlocka, Amy E.; Cartera, Michael; Daileya, Tamara A.; Daileya, Harry A.; Lanzilotta, William N.

    2009-11-16

    Ferrochelatase (protoheme ferrolyase, E.C. 4.99.1.1) is the terminal enzyme in heme biosynthesis and catalyzes the insertion of ferrous iron into protoporphyrin IX to form protoheme IX (heme). Within the past two years, X-ray crystallographic data obtained with human ferrochelatase have clearly shown that significant structural changes occur during catalysis that are predicted to facilitate metal insertion and product release. One unanswered question about ferrochelatase involves defining the mechanism whereby some metals, such as divalent Fe, Co, Ni, and Zn, can be used by the enzyme in vitro to produce the corresponding metalloporphyrins, while other metals, such as divalent Mn, Hg, Cd, or Pb, are inhibitors of the enzyme. Through the use of high-resolution X-ray crystallography along with characterization of metal species via their anomalous diffraction, the identity and position of Hg, Cd, Ni, or Mn in the center of enzyme-bound porphyrin macrocycle were determined. When Pb, Hg, Cd, or Ni was present in the macrocycle, the conserved {pi} helix was in the extended, partially unwound 'product release' state. Interestingly, in the structure of ferrochelatase with Mn-porphyrin bound, the {pi} helix is not extended or unwound and is in the 'substrate-bound' conformation. These findings show that at least in the cases of Mn, Pb, Cd, and Hg, metal 'inhibition' of ferrochelatase is not due to the inability of the enzyme to insert the metal into the macrocycle or by binding to a second metal binding site as has been previously proposed. Rather, inhibition occurs after metal insertion and results from poor or diminished product release. Possible explanations for the lack of product release are proposed herein.

  15. Histamine-releasing activity and bronchoconstricting effects of sisal

    PubMed Central

    Nicholls, P. J.; Evans, Elizabeth; Valić, F.; Žuškin, Eugenija

    1973-01-01

    Nicholls, P. J., Evans, E., Valić, F., and Žuškin, E. (1973).British Journal of Industrial Medicine,30, 142-145. Histamine-releasing activity and bronchoconstricting effects of sisal. Extracts of dry and oiled sisal released histamine from pig and human but not from rat lung tissue. A suspension in Tyrode solution of the oil used for softening the sisal fibres had a pH of 8·1 and also released histamine from pig and human lung. The releasing activity was abolished when the pH of this suspension was adjusted to pH 7·4. As all the sisal extracts were adjusted to pH 7·4 for incubation with lung tissue, the histamine-releasing activity of sisal in vitro is unrelated to the presence of the oil. Significant (P < 0·01) mean reductions over the work shift of ventilatory capacity (PEF and FEV1·0) were recorded in all the workers exposed to airborne sisal dust. These reductions were greater in combers than in drawers and spinners. Sisal collected from combing machines possessed more histamine-releasing activity than material from drawing and spinning machines. These results indicate that histamine release by sisal may be the cause of acute ventilatory capacity changes in sisal exposure. PMID:4122162

  16. ASBESTOS RELEASE DURING BUILDING DEMOLITION ACTIVITIES

    EPA Science Inventory

    The U.S. Environmental Protection Agency's (EPA) Risk Reduction Engineering Laboratory (RREL) monitored block-wide building demolition and debris disposal activities at Santa Cruz and Watsonsville, California following the 1989 earthquake; an implosion demolition of a 26-story bu...

  17. Evaluation of research products released during a national project funded by the Italian Ministry of Health.

    PubMed

    Santori, G; Valente, R; Ghirelli, R; Valente, U

    2008-01-01

    Evaluation of research products released during activities that have received public funds should be a mandatory practice. In this study, we evaluated the research products released during the research program "Innovative Strategies to Expand Cadaveric Donor Pool for Liver Transplantation" (SITF Project), funded by the Italian Ministry of Health. The SITF Project prefigured the participation of Italian transplantation centers with more advanced experience in the field of liver transplantation. The research products released during the SITF Project were evaluated according to Guidelines for Research Evaluation of the Committee for Evaluation of Research (CIVR) from the Italian Ministry of Education, University and Research. Thus, we considered as the research products released during the SITF Project the number of articles published in English language in peer-reviewed scientific journals by each operative unit (OU), as returned by PubMed. The articles were included on the basis of relationship with the research lines of the SITF Project and availability of the impact factor (IF) calculated by Thomson Scientific for each journal. Following these criteria, 62 research products were released during the executive phase of the SITF Project (January 1, 2004-December 31, 2005). All research products were original articles, with no reviews or letters. The articles were published in 10 different scientific journals (mean IF, 2.64+/-1.74). Spearman's rank test found a weak negative correlation between journal IF and number of published articles (r= -.2919; P= .413). Although the OU involved in the coordination of the SITF Project released a relatively high number of articles (n=8; IF, 0.923+/-0.352), several other OUs obtained better results for number of articles (9-11) and/or IF (3.071+/-2.248 or 2.959+/-1.779). In projects that benefit from public funds, the potential negative impact of coordination activities to scientific production should be adequately considered.

  18. Vagal hyperactivity due to ventromedial hypothalamic lesions increases adiponectin production and release.

    PubMed

    Suzuki, Yoko; Shimizu, Hiroyuki; Ishizuka, Noriko; Kubota, Naoto; Kubota, Tetsuya; Senoo, Akira; Kageyama, Haruaki; Osaka, Toshimasa; Hirako, Satoshi; Kim, Hyoun-Ju; Matsumoto, Akiyo; Shioda, Seiji; Mori, Masatomo; Kadowaki, Takashi; Inoue, Shuji

    2014-05-01

    In obese humans and animals, adiponectin production and release in adipose tissue are downregulated by feedback inhibition, resulting in decreased serum adiponectin. We investigated adiponectin production and release in ventromedial hypothalamic (VMH)-lesioned animals. VMH-lesioned mice showed significant increases in food intake and body weight gain, with hyperinsulinemia and hyperleptinemia at 1 and 4 weeks after VMH-lesioning. Serum adiponectin was elevated in VMH-lesioned mice at 1 and 4 weeks, despite adipocyte hypertrophy in subcutaneous and visceral adipose tissues and increased body fat. Adiponectin production and mRNA were also increased in both adipose tissues in VMH-lesioned mice at 1 week. These results were replicated in VMH-lesioned rats at 1 week. Daily atropine administration for 5 days or subdiaphragmatic vagotomy completely reversed the body weight gain and eliminated the increased adiponectin production and release in these rats, with reversal to a normal serum adiponectin level. Parasympathetic nerve activation by carbachol infusion for 5 days in rats increased serum adiponectin, with increased adiponectin production in visceral and subcutaneous adipose tissues without changes of body weight. These results demonstrate that activation of the parasympathetic nerve by VMH lesions stimulates production of adiponectin in visceral and subcutaneous adipose tissues and adiponectin release, resulting in elevated serum adiponectin. PMID:24487025

  19. Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.

    PubMed

    Harvey, S; Gineste, C; Gaylinn, B D

    2014-08-01

    Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor.

  20. Production of ascorbic acid releasing biomaterials for pelvic floor repair

    PubMed Central

    Mangır, Naşide; Bullock, Anthony J.; Roman, Sabiniano; Osman, Nadir; Chapple, Christopher; MacNeil, Sheila

    2016-01-01

    Objective An underlying abnormality in collagen turnover is implied in the occurrence of complications and recurrences after mesh augmented pelvic floor repair surgeries. Ascorbic acid is a potent stimulant of collagen synthesis. The aim of this study is to produce ascorbic acid releasing poly-lactic acid (PLA) scaffolds and evaluate them for their effects on extracellular matrix production and the strength of the materials. Materials and methods Scaffolds which contained either l-ascorbic acid (AA) and Ascorbate-2-Phosphate (A2P) were produced with emulsion electrospinning. The release of both drugs was measured by UV spectrophotometry. Human dermal fibroblasts were seeded on scaffolds and cultured for 2 weeks. Cell attachment, viability and total collagen production were evaluated as well as mechanical properties. Results No significant differences were observed between AA, A2P, Vehicle and PLA scaffolds in terms of fibre diameter and pore size. The encapsulation efficiency and successful release of both AA and A2P were demonstrated. Both AA and A2P containing scaffolds were significantly more hydrophilic and stronger in both dry and wet states compared to PLA scaffolds. Fibroblasts produced more collagen on scaffolds containing either AA or A2P compared to cells grown on control scaffolds. Conclusion This study is the first to directly compare the two ascorbic acid derivatives in a tissue engineered scaffold and shows that both AA and A2P releasing electrospun PLA scaffolds increased collagen production of fibroblasts to similar extents but AA scaffolds seemed to be more hydrophilic and stronger compared to A2P scaffolds. Statement of significance Mesh augmented surgical repair of the pelvic floor currently relies on non-degradable materials which results in severe complications in some patients. There is an unmet and urgent need for better pelvic floor repair materials. Our current understanding suggests that the ideal material should be able to better

  1. Data summary report for fission product release Test VI-7

    SciTech Connect

    Osborne, M.F.; Lorentz, R.A.; Travis, J.R.; Collins, J.L.; Webster, C.S.

    1995-05-01

    Test VI-7 was the final test in the VI series conducted in the vertical furnace. The fuel specimen was a 15.2-cm-long section of a fuel rod from the Monticello boiling water reactor (BWR). The fuel had experienced a burnup of {approximately}-40 Mwd/kg U. It was heated in an induction furnace for successive 20-min periods at 2000 and 2300 K in a moist air-helium atmosphere. Integral releases were 69% for {sup 85}Kr, 52% for {sup 125}Sb, 71% for both {sup 134}Cs and {sup 137}Cs, and 0.04% for {sup 154}Eu. For the non-gamma-emitting species, release values for 42% for I, 4.1% for Ba, 5.3% for Mo, and 1.2% for Sr were determined. The total mass released from the furnace to the collection system, including fission products, fuel, and structural materials, was 0.89 g, with 37% being collected on the thermal gradient tubes and 63% downstream on filters. Posttest examination of the fuel specimen indicated that most of the cladding was completely oxidized to ZrO{sub 2}, but that oxidation was not quite complete at the upper end. The release behaviors for the most volatile elements, Kr and Cs, were in good agreement with the ORNL-Booth Model.

  2. Technical Report Series on Global Modeling and Data Assimilation. Volume 40; Soil Moisture Active Passive (SMAP) Project Assessment Report for the Beta-Release L4_SM Data Product

    NASA Technical Reports Server (NTRS)

    Koster, Randal D.; Reichle, Rolf H.; De Lannoy, Gabrielle J. M.; Liu, Qing; Colliander, Andreas; Conaty, Austin; Jackson, Thomas; Kimball, John

    2015-01-01

    During the post-launch SMAP calibration and validation (Cal/Val) phase there are two objectives for each science data product team: 1) calibrate, verify, and improve the performance of the science algorithm, and 2) validate the accuracy of the science data product as specified in the science requirements and according to the Cal/Val schedule. This report provides an assessment of the SMAP Level 4 Surface and Root Zone Soil Moisture Passive (L4_SM) product specifically for the product's public beta release scheduled for 30 October 2015. The primary objective of the beta release is to allow users to familiarize themselves with the data product before the validated product becomes available. The beta release also allows users to conduct their own assessment of the data and to provide feedback to the L4_SM science data product team. The assessment of the L4_SM data product includes comparisons of SMAP L4_SM soil moisture estimates with in situ soil moisture observations from core validation sites and sparse networks. The assessment further includes a global evaluation of the internal diagnostics from the ensemble-based data assimilation system that is used to generate the L4_SM product. This evaluation focuses on the statistics of the observation-minus-forecast (O-F) residuals and the analysis increments. Together, the core validation site comparisons and the statistics of the assimilation diagnostics are considered primary validation methodologies for the L4_SM product. Comparisons against in situ measurements from regional-scale sparse networks are considered a secondary validation methodology because such in situ measurements are subject to upscaling errors from the point-scale to the grid cell scale of the data product. Based on the limited set of core validation sites, the assessment presented here meets the criteria established by the Committee on Earth Observing Satellites for Stage 1 validation and supports the beta release of the data. The validation against

  3. Influences of use activities and waste management on environmental releases of engineered nanomaterials.

    PubMed

    Wigger, Henning; Hackmann, Stephan; Zimmermann, Till; Köser, Jan; Thöming, Jorg; von Gleich, Arnim

    2015-12-01

    Engineered nanomaterials (ENM) offer enhanced or new functionalities and properties that are used in various products. This also entails potential environmental risks in terms of hazard and exposure. However, hazard and exposure assessment for ENM still suffer from insufficient knowledge particularly for product-related releases and environmental fate and behavior. This study therefore analyzes the multiple impacts of the product use, the properties of the matrix material, and the related waste management system (WMS) on the predicted environmental concentration (PEC) by applying nine prospective life cycle release scenarios based on reasonable assumptions. The products studied here are clothing textiles treated with silver nanoparticles (AgNPs), since they constitute a controversial application. Surprisingly, the results show counter-intuitive increases by a factor of 2.6 in PEC values for the air compartment in minimal AgNP release scenarios. Also, air releases can shift from washing to wearing activity; their associated release points may shift accordingly, potentially altering release hot spots. Additionally, at end-of-life, the fraction of AgNP-residues contained on exported textiles can be increased by 350% when assuming short product lifespans and globalized WMS. It becomes evident that certain combinations of use activities, matrix material characteristics, and WMS can influence the regional PEC by several orders of magnitude. Thus, in the light of the findings and expected ENM market potential, future assessments should consider these aspects to derive precautionary design alternatives and to enable prospective global and regional risk assessments.

  4. Explosive Products EOS: Adjustment for detonation speed and energy release

    SciTech Connect

    Menikoff, Ralph

    2014-09-05

    Propagating detonation waves exhibit a curvature effect in which the detonation speed decreases with increasing front curvature. The curvature effect is due to the width of the wave profile. Numerically, the wave profile depends on resolution. With coarse resolution, the wave width is too large and results in a curvature effect that is too large. Consequently, the detonation speed decreases as the cell size is increased. We propose a modification to the products equation of state (EOS) to compensate for the effect of numerical resolution; i.e., to increase the CJ pressure in order that a simulation propagates a detonation wave with a speed that is on average correct. The EOS modification also adjusts the release isentrope to correct the energy release.

  5. Explanatory Supplement to the NEOWISE Data Release Products

    NASA Astrophysics Data System (ADS)

    Cutri, R. M.; Mainzer, A.; Conrow, T.; Masci, F.; Bauer, J.; Dailey, J.; Kirkpatrick, J. D.; Fajardo-Acosta, S.; Gelino, C.; Grillmair, C.; Wheelock, S. L.; Yan, L.; Harbut, M.; Beck, R.; Wittman, M.; Wright, E. L.; Masiero, J.; Grav, T.; Sonnett, S.; Nugent, C.; Kramer, E.; Stevenson, R.; Eisenhardt, P. R. M.; Fabinsky, B.; Tholen, D.; Papin, M.; Fowler, J.; McCallon, H.

    2015-03-01

    's survey observations. The Explanatory Supplement to the NEOWISE Data Release Products is a general guide for users of the NEOWISE data. The Supplement contains an overview of the NEOWISE mission, facilities, and operations, a description of the contents and formats of the NEOWISE image and tabular data products, and cautionary notes that describe known limitations of the Release products. Instructions for accessing the NEOWISE data products via the services of the NASA/IPAC Infrared Science Archive are provided. Descriptions of the data processing system and algorithms used to ingest and convert raw NEOWISE images to the calibrated data products are presented, along with assessments of the sky coverage, photometric and astrometric characteristics and completeness and reliability of the NEOWISE Release data products. The NEOWISE Data Release Explanatory Supplement is an on-line document that is updated frequently to provide the most current information for users of the NEOWISE data products. The Explanatory Supplement is maintained at: http://wise2.ipac.caltech.edu/docs/release/neowise/expsup/ NEOWISE is a project of the Jet Propulsion Laboratory/California Institute of Technology, funded by the Planetary Science Division of the National Aeronautics and Space Administration.

  6. Explanatory Supplement to the AllWISE Data Release Products

    NASA Astrophysics Data System (ADS)

    Cutri, R. M.; Wright, E. L.; Conrow, T.; Fowler, J. W.; Eisenhardt, P. R. M.; Grillmair, C.; Kirkpatrick, J. D.; Masci, F.; McCallon, H. L.; Wheelock, S. L.; Fajardo-Acosta, S.; Yan, L.; Benford, D.; Harbut, M.; Jarrett, T.; Lake, S.; Leisawitz, D.; Ressler, M. E.; Stanford, S. A.; Tsai, C. W.; Liu, F.; Helou, G.; Mainzer, A.; Gettings, D.; Gonzalez, A.; Hoffman, D.; Marsh, K. A.; Padgett, D.; Skrutskie, M. F.; Beck, R. P.; Papin, M.; Wittman, M.

    2013-11-01

    The AllWISE program builds upon the successful Wide-field Infrared Survey Explorer (WISE; Wright et al. 2010) mission by combining data from all WISE and NEOWISE (Mainzer et al. 2011) survey phases to form the most comprehensive view of the mid-infrared sky currently available. By combining the data from two complete sky coverage epochs in an advanced data processing system, AllWISE has generated new products that have enhanced photometric sensitivity and accuracy, and improved astrometric precision compared with the earlier WISE All-Sky Data Release. Exploiting the 6 month baseline between the WISE sky coverage epochs enables AllWISE to measure source motions for the first time, and to compute improved flux variability statistics. AllWISE data release products include: a Source Catalog that contains 4-band fluxes, positions, apparent motion measurements, and flux variability statistics for over 747 million objects detected at SNR>5 in the combined exposures; a Multiepoch Photometry Database containing over 42 billion time-tagged, single-exposure fluxes for each object detected on the combined exposures; and an Image Atlas of 18,240 4-band calibrated FITS images, depth-of-coverage and noise maps that cover the sky produced by coadding nearly 7.9 million single-exposure images from the cryogenic and post-cryogenic survey phases. The Explanatory Supplement to the AllWISE Data Release Products is a general guide for users of the AllWISE data. The Supplement contains detailed descriptions of the format and characteristics of the AllWISE data products, as well as a summary of cautionary notes that describe known limitations. The Supplement is an on-line document that is updated frequently to provide the most current information for users of the AllWISE data products. The Explanatory Supplement is maintained at: http://wise2.ipac.caltech.edu/docs/release/allwise/expsup/index.html AllWISE makes use of data from WISE, which is a joint project of the University of

  7. Infralimbic cortex activation and motivated arousal induce histamine release

    PubMed Central

    Forray, María Inés; Torrealba, Fernando

    2015-01-01

    Appetitive behaviours occur in a state of behavioural and physiological activation that allows the optimal performance of these goal-directed behaviours. Here, we tested the hypothesis that histamine neurons under the command of the infralimbic cortex are important to provide behavioural activation. Extracellular histamine and serotonin were measured by microdialysis of the medial prefrontal cortex in behaving rats in parallel with a picrotoxin microinjection into the infralimbic cortex. The injection aroused the rats behaviourally, increased histamine release and decreased serotonin levels. Inhibition of the infralimbic cortex with muscimol produced the opposite effects on neurotransmitter release. The behavioural activation induced by motivating hungry rats with caged food was paralleled by an immediate histamine release, whereas awakening induced by tapping their microdialysis bowl increased serotonin, but not histamine levels. In conclusion, picrotoxin injection into the infralimbic cortex produces behavioural activation together with histamine release; in a similar manner, induction of an appetitive state produced histamine release, likely related to increased behavioural activation characteristic of an appetitive behaviour. PMID:25746330

  8. Optical investigation of heat release and NOx production in combustion

    NASA Astrophysics Data System (ADS)

    Timmerman, B. H.; Bryanston-Cross, P. J.

    2007-10-01

    Two novel optical techniques are presented for non-intrusive, spatially resolved study of combustion, both based on passive Optical Emission Tomography (OET). Firstly, OET is used for non-intrusive study of heat release through the detection of chemiluminescence by the hydroxyl radical that is generated in the burning process. The OET technique presented here is based on a passive fibre-optic detection system, which allows spatially resolved high-frequency detection of the flame front in a combustion flame, where all fibres detect the emission signals simultaneously. The system withstands the high pressures and temperatures typically encountered in the harsh environments of gas turbine combustors and IC engines. The sensor-array is non-intrusive, low-cost, compact, simple to configure and can be quickly set up around a combustion field. The maximum acquisition rate is 2 kHz. This allows spatially resolved study of the fast phenomena in combustion. Furthermore, a method is presented for study of the production of NOx through chemiluminescence from tri-methyl-borate (TMB). In combustion, the tri-methyl-borate produces green luminescence in locations where NOx would be produced. Combining the green luminescence visualisation with UV detection of the hydroxyl radical allows monitoring of heat release and of NOx production areas, thus giving a means of studying both the burning process and the resulting NOx pollution.

  9. Optical investigation of heat release and NOx production in combustion

    NASA Astrophysics Data System (ADS)

    Timmerman, B. H.; Patel, S.; Dunkley, P.; Bryanston-Cross, P. J.

    2005-08-01

    Two passive optical techniques are described to investigate combustion. Optical Emission Tomography (OET) is used for non-intrusive study of heat release through the detection of chemiluminescence by the hydroxyl radical that is generated in the burning process. The OET technique described here is based on a passive fibre-optic detection system, which allows spatially resolved high-frequency detection of the flame front in a combustion flame, where all fibres detect the emission signals simultaneously. The system withstands the high pressures and temperatures typically encountered in the harsh environments of gas turbine combustors and IC engines. The sensor-array is non-intrusive, low-cost, compact, simple to configure and can be quickly set up around a combustion field. The maximum acquisition rate is 2 kHz. This allows spatially resolved study of the fast phenomena in combustion. Furthermore, the production of NOx is investigated through the emission of green light as a result of adding tri-methyl-borate to a flame. In combustion, the tri-methyl-borate produces green luminescence in locations where NOx would be produced. Combining the green luminescence visualisation with OET detection of the hydroxyl radical allows monitoring of heat release and of NOx production areas, thus giving a means of studying both the burning process and the resulting NOx pollution.

  10. Borrelia burgdorferi Spirochetes Induce Mast Cell Activation and Cytokine Release

    PubMed Central

    Talkington, Jeffrey; Nickell, Steven P.

    1999-01-01

    The Lyme disease spirochete, Borrelia burgdorferi, is introduced into human hosts via tick bites. Among the cell types present in the skin which may initially contact spirochetes are mast cells. Since spirochetes are known to activate a variety of cell types in vitro, we tested whether B. burgdorferi spirochetes could activate mast cells. We report here that freshly isolated rat peritoneal mast cells or mouse MC/9 mast cells cultured in vitro with live or freeze-thawed B. burgdorferi spirochetes undergo low but detectable degranulation, as measured by [5-3H] hydroxytryptamine release, and they synthesize and secrete the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In contrast to findings in previous studies, where B. burgdorferi-associated activity was shown to be dependent upon protein lipidation, mast cell TNF-α release was not induced by either lipidated or unlipidated recombinant OspA. This activity was additionally shown to be protease sensitive and surface expressed. Finally, comparisons of TNF-α-inducing activity in known low-, intermediate-, and high-passage B. burgdorferi B31 isolates demonstrated passage-dependent loss of activity, indicating that the activity is probably plasmid encoded. These findings document the presence in low-passage B. burgdorferi spirochetes of a novel lipidation-independent activity capable of inducing cytokine release from host cells. PMID:10024550

  11. Fission Product Monitoring and Release Data for the Advanced Gas Reactor -1 Experiment

    SciTech Connect

    Dawn M. Scates; John B. Walter; Jason M. Harp; Mark W. Drigert; Edward L. Reber

    2010-10-01

    The AGR-1 experiment is a fueled multiple-capsule irradiation experiment that was irradiated in the Advanced Test Reactor (ATR) from December 26, 2006 until November 6, 2009 in support of the Very High Temperature Reactor (VHTR) Technology Development Office (TDO) Fuel Development and Qualification program. An important measure of the fuel performance is the quantification of the fission product releases over the duration of the experiment. To provide this data for the inert fission gasses(Kr and Xe), a fission product monitoring system (FPMS) was developed and implemented to monitor the individual capsule effluents for the radioactive species. The FPMS continuously measured the concentrations of various krypton and xenon isotopes in the sweep gas from each AGR-1 capsule to provide an indicator of fuel irradiation performance. Spectrometer systems quantified the concentrations of Kr-85m, Kr-87, Kr-88, Kr-89, Kr-90, Xe-131m, Xe-133, Xe 135, Xe 135m, Xe-137, Xe-138, and Xe-139 accumulated over repeated eight hour counting intervals.-. To determine initial fuel quality and fuel performance, release activity for each isotope of interest was derived from FPMS measurements and paired with a calculation of the corresponding isotopic production or birthrate. The release activities and birthrates were combined to determine Release-to-Birth ratios for the selected nuclides. R/B values provide indicators of initial fuel quality and fuel performance during irradiation. This paper presents a brief summary of the FPMS, the release to birth ratio data for the AGR-1 experiment and preliminary comparisons of AGR-1 experimental fuels data to fission gas release models.

  12. Controlled release of volatiles under mild reaction conditions: from nature to everyday products.

    PubMed

    Herrmann, Andreas

    2007-01-01

    Volatile organic compounds serve in nature as semiochemicals for communication between species, and are often used as flavors and fragrances in our everyday life. The quite limited longevity of olfactive perception has led to the development of pro-perfumes or pro-fragrances--ideally nonvolatile and odorless fragrance precursors which release the active volatiles by bond cleavage. Only a limited amount of reaction conditions, such as hydrolysis, temperature changes, as well as the action of light, oxygen, enzymes, or microorganisms, can be used to liberate the many different chemical functionalities. This Review describes the controlled chemical release of fragrances and discusses additional challenges such as precursor stability during product storage as well as some aspects concerning toxicity and biodegradability. As the same systems can be applied in different areas of research, the scope of this Review covers fragrance delivery as well as the controlled release of volatiles in general.

  13. Macrophage activation by factors released from acetaminophen-injured hepatocytes: Potential role of HMGB1

    SciTech Connect

    Dragomir, Ana-Cristina; Laskin, Jeffrey D.; Laskin, Debra L.

    2011-06-15

    Toxic doses of acetaminophen (AA) cause hepatocellular necrosis. Evidence suggests that activated macrophages contribute to the pathogenic process; however, the factors that activate these cells are unknown. In these studies, we assessed the role of mediators released from AA-injured hepatocytes in macrophage activation. Treatment of macrophages with conditioned medium (CM) collected 24 hr after treatment of mouse hepatocytes with 5 mM AA (CM-AA) resulted in increased production of reactive oxygen species (ROS). Macrophage expression of heme oxygenase-1 (HO-1) and catalase mRNA was also upregulated by CM-AA, as well as cyclooxygenase (COX)-2 and 12/15-lipoxygenase (LOX). CM-AA also upregulated expression of the proinflammatory chemokines, MIP-1{alpha} and MIP-2. The effects of CM-AA on expression of COX-2, MIP-1{alpha} and MIP-2 were inhibited by blockade of p44/42 MAP kinase, suggesting a biochemical mechanism mediating macrophage activation. Hepatocytes injured by AA were found to release HMGB1, a potent macrophage activator. This was inhibited by pretreatment of hepatocytes with ethyl pyruvate (EP), which blocks HMGB1 release. EP also blocked CM-AA induced ROS production and antioxidant expression, and reduced expression of COX-2, but not MIP-1{alpha} or MIP-2. These findings suggest that HMGB1 released by AA-injured hepatocytes contributes to macrophage activation. This is supported by our observation that expression of the HMGB1 receptor RAGE is upregulated in macrophages in response to CM-AA. These data indicate that AA-injured hepatocytes contribute to the inflammatory environment in the liver through the release of mediators such as HMGB1. Blocking HMGB1/RAGE may be a useful approach to limiting classical macrophage activation and AA-induced hepatotoxicity. - Research Highlights: > These studies analyze macrophage activation by mediators released from acetaminophen-damaged hepatocytes. > Factors released from acetaminophen-injured hepatocytes induce

  14. Nonexocytotic serotonin release tonically suppresses serotonergic neuron activity

    PubMed Central

    Montalbano, Alberto; Baccini, Gilda; Tatini, Francesca; Palmini, Rolando Berlinguer; Corradetti, Renato

    2015-01-01

    The firing activity of serotonergic neurons in raphe nuclei is regulated by negative feedback exerted by extracellular serotonin (5-HT)o acting through somatodendritic 5-HT1A autoreceptors. The steady-state [5-HT]o, sensed by 5-HT1A autoreceptors, is determined by the balance between the rates of 5-HT release and reuptake. Although it is well established that reuptake of 5-HTo is mediated by 5-HT transporters (SERT), the release mechanism has remained unclear. It is also unclear how selective 5-HT reuptake inhibitor (SSRI) antidepressants increase the [5-HT]o in raphe nuclei and suppress serotonergic neuron activity, thereby potentially diminishing their own therapeutic effect. Using an electrophysiological approach in a slice preparation, we show that, in the dorsal raphe nucleus (DRN), continuous nonexocytotic 5-HT release is responsible for suppression of phenylephrine-facilitated serotonergic neuron firing under basal conditions as well as for autoinhibition induced by SSRI application. By using 5-HT1A autoreceptor-activated G protein–gated inwardly rectifying potassium channels of patched serotonergic neurons as 5-HTo sensors, we show substantial nonexocytotic 5-HT release under conditions of abolished firing activity, Ca2+ influx, vesicular monoamine transporter 2–mediated vesicular accumulation of 5-HT, and SERT-mediated 5-HT transport. Our results reveal a cytosolic origin of 5-HTo in the DRN and suggest that 5-HTo may be supplied by simple diffusion across the plasma membrane, primarily from the dense network of neurites of serotonergic neurons surrounding the cell bodies. These findings indicate that the serotonergic system does not function as a sum of independently acting neurons but as a highly interdependent neuronal network, characterized by a shared neurotransmitter pool and the regulation of firing activity by an interneuronal, yet activity-independent, nonexocytotic mechanism. PMID:25712017

  15. Selective release of phosphorus and nitrogen from waste activated sludge with combined thermal and alkali treatment.

    PubMed

    Kim, Minwook; Han, Dong-Woo; Kim, Dong-Jin

    2015-08-01

    Selective release characteristics of phosphorus and nitrogen from waste activated sludge (WAS) were investigated during combined thermal and alkali treatment. Alkali (0.001-1.0N NaOH) treatment and combined thermal-alkali treatment were applied to WAS for releasing total P(T-P) and total nitrogen(T-N). Combined thermal-alkali treatment released 94%, 76%, and 49% of T-P, T-N, and COD, respectively. Release rate was positively associated with NaOH concentration, while temperature gave insignificant effect. The ratio of T-N and COD to T-P that released with alkali treatment ranged 0.74-0.80 and 0.39-0.50, respectively, while combined thermal-alkali treatment gave 0.60-0.90 and 0.20-0.60, respectively. Selective release of T-P and T-N was negatively associated with NaOH. High NaOH concentration created cavities on the surface of WAS, and these cavities accelerated the release rate, but reduced selectivity. Selective release of P and N from sludge has a beneficial effect on nutrient recovery with crystallization processes and it can also enhance methane production. PMID:25690681

  16. Linear Free Energy Correlations for Fission Product Release from the Fukushima-Daiichi Nuclear Accident

    SciTech Connect

    Abrecht, David G.; Schwantes, Jon M.

    2015-03-03

    This paper extends the preliminary linear free energy correlations for radionuclide release performed by Schwantes, et al., following the Fukushima-Daiichi Nuclear Power Plant accident. Through evaluations of the molar fractionations of radionuclides deposited in the soil relative to modeled radionuclide inventories, we confirm the source of the radionuclides to be from active reactors rather than the spent fuel pool. Linear correlations of the form ln χ = -α (ΔGrxn°(TC))/(RTC)+β were obtained between the deposited concentration and the reduction potential of the fission product oxide species using multiple reduction schemes to calculate ΔG°rxn(TC). These models allowed an estimate of the upper bound for the reactor temperatures of TC between 2130 K and 2220 K, providing insight into the limiting factors to vaporization and release of fission products during the reactor accident. Estimates of the release of medium-lived fission products 90Sr, 121mSn, 147Pm, 144Ce, 152Eu, 154Eu, 155Eu, 151Sm through atmospheric venting and releases during the first month following the accident were performed, and indicate large quantities of 90Sr and radioactive lanthanides were likely to remain in the damaged reactor cores.

  17. Modifying release characteristics from 3D printed drug-eluting products.

    PubMed

    Boetker, Johan; Water, Jorrit Jeroen; Aho, Johanna; Arnfast, Lærke; Bohr, Adam; Rantanen, Jukka

    2016-07-30

    This work describes an approach to modify the release of active compound from a 3D printed model drug product geometry intended for flexible dosing and precision medication. The production of novel polylactic acid and hydroxypropyl methylcellulose based feed materials containing nitrofurantoin for 3D printing purposes is demonstrated. Nitrofurantoin, Metolose® and polylactic acid were successfully co-extruded with up to 40% Metolose® content, and subsequently 3D printed into model disk geometries (ø10mm, h=2mm). Thermal analysis with differential scanning calorimetry and solid phase identification with Raman spectroscopy showed that nitrofurantoin remained in its original solid form during both hot-melt extrusion and subsequent 3D printing. Rheological measurements of the different compositions showed that the flow properties were sensitive to the amount of undissolved particles present in the formulation. Release of nitrofurantoin from the disks was dependent on Metolose® loading, with higher accumulated release observed for higher Metolose® loads. This work shows the potential of custom-made, drug loaded feed materials for 3D printing of precision drug products with tailored drug release characteristics.

  18. Modifying release characteristics from 3D printed drug-eluting products.

    PubMed

    Boetker, Johan; Water, Jorrit Jeroen; Aho, Johanna; Arnfast, Lærke; Bohr, Adam; Rantanen, Jukka

    2016-07-30

    This work describes an approach to modify the release of active compound from a 3D printed model drug product geometry intended for flexible dosing and precision medication. The production of novel polylactic acid and hydroxypropyl methylcellulose based feed materials containing nitrofurantoin for 3D printing purposes is demonstrated. Nitrofurantoin, Metolose® and polylactic acid were successfully co-extruded with up to 40% Metolose® content, and subsequently 3D printed into model disk geometries (ø10mm, h=2mm). Thermal analysis with differential scanning calorimetry and solid phase identification with Raman spectroscopy showed that nitrofurantoin remained in its original solid form during both hot-melt extrusion and subsequent 3D printing. Rheological measurements of the different compositions showed that the flow properties were sensitive to the amount of undissolved particles present in the formulation. Release of nitrofurantoin from the disks was dependent on Metolose® loading, with higher accumulated release observed for higher Metolose® loads. This work shows the potential of custom-made, drug loaded feed materials for 3D printing of precision drug products with tailored drug release characteristics. PMID:26987609

  19. Cannabinoid receptor activation shifts temporally engendered patterns of dopamine release.

    PubMed

    Oleson, Erik B; Cachope, Roger; Fitoussi, Aurelie; Tsutsui, Kimberly; Wu, Sharon; Gallegos, Jacqueline A; Cheer, Joseph F

    2014-05-01

    The ability to discern temporally pertinent environmental events is essential for the generation of adaptive behavior in conventional tasks, and our overall survival. Cannabinoids are thought to disrupt temporally controlled behaviors by interfering with dedicated brain timing networks. Cannabinoids also increase dopamine release within the mesolimbic system, a neural pathway generally implicated in timing behavior. Timing can be assessed using fixed-interval (FI) schedules, which reinforce behavior on the basis of time. To date, it remains unknown how cannabinoids modulate dopamine release when responding under FI conditions, and for that matter, how subsecond dopamine release is related to time in these tasks. In the present study, we hypothesized that cannabinoids would accelerate timing behavior in an FI task while concurrently augmenting a temporally relevant pattern of dopamine release. To assess this possibility, we measured subsecond dopamine concentrations in the nucleus accumbens while mice responded for food under the influence of the cannabinoid agonist WIN 55,212-2 in an FI task. Our data reveal that accumbal dopamine concentrations decrease proportionally to interval duration--suggesting that dopamine encodes time in FI tasks. We further demonstrate that WIN 55,212-2 dose-dependently increases dopamine release and accelerates a temporal behavioral response pattern in a CB1 receptor-dependent manner--suggesting that cannabinoid receptor activation modifies timing behavior, in part, by augmenting time-engendered patterns of dopamine release. Additional investigation uncovered a specific role for endogenous cannabinoid tone in timing behavior, as elevations in 2-arachidonoylglycerol, but not anandamide, significantly accelerated the temporal response pattern in a manner akin to WIN 55,212-2. PMID:24345819

  20. Commercial Product Activation Using RFID

    NASA Technical Reports Server (NTRS)

    Jedrey, Thomas

    2008-01-01

    Radio-frequency identification (RFID) would be used for commercial product activation, according to a proposal. What is new here is the concept of combining RFID with activation - more specifically, using RFID for activating commercial products (principally, electronic ones) and for performing such ancillary functions as tracking individual product units on production lines, tracking shipments, and updating inventories. According to the proposal, an RFID chip would be embedded in each product. The information encoded in the chip would include a unique number for identifying the product. An RFID reader at the point of sale would record the number of the product and would write digital information to the RFID chip for either immediate activation of the product or for later interrogation and processing. To be practical, an RFID product-activation system should satisfy a number of key requirements: the system should be designed to be integrable into the inventory-tracking and the data-processing and -communication infrastructures of businesses along the entire supply chain from manufacture to retail; the system should be resistant to sophisticated hacking; activation codes should be made sufficiently complexity to minimize the probability of activating stolen products; RFID activation equipment at points of sale must be capable to two-way RF communication for the purposes of reading information from, and writing information to, embedded RFID chips; the equipment at points of sale should be easily operable by sales clerks with little or no training; the point-of-sale equipment should verify activation and provide visible and/or audible signals indicating verification or lack thereof; and, the system should be able to handle millions of products per year with minimal human intervention, among other requirements.

  1. Nanovalve-controlled cargo release activated by plasmonic heating.

    PubMed

    Croissant, Jonas; Zink, Jeffrey I

    2012-05-01

    The synthesis and operation of a light-operated nanovalve that controls the pore openings of mesoporous silica nanoparticles containing gold nanoparticle cores is described. The nanoparticles, consisting of 20 nm gold cores inside ~150 nm mesoporous silica spheres, were synthesized using a unique one-pot method. The nanovalves consist of cucurbit[6]uril rings encircling stalks that are attached to the ~2 nm pore openings. Plasmonic heating of the gold core raises the local temperature and decreases the ring-stalk binding constant, thereby unblocking the pore and releasing the cargo molecules that were preloaded inside. Bulk heating of the suspended particles to 60 °C is required to release the cargo, but no bulk temperature change was observed in the plasmonic heating release experiment. High-intensity irradiation caused thermal damage to the silica particles, but low-intensity illumination caused a local temperature increase sufficient to operate the valves without damaging the nanoparticle containers. These light-stimulated, thermally activated, mechanized nanoparticles represent a new system with potential utility for on-command drug release.

  2. Analysis of fission product release behavior during the TMI-2 accident

    SciTech Connect

    Petti, D. A.; Adams, J. P.; Anderson, J. L.; Hobbins, R. R.

    1987-01-01

    An analysis of fission product release during the Three Mile Island Unit 2 (TMI-2) accident has been initiated to provide an understanding of fission product behavior that is consistent with both the best estimate accident scenario and fission product results from the ongoing sample acquisition and examination efforts. ''First principles'' fission product release models are used to describe release from intact, disrupted, and molten fuel. Conclusions relating to fission product release, transport, and chemical form are drawn. 35 refs., 12 figs., 7 tabs.

  3. Production and release of asexual sporangia in Plasmopara viticola.

    PubMed

    Caffi, Tito; Gilardi, Giovanna; Monchiero, Matteo; Rossi, Vittorio

    2013-01-01

    To study the influence of environmental conditions on sporulation of Plasmopara viticola lesions under vineyard's conditions, unsprayed vines were inspected every second or third day and the numbers of sporulating and nonsporulating lesions were counted in two North Italy vineyards in 2008 to 2010. Infected leaves were removed so that only fresh lesions were assessed at each field assessment. Sporulation was studied at two scales, across field assessments and across the seasonal population of lesions. Frequencies of sporulating lesions were positively correlated with the numbers of moist hours in the preceding dark period (i.e., the number of hours between 8:00 p.m. and 7:00 a.m. with relative humidity ≥80%, rainfall >0 mm, or wetness duration >30 min). In a receiver operating characteristic analysis, predicted sporulation based on the occurrence of ≥3 moist hours at night provided overall accuracy of 0.85. To study the time course of sporulation on lesions which were not washed by rainfall, numbers of sporangia produced per square millimeter of lesion were estimated on individual cohorts of lesions over the whole infectious period. The numbers of sporangia per square millimeter of lesion increased rapidly during the first 4 days after the beginning of sporulation and then tapered off prior to a halt; the time course of cumulative sporangia production by a lesion followed a monomolecular growth model (R(2) = 0.97). The total number of sporangia produced by a square millimeter of lesion increased as the maximum temperature decreased and moist hours in the dark increased. To study the release pattern of the sporangia, spore samplers were placed near grapevines with sporulating lesions. Airborne sporangia were caught in 91.2% of the days over a wide range of weather conditions, including rainless periods. The results of this study provide quantitative information on production of P. viticola sporangia that may help refine epidemiological models used as decision

  4. Bronchial epithelial cells release monocyte chemotactic activity in response to smoke and endotoxin

    SciTech Connect

    Koyama, S.; Rennard, S.I.; Leikauf, G.D.; Robbins, R.A. )

    1991-08-01

    An increase in mononuclear phagocytes occurs within the airways during airway inflammation. Bronchial epithelial cells could release monocyte chemotactic activity and contribute to this increase. To test this hypothesis, bovine bronchial epithelial cells were isolated and maintained in culture. Bronchial epithelial cell culture supernatant fluids were evaluated for monocyte chemotactic activity. Epithelial cell culture supernatant fluids attracted significantly greater numbers of monocytes compared to media alone and the number of monocytes attracted increased in a time dependent manner. Endotoxin and smoke extract induced a dose and time dependent release of monocyte chemotactic activity compared with cells cultured in media (52.5 {plus minus} 2.6 (endotoxin), 30.5 {plus minus} 2.3 (smoke) vs 20.5 {plus minus} 2.2 cells/high power field (HPF) p less than 0.001). The released activity was chemotactic by checkerboard analysis. Stimulation of the epithelial cells by opsonized zymosan, calcium ionophore (A23187), and PMA also resulted in an increase in monocyte chemotactic activity (p less than 0.01). Because the release of activity was blocked by the lipoxygenase inhibitors, nordihydroguaiaretic acid and diethycarbamazine, epithelial cell monolayers were cultured with 3 microCi (3H)arachidonic acid for 24 h and then exposed to A23187, PMA, or both stimuli, for 4, 8, and 24 h. Analysis of the released 3H activity was performed with reverse-phase HPLC and revealed that the major lipoxygenase product was leukotriene B4. These data suggest that monocytes may be recruited into airways in response to chemotactic factors released by bronchial epithelial cells.

  5. Calcium regulation of tissue plasminogen activator and plasminogen activator inhibitor-1 release from cultured human vascular endothelial cells.

    PubMed

    Yamamoto, C; Kaji, T; Sakamoto, M; Kozuka, H; Koizumi, F

    1994-04-15

    Tissue plasminogen activator (t-PA) produced by vascular endothelial cells converts plasminogen to plasmin which degrades fibrin. Since t-PA activity is greatly potentiated in the presence of fibrin (1,2), the activator is implicated in intravascular fibrinolysis. On the other hand, endothelial cells also produce plasminogen activator inhibitor-1 (PAI-1) (3). The inhibitor associated with vascular endothelium rapidly inhibits t-PA, while that released into the liquid phase has a little anti-activator activity (4). However, clinical studies have shown that elevation of plasma PAI-1 level is a risk factor of thrombosis (5,6). It is thus suggested that the balance between t-PA and PAI-1 is important for the regulation of fibrinolysis. The release of t-PA and PAI-1 from vascular endothelial cells is regulated by physiological factors including thrombin (3,7), histamine (8), vasoconstrictor peptide endothelins (9,10) and cytokines (11). In addition, the regulation of the t-PA release and that of the PAI-1 release are not necessarily coupled. It has been shown that activated protein kinase C and cyclic AMP are involved in the stimulation and suppression, respectively, of the endothelial t-PA and PAI-1 production (12,13). However, the role of intracellular calcium in the regulation of endothelial t-PA and PAI-1 release has remained to be elucidated. In the present study, we investigated the effect of calcium ionophore A23187 on the release of t-PA antigen (t-PA:Ag) and PAI-1 antigen (PAI-1:Ag) from cultured vascular endothelial cells derived from human umbilical vein.

  6. Linear free energy correlations for fission product release from the Fukushima-Daiichi nuclear accident.

    PubMed

    Abrecht, David G; Schwantes, Jon M

    2015-03-01

    This paper extends the preliminary linear free energy correlations for radionuclide release performed by Schwantes et al., following the Fukushima-Daiichi Nuclear Power Plant accident. Through evaluations of the molar fractionations of radionuclides deposited in the soil relative to modeled radionuclide inventories, we confirm the initial source of the radionuclides to the environment to be from active reactors rather than the spent fuel pool. Linear correlations of the form In χ = −α ((ΔGrxn°(TC))/(RTC)) + β were obtained between the deposited concentrations, and the reduction potentials of the fission product oxide species using multiple reduction schemes to calculate ΔG°rxn (TC). These models allowed an estimate of the upper bound for the reactor temperatures of TC between 2015 and 2060 K, providing insight into the limiting factors to vaporization and release of fission products during the reactor accident. Estimates of the release of medium-lived fission products 90Sr, 121mSn, 147Pm, 144Ce, 152Eu, 154Eu, 155Eu, and 151Sm through atmospheric venting during the first month following the accident were obtained, indicating that large quantities of 90Sr and radioactive lanthanides were likely to remain in the damaged reactor cores.

  7. Linear free energy correlations for fission product release from the Fukushima-Daiichi nuclear accident.

    PubMed

    Abrecht, David G; Schwantes, Jon M

    2015-03-01

    This paper extends the preliminary linear free energy correlations for radionuclide release performed by Schwantes et al., following the Fukushima-Daiichi Nuclear Power Plant accident. Through evaluations of the molar fractionations of radionuclides deposited in the soil relative to modeled radionuclide inventories, we confirm the initial source of the radionuclides to the environment to be from active reactors rather than the spent fuel pool. Linear correlations of the form In χ = −α ((ΔGrxn°(TC))/(RTC)) + β were obtained between the deposited concentrations, and the reduction potentials of the fission product oxide species using multiple reduction schemes to calculate ΔG°rxn (TC). These models allowed an estimate of the upper bound for the reactor temperatures of TC between 2015 and 2060 K, providing insight into the limiting factors to vaporization and release of fission products during the reactor accident. Estimates of the release of medium-lived fission products 90Sr, 121mSn, 147Pm, 144Ce, 152Eu, 154Eu, 155Eu, and 151Sm through atmospheric venting during the first month following the accident were obtained, indicating that large quantities of 90Sr and radioactive lanthanides were likely to remain in the damaged reactor cores. PMID:25675358

  8. Substrate lability and plant activity controls greenhouse gas release from Neotropical peatland

    NASA Astrophysics Data System (ADS)

    Sjogersten, Sofie; Hoyos, Jorge; Lomax, Barry; Turner, Ben; Wright, Emma

    2014-05-01

    Almost one third of global CO2 emissions resulting from land use change and substantial CH4 emissions originate from tropical peatlands. However, our understanding of the controls of CO2 and CH4 release from tropical peatlands are limited. The aim of this study was to investigate the role of peat lability and the activity of the vegetation on gas release using a combination of field and laboratory experiments. We demonstrated that peat lability constrained CH4 production to the surface peat under anaerobic conditions. The presence of plants shifted the C balance from a C source to a C sink with respect to CO2 while the activity of the root system strongly influenced CH4 emissions through its impact on soil O2 inputs. Both field and laboratory data suggest a coupling between the photosynthetic activity of the vegetation and the release of both CO2 and CH4 following the circadian rhythm of the dominant plant functional types. Forest clearance for agriculture resulted in elevated CH4 release, which we attribute in part to the cessation of root O2 inputs to the peat. We conclude that high emissions of CO2 and CH4 from forested tropical peatlands are likely driven by labile C inputs from the vegetation but that root O2 release may limit CH4 emissions.

  9. 14 CFR § 1213.109 - News releases concerning international activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false News releases concerning international... ADMINISTRATION RELEASE OF INFORMATION TO NEWS AND INFORMATION MEDIA § 1213.109 News releases concerning international activities. (a) Releases of information involving NASA activities, views, programs, or...

  10. Reducing implant-related infections: active release strategies.

    PubMed

    Hetrick, Evan M; Schoenfisch, Mark H

    2006-09-01

    Despite sterilization and aseptic procedures, bacterial infection remains a major impediment to the utility of medical implants including catheters, artificial prosthetics, and subcutaneous sensors. Indwelling devices are responsible for over half of all nosocomial infections, with an estimate of 1 million cases per year (2004) in the United States alone. Device-associated infections are the result of bacterial adhesion and subsequent biofilm formation at the implantation site. Although useful for relieving associated systemic infections, conventional antibiotic therapies remain ineffective against biofilms. Unfortunately, the lack of a suitable treatment often leaves extraction of the contaminated device as the only viable option for eliminating the biofilm. Much research has focused on developing polymers that resist bacterial adhesion for use as medical device coatings. This tutorial review focuses on coatings that release antimicrobial agents (i.e., active release strategies) for reducing the incidence of implant-associated infection. Following a brief introduction to bacteria, biofilms, and infection, the development and study of coatings that slowly release antimicrobial agents such as antibiotics, silver ions, antibodies, and nitric oxide are covered. The success and limitations of these strategies are highlighted.

  11. On the Periodicity of Energy Release in Solar Active Regions

    NASA Astrophysics Data System (ADS)

    Goldvarg, T. B.; Nagovitsyn, Yu. A.; Solov'Ev, A. A.

    2005-06-01

    We investigate the periodic regimes of energy release on the Sun, namely, the recurrence of solar flares in active regions using the Solar Geophysical Data Journal on Hα flares from 1979 until 1981, which corresponds to the maximum of solar cycle 21. We obtained the following series of periods in the manifestation of flare activity bymeans of a correlation periodogram analysis, a self-similarity function, and a wavelet analysis: ˜1, 2, 3 h as well as ˜0.4, 1, 2, 5 days. We suggest a diffusive model for the quasi-periodic transfer of toroidal magnetic fields from under the photosphere to interpret the retrieved sequence of periods in the enhancement of flare activity. We estimated the typical spatial scales of the magnetic field variations in the solar convection zone: ˜17 000 km.

  12. Radiation Damage and Fission Product Release in Zirconium Nitride

    SciTech Connect

    Egeland, Gerald W.

    2005-08-29

    Zirconium nitride is a material of interest to the AFCI program due to some of its particular properties, such as its high melting point, strength and thermal conductivity. It is to be used as an inert matrix or diluent with a nuclear fuel based on transuranics. As such, it must sustain not only high temperatures, but also continuous irradiation from fission and decay products. This study addresses the issues of irradiation damage and fission product retention in zirconium nitride through an assessment of defects that are produced, how they react, and how predictions can be made as to the overall lifespan of the complete nuclear fuel package. Ion irradiation experiments are a standard method for producing radiation damage to a surface for observation. Cryogenic irradiations are performed to produce the maximum accumulation of defects, while elevated temperature irradiations may be used to allow defects to migrate and react to form clusters and loops. Cross-sectional transmission electron microscopy and grazing-incidence x-ray diffractometry were used in evaluating the effects that irradiation has on the crystal structure and microstructure of the material. Other techniques were employed to evaluate physical effects, such as nanoindentation and helium release measurements. Results of the irradiations showed that, at cryogenic temperatures, ZrN withstood over 200 displacements per atom without amorphization. No significant change to the lattice or microstructure was observed. At elevated temperatures, the large amount of damage showed mobility, but did not anneal significantly. Defect clustering was possibly observed, yet the size was too small to evaluate, and bubble formation was not observed. Defects, specifically nitrogen vacancies, affect the mechanical behavior of ZrN dramatically. Current and previous work on dislocations shows a distinct change in slip plane, which is evidence of the bonding characteristics. The stacking-fault energy changes dramatically with

  13. Presynaptic Kainate Receptor Activation Preserves Asynchronous GABA Release Despite the Reduction in Synchronous Release from Hippocampal CCK Interneurons

    PubMed Central

    Daw, Michael I.; Pelkey, Kenneth A.; Chittajallu, Ramesh; McBain, Chris J.

    2010-01-01

    Inhibitory synaptic transmission in the hippocampus in mediated by a wide variety of different interneuron classes which are assumed to play different roles in network activity. Activation of presynaptic kainate receptors (KARs) has been shown to reduce inhibitory transmission but the interneuron class(es) at which they act is only recently beginning to emerge. Using paired recordings we show that KAR activation causes a decrease in presynaptic release from CCK- but not PV-containing interneurons and that this decrease is observed when pyramidal cells, but not interneurons, are the postsynaptic target. We also show that although the synchronous release component is reduced, the barrage of asynchronous GABA release from CCK interneurons during sustained firing is unaffected by KAR activation. This indicates that presynaptic KARs preserve and act in concert with asynchronous release to switch CCK interneurons from a phasic inhibition mode to produce prolonged inhibition during periods of intense activity. PMID:20720128

  14. Cholecystokinin receptors: disparity between phosphoinositide breakdown and amylase releasing activity of CCK analogues in pancreas

    SciTech Connect

    Lin, C.W.; Grant, D.; Bianchi, B.; Miller, T.; Witte, D.; Shue, Y.K.; Nadzan, A.

    1986-03-05

    Cholecystokinin (CCK) peptides are a family of hormones which also occur in brain. In pancreas CCK stimulates the release of amylase, a process that is dependent on the mobilization of intracellular Ca/sup 2 +/. Recent evidence suggests that inositol 1,4,5-trisphosphate, the breakdown product of phosphatidylinositol 4,5-bisphosphate, is responsible for the rise in intracellular Ca/sup 2 +/. Their laboratory has developed assays to study synthetic CCK analogues using radioligand binding, PI breakdown and amylase release. They have shown that there are good correlations among these three assay systems for the carboxy terminal fragments of CCK/sub 8/. Recently, they have discovered synthetic analogues of CCK/sub 4/ that are full agonists in amylase release but are ineffective in causing PI breakdown. In particular, A-61576, Boc-5-amino-2-indolemethylene-pent-2-ene-1-oyl-Leu-Asp-Phe-NH/sub 2/, is a full agonist in the amylase releasing assay, but is devoid of PI stimulating activity. A-61576 completely reverses the stimulation of PI response induced by CCK/sub 8/, indicative of an antagonist. Since a mechanism other than the PI breakdown is responsible for amylase release by A-61576, they suggest that separate receptors are responsible for PI breakdown and amylase release.

  15. Histamine release inhibitory activity of Piper nigrum leaf.

    PubMed

    Hirata, Noriko; Naruto, Shunsuke; Inaba, Kazunori; Itoh, Kimihisa; Tokunaga, Masashi; Iinuma, Munekazu; Matsuda, Hideaki

    2008-10-01

    Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200 and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after and 24 h [late phase response (LPR)] after DNFB challenge in mice which were passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late phase response (vLPR) in the model mice was significant but weaker than that on IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited in vitro inhibitory effect on compound 48/80-induced histamine release from rat peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active principles having histamine release inhibitory activity.

  16. Interleukin 10 release during endotoxaemia in chimpanzees: role of platelet-activating factor and interleukin 6.

    PubMed

    van der Poll, T; Jansen, J; Levi, M; ten Cate, H; Hack, C E; Aarden, L A; ten Cate, J W; van Deventer, S J

    1996-01-01

    Interleukin (IL-)10 has been demonstrated to inhibit endotoxin-induced production of a number of pro-inflammatory cytokines. The present study sought to compare the appearances in the circulation of IL-10, IL-6 and IL-8, and to assess the roles of endogenously produced platelet-activating factor (PAF) and IL-6 in IL-10 release during endotoxaemia in chimpanzees. Intravenous injection of endotoxin (lot EC-5, 4 ng/kg, n = 8) induced a transient rise in serum IL-10 concentrations, peaking after 2 h (213 +/- 70 pg/ml; P < 0.05). No correlations existed between peak IL-10 levels, and peak IL-6 and IL-8 levels. Neither infusion of the specific PAF antagonist TCV-309 (n = 4), nor infusion of a neutralizing anti-IL-6 monoclonal antibody (n = 4) influenced endotoxin-induced IL-10 release. IL-10 release elicited by injection of endotoxin is not mediated by PAF or IL6.

  17. REEVALUATION OF WATERBORNE RELEASES OF RADIOACTIVE MATERIALS FROM THE MAYAK PRODUCTION ASSOCIATION INTO THE TECHA RIVER IN 1949-1951

    SciTech Connect

    Degteva, M. O.; Shagina, N. B.; Vorobiova, M. I.; Anspaugh, L. R.; Napier, Bruce A.

    2012-01-01

    The Mayak Production Association was the first site for the production of weapon-grade plutonium in Russia. Early operations led to the waterborne release of large amounts of radioactive materials into the small Techa River. Residents living downstream used river water for drinking and other purposes. The releases and subsequent flooding resulted in the deposition of sediments along the shoreline and on floodplain soil. Primary routes of exposure were external dose from the deposited sediments and the ingestion of 90Sr and other radionuclides. Study of the Techa River Cohort has revealed an increased incidence of leukemia and solid cancers. These epidemiologic studies are supported by extensive dose-reconstruction activities that have led to the creation of various versions of a Techa River Dosimetry System (TRDS). The correctness of the TRDS has been challenged by the allegation that releases of short-lived radionuclides were much larger than those used in the TRDS. Although the dosimetry system depends more upon the measurements of 90Sr in humans and additional measurements of radionuclides and of exposure rates in the environment, a major activity has been undertaken to define more precisely the time-dependent rates of release and radionuclide composition of the releases. The major releases occurred during 1950-1951. In addition to routine releases major accidental releases occurred. The re-evaluated amount of total release is 114 PBq, about half of which was from accidents that occurred in late 1951. The composition of the radionuclides released has also been re-evaluated; this composition changed with time.

  18. CSR GRACE Release-05 Data Products: Status & Assessments

    NASA Astrophysics Data System (ADS)

    Bettadpur, S. V.

    2013-12-01

    The joint NASA/DLR mission has provided a decade of ground-breaking insights into several aspects of the Earth system mass flux variability. The GRACE Science Data System has released the latest revision of the monthly gravity field time-series, dubbed Release-05 (RL05). Examination of this series shows a factor of two to three improvement, in terms of variance reduction, relative to the previous (RL04) release. In this paper, we provide a detailed assessment of the CSR RL05 time-series and describe the manner in which it improves upon the RL04 series. The focus of this paper is a characterization and detailed description of the errors in the CSR monthly gravity field time-series, including the changing character of the errors as the flight system passes through different stages in its 11 year lifetime.

  19. Improvement of aromatic thiol release through the selection of yeasts with increased β-lyase activity.

    PubMed

    Belda, Ignacio; Ruiz, Javier; Navascués, Eva; Marquina, Domingo; Santos, Antonio

    2016-05-16

    The development of a selective medium for the rapid differentiation of yeast species with increased aromatic thiol release activity has been achieved. The selective medium was based on the addition of S-methyl-l-cysteine (SMC) as β-lyase substrate. In this study, a panel of 245 strains of Saccharomyces cerevisiae strains was tested for their ability to grow on YCB-SMC medium. Yeast strains with an increased β-lyase activity grew rapidly because of their ability to release ammonium from SMC in comparison to others, and allowed for the easy isolation and differentiation of yeasts with promising properties in oenology, or another field, for aromatic thiol release. The selective medium was also helpful for the discrimination between those S. cerevisiae strains, which present a common 38-bp deletion in the IRC7 sequence (present in around 88% of the wild strains tested and are likely to be less functional for 4-mercapto-4-methylpentan-2-one (4MMP) production), and those S. cerevisiae strains homozygous for the full-length IRC7 allele. The medium was also helpful for the selection of non-Saccharomyces yeasts with increased β-lyase activity. Based on the same medium, a highly sensitive, reproducible and non-expensive GC-MS method for the evaluation of the potential volatile thiol release by different yeast isolates was developed. PMID:26971012

  20. Improvement of aromatic thiol release through the selection of yeasts with increased β-lyase activity.

    PubMed

    Belda, Ignacio; Ruiz, Javier; Navascués, Eva; Marquina, Domingo; Santos, Antonio

    2016-05-16

    The development of a selective medium for the rapid differentiation of yeast species with increased aromatic thiol release activity has been achieved. The selective medium was based on the addition of S-methyl-l-cysteine (SMC) as β-lyase substrate. In this study, a panel of 245 strains of Saccharomyces cerevisiae strains was tested for their ability to grow on YCB-SMC medium. Yeast strains with an increased β-lyase activity grew rapidly because of their ability to release ammonium from SMC in comparison to others, and allowed for the easy isolation and differentiation of yeasts with promising properties in oenology, or another field, for aromatic thiol release. The selective medium was also helpful for the discrimination between those S. cerevisiae strains, which present a common 38-bp deletion in the IRC7 sequence (present in around 88% of the wild strains tested and are likely to be less functional for 4-mercapto-4-methylpentan-2-one (4MMP) production), and those S. cerevisiae strains homozygous for the full-length IRC7 allele. The medium was also helpful for the selection of non-Saccharomyces yeasts with increased β-lyase activity. Based on the same medium, a highly sensitive, reproducible and non-expensive GC-MS method for the evaluation of the potential volatile thiol release by different yeast isolates was developed.

  1. Effects of corticotropin-releasing hormone on ovarian estrogen production in vitro.

    PubMed

    Calogero, A E; Burrello, N; Negri-Cesi, P; Papale, L; Palumbo, M A; Cianci, A; Sanfilippo, S; D'Agata, R

    1996-10-01

    It is a common clinical observation that stress is accompanied by dysfunction of the hypothalamic-pituitary-ovarian axis, and there is mounting experimental evidence that CRH, the principal regulator of ACTH release and the central coordinator of the stress response, is able to suppress gonadal function by inhibiting hypothalamic GnRH release. Recently, it has been shown that immunoreactive CRH, CRH messenger RNA, and CRH receptors are also present in the ovary. This prompted us to examine the role of CRH on ovarian function. To accomplish this, we studied the effects of this neuropeptide on estrogen production and cAMP intracellular content from rat granulosa and human granulosa-luteal cells. We also evaluated the activity of the enzyme aromatase by measuring the production of tritiated water from homogenates of cultured rat granulosa cells. CRH inhibited FSH-stimulated estrogen production from rat granulosa cells in a dose-dependent fashion. The maximal effect was achieved at a concentration of 10(-8) M, which suppressed estrogen production by about 30%. Low concentrations of CRH (10(-10) M), incapable of modulating maximal estrogen production in response to FSH, provoked a right-ward shift of the estrogen dose-response curve to FSH. CRH (10(-8) M) suppressed the production of tritiated water (equivalent to estrogen production) from homogenates of rat granulosa cells incubated with a half-maximal concentration of FSH. Basal estrogen production by human granulosa-luteal cells was also inhibited by CRH at a concentration of 10(-10) M. The maximal effect was achieved with a concentration of 10(-8) M, which lowered estrogen production by 25%. The CRH receptor antagonist alpha-helical CRH-(9-41) antagonized the inhibitory effect of CRH on estrogen production from rat granulosa and human granulosa-luteal cells, whereas alone it had no effect. CRH did not have any effect on the intracellular cAMP content of rat granulosa and human granulosa-luteal cells. In conclusion

  2. Computational study of a calcium release-activated calcium channel

    NASA Astrophysics Data System (ADS)

    Talukdar, Keka; Shantappa, Anil

    2016-05-01

    The naturally occurring proteins that form hole in membrane are commonly known as ion channels. They play multiple roles in many important biological processes. Deletion or alteration of these channels often leads to serious problems in the physiological processes as it controls the flow of ions through it. The proper maintenance of the flow of ions, in turn, is required for normal health. Here we have investigated the behavior of a calcium release-activated calcium ion channel with pdb entry 4HKR in Drosophila Melanogaster. The equilibrium energy as well as molecular dynamics simulation is performed first. The protein is subjected to molecular dynamics simulation to find their energy minimized value. Simulation of the protein in the environment of water and ions has given us important results too. The solvation energy is also found using Charmm potential.

  3. Reevaluation of waterborne releases of radioactive materials from the Mayak Production Association into the Techa River in 1949-1951.

    PubMed

    Degteva, M O; Shagina, N B; Vorobiova, M I; Anspaugh, L R; Napier, B A

    2012-01-01

    The Mayak Production Association was the first site for the production of weapons-grade plutonium in Russia. Early operations led to the waterborne release of radioactive materials into the small Techa River. Residents living downstream used river water for drinking and other purposes. The releases and subsequent flooding resulted in deposition of sediments along the shoreline and on floodplain soil. Primary routes of exposure were external dose from the deposited sediments and ingestion of 90Sr and other radionuclides. Study of the Techa River Cohort has revealed an increased incidence of leukemia and solid cancers. Epidemiologic studies are supported by extensive dose-reconstruction activities that have led to various versions of a Techa River Dosimetry System (TRDS). The correctness of the TRDS has been challenged by the allegation that releases of short-lived radionuclides were much larger than those used in the TRDS. Although the dosimetry system depends more upon measurements of 90Sr in humans and additional measurements of radionuclides and of exposure rates in the environment, a major activity has been undertaken to define more precisely the time-dependent rates of release and their radionuclide composition. The major releases occurred during 1950-1951 in the form of routine releases and major accidental releases. The reevaluated amount of total release is 114 PBq, about half of which was from accidents that occurred in late 1951. The time-dependent composition of the radionuclides released has also been reevaluated. The improved understanding presented in this paper is possible because of access to many documents not previously available. PMID:22134076

  4. Synaptic scaling stabilizes persistent activity driven by asynchronous neurotransmitter release.

    PubMed

    Volman, Vladislav; Gerkin, Richard C

    2011-04-01

    Small networks of cultured hippocampal neurons respond to transient stimulation with rhythmic network activity (reverberation) that persists for several seconds, constituting an in vitro model of synchrony, working memory, and seizure. This mode of activity has been shown theoretically and experimentally to depend on asynchronous neurotransmitter release (an essential feature of the developing hippocampus) and is supported by a variety of developing neuronal networks despite variability in the size of populations (10-200 neurons) and in patterns of synaptic connectivity. It has previously been reported in computational models that "small-world" connection topology is ideal for the propagation of similar modes of network activity, although this has been shown only for neurons utilizing synchronous (phasic) synaptic transmission. We investigated how topological constraints on synaptic connectivity could shape the stability of reverberations in small networks that also use asynchronous synaptic transmission. We found that reverberation duration in such networks was resistant to changes in topology and scaled poorly with network size. However, normalization of synaptic drive, by reducing the variance of synaptic input across neurons, stabilized reverberation in such networks. Our results thus suggest that the stability of both normal and pathological states in developing networks might be shaped by variance-normalizing constraints on synaptic drive. We offer an experimental prediction for the consequences of such regulation on the behavior of small networks.

  5. The release of nanosilver from consumer products used in the home.

    PubMed

    Benn, Troy; Cavanagh, Bridget; Hristovski, Kiril; Posner, Jonathan D; Westerhoff, Paul

    2010-01-01

    Nanosilver has become one of the most widely used nanomaterials in consumer products because of its antimicrobial properties. Public concern over the potential adverse effects of nanosilver's environmental release has prompted discussion of federal regulation. In this paper, we assess several classes of consumer products for their silver content and potential to release nanosilver into water, air, or soil. Silver was quantified in a shirt, a medical mask and cloth, toothpaste, shampoo, detergent, a towel, a toy teddy bear, and two humidifiers. Silver concentrations ranged from 1.4 to 270,000 microg Ag g product(-1). Products were washed in 500 mL of tap water to assess the potential release of silver into aqueous environmental matrices (wastewater, surface water, saliva, etc.). Silver was released in quantities up to 45 microg Ag g product(-1), and size fractions were both larger and smaller than 100 nm. Scanning electron microscopy confirmed the presence of nanoparticle silver in most products as well as in the wash water samples. Four products were subjected to a toxicity characterization leaching procedure to assess the release of silver in a landfill. The medical cloth released an amount of silver comparable to the toxicity characterization limit. This paper presents methodologies that can be used to quantify and characterize silver and other nanomaterials in consumer products. The quantities of silver in consumer products can in turn be used to estimate real-world human and environmental exposure levels. PMID:21284285

  6. Fate of corrosion products released from stainless steel in marine sediments and seawater. Part 1. Northeast Pacific pelagic red clay

    SciTech Connect

    Schmidt, R.L.

    1982-03-01

    To provide information useful for determining the biogeochemical cycling of corrosion products in the benthic boundary layer of the deep ocean, neutron-activated stainless steel was exposed to seawater and to Northeast Pacific red clay under aerobic and non-oxygenated conditions. This report describes the trace metal geochemistry of the sediment and the chemical speciation of the corrosion products. The sediments generally consisted of reddish-brown clay at the surface grading to a dark-brown transition zone below which mottled olive-gray clay prevailed. Neutron-irradiated 347 stainless steel specimens were exposed to seawater and sediment slurry under aerobic and non-oxygenated conditions for 108 days. The presence of aerated sediment more than doubled the amount of corrosion products released compared to aerated seawater and non-oxygenated sediment treatments. The distribution of /sup 60/Co released from the stainless steel exposed to aerated seawater show that almost 70% of /sup 60/Co activity became associated with suspended particulate matter. No detectable /sup 60/Co activity was present in the soluble, readily dissolved, or inorganic or weakly complexed fractions of aerated sediment which had been used to treat neutron-activated stainless steel. Almost 50% of the /sup 60/Co activity was extracted in the combined soluble, easily dissolved, adsorbed, and organically complexed fractions from the non-oxygenated sediment treatment indicating that this much of the corrosion products may be initially released in ionic form.

  7. Phenazine production enhances extracellular DNA release via hydrogen peroxide generation in Pseudomonas aeruginosa

    PubMed Central

    Das, Theerthankar; Manefield, Mike

    2013-01-01

    In Pseudomonas aeruginosa eDNA is a crucial component essential for biofilm formation and stability. In this study we report that release of eDNA is influenced by the production of phenazine in P. aeruginosa. A ∆phzA-G mutant of P. aeruginosa PA14 deficient in phenazine production generated significantly less eDNA in comparison with the phenazine producing strains. The relationship between eDNA release and phenazine production is bridged via hydrogen peroxide (H2O2) generation and subsequent H2O2 mediated cell lysis and ultimately release of chromosomal DNA into the extracellular environment as eDNA. PMID:23710274

  8. Structural aspects of calcium-release activated calcium channel function

    PubMed Central

    Stathopulos, Peter B; Ikura, Mitsuhiko

    2013-01-01

    Store-operated calcium (Ca2+) entry is the process by which molecules located on the endo/sarcoplasmic reticulum (ER/SR) respond to decreased luminal Ca2+ levels by signaling Ca2+ release activated Ca2+ channels (CRAC) channels to open on the plasma membrane (PM). This activation of PM CRAC channels provides a sustained cytosolic Ca2+ elevation associated with myriad physiological processes. The identities of the molecules which mediate SOCE include stromal interaction molecules (STIMs), functioning as the ER/SR luminal Ca2+ sensors, and Orai proteins, forming the PM CRAC channels. This review examines the current available high-resolution structural information on these CRAC molecular components with particular focus on the solution structures of the luminal STIM Ca2+ sensing domains, the crystal structures of cytosolic STIM fragments, a closed Orai hexameric crystal structure and a structure of an Orai1 N-terminal fragment in complex with calmodulin. The accessible structural data are discussed in terms of potential mechanisms of action and cohesiveness with functional observations. PMID:24213636

  9. Isomer Research: Energy Release Validation, Production, and Applications

    SciTech Connect

    Becker, J A; Rundberg, B

    2003-04-10

    The goal of this applied nuclear isomer research program is the search for, discovery of, and practical application of a new type of high energy density material (HEDM). Nuclear isomers could yield an energy source with a specific energy as much as a hundred thousand times as great as that of chemical fuels. There would be enormous payoffs to the Department of Energy and to the country as a whole if such energy sources could be identified and applied to a range of civilian and defense applications. Despite the potential payoff, efforts in applied isomer research have been rather limited and sporadic. Basic research on nuclear isomers dates back to their discovery in 1935 with occasional hints to tantalize interest in HEDM. In most cases, these hints were refuted following careful examination by other groups. The isomer research area is rich with possibilities: we prioritized several areas likely to be the most rewarding and fruitful for initial experimental investigation because these areas directly bear on important issues: Can the energy stored in nuclear isomers be released on demand? Is the size of the atomic-nuclear mixing matrix element large enough to be useful? Under what circumstances? Can we initiate quantal collective release of isomeric energy from a Moessbauer crystal?

  10. Gonadotrophin-releasing activity of neurohypophysial hormones: II. The pituitary oxytocin receptor mediating gonadotrophin release differs from that of corticotrophs.

    PubMed

    Evans, J J; Catt, K J

    1989-07-01

    Neurohypophysial hormones stimulate gonadotrophin release from dispersed rat anterior pituitary cells in vitro, acting through receptors distinct from those which mediate the secretory response to gonadotrophin-releasing hormone (GnRH). The LH response to oxytocin was not affected by the presence of the phosphodiesterase inhibitor, methyl isobutylxanthine, but was diminished in the absence of extracellular calcium and was progressively increased as the calcium concentration in the medium was raised to normal. In addition, the calcium channel antagonist, nifedipine, suppressed oxytocin-stimulated secretion of LH. It is likely that the mechanisms of LH release induced by GnRH and neurohypophysial hormones are similar, although stimulation of gonadotrophin secretion is mediated by separate receptor systems. Oxytocin was more active than vasopressin in releasing LH, but less active in releasing ACTH. The highly selective oxytocin agonist, [Thr4,Gly7]oxytocin, elicited concentration-dependent secretion of LH but had little effect on corticotrophin secretion. The neurohypophysial hormone antagonist analogues, [d(CH2)5Tyr(Me)2]vasopressin, [d(CH2)5Tyr(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2Val4,Cit8]vasopressin, inhibited the LH response to both oxytocin and vasopressin. However, [d(CH2)5Tyr(Me)2]vasopressin was much less effective in inhibiting the ACTH response to the neurohypophysial hormones, and [d(CH2)5Tyr-(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2,Val4,Cit8]vasopressin exhibited no inhibitory activity against ACTH release. Thus, agonist and antagonist analogues of neurohypophysial hormones display divergent activities with regard to LH and ACTH responses, and the neuropeptide receptor mediating gonadotroph activation is clearly different from that on the corticotroph. Whereas the corticotroph receptor is a vasopressin-type receptor an oxytocin-type receptor is responsible for gonadotrophin release by neurohypophysial hormones.

  11. The Release of Nanosilver from Consumer Products Used in the Home

    PubMed Central

    Benn, Troy; Cavanagh, Bridget; Hristovski, Kiril; Posner, Jonathan D.; Westerhoff, Paul

    2016-01-01

    Nanosilver has become one of the most widely used nanomaterials in consumer products because of its antimicrobial properties. Public concern over the potential adverse effects of nanosilver's environmental release has prompted discussion of federal regulation. In this paper, we assess several classes of consumer products for their silver content and potential to release nanosilver into water, air, or soil. Silver was quantified in a shirt, a medical mask and cloth, toothpaste, shampoo, detergent, a towel, a toy teddy bear, and two humidifiers. Silver concentrations ranged from 1.4 to 270,000 μg Ag g product−1. Products were washed in 500 mL of tap water to assess the potential release of silver into aqueous environmental matrices (wastewater, surface water, saliva, etc.). Silver was released in quantities up to 45 μg Ag g product−1, and size fractions were both larger and smaller than 100 nm. Scanning electron microscopy confirmed the presence of nanoparticle silver in most products as well as in the wash water samples. Four products were subjected to a toxicity characterization leaching procedure to assess the release of silver in a landfill. The medical cloth released an amount of silver comparable to the toxicity characterization limit. This paper presents methodologies that can be used to quantify and characterize silver and other nanomaterials in consumer products. The quantities of silver in consumer products can in turn be used to estimate real-world human and environmental exposure levels. PMID:21284285

  12. Get Up to Speed on the Latest Product Releases in the Education Market

    ERIC Educational Resources Information Center

    Technology & Learning, 2007

    2007-01-01

    This article provides brief descriptions of the latest product releases in the education market. These products include hardware, software, and resources. The following products are presented in this article, but not limited to: (1) Radius Audio Learning System(www.learningresources.com); (2) The Indigo Learning System from LearningSoft, LLC…

  13. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro

    SciTech Connect

    Rubin, L.A.; Kurman, C.C.; Fritz, M.E.; Biddison, W.E.; Boutin, B.; Yarchoan, R.; Nelson, D.L.

    1985-11-01

    With the use of an enzyme-linked immunoabsorbent assay to measure soluble human interleukin 2 receptors (IL 2R), certain human T cell leukemia virus I (HTLV I)-positive T cell lines were found to spontaneously release large quantities of IL 2R into culture supernatants. This was not found with HTLV I-negative and IL 2 independent T cell lines, and only one of seven B cell-derived lines examined produced small amounts of IL 2R. In addition to this constitutive production of soluble IL 2R by certain cell lines, normal human peripheral blood mononuclear cells (PBMC) could be induced to release soluble IL 2R by plant lectins, the murine monoclonal antibody OKT3, tetanus toxoid, and allogeneic cells. Such activated cells also expressed cellular IL 2R measurable in detergent solubilized cell extracts. The generation of cellular and supernatant IL 2R was: dependent on cellular activation, rapid, radioresistant (3000 rad), and inhibited by cycloheximide treatment. NaDodSO4-polyacrylamide gel electrophoresis analysis of soluble IL 2R demonstrated molecules of apparent Mr = 35,000 to 40,000, and 45,000 to 50,000, respectively, somewhat smaller than the mature surface receptor on these cells. The release of soluble IL 2R appears to be a characteristic marker of T lymphocyte activation and might serve an immunoregulatory function during both normal and abnormal cell growth and differentiation.

  14. Microvesicles released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism

    PubMed Central

    Antonucci, Flavia; Turola, Elena; Riganti, Loredana; Caleo, Matteo; Gabrielli, Martina; Perrotta, Cristiana; Novellino, Luisa; Clementi, Emilio; Giussani, Paola; Viani, Paola; Matteoli, Michela; Verderio, Claudia

    2012-01-01

    Microvesicles (MVs) released into the brain microenvironment are emerging as a novel way of cell-to-cell communication. We have recently shown that microglia, the immune cells of the brain, shed MVs upon activation but their possible role in microglia-to-neuron communication has never been explored. To investigate whether MVs affect neurotransmission, we analysed spontaneous release of glutamate in neurons exposed to MVs and found a dose-dependent increase in miniature excitatory postsynaptic current (mEPSC) frequency without changes in mEPSC amplitude. Paired-pulse recording analysis of evoked neurotransmission showed that MVs mainly act at the presynaptic site, by increasing release probability. In line with the enhancement of excitatory transmission in vitro, injection of MVs into the rat visual cortex caused an acute increase in the amplitude of field potentials evoked by visual stimuli. Stimulation of synaptic activity occurred via enhanced sphingolipid metabolism. Indeed, MVs promoted ceramide and sphingosine production in neurons, while the increase of excitatory transmission induced by MVs was prevented by pharmacological or genetic inhibition of sphingosine synthesis. These data identify microglia-derived MVs as a new mechanism by which microglia influence synaptic activity and highlight the involvement of neuronal sphingosine in this microglia-to-neuron signalling pathway. PMID:22246184

  15. 14 CFR 1213.109 - News releases concerning international activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... RELEASE OF INFORMATION TO NEWS AND INFORMATION MEDIA § 1213.109 News releases concerning international... Headquarters offices of External Relations and Public Affairs. (b) NASA Centers and Headquarters offices will report all visits proposed by representatives of foreign news media to the Public Affairs Officer of...

  16. ATP Released by Injured Neurons Activates Schwann Cells

    PubMed Central

    Negro, Samuele; Bergamin, Elisanna; Rodella, Umberto; Duregotti, Elisa; Scorzeto, Michele; Jalink, Kees; Montecucco, Cesare; Rigoni, Michela

    2016-01-01

    Injured nerve terminals of neuromuscular junctions (NMJs) can regenerate. This remarkable and complex response is governed by molecular signals that are exchanged among the cellular components of this synapse: motor axon nerve terminal (MAT), perisynaptic Schwann cells (PSCs), and muscle fiber. The nature of signals that govern MAT regeneration is ill-known. In the present study the spider toxin α-latrotoxin has been used as tool to investigate the mechanisms underlying peripheral neuroregeneration. Indeed this neurotoxin induces an acute, specific, localized and fully reversible damage of the presynaptic nerve terminal, and its action mimics the cascade of events that leads to nerve terminal degeneration in injured patients and in many neurodegenerative conditions. Here we provide evidence of an early release by degenerating neurons of adenosine triphosphate as alarm messenger, that contributes to the activation of a series of intracellular pathways within Schwann cells that are crucial for nerve regeneration: Ca2+, cAMP, ERK1/2, and CREB. These results contribute to define the cross-talk taking place among degenerating nerve terminals and PSCs, involved in the functional recovery of the NMJ. PMID:27242443

  17. Consequences of tritium release to water pathways from postulated accidents in a DOE production reactor (U)

    SciTech Connect

    O'Kula, K.R.; Olson, R.L.; Hamby, D.M. )

    1992-03-01

    A full-scale PRA of a DOE production reactor has been completed that considers full release of tritium as part of the severe accident source term. Two classes of postulated reactor accidents, a loss-of-moderator pumping accident and a loss-of-coolant accident, are used to bound the expected dose consequence from liquid pathway release. Population doses from the radiological release associated with the two accidents are compared for aqueous discharge and atmospheric release modes. The expectation values of the distribution of possible values for the societal effective dose equivalent to the general public, given a tritium release to the atmosphere, is 2.8 person-Sv/PBq (9.9 {times} 10{sup {minus}3} person-rem/Ci). The general public drinking water dose to downstream water consumers is 6.5 {times} 10{sup {minus}2} person-Sv/PBq(2.4 {times} 10{sup {minus}4} person-rem/Ci) for aqueous releases to the surface streams eventually reaching the Savannah River. Negligible doses are calculated for freshwater fish and saltwater invertebrate consumption, irrigation, and recreational use of the river, given that an aqueous release is assumed to occur. Relative to the balance of fission products released in a hypothetical severe accident, the tritium-related dose is small. This paper suggests that application of regional models (1610 km radius) will indicate larger dose consequences from short-term tritium releases to the atmosphere than from comparable tritium source terms to water pathways.

  18. Improving methane production and phosphorus release in anaerobic digestion of particulate saline sludge from a brackish aquaculture recirculation system.

    PubMed

    Zhang, Xuedong; Ferreira, Rui B; Hu, Jianmei; Spanjers, Henri; van Lier, Jules B

    2014-06-01

    In this study, batch tests were conducted to examine the effects of trehalose and glycine betaine as well as potassium on the specific methanogenic activity (SMA), acid and alkaline phosphatase activity of anaerobic biomass and phosphorus release in anaerobic digestion of saline sludge from a brackish recirculation aquaculture system. The results of ANOVA and Tukey's HSD (honestly significant difference) tests showed that glycine betaine and trehalose enhanced SMA of anaerobic biomass and reactive phosphorus release from the particulate waste. Moreover, SMA tests revealed that methanogenic sludge, which was long-term acclimatized to a salinity level of 17 g/L was severely affected by the increase in salinity to values exceeding 35 g/L. Addition of compatible solutes, such as glycine betaine and trehalose, could be used to enhance the specific methane production rate and phosphorus release in anaerobic digestion from particulate organic waste produced in marine or brackish aquaculture recirculation systems.

  19. Spontaneous and Evoked Release Are Independently Regulated at Individual Active Zones

    PubMed Central

    Melom, Jan E.; Akbergenova, Yulia; Gavornik, Jeffrey P.

    2013-01-01

    Neurotransmitter release from synaptic vesicle fusion is the fundamental mechanism for neuronal communication at synapses. Evoked release following an action potential has been well characterized for its function in activating the postsynaptic cell, but the significance of spontaneous release is less clear. Using transgenic tools to image single synaptic vesicle fusion events at individual release sites (active zones) in Drosophila, we characterized the spatial and temporal dynamics of exocytotic events that occur spontaneously or in response to an action potential. We also analyzed the relationship between these two modes of fusion at single release sites. A majority of active zones participate in both modes of fusion, although release probability is not correlated between the two modes of release and is highly variable across the population. A subset of active zones is specifically dedicated to spontaneous release, indicating a population of postsynaptic receptors is uniquely activated by this mode of vesicle fusion. Imaging synaptic transmission at individual release sites also revealed general rules for spontaneous and evoked release, and indicate that active zones with similar release probability can cluster spatially within individual synaptic boutons. These findings suggest neuronal connections contain two information channels that can be spatially segregated and independently regulated to transmit evoked or spontaneous fusion signals. PMID:24174659

  20. Primary system fission product release and transport: A state-of-the-art report to the committee on the safety of nuclear installations

    SciTech Connect

    Wright, A.L.

    1994-06-01

    This report presents a summary of the status of research activities associated with fission product behavior (release and transport) under severe accident conditions within the primary systems of water-moderated and water-cooled nuclear reactors. For each of the areas of fission product release and fission product transport, the report summarizes relevant information on important phenomena, major experiments performed, relevant computer models and codes, comparisons of computer code calculations with experimental results, and general conclusions on the overall state of the art. Finally, the report provides an assessment of the overall importance and knowledge of primary system release and transport phenomena and presents major conclusions on the state of the art.

  1. Optimization of intracellular product release from Neisseria denitrificans using microfluidizer.

    PubMed

    Stupak, Robert; Makauskas, Nerijus; Radzevičius, Kostas; Valančius, Zenonas

    2015-01-01

    Disruption of Neisseria denitrificans cells by microfluidizer was optimized using a factorial experiments design. The pH, pretreatment time, cell concentration, NaCl, ethylenediamine tetraacetic acid (EDTA) and Triton X-100 concentrations showed significant impact on disruption process and the process was optimized using central composite design and response surface methodology (RSM). Investigation revealed optimum conditions: 90 min pretreatment at pH 9.0 containing 110 g L(-1) cells (dry cell weight), 50 mM NaCl, 10 mM EDTA, and 0.2% Triton X-100. At optimized conditions, the disruption rate increased twofold, up to 5.62 ± 0.27 × 10(-3) MPa(-a); meanwhile, yield of intracellular content was increased by 26%, with 1 g of cells resulting in 113.2 ± 8.2 mg proteins, 12.1 ± 0.7 mg nucleic acids, 21.0 ± 1.2 mg polysaccharides, 0.99 ± 0.08 kU glucose-6-phosphate dehydrogenase (G6PD), and 10,100 ± 110 kU restriction endonuclease NdeI endonuclease. Particle size distribution analysis revealed nearly twofold larger cell lysate particles with diameter of 120 nm. For optimal release of intracellular content, 9200 J/g of energy was needed (95% confidence), yielding 6900 J/g energy savings. Model equations generated from RSM on cell disruption of N. denitrificans were found adequate to determine significant factors and its interaction. The results showed that optimized combination of known pretreatment and disruption methods could considerably improve cell disruption efficiency.

  2. Spectroscopic measurement of cortical nitric oxide release induced by ascending activation.

    PubMed

    Espinosa, N; Cudeiro, J; Mariño, J

    2015-01-29

    The transition from sleep to the awake state is regulated by the activation of subcortical nuclei of the brainstem (BS) and basal forebrain (BF), releasing acetylcholine and glutamate throughout the cortex and inducing a tonic state of neural activity. It has been suggested that such activation is also mediated by the massive and diffuse cortical release of nitric oxide (NO). In this work we have combined the spectroscopic measurement of NO levels in the somatosensory cortex of the cat through its marker methemoglobin, as well as two other hemodynamic markers (oxyhemoglobin--oxyHb--and deoxyhemoglobin--deoxyHb), together with the electrical stimulation of BS and BF--to induce an experimental transition from a sleep-like state to an awake-like mode. The results show an increase of NO levels either after BS or BF activation. The response induced by BS stimulation was biphasic in the three studied markers, and lasted for up to 30s. The changes induced by BF were monophasic lasting for up to 20s. The systemic blockade of NO production abolished the observed responses to BS whereas responses to BF stimulation were much less affected. These results indicate a crucial role for NO in the neuronal activation induced by the ascending systems. PMID:25463513

  3. Activation of Src and release of intracellular calcium by phosphatidic acid during Xenopus laevis fertilization

    PubMed Central

    Bates, Ryan C.; Fees, Colby P.; Holland, William L.; Winger, Courtney C.; Batbayar, Khulan; Ancar, Rachel; Bergren, Todd; Petcoff, Douglas; Stith, Bradley J.

    2014-01-01

    We report a new step in the fertilization in Xenopus laevis which has been found to involve activation of Src tyrosine kinase to stimulate phospholipase C-γ (PLC- γ) which increases inositol 1,4,5-trisphosphate (IP3) to release intracellular calcium ([Ca]i). Molecular species analysis and mass measurements suggested that sperm activate phospholipase D (PLD) to elevate phosphatidic acid (PA). We now report that PA mass increased 2.7 fold by 1 minute after insemination and inhibition of PA production by two methods inhibited activation of Src and PLCγ, increased [Ca]i and other fertilization events. As compared to 14 other lipids, PA strongly bound Xenopus Src but not PLCγ. Addition of synthetic PA activated egg Src (an action requiring intact lipid rafts) and PLCγ as well as doubling the amount of PLCγ in rafts. In the absence of elevated [Ca]i, PA addition elevated IP3 mass to levels equivalent to that induced by sperm (but twice that achieved by calcium ionophore). Finally, PA induced [Ca]i release that was blocked by an IP3 receptor inhibitor. As only PLD1b message was detected, and Western blotting did not detect PLD2, we suggest that sperm activate PLD1b to elevate PA which then binds to and activates Src leading to PLCγ stimulation, IP3 elevation and [Ca]i release. Due to these and other studies, PA may also play a role in membrane fusion events such as sperm-egg fusion, cortical granule exocytosis, the elevation of phosphatidylinositol 4,5-bisphosphate and the large, late increase in sn 1,2-diacylglycerol in fertilization. PMID:24269904

  4. CME Productivity of Active Regions.

    NASA Astrophysics Data System (ADS)

    Liu, L.; Wang, Y.; Wang, J.; Shen, C.; Ye, P.; Zhang, Q.; Liu, R.; Wang, S.

    2015-12-01

    Solar active regions (ARs) are the major sources of two kinds of the most violent solar eruptions, namely flares and coronal mass ejections (CMEs). Although they are believed to be two phenomena in the same eruptive process, the productivity of them could be quiet different for various ARs. Why is an AR productive? And why is a flare-rich AR CME-poor? To answer these questions, we compared the recent super flare-rich but CME-poor AR 12192, with other four ARs; two were productive in both flares and CMEs and the other two were inert to produce any M-class or intenser flares or CMEs. By investigating the photospheric parameters based on the SDO/HMI vector magnetogram, we find the three productive ARs have larger magnetic flux, current and free magnetic energy than the inert ARs. Furthermore, the two ARs productive in both flares and CMEs contain higher current helicity, concentrating along both sides of the flaring neutral lines, indicating the presence of a seed magnetic structure( that is highly sheared or twisted) of a CME; they also have higher decay index in the low corona, showing weak constraint. The results suggest that productive ARs are always large and have strong current system and sufficient free energy to power flares, and more importantly whether or not a flare is accompanied by a CME is seemingly related to (1) if there is significant sheared or twisted core field serving as the seed of the CME and (2) if the constraint of the overlying arcades is weak enough. Moreover, some productive ARs may frequently produce more than one CME. How does this happen? We do a statistical investigation of waiting times of quasi-homologous CMEs ( CME ssuccessive originating from the same ARs within short intervals) from super ARs in solar cycle 23 to answer this question. The waiting times of quasi-homologous CMEs have a two-component distribution with a separation at about 18 hours, the first component peaks at 7 hours. The correlation analysis among CME waiting times

  5. Borrelia burgdorferi Induces the Production and Release of Proinflammatory Cytokines in Canine Synovial Explant Cultures

    PubMed Central

    Straubinger, Reinhard K.; Straubinger, Alix F.; Summers, Brian A.; Erb, Hollis N.; Härter, Luc; Appel, Max J. G.

    1998-01-01

    Canine synovial membrane explants were exposed to high- or low-passage Borrelia burgdorferi for 3, 6, 12, and 24 h. Spirochetes received no treatment, were UV light irradiated for 16 h, or were sonicated prior to addition to synovial explant cultures. In explant tissues, mRNA levels for the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1α (IL-1α), IL-1β, and IL-8 were surveyed semiquantitatively by reverse transcription-PCR. Culture supernatants were examined for numbers of total and motile (i.e., viable) spirochetes, TNF-like and IL-1-like activities, polymorphonuclear neutrophil (PMN) chemotaxis-inducing activities, and IL-8. During exposure to synovial explant tissues, the total number of spirochetes in the supernatants decreased gradually by ∼30%, and the viability also declined. mRNAs for TNF-α, IL-1α, IL-1β, and IL-8 were up-regulated in synovial explant tissues within 3 h after infection with untreated or UV light-irradiated B. burgdorferi, and mRNA levels corresponded to the results obtained with bioassays. During 24 h of coincubation, cultures challenged with untreated or UV light-irradiated spirochetes produced similar levels of TNF-like and IL-1-like activities. In contrast, explant tissues exposed to untreated B. burgdorferi generated significantly higher levels of chemotactic factors after 24 h of incubation than did explant tissues exposed to UV light-treated spirochetes. In identical samples, a specific signal for IL-8 was identified by Western blot analysis. High- and low-passage borreliae did not differ in their abilities to induce proinflammatory cytokines. No difference in cytokine induction between untreated and sonicated high-passage spirochetes was observed, suggesting that fractions of the organism can trigger the production and release of inflammatory mediators. The titration of spirochetes revealed a dose-independent cytokine response, where 103 to 107 B. burgdorferi organisms induced similar TNF

  6. Lipoprotein lipase release from BFC-1 beta adipocytes. Effects of triglyceride-rich lipoproteins and lipolysis products.

    PubMed

    Sasaki, A; Goldberg, I J

    1992-07-25

    Lipoprotein lipase (LPL), synthesized by adipocytes and myocytes, must be transported to the luminal endothelial cell surface where it then interacts with circulating lipoproteins. The first step in this extracellular LPL transport pathway is LPL release from the surface of LPL-synthesizing cells. Because hydrolysis of triglyceride (TG)-rich lipoproteins releases LPL from the apical surface of endothelial cells, we hypothesized that the same substances dissociate LPL from adipocytes. 125I-LPL was bound to the surface of brown adipocytes (BFC-1 beta). LPL binding to the adipocyte surface was greater than to endothelial cell surfaces. Using low concentrations of heparin, more LPL was released from endothelial cells than BFC-1 beta, suggesting that the affinity of LPL binding to the adipocytes was greater than LPL affinity for endothelial cells. Greater than 3-fold more LPL was released from the cell surface when very low density lipoproteins (VLDL) were added to culture medium containing 3% bovine serum albumin. LPL remaining on the cell surface decreased with VLDL addition. Endogenously produced LPL activity was also released from the cells by VLDL. Low and high density lipoproteins did not release 125I-LPL or LPL activity from the adipocytes. To assess whether lipolysis was necessary for LPL release, BFC-1 beta were incubated with TG-rich lipoproteins from a patient with apoCII deficiency. The apoCII-deficient lipoproteins did not release LPL unless an exogenous source of apoCII was added. Apolipoproteins E and Cs and high molar ratios of oleic acid:bovine serum albumin did not release surface-associated LPL. Lysolecithin (25 and 100 microM), but not lecithin, monoglycerides, or diglycerides, released adipocyte surface LPL. Because lysolecithin also released LPL during a 4 degrees C incubation, cellular metabolic functions are not required for LPL dissociation from the cells. Lysolecithin also inhibited LPL binding to endothelial cells; however, this effect was

  7. Fission product iodine release and retention in nuclear reactor accidents— experimental programme at PSI

    NASA Astrophysics Data System (ADS)

    Bruchertseifer, H.; Cripps, R.; Guentay, S.; Jaeckel, B.

    2003-01-01

    Iodine radionuclides constitute one of the most important fission products of uranium and plutonium. If the volatile forms would be released into the environment during a severe accident, a potential health hazard would then ensue. Understanding its behaviour is an important prerequisite for planning appropriate mitigation measures. Improved and extensive knowledge of the main iodine species and their reactions important for the release and retention processes in the reactor containment is thus mandatory. The aim of PSI's radiolytical studies is to improve the current thermodynamic and kinetic databases and the models for iodine used in severe accident computer codes. Formation of sparingly soluble silver iodide (AgI) in a PWR containment sump can substantially reduce volatile iodine fraction in the containment atmosphere. However, the effectiveness is dependent on its radiation stability. The direct radiolytic decomposition of AgI and the effect of impurities on iodine volatilisation were experimentally determined at PSI using a remote-controlled and automated high activity 188W/Re generator (40 GBq/ml). Low molecular weight organic iodides are difficult to be retained in engineered safety systems. Investigation of radiolytic decomposition of methyl iodide in aqueous solutions, combined with an on-line analysis of iodine species is currently under investigation at PSI.

  8. Nanostructural control of methane release in kerogen and its implications to wellbore production decline

    NASA Astrophysics Data System (ADS)

    Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

    2016-06-01

    Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix-a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30-47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3-35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.

  9. Nanostructural control of methane release in kerogen and its implications to wellbore production decline

    DOE PAGES

    Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

    2016-06-16

    In spite of the massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Here we show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases, and we usemore » molecular simulations to demonstrate it. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Finally, our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.« less

  10. Nanostructural control of methane release in kerogen and its implications to wellbore production decline

    PubMed Central

    Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

    2016-01-01

    Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release. PMID:27306967

  11. Nanostructural control of methane release in kerogen and its implications to wellbore production decline

    NASA Astrophysics Data System (ADS)

    Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

    2016-06-01

    Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.

  12. Nanostructural control of methane release in kerogen and its implications to wellbore production decline.

    PubMed

    Ho, Tuan Anh; Criscenti, Louise J; Wang, Yifeng

    2016-01-01

    Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix-a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30-47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3-35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release. PMID:27306967

  13. Characterization of a novel cross-linked lipase: impact of cross-linking on solubility and release from drug product.

    PubMed

    Hetrick, Evan M; Sperry, David C; Nguyen, Hung K; Strege, Mark A

    2014-04-01

    Liprotamase is a novel non-porcine pancreatic enzyme replacement therapy containing purified biotechnology-derived lipase, protease, and amylase together with excipients in a capsule formulation. To preserve the structural integrity and biological activity of lipase (the primary drug substance) through exposure of the drug product to the low-pH gastric environment, the enzyme was processed through the use of cross-linked enzyme crystal (CLEC) technology, making the lipase-CLEC drug substance insoluble under acidic conditions but fully soluble at neutral pH and in alkaline environments. In this report we characterize the degree of cross-linking for lipase-CLEC and demonstrate its impact on lipase-CLEC solubility and release from the drug product under relevant physiological pH conditions. Cross-linked lipase-CLEC was characterized via size exclusion chromatography (SEC) and capillary electrophoresis sodium dodecyl sulfate polyacrylamide gel electrophoresis (CE-SDS-PAGE). A combination of methodologies was developed to understand the impact of cross-linking on drug product release. Dissolution evaluation using USP Apparatus 2 at pH 5.0 with an enzyme activity-based end point demonstrated solubility discrimination based on degree of cross-linking, while full release was demonstrated at pH 6.5. The dissolution of the drug product was also evaluated using a dual-stage test employing a USP Apparatus 4 flow-through system to mimic the changing pH environments experienced in the stomach and intestine to understand the impact of cross-linking on drug product performance. Use of USP Apparatus 4 to characterize the pH-dependent release of lipase-CLEC represents a novel approach compared to the Apparatus 1 test employing an acid-challenge stage outlined in the USP for delayed-release pancrelipase, and the advantages of this approach may prove useful for understanding the pH-dependence of release for other drug products. Collectively, these studies confirmed that degree of

  14. Effects of Controlled Release Fertilizer on the Post-Production Performance of Impatiens Wallerana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controlled release fertilizers (CRF) in production systems have been known to reduce environmental contamination. However, there is a lot to be explored as per its use in bedding plant production. Bedding plant growers have not adapted CRF use because there is little information about its use and ...

  15. Environmental fate and effects of nicotine released during cigarette production.

    PubMed

    Seckar, Joel A; Stavanja, Mari S; Harp, Paul R; Yi, Yongsheng; Garner, Charles D; Doi, Jon

    2008-07-01

    A variety of test methods were used to study the gradation, bioaccumulation, and toxicity of nicotine. Studies included determination of the octanol-water partition coefficient, conversion to CO2 in soil and activated sludge, and evaluation of the effects on microbiological and algal inhibition as well as plant germination and root elongation. The partitioning of nicotine between octanol and water indicated that nicotine will not bioaccumulate regardless of the pH of the medium. The aqueous and soil-based biodegradation studies indicated that nicotine is readily biodegradable in both types of media. The microbiological inhibition and aquatic and terrestrial toxicity tests indicated that nicotine has low toxicity. The U.S. Environmental Protection Agency Persistence, Bioaccumulation, and Toxicity Profiler model, based on the structure of nicotine and the predictive rates of hydroxyl radical and ozone reactions, estimated an atmospheric half-life of less than 5.0 h. Using this value in the Canadian Environmental Modeling Center level III model, the half-life of nicotine was estimated as 3.0 d in water and 0.5 d in soil. This model also estimated nicotine discharge into the environment; nicotine would be expected to be found predominantly in water (93%), followed by soil (4%), air (3%), and sediment (0.4%). Using the estimated nicotine concentrations in water, soil, and sediment and the proper median effective concentrations derived from the algal growth, biomass inhibition, and buttercrunch lettuce (Lactuca sativa) seed germination and root elongation studies, hazard quotients of between 10(-7) and 10(-8) were calculated, providing further support for the conclusion that the potential for nicotine toxicity to aquatic and terrestrial species in the environment is extremely low.

  16. Environmental fate and effects of nicotine released during cigarette production.

    PubMed

    Seckar, Joel A; Stavanja, Mari S; Harp, Paul R; Yi, Yongsheng; Garner, Charles D; Doi, Jon

    2008-07-01

    A variety of test methods were used to study the gradation, bioaccumulation, and toxicity of nicotine. Studies included determination of the octanol-water partition coefficient, conversion to CO2 in soil and activated sludge, and evaluation of the effects on microbiological and algal inhibition as well as plant germination and root elongation. The partitioning of nicotine between octanol and water indicated that nicotine will not bioaccumulate regardless of the pH of the medium. The aqueous and soil-based biodegradation studies indicated that nicotine is readily biodegradable in both types of media. The microbiological inhibition and aquatic and terrestrial toxicity tests indicated that nicotine has low toxicity. The U.S. Environmental Protection Agency Persistence, Bioaccumulation, and Toxicity Profiler model, based on the structure of nicotine and the predictive rates of hydroxyl radical and ozone reactions, estimated an atmospheric half-life of less than 5.0 h. Using this value in the Canadian Environmental Modeling Center level III model, the half-life of nicotine was estimated as 3.0 d in water and 0.5 d in soil. This model also estimated nicotine discharge into the environment; nicotine would be expected to be found predominantly in water (93%), followed by soil (4%), air (3%), and sediment (0.4%). Using the estimated nicotine concentrations in water, soil, and sediment and the proper median effective concentrations derived from the algal growth, biomass inhibition, and buttercrunch lettuce (Lactuca sativa) seed germination and root elongation studies, hazard quotients of between 10(-7) and 10(-8) were calculated, providing further support for the conclusion that the potential for nicotine toxicity to aquatic and terrestrial species in the environment is extremely low. PMID:18399728

  17. Release-Modulated Antioxidant Activity of a Composite Curcumin-Chitosan Polymer.

    PubMed

    O'Toole, Martin G; Soucy, Patricia A; Chauhan, Rajat; Raju, Mandapati V Ramakrishnam; Patel, Dhruvina N; Nunn, Betty M; Keynton, Megan A; Ehringer, William D; Nantz, Michael H; Keynton, Robert S; Gobin, Andrea S

    2016-04-11

    Curcumin is known to have immense therapeutic potential but is hindered by poor solubility and rapid degradation in solution. To overcome these shortcomings, curcumin has been conjugated to chitosan through a pendant glutaric anhydride linker using amide bond coupling chemistry. The hybrid polymer has been characterized by UV-visible, fluorescence, and infrared spectroscopies as well as zeta potential measurements and SEM imaging. The conjugation reactivity was confirmed through gel permeation chromatography and quantification of unconjugated curcumin. An analogous reaction of curcumin with glucosamine, a small molecule analogue for chitosan, was performed and the purified product characterized by mass spectrometry, UV-visible, fluorescence, and infrared spectroscopies. Conjugation of curcumin to chitosan has greatly improved curcumin aqueous solubility and stability, with no significant curcumin degradation detected after one month in solution. The absorbance and fluorescence properties of curcumin are minimally perturbed (λmax shifts of 2 and 5 nm, respectively) by the conjugation reaction. This conjugation strategy required use of one out of two curcumin phenols (one of the main antioxidant functional groups) for covalent linkage to chitosan, thus temporarily attenuating its antioxidant capacity. Hydrolysis-based release of curcumin from the polymer, however, is accompanied by full restoration of curcumin's antioxidant potential. Antioxidant assays show that curcumin radical scavenging potential is reduced by 40% after conjugation, but that full antioxidant potential is restored upon hydrolytic release from chitosan. Release studies show that curcumin is released over 19 days from the polymer and maintains a concentration of 0.23 ± 0.12 μM curcumin/mg polymer/mL solution based on 1% curcumin loading on the polymer. Release studies in the presence of carbonic anhydrase, an enzyme with known phenolic esterase activity, show no significant difference from

  18. Pluronic/gelatin composites for controlled release of actives.

    PubMed

    Tatini, Duccio; Tempesti, Paolo; Ridi, Francesca; Fratini, Emiliano; Bonini, Massimo; Baglioni, Piero

    2015-11-01

    This paper describes the preparation and the release properties of composite materials based on Pluronic F127 and gelatin hydrogels, which could be of interest in the field of enteral nutrition or drug administration. The composites were prepared by exploiting the opposite responsivity to temperature of a 20% w/w Pluronic F127 aqueous solution (critical gelation temperature around 23 °C) and gelatin (gel-sol temperature transition around 30 °C). Pluronic domains dispersed within a gelatin matrix were obtained by injecting cold Pluronic F127 solutions inside hot gelatin solutions, while homogenizing either with a magnetic stirrer or a high-energy mechanical disperser. Calorimetry indicates that the composites retain the individual gelling properties of Pluronic and gelatin. Different releasing properties were obtained as a function of the preparation protocol, the temperature and the pH. The release profiles have been studied by a Weibull analysis that clearly points out the dominating role of gelatin at 25 °C. At 37 °C the release accounts for a combined effect from both Pluronic F127 and gelatin, showing a more sustained profile with respect to gelatin hydrogels. This behavior, together with the ability of Pluronic F127 to upload both hydrophilic and hydrophobic drugs and flavors, makes these innovative composite materials very good candidates as FDA-approved carriers for enteral administration.

  19. Products of Leishmania braziliensis glucose catabolism: release of D-lactate and, under anaerobic conditions, glycerol

    SciTech Connect

    Darling, T.N.; Davis, D.G.; London, R.E.; Blum, J.J.

    1987-10-01

    Leishmania braziliensis panamensis promastigotes were incubated with glucose as the sole carbon source. About one-fifth of the glucose consumed under aerobic conditions was oxidized to CO/sub 2/. Nuclear magnetic resonance studies with (1-/sup 13/C)glucose showed that the other products released were succinate, acetate, alanine, pyruvate, and lactate. Under anaerobic conditions, lactate output increased, glycerol became a major product, and, surprisingly, glucose consumption decreased. Enzymatic assays showed that the lactate formed was D(-)-lactate. The release of alanine during incubation with glucose as the sole carbon source suggested that appreciable proteolysis occurred, consistent with our observation that a large amount of ammonia was released under these conditions. The discoveries that D-lactate is a product of L. braziliensis glucose catabolism, that glycerol is produced under anaerobic conditions, and that the cells exhibit a reverse Pasteur effect open the way for detailed studies of the pathways of glucose metabolism and their regulation in this organism.

  20. Consequences of tritium release to water pathways from postulated accidents in a DOE production reactor

    SciTech Connect

    O`Kula, K.R.; Olson, R.L.; Hamby, D.M.

    1991-12-31

    A full-scale PRA of a DOE production reactor has been completed that considers full release of tritium as part of the severe accident source term. Two classes of postulated reactor accidents, a loss-of-moderator pumping accident and a loss-of-coolant accident, are used to bound the expected dose consequence from liquid pathway release. Population doses from the radiological release associated with the two accidents are compared for aqueous discharge and atmospheric release modes. The expectation values of the distribution of possible values for the societal effective dose equivalent to the general public, given a tritium release to the atmosphere, is 2.8 person-Sv/PBq (9.9 {times} 10{sup {minus}3} person-rem/Ci). The general public drinking water dose to downstream water consumers is 6.5 {times} 10{sup {minus}2} person-Sv/Pbq (2.4 {times} 10{sup {minus}4} person-rem/Ci) for aqueous releases to the surface streams eventually reaching the Savannah River. Negligible doses are calculated for freshwater fish and saltwater invertebrate consumption, irrigation, and recreational use of the river, given that an aqueous release is assumed to occur. Relative to the balance of fission products released in a hypothetical severe accident, the tritium-related dose is small. This study suggests that application of regional models (1610 km radius) will indicate larger dose consequences from short-term tritium release to the atmosphere than from comparable tritium source terms to water pathways. However, the water pathways assessment is clearly site-specific, and the overall aqueous dose will be dependent on downstream receptor populations and uses of the river.

  1. Consequences of tritium release to water pathways from postulated accidents in a DOE production reactor

    SciTech Connect

    O'Kula, K.R.; Olson, R.L.; Hamby, D.M.

    1991-01-01

    A full-scale PRA of a DOE production reactor has been completed that considers full release of tritium as part of the severe accident source term. Two classes of postulated reactor accidents, a loss-of-moderator pumping accident and a loss-of-coolant accident, are used to bound the expected dose consequence from liquid pathway release. Population doses from the radiological release associated with the two accidents are compared for aqueous discharge and atmospheric release modes. The expectation values of the distribution of possible values for the societal effective dose equivalent to the general public, given a tritium release to the atmosphere, is 2.8 person-Sv/PBq (9.9 {times} 10{sup {minus}3} person-rem/Ci). The general public drinking water dose to downstream water consumers is 6.5 {times} 10{sup {minus}2} person-Sv/Pbq (2.4 {times} 10{sup {minus}4} person-rem/Ci) for aqueous releases to the surface streams eventually reaching the Savannah River. Negligible doses are calculated for freshwater fish and saltwater invertebrate consumption, irrigation, and recreational use of the river, given that an aqueous release is assumed to occur. Relative to the balance of fission products released in a hypothetical severe accident, the tritium-related dose is small. This study suggests that application of regional models (1610 km radius) will indicate larger dose consequences from short-term tritium release to the atmosphere than from comparable tritium source terms to water pathways. However, the water pathways assessment is clearly site-specific, and the overall aqueous dose will be dependent on downstream receptor populations and uses of the river.

  2. Highly Sensitive and Multiple Enzyme Activity Assay Using Reagent-release Capillary-Isoelectric Focusing with Rhodamine 110-based Substrates.

    PubMed

    Sueyoshi, Kenji; Nogawa, Yuto; Sugawara, Kasumi; Endo, Tatsuro; Hisamoto, Hideaki

    2015-01-01

    In this study, a simple and highly sensitive enzyme activity assay based on reagent-release capillary-isoelectric focusing is described. Reagent-release capillaries containing a fluorescent substrate, which produces fluorescent products possessing an isoelectric point after reaction with enzymes, provides a simple procedure. This is because it allows to spontaneously inject a sample solution into the capillary by capillary action, mixing reagents, and subsequently concentrating the fluorescent products based on isoelectric focusing. Fluorescent rhodamine 110 and its monoamide derivative, which were generated as a final product and an intermediate, respectively, were then focused and separated by reagent-release capillary-isoelectric focusing. After 30 min of enzyme reactions, two focused fluorescent bands were clearly isolated along the prepared capillaries. Employing the focused band of rhodamine 110 monoamide allowed for highly sensitive detection of enzyme activity in the 10 pg mL(-1) order, while that of the conventional assay using a microplate was in the ng mL(-1) order. Furthermore, arraying reagent-release capillaries of different substrates on a chip allowed for simultaneous multi-assay of enzyme activity with good sensitivity in the pg mL(-1) order for each protein.

  3. Activation of nicotinic ACh receptors with α4 subunits induces adenosine release at the rat carotid body

    PubMed Central

    Conde, Sílvia V; Monteiro, Emília C

    2006-01-01

    The effect of ACh on the release of adenosine was studied in rat whole carotid bodies, and the nicotinic ACh receptors involved in the stimulation of this release were characterized. ACh and nicotinic ACh receptor agonists, cytisine, DMPP and nicotine, caused a concentration-dependent increase in adenosine production during normoxia, with nicotine being more potent and efficient in stimulating adenosine release from rat CB than cytisine and DMPP. D-Tubocurarine, mecamylamine, DHβE and α-bungarotoxin, nicotinic ACh receptor antagonists, caused a concentration-dependent reduction in the release of adenosine evoked by hypoxia. The rank order of potency for nicotinic ACh receptor antagonists that inhibit adenosine release was DHβE>mecamylamine>D-tubocurarine>α-bungarotoxin. The effect of the endogenous agonist, ACh, which was mimicked by nicotine, was antagonized by DHβE, a selective nicotinic receptor antagonist. The ecto-5′-nucleotidase inhibitor AOPCP produces a 72% inhibition in the release of adenosine from CB evoked by nicotine. Taken together, these data indicate that ACh induced the production of adenosine, mainly from extracellular ATP catabolism at the CB through a mechanism that involves the activation of nicotinic receptors with α4 and β2 receptor subunits. PMID:16444287

  4. Phosphorylation of Complexin by PKA Regulates Activity-Dependent Spontaneous Neurotransmitter Release and Structural Synaptic Plasticity.

    PubMed

    Cho, Richard W; Buhl, Lauren K; Volfson, Dina; Tran, Adrienne; Li, Feng; Akbergenova, Yulia; Littleton, J Troy

    2015-11-18

    Synaptic plasticity is a fundamental feature of the nervous system that allows adaptation to changing behavioral environments. Most studies of synaptic plasticity have examined the regulated trafficking of postsynaptic glutamate receptors that generates alterations in synaptic transmission. Whether and how changes in the presynaptic release machinery contribute to neuronal plasticity is less clear. The SNARE complex mediates neurotransmitter release in response to presynaptic Ca(2+) entry. Here we show that the SNARE fusion clamp Complexin undergoes activity-dependent phosphorylation that alters the basic properties of neurotransmission in Drosophila. Retrograde signaling following stimulation activates PKA-dependent phosphorylation of the Complexin C terminus that selectively and transiently enhances spontaneous release. Enhanced spontaneous release is required for activity-dependent synaptic growth. These data indicate that SNARE-dependent fusion mechanisms can be regulated in an activity-dependent manner and highlight the key role of spontaneous neurotransmitter release as a mediator of functional and structural plasticity.

  5. Relationship between membrane potential changes and superoxide-releasing capacity in resident and activated mouse peritoneal macrophages

    SciTech Connect

    Kitagawa, S.; Johnston, R.B. Jr.

    1985-11-01

    To understand better the molecular basis for the enhanced respiratory burst of activated macrophages (M phi), the relationship between the stimulus-induced changes in membrane potential and release of superoxide anion (O/sub 2//sup -/) in mouse peritoneal M phi was investigated. Resident M phi and M phi elicited by injection of lipopolysaccharide (LPS-M phi) or obtained from animals infected with bacille Calmette-Guerin (BCG-M phi) were used. LPS-M phi and BCG-M phi showed more pronounced changes in membrane potential (depolarization) and greater release of O/sub 2//sup -/ on contact with phorbol myristate acetate (PMA) than did resident macrophages. The lag time between addition of stimulus and onset of release of O/sub 2//sup -/ was reduced in activated compared with resident cells. Membrane potential changes began 60 to 90 sec before release of O/sub 2//sup -/ could be detected in each cell type. The dose-response curves for triggering of membrane potential changes and O/sub 2//sup -/ release by PMA were identical. The magnitude of membrane potential changes and of O/sub 2//sup -/ release in LPS-M phi and BCG-M phi declined progressively during in vitro culture, and values on day 3 approached those in resident macrophages (deactivation). Extracellular glucose was required for effective stimulated change in membrane potential and O/sub 2//sup -/ release. These findings indicate that membrane potential changes are closely associated with O/sub 2//sup -/-releasing capacity in macrophages, and that the systems that mediate membrane potential changes and production of O/sub 2//sup -/ develop or decline concomitantly during activation or deactivation of the cells.

  6. Cytotoxicity of release products from magnetic nanocomposites in targeted drug delivery.

    PubMed

    Wamocha, H L; Misak, H E; Song, Z; Chu, H Y; Chen, Y Y; Asmatulu, R; Yang, S-Y; Ho, J C

    2013-02-01

    The efficacy of chemotherapy can be significantly improved if the therapeutic agent remains localized at the afflicted area and released at controlled rates. Such a targeted drug delivery can be achieved using magnetic nanocomposite (MNC), which incorporates drug and magnetic nanoparticles in biodegradable polymer microspheres. Reported here are results from an in vitro study on drug release rate and cytotoxicity of other release products from MNC. The model system contains an anti-cancer chemotherapy agent 5-flurouracil (5-FU) and (Co(0.5)Zn(0.5))Fe(2)O(4) in poly(lactic-co-glycolic acid) (PLGA) matrix produced by an oil/oil emulsion technique. Cell proliferation data indicate a sustained release of 5-FU for mouse macrophage cell eradication, whereas other microsphere components of magnetic nanoparticles and PLGA have little cytotoxic effects. PMID:22071353

  7. Polarized release of lipid mediators derived from phospholipase A2 activity in a human bronchial cell line.

    PubMed

    Madden, M C; Smith, J P; Dailey, L A; Friedman, M

    1994-09-01

    The release of arachidonic acid (AA) and platelet activating factor (PAF) from airway epithelial cells may be an important mediating factor in lung physiological and inflammatory processes. The type of lung response may be determined by the directional release of AA and PAF. We used the human bronchial epithelial cell line, BEAS2B (S6 subclone; BEAS), to investigate the polarized release of AA and PAF from lung epithelial cells. BEAS, grown on Transwell filters, were prelabeled with either 3H-AA or 3H-lyso-PAF. 3H-AA products and 3H-PAF were analyzed by high performance liquid chromatography and thin layer chromatography, respectively. BEAS incubated with melittin (2-4 micrograms/ml for 15 min) had an increased release (compared to vehicle-incubated cells) of both free 3H-AA and 3H-PAF into the apical compartment but not into the basolateral compartment. Treatment of the BEAS cells with the phospholipase A2 (PLA2) inhibitor mepacrine (1 mM) prior to, and during, incubation with melittin inhibited the increase in 3H-AA and 3H-PAF release into the apical compartment by 65% and 100%, respectively. Exposure of BEAS cells to ozone (O3; 1.0 ppm for 15 min) increased the release of polar 3H-AA products as well as 3H-PAF into both the apical and basolateral compartments. Mepacrine did not significantly inhibit the O3-induced release of polar 3H-AA products or 3H-PAF into either the apical or basolateral compartments. These data suggest the direction of the release of 3H-AA (or 3H-AA products) and 3H-PAF is stimulus-specific and that PLA2 involvement in the release of the lipids is also dependent on the stimulus. The directional release of AA, AA products, and PAF may be important in the airways responses to various agonists and oxidants.

  8. Antibacterial activity and ion release of bonding agent containing amorphous calcium phosphate nanoparticles

    PubMed Central

    Chen, Chen; Weir, Michael D.; Cheng, Lei; Lin, Nancy; Lin-Gibson, Sheng; Chow, Laurence C.; Zhou, Xuedong; Xu, Hockin H. K.

    2015-01-01

    Objectives Recurrent caries at the margins is a primary reason for restoration failure. The objectives of this study were to develop bonding agent with the double benefits of antibacterial and remineralizing capabilities, to investigate the effects of NACP filler level and solution pH on Ca and P ion release from adhesive, and to examine the antibacterial and dentin bond properties. Methods Nanoparticles of amorphous calcium phosphate (NACP) and a quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) were synthesized. Scotchbond Multi-Purpose (SBMP) primer and adhesive served as control. DMADDM was incorporated into primer and adhesive at 5% by mass. NACP was incorporated into adhesive at filler mass fractions of 10%, 20%, 30% and 40%. A dental plaque microcosm biofilm model was used to test the antibacterial bonding agents. Calcium (Ca) and phosphate (P) ion releases from the cured adhesive samples were measured vs. filler level and solution pH of 7, 5.5 and 4. Results Adding 5% DMADDM and 10–40% NACP into bonding agent, and water-aging for 28 days, did not affect dentin bond strength, compared to SBMP control at 1 day (p > 0.1). Adding DMADDM into bonding agent substantially decreased the biofilm metabolic activity and lactic acid production. Total microorganisms, total streptococci, and mutans streptococci were greatly reduced for bonding agents containing DMADDM. Increasing NACP filler level from 10% to 40% in adhesive increased the Ca and P ion release by an order of magnitude. Decreasing solution pH from 7 to 4 increased the ion release from adhesive by 6–10 folds. Significance Bonding agents containing antibacterial DMADDM and remineralizer NACP were formulated to have Ca and P ion release, which increased with NACP filler level from 10% to 40% in adhesive. NACP adhesive was “smart” and dramatically increased the ion release at cariogenic pH 4, when these ions would be most-needed to inhibit caries. Therefore, bonding agent

  9. Doxorubicin resistant cancer cells activate myeloid-derived suppressor cells by releasing PGE2

    PubMed Central

    Rong, Yuan; Yuan, Chun-Hui; Qu, Zhen; Zhou, Hu; Guan, Qing; Yang, Na; Leng, Xiao-Hua; Bu, Lang; Wu, Ke; Wang, Fu-Bing

    2016-01-01

    Chemotherapies often induce drug-resistance in cancer cells and simultaneously stimulate proliferation and activation of Myeloid-Derived Suppressor Cells (MDSCs) to inhibit anti-tumor T cells, thus result in poor prognosis of patients with breast cancers. To date, the mechanism underlying the expansion of MDSCs in response to chemotherapies is poorly understood. In the present study, we used in vitro cell culture and in vivo animal studies to demonstrate that doxorubicin-resistant breast cancer cells secret significantly more prostaglandin E2 (PGE2) than their parental doxorubicin-sensitive cells. The secreted PGE2 can stimulate expansion and polymerization of MDSCs by directly target to its receptors, EP2/EP4, on the surface of MDSCs, which consequently triggers production of miR-10a through activating PKA signaling. More importantly, activated MDSCs can inhibit CD4+CD25− T cells as evidenced by reduced proliferation and IFN-γ release. In order to determine the molecular pathway that involves miR-10a mediated activation of MDSCs, biochemical and pharmacological studies were carried out. We found that miR-10a can activate AMPK signaling to promote expansion and activation of MDSCs. Thus, these results reveal, for the first time, a novel role of PGE2/miR-10a/AMPK signaling axis in chemotherapy-induced immune resistance, which might be targeted for treatment of chemotherapy resistant tumors. PMID:27032536

  10. Doxorubicin resistant cancer cells activate myeloid-derived suppressor cells by releasing PGE2.

    PubMed

    Rong, Yuan; Yuan, Chun-Hui; Qu, Zhen; Zhou, Hu; Guan, Qing; Yang, Na; Leng, Xiao-Hua; Bu, Lang; Wu, Ke; Wang, Fu-Bing

    2016-01-01

    Chemotherapies often induce drug-resistance in cancer cells and simultaneously stimulate proliferation and activation of Myeloid-Derived Suppressor Cells (MDSCs) to inhibit anti-tumor T cells, thus result in poor prognosis of patients with breast cancers. To date, the mechanism underlying the expansion of MDSCs in response to chemotherapies is poorly understood. In the present study, we used in vitro cell culture and in vivo animal studies to demonstrate that doxorubicin-resistant breast cancer cells secret significantly more prostaglandin E2 (PGE2) than their parental doxorubicin-sensitive cells. The secreted PGE2 can stimulate expansion and polymerization of MDSCs by directly target to its receptors, EP2/EP4, on the surface of MDSCs, which consequently triggers production of miR-10a through activating PKA signaling. More importantly, activated MDSCs can inhibit CD4(+)CD25(-) T cells as evidenced by reduced proliferation and IFN-γ release. In order to determine the molecular pathway that involves miR-10a mediated activation of MDSCs, biochemical and pharmacological studies were carried out. We found that miR-10a can activate AMPK signaling to promote expansion and activation of MDSCs. Thus, these results reveal, for the first time, a novel role of PGE2/miR-10a/AMPK signaling axis in chemotherapy-induced immune resistance, which might be targeted for treatment of chemotherapy resistant tumors. PMID:27032536

  11. Concentration-triggered fission product release from zirconia: consequences for nuclear safety

    NASA Astrophysics Data System (ADS)

    Gentils, A.; Thomé, L.; Jagielski, J.; Garrido, F.

    2002-02-01

    Crystalline oxide ceramics, more particularly zirconia and spinel, are promising matrices for plutonium and minor actinide transmutation. An important issue concerning these materials is the investigation of their ability to confine radiotoxic elements resulting from the fission of actinides. This letter reports the study of the release, upon annealing or irradiation at high temperature, of one of the most toxic fission product (Cs) in zirconia. The foreign species are introduced by ion implantation and the release is studied by Rutherford backscattering experiments. The results emphasize the decisive influence of the fission product concentration on the release properties. The Cs mobility in zirconia is strongly increased when the impurity concentration exceeds a threshold of the order of a few atomic per cent. Irradiation with medium-energy heavy ions is shown to enhance Cs outdiffusion with respect to annealing at the same temperature.

  12. Activation and regulation of arachidonic acid release in rabbit peritoneal neutrophils

    SciTech Connect

    Tao, W.

    1988-01-01

    Arachidonic acid release in rabbit neutrophils can be enhanced by the addition of chemotactic fMet-Leu-Phe, platelet-activating factor, PAF, or the calcium ionophore A23187. Over 80% of the release ({sup 3}H)arachidonic acid comes from phosphatidylcholine and phosphatidylinositol. The release is dose-dependent and increases with increasing concentration of the stimulus. The A23187-induced release increases with increasing time of the stimulation. ({sup 3}H)arachidonic acid release, but not the rise in the concentration of intracellular calcium, is inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The ({sup 3}H)arachidonic acid released by A23187 is potentiated while that release by fMET-Leu-Phe or PAF is inhibited in phorbol 12-myristate 13-acetate, PMA, treated rabbit neutrophils. The protein kinase C inhibitor 1-(5-isoquinoline sulfonyl)-2-methylpiperazine, H-7, has no effect on the potentiation by PMA of the A23187-induced release, it prevents the inhibition by PMA of the release produced by PAF or fMet-Leu-Phe. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. The diacylglycerol kinase inhibitor R59022 increases the level of diacylglycerol in neutrophils stimulated with fMet-Leu-Phe. Furthermore, R59022 potentiates ({sup 3}H) arachidonic acid release produced by fMet-Leu-Phe. This potentiation is not inhibited by H-7, in fact, it is increased in H-7-treated neutrophils.

  13. Esomeprazole immediate release tablets: Gastric mucosa ex vivo permeation, absorption and antisecretory activity in conscious rats.

    PubMed

    Benetti, Camillo; Flammini, Lisa; Vivo, Valentina; Colombo, Paolo; Colombo, Gaia; Elviri, Lisa; Scarpignato, Carmelo; Buttini, Francesca; Bettini, Ruggero; Barocelli, Elisabetta; Rossi, Alessandra

    2016-10-10

    The aim of this work was to study the esomeprazole activity on the control of gastric secretion after administration of a novel immediate release tablet. The ex vivo permeation of esomeprazole across porcine gastric mucosa from immediate release tablets, containing sodium carbonate or magnesium oxide as alkalinizing agents, was firstly assessed. Pharmacokinetics and pharmacodynamics studies in conscious rats following the administration of immediate release tablets with sodium carbonate, in comparison with delayed-release tablets having the same formula, were also conducted. The results showed an important effect of sodium carbonate and magnesium oxide on the drug release, on the ex vivo trans-mucosal transport and the stability in acid environment. In particular, the presence of sodium carbonate in esomeprazole tablet formulation provided the maximum increase of the drug in vitro transport across the mucosa. Then, the absorption and the antisecretory activity of this proton pump inhibitor orally administered in rats as immediate release tablets containing Na2CO3, was superior but not significantly different compared to delayed-release tablets having the same formula. In the adopted animal model, an activity of esomeprazole from immediate release alkaline formulation was seen also in presence of partial gastric absorption allowing inhibition of proton pumps reached via systemic circulation. This esomeprazole immediate release formulation could be used for the on-demand treatment of acid-related disorders such as gastro-esophageal reflux disease.

  14. Esomeprazole immediate release tablets: Gastric mucosa ex vivo permeation, absorption and antisecretory activity in conscious rats.

    PubMed

    Benetti, Camillo; Flammini, Lisa; Vivo, Valentina; Colombo, Paolo; Colombo, Gaia; Elviri, Lisa; Scarpignato, Carmelo; Buttini, Francesca; Bettini, Ruggero; Barocelli, Elisabetta; Rossi, Alessandra

    2016-10-10

    The aim of this work was to study the esomeprazole activity on the control of gastric secretion after administration of a novel immediate release tablet. The ex vivo permeation of esomeprazole across porcine gastric mucosa from immediate release tablets, containing sodium carbonate or magnesium oxide as alkalinizing agents, was firstly assessed. Pharmacokinetics and pharmacodynamics studies in conscious rats following the administration of immediate release tablets with sodium carbonate, in comparison with delayed-release tablets having the same formula, were also conducted. The results showed an important effect of sodium carbonate and magnesium oxide on the drug release, on the ex vivo trans-mucosal transport and the stability in acid environment. In particular, the presence of sodium carbonate in esomeprazole tablet formulation provided the maximum increase of the drug in vitro transport across the mucosa. Then, the absorption and the antisecretory activity of this proton pump inhibitor orally administered in rats as immediate release tablets containing Na2CO3, was superior but not significantly different compared to delayed-release tablets having the same formula. In the adopted animal model, an activity of esomeprazole from immediate release alkaline formulation was seen also in presence of partial gastric absorption allowing inhibition of proton pumps reached via systemic circulation. This esomeprazole immediate release formulation could be used for the on-demand treatment of acid-related disorders such as gastro-esophageal reflux disease. PMID:27574989

  15. ENVIRONMENTAL RELEASE OF ASBESTOS/SUBSTITUTES FROM COMMERCIAL PRODUCTS USE AND DISPOSAL

    EPA Science Inventory

    For the first time, the release of respirable asbestos fibers has been quantified in terms of standard mechanical forces using widely accepted methodology and specified QA/QC procedures. Both fabrication of new products from asbestos containing materials and repair or removal of ...

  16. 77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Single-Ingredient, Immediate-Release Drug Products... AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and...

  17. The production and release to the atmosphere of chlorodifluoromethane (HCFC 22)

    NASA Astrophysics Data System (ADS)

    Midgley, P. M.; Fisher, D. A.

    The results of an audited production and use survey for chlorodifluoromethane (HCFC 22) for the years 1980-1991 are reported. Annual production figures for 1970-1979 have also been collected. The time delays for release to the atmosphere for the various uses of this commercial gas are estimated in order to calculate annual emissions. Calculated atmospheric concentrations and trends are compared with available measurements. Uncertainties in calculated parameters are examined relative to assumptions made in the analysis.

  18. Studies on the Release of Renin by Direct and Reflex Activation of Renal Sympathetic Nerves.

    ERIC Educational Resources Information Center

    Donald, David E.

    1979-01-01

    Presents data on release of renin during direct and indirect stimulation of renal nerves. Conclusions show that renin release is influenced by change in activity of carotid and cardiopulmonary baroreceptor systems, and excitation of discrete areas of brain and hypothalamus by changes in renal sympathetic nerve. (Author/SA)

  19. Affinity-mediated capture and release of amphiphilic copolymers for controlling antimicrobial activity.

    PubMed

    Takahashi, Haruko; Akiyoshi, Kazunari; Kuroda, Kenichi

    2015-08-14

    Capture and release of amphiphilic copolymers by a nano-sized polysaccharide gel (nanogel) was controlled by altering the hydrophobic binding affinity between the copolymer chains and nanogel. The antimicrobial activity of captured copolymer chains was suppressed, and regained upon release from the nanogel. PMID:26154063

  20. [Release amount of heavy metals in cement product from co-processing waste in cement kiln].

    PubMed

    Yang, Yu-Fei; Huang, Qi-Fei; Zhang, Xia; Yang, Yu; Wang, Qi

    2009-05-15

    Clinker was produced by Simulating cement calcination test, and concrete samples were also prepared according to national standard GB/T 17671-1999. Long-term cumulative release amount of heavy metals in cement product from co-processing waste in cement kiln was researched through leaching test which refers to EA NEN 7371 and EA NEN 7375, and one-dimensional diffusion model which is on the base of Fick diffusion law. The results show that availabilities of heavy metals are lower than the total amounts in concrete. The diffusion coefficients of heavy metals are different (Cr > As > Ni > Cd). During 30 years service, the cumulative release amounts of Cr, As, Ni and Cd are 4.43 mg/kg, 0.46 mg/kg, 1.50 mg/kg and 0.02 mg/kg, respectively, and the ratios of release which is the division of cumulative release amount and availability are 27.0%, 18.0%, 3.0% and 0.2%, respectively. The most important influence factor of cumulative release amount of heavy metal is the diffusion coefficient, and it is correlative to cumulative release amount. The diffusion coefficient of Cr and As should be controlled exactly in the processing of input the cement-kiln.

  1. Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae.

    PubMed

    Barros, Mario H; Bandy, Brian; Tahara, Erich B; Kowaltowski, Alicia J

    2004-11-26

    Increased replicative longevity in Saccharomyces cerevisiae because of calorie restriction has been linked to enhanced mitochondrial respiratory activity. Here we have further investigated how mitochondrial respiration affects yeast life span. We found that calorie restriction by growth in low glucose increased respiration but decreased mitochondrial reactive oxygen species production relative to oxygen consumption. Calorie restriction also enhanced chronological life span. The beneficial effects of calorie restriction on mitochondrial respiration, reactive oxygen species release, and replicative and chronological life span could be mimicked by uncoupling agents such as dinitrophenol. Conversely, chronological life span decreased in cells treated with antimycin (which strongly increases mitochondrial reactive oxygen species generation) or in yeast mutants null for mitochondrial superoxide dismutase (which removes superoxide radicals) and for RTG2 (which participates in retrograde feedback signaling between mitochondria and the nucleus). These results suggest that yeast aging is linked to changes in mitochondrial metabolism and oxidative stress and that mild mitochondrial uncoupling can increase both chronological and replicative life span.

  2. NASA/GEWEX Surface Radiation Budget: First Results From The Release 4 GEWEX Integrated Data Products

    NASA Astrophysics Data System (ADS)

    Stackhouse, Paul; Cox, Stephen; Gupta, Shashi; Mikovitz, J. Colleen; zhang, taiping

    2016-04-01

    The NASA/GEWEX Surface Radiation Budget (SRB) project produces shortwave and longwave surface and top of atmosphere radiative fluxes for the 1983-near present time period. Spatial resolution is 1 degree. The current release 3 (available at gewex-srb.larc.nasa.gov) uses the International Satellite Cloud Climatology Project (ISCCP) DX product for pixel level radiance and cloud information. This product is subsampled to 30 km. ISCCP is currently recalibrating and recomputing their entire data series, to be released as the H product, at 10km resolution. The ninefold increase in pixel number should help improve the RMS of the existing products and allow for future higher resolution SRB gridded product (e.g. 0.5 degree). In addition to the input data improvements, several important algorithm improvements have been made. Most notable has been the adaptation of Angular Distribution Models (ADMs) from CERES to improve the initial calculation of shortwave TOA fluxes, from which the surface flux calculations follow. Other key input improvements include a detailed aerosol history using the Max Planck Institut Aerosol Climatology (MAC), temperature and moisture profiles from HIRS, and new topography, surface type, and snow/ice. Here we present results for the improved GEWEX Shortwave and Longwave algorithm (GSW and GLW) with new ISCCP data, the various other improved input data sets and the incorporation of many additional internal SRB model improvements. As of the time of abstract submission, results from 2007 have been produced with ISCCP H availability the limiting factor. More SRB data will be produced as ISCCP reprocessing continues. The SRB data produced will be released as part of the Release 4.0 Integrated Product, recognizing the interdependence of the radiative fluxes with other GEWEX products providing estimates of the Earth's global water and energy cycle (I.e., ISCCP, SeaFlux, LandFlux, NVAP, etc.).

  3. Controlled continuous bio-hydrogen production using different biogas release strategies.

    PubMed

    Esquivel-Elizondo, S; Chairez, I; Salgado, E; Aranda, J S; Baquerizo, G; Garcia-Peña, E I

    2014-08-01

    Dark fermentation for bio-hydrogen (bio-H2) production is an easily operated and environmentally friendly technology. However, low bio-H2 production yield has been reported as its main drawback. Two strategies have been followed in the past to improve this fact: genetic modifications and adjusting the reaction conditions. In this paper, the second one is followed to regulate the bio-H2 release from the reactor. This operating condition alters the metabolic pathways and increased the bio-H2 production twice. Gas release was forced in the continuous culture to study the equilibrium in the mass transfer between the gaseous and liquid phases. This equilibrium depends on the H2, CO2, and volatile fatty acids production. The effect of reducing the bio-H2 partial pressure (bio-H2 pp) to enhance bio-H2 production was evaluated in a 30 L continuous stirred tank reactor. Three bio-H2 release strategies were followed: uncontrolled, intermittent, and constant. In the so called uncontrolled fermentation, without bio-H2 pp control, a bio-H2 molar yield of 1.2 mol/mol glucose was obtained. A sustained low bio-H2 pp of 0.06 atm increased the bio-H2 production rate from 16.1 to 108 mL/L/h with a stable bio-H2 percentage of 55% (v/v) and a molar yield of 1.9 mol/mol glucose. Biogas release enhanced bio-H2 production because lower bio-H2 pp, CO2 concentration, and reduced volatile fatty acids accumulation prevented the associated inhibitions and bio-H2 consumption.

  4. Serotonin 5-HT(2A) receptor activation induces 2-arachidonoylglycerol release through a phospholipase c-dependent mechanism.

    PubMed

    Parrish, Jason C; Nichols, David E

    2006-11-01

    To date, several studies have demonstrated that phospholipase C-coupled receptors stimulate the production of endocannabinoids, particularly 2-arachidonoylglycerol. There is now evidence that endocannabinoids are involved in phospholipase C-coupled serotonin 5-HT(2A) receptor-mediated behavioral effects in both rats and mice. The main objective of this study was to determine whether activation of the 5-HT(2A) receptor leads to the production and release of the endocannabinoid 2-arachidonoylglycerol. NIH3T3 cells stably expressing the rat 5-HT(2A) receptor were first incubated with [(3)H]-arachidonic acid for 24 h. Following stimulation with 10 mum serotonin, lipids were extracted from the assay medium, separated by thin layer chromatography, and analyzed by liquid scintillation counting. Our results indicate that 5-HT(2A) receptor activation stimulates the formation and release of 2-arachidonoylglycerol. The 5-HT(2A) receptor-dependent release of 2-arachidonoylglycerol was partially dependent on phosphatidylinositol-specific phospholipase C activation. Diacylglycerol produced downstream of 5-HT(2A) receptor-mediated phospholipase D or phosphatidylcholine-specific phospholipase C activation did not appear to contribute to 2-arachidonoylglycerol formation in NIH3T3-5HT(2A) cells. In conclusion, our results support a functional model where neuromodulatory neurotransmitters such as serotonin may act as regulators of endocannabinoid tone at excitatory synapses through the activation of phospholipase C-coupled G-protein coupled receptors. PMID:17010161

  5. Gastric inhibitory polypeptide (GIP) release by actively transported, structurally similar carbohydrates.

    PubMed

    Sirinek, K R; Levine, B A; O'Dorisio, T M; Cataland, S

    1983-07-01

    Six awake adult dogs prepared with a duodenocutaneous fistula were infused intraduodenally with one of the following solutions: 3% saline, 10% glucose, 20% glucose, 20% galactose, 20% fructose, 20% mannose, 20% sorbitol, 20% maltose, 20% lactose, or 20% sucrose. Both 10 and 20% glucose stimulated GIP release, and the response appeared to be dose related. Actively transported galactose (C-4 epimer) stimulated GIP release, but less than glucose. Fructose (C-2 keto sugar) which is absorbed by facilitated transport did not stimulate GIP release. Mannose (C-2 epimer) which is passively absorbed by diffusion did not release GIP. Sorbitol (reduced alcohol of glucose) which is not absorbed did not release GIP. Of the disaccharides tested, only maltose stimulated the release of GIP. The results suggest that structural integrity of the glucose molecule from the C-1 to C-4 carbon atoms, a free aldehyde group on the C-1 carbon atom, and a cyclic structure are all necessary for both the active transport of glucose and the release of endogenous GIP. It would appear that structurally similar receptors exist for both the active transport of glucose and for the release of GIP. PMID:6867011

  6. Motor activity-induced dopamine release in the substantia nigra is regulated by muscarinic receptors.

    PubMed

    Andersson, Daniel R; Björnsson, Evelina; Bergquist, Filip; Nissbrandt, Hans

    2010-01-01

    Nigro-striatal neurons release dopamine not only from their axon terminals in the striatum, but also from somata and dendrites in the substantia nigra. Somatodendritic dopamine release in the substantia nigra can facilitate motor function by mechanisms that may act independently of axon terminal dopamine release in the striatum. The dopamine neurons in the substantia nigra receive a cholinergic input from the pedunculopontine nucleus. Despite recent efforts to introduce this nucleus as a potential target for deep brain stimulation to treat motor symptoms in Parkinson's disease; and the well-known antiparkinsonian effects of anticholinergic drugs; the cholinergic influence on somatodendritic dopamine release is not well understood. The aim of this study was to investigate the possible regulation of locomotor-induced dopamine release in the substantia nigra by endogenous acetylcholine release. In intact and 6-OHDA hemi-lesioned animals alike, the muscarinic antagonist scopolamine, when perfused in the substantia nigra, amplified the locomotor-induced somatodendritic dopamine release to approximately 200% of baseline, compared to 120-130% of baseline in vehicle-treated animals. A functional importance of nigral muscarinic receptor activation was demonstrated in hemi-lesioned animals, where motor performance was significantly improved by scopolamine to 82% of pre-lesion performance, as compared to 56% in vehicle-treated controls. The results indicate that muscarinic activity in the substantia nigra is of functional importance in an animal Parkinson's disease model, and strengthen the notion that nigral dopaminergic regulation of motor activity/performance is independent of striatal dopamine release.

  7. Comparison of fission product release predictions using PARFUME with results from the AGR-1 irradiation experiment

    SciTech Connect

    Blaise Collin

    2014-09-01

    This report documents comparisons between post-irradiation examination measurements and model predictions of silver (Ag), cesium (Cs), and strontium (Sr) release from selected tristructural isotropic (TRISO) fuel particles and compacts during the first irradiation test of the Advanced Gas Reactor program that occurred from December 2006 to November 2009 in the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL). The modeling was performed using the particle fuel model computer code PARFUME (PARticle FUel ModEl) developed at INL. PARFUME is an advanced gas-cooled reactor fuel performance modeling and analysis code (Miller 2009). It has been developed as an integrated mechanistic code that evaluates the thermal, mechanical, and physico-chemical behavior of fuel particles during irradiation to determine the failure probability of a population of fuel particles given the particle-to-particle statistical variations in physical dimensions and material properties that arise from the fuel fabrication process, accounting for all viable mechanisms that can lead to particle failure. The code also determines the diffusion of fission products from the fuel through the particle coating layers, and through the fuel matrix to the coolant boundary. The subsequent release of fission products is calculated at the compact level (release of fission products from the compact) but it can be assessed at the particle level by adjusting the diffusivity in the fuel matrix to very high values. Furthermore, the diffusivity of each layer can be individually set to a high value (typically 10-6 m2/s) to simulate a failed layer with no capability of fission product retention. In this study, the comparison to PIE focused on fission product release and because of the lack of failure in the irradiation, the probability of particle failure was not calculated. During the AGR-1 irradiation campaign, the fuel kernel produced and released fission products, which migrated through the successive

  8. Effects of Globally Waste Disturbing Activities on Gas Generation, Retention, and Release in Hanford Waste Tanks

    SciTech Connect

    Stewart, Charles W.; Fountain, Matthew S.; Huckaby, James L.; Mahoney, Lenna A.; Meyer, Perry A.; Wells, Beric E.

    2005-08-02

    Various operations are authorized in Hanford single- and double-shell tanks that disturb all or a large fraction of the waste. These globally waste-disturbing activities have the potential to release a large fraction of the retained flammable gas and to affect future gas generation, retention, and release behavior. This report presents analyses of the expected flammable gas release mechanisms and the potential release rates and volumes resulting from these activities. The background of the flammable gas safety issue at Hanford is summarized, as is the current understanding of gas generation, retention, and release phenomena. Considerations for gas monitoring and assessment of the potential for changes in tank classification and steady-state flammability are given.

  9. Antarctic stratospheric chemistry of chlorine nitrate, hydrogen chloride, and ice - Release of active chlorine

    NASA Technical Reports Server (NTRS)

    Molina, Mario J.; Tso, Tai-Ly; Molina, Luisa T.; Wang, Frank C.-Y.

    1987-01-01

    The reaction rate between atmospheric hydrogen chloride (HCl) and chlorine nitrate (ClONO2) is greatly enhanced in the presence of ice particles; HCl dissolves readily into ice, and the collisional reaction probability for ClONO2 on the surface of ice with HCl in the mole fraction range from about 0.003 to 0.010 is in the range from about 0.05 to 0.1 for temperatures near 200 K. Chlorine is released into the gas phase on a time scale of at most a few milliseconds, whereas nitric acid (HNO3), the other product, remains in the condensed phase. This reaction could play an important role in explaining the observed depletion of ozone over Antarctica; it releases photolytically active chlorine from its most abundant reservoir species, and it promotes the formation of HNO3 and thus removes nitrogen dioxide from the gas phase. Hence it establishes the necessary conditions for the efficient catalytic destruction of ozone by halogenated free radicals.

  10. Explanatory Supplement to the WISE All-Sky Data Release Products

    NASA Astrophysics Data System (ADS)

    Cutri, R. M.; Wright, E. L.; Conrow, T.; Bauer, J.; Benford, D.; Brandenburg, H.; Dailey, J.; Eisenhardt, P. R. M.; Evans, T.; Fajardo-Acosta, S.; Fowler, J.; Gelino, C.; Grillmair, C.; Harbut, M.; Hoffman, D.; Jarrett, T.; Kirkpatrick, J. D.; Leisawitz, D.; Liu, W.; Mainzer, A.; Marsh, K.; Masci, F.; McCallon, H.; Padgett, D.; Ressler, M. E.; Royer, D.; Skrutskie, M. F.; Stanford, S. A.; Wyatt, P. L.; Tholen, D.; Tsai, C. W.; Wachter, S.; Wheelock, S. L.; Yan, L.; Alles, R.; Beck, R.; Grav, T.; Masiero, J.; McCollum, B.; McGehee, P.; Papin, M.; Wittman, M.

    2012-03-01

    The Wide-field Infrared Survey Explorer (WISE; Wright et al. 2010) surveyed the entire sky at 3.4, 4.6, 12 and 22 microns in 2010, achieving 5-sigma point source sensitivities per band better than 0.08, 0.11, 1 and 6 mJy in unconfused regions on the ecliptic. The WISE All-Sky Data Release, conducted on March 14, 2012, incorporates all data taken during the full cryogenic mission phase, 7 January 2010 to 6 August 2010, that were processed with improved calibrations and reduction algorithms. Release data products include: (1) an Atlas of 18,240 match-filtered, calibrated and coadded image sets; (2) a Source Catalog containing positions and four-band photometry for over 563 million objects, and (3) an Explanatory Supplement. Ancillary products include a Reject Table that contains 284 million detections that were not selected for the Source Catalog because they are low signal-to-noise ratio or spurious detections of image artifacts, an archive of over 1.5 million sets of calibrated WISE Single-exposure images, and a database of 9.4 billion source extractions from those single-images, and moving object tracklets identified by the NEOWISE program (Mainzer et al. 2011). The WISE All-Sky Data Release products supersede those from the WISE Preliminary Data Release (Cutri et al. 2011). The Explanatory Supplement to the WISE All-Sky Data Release Products is a general guide for users of the WISE data. The Supplement contains an overview of the WISE mission, facilities, and operations, a detailed description of WISE data processing algorithms, a guide to the content and formats of the image and tabular data products, and cautionary notes that describe known limitations of the All-Sky Release products. Instructions for accessing the WISE data products via the services of the NASA/IPAC Infrared Science Archive are provided. The Supplement also provides analyses of the achieved sky coverage, photometric and astrometric characteristics and completeness and reliability of the All

  11. Release of primary microplastics from consumer products to wastewater in the Netherlands.

    PubMed

    van Wezel, Annemarie; Caris, Inez; Kools, Stefan A E

    2016-07-01

    The authors estimate the release of primary microplastics from consumer products-cosmetics and personal care products, cleaning agents, and paint and coatings-via sewage effluent as an expected relevant route to the marine environment. Total estimated concentrations in the 3 scenarios are 0.2 μg/L, 2.7 μg/L, and 66 μg/L in sewage-treatment plant (STP) effluent, respectively. All product categories relevantly contribute. Predicted concentrations are compared with reported actual concentrations in STP effluents. Environ Toxicol Chem 2016;35:1627-1631. © 2015 SETAC.

  12. Activation of the inositol (1,4,5)-triphosphate calcium gate receptor is required for HIV-1 Gag release.

    PubMed

    Ehrlich, Lorna S; Medina, Gisselle N; Khan, Mahfuz B; Powell, Michael D; Mikoshiba, Katsuhiko; Carter, Carol A

    2010-07-01

    The structural precursor polyprotein, Gag, encoded by all retroviruses, including the human immunodeficiency virus type 1 (HIV-1), is necessary and sufficient for the assembly and release of particles that morphologically resemble immature virus particles. Previous studies have shown that the addition of Ca(2+) to cells expressing Gag enhances virus particle production. However, no specific cellular factor has been implicated as mediator of Ca(2+) provision. The inositol (1,4,5)-triphosphate receptor (IP3R) gates intracellular Ca(2+) stores. Following activation by binding of its ligand, IP3, it releases Ca(2+) from the stores. We demonstrate here that IP3R function is required for efficient release of HIV-1 virus particles. Depletion of IP3R by small interfering RNA, sequestration of its activating ligand by expression of a mutated fragment of IP3R that binds IP3 with very high affinity, or blocking formation of the ligand by inhibiting phospholipase C-mediated hydrolysis of the precursor, phosphatidylinositol-4,5-biphosphate, inhibited Gag particle release. These disruptions, as well as interference with ligand-receptor interaction using antibody targeted to the ligand-binding site on IP3R, blocked plasma membrane accumulation of Gag. These findings identify IP3R as a new determinant in HIV-1 trafficking during Gag assembly and introduce IP3R-regulated Ca(2+) signaling as a potential novel cofactor in viral particle release.

  13. Fission Product Release from Molten U/Al Alloy Fuel: A Vapor Transpiration Model

    SciTech Connect

    Whitkop, P.G.

    2001-06-26

    This report describes the application of a vapor transportation model to fission product release data obtained for uranium/aluminum alloy fuel during early Oak Ridge fuel melt experiments. The Oak Ridge data validates the vapor transpiration model and suggests that iodine and cesium are released from the molten fuel surface in elemental form while tellurium and ruthenium are released as oxides. Cesium iodide is postulated to form in the vapor phase outside of the fuel matrix. Kinetic data indicates that cesium iodide can form from Cs atoms and diatomic iodine in the vapor phase. Temperatures lower than those capable of melting fuel are necessary in order to maintain a sufficient I2 concentration. At temperatures near the fuel melting point, cesium can react with iodine atoms to form CsI only on solid surfaces such as aerosols.

  14. Impact of biodiversity loss on production in complex marine food webs mitigated by prey-release

    PubMed Central

    Fung, Tak; Farnsworth, Keith D.; Reid, David G.; Rossberg, Axel G.

    2015-01-01

    Public concern over biodiversity loss is often rationalized as a threat to ecosystem functioning, but biodiversity-ecosystem functioning (BEF) relations are hard to empirically quantify at large scales. We use a realistic marine food-web model, resolving species over five trophic levels, to study how total fish production changes with species richness. This complex model predicts that BEF relations, on average, follow simple Michaelis–Menten curves when species are randomly deleted. These are shaped mainly by release of fish from predation, rather than the release from competition expected from simpler communities. Ordering species deletions by decreasing body mass or trophic level, representing ‘fishing down the food web’, accentuates prey-release effects and results in unimodal relationships. In contrast, simultaneous unselective harvesting diminishes these effects and produces an almost linear BEF relation, with maximum multispecies fisheries yield at ≈40% of initial species richness. These findings have important implications for the valuation of marine biodiversity. PMID:25799523

  15. Nattokinase-promoted tissue plasminogen activator release from human cells.

    PubMed

    Yatagai, Chieko; Maruyama, Masugi; Kawahara, Tomoko; Sumi, Hiroyuki

    2008-01-01

    When heated to a temperature of 70 degrees C or higher, the strong fibrinolytic activity of nattokinase in a solution was deactivated. Similar results were observed in the case of using Suc-Ala-Ala-Pro-Phe-pNA and H-D-Val-Leu-Lys-pNA, which are synthetic substrates of nattokinase. In the current study, tests were conducted on the indirect fibrinolytic effects of the substances containing nattokinase that had been deactivated through heating at 121 degrees C for 15 min. Bacillus subtilis natto culture solutions made from three types of bacteria strain were heat-treated and deactivated, and it was found that these culture solutions had the ability to generate tissue plasminogen activators (tPA) from vascular endothelial cells and HeLa cells at certain concentration levels. For example, it was found that the addition of heat-treated culture solution of the Naruse strain (undiluted solution) raises the tPA activity of HeLa cells to about 20 times that of the control. Under the same conditions, tPA activity was raised to a level about 5 times higher for human vascular endothelial cells (HUVEC), and to a level about 24 times higher for nattokinase sold on the market. No change in cell count was observed for HeLa cells and HUVEC in the culture solution at these concentrations, and the level of activity was found to vary with concentration.

  16. Nonsynaptic Communication Through ATP Release from Volume-Activated Anion Channels in Axons

    PubMed Central

    Fields, R. Douglas; Ni, Yingchun

    2016-01-01

    The release of neuronal messengers outside synapses has broad biological implications, particularly with regard to communication between axons and glia. We identify a mechanism for nonsynaptic, nonvesicular release of adenosine triphosphate (ATP) from axons through volume-activated anion channels (VAACs) activated by microscopic axon swelling during action potential firing. We used a combination of single-photon imaging of ATP release, together with imaging for intrinsic optical signals, intracellular calcium ions (Ca2+), time-lapse video, and confocal microscopy, to investigate action potential–induced nonsynaptic release of this neurotransmitter. ATP release from cultured embryonic dorsal root ganglion axons persisted when bafilomycin or botulinum toxin was used to block vesicular release, whereas pharmacological inhibition of VAACs or prevention of action potential–induced axon swelling inhibited ATP release and disrupted activity-dependent signaling between axons and astrocytes. This nonvesicular, nonsynaptic communication could mediate various activity-dependent interactions between axons and nervous system cells in normal conditions, development, and disease. PMID:20923934

  17. Enzymatic production by tissue extracts of a metabolite of nicotinamide adenine dinucleotide with calcium-releasing ability

    SciTech Connect

    Tich, N.R.

    1989-01-01

    This research investigated the occurrence and characterization of the metabolite in mammalian tissues. In all mammalian tissues tested, including rabbit liver, heart, spleen, kidney, and brain, the factor to convert NAD into its active metabolite was present. The conversion exhibited many characteristics of an enzymatic process such as temperature sensitivity, concentration dependence and protease sensitivity. Production of the NAD metabolite occurred within a time frame of 15-45 minutes at 37{degree}C, depending upon the particular preparation. The metabolite was isolated using high performance liquid chromatography from all mammalian tissues. This purified metabolite was then tested for its effectiveness in releasing intracellular calcium in an intact cell by microinjecting it into unfertilized sea urchin eggs. These eggs undergo a massive morphological change upon fertilization which is dependent upon the release of calcium from inside the cell. Upon injection of the NAD metabolite into unfertilized eggs, this same morphological change was observed showing indirectly that the metabolite released intracellular calcium from an intact, viable cell. In addition, radioactive studies using {sup 45}Ca{sup 2+} loaded into permeabilized hepatocytes, indicated in preliminary studies that the NAD metabolite could also release calcium from intracellular stores of mammalian cells.

  18. Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules

    PubMed Central

    Cavallo, Carola; Mariani, Erminia; Pratelli, Loredana; Merli, Giulia; Marcacci, Maurilio

    2016-01-01

    Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl2, 10% of autologous thrombin, 10% of a mixture of CaCl2 + thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-β1, PDGF-AB, IL-1β, and TNF-α. PRP activated with CaCl2, thrombin, and CaCl2/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl2/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF-β1 that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl2 induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic.

  19. Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules

    PubMed Central

    Cavallo, Carola; Mariani, Erminia; Pratelli, Loredana; Merli, Giulia; Marcacci, Maurilio

    2016-01-01

    Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl2, 10% of autologous thrombin, 10% of a mixture of CaCl2 + thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-β1, PDGF-AB, IL-1β, and TNF-α. PRP activated with CaCl2, thrombin, and CaCl2/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl2/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF-β1 that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl2 induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic. PMID:27672658

  20. Comparison of fission product release predictions using PARFUME with results from the AGR-1 safety tests

    DOE PAGES

    Collin, Blaise P.; Petti, David A.; Demkowicz, Paul A.; Maki, John T.

    2016-04-07

    Safety tests were conducted on fuel compacts from AGR-1, the first irradiation experiment of the Advanced Gas Reactor (AGR) Fuel Development and Qualification program, at temperatures ranging from 1600 to 1800 °C to determine fission product release at temperatures that bound reactor accident conditions. The PARFUME (PARticle FUel ModEl) code was used to predict the release of fission products silver, cesium, strontium, and krypton from fuel compacts containing tristructural isotropic (TRISO) coated particles during 15 of these safety tests. Comparisons between PARFUME predictions and post-irradiation examination results of the safety tests were conducted on two types of AGR-1 compacts: compactsmore » containing only intact particles and compacts containing one or more particles whose SiC layers failed during safety testing. In both cases, PARFUME globally over-predicted the experimental release fractions by several orders of magnitude: more than three (intact) and two (failed SiC) orders of magnitude for silver, more than three and up to two orders of magnitude for strontium, and up to two and more than one orders of magnitude for krypton. The release of cesium from intact particles was also largely over-predicted (by up to five orders of magnitude) but its release from particles with failed SiC was only over-predicted by a factor of about 3. These over-predictions can be largely attributed to an over-estimation of the diffusivities used in the modeling of fission product transport in TRISO-coated particles. The integral release nature of the data makes it difficult to estimate the individual over-estimations in the kernel or each coating layer. Nevertheless, a tentative assessment of correction factors to these diffusivities was performed to enable a better match between the modeling predictions and the safety testing results. The method could only be successfully applied to silver and cesium. In the case of strontium, correction factors could not be assessed

  1. Mass Production of Genetically Modified Aedes aegypti for Field Releases in Brazil

    PubMed Central

    Carvalho, Danilo O.; Nimmo, Derric; Naish, Neil; McKemey, Andrew R.; Gray, Pam; Wilke, André B. B.; Marrelli, Mauro T.; Virginio, Jair F.; Alphey, Luke; Capurro, Margareth L.

    2014-01-01

    New techniques and methods are being sought to try to win the battle against mosquitoes. Recent advances in molecular techniques have led to the development of new and innovative methods of mosquito control based around the Sterile Insect Technique (SIT)1-3. A control method known as RIDL (Release of Insects carrying a Dominant Lethal)4, is based around SIT, but uses genetic methods to remove the need for radiation-sterilization5-8. A RIDL strain of Ae. aegypti was successfully tested in the field in Grand Cayman9,10; further field use is planned or in progress in other countries around the world. Mass rearing of insects has been established in several insect species and to levels of billions a week. However, in mosquitoes, rearing has generally been performed on a much smaller scale, with most large scale rearing being performed in the 1970s and 80s. For a RIDL program it is desirable to release as few females as possible as they bite and transmit disease. In a mass rearing program there are several stages to produce the males to be released: egg production, rearing eggs until pupation, and then sorting males from females before release. These males are then used for a RIDL control program, released as either pupae or adults11,12. To suppress a mosquito population using RIDL a large number of high quality male adults need to be reared13,14. The following describes the methods for the mass rearing of OX513A, a RIDL strain of Ae. aegypti 8, for release and covers the techniques required for the production of eggs and mass rearing RIDL males for a control program. PMID:24430003

  2. Newly Released TRMM Version 7 Products, Other Precipitation Datasets and Data Services at NASA GES DISC

    NASA Technical Reports Server (NTRS)

    Liu, Zhong; Ostrenga, D.; Teng, W. L.; Trivedi, Bhagirath; Kempler, S.

    2012-01-01

    The NASA Goddard Earth Sciences Data and Information Services Center (GES DISC) is home of global precipitation product archives, in particular, the Tropical Rainfall Measuring Mission (TRMM) products. TRMM is a joint U.S.-Japan satellite mission to monitor tropical and subtropical (40 S - 40 N) precipitation and to estimate its associated latent heating. The TRMM satellite provides the first detailed and comprehensive dataset on the four dimensional distribution of rainfall and latent heating over vastly undersampled tropical and subtropical oceans and continents. The TRMM satellite was launched on November 27, 1997. TRMM data products are archived at and distributed by GES DISC. The newly released TRMM Version 7 consists of several changes including new parameters, new products, meta data, data structures, etc. For example, hydrometeor profiles in 2A12 now have 28 layers (14 in V6). New parameters have been added to several popular Level-3 products, such as, 3B42, 3B43. Version 2.2 of the Global Precipitation Climatology Project (GPCP) dataset has been added to the TRMM Online Visualization and Analysis System (TOVAS; URL: http://disc2.nascom.nasa.gov/Giovanni/tovas/), allowing online analysis and visualization without downloading data and software. The GPCP dataset extends back to 1979. Version 3 of the Global Precipitation Climatology Centre (GPCC) monitoring product has been updated in TOVAS as well. The product provides global gauge-based monthly rainfall along with number of gauges per grid. The dataset begins in January 1986. To facilitate data and information access and support precipitation research and applications, we have developed a Precipitation Data and Information Services Center (PDISC; URL: http://disc.gsfc.nasa.gov/precipitation). In addition to TRMM, PDISC provides current and past observational precipitation data. Users can access precipitation data archives consisting of both remote sensing and in-situ observations. Users can use these data

  3. Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity

    PubMed Central

    1990-01-01

    Cultured bovine capillary endothelial (BCE) cells synthesize heparan sulfate proteoglycans (HSPG), which are both secreted into the culture medium and deposited in the cell layer. The nonsoluble HSPGs can be isolated as two predominant species: a larger 800-kD HSPG, which is recovered from preparations of extracellular matrix, and a 250-kD HSPG, which is solubilized by nonionic detergent extraction of the cells. Both HSPG species bind bFGF. 125I-bFGF bound to BCE cell cultures is readily released by either heparinase or plasmin. When released by plasmin, the growth factor is recovered from the incubation medium as a complex with the partly degraded high molecular mass HSPG. Endogenous bFGF activity is released by a proteolytic treatment of cultured BCE cells. The bFGF-binding HSPGs are also released when cultures are incubated with the inactive proenzyme plasminogen. Under such experimental conditions, the release of the extracellular proteoglycans can be enhanced by treating the cells either with bFGF, which increases the plasminogen activating activity expressed by the cells, or decreased by treating the cells with transforming growth factor beta, which decreases the plasminogen activating activity of the cells. Specific immune antibodies raised against bovine urokinase also block the release of HSPG from BCE cell cultures. We propose that this plasminogen activator-mediated proteolysis provides a mechanism for the release of biologically active bFGF-HSPG complexes from the extracellular matrix and that bFGF release can be regulated by the balance between factors affecting the pericellular proteolytic activity. PMID:2137829

  4. Biopharmaceutical characterization of oral immediate release drug products. In vitro/in vivo comparison of phenoxymethylpenicillin potassium, glimepiride and levofloxacin.

    PubMed

    Frick, A; Möller, H; Wirbitzki, E

    1998-11-01

    The development of in vitro dissolution tests using the paddle and basket apparatus is described with respect to the qualification/validation of the testing procedure. Three examples of immediate release products containing phenoxymethylpenicillin potassium, glimepiride, and levofloxacin providing different solubility characteristics are evaluated. The solubility was high in the case of phenoxymethylpenicillin potassium and levofloxacin and low for glimepiride according to the biopharmaceutics classification system. The permeability is studied using the human colorectal carcinoma cell line CaCo-2. The permeability (10(-6) cm/s) of phenoxymethylpenicillin potassium, glimepiride, and levofloxacin was high. The determined permeability data are confirmed by absorption data obtained by means of numerical deconvolution of plasma concentrations. Recommendations are given for the biopharmaceutical characterization of the three immediate release drug products, taking into account in vitro and in vivo comparison as well as the biopharmaceutics drug classification system. The evaluated acceptance criteria are the following: phenoxymethylpenicillin potassium (80% in 30 min), glimepiride (80% in 15 min) and levofloxacin (80% in 30 min). Typically, for immediate release formulations, one limit is specified for the dissolution to ensure the release of the active ingredient within the present time period. Since phenoxymethylpenicillin potassium and levofloxacin belong to Case 1, no in vitro/in vivo correlation is expected, absorption may be gastric emptying dependent. Glimepiride is categorized to Case 2. Nevertheless, a correlation with the in vivo dissolution profile does not exist, because of the pH-dependent low solubility of the drug. Finally, recommendations are made for the batch control of drug products in accordance with the four Cases.

  5. Glycosylation and Activities of Natural Products.

    PubMed

    Huang, Gangliang; Lv, Meijiao; Hu, Jinchuan; Huang, Kunlin; Xu, Hong

    2016-01-01

    Natural products are widely found in nature, their number and variety are numerous, the structures are complex and diverse. These natural products have many physiological and pharmacological activities. Glycosylation can increase the diversity of structure and function of natural product, it has become the focus of drug research and development. The impacts of glycosylation of natural products to water solubility, pharmacological activities, bioavailability, or others were described in this review, which provides a reference for the development and application of glycosylated natural products. PMID:27499190

  6. Diffusion modeling of fission product release during depressurized core conduction cooldown conditions

    SciTech Connect

    Martin, R.C.

    1990-01-01

    A simple model for diffusion through the silicon carbide layer of TRISO particles is applied to the data for accident condition testing of fuel spheres for the High-Temperature Reactor program of the Federal Republic of Germany (FRG). Categorization of sphere release of {sup 137}Cs based on fast neutron fluence permits predictions of release with an accuracy comparable to that of the US/FRG accident condition fuel performance model. Calculations are also performed for {sup 85}Kr, {sup 90}Sr, and {sup 110m}Ag. Diffusion of cesium through SiC suggests that models of fuel failure should consider fuel performance during repeated accident condition thermal cycling. Microstructural considerations in models in fission product release are discussed. The neutron-induced segregation of silicon within the SiC structure is postulated as a mechanism for enhanced fission product release during accident conditions. An oxygen-enhanced SiC decomposition mechanism is also discussed. 12 refs., 11 figs., 2 tabs.

  7. Hydrogen peroxide release kinetics into saliva from different whitening products: a double-blind, randomized clinical trial.

    PubMed

    Marques, Duarte Nuno da Silva; da Mata, António Duarte Sola Pereira; Silveira, João Miguel Lourenço; Marques, Joana Rita Oliveira Faria; Amaral, João Pedro de Almeida Rato; Guilherme, Nuno Filipe Rito Parada Marques

    2012-02-01

    The objective of this study is to compare salivary hydrogen peroxide (HP) release kinetics and potential toxicity of systemic exposure of four different whitening products. A double-blind, randomized controlled trial was conducted in a Portuguese dental faculty clinic. Two hundred forty volunteers were randomized to eight intervention groups. Participants were randomly assigned to receive active or placebo applications of one of four different products: Opalescence 10% PF™ (OPL), Vivastyle® 10%™ (VS10%), Vivadent Paint On Plus™ (PO+), and Trés White Supreme™ (TWS). Saliva collection was obtained by established methods at different times. The HP salivary content was determined by a photometric method. Salivary HP variations, total amount of salivary HP, and counts of subjects above the safe daily HP dose were the main outcome measures. All whitening systems significantly released HP to the saliva when compared to placebo, and all showed different release kinetics. The adaptable tray system (TWS) presented a risk increase of 37% [20-54%, 95% confidence interval] when compared to the other systems. The use of an adaptable tray whitening system with higher concentration of HP increases the toxicity potential.

  8. Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters

    PubMed Central

    Newman, Eric A.

    2015-01-01

    Astrocytes in the brain release transmitters that actively modulate neuronal excitability and synaptic efficacy. Astrocytes also release vasoactive agents that contribute to neurovascular coupling. As reviewed in this article, Müller cells, the principal retinal glial cells, modulate neuronal activity and blood flow in the retina. Stimulated Müller cells release ATP which, following its conversion to adenosine by ectoenzymes, hyperpolarizes retinal ganglion cells by activation of A1 adenosine receptors. This results in the opening of G protein-coupled inwardly rectifying potassium (GIRK) channels and small conductance Ca2+-activated K+ (SK) channels. Tonic release of ATP also contributes to the generation of tone in the retinal vasculature by activation of P2X receptors on vascular smooth muscle cells. Vascular tone is lost when glial cells are poisoned with the gliotoxin fluorocitrate. The glial release of vasoactive metabolites of arachidonic acid, including prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs), contributes to neurovascular coupling in the retina. Neurovascular coupling is reduced when neuronal stimulation of glial cells is interrupted and when the synthesis of arachidonic acid metabolites is blocked. Neurovascular coupling is compromised in diabetic retinopathy owing to the loss of glial-mediated vasodilation. This loss can be reversed by inhibiting inducible nitric oxide synthase. It is likely that future research will reveal additional important functions of the release of transmitters from glial cells. PMID:26009774

  9. Release of plasminogen activator inhibitor-1 from human astrocytes is regulated by intracellular ceramide.

    PubMed

    Kimura, M; Soeda, S; Oda, M; Ochiai, T; Kihara, T; Ono, N; Shimeno, H

    2000-12-15

    The present study underscores a regulatory role of intracellular ceramide in astrocytes for the release of an extracellular serine protease, tissue-type plasminogen activator (t-PA), and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). Treatment of cultured human astrocytes with N-acetylsphingosine, a cell-permeable short-chain ceramide analogue or daunorubicin that could increase intracellular ceramide via activation of ceramide synthase or sphingomyelin hydrolysis increased the release of t-PA and conversely decreased the PAI-1 release. Interestingly, treatment of the astrocytes with tumor necrosis factor (TNF)-alpha also increased the intracellular ceramide levels but caused the elevation of PAI-1 release without altering the t-PA release. These data suggest that the generation of ceramide in astrocytes is linked at least with the regulation of PAI-1 release. We also demonstrate that the suppression of PAI-1 release with daunorubicin accelerates the cell death of neuronally differentiated PC12 cells and suggest an antiapoptotic role of PAI-1 in the nervous system.

  10. Role of calcium-activated potassium channels in transmitter release at the squid giant synapse.

    PubMed Central

    Augustine, G J; Charlton, M P; Horn, R

    1988-01-01

    1. Several compounds known to block Ca2+-activated K+ channels were microinjected into squid 'giant' presynaptic terminals to test the hypothesis that these channels mediate Ca2+-dependent neurotransmitter release. 2. Injection of tetrapentylammonium, nonyl-triethylammonium and decamethonium all reversibly blocked transmission evoked by presynaptic action potentials. 3. All three of these compounds blocked presynaptic Ca2+ channels. The actions of tetrapentylammonium on presynaptic Ca2+ influx were examined in detail and found to be quantitatively sufficient to account for the ability of this compound to inhibit transmitter release. 4. Injection of Ba2+, another agent known to block Ca2+-activated K+ channels, also reversibly blocked evoked transmitter release. Ba2+ simultaneously enhanced basal (asynchronous) transmitter release and thus may be decreasing evoked release by depleting transmitter quanta available for release. 5. None of these results provide any support for the hypothesis that Ca2+-activated K+ channels mediate Ca2+-dependent release of transmitter at the squid synapse. However, our results have identified a new class of compounds that block Ca2+ channels from their cytoplasmic surface. PMID:2455797

  11. Alkalinity, pH, and copper corrosion by-product release

    SciTech Connect

    Edwards, M.; Meyer, T.E.; Schock, M.R.

    1996-03-01

    Contrary to expectations, higher bicarbonate concentrations exacerbate copper corrosion rates and by-product release. In fact, as illustrated by monitoring experiences of large utilities and by laboratory data, the concentration of copper corrosion by-products in drinking water increases linearly with bicarbonate concentration at constant pH. This relationship implicates cupric hydroxide solubility in control of copper release from relatively new (less than a few years old) copper plumbing. Decision-marking guidance from a traditional Larson`s ratio or Langelier index approach can aggravate copper corrosion problems; consequently, their use should be discontinued for copper corrosion mitigation. In contrast, aeration-CO{sub 2} stripping is a particularly attractive strategy because benefits from higher pH are realized without adverse effects from higher alkalinity.

  12. Estimation of (41)Ar activity concentration and release rate from the TRIGA Mark-II research reactor.

    PubMed

    Hoq, M Ajijul; Soner, M A Malek; Rahman, A; Salam, M A; Islam, S M A

    2016-03-01

    The BAEC TRIGA research reactor (BTRR) is the only nuclear reactor in Bangladesh. Bangladesh Atomic Energy Regulatory Authority (BAERA) regulations require that nuclear reactor licensees undertake all reasonable precautions to protect the environment and the health and safety of persons, including identifying, controlling and monitoring the release of nuclear substances to the environment. The primary activation product of interest in terms of airborne release from the reactor is (41)Ar. (41)Ar is a noble gas readily released from the reactor stacks and most has not decayed by the time it moves offsite with normal wind speed. Initially (41)Ar is produced from irradiation of dissolved air in the primary water which eventually transfers into the air in the reactor bay. In this study, the airborne radioisotope (41)Ar generation concentration, ground level concentration and release rate from the BTRR bay region are evaluated theoretically during the normal reactor operation condition by several governing equations. This theoretical calculation eventually minimizes the doubt about radiological safety to determine the radiation level for (41)Ar activity whether it is below the permissible limit or not. Results show that the estimated activity for (41)Ar is well below the maximum permissible concentration limit set by the regulatory body, which is an assurance for the reactor operating personnel and general public. Thus the analysis performed within this paper is so much effective in the sense of ensuring radiological safety for working personnel and the environment.

  13. Estimation of (41)Ar activity concentration and release rate from the TRIGA Mark-II research reactor.

    PubMed

    Hoq, M Ajijul; Soner, M A Malek; Rahman, A; Salam, M A; Islam, S M A

    2016-03-01

    The BAEC TRIGA research reactor (BTRR) is the only nuclear reactor in Bangladesh. Bangladesh Atomic Energy Regulatory Authority (BAERA) regulations require that nuclear reactor licensees undertake all reasonable precautions to protect the environment and the health and safety of persons, including identifying, controlling and monitoring the release of nuclear substances to the environment. The primary activation product of interest in terms of airborne release from the reactor is (41)Ar. (41)Ar is a noble gas readily released from the reactor stacks and most has not decayed by the time it moves offsite with normal wind speed. Initially (41)Ar is produced from irradiation of dissolved air in the primary water which eventually transfers into the air in the reactor bay. In this study, the airborne radioisotope (41)Ar generation concentration, ground level concentration and release rate from the BTRR bay region are evaluated theoretically during the normal reactor operation condition by several governing equations. This theoretical calculation eventually minimizes the doubt about radiological safety to determine the radiation level for (41)Ar activity whether it is below the permissible limit or not. Results show that the estimated activity for (41)Ar is well below the maximum permissible concentration limit set by the regulatory body, which is an assurance for the reactor operating personnel and general public. Thus the analysis performed within this paper is so much effective in the sense of ensuring radiological safety for working personnel and the environment. PMID:26736180

  14. Agonist Activation of F-Actin-Mediated Eosinophil Shape Change and Mediator Release Is Dependent on Rac2

    PubMed Central

    Lacy, Paige; Willetts, Lian; Kim, John D.; Lo, Andrea N.; Lam, Bon; MacLean, Emily I.; Moqbel, Redwan; Rothenberg, Marc E.; Zimmermann, Nives

    2011-01-01

    Background Tissue recruitment and activation of eosinophils contribute to allergic symptoms by causing airway hyperresponsiveness and inflammation. Shape changes and mediator release in eosinophils may be regulated by mammalian Rho-related guanosine triphosphatases. Of these, Rac2 is essential for F-actin formation as a central process underlying cell motility, exocytosis, and respiratory burst in neutrophils, while the role of Rac2 in eosinophils is unknown. We set out to determine the role of Rac2 in eosinophil mediator release and F-actin-dependent shape change in response to chemotactic stimuli. Methods Rac2-deficient eosinophils from CD2-IL-5 transgenic mice crossed with rac2 gene knockout animals were examined for their ability to release superoxide through respiratory burst or eosinophil peroxidase by degranulation. Eosinophil shape change and actin polymerization were also assessed by flow cytometry and confocal microscopy following stimulation with eotaxin-2 or platelet-activating factor. Results Eosinophils from wild-type mice displayed inducible superoxide release, but at a small fraction (4–5%) of human eosinophils. Rac2-deficient eosinophils showed significantly less superoxide release (p < 0.05, 26% less than wild type). Eosinophils lacking Rac2 had diminished degranulation (p < 0.05, 62% less eosinophil peroxidase) and shape changes in response to eotaxin-2 or platelet-activating factor (with 68 and 49% less F-actin formation, respectively; p < 0.02) compared with wild-type cells. Conclusion These results demonstrate that Rac2 is an important regulator of eosinophil function by contributing to superoxide production, granule protein release, and eosinophil shape change. Our findings suggest that Rho guanosine triphosphatases are key regulators of cellular inflammation in allergy and asthma. PMID:21576984

  15. Mechanistic determination of fission product releases for a Mark III BWR plant

    SciTech Connect

    Ludewig, H.; Yu, W.S.; Jaung, R.; Pratt, W.T.

    1986-01-01

    During the review of the GESSAR-II PRA by the Nuclear Regulatory Commission (NRC) and their contractors at Brookhaven National Laboratory (BNL) it was necessary to reanalyze potential fission product releases to the environment for several core meltdown accident sequences. The reanalysis was performed at BNL in two stages. The first stage was carried out prior to detailed mechanistic models were available at BNL and consisted of a sensitivity analysis using the MARCH and CORRAL computer codes. The effects of uncertainties in primary system retention, suppression pool scrubbing and core/concrete interactions on fission product release were handled by varying inputs to the MARCH/CORRAL codes. In this paper we outline the second stage of fission product release calculations, which was based on a system of codes developed under sponsorship of the Accident Source Term Program Office (ASTPO), USNRC. A comparison will be made between the range of source terms calculated by the first approach and the point estimate calculations provided by the more mechanistic codes. 8 refs., 2 tabs.

  16. Release 2 data products from the Ozone Mapping and Profiler Suite (OMPS) Limb Profiler

    NASA Technical Reports Server (NTRS)

    Xu, Q. Philippe; Bhartia, Pawan K.; Jaross, Glen R.; Deland, Matthew T.; Larsen, Jack C.; Fleig, Albert; Kahn, Daniel; Zhu, Tong; Chen, Zhong; Gorkavyi, Nick; Warner, Jeremy; Linda, Mike; Chen, Hong; Kowitt, Mark; Haken, Michael; Hall, Peter

    2014-01-01

    The OMPS Limb Profiler (LP) was launched on board the NASA Suomi National Polar-orbiting Partnership (SNPP) satellite in October 2011. OMPS-LP is a limb-scattering hyperspectral sensor that provides ozone profiling capability at 1.5 km vertical resolution from cloud top to 60 km altitude. The use of three parallel slits allows global coverage in approximately four days. We have recently completed a full reprocessing of all LP data products, designated as Release 2, that improves the accuracy and quality of these products. Level 1 gridded radiance (L1G) changes include intra-orbit and seasonal correction of variations in wavelength registration, revised static and intra-orbit tangent height adjustments, and simplified pixel selection from multiple images. Ozone profile retrieval changes include removal of the explicit aerosol correction, exclusion of channels contaminated by stratospheric OH emission, a revised instrument noise characterization, improved synthetic solar spectrum, improved pressure and temperature ancillary data, and a revised ozone climatology. Release 2 data products also include aerosol extinction coefficient profiles derived with the prelaunch retrieval algorithm. Our evaluation of OMPS LP Release 2 data quality is good. Zonal average ozone profile comparisons with Aura MLS data typically show good agreement, within 5-10% over the altitude range 20-50 km between 60 deg S and 60 deg N. The aerosol profiles agree well with concurrent satellite measurements such as CALIPSO and OSIRIS, and clearly detect exceptional events such as volcanic eruptions and the Chelyabinsk bolide in February 2013.

  17. RADIOLOGICAL RELEASES DUE TO AIR AND SILICA DUST ACTIVATION IN EMPLACEMENT DRIFTS

    SciTech Connect

    J.S. Tang

    2003-05-07

    The purpose of this calculation is to determine the quantity and significance of annual Monitored Geologic Repository (MGR) subsurface normal radiological releases due to neutron activation of air and silica dust in emplacement drifts. This calculation includes the following items: (1) Calculate activation of ventilation airflow through emplacement drifts to quantify radioactive gaseous releases; and (2) Calculate the bounding potential activated silica dust concentration and releases. The sources of silica dust may arise from air supply to emplacement drifts as well as host rock around emplacement drifts. For this calculation, the source of dust is conservatively assumed to be the host rock (Assumption 3.6), which is subject to long-term neutron exposure resulting in saturated radioactivity. The scope of this calculation is limited to releases from activated air and silica dust only, excluding natural radioactive releases such as radon or releases from defective waste packages (breached or contaminated). This work supports the repository ventilation system design and Preclosure Safety Analysis. This includes MGR items classified as Quality Level 1, for example, the Uncanistered Spent Nuclear Fuel Waste Package (CRWMS M&O [Civilian Radioactive Waste Management and Operation Contractor] 1999a, page 7). Therefore, this calculation is subject to the requirements of the ''Quality Assurance Requirements and Description'' (DOE [U.S. Department of Energy] 2003). The performance of the calculation and development of this document are carried out in accordance with AP-3.12Q, ''Design Calculation and Analyses'' and LP-3.30Q-BSC, ''Hazards Analysis System''.

  18. Energy release properties of amorphous boron and boron-based propellant primary combustion products

    NASA Astrophysics Data System (ADS)

    Liang, Daolun; Liu, Jianzhong; Xiao, Jinwu; Xi, Jianfei; Wang, Yang; Zhang, Yanwei; Zhou, Junhu

    2015-07-01

    The microstructure of amorphous boron and the primary combustion products of boron-based fuel-rich propellant (hereafter referred to as primary combustion products) was analyzed by scanning electron microscope. Composition analysis of the primary combustion products was carried out by X-ray diffraction and X-ray photoelectron spectroscopy. The energy release properties of amorphous boron and the primary combustion products were comparatively studied by laser ignition experimental system and thermogravimetry-differential scanning calorimetry. The primary combustion products contain B, C, Mg, Al, B4C, B13C2, BN, B2O3, NH4Cl, H2O, and so on. The energy release properties of primary combustion products are different from amorphous boron, significantly. The full-time spectral intensity of primary combustion products at a wavelength of 580 nm is ~2% lower than that of amorphous boron. The maximum spectral intensity of the former at full wave is ~5% higher than that of the latter. The ignition delay time of primary combustion products is ~150 ms shorter than that of amorphous boron, and the self-sustaining combustion time of the former is ~200 ms longer than that of the latter. The thermal oxidation process of amorphous boron involves water evaporation (weight loss) and boron oxidation (weight gain). The thermal oxidation process of primary combustion products involves two additional steps: NH4Cl decomposition (weight loss) and carbon oxidation (weight loss). CL-20 shows better combustion-supporting effect than KClO4 in both the laser ignition experiments and the thermal oxidation experiments.

  19. Increased Asynchronous Release and Aberrant Calcium Channel Activation in Amyloid Precursor Protein Deficient Neuromuscular Synapses

    PubMed Central

    Yang, Li; Wang, Baiping; Long, Cheng; Wu, Gangyi; Zheng, Hui

    2007-01-01

    Despite the critical roles of the amyloid precursor protein (APP) in Alzheimer's disease pathogenesis, its physiological function remains poorly established. Our previous studies implicated a structural and functional activity of the APP family of proteins in the developing neuromuscular junction (NMJ). Here we performed comprehensive analyses of neurotransmission in mature neuromuscular synapse of APP deficient mice. We found that APP deletion led to reduced paired-pulse facilitation and increased depression of synaptic transmission with repetitive stimulation. Readily releasable pool size and total releasable vesicles were not affected, but probability of release was significantly increased. Strikingly, the amount of asynchronous release, a measure sensitive to presynaptic calcium concentration, was dramatically increased, and pharmacological studies revealed that it was attributed to aberrant activation of N- and L-type Ca2+ channels. We propose that APP modulates synaptic transmission at the NMJ by ensuring proper Ca2+ channel function. PMID:17919826

  20. A slow-release system of bacterial cellulose gel and nanoparticles for hydrophobic active ingredients.

    PubMed

    Numata, Yukari; Mazzarino, Leticia; Borsali, Redouane

    2015-01-01

    A combination of bacterial cellulose (BC) gel and amphiphilic block copolymer nanoparticles was investigated as a drug delivery system (DDS) for hydrophobic active ingredients. Poly(ethylene oxide)-b-poly(caprolactone) (PEO-b-PCL) and retinol were used as the block copolymer and hydrophobic active ingredient, respectively. The BC gel was capable of incorporating copolymer nanoparticles and releasing them in an acetic acid-sodium acetate buffer solution (pH 5.2) at 37 °C. The percentage of released copolymer reached a maximum value of approximately 60% after 6h and remained constant after 24h. The percentage of retinol released from the copolymer-containing BC gel reached a maximum value at 4h. These results show that the combination of BC gel and nanoparticles is a slow-release system that may be useful in the cosmetic and biomedical fields for skin treatment and preparation. PMID:25840273

  1. A slow-release system of bacterial cellulose gel and nanoparticles for hydrophobic active ingredients.

    PubMed

    Numata, Yukari; Mazzarino, Leticia; Borsali, Redouane

    2015-01-01

    A combination of bacterial cellulose (BC) gel and amphiphilic block copolymer nanoparticles was investigated as a drug delivery system (DDS) for hydrophobic active ingredients. Poly(ethylene oxide)-b-poly(caprolactone) (PEO-b-PCL) and retinol were used as the block copolymer and hydrophobic active ingredient, respectively. The BC gel was capable of incorporating copolymer nanoparticles and releasing them in an acetic acid-sodium acetate buffer solution (pH 5.2) at 37 °C. The percentage of released copolymer reached a maximum value of approximately 60% after 6h and remained constant after 24h. The percentage of retinol released from the copolymer-containing BC gel reached a maximum value at 4h. These results show that the combination of BC gel and nanoparticles is a slow-release system that may be useful in the cosmetic and biomedical fields for skin treatment and preparation.

  2. Platelet activating factor induces dopamine release in PC-12 cell line

    SciTech Connect

    Bussolino, F.; Tessari, F.; Turrini, F.; Braquet, P.; Camussi, G.; Prosdocimi, M.; Bosia, A. Institut Henri Beaufour, Le Plessis Robinson )

    1988-10-01

    The ability of platelet activating factor (PAF) to stimulate dopamine release and modify calcium homeostasis in PC-12 cell line was studied. PAF-induced dopamine release is related to its molecular form, with only the R-form steric configuration ((R)PAF), but not its S-form or its 2-lyso derivative, effective at being active. In addition, PAF acts at very low concentrations in a dose-dependent manner (0.1-30 nM). Preincubation with PAF receptor antagonists (CV-3988 and BN52021) as well as the specific desensitization of PC-12 cells to (R)PAF abolish the (R)PAF-induced dopamine release. Several lines of evidence suggest that dopamine release is dependent on a (R)PAF-induced calcium influx and efflux modulation. Dopamine release by PC-12 cells challenged with (R)PAF is associated with a rapid {sup 45}Ca influx and efflux and a rise in cytoplasmic calcium concentrations ((Ca{sup 2+}){sub i}) evaluated by using the calcium indicators fura-2 and quin2. At 30 nM (R)PAF, the absence of extracellular calcium inhibits the dopamine release but not the rise of (Ca{sup 2+}){sub i} from the internal stores, suggesting the importance of calcium influx in (R)PAF-induced dopamine release. PAF, which has been reported to be synthesized by stimulated neuronal cells may thus have a physiological modulatory role on cells with neurosecretory properties.

  3. Effect of the releases of certain chemically active gases on the upper atmosphere

    NASA Astrophysics Data System (ADS)

    Vlasov, M. N.; Pokhunkov, S. A.

    1986-10-01

    A theoretical model for the behavior of chemically active gases released into the upper atmosphere (the E and F regions) from rockets and satellites is proposed which is based on the diffusion approximation with allowance for the photochemical kinetics. The model is used to assess the effect of the release of the following gases on the upper atmosphere: 02, NO, NO2, and vibrationally excited N2. The characteristic times and spatial scales of the variation of upper-atmosphere parameters are determined for various masses of released gases.

  4. Suppression of Active-Region CME Production by the Presence of Other Active Regions

    NASA Technical Reports Server (NTRS)

    Falconer, David; Moore, Ron; Barghouty, Abdulnasser; Khazanov, Igor

    2009-01-01

    From the SOHO mission s data base of MDI full-disk magnetograms spanning solar cycle 23, we have obtained a set of 40,000 magnetograms of 1,300 active regions, tracking each active region across the 30 degree central solar disk. Each active region magnetogram is cropped from the full-disk magnetogram by an automated code. The cadence is 96 minutes. From each active-region magnetogram, we have measured two whole-active-region magnetic quantities: (1) the magnetic size of the active region (the active region s total magnetic flux), and (2) a gauge of the active region s free magnetic energy (part of the free energy is released in the production of a flare and/or CME eruption). From NOAA Flare/CME catalogs, we have obtained the event (Flare/CME/SEP event) production history of each active region. Using all these data, we find that for each type of eruptive event, an active region s expected rate of event production increases as a power law of our gauge of active-region free magnetic energy. We have also found that, among active regions having nearly the same free energy, the rate of the CME production is less when there are many other active regions on the disk than when there are few or none, but there is no significant discernible suppression of the rate of flare production. This indicates that the presence of other active regions somehow tends to inhibit an active region s flare-producing magnetic explosions from becoming CMEs, contrary to the expectation from the breakout model for the production of CMEs.

  5. Activity-dependent release of transforming growth factor-beta in a neuronal network in vitro.

    PubMed

    Lacmann, A; Hess, D; Gohla, G; Roussa, E; Krieglstein, K

    2007-12-12

    For neurotrophins and also for members of the transforming growth factor beta (TGF-beta) family an activity-dependent regulation of synthesis and release has been proposed. Together with the observation that the secretion of neurotransmitters is initiated by neurotrophic factors, it is reasonable to assume that they might act as retrograde modulators enhancing the efficacy and stabilization of synapses. In the present study, we have tested this hypothesis and studied the release and regulation of TGF-beta in vitro using mouse primary hippocampal neurons at embryonic day E16.5 as model. We show that neuronal activity regulates TGF-beta release and TGF-beta expression in vitro. Treatment of the cultures with KCl, 3-veratroylveracevine (veratridine), glutamate or carbamylcholine chloride (carbachol) increased the levels of secreted TGF-beta, as assessed by the MLEC/plasminogen activator inhibitor (PAI)-luciferase-assay, whereas TGF-beta release stimulated by KCl or veratridine was reduced in the presence of tetrodotoxin or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). In addition, application of glutamate significantly upregulated expression of TGF-beta2 and TGF-beta3 in the culture. Notably, KCl stimulation caused Smad (composite term from SMA (C. elegans) and MAD=mothers against dpp (Drosophila)) translocation into the nucleus and upregulated TGF-beta inducible early gene (Tieg1) expression, demonstrating that activity-dependent released TGF-beta may exert autocrine actions and thereby activate the TGF-beta-dependent signaling pathway. Together, these results suggest an activity-dependent release and gene transcription of TGF-beta from mouse hippocampal neurons in vitro as well as subsequent autocrine functions of the released TGF-beta within the hippocampal network.

  6. Released products of pathogenic bacteria stimulate biofilm formation by Escherichia coli K-12 strains.

    PubMed

    Vacheva, Anna; Ivanova, Radka; Paunova-Krasteva, Tsvetelina; Stoitsova, Stoyanka

    2012-06-01

    It has recently been shown that pathogens with a limited capacity for sessile growth (like some Escherichia coli O157 strains) can benefit from the presence of other bacteria and form mixed biofilms with companion strains. This study addresses the question whether pathogens may influence attached growth of E. coli non-pathogenic strains via secreted factors. We compared the biofilm-modulating effects of sterile stationary-phase culture media of a biofilm non-producing strain of E. coli O157:H, a laboratory biofilm-producing E. coli K-12 strain and a biofilm-forming strain of the pathogen Yersina enterocolitica O:3. Sessile growth was monitored as biomass (crystal violet assay), exopolysaccharide (ELLA) and morphology (scanning electron and confocal laser microscopy). With two of the E. coli K-12 strains stimulation of biofilm formation by all supernatants was achieved, but only the pathogens' secreted products induced biomass increase in some 'biofilm-deficient' K-12 strains. Lectin-peroxidase labeling indicated changes in colanic acid and poly-N-acetylglucosamine amounts in extracellular matrices. The contribution of indole, protein and polysaccharide to the biofilm-modulating activities of the supernatants was compared. Indole, in concentrations equal to those established in the supernatants, suppressed sessile growth in one K-12 strain. Proteinase K significantly reduced the stimulatory effects of all supernatants, indicating a prominent role of protein/peptide factor(s) in biofilm promotion. The amount of released polysaccharides (rPS) in the supernatants was quantitated then comparable quantities of isolated rPS were applied during biofilm growth. The three rPS had notable strain-specific effects with regard to both the strain-source of the rPS and the E. coli K-12 target strain.

  7. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    SciTech Connect

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-07-31

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  8. Evidence of arsenic release promoted by disinfection by-products within drinking-water distribution systems.

    PubMed

    Andra, Syam S; Makris, Konstantinos C; Botsaris, George; Charisiadis, Pantelis; Kalyvas, Harris; Costa, Costas N

    2014-02-15

    Changes in disinfectant type could trigger a cascade of reactions releasing pipe-anchored metals/metalloids into finished water. However, the effect of pre-formed disinfection by-products on the release of sorbed contaminants (arsenic-As in particular) from drinking water distribution system pipe scales remains unexplored. A bench-scale study using a factorial experimental design was performed to evaluate the independent and interaction effects of trihalomethanes (TTHM) and haloacetic acids (HAA) on arsenic (As) release from either scales-only or scale-biofilm conglomerates (SBC) both anchored on asbestos/cement pipe coupons. A model biofilm (Pseudomonas aeruginosa) was allowed to grow on select pipe coupons prior experimentation. Either TTHM or HAA individual dosing did not promote As release from either scales only or SBC, detecting <6 μg AsL(-1) in finished water. In the case of scales-only coupons, the combination of the highest spike level of TTHM and HAA significantly (p<0.001) increased dissolved and total As concentrations to levels up to 16 and 95 μg L(-1), respectively. Similar treatments in the presence of biofilm (SBC) resulted in significant (p<0.001) increase in dissolved and total recoverable As up to 20 and 47 μg L(-1), respectively, exceeding the regulatory As limit. Whether or not, our laboratory-based results truly represent mechanisms operating in disinfected finished water in pipe networks remains to be investigated in the field.

  9. Release of platelet activating factor (PAF) and eicosanoids in UVC-irradiated corneal stromal cells.

    PubMed

    Sheng, Y; Birkle, D L

    1995-05-01

    Ultraviolet (UV) irradiation provokes acute inflammation of the eye, and can be used to model processes that occur in response to damage to the anterior segment. This study characterized ultraviolet-C (UVC, 254 nm) irradiation-induced PAF synthesis, and arachidonic acid (20:4) and eicosanoid release in rabbit corneal stromal cells maintained in vitro. PAF was measured by radioimmunoassay (RIA) after exposing cultured corneal stromal cells to UVC irradiation (20 min, 2, 5, 10 mW/cm2). 14C-20:4-labeled stromal cells were also stimulated with UVC and radiolabeled phospholipids, neutral lipids and eicosanoids were measured. Synthesis of cell-associated and secreted PAF from corneal stromal cells was increased by UV irradiation. UV irradiation (254 nm, 5mW/cm2) enhanced 20:4 release from triacylglycerols, phosphatidylinositol, phosphatidylserine and phosphatidylethanolamine, and increased levels of 20:4-diacylglycerol and unesterified 20:4. The released 20:4 entered both the cyclooxygenase and lipoxygenase pathways after UVC irradiation. The PAF antagonist, BN52021 (10 microM) reduced UVC irradiation-induced stimulation of prostaglandin production, but failed to inhibit UVC-induced 20:4 release and synthesis of lipoxygenase products. Furthermore, exogenous PAF (1 microM) stimulated prostaglandin production, but did not increase the synthesis of lipoxygenase products from radiolabeled 20:4. The effects of PAF on prostaglandin synthesis were inhibited by BN52021. These findings indicate that responses to injury in cultured corneal stromal cells include PAF synthesis, release of 20:4 from glycerolipids, accumulation of diacylglycerol and synthesis of eicosanoids. The data further suggest that during UVC irradiation in vitro, PAF is not a primary or initial mediator of 20:4 release and synthesis of lipoxygenase products, but may mediate UVC-induced prostaglandin synthesis. PMID:7648859

  10. Source Term Estimates of Radioxenon Released from the BaTek Medical Isotope Production Facility Using External Measured Air Concentrations

    SciTech Connect

    Eslinger, Paul W.; Cameron, Ian M.; Dumais, Johannes R.; Imardjoko, Yudi; Marsoem, Pujadi; McIntyre, Justin I.; Miley, Harry S.; Stoehlker, Ulrich; Widodo, Susilo; Woods, Vincent T.

    2015-10-01

    Abstract Batan Teknologi (BaTek) operates an isotope production facility in Serpong, Indonesia that supplies 99mTc for use in medical procedures. Atmospheric releases of Xe-133 in the production process at BaTek are known to influence the measurements taken at the closest stations of the International Monitoring System (IMS). The purpose of the IMS is to detect evidence of nuclear explosions, including atmospheric releases of radionuclides. The xenon isotopes released from BaTek are the same as those produced in a nuclear explosion, but the isotopic ratios are different. Knowledge of the magnitude of releases from the isotope production facility helps inform analysts trying to decide whether a specific measurement result came from a nuclear explosion. A stack monitor deployed at BaTek in 2013 measured releases to the atmosphere for several isotopes. The facility operates on a weekly cycle, and the stack data for June 15-21, 2013 show a release of 1.84E13 Bq of Xe-133. Concentrations of Xe-133 in the air are available at the same time from a xenon sampler located 14 km from BaTek. An optimization process using atmospheric transport modeling and the sampler air concentrations produced a release estimate of 1.88E13 Bq. The same optimization process yielded a release estimate of 1.70E13 Bq for a different week in 2012. The stack release value and the two optimized estimates are all within 10 percent of each other. Weekly release estimates of 1.8E13 Bq and a 40 percent facility operation rate yields a rough annual release estimate of 3.7E13 Bq of Xe-133. This value is consistent with previously published estimates of annual releases for this facility, which are based on measurements at three IMS stations. These multiple lines of evidence cross-validate the stack release estimates and the release estimates from atmospheric samplers.

  11. Glycoconjugates Influence Caspase Release and Minimize Production of Lactate Dehydrogenase upon Pathogen Exposure

    NASA Astrophysics Data System (ADS)

    Eassa, Souzan; Tarasenko, Olga

    2010-04-01

    Many pathogens stimulate cell death of immune cells while promoting survival of pathogens. Early cell death is characterized by the release of mediators, namely Caspases (Cas). Infections caused by pathogens can be eradicated if immune cells could resist cell death and kill pathogens upon exposure. In this research, we studied whether glycoconjugates (GCs) influence Cas release and cytotoxicity upon pathogen damage. GC1 and GC3 constituted samples studied principally. Bacterial spores were used as a pathogen model. GC effects were determined "prior to," "during," and "following" pathogen exposure throughout phagocytosis. Cytotoxic damage was assessed by measuring lactate dehydrogenase (LDH) production. Our data show that GC3 was more effective than GC1 during phagocytosis. GC3 controls Cas release under all three exposure conditions. Minimum production of LDH was noticed in the "following" exposure condition compared to the "prior to" and "during" exposure conditions for GC1 and GC3. The present study provided the selection method of GC ligands bearing anti-cytotoxic and anti-apoptotic properties.

  12. Spatial and activity-dependent catecholamine release in rat adrenal medulla under native neuronal stimulation.

    PubMed

    Wolf, Kyle; Zarkua, Georgy; Chan, Shyue-An; Sridhar, Arun; Smith, Corey

    2016-09-01

    Neuroendocrine chromaffin cells of the adrenal medulla in rat receive excitatory synaptic input through anterior and posterior divisions of the sympathetic splanchnic nerve. Upon synaptic stimulation, the adrenal medulla releases the catecholamines, epinephrine, and norepinephrine into the suprarenal vein for circulation throughout the body. Under sympathetic tone, catecholamine release is modest. However, upon activation of the sympathoadrenal stress reflex, and increased splanchnic firing, adrenal catecholamine output increases dramatically. Moreover, specific stressors can preferentially increase release of either epinephrine (i.e., hypoglycemia) or norepinephrine (i.e., cold stress). The mechanism for this stressor-dependent segregated release of catecholamine species is not yet fully understood. We tested the hypothesis that stimulation of either division of the splanchnic selects for epinephrine over norepinephrine release. We introduce an ex vivo rat preparation that maintains native splanchnic innervation of the adrenal gland and we document experimental advantages and limitations of this preparation. We utilize fast scanning cyclic voltammetry to detect release of both epinephrine and norepinephrine from the adrenal medulla, and report that epinephrine and norepinephrine release are regulated spatially and in a frequency-dependent manner. We provide data to show that epinephrine is secreted preferentially from the periphery of the medulla and exhibits a higher threshold and steeper stimulus-secretion function than norepinephrine. Elevated stimulation of the whole nerve specifically enhances epinephrine release from the peripheral medulla. Our data further show that elimination of either division from stimulation greatly attenuated epinephrine release under elevated stimulation, while either division alone can largely support norepinephrine release. PMID:27597763

  13. Force and number of myosin motors during muscle shortening and the coupling with the release of the ATP hydrolysis products

    PubMed Central

    Caremani, Marco; Melli, Luca; Dolfi, Mario; Lombardi, Vincenzo; Linari, Marco

    2015-01-01

    The chemo-mechanical cycle of the myosin II–actin reaction in situ has been investigated in Ca2+-activated skinned fibres from rabbit psoas, by determining the number and strain (s) of myosin motors interacting during steady shortening at different velocities (V) and the effect of raising inorganic phosphate (Pi) concentration. It was found that in control conditions (no added Pi), shortening at V ≤ 350 nm s–1 per half-sarcomere, corresponding to force (T) greater than half the isometric force (T0), decreases the number of myosin motors in proportion to the reduction of T, so that s remains practically constant and similar to the T0 value independent of V. At higher V the number of motors decreases less than in proportion to T, so that s progressively decreases. Raising Pi concentration by 10 mm, which reduces T0 and the number of motors by 40–50%, does not influence the dependence on V of number and strain. A model simulation of the myosin–actin reaction in which the structural transitions responsible for the myosin working stroke and the release of the hydrolysis products are orthogonal explains the results assuming that Pi and then ADP are released with rates that increase as the motor progresses through the working stroke. The rate of ADP release from the conformation at the end of the working stroke is also strain-sensitive, further increasing by one order of magnitude within a few nanometres of negative strain. These results provide the molecular explanation of the relation between the rate of energy liberation and the load during muscle contraction. Key points Muscle contraction is due to cyclical ATP-driven working strokes in the myosin motors while attached to the actin filament. Each working stroke is accompanied by the release of the hydrolysis products, orthophosphate and ADP. The rate of myosin–actin interactions increases with the increase in shortening velocity. We used fast half-sarcomere mechanics on skinned muscle fibres to

  14. Comparison of fission product release predictions using PARFUME with results from the AGR-1 safety tests

    SciTech Connect

    Blaise Collin

    2014-09-01

    Safety tests were conducted on fourteen fuel compacts from AGR-1, the first irradiation experiment of the Advanced Gas Reactor (AGR) Fuel Development and Qualification program, at temperatures ranging from 1600 to 1800°C to determine fission product release at temperatures that bound reactor accident conditions. The PARFUME (PARticle FUel ModEl) code was used to predict the release of fission products silver, cesium, strontium, and krypton from fuel compacts containing tristructural isotropic (TRISO) coated particles during the safety tests, and the predicted values were compared with experimental results. Preliminary comparisons between PARFUME predictions and post-irradiation examination (PIE) results of the safety tests show different trends in the prediction of the fractional release depending on the species, and it leads to different conclusions regarding the diffusivities used in the modeling of fission product transport in TRISO-coated particles: • For silver, the diffusivity in silicon carbide (SiC) might be over-estimated by a factor of at least 102 to 103 at 1600°C and 1700°C, and at least 10 to 102 at 1800°C. The diffusivity of silver in uranium oxy-carbide (UCO) might also be over-estimated, but the available data are insufficient to allow definitive conclusions to be drawn. • For cesium, the diffusivity in UCO might be over-estimated by a factor of at least 102 to 103 at 1600°C, 105 at 1700°C, and 103 at 1800°C. The diffusivity of cesium in SiC might also over-estimated, by a factor of 10 at 1600°C and 103 at 1700°C, based upon the comparisons between calculated and measured release fractions from intact particles. There is no available estimate at 1800°C since all the compacts heated up at 1800°C contain particles with failed SiC layers whose release dominates the release from intact particles. • For strontium, the diffusivity in SiC might be over-estimated by a factor of 10 to 102 at 1600 and 1700°C, and 102 to 103 at 1800°C. These

  15. Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin

    PubMed Central

    Wong, Yu-Hui; Lee, Chia-Ming; Xie, Wenjun; Cui, Bianxiao; Poo, Mu-ming

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is known to modulate synapse development and plasticity, but the source of synaptic BDNF and molecular mechanisms regulating BDNF release remain unclear. Using exogenous BDNF tagged with quantum dots (BDNF-QDs), we found that endocytosed BDNF-QDs were preferentially localized to postsynaptic sites in the dendrite of cultured hippocampal neurons. Repetitive neuronal spiking induced the release of BDNF-QDs at these sites, and this process required activation of glutamate receptors. Down-regulating complexin 1/2 (Cpx1/2) expression eliminated activity-induced BDNF-QD secretion, although the overall activity-independent secretion was elevated. Among eight synaptotagmin (Syt) isoforms examined, down-regulation of only Syt6 impaired activity-induced BDNF-QD secretion. In contrast, activity-induced release of endogenously synthesized BDNF did not depend on Syt6. Thus, neuronal activity could trigger the release of endosomal BDNF from postsynaptic dendrites in a Cpx- and Syt6-dependent manner, and endosomes containing BDNF may serve as a source of BDNF for activity-dependent synaptic modulation. PMID:26216953

  16. Inhibitory effects of compounds from Phyllanthus amarus on nitric oxide production, lymphocyte proliferation, and cytokine release from phagocytes.

    PubMed

    Yuandani; Jantan, Ibrahim; Ilangkovan, Menaga; Husain, Khairana; Chan, Kok Meng

    2016-01-01

    Standardized extract of Phyllanthus amarus has previously been shown to have a strong inhibitory effect on phagocytic activity of human neutrophils. The current study was carried out to evaluate the effects of constituents of the extract of P. amarus on nitric oxide (NO) production as well as lymphocyte proliferation and cytokine release from phagocytes. Three compounds, ethyl 8-hydroxy-8-methyl-tridecanoate, 7β,19α dihydroxy-urs-12-ene, and 1,7,8-trihydroxy-2-naphtaldehyde, together with seven known compounds were isolated from the whole plant of P. amarus. The isolated compounds and reference standards, ie, gallic acid, ellagic acid, corilagin, and geraniin, which were quantitatively analyzed in the extracts, were evaluated for their effects on immune cells. Among the compounds tested, the lignans, especially phyltetralin and phyllanthin, showed strong inhibition on lymphocyte proliferation with half maximal inhibitory concentration (IC50) values of 1.07 μM and 1.82 μM, respectively. Ethyl 8-hydroxy-8-methyl-tridecanoate and 1,7,8-trihydroxy-2-naphtaldehyde exhibited strong inhibition on nitric oxide production with IC50 values of 0.91 μM and 1.07 μM, respectively. Of all the compounds, corilagin was the strongest inhibitor of tumor necrosis factor-α release with an IC50 value of 7.39 μM, whereas geraniin depicted the strongest inhibitory activity on interleukin-1β release with an IC50 value of 16.41 μM. The compounds constituting the extract of P. amarus were able to inhibit the innate immune response of phagocytes at different steps. PMID:27354767

  17. Inhibitory effects of compounds from Phyllanthus amarus on nitric oxide production, lymphocyte proliferation, and cytokine release from phagocytes

    PubMed Central

    Yuandani; Jantan, Ibrahim; Ilangkovan, Menaga; Husain, Khairana; Chan, Kok Meng

    2016-01-01

    Standardized extract of Phyllanthus amarus has previously been shown to have a strong inhibitory effect on phagocytic activity of human neutrophils. The current study was carried out to evaluate the effects of constituents of the extract of P. amarus on nitric oxide (NO) production as well as lymphocyte proliferation and cytokine release from phagocytes. Three compounds, ethyl 8-hydroxy-8-methyl-tridecanoate, 7β,19α dihydroxy-urs-12-ene, and 1,7,8-trihydroxy-2-naphtaldehyde, together with seven known compounds were isolated from the whole plant of P. amarus. The isolated compounds and reference standards, ie, gallic acid, ellagic acid, corilagin, and geraniin, which were quantitatively analyzed in the extracts, were evaluated for their effects on immune cells. Among the compounds tested, the lignans, especially phyltetralin and phyllanthin, showed strong inhibition on lymphocyte proliferation with half maximal inhibitory concentration (IC50) values of 1.07 μM and 1.82 μM, respectively. Ethyl 8-hydroxy-8-methyl-tridecanoate and 1,7,8-trihydroxy-2-naphtaldehyde exhibited strong inhibition on nitric oxide production with IC50 values of 0.91 μM and 1.07 μM, respectively. Of all the compounds, corilagin was the strongest inhibitor of tumor necrosis factor-α release with an IC50 value of 7.39 μM, whereas geraniin depicted the strongest inhibitory activity on interleukin-1β release with an IC50 value of 16.41 μM. The compounds constituting the extract of P. amarus were able to inhibit the innate immune response of phagocytes at different steps. PMID:27354767

  18. Effect of gamma irradiation on fluoride release and antibacterial activity of resin dental materials.

    PubMed

    Carvalho, Fabíola Galbiatti de; Fucio, Suzana Beatriz Portugal de; Pascon, Fernanda Miori; Kantovitz, Kamila Rosamilia; Correr-Sobrinho, Lourenço; Puppin-Rontani, Regina Maria

    2009-01-01

    This study evaluated the effect of gamma irradiation on fluoride release and antibacterial activity of FluroShield (FS) and Clearfil Protect Bond (CPB). Four groups were formed: G1-FS + gamma; G2-FS without gamma; G3-CPB + gamma; G4-CPB without gamma. For fluoride release analysis, 12 disks of each material were prepared and covered with nail polish, except for one side (50.4 mm(2) area). G1 and G3 were sterilized with a 14.5 KGy dose at 27 degrees C for 24 h, while G2 and G4 (controls) were not sterilized and were maintained under the same time and temperature conditions. Fluoride release measurements were made in duplicate (n=6) by an ion specific electrode. The antibacterial activity of the CPB and FS against Streptococcus mutans after gamma sterilization was evaluated by the agar-disc diffusion method. The diameter of the zones of microbial growth inhibition was recorded after 48 h. Data were analyzed statistically by ANOVA and Tukey's test (alpha=5%). Gamma sterilization decreased the fluoride release of FS by approximately 50%, while CPB was not affected. There was no statistically significant difference (p>0.05) in the antibacterial effect of CPB between gamma and non-gamma sterilization groups. FS presented no antibacterial activity. Gamma irradiation decreased the fluoride release of FS, but did not affect the antibacterial activity of the studied materials. PMID:19738944

  19. Covalent incorporation and controlled release of active dexamethasone from injectable polyethylene glycol hydrogels.

    PubMed

    Bezuidenhout, Deon; Oosthuysen, Anel; Davies, Neil; Ahrenstedt, Lage; Dobner, Stephan; Roberts, Peter; Zilla, Peter

    2013-05-01

    Dexamethasone (Dex) is used in a wide range of applications, but may have undesirable systemic side effects. A number of techniques have thus been developed to deliver the substance locally. In this study, dexamethasone was acrylated, pegylated, and tethered to hydrolytically degradable (acrylate based) and nondegradable (vinyl sulfone based) polyethylene glycol hydrogels by nucleophilic addition. Hydrogel swelling, drug elution and drug activity were followed over an extended period in vitro. Nondegradable gels were stable for more than a year, while degradable gels showed increasing swelling ratios due to degradation that resulted in disintegration after ~12 days. Near-linear (zero order) release could be achieved in some cases with the degradable gels, while release from the nondegradable gels approximated first order initial release kinetics. Significantly delayed release was observed in all cases where the Dex was linked to the gels, when compared with controls where the drug was merely physically incorporated. Eluates from the gels containing the tethered drug showed high levels of activity for extended time periods, while the activity of the eluates from gels containing nonbound dexamethasone decreased rapidly within the first few days. Dexamethasone can thus be incorporated using nucleophilic addition chemistry to produce gels that are capable of sustained release of the active drug. The methodology is applicable to a variety of drugs that contain hydroxyl groups.

  20. Activation and propagation of Ca2+ release from inside the sarcoplasmic reticulum network of mammalian skeletal muscle.

    PubMed

    Cully, Tanya R; Edwards, Joshua N; Launikonis, Bradley S

    2014-09-01

    Skeletal muscle fibres are large and highly elongated cells specialized for producing the force required for posture and movement. The process of controlling the production of force within the muscle, known as excitation-contraction coupling, requires virtually simultaneous release of large amounts of Ca(2+) from the sarcoplasmic reticulum (SR) at the level of every sarcomere within the muscle fibre. Here we imaged Ca(2+) movements within the SR, tubular (t-) system and in the cytoplasm to observe that the SR of skeletal muscle is a connected network capable of allowing diffusion of Ca(2+) within its lumen to promote the propagation of Ca(2+) release throughout the fibre under conditions where inhibition of SR ryanodine receptors (RyRs) was reduced. Reduction of cytoplasmic [Mg(2+)] ([Mg(2+)]cyto) induced a leak of Ca(2+) through RyRs, causing a reduction in SR Ca(2+) buffering power argued to be due to a breakdown of SR calsequestrin polymers, leading to a local elevation of [Ca(2+)]SR. The local rise in [Ca(2+)]SR, an intra-SR Ca(2+) transient, induced a local diffusely rising [Ca(2+)]cyto. A prolonged Ca(2+) wave lasting tens of seconds or more was generated from these events. Ca(2+) waves were dependent on the diffusion of Ca(2+) within the lumen of the SR and ended as [Ca(2+)]SR dropped to low levels to inactivate RyRs. Inactivation of RyRs allowed re-accumulation of [Ca(2+)]SR and the activation of secondary Ca(2+) waves in the persistent presence of low [Mg(2+)]cyto if the threshold [Ca(2+)]SR for RyR opening could be reached. Secondary Ca(2+) waves occurred without an abrupt reduction in SR Ca(2+) buffering power. Ca(2+) release and wave propagation occurred in the absence of Ca(2+)-induced Ca(2+) release. These observations are consistent with the activation of Ca(2+) release through RyRs of lowered cytoplasmic inhibition by [Ca(2+)]SR or store overload-induced Ca(2+) release. Restitution of SR Ca(2+) buffering power to its initially high value required

  1. Shockwaves induce osteogenic differentiation of human mesenchymal stem cells through ATP release and activation of P2X7 receptors.

    PubMed

    Sun, Dahui; Junger, Wolfgang G; Yuan, Changji; Zhang, Wenyan; Bao, Yi; Qin, Daming; Wang, Chengxue; Tan, Lei; Qi, Baochang; Zhu, Dong; Zhang, Xizheng; Yu, Tiecheng

    2013-06-01

    Shockwave treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5'-triphosphate (ATP) release-induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c-fos and c-jun mRNA was determined with real-time reverse transcription polymerase chain reaction and Western blotting. P2X7-siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK signaling in shockwave-induced osteogenic hMSCs differentiation. Shockwave treatment released significant amounts (≈ 7 μM) of ATP from hMSCs. Shockwaves and exogenous ATP induced c-fos and c-jun mRNA transcription, p38 MAPK activation, and hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7-siRNA or selective antagonists, or blockade of p38 MAPK with SB203580 prevented osteogenic differentiation of hMSCs. Our findings indicate that shockwaves release cellular ATP that activates P2X7 receptors and downstream signaling events that caused osteogenic differentiation of hMSCs. We conclude that shockwave therapy promotes bone healing through P2X7 receptor signaling, which contributes to hMSC differentiation.

  2. Shockwaves Induce Osteogenic Differentiation of Human Mesenchymal Stem Cells Through ATP Release and Activation of P2X7 Receptors

    PubMed Central

    Sun, Dahui; Junger, Wolfgang G.; Yuan, Changji; Zhang, Wenyan; Bao, Yi; Qin, Daming; Wang, Chengxue; Tan, Lei; Qi, Baochang; Zhu, Dong; Zhang, Xizheng; Yu, Tiecheng

    2014-01-01

    Shockwave fractures treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5’-triphosphate (ATP) release-induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c-fos and c-jun mRNA was determined with real-time reverse transcription polymerase chain reaction and Western blotting. P2X7-siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK sig naling in shockwave-induced osteogenic hMSCs differentiation. Shockwave treatment released significant amounts (~7 μM) of ATP from hMSCs. Shockwaves and exogenous ATP induced c-fos and c-jun mRNA transcription, p38 MAPK activation, and hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7-siRNA or selective antagonists, or blockade of p38 MAPK with SB203580 prevented osteogenic differentiation of hMSCs. Our findings indicate that shockwaves release cellular ATP that activates P2X7 receptors and downstream signaling events that caused osteogenic differentiation of hMSCs. We conclude that shockwave therapy promotes bone healing through P2X7 receptor signaling, which contributes to hMSC differentiation. PMID:23404811

  3. Implementation of a Thermodynamic Solver within a Computer Program for Calculating Fission-Product Release Fractions

    NASA Astrophysics Data System (ADS)

    Barber, Duncan Henry

    During some postulated accidents at nuclear power stations, fuel cooling may be impaired. In such cases, the fuel heats up and the subsequent increased fission-gas release from the fuel to the gap may result in fuel sheath failure. After fuel sheath failure, the barrier between the coolant and the fuel pellets is lost or impaired, gases and vapours from the fuel-to-sheath gap and other open voids in the fuel pellets can be vented. Gases and steam from the coolant can enter the broken fuel sheath and interact with the fuel pellet surfaces and the fission-product inclusion on the fuel surface (including material at the surface of the fuel matrix). The chemistry of this interaction is an important mechanism to model in order to assess fission-product releases from fuel. Starting in 1995, the computer program SOURCE 2.0 was developed by the Canadian nuclear industry to model fission-product release from fuel during such accidents. SOURCE 2.0 has employed an early thermochemical model of irradiated uranium dioxide fuel developed at the Royal Military College of Canada. To overcome the limitations of computers of that time, the implementation of the RMC model employed lookup tables to pre-calculated equilibrium conditions. In the intervening years, the RMC model has been improved, the power of computers has increased significantly, and thermodynamic subroutine libraries have become available. This thesis is the result of extensive work based on these three factors. A prototype computer program (referred to as SC11) has been developed that uses a thermodynamic subroutine library to calculate thermodynamic equilibria using Gibbs energy minimization. The Gibbs energy minimization requires the system temperature (T) and pressure (P), and the inventory of chemical elements (n) in the system. In order to calculate the inventory of chemical elements in the fuel, the list of nuclides and nuclear isomers modelled in SC11 had to be expanded from the list used by SOURCE 2.0. A

  4. Release and Skin Permeation of Scopolamine From Thin Polymer Films in Relation to Thermodynamic Activity.

    PubMed

    Kunst, Anders; Lee, Geoffrey

    2016-04-01

    The object was to demonstrate if the diffusional flux of the drug out of a drug-in-adhesive-type matrix and its subsequent permeation through an excised skin membrane is a linear function of the drug's thermodynamic activity in the thin polymer film. The thermodynamic activity, ap(*), is defined here as the degree of saturation of the drug in the polymer. Both release and release/permeation of scopolamine base from 3 different poylacrylate pressure-sensitive adhesives (PSAs) were measured. The values for ap(*) were calculated using previous published saturation solubilities, wp(s), of the drug in the PSAs. Different rates of release and release/permeation were determined between the 3 PSAs. These differences could be accounted for quantitatively by correlating with ap(*) rather than the concentration of the drug in the polymer films. At similar values for ap(*) the same release or release/permeation rates from the different polymers were measured. The differences could not be related to cross-linking or presence of ionizable groups of the polymers that should influence diffusivity.

  5. Release and Skin Permeation of Scopolamine From Thin Polymer Films in Relation to Thermodynamic Activity.

    PubMed

    Kunst, Anders; Lee, Geoffrey

    2016-04-01

    The object was to demonstrate if the diffusional flux of the drug out of a drug-in-adhesive-type matrix and its subsequent permeation through an excised skin membrane is a linear function of the drug's thermodynamic activity in the thin polymer film. The thermodynamic activity, ap(*), is defined here as the degree of saturation of the drug in the polymer. Both release and release/permeation of scopolamine base from 3 different poylacrylate pressure-sensitive adhesives (PSAs) were measured. The values for ap(*) were calculated using previous published saturation solubilities, wp(s), of the drug in the PSAs. Different rates of release and release/permeation were determined between the 3 PSAs. These differences could be accounted for quantitatively by correlating with ap(*) rather than the concentration of the drug in the polymer films. At similar values for ap(*) the same release or release/permeation rates from the different polymers were measured. The differences could not be related to cross-linking or presence of ionizable groups of the polymers that should influence diffusivity. PMID:27019963

  6. Zinc polycarboxylate dental cement for the controlled release of an active organic substance: proof of concept.

    PubMed

    Ali, Mohammad Naseem; Edwards, Mark; Nicholson, John W

    2010-04-01

    The potential of employing zinc polycarboxylate dental cement as a controlled release material has been studied. Benzalkonium chloride was used as the active ingredient, and incorporated at concentrations of 1, 2 and 3% by mass within the cement. At these levels, there was no observable effect on the speed of setting. Release was followed using an ion-selective electrode to determine changes in chloride ion concentration with time. This technique showed that the additive was released when the cured cement was placed in water, with release occurring by a diffusion mechanism for the first 3 h, but continuing beyond that for up to 1 week. Diffusion coefficients were in the range 5.62 x 10(-6) cm(2) s(-1) (for 1% concentration) to 10.90 x 10(-6) cm(2) s(-1) (for 3% concentration). Up to 3% of the total loading of benzalkonium chloride was released from the zinc polycarboxylate after a week, which is similar to that found in previous studies with glass-ionomer cement. It is concluded that zinc polycarboxylate cement is capable of acting as a useful material for the controlled release of active organic compounds.

  7. Asbestos fibre release by corroded and weathered asbestos-cement products.

    PubMed

    Spurny, K R

    1989-01-01

    A description is given of portable equipment and a method of sampling and measuring asbestos fibre emissions from solid plane surfaces of asbestos-cement products (roofs and facades). Asbestos-cement products, e.g., roof tiles, contain as much as 11-12% of chrysotile asbestos. As a result of continuing exposure to the weather and to acid rain, the surface of asbestos-cement products becomes corroded and weathered. Cement particles, asbestos fibres and agglomerates of particles and fibres are therefore released from the surface and dispersed in air and water. The method described has been used to measure asbestos fibre emissions and ambient air concentrations in the Federal Republic of Germany over the period 1984-1986.

  8. Participation of the Na+/H+ exchanger in the phospholipase-A2 activation of luteinizing hormone-releasing hormone release in rat hypothalamic fragments.

    PubMed

    Nava, L E; Tinajero, J C; Malacara, J M

    1992-01-01

    The role of the Na+/H+ exchanger in the phospholipase-A2 (PLA2) stimulation of LHRH release was investigated using in vitro incubations of rat hypothalamic fragments. It was found that monensin, the Na+/H+ ionophore, increased LHRH release in a dose-related manner. That effect diminished in the absence of calcium as well as after the addition of 2,4'-dibromoacetophenone, a blocker of PLA2 action. Amiloride, a blocker of the Na+/H+ exchanger, did not alter the effect of monensin. However, amiloride significantly diminished the effect of melittin, an activator of PLA2 action. LHRH release under PLA2 did not change when amiloride was added to the incubation medium. Lysophosphatidylcholine also increased LHRH release. These results were interpreted as evidence of the participation of Na+/H+ exchange in PLA2 activation in the release of LHRH in rat hypothalamic fragments. A role of lysophospholipids in this process is also suggested.

  9. Suomi NPP VIIRS active fire product status

    NASA Astrophysics Data System (ADS)

    Ellicott, E. A.; Csiszar, I. A.; Schroeder, W.; Giglio, L.; Wind, B.; Justice, C. O.

    2012-12-01

    We provide an overview of the evaluation and development of the Active Fires product derived from the Visible Infrared Imager Radiometer Suite (VIIRS) sensor on the Suomi National Polar-orbiting Partnership (SNPP) satellite during the first year of on-orbit data. Results from the initial evaluation of the standard SNPP Active Fires product, generated by the SNPP Interface Data Processing System (IDPS), supported the stabilization of the VIIRS Sensor Data Record (SDR) product. This activity focused in particular on the processing of the dual-gain 4 micron VIIRS M13 radiometric measurements into 750m aggregated data, which are fundamental for active fire detection. Following the VIIRS SDR product's Beta maturity status in April 2012, correlative analysis between VIIRS and near-simultaneous fire detections from the Moderate Resolution Imaging Spectroradiometer (MODIS) on the NASA Earth Observing System Aqua satellite confirmed the expected relative detection rates driven primarily by sensor differences. The VIIRS Active Fires Product Development and Validation Team also developed a science code that is based on the latest MODIS Collection 6 algorithm and provides a full spatially explicit fire mask to replace the sparse array output of fire locations from a MODIS Collection 4 equivalent algorithm in the current IDPS product. The Algorithm Development Library (ADL) was used to support the planning for the transition of the science code into IDPS operations in the future. Product evaluation and user outreach was facilitated by a product website that provided end user access to fire data in user-friendly format over North America as well as examples of VIIRS-MODIS comparisons. The VIIRS fire team also developed an experimental product based on 375m VIIRS Imagery band measurements and provided high quality imagery of major fire events in US. By August 2012 the IDPS product achieved Beta maturity, with some known and documented shortfalls related to the processing of

  10. Platelet-activating factor induces eosinophil peroxidase release from purified human eosinophils.

    PubMed Central

    Kroegel, C; Yukawa, T; Dent, G; Chanez, P; Chung, K F; Barnes, P J

    1988-01-01

    The degranulation response of purified human eosinophils to platelet-activating factor (PAF) has been studied. PAF induced release of eosinophil peroxidase (EPO) and beta-glucuronidase from highly purified human eosinophils with an EC50 of 0.9 nM. The order of release was comparable with that induced by phorbol myristate acetate (PMA). The new specific PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-H-thieno[3,2-f] [1,2,4]triazolo-[4,3a][1,4]-diazepin-2-yl](4-morpholinyl)- 1-propane-one (WEB 2086) inhibited the PAF-induced enzyme release by human eosinophils in a dose-dependent manner. The viability of eosinophils were unaffected both by PAF and WEB 2086. The results suggest that PAF may amplify allergic and inflammatory reactions by release of preformed proteins from eosinophil granules. PMID:3410498

  11. Postsynaptic activation at the squid giant synapse by photolytic release of L-glutamate from a 'caged' L-glutamate.

    PubMed Central

    Corrie, J E; DeSantis, A; Katayama, Y; Khodakhah, K; Messenger, J B; Ogden, D C; Trentham, D R

    1993-01-01

    1. Pharmacological evidence suggests L-glutamate is a strong candidate as a transmitter at the giant synapse of the squid. Postsynaptic activation at the giant synapse cannot be effected by conventional application of putative neurotransmitters by iontophoresis or perfusion, apparently because the complex structure of the synapse prevents a sufficiently rapid change in concentration at the postsynaptic membrane. Flash photolytic release of L-glutamate from a pharmacologically inert 'caged' L-glutamate pre-equilibrated in the stellate ganglion of Alloteuthis or Loligo was used to determine whether L-glutamate can produce postsynaptic activation when released rapidly in the synaptic clefts. 2. The preparation, reaction mechanism and properties of the caged L-glutamate, N-1-(2-nitrophenyl)ethoxycarbonyl-L-glutamate, are described. The product quantum yield on photolysis was 0.65 (+/- 0.05). On flash photolysis glutamate release followed a single exponential time-course in the pH range 5.5-7.8. The rate constant was proportional to [H+] and was 93 s-1 at pH 5.5 and 16 degrees C in artificial sea water (ionic strength, I = 0.68 M). 3. At pH 7.8 flash photolysis of caged glutamate pre-equilibrated in the synapse caused only a slow depolarization. A second photolytic release of L-glutamate or transsynaptic activation produced no further depolarization, suggesting desensitization and inactivation of postsynaptic mechanisms by the initial pulse of L-glutamate. 4. Synaptic transmission in the giant synapse was normal at pH 5.5. Flash photolysis at pH 5.5 caused rapid production of L-glutamate within the synaptic cleft and a fast postsynaptic depolarization which generated postsynaptic action potentials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7901400

  12. Properties and active substance release kinetics from gelatin-alginate matrices.

    PubMed

    Pluta, Janusz; Haznar, Dorota

    2006-01-01

    The aim of the study was to evaluate the effect of composition and technological processing on pharmaceutical availability of active substance as well as on the properties of porous gelatin-alginate matrices. The active substance carrier included glycerol or peanut oil apart from gelatin and sodium alginate, and some matrices were additionally modified with calcium lactate. The obtained matrices were characterized by good sorption properties and high resistance to proteolytic enzymes. The release of the model antibiotic followed the pattern of first order kinetics, while half-release time in vitro (in the experimental conditions) was 1.5 to 3 hrs.

  13. Developmental changes in hypothalamic Kiss1 expression during activation of the pulsatile release of luteinising hormone in maturing ewe lambs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Onset of puberty is characterized by a marked increase in the frequency of release of gonadotrophin-releasing hormone (GnRH) and luteinizing hormone (LH). The KISS1 gene plays a critical role in pubertal development and its product, kisspeptin, stimulates GnRH and LH release. In the study reported h...

  14. Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase.

    PubMed

    Zhang, Qin; Itagaki, Kiyoshi; Hauser, Carl J

    2010-07-01

    Bacterial DNA (bDNA) can activate an innate-immune stimulatory "danger" response via toll-like receptor 9 (TLR9). Mitochondrial DNA (mtDNA) is unique among endogenous molecules in that mitochondria evolved from prokaryotic ancestors. Thus, mtDNA retains molecular motifs similar to bDNA. It is unknown, however, whether mtDNA is released by shock or is capable of eliciting immune responses like bDNA. We hypothesized shock-injured tissues might release mtDNA and that mtDNA might act as a danger-associated molecular pattern (or "alarmin") that can activate neutrophils (PMNs) and contribute to systemic inflammatory response syndrome. Standardized trauma/hemorrhagic shock caused circulation of mtDNA as well as nuclear DNA. Human PMNs were incubated in vitro with purified mtDNA or nuclear DNA, with or without pretreatment by chloroquine (an inhibitor of endosomal receptors like TLR9). Neutrophil activation was assessed as matrix metalloproteinase (MMP) 8 and MMP-9 release as well as p38 and p44/42 mitogen-activated protein kinase (MAPK) phosphorylation. Mitochondrial DNA induced PMN MMP-8/MMP-9 release and p38 phosphorylation but did not activate p44/42. Responses were inhibited by chloroquine. Nuclear DNA did not induce PMN activation. Intravenous injection of disrupted mitochondria (mitochondrial debris) into rats induced p38 MAPK activation and IL-6 and TNF-alpha accumulation in the liver. In summary, mtDNA is released into the circulation by shock. Mitochondrial DNA activates PMN p38 MAPK, probably via TLR9, inducing an inflammatory phenotype. Mitochondrial DNA may act as a danger-associated molecular pattern or alarmin after shock, contributing to the initiation of systemic inflammatory response syndrome.

  15. Overview of the National Atmospheric Release Advisory Center's Urban Research and Development Activities

    NASA Astrophysics Data System (ADS)

    Lundquist, J. K.; Sugiyama, G.; Nasstrom, J.

    2007-12-01

    Administration (NOAA), U.S. Navy, and U.S. Air Force, as well as an in-house mesoscale numerical weather prediction model. NARAC provides an easy-to-use Geographical Information System (GIS) for display of plume predictions with affected population counts and detailed maps, and the ability to export plume predictions to other standard GIS capabilities. Data collection and product distribution is provided through a variety of communication methods, including dial-up, satellite, and wired and wireless networks. Ongoing research and development activities will be highlighted. The NARAC scientific support team is developing urban parameterizations for use in a regional dispersion model (see companion paper by Delle Monache). Modifications to the numerical weather prediction model WRF to account for characteristics of urban dynamics are also in progress, as is boundary-layer turbulence model development for simulations with resolutions greater than 1km. The NARAC building-resolving computational fluid dynamics capability, FEM3MP, enjoys ongoing development activities such as the expansion of its ability to model releases of dense gases. Other research activities include sensor-data fusion, such as the reconstruction of unknown source terms from sparse and disparate observations. This work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48. The Department of Homeland Security sponsored the production of this material under the Department of Energy contract for the management and operation of Lawrence Livermore National Laboratory. UCRL-PROC-234355

  16. Comparison of dust release from epoxy and paint nanocomposites and conventional products during sanding and sawing.

    PubMed

    Gomez, Virginia; Levin, Marcus; Saber, Anne T; Irusta, Silvia; Dal Maso, Miikka; Hanoi, Roberto; Santamaria, Jesus; Jensen, Keld A; Wallin, Håkan; Koponen, Ismo K

    2014-10-01

    The release of dust generated during sanding or sawing of nanocomposites was compared with conventional products without nanomaterials. Epoxy-based polymers with and without carbon nanotubes, and paints with different amounts of nano-sized titanium dioxide, were machined in a closed aerosol chamber. The temporal evolution of the aerosol concentration and size distribution were measured simultaneously. The morphology of collected dust by scanning electron microscopy was different depending on the type of nanocomposites: particles from carbon nanotubes (CNTs) nanocomposites had protrusions on their surfaces and aggregates and agglomerates are attached to the paint matrix in particles emitted from alkyd paints. We observed no significant differences in the particle size distributions when comparing sanding dust from nanofiller containing products with dust from conventional products. Neither did we observe release of free nanomaterials. Instead, the nanomaterials were enclosed or partly enclosed in the matrix. A source strength term Si (cm(-3) s(-1)) that describes particle emission rates from continuous sources was introduced. Comparison between the Si parameters derived from sanding different materials allows identification of potential effects of addition of engineered nanoparticles to a composite.

  17. Releasing Activity Disengages Cohesin's Smc3/Scc1 Interface in a Process Blocked by Acetylation.

    PubMed

    Beckouët, Frederic; Srinivasan, Madhusudhan; Roig, Maurici Brunet; Chan, Kok-Lung; Scheinost, Johanna C; Batty, Paul; Hu, Bin; Petela, Naomi; Gligoris, Thomas; Smith, Alexandra C; Strmecki, Lana; Rowland, Benjamin D; Nasmyth, Kim

    2016-02-18

    Sister chromatid cohesion conferred by entrapment of sister DNAs within a tripartite ring formed between cohesin's Scc1, Smc1, and Smc3 subunits is created during S and destroyed at anaphase through Scc1 cleavage by separase. Cohesin's association with chromosomes is controlled by opposing activities: loading by Scc2/4 complex and release by a separase-independent releasing activity as well as by cleavage. Coentrapment of sister DNAs at replication is accompanied by acetylation of Smc3 by Eco1, which blocks releasing activity and ensures that sisters remain connected. Because fusion of Smc3 to Scc1 prevents release and bypasses the requirement for Eco1, we suggested that release is mediated by disengagement of the Smc3/Scc1 interface. We show that mutations capable of bypassing Eco1 in Smc1, Smc3, Scc1, Wapl, Pds5, and Scc3 subunits reduce dissociation of N-terminal cleavage fragments of Scc1 (NScc1) from Smc3. This process involves interaction between Smc ATPase heads and is inhibited by Smc3 acetylation. PMID:26895425

  18. Investigation of active substance release from poly(ethylene oxide) hydrogels.

    PubMed

    Savaş, H; Güven, O

    2001-08-14

    The uptake and controlled release of model active substances from poly(ethylene oxide), (PEO), hydrogels synthesized by irradiation were investigated. For the characterization of network structure of PEO hydrogels, swelling properties in water and the number average molecular weight between crosslinks were determined. Salicylic acid, phthalic acid and resorcinol were used as model substances for their controlled release from PEO hydrogels. The effects of dose rate, total dose and chemical structure of active substance on the uptake and release have been studied. The active substance uptake capacity of hydrogels was found to be lowest for phthalic acid and highest for resorcinol in the gel system obtained by irradiation both at low and high dose rates. The release was lowest both in rate and in total amounts in hydrogels containing phthalic acid, more in those with salicylic acid and highest in those with resorcinol. The physical and chemical factors affecting the release of model compounds such as the network structure of hydrogels and hydrogen bond formation between the adsorbent and PEO chains were discussed.

  19. Biological activity of recombinant human growth factors released from biocompatible bone implants.

    PubMed

    Ziegler, Joerg; Anger, Dominique; Krummenauer, Frank; Breitig, Dieter; Fickert, Stefan; Guenther, Klaus-Peter

    2008-07-01

    The present investigation was performed to study the bioactivity of osteoinductive and osteoproliferative growth factors after release from biocompatible bone implants. Three types of porous carriers were used in this study: hydroxyapatite, alpha tricalcium phosphate, and a neutralized glass ceramic. Implants were loaded with recombinant human bone morphogenetic protein 2 (rh-BMP-2) and recombinant human basic fibroblast growth factor (rh-bFGF) in a concentration of 2 microg/150 microL PBS each. The released growth factors were then applicated into SAOS-2-cell cultures. After 3, 5, and 7 days cell differentiation was measured by the activity of alkaline phosphatase (ALP), cell proliferation by using a MTT assay as well as a cell counter. Rh-BMP-2 released during the first hour from the scaffolds led to a significant increase of the activity of ALP in the incubated SAOS-2-cell culture after 3, 5, and 7 days. However, the incubation with rh-BMP-2 released after 24 h was not found to increase the expression of ALP. The incubation of cell cultures with rh-bFGF released during the first hour led to a significant increase of cell number and of extinction in the MTT assay, whereas this increase was not observed after incubation with rh-bFGF released after 24 h. The in vitro measured biological activity of released growth factors from the surface of synthetic implants is time-depending. If prolonged osteoinductive and osteoproliferative potency of growth factors is desired, a modified application technique should be chosen to stabilize those proteins.

  20. SDSS-IV MaNGA: Data Products, Quality, and Initial Public Release

    NASA Astrophysics Data System (ADS)

    Law, David R.; Cherinka, Brian; MaNGA Team

    2016-01-01

    As a spectroscopic imaging survey, MaNGA presents a host of technical challenges ranging from spectrophotometic calibration to image reconstruction. I will present an overview of the MaNGA data reduction pipeline (DRP) and the algorithms used to process the MaNGA data. Additionally, I will describe the format and quality of the MaNGA data products, and the means by which the first year of survey data will be made publicly available in SDSS Data Release 13 (DR-13).

  1. Fission product release phenomena during core melt accidents in metal fueled heavy water reactors

    SciTech Connect

    Ellison, P G; Hyder, M L; Monson, P R; Randolph, H W; Hagrman, D L; McClure, P R; Leonard, M T

    1990-01-01

    The phenomena that determine fission product release rates from a core melting accident in a metal-fueled, heavy water reactor are described in this paper. This information is obtained from the analysis of the current metal fuel experimental data base and from the results of analytical calculations. Experimental programs in place at the Savannah River Site are described that will provide information to resolve uncertainties in the data base. The results of the experiments will be incorporated into new severe accident computer codes recently developed for this reactor design. 47 refs., 4 figs.

  2. Role of Fc Gamma Receptors in Triggering Host Cell Activation and Cytokine Release by Borrelia burgdorferi

    PubMed Central

    Talkington, Jeffrey; Nickell, Steven P.

    2001-01-01

    Borrelia burgdorferi, the spirochetal bacterium that causes human Lyme disease, encodes numerous lipoproteins which have the capacity to trigger the release of proinflammatory cytokines from a variety of host cell types, and it is generally believed that these cytokines contribute to the disease process in vivo. We previously reported that low-passage-number infectious B. burgdorferi spirochetes express a novel lipidation-independent activity which induces secretion of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) by the mouse MC/9 mast cell line. Using RNase protection assays, we determined that mast cells exposed in vitro to low-passage-number, but not high-passage-number, B. burgdorferi spirochetes show increased expression of additional mRNAs representing several chemokines, including macrophage-inflammatory protein 1α (MIP-1α), MIP-1β, and TCA3, as well as the proinflammatory cytokine interleukin-6. Furthermore, mast cell TNF-α secretion can be inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin and also by preincubation with purified mouse immunoglobulin G1 (IgG1) and IgG2a, but not mouse IgG3, and by a mouse Fc gamma receptor II and III (FcγRII/III)-specific rat monoclonal antibody, suggesting the likely involvement of host FcγRIII in B. burgdorferi-mediated signaling. A role for passively adsorbed rabbit or bovine IgG or serum components in B. burgdorferi-mediated FcγR signaling was excluded in control experiments. These studies confirm that low-passage-number B. burgdorferi spirochetes express a novel activity which upregulates the expression of a variety of host cell chemokine and cytokine genes, and they also establish a novel antibody-independent role for FcγRs in transduction of activation signals by bacterial products. PMID:11119532

  3. Developmental changes in hypothalamic Kiss1 expression during activation of the pulsatile release of luteinising hormone in maturing ewe lambs.

    PubMed

    Redmond, J S; Baez-Sandoval, G M; Spell, K M; Spencer, T E; Lents, C A; Williams, G L; Amstalden, M

    2011-09-01

    Onset of puberty is characterised by a marked increase in the frequency of release of gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH). The Kiss1 gene plays a critical role in pubertal development, and its product, kisspeptin, stimulates GnRH and LH release. In the present study, we tested the hypothesis that Kiss1 gene expression in the preoptic area (POA) and hypothalamus increases during maturation of the reproductive neuroendocrine axis in association with increased LH pulsatility. Ovariectomised, oestradiol-replaced lambs were euthanised at 25, 30 and 35 weeks of age. Blood samples were collected before euthanasia to characterise the pattern of LH release. Kiss1 mRNA was detected in coronal sections of the POA and hypothalamus and Kiss1-expressing cells were identified on the basis of silver grain density. The mean number of Kiss1-expressing cells in the POA/periventricular (PeV) areas increased from 25 to 30 weeks of age. No further increase at 35 weeks of age was observed, and the changes in Kiss1 expression in the POA/PeV were independent of changes in LH pulse frequency. The mean number of Kiss1-expressing cells in the arcuate (ARC) nucleus did not differ among age groups, although it was greater in the middle ARC of lambs exhibiting increased frequency of LH release. The density of silver grains per cell did not differ among groups in any of the areas studied. The results obtained indicate that the Kiss1 gene is activated in the POA/PeV and ARC of ewe lambs during juvenile development, and that kisspeptin neurones in the middle ARC, in particular, are involved in the acceleration of pulsatile LH release during maturation of the reproductive neuroendocrine axis in ewe lambs.

  4. Activity-dependent, homeostatic regulation of neurotransmitter release from auditory nerve fibers

    PubMed Central

    Ngodup, Tenzin; Goetz, Jack A.; McGuire, Brian C.; Sun, Wei; Lauer, Amanda M.; Xu-Friedman, Matthew A.

    2015-01-01

    Information processing in the brain requires reliable synaptic transmission. High reliability at specialized auditory nerve synapses in the cochlear nucleus results from many release sites (N), high probability of neurotransmitter release (Pr), and large quantal size (Q). However, high Pr also causes auditory nerve synapses to depress strongly when activated at normal rates for a prolonged period, which reduces fidelity. We studied how synapses are influenced by prolonged activity by exposing mice to constant, nondamaging noise and found that auditory nerve synapses changed to facilitating, reflecting low Pr. For mice returned to quiet, synapses recovered to normal depression, suggesting that these changes are a homeostatic response to activity. Two additional properties, Q and average excitatory postsynaptic current (EPSC) amplitude, were unaffected by noise rearing, suggesting that the number of release sites (N) must increase to compensate for decreased Pr. These changes in N and Pr were confirmed physiologically using the integration method. Furthermore, consistent with increased N, endbulbs in noise-reared animals had larger VGlut1-positive puncta, larger profiles in electron micrographs, and more release sites per profile. In current-clamp recordings, noise-reared BCs had greater spike fidelity even during high rates of synaptic activity. Thus, auditory nerve synapses regulate excitability through an activity-dependent, homeostatic mechanism, which could have major effects on all downstream processing. Our results also suggest that noise-exposed bushy cells would remain hyperexcitable for a period after returning to normal quiet conditions, which could have perceptual consequences. PMID:25944933

  5. Effect of substrate concentration and nitrate inhibition on product release and heavy metal removal by a Citrobacter sp.

    SciTech Connect

    Yong, P.; Macaskie, L.E.

    1997-09-20

    The biological treatment of industrial effluent containing heavy metals has received increased attention for its advantages compared to traditional wastewater treatment processes. A Citrobacter sp. accumulates heavy metals as cell-bound metal phosphates, utilizing phosphate released by the enzymatic cleavage of a phosphomonoester substrate. The effect of increased substrate concentration on phosphate release and heavy metal accumulation was evaluated using a stirred tank reactor (STR) and a plug flow reactor (PFR). A significant improvement in metal removal was achieved with increased substrate concentration using immobilized Citrobacter cells in the PFR, which was not observed using free cells in the STR. Nitrate is an inhibitor of the Citrobacter phosphatase. This inhibition was concentration dependent and reversible. The rate of product release was restored by increasing the concentration of substrate (G2P). The ratio of rates of phosphate release under two different conditions (different nitrate and G2P concentrations) can be described by an equation developed from Michaelis-Menten kinetics. The concentration of substrate required for restoration of maximum velocity, V{sub max}, in a batch and continuous-flow system can be predicted by substitution and calculation; this was confirmed by an experiment in model systems using cell suspensions and polyacrylamide gel immobilized cells in a flow-though column. For use in industrial situations it may be uneconomical or infeasible to supply additional substrate. Bioreactor activity was also restored by increasing the flow residence time, in accordance with a Michaelis-Menten-based model to describe removal of lanthanum from nitrate-supplemented flow in a PFR.

  6. Release of platelet-activating factor (PAF) and histamine. II. The cellular origin of human PAF: monocytes, polymorphonuclear neutrophils and basophils.

    PubMed Central

    Camussi, G; Aglietta, M; Coda, R; Bussolino, F; Piacibello, W; Tetta, C

    1981-01-01

    The origin of platelet activating factor (PAF) from human leucocytes was investigated. Purified monocytes release PAF passively at pH 10.6, when challenged with Ionophore A 23187 or under phagocytic stimuli. Pure preparations of polymorphonuclear neutrophils liberate PAF passively, when challenged with C5a, neutrophil cationic proteins (CP), their carboxypeptidase B derived products (C5a des Arg, CP des Arg) or under phagocytic stimuli. Basophil rich buffy coat cells release PAF when challenged with C5a, CP, anti-IgE (in low amount) or Synacthen concomitantly with basophil degranulation and histamine release. Electron microscopy studies, carried out on Synacthen-stimulated basophil rich buffy coat, provide morphological evidence for platelet-basophil interaction. In conclusion our data demonstrate that PAF can be released from different leucocyte populations. However, the stimuli able to trigger such release appear to have some specificity for the cell target. Images Figure 5 PMID:6161885

  7. Production and Release of Selenomethionine and Related Organic Selenium Species by Microorganisms in Natural and Industrial Waters.

    PubMed

    LeBlanc, Kelly L; Wallschläger, Dirk

    2016-06-21

    Laboratory algal cultures exposed to selenate were shown to produce and release selenomethionine, selenomethionine oxide, and several other organic selenium metabolites. Released discrete organic selenium species accounted for 1.6-13.1% of the selenium remaining in the media after culture death, with 1.3-6.1% of the added selenate recovered as organic metabolites. Analysis of water from an industrially impacted river collected immediately after the death of massive annual algal blooms showed that no selenomethionine or selenomethionine oxide was present. However, other discrete organic selenium species, including a cyclic oxidation product of selenomethionine, were observed, indicating the previous presence of selenomethionine. Industrial biological treatment systems designed for remediation of selenium-contaminated waters were shown to increase both the concentration of organic selenium species in the effluent, relative to influent water, and the fraction of organic selenium to up to 8.7% of the total selenium in the effluent, from less than 1.1% in the influent. Production and emission of selenomethionine, selenomethionine oxide, and other discrete organic selenium species were observed. These findings are discussed in the context of potentially increased selenium bioavailability caused by microbial activity in aquatic environments and biological treatment systems, despite overall reductions in total selenium concentration. PMID:27228300

  8. A curcumin activated carboxymethyl cellulose-montmorillonite clay nanocomposite having enhanced curcumin release in aqueous media.

    PubMed

    Madusanka, Nadeesh; de Silva, K M Nalin; Amaratunga, Gehan

    2015-12-10

    A novel curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is reported. A superabsorbent biopolymer; carboxymethyl cellulose (CMC) was used as an emulsifier for curcumin which is a turmeric derived water insoluble polyphenolic compound with antibacterial/anti-cancer properties. Montmorillonite (MMT) nanoclay was incorporated in the formulation as a matrix material which also plays a role in release kinetics. It was observed that water solubility of curcumin in the nanocomposite has significantly increased (60% release within 2h and 30 min in distilled water at pH 5.4) compared to pure curcumin. The prepared curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is suitable as a curcumin carrier having enhanced release and structural properties.

  9. Promotion of Hydrogen Release from Ammonia Borane with Mechanically Activated Hexagonal Boron Nitride

    SciTech Connect

    Neiner, Doinita; Karkamkar, Abhijeet J.; Linehan, John C.; Arey, Bruce W.; Autrey, Thomas; Kauzlarich, Susan M.

    2009-01-22

    We present the activation of hydrogen release from AB by the presence of mechanically activated h–BN. Hydrogen is released at lower temperatures and the dehydrogenation is less exothermic than neat AB. This approach provides all the benefits of a light-weight scaffold without additional foreign contamination that might complicate AB recycling. Several beneficial effects that pertain to the hydrogen desorption properties of the mixtures of AB:nano-BN are notable, such as the decrease of hydrogen desorption temperature, the decrease in NH3 formation as well as the decrease of the exothermicity of hydrogen desorption with increasing the nano-BN concentration. The lower exothermicity of H2 release from AB in the mesoporous silica and the nano-BN may be due physical and chemical interactions between the PAB oligomers and the interface of the silica scaffold or BN support. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.

  10. Controlling the release of active compounds from the inorganic carrier halloysite

    NASA Astrophysics Data System (ADS)

    Tescione, F.; Buonocore, G. G.; Stanzione, M.; Oliviero, M.; Lavorgna, M.

    2014-05-01

    Halloysite (HNTs), a natural material characterized by a nanotube structure, has been used as an inorganic carrier of active compounds in several applications from medicine to anticorrosion coatings. In this present work, vanillin (VAN) used as a antimicrobial model, has been encapsulated within HNTs for exploiting its applicability in the active food packaging sector. The molecule release rate has been controlled by crosslinking at the tube ends the loaded vanillin with copper ions, thus producing a stopper network. The vanillin-loaded HNTs were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and thermo gravimetric analysis. The antimicrobial release kinetics from the loaded nanoparticles (VAN/HNTs) in water was investigated using UV-vis spectroscopy. The results show that the vanillin crosslinked with cupper ions is a feasible method to tailor the release rate of antimicrobial model from HTNs nanoparticles.

  11. Controlling the release of active compounds from the inorganic carrier halloysite

    SciTech Connect

    Tescione, F.; Buonocore, G. G.; Stanzione, M.; Oliviero, M.; Lavorgna, M.

    2014-05-15

    Halloysite (HNTs), a natural material characterized by a nanotube structure, has been used as an inorganic carrier of active compounds in several applications from medicine to anticorrosion coatings. In this present work, vanillin (VAN) used as a antimicrobial model, has been encapsulated within HNTs for exploiting its applicability in the active food packaging sector. The molecule release rate has been controlled by crosslinking at the tube ends the loaded vanillin with copper ions, thus producing a stopper network. The vanillin-loaded HNTs were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and thermo gravimetric analysis. The antimicrobial release kinetics from the loaded nanoparticles (VAN/HNTs) in water was investigated using UV-vis spectroscopy. The results show that the vanillin crosslinked with cupper ions is a feasible method to tailor the release rate of antimicrobial model from HTNs nanoparticles.

  12. A curcumin activated carboxymethyl cellulose-montmorillonite clay nanocomposite having enhanced curcumin release in aqueous media.

    PubMed

    Madusanka, Nadeesh; de Silva, K M Nalin; Amaratunga, Gehan

    2015-12-10

    A novel curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is reported. A superabsorbent biopolymer; carboxymethyl cellulose (CMC) was used as an emulsifier for curcumin which is a turmeric derived water insoluble polyphenolic compound with antibacterial/anti-cancer properties. Montmorillonite (MMT) nanoclay was incorporated in the formulation as a matrix material which also plays a role in release kinetics. It was observed that water solubility of curcumin in the nanocomposite has significantly increased (60% release within 2h and 30 min in distilled water at pH 5.4) compared to pure curcumin. The prepared curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is suitable as a curcumin carrier having enhanced release and structural properties. PMID:26428174

  13. Low pH anaerobic digestion of waste activated sludge for enhanced phosphorous release.

    PubMed

    Latif, Muhammad A; Mehta, Chirag M; Batstone, Damien J

    2015-09-15

    This paper assesses anaerobic digestion of waste activated sludge (WAS) at low pH to enhance phosphorous solubility. Batch biochemical methane potential tests were conducted at a pH range of 5 to 7.2 in two separate sets (two different WAS samples collected from municipal WWTP). Low pH (<5.7) caused a significant (p = 0.004) decrease in methane potential (B0) up to 33% and 3.6 times increase in phosphorus release compared to neutral pH (7-7.7), but with no major change in methane production rate coefficient (khyd). The loss in methane yield was mainly due to decrease in hydrolytic capability rather than inhibition of methanogenesis with volatile fatty acids being <300 mgCOD L(-1) and soluble COD <1300 mgCOD L(-1) even at low pH. While pH did not influence the acetoclastic community (Methanosaeta dominated), it was the primary driver for the remaining community (p = 0.004), and caused a loss of diversity and shift to Clostridia.

  14. Release of an acid phosphatase activity during lily pollen tube growth involves components of the secretory pathway.

    PubMed

    Ibrahim, Hala; Pertl, Heidi; Pittertschatscher, Klaus; Fadl-Allah, Ezzat; el-Shahed, Ahmed; Bentrup, Friedrich-Wilhelm; Obermeyer, Gerhard

    2002-05-01

    An acid phosphatase (acPAse) activity was released during germination and tube growth of pollen of Lilium longiflorum Thunb. By inhibiting components of the secretory pathway, the export of the acPase activity was affected and tube growth stopped. Brefeldin A (1 microM) and cytochalasin D (1 microM), which block the production and transport of secretory vesicles, respectively, inhibited the acPase secretion. The Ca2+ channel blocker gadolinium (100 microM Gd3+) also inhibited acPase secretion and tube growth, whereas 3 mM caffeine, another Ca2+ uptake inhibitor, stimulated the acPase release, while tube growth was inhibited. The Yariv reagent (beta-D-glucosyl)3 Yariv phenylglycoside stopped tube growth by binding to arabinogalactan proteins of the tube tip cell wall but did not affect acPase secretion. A strong correlation between tube growth and acPase release was detected. The secreted acPase activity had a pH optimum at pH 5.5, a KM of 0.4 mM for p-nitrophenyl phosphate, and was inhibited by zinc, molybdate, phosphate, and fluoride ions, but not by tartrate. In electrophoresis gels the main acPase activity was detected at 32 kDa. The conspicuous correlation between activity of the secretory pathway and acPase secretion during tube elongation strongly indicates an important role of the acPase during pollen tube growth and the secreted acPase activity may serve as a useful marker enzyme assay for secretory activity in pollen tubes.

  15. Estimates of Radioxenon Released from Southern Hemisphere Medical isotope Production Facilities Using Measured Air Concentrations and Atmospheric Transport Modeling

    SciTech Connect

    Eslinger, Paul W.; Friese, Judah I.; Lowrey, Justin D.; McIntyre, Justin I.; Miley, Harry S.; Schrom, Brian T.

    2014-09-01

    Abstract The International Monitoring System (IMS) of the Comprehensive-Nuclear-Test-Ban-Treaty monitors the atmosphere for radioactive xenon leaking from underground nuclear explosions. Emissions from medical isotope production represent a challenging background signal when determining whether measured radioxenon in the atmosphere is associated with a nuclear explosion prohibited by the treaty. The Australian Nuclear Science and Technology Organisation (ANSTO) operates a reactor and medical isotope production facility in Lucas Heights, Australia. This study uses two years of release data from the ANSTO medical isotope production facility and Xe-133 data from three IMS sampling locations to estimate the annual releases of Xe-133 from medical isotope production facilities in Argentina, South Africa, and Indonesia. Atmospheric dilution factors derived from a global atmospheric transport model were used in an optimization scheme to estimate annual release values by facility. The annual releases of about 6.8×1014 Bq from the ANSTO medical isotope production facility are in good agreement with the sampled concentrations at these three IMS sampling locations. Annual release estimates for the facility in South Africa vary from 1.2×1016 to 2.5×1016 Bq and estimates for the facility in Indonesia vary from 6.1×1013 to 3.6×1014 Bq. Although some releases from the facility in Argentina may reach these IMS sampling locations, the solution to the objective function is insensitive to the magnitude of those releases.

  16. Activation of glutamate transport evokes rapid glutamine release from perisynaptic astrocytes

    PubMed Central

    Uwechue, Nneka M; Marx, Mari-Carmen; Chevy, Quentin; Billups, Brian

    2012-01-01

    Stimulation of astrocytes by neuronal activity and the subsequent release of neuromodulators is thought to be an important regulator of synaptic communication. In this study we show that astrocytes juxtaposed to the glutamatergic calyx of Held synapse in the rat medial nucleus of the trapezoid body (MNTB) are stimulated by the activation of glutamate transporters and consequently release glutamine on a very rapid timescale. MNTB principal neurones express electrogenic system A glutamine transporters, and were exploited as glutamine sensors in this study. By simultaneous whole-cell voltage clamping astrocytes and neighbouring MNTB neurones in brainstem slices, we show that application of the excitatory amino acid transporter (EAAT) substrate d-aspartate stimulates astrocytes to rapidly release glutamine, which is detected by nearby MNTB neurones. This release is significantly reduced by the toxins l-methionine sulfoximine and fluoroacetate, which reduce glutamine concentrations specifically in glial cells. Similarly, glutamine release was also inhibited by localised inactivation of EAATs in individual astrocytes, using internal dl-threo-β-benzyloxyaspartic acid (TBOA) or dissipating the driving force by modifying the patch-pipette solution. These results demonstrate that astrocytes adjacent to glutamatergic synapses can release glutamine in a temporally precise, controlled manner in response to glial glutamate transporter activation. Since glutamine can be used by neurones as a precursor for glutamate and GABA synthesis, this represents a potential feedback mechanism by which astrocytes can respond to synaptic activation and react in a way that sustains or enhances further communication. This would therefore represent an additional manifestation of the tripartite relationship between synapses and astrocytes. PMID:22411007

  17. Glyceryl monooleate-based otic delivery system of ofloxacin: release profile and bactericidal activity.

    PubMed

    Adwan, Samer; Abu-Dahab, Rana; Al-Bakri, Amal G; Sallam, Alsayyed

    2015-05-01

    This study investigated the preparation and characterization of glyceryl monooleate- (GMO) based drug delivery system containing ofloxacin for the treatment of otitis externa. Acetate buffer (pH 4.5) containing dissolved ofloxacin was added to molten GMO as an aqueous phase, this resulted in the formation of a cubic and a reverse hexagonal phases. The release behavior of ofloxacin from the drug delivery system was studied using three different methods. The mechanism of drug release using paddles/dissolution apparatus and Franz diffusion cells followed Higuchi and Fickian diffusion models; whereas intrinsic release rate method showed zero-order kinetics. The intrinsic release rate was estimated and found to be 187.2 µg/cm(2)/h. The release mechanisms were similar irrespective of the loaded ofloxacin amount, however, the higher drug load displayed higher release rate. The drug delivery system was proven to be microbiologically effective by using agar diffusion method, against Staphylococcus aureus, and Pseudomonas aeruginosa. The GMO/ofloxacin formulation was stable for 6 months after preparation at room temperature as measured with respect to phase stability and antibacterial activity.

  18. 27 CFR 41.85 - Release from customs custody of imported tobacco products or cigarette papers or tubes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Release from customs custody of imported tobacco products or cigarette papers or tubes. 41.85 Section 41.85 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY...

  19. Greenhouse production of Impatiens wallerana using a controlled-release fertiliser produces quality finished plants with enhanced garden performance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrient management during production can greatly influence post-production quality of plants. The objective of this research was to evaluate the effect of controlled release fertilizer (CRF) applied at the time of plug planting on the garden performance (post-production) of impatiens (Impatiens wal...

  20. Vanadium(V) and -(IV) complexes of anionic polysaccharides: Controlled release pharmaceutical formulations and models of vanadium biotransformation products.

    PubMed

    Kremer, Lauren E; McLeod, Andrew I; Aitken, Jade B; Levina, Aviva; Lay, Peter A

    2015-06-01

    Uncontrolled reactions in biological media are a main obstacle for clinical translation of V-based anti-diabetic or anti-cancer pro-drugs. We investigated the use of controlled-release pharmaceutical formulations to ameliorate this issue with a series of V(V) and (IV) complexes of anionic polysaccharides. Carboxymethyl cellulose, xanthan gum, or alginic acid formulations were prepared by the reactions of [VO4](3-) with one or two molar equivalents of biological reductants, L-ascorbic acid (AA) or L-cysteine (Cys), in the presence of excess polysaccharide at pH~7 or pH~4. XANES studies with the use of a previously developed library of model V(V), V(IV) and V(III) complexes showed that reactions in the presence of AA led mostly to the mixtures of five- and six-coordinate V(IV) species, while the reactions in the presence of Cys led predominantly to the mixtures of five- and six-coordinate V(V) species. The XANES spectra of some of these samples closely matched those reported previously for [VO4](3-) biotransformation products in isolated blood plasma, red blood cells, or cultured adipocytes, which supports the hypothesis that modified polysaccharides are major binders of V(V) and V(IV) in biological systems. Studies by EPR spectroscopy suggested predominant V(IV)-carboxylato binding in complexes with polysaccharides. One of the isolated products (a V(IV)-alginato complex) showed selective release of low-molecular-mass V species at pH~8, but not at pH~2, which makes it a promising lead for the development of V-containing formulations for oral administration that are stable in the stomach, but release the active ingredient in the intestines.

  1. Characterizing the release of bioactive N-glycans from dairy products by a novel endo-β-N-acetylglucosaminidase.

    PubMed

    Karav, Sercan; Bell, Juliana Maria Leite Nobrega De Moura; Le Parc, Annabelle; Liu, Yan; Mills, David A; Block, David E; Barile, Daniela

    2015-01-01

    Endo-β-N-acetylglucosaminidase isolated from B. infantis ATCC 15697 (EndoBI-1) is a novel enzyme that cleaves N-N'-diacetyl chitobiose moieties found in the N-glycan core of high mannose, hybrid, and complex N-glycans. These conjugated N-glycans are recently shown as a new prebiotic source that stimulates the growth of a key infant gut microbe, Bifidobacterium longum subsp. Infantis. The effects of pH (4.45-8.45), temperature (27.5-77.5°C), reaction time (15-475 min), and enzyme/protein ratio (1:3,000-1:333) were evaluated on the release of N-glycans from bovine colostrum whey by EndoBI-1. A central composite design was used, including a two-level factorial design (2(4)) with four center points and eight axial points. In general, low pH values, longer reaction times, higher enzyme/protein ratio, and temperatures around 52°C resulted in the highest yield. The results demonstrated that bovine colostrum whey, considered to be a by/waste product, can be used as a glycan source with a yield of 20 mg N-glycan/g total protein under optimal conditions for the ranges investigated. Importantly, these processing conditions are suitable to be incorporated into routine dairy processing activities, opening the door for an entirely new class of products (released bioactive glycans and glycan-free milk). The new enzyme's activity was also compared with a commercially available enzyme, showing that EndoBI-1 is more active on native proteins than PNGase F and can be efficiently used during pasteurization, streamlining its integration into existing processing strategies. PMID:26097235

  2. Characterizing the Release of Bioactive N-Glycans from Dairy Products by a Novel Endo-β-N-Acetylglucosaminidase

    PubMed Central

    Karav, Sercan; Bell, Juliana Maria Leite Nobrega De Moura; Le Parc, Annabelle; Liu, Yan; Mills, David A.; Block, David E.; Barile, Daniela

    2015-01-01

    Endo-β-N-acetylglucosaminidase isolated from B. infantis ATCC 15697 (EndoBI-1) is a novel enzyme that cleaves N-N′-diacetyl chitobiose moieties found in the N-glycan core of high mannose, hybrid, and complex N-glycans. These conjugated N-glycans are recently shown as a new prebiotic source that stimulates the growth of a key infant gut microbe, Bifi-dobacterium longum subsp. Infantis. The effects of pH (4.45–8.45), temperature (27.5–77.5°C), reaction time (15–475 min), and enzyme/protein ratio (1:3,000–1:333) were evaluated on the release of N-glycans from bovine colostrum whey by EndoBI-1. A central composite design was used, including a two-level factorial design (24) with four center points and eight axial points. In general, low pH values, longer reaction times, higher enzyme/protein ratio, and temperatures around 52°C resulted in the highest yield. The results demonstrated that bovine colostrum whey, considered to be a by/waste product, can be used as a glycan source with a yield of 20 mg N-glycan/g total protein under optimal conditions for the ranges investigated. Importantly, these processing conditions are suitable to be incorporated into routine dairy processing activities, opening the door for an entirely new class of products (released bioactive glycans and glycan-free milk). The new enzyme’s activity was also compared with a commercially available enzyme, showing that EndoBI-1 is more active on native proteins than PNGase F and can be efficiently used during pasteurization, streamlining its integration into existing processing strategies. PMID:26097235

  3. Production and release of yessotoxins by the dinoflagellates Protoceratium reticulatum and Lingulodinium polyedrum in culture.

    PubMed

    Paz, Beatriz; Riobó, Pilar; Fernández, M Luisa; Fraga, Santiago; Franco, José M

    2004-09-01

    The presence of YTX was confirmed in Protoceratium reticulatum cultures and detected for the first time in Lingulodinium polyedrum cultures, mainly in the cells but also, to a lesser extent, dissolved in the culture medium. The production of yessotoxins (YTXs) by cultures of different strains of P. reticulatum and L. polyedrum was studied with liquid chromatography coupled to fluorometric detection using the dienophile reagent DMEQ-TAD and liquid chromatography-mass spectrometry. When comparing toxin production at different stages of culture growth, larger amounts of toxins were observed in the cellular fraction and in the culture medium at the last stage of the culture (day 21) in both species. Although YTX was detected in culture medium, with this study it was not possible to explain which is the release mechanism of the toxin in the medium.

  4. Effect of a controlled-release albendazole capsule on parasitism and productivity of sheep.

    PubMed

    Corba, J; Krupicer, I; Legény, J; Juris, P; Veselý, L

    1991-11-01

    The efficacy of intraruminal albendazole (ABZ) capsules (Profitril-Captec) and the effect of treatment on productivity were studied in 300 ewes infected with gastrointestinal nematodes and the trematode Dicrocoelium dendriticum. Coprological tests revealed that treated animals remained negative for 10 weeks after the administration of capsules. Contamination of pasture with nematode larvae was significantly reduced during the whole experiment. Necropsy of 14 animals (seven treated and seven untreated) showed 96.9-99.2% efficacy against the nematodes Nematodirus spp., Oesophagostomum spp., Cooperia spp., Trichostrongylus spp. and Trichuris ovis, while efficacy was 88.5% against D. dendriticum. During the 6 month pasture season (May-October 1989), treated ewes produced on average 2.56 kg cheese and 0.6 kg wool per ewe more than untreated controls. Our study confirms the reliability of the ABZ slow-release capsules over 90 days and the positive effect of treatment on nematode contamination of pasture and ewe productivity.

  5. Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator.

    PubMed Central

    Cooke, J P; Rossitch, E; Andon, N A; Loscalzo, J; Dzau, V J

    1991-01-01

    Flow-mediated vasodilation is endothelium dependent. We hypothesized that flow activates a potassium channel on the endothelium, and that activation of this channel leads to the release of the endogenous nitrovasodilator, nitric oxide. To test this hypothesis, rabbit iliac arteries were perfused at varying flow rates, at a constant pressure of 60 mm Hg. Increments in flow induced proportional increases in vessel diameter, which were abolished by L,N-mono-methylarginine (the antagonist of nitric-oxide synthesis). Barium chloride, depolarizing solutions of potassium, verapamil, calcium-free medium, and antagonists of the KCa channel (charybdotoxin, iberiotoxin) also blocked flow-mediated vasodilation. Conversely, responses to other agonists of endothelium-dependent and independent vasodilation were unaffected by charybdotoxin or iberiotoxin. To confirm that flow activated a specific potassium channel to induce the release of nitric oxide, endothelial cells cultured on micro-carrier beads were added to a flow chamber containing a vascular ring without endothelium. Flow-stimulated endothelial cells released a diffusible vasodilator; the degree of vasorelaxation was dependent upon the flow rate. Relaxation was abrogated by barium, tetraethylammonium ion, or charybdotoxin, but was not affected by apamin, glybenclamide, tetrodotoxin, or ouabain. The data suggest that transmission of a hyperpolarizing current from endothelium to the vascular smooth muscle is not necessary for flow-mediated vasodilation. Flow activates a potassium channel (possibly the KCa channel) on the endothelial cell membrane that leads to the release of nitric oxide. Images PMID:1719029

  6. Release probability of hippocampal glutamatergic terminals scales with the size of the active zone.

    PubMed

    Holderith, Noemi; Lorincz, Andrea; Katona, Gergely; Rózsa, Balázs; Kulik, Akos; Watanabe, Masahiko; Nusser, Zoltan

    2012-06-10

    Cortical synapses have structural, molecular and functional heterogeneity; our knowledge regarding the relationship between their ultrastructural and functional parameters is still fragmented. Here we asked how the neurotransmitter release probability and presynaptic [Ca(2+)] transients relate to the ultrastructure of rat hippocampal glutamatergic axon terminals. Two-photon Ca(2+) imaging-derived optical quantal analysis and correlated electron microscopic reconstructions revealed a tight correlation between the release probability and the active-zone area. Peak amplitude of [Ca(2+)] transients in single boutons also positively correlated with the active-zone area. Freeze-fracture immunogold labeling revealed that the voltage-gated calcium channel subunit Cav2.1 and the presynaptic protein Rim1/2 are confined to the active zone and their numbers scale linearly with the active-zone area. Gold particles labeling Cav2.1 were nonrandomly distributed in the active zones. Our results demonstrate that the numbers of several active-zone proteins, including presynaptic calcium channels, as well as the number of docked vesicles and the release probability, scale linearly with the active-zone area.

  7. Structural Evidence for a Sequential Release Mechanism for Activation of Heterotrimeric G Proteins

    SciTech Connect

    Kapoor, Neeraj; Menon, Santosh T.; Chauhan, Radha; Sachdev, Pallavi; Sakmar, Thomas P.

    2010-01-12

    Heptahelical G-protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors couple to heterotrimeric G proteins to relay extracellular signals to intracellular signaling networks, but the molecular mechanism underlying guanosine 5'-diphosphate (GDP) release by the G protein {alpha}-subunit is not well understood. Amino acid substitutions in the conserved {alpha}5 helix of Gi, which extends from the C-terminal region to the nucleotide-binding pocket, cause dramatic increases in basal (receptor-independent) GDP release rates. For example, mutant G{alpha}{sub i1}-T329A shows an 18-fold increase in basal GDP release rate and, when expressed in culture, it causes a significant decrease in forskolin-stimulated cAMP accumulation. The crystal structure of G{alpha}{sub i1}-T329A {center_dot} GDP shows substantial conformational rearrangement of the switch I region and additional striking alterations of side chains lining the catalytic pocket that disrupt the Mg{sup +2} coordination sphere and dislodge bound Mg{sup +2}. We propose a 'sequential release' mechanism whereby a transient conformational change in the {alpha}5 helix alters switch I to induce GDP release. Interestingly, this mechanistic model for heterotrimeric G protein activation is similar to that suggested for the activation of the plant small G protein Rop4 by RopGEF8.

  8. RCAN1 regulates vesicle recycling and quantal release kinetics via effects on calcineurin activity.

    PubMed

    Zanin, Mark P; Mackenzie, Kimberly D; Peiris, Heshan; Pritchard, Melanie A; Keating, Damien J

    2013-02-01

    We have previously shown that Regulator of Calcineurin 1 (RCAN1) regulates multiple stages of vesicle exocytosis. However, the mechanisms by which RCAN1 affects secretory vesicle exocytosis and quantal release kinetics remain unknown. Here, we use carbon fibre amperometry to detect exocytosis from chromaffin cells and identify these underlying mechanisms. We observe reduced exocytosis with repeated stimulations in chromaffin cells over-expressing RCAN1 (RCAN1(ox)), but not in wild-type (WT) cells, indicating a negative effect of RCAN1 on vesicle recycling and endocytosis. Acute exposure to calcineurin inhibitors, cyclosporine A and FK-506, replicates this effect in WT cells but has no additional effect in RCAN1(ox) cells. When we chronically expose WT cells to cyclosporine A and FK-506 we find that catecholamine release per vesicle and pre-spike foot (PSF) signal parameters are decreased, similar to that in RCAN1(ox) cells. Inhibiting calcineurin activity in RCAN1(ox) cells has no additional effect on the amount of catecholamine release per vesicle but further reduces PSF signal parameters. Although electron microscopy studies indicate these changes are not because of altered vesicle number or distribution in RCAN1(ox) cells, the smaller vesicle and dense core size we observe in RCAN1(ox) cells may underlie the reduced quantal release in these cells. Thus, our results indicate that RCAN1 most likely affects vesicle recycling and quantal release kinetics via the inhibition of calcineurin activity.

  9. A controlled release system of titanocene dichloride by electrospun fiber and its antitumor activity in vitro.

    PubMed

    Chen, Ping; Wu, Qing-Sheng; Ding, Ya-Ping; Chu, Maoquan; Huang, Zheng-Ming; Hu, Wen

    2010-11-01

    In order to improve both safety and efficacy of cancer chemotherapy of titanocene dichloride and overcome the shortcomings such as instability and short half-life in the human body, we report a controlled release system of titanocene dichloride by electrospun fiber and its in vitro antitumor activity against human lung tumor spca-1 cells. The system was developed by electrospinning. The release profiles of titanocene dichloride in PBS were researched by UV-Vis spectrophotometer. In vitro antitumor activities of the fibers were examined by MTT method. Titanocene dichloride was well incorporated in biodegradable poly(L-lactic acid) fibers. XRD results suggest that titanocene dichloride exists in the amorphous form in the fibers. The controlled release of titanocene dichloride can be gained for long time. MTT showed actual titanocene dichloride content 40, 80, 160 and 240 mg/L from the fibers mat, cell growth inhibition rates of 11.2%, 22.1%, 44.2% and 68.2% were achieved, respectively. The titanocene dichloride released has obvious inhibition effect against lung tumor cells. The system has an effect of controlled release of titanocene dichloride and may be used as an implantable anticancer drug in clinical applications in the future.

  10. Fission product release and survivability of UN-kernel LWR TRISO fuel

    NASA Astrophysics Data System (ADS)

    Besmann, T. M.; Ferber, M. K.; Lin, H.-T.; Collin, B. P.

    2014-05-01

    A thermomechanical assessment of the LWR application of TRISO fuel with UN kernels was performed. Fission product release under operational and transient temperature conditions was determined by extrapolation from fission product recoil calculations and limited data from irradiated UN pellets. Both fission recoil and diffusive release were considered and internal particle pressures computed for both 650 and 800 μm diameter kernels as a function of buffer layer thickness. These pressures were used in conjunction with a finite element program to compute the radial and tangential stresses generated within a TRISO particle undergoing burnup. Creep and swelling of the inner and outer pyrolytic carbon layers were included in the analyses. A measure of reliability of the TRISO particle was obtained by computing the probability of survival of the SiC barrier layer and the maximum tensile stress generated in the pyrolytic carbon layers from internal pressure and thermomechanics of the layers. These reliability estimates were obtained as functions of the kernel diameter, buffer layer thickness, and pyrolytic carbon layer thickness. The value of the probability of survival at the end of irradiation was inversely proportional to the maximum pressure.

  11. Fission product release and survivability of UN-kernel LWR TRISO fuel

    SciTech Connect

    T. M. Besmann; M. K. Ferber; H.-T. Lin; B. P. Collin

    2014-05-01

    A thermomechanical assessment of the LWR application of TRISO fuel with UN kernels was performed. Fission product release under operational and transient temperature conditions was determined by extrapolation from fission product recoil calculations and limited data from irradiated UN pellets. Both fission recoil and diffusive release were considered and internal particle pressures computed for both 650 and 800 um diameter kernels as a function of buffer layer thickness. These pressures were used in conjunction with a finite element program to compute the radial and tangential stresses generated within a TRISO particle undergoing burnup. Creep and swelling of the inner and outer pyrolytic carbon layers were included in the analyses. A measure of reliability of the TRISO particle was obtained by computing the probability of survival of the SiC barrier layer and the maximum tensile stress generated in the pyrolytic carbon layers from internal pressure and thermomechanics of the layers. These reliability estimates were obtained as functions of the kernel diameter, buffer layer thickness, and pyrolytic carbon layer thickness. The value of the probability of survival at the end of irradiation was inversely proportional to the maximum pressure.

  12. Remote modulation of neural activities via near-infrared triggered release of biomolecules.

    PubMed

    Li, Wei; Luo, Rongcong; Lin, Xudong; Jadhav, Amol D; Zhang, Zicong; Yan, Li; Chan, Chung-Yuan; Chen, Xianfeng; He, Jufang; Chen, Chia-Hung; Shi, Peng

    2015-10-01

    The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically

  13. Phosphatidylinositol turnover (PI) during synaptic activation results from the release of a stimulatory and in inhibitory agonist

    SciTech Connect

    Bencherif, M.; Rubio, R.; Berne, R.M.

    1986-03-05

    PI has been implicated in the process of synaptic transmission and is increased by agonists. It has been suggested that PI is involved in cellular Ca/sup + +/ mobilization and the process represents a series of hydrolytic reactions with inositol as the final product. Hence, the rate of release of /sup 3/H-inositol (/sup 3/H-Ins) from prelabelled inositol phospholipids can be used as an index of PI. In the /sup 3/H-inositol prelabelled frog sympathetic ganglia, they studied the effect of synaptic activity on PI. PI did not change during orthodromic stimulation (20 Hz, 5 min). However, upon cessation of the stimulation, PI increased rapidly and remained elevated for at least 30 min. This increase in PI was reduced by suffusing the ganglia with either acetylcholine or adenosine. In the presence of atropine (5 ..mu..M), orthodromic stimulation increased PI. They hypothesized that synaptic activation releases a long-lasting stimulatory agonist and a short-lived inhibitory (Ach/adenosine) agonist(s) affecting PI. To test this idea, 2 sympathetic ganglia were used. One was prelabelled with /sup 3/H-inositol and the other was not. The two ganglia were placed together in a 5 ..mu..l drop of Ringers solution containing atropine. Orthodromic stimuli were applied to the non-labelled ganglion and elicited release of /sup 3/H-Ins from the non-stimulated ganglion.

  14. Interaction of urokinase A chain with the receptor of human keratinocytes stimulates release of urokinase-like plasminogen activator

    SciTech Connect

    Fibbi, G.; Magnelli, L.; Pucci, M.; Del Rosso, M. )

    1990-03-01

    On the basis of a fibrinolytic assay with {sup 125}I-fibrin, zymography, and immunoprobing with anti-human urokinase antibody, the authors have observed that the in vitro established NCTC human keratinocyte cell line releases into the culture medium a 54,000-Da plasminogen activator which is indistinguishable from human urokinase. Only the early release following the washing of keratinocyte monolayers is accounted for by secretion of preformed enzyme, while late secretory events require the de novo synthesis of urokinase. The released enzyme can interact by autocriny with its own receptor present on keratinocytes. The addition to the keratinocyte culture medium of the urokinase A chain can stimulate a concentration-dependent urokinase oversecretion, which is not paralleled by oversecretion of plasminogen activator inhibitor-1. Since stimulation of urokinase production can be obtained by an A chain concentration which was previously shown to be efficient in inducing keratinocyte mobilization in an in vitro migration model system, they hypothesize that this mechanism may be important in vivo during the process of wound repair.

  15. Tonically active protein kinase A regulates neurotransmitter release at the squid giant synapse

    PubMed Central

    Hilfiker, Sabine; Czernik, Andrew J; Greengard, Paul; Augustine, George J

    2001-01-01

    Electrophysiological and microinjection methods were used to examine the role of cyclic AMP-dependent protein kinase A (PKA) in regulating transmitter release at the squid giant synapse. Excitatory postsynaptic potentials (EPSPs) evoked by presynaptic action potentials were not affected by presynaptic injection of an exogenous active catalytic subunit of mammalian PKA. In contrast, presynaptic injection of PKI-amide, a peptide that inhibits PKA with high potency and specificity, led to a reversible inhibition of EPSPs. Injection of several other peptides that serve as substrates for PKA also reversibly inhibited neurotransmitter release. The ability of these peptides to inhibit release was correlated with their ability to serve as PKA substrates, suggesting that these peptides act by competing with endogenous substrates for phosphorylation by active endogenous PKA. We suggest that the phosphorylation of PKA substrates is maintained at a relatively high state under basal conditions and that this tonic activity of PKA is to a large degree required for evoked neurotransmitter release at the squid giant presynaptic terminal. PMID:11179398

  16. Tonically active protein kinase A regulates neurotransmitter release at the squid giant synapse.

    PubMed

    Hilfiker, S; Czernik, A J; Greengard, P; Augustine, G J

    2001-02-15

    1. Electrophysiological and microinjection methods were used to examine the role of cyclic AMP-dependent protein kinase A (PKA) in regulating transmitter release at the squid giant synapse. 2. Excitatory postsynaptic potentials (EPSPs) evoked by presynaptic action potentials were not affected by presynaptic injection of an exogenous active catalytic subunit of mammalian PKA. 3. In contrast, presynaptic injection of PKI-amide, a peptide that inhibits PKA with high potency and specificity, led to a reversible inhibition of EPSPs. 4. Injection of several other peptides that serve as substrates for PKA also reversibly inhibited neurotransmitter release. The ability of these peptides to inhibit release was correlated with their ability to serve as PKA substrates, suggesting that these peptides act by competing with endogenous substrates for phosphorylation by active endogenous PKA. 5. We suggest that the phosphorylation of PKA substrates is maintained at a relatively high state under basal conditions and that this tonic activity of PKA is to a large degree required for evoked neurotransmitter release at the squid giant presynaptic terminal.

  17. NIR-Activated Content Release from Plasmon Resonant Liposomes for Probing Single-Cell Responses

    PubMed Central

    Leung, Sarah J.

    2013-01-01

    Technological limitations have prevented the interrogation and manipulation of cellular activity in response to bioactive molecules within model and living systems that is required for the development of diagnostic and treatment modalities for diseases, such as cancer. In this work, we demonstrate that gold-coated liposomes are capable of encapsulation and on-demand release of signaling molecules with a spatial and temporal resolution leading to activation of individual cells. As a model system, we used cells modified to overexpress a certain G-protein coupled receptor, the CCK2 receptor, and achieved its activation in a single cell via the localized release of its agonist. This content release was triggered by illumination of the liposomes at wavelengths corresponding to the plasmon resonance of the gold coating. The use of plasmon resonant liposomes may enable on-demand release of a broad range of molecules using biologically safe near infrared light and without molecule chemical modification. In combination with the spectral tunability of plasmon resonant coating, this technology may allow for multiplexed interrogation of complex and diverse signaling pathways in model or living tissues with unprecedented spatial and temporal control. PMID:23106797

  18. Feruloyl esterases as a tool for the release of phenolic compounds from agro-industrial by-products.

    PubMed

    Benoit, Isabelle; Navarro, David; Marnet, Nathalie; Rakotomanomana, Nnjara; Lesage-Meessen, Laurence; Sigoillot, Jean-Claude; Asther, Marcel; Asther, Michèle

    2006-08-14

    Agro-industrial by-products are a potential source of added-value phenolic acids with promising applications in the food and pharmaceutical industries. Here two purified feruloyl esterases from Aspergillus niger, FAEA and FAEB were tested for their ability to release phenolic acids such as caffeic acid, p-coumaric acid and ferulic acid from coffee pulp, apple marc and wheat straw. Their hydrolysis activity was evaluated and compared with their action on maize bran and sugar beet pulp. The specificity of both enzymes against natural and synthetic substrates was evaluated; particular attention was paid to quinic esters and lignin monomers. The efficiency of both enzymes on model substrates was studied. We show the ability of these enzymes to hydrolyze quinic esters and ester linkages between phenolic acids and lignin monomer.

  19. Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward

    PubMed Central

    Stouffer, Melissa A.; Woods, Catherine A.; Patel, Jyoti C.; Lee, Christian R.; Witkovsky, Paul; Bao, Li; Machold, Robert P.; Jones, Kymry T.; de Vaca, Soledad Cabeza; Reith, Maarten E. A.; Carr, Kenneth D.; Rice, Margaret E.

    2015-01-01

    Insulin activates insulin receptors (InsRs) in the hypothalamus to signal satiety after a meal. However, the rising incidence of obesity, which results in chronically elevated insulin levels, implies that insulin may also act in brain centres that regulate motivation and reward. We report here that insulin can amplify action potential-dependent dopamine (DA) release in the nucleus accumbens (NAc) and caudate–putamen through an indirect mechanism that involves striatal cholinergic interneurons that express InsRs. Furthermore, two different chronic diet manipulations in rats, food restriction (FR) and an obesogenic (OB) diet, oppositely alter the sensitivity of striatal DA release to insulin, with enhanced responsiveness in FR, but loss of responsiveness in OB. Behavioural studies show that intact insulin levels in the NAc shell are necessary for acquisition of preference for the flavour of a paired glucose solution. Together, these data imply that striatal insulin signalling enhances DA release to influence food choices. PMID:26503322

  20. Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward.

    PubMed

    Stouffer, Melissa A; Woods, Catherine A; Patel, Jyoti C; Lee, Christian R; Witkovsky, Paul; Bao, Li; Machold, Robert P; Jones, Kymry T; de Vaca, Soledad Cabeza; Reith, Maarten E A; Carr, Kenneth D; Rice, Margaret E

    2015-01-01

    Insulin activates insulin receptors (InsRs) in the hypothalamus to signal satiety after a meal. However, the rising incidence of obesity, which results in chronically elevated insulin levels, implies that insulin may also act in brain centres that regulate motivation and reward. We report here that insulin can amplify action potential-dependent dopamine (DA) release in the nucleus accumbens (NAc) and caudate-putamen through an indirect mechanism that involves striatal cholinergic interneurons that express InsRs. Furthermore, two different chronic diet manipulations in rats, food restriction (FR) and an obesogenic (OB) diet, oppositely alter the sensitivity of striatal DA release to insulin, with enhanced responsiveness in FR, but loss of responsiveness in OB. Behavioural studies show that intact insulin levels in the NAc shell are necessary for acquisition of preference for the flavour of a paired glucose solution. Together, these data imply that striatal insulin signalling enhances DA release to influence food choices. PMID:26503322

  1. Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward.

    PubMed

    Stouffer, Melissa A; Woods, Catherine A; Patel, Jyoti C; Lee, Christian R; Witkovsky, Paul; Bao, Li; Machold, Robert P; Jones, Kymry T; de Vaca, Soledad Cabeza; Reith, Maarten E A; Carr, Kenneth D; Rice, Margaret E

    2015-10-27

    Insulin activates insulin receptors (InsRs) in the hypothalamus to signal satiety after a meal. However, the rising incidence of obesity, which results in chronically elevated insulin levels, implies that insulin may also act in brain centres that regulate motivation and reward. We report here that insulin can amplify action potential-dependent dopamine (DA) release in the nucleus accumbens (NAc) and caudate-putamen through an indirect mechanism that involves striatal cholinergic interneurons that express InsRs. Furthermore, two different chronic diet manipulations in rats, food restriction (FR) and an obesogenic (OB) diet, oppositely alter the sensitivity of striatal DA release to insulin, with enhanced responsiveness in FR, but loss of responsiveness in OB. Behavioural studies show that intact insulin levels in the NAc shell are necessary for acquisition of preference for the flavour of a paired glucose solution. Together, these data imply that striatal insulin signalling enhances DA release to influence food choices.

  2. Antioxidant activity and nutrient release from polyphenol-enriched cheese in a simulated gastrointestinal environment.

    PubMed

    Lamothe, Sophie; Langlois, Ariane; Bazinet, Laurent; Couillard, Charles; Britten, Michel

    2016-03-01

    Green tea polyphenols are recognized for their antioxidant properties and their effects on lipid digestion kinetics. Polyphenols are sensitive to degradation in the intestinal environment. Interactions with dairy proteins could modulate the stability and biological activity of polyphenols during digestion. The objective of this study was to evaluate the release of nutrients (polyphenols, fatty acids and peptides) and the antioxidant activity in polyphenol-enriched cheese containing different levels of calcium in a simulated gastrointestinal environment. The relationship between cheese matrix texture, matrix degradation and nutrient release during digestion was also studied. Green tea extract was added to milk at 0% or 0.1%, and cheeses were produced on a laboratory scale. The level of available calcium was adjusted to low (Ca(low)), regular (Ca(reg)) or high (Ca(high)) during the salting step of the cheese-making process. Cheeses were subjected to simulated digestion. The rate and extent of fatty acid release were 21% lower for Ca(low) cheese than for Ca(reg) and Ca(high) cheeses. The greater adhesiveness of Ca(low) cheese, which resulted in lower rates of matrix degradation and proteolysis, contributed to the reduced rate of lipolysis. The presence of green tea extract in cheese reduced the release of free fatty acids at the end of digestion by 7%. The addition of green tea extract increased cheese hardness but did not influence matrix degradation or proteolysis profiles. The formation of complexes between tea polyphenols and proteins within the cheese matrix resulted in a more than twofold increase in polyphenol recovery in the intestinal phase compared with the control (tea polyphenol extract incubated with polyphenol-free cheese). Antioxidant activity was 14% higher in the digest from polyphenol-enriched cheese than in the control. These results suggest that cheese is an effective matrix for the controlled release of nutrients and for the protection of green

  3. Health Effects of Cut Gas Lines and Other Petroleum Product Release Incidents - Seven States, 2010-2012.

    PubMed

    Anderson, Ayana R

    2015-06-12

    Large mass casualty gas explosions and catastrophic oil spills are widely reported and receive considerable regulatory attention. Smaller, less catastrophic petroleum product releases are less likely to receive publicity, although study of these incidents might help focus and prioritize prevention efforts. To describe the causes and health impacts of petroleum product release incidents (including gas explosions and oil spills), the Agency for Toxic Substances and Disease Registry (ATSDR) analyzed 2010-2012 data from the National Toxic Substance Incidents Program (NTSIP). A total of 1,369 petroleum product release incidents were reported from seven states, resulting in 512 injuries and 36 deaths. Approximately one fourth of the incidents were associated with utilities, and approximately one fifth were associated with private vehicles or residences. Approximately 10% of petroleum product releases resulted from inadvertent damage to utility lines. Understanding the characteristics of acute petroleum product releases can aid the public and utility workers in the development of preventive strategies and reduce the morbidity and mortality associated with such releases.

  4. Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production

    SciTech Connect

    Duan, Erzhen; Wang, Dang; Luo, Rui; Luo, Jingyi; Gao, Li; Chen, Huanchun; Fang, Liurong Xiao, Shaobo

    2014-11-15

    The high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC-145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV replication, HMGB1 promotes PRRSV-induced NF-κB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection. - Highlights: • PRRSV infection triggers HMGB1 release from MARC-145 cells and PAMs. • HMGB1 does not significantly affect PRRSV proliferation. • HMGB1 is involved in PRRSV-induced NF-κB activation and inflammatory responses. • HMGB1 promotes PRRSV-induced inflammatory responses through TLR2/4 and RAGE.

  5. Soft computing analysis of the possible correlation between temporal and energy release patterns in seismic activity

    NASA Astrophysics Data System (ADS)

    Konstantaras, Anthony; Katsifarakis, Emmanouil; Artzouxaltzis, Xristos; Makris, John; Vallianatos, Filippos; Varley, Martin

    2010-05-01

    This paper is a preliminary investigation of the possible correlation of temporal and energy release patterns of seismic activity involving the preparation processes of consecutive sizeable seismic events [1,2]. The background idea is that during periods of low-level seismic activity, stress processes in the crust accumulate energy at the seismogenic area whilst larger seismic events act as a decongesting mechanism releasing considerable energy [3,4]. A dynamic algorithm is being developed aiming to identify and cluster pre- and post- seismic events to the main earthquake following on research carried out by Zubkov [5] and Dobrovolsky [6,7]. This clustering technique along with energy release equations dependent on Richter's scale [8,9] allow for an estimate to be drawn regarding the amount of the energy being released by the seismic sequence. The above approach is being implemented as a monitoring tool to investigate the behaviour of the underlying energy management system by introducing this information to various neural [10,11] and soft computing models [1,12,13,14]. The incorporation of intelligent systems aims towards the detection and simulation of the possible relationship between energy release patterns and time-intervals among consecutive sizeable earthquakes [1,15]. Anticipated successful training of the imported intelligent systems may result in a real-time, on-line processing methodology [1,16] capable to dynamically approximate the time-interval between the latest and the next forthcoming sizeable seismic event by monitoring the energy release process in a specific seismogenic area. Indexing terms: pattern recognition, long-term earthquake precursors, neural networks, soft computing, earthquake occurrence intervals References [1] Konstantaras A., Vallianatos F., Varley M.R. and Makris J. P.: ‘Soft computing modelling of seismicity in the southern Hellenic arc', IEEE Geoscience and Remote Sensing Letters, vol. 5 (3), pp. 323-327, 2008 [2] Eneva M. and

  6. Alternaria extract activates autophagy that induces IL-18 release from airway epithelial cells.

    PubMed

    Murai, Hiroki; Okazaki, Shintaro; Hayashi, Hisako; Kawakita, Akiko; Hosoki, Koa; Yasutomi, Motoko; Sur, Sanjiv; Ohshima, Yusei

    2015-09-01

    Alternaria alternata is a major outdoor allergen that causes allergic airway diseases. Alternaria extract (ALT-E) has been shown to induce airway epithelial cells to release IL-18 and thereby initiate Th2-type responses. We investigated the underlying mechanisms involved in IL-18 release from ALT-E-stimulated airway epithelial cells. Normal human bronchial epithelial cells and A549 human lung adenocarcinoma cells were stimulated with ALT-E in the presence of different inhibitors of autophagy or caspases. IL-18 levels in culture supernatants were measured by ELISA. The numbers of autophagosomes, an LC3-I to LC3-II conversion, and p62 degradation were determined by immunofluorescence staining and immunoblotting. 3-methyladenine and bafilomycin, which inhibit the formation of preautophagosomal structures and autolysosomes, respectively, suppressed ALT-E-induced IL-18 release by cells, whereas caspase 1 and 8 inhibitors did not. ALT-E-stimulation increased autophagosome formation, LC-3 conversion, and p62 degradation in airway epithelial cells. LPS-stimulation induced the LC3 conversion in A549 cells, but did not induce IL-18 release or p62 degradation. Unlike LPS, ALT-E induced airway epithelial cells to release IL-18 via an autophagy dependent, caspase 1 and 8 independent pathway. Although autophagy has been shown to negatively regulate canonical inflammasome activity in TLR-stimulated macrophages, our data indicates that this process is an unconventional mechanism of IL-18 secretion by airway epithelial cells.

  7. Fouling-release and chemical activity effects of a siloxane-based material on tunicates.

    PubMed

    Filip, Natalia; Pustam, Amanda; Ells, Veronica; Grosicki, Kathleen M T; Yang, Jin; Oguejiofor, Ikenna; Bishop, Cory D; DeMont, M Edwin; Smith-Palmer, Truis; Wyeth, Russell C

    2016-05-01

    The antifouling performance of a siloxane-based elastomeric impression material (EIM) was compared to that of two silicone fouling-release coatings, Intersleek 757 and RTV-11. In field immersion trials, the EIM caused the greatest reduction in fouling by the solitary tunicate Ciona intestinalis and caused the longest delay in the progression of fouling by two species of colonial tunicate. However, in pseudobarnacle adhesion tests, the EIM had higher attachment strengths. Further laboratory analyses showed that the EIM leached alkylphenol ethoxylates (APEs) that were toxic to C. intestinalis larvae. The EIM thus showed the longest duration of chemical activity measured to date for a siloxane-based coating (4 months), supporting investigations of fouling-release coatings that release targeted biocides. However, due to potential widespread effects of APEs, the current EIM formulation should not be considered as an environmentally-safe antifoulant. Thus, the data also emphasize consideration of both immediate and long-term effects of potentially toxic constituents released from fouling-release coatings. PMID:26986763

  8. Magnetic field activated lipid-polymer hybrid nanoparticles for stimuli-responsive drug release.

    PubMed

    Kong, Seong Deok; Sartor, Marta; Hu, Che-Ming Jack; Zhang, Weizhou; Zhang, Liangfang; Jin, Sungho

    2013-03-01

    Stimuli-responsive nanoparticles (SRNPs) offer the potential of enhancing the therapeutic efficacy and minimizing the side-effects of chemotherapeutics by controllably releasing the encapsulated drug at the target site. Currently controlled drug release through external activation remains a major challenge during the delivery of therapeutic agents. Here we report a lipid-polymer hybrid nanoparticle system containing magnetic beads for stimuli-responsive drug release using a remote radio frequency (RF) magnetic field. These hybrid nanoparticles show long-term stability in terms of particle size and polydispersity index in phosphate-buffered saline (PBS). Controllable loading of camptothecin (CPT) and Fe(3)O(4) in the hybrid nanoparticles was demonstrated. RF-controlled drug release from these nanoparticles was observed. In addition, cellular uptake of the SRNPs into MT2 mouse breast cancer cells was examined. Using CPT as a model anticancer drug the nanoparticles showed a significant reduction in MT2 mouse breast cancer cell growth in vitro in the presence of a remote RF field. The ease of preparation, stability, and controllable drug release are the strengths of the platform and provide the opportunity to improve cancer chemotherapy.

  9. Luteinizing hormone release and androgen production of avian hybrids in response to luteinizing hormone releasing hormone injection.

    PubMed

    Mathis, G F; Burke, W H; McDougald, L R

    1983-04-01

    The levels of luteinizing hormone (LH) and androgens were measured in sterile avian hybrids. Guinea fowl-chicken and peafowl-guinea fowl hybrids were bled before and after injection with LH- releasing hormone (LHRH). The preinjection LH levels for the guinea fowl-chicken hybrids were below or at the very lower limit of the assay sensitivity and the peafowl-guinea fowl hybrids averaged 1.3 ng/ml. Within 10 min after LHRH injection, LH had increased dramatically in both hybrids and then began to slowly decline. Androgen levels in the guinea fowl-chicken hybrids increased from 16.2 pg/ml to 95.2 pg/ml and continued to increase, reaching 287 pg/ml at the last bleeding 60 min after injection.

  10. Luteinizing hormone release and androgen production of avian hybrids in response to luteinizing hormone releasing hormone injection.

    PubMed

    Mathis, G F; Burke, W H; McDougald, L R

    1983-04-01

    The levels of luteinizing hormone (LH) and androgens were measured in sterile avian hybrids. Guinea fowl-chicken and peafowl-guinea fowl hybrids were bled before and after injection with LH- releasing hormone (LHRH). The preinjection LH levels for the guinea fowl-chicken hybrids were below or at the very lower limit of the assay sensitivity and the peafowl-guinea fowl hybrids averaged 1.3 ng/ml. Within 10 min after LHRH injection, LH had increased dramatically in both hybrids and then began to slowly decline. Androgen levels in the guinea fowl-chicken hybrids increased from 16.2 pg/ml to 95.2 pg/ml and continued to increase, reaching 287 pg/ml at the last bleeding 60 min after injection. PMID:6346309

  11. Activated platelets release sphingosine 1-phosphate and induce hypersensitivity to noxious heat stimuli in vivo

    PubMed Central

    Weth, Daniela; Benetti, Camilla; Rauch, Caroline; Gstraunthaler, Gerhard; Schmidt, Helmut; Geisslinger, Gerd; Sabbadini, Roger; Proia, Richard L.; Kress, Michaela

    2015-01-01

    At the site of injury activated platelets release various mediators, one of which is sphingosine 1-phosphate (S1P). It was the aim of this study to explore whether activated human platelets had a pronociceptive effect in an in vivo mouse model and whether this effect was based on the release of S1P and subsequent activation of neuronal S1P receptors 1 or 3. Human platelets were prepared in different concentrations (105/μl, 106/μl, 107/μl) and assessed in mice with different genetic backgrounds (WT, S1P1fl/fl, SNS-S1P1−/−, S1P3−/−). Intracutaneous injections of activated human platelets induced a significant, dose-dependent hypersensitivity to noxious thermal stimulation. The degree of heat hypersensitivity correlated with the platelet concentration as well as the platelet S1P content and the amount of S1P released upon platelet activation as measured with LC MS/MS. Despite the significant correlations between S1P and platelet count, no difference in paw withdrawal latency (PWL) was observed in mice with a global null mutation of the S1P3 receptor or a conditional deletion of the S1P1 receptor in nociceptive primary afferents. Furthermore, neutralization of S1P with a selective anti-S1P antibody did not abolish platelet induced heat hypersensitivity. Our results suggest that activated platelets release S1P and induce heat hypersensitivity in vivo. However, the platelet induced heat hypersensitivity was caused by mediators other than S1P. PMID:25954148

  12. Sum Product Networks for Activity Recognition.

    PubMed

    Amer, Mohamed R; Todorovic, Sinisa

    2016-04-01

    This paper addresses detection and localization of human activities in videos. We focus on activities that may have variable spatiotemporal arrangements of parts, and numbers of actors. Such activities are represented by a sum-product network (SPN). A product node in SPN represents a particular arrangement of parts, and a sum node represents alternative arrangements. The sums and products are hierarchically organized, and grounded onto space-time windows covering the video. The windows provide evidence about the activity classes based on the Counting Grid (CG) model of visual words. This evidence is propagated bottom-up and top-down to parse the SPN graph for the explanation of the video. The node connectivity and model parameters of SPN and CG are jointly learned under two settings, weakly supervised, and supervised. For evaluation, we use our new Volleyball dataset, along with the benchmark datasets VIRAT, UT-Interactions, KTH, and TRECVID MED 2011. Our video classification and activity localization are superior to those of the state of the art on these datasets.

  13. Carbon dioxide absorption and release properties of pyrolysis products of dolomite calcined in vacuum atmosphere.

    PubMed

    Wang, Fei; Kuzuya, Toshihiro; Hirai, Shinji; Li, Jihua; Li, Te

    2014-01-01

    The decomposition of dolomite into CaO and MgO was performed at 1073 K in vacuum and at 1273 K in an Ar atmosphere. The dolomite calcined in vacuum was found to have a higher specific surface area and a higher micropore volume when compared to the dolomite calcined in the Ar atmosphere. These pyrolysis products of dolomite were reacted with CO2 at 673 K for 21.6 ks. On the absorption of CO2, the formation of CaCO3 was observed. The degree of absorption of the dolomite calcined in vacuum was determined to be above 50%, which was higher than the degree of absorption of the dolomite calcined in the Ar atmosphere. The CO2 absorption and release procedures were repeated three times for the dolomite calcined in vacuum. The specific surface area and micropore volume of calcined dolomite decreased with successive repetitions of the CO2 absorption and release cycles leading to a decrease in the degree of absorption of CO2. PMID:25136696

  14. Carbon Dioxide Absorption and Release Properties of Pyrolysis Products of Dolomite Calcined in Vacuum Atmosphere

    PubMed Central

    Wang, Fei; Kuzuya, Toshihiro; Hirai, Shinji; Li, Jihua; Li, Te

    2014-01-01

    The decomposition of dolomite into CaO and MgO was performed at 1073 K in vacuum and at 1273 K in an Ar atmosphere. The dolomite calcined in vacuum was found to have a higher specific surface area and a higher micropore volume when compared to the dolomite calcined in the Ar atmosphere. These pyrolysis products of dolomite were reacted with CO2 at 673 K for 21.6 ks. On the absorption of CO2, the formation of CaCO3 was observed. The degree of absorption of the dolomite calcined in vacuum was determined to be above 50%, which was higher than the degree of absorption of the dolomite calcined in the Ar atmosphere. The CO2 absorption and release procedures were repeated three times for the dolomite calcined in vacuum. The specific surface area and micropore volume of calcined dolomite decreased with successive repetitions of the CO2 absorption and release cycles leading to a decrease in the degree of absorption of CO2. PMID:25136696

  15. cAMP-dependent protein kinase activation decreases cytokine release in bronchial epithelial cells

    PubMed Central

    Poole, Jill A.; Nordgren, Tara M.; DeVasure, Jane M.; Heires, Art J.; Bailey, Kristina L.; Romberger, Debra J.

    2014-01-01

    Lung injury caused by inhalation of dust from swine-concentrated animal-feeding operations (CAFO) involves the release of inflammatory cytokine interleukin 8 (IL-8), which is mediated by protein kinase C-ε (PKC-ε) in airway epithelial cells. Once activated by CAFO dust, PKC-ε is responsible for slowing cilia beating and reducing cell migration for wound repair. Conversely, the cAMP-dependent protein kinase (PKA) stimulates contrasting effects, such as increased cilia beating and an acceleration of cell migration for wound repair. We hypothesized that a bidirectional mechanism involving PKA and PKC regulates epithelial airway inflammatory responses. To test this hypothesis, primary human bronchial epithelial cells and BEAS-2B cells were treated with hog dust extract (HDE) in the presence or absence of cAMP. PKC-ε activity was significantly reduced in cells that were pretreated for 1 h with 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP) before exposure to HDE (P < 0.05). HDE-induced IL-6, and IL-8 release was significantly lower in cells that were pretreated with 8-Br-cAMP (P < 0.05). To exclude exchange protein activated by cAMP (EPAC) involvement, cells were pretreated with either 8-Br-cAMP or 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8-CPT-2Me-cAMP) (EPAC agonist). 8-CPT-2Me-cAMP did not activate PKA and did not reduce HDE-stimulated IL-6 release. In contrast, 8-Br-cAMP decreased HDE-stimulated tumor necrosis factor (TNF)-α-converting enzyme (TACE; ADAM-17) activity and subsequent TNF-α release (P < 0.001). 8-Br-cAMP also blocked HDE-stimulated IL-6 and keratinocyte-derived chemokine release in precision-cut mouse lung slices (P < 0.05). These data show bidirectional regulation of PKC-ε via a PKA-mediated inhibition of TACE activity resulting in reduced PKC-ε-mediated release of IL-6 and IL-8. PMID:25150062

  16. cAMP-dependent protein kinase activation decreases cytokine release in bronchial epithelial cells.

    PubMed

    Wyatt, Todd A; Poole, Jill A; Nordgren, Tara M; DeVasure, Jane M; Heires, Art J; Bailey, Kristina L; Romberger, Debra J

    2014-10-15

    Lung injury caused by inhalation of dust from swine-concentrated animal-feeding operations (CAFO) involves the release of inflammatory cytokine interleukin 8 (IL-8), which is mediated by protein kinase C-ε (PKC-ε) in airway epithelial cells. Once activated by CAFO dust, PKC-ε is responsible for slowing cilia beating and reducing cell migration for wound repair. Conversely, the cAMP-dependent protein kinase (PKA) stimulates contrasting effects, such as increased cilia beating and an acceleration of cell migration for wound repair. We hypothesized that a bidirectional mechanism involving PKA and PKC regulates epithelial airway inflammatory responses. To test this hypothesis, primary human bronchial epithelial cells and BEAS-2B cells were treated with hog dust extract (HDE) in the presence or absence of cAMP. PKC-ε activity was significantly reduced in cells that were pretreated for 1 h with 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) before exposure to HDE (P < 0.05). HDE-induced IL-6, and IL-8 release was significantly lower in cells that were pretreated with 8-Br-cAMP (P < 0.05). To exclude exchange protein activated by cAMP (EPAC) involvement, cells were pretreated with either 8-Br-cAMP or 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8-CPT-2Me-cAMP) (EPAC agonist). 8-CPT-2Me-cAMP did not activate PKA and did not reduce HDE-stimulated IL-6 release. In contrast, 8-Br-cAMP decreased HDE-stimulated tumor necrosis factor (TNF)-α-converting enzyme (TACE; ADAM-17) activity and subsequent TNF-α release (P < 0.001). 8-Br-cAMP also blocked HDE-stimulated IL-6 and keratinocyte-derived chemokine release in precision-cut mouse lung slices (P < 0.05). These data show bidirectional regulation of PKC-ε via a PKA-mediated inhibition of TACE activity resulting in reduced PKC-ε-mediated release of IL-6 and IL-8. PMID:25150062

  17. Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

    SciTech Connect

    Deng Xue; Tamai, Riyoko; Endo, Yasuo; Kiyoura, Yusuke

    2009-02-15

    Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1{beta}, but not TNF{alpha}, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1{beta} production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1{beta} production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1{beta} induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1{beta} release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.

  18. Production of bromoform and dibromomethane by Giant Kelp: Factors affecting release and comparison to anthropogenic bromine sources

    USGS Publications Warehouse

    Goodwin, K.D.; North, W.J.; Lidstrom, M.E.

    1998-01-01

    Macrocystis pyrifera (Giant Kelp), a dominant macroalgal species in southern California, produced 171 ng per g fresh wt (gfwt) per day of CHBr3 and 48 ng gfwt-1 d-1 of CH2Br2 during laboratory incubations of whole blades. Comparable rates were measured during in situ incubations of intact fronds. Release of CHBr3 and CH2Br2 by M. pyrifera was affected by light and algal photosynthetic activity, suggesting that environmental factors influencing kelp physiology can affect halomethane release to the atmosphere. Data from H2O2 additions suggest that brominated methane production during darkness is limited by bromide oxidant supply. A bromine budget constructed for a region of southern California indicated that bromine emitted from the use of CH3Br as a fumigant (1 x 108 g Br yr-1) dominates macroalgal sources (3 x 106 g Br yr-1). Global projections, however, suggest that combined emissions of marine algae (including microalgae) contribute substantial amounts of bromine to the global cycle, perhaps on the same order of magnitude as anthropogenic sources.

  19. Determinants of carbon release from the active layer and permafrost deposits on the Tibetan Plateau

    PubMed Central

    Chen, Leiyi; Liang, Junyi; Qin, Shuqi; Liu, Li; Fang, Kai; Xu, Yunping; Ding, Jinzhi; Li, Fei; Luo, Yiqi; Yang, Yuanhe

    2016-01-01

    The sign and magnitude of permafrost carbon (C)-climate feedback are highly uncertain due to the limited understanding of the decomposability of thawing permafrost and relevant mechanistic controls over C release. Here, by combining aerobic incubation with biomarker analysis and a three-pool model, we reveal that C quality (represented by a higher amount of fast cycling C but a lower amount of recalcitrant C compounds) and normalized CO2–C release in permafrost deposits were similar or even higher than those in the active layer, demonstrating a high vulnerability of C in Tibetan upland permafrost. We also illustrate that C quality exerts the most control over CO2–C release from the active layer, whereas soil microbial abundance is more directly associated with CO2–C release after permafrost thaw. Taken together, our findings highlight the importance of incorporating microbial properties into Earth System Models when predicting permafrost C dynamics under a changing environment. PMID:27703168

  20. Comparative Mutagenesis Studies of Retinal Release in Light-Activated Zebrafish Rhodopsin Using Fluorescence Spectroscopy.

    PubMed

    Morrow, J M; Chang, B S W

    2015-07-28

    Rhodopsin is the visual pigment responsible for initiating scotopic (dim-light) vision in vetebrates. Once activated by light, release of all-trans-retinal from rhodopsin involves hydrolysis of the Schiff base linkage, followed by dissociation of retinal from the protein moiety. This kinetic process has been well studied in model systems such as bovine rhodopsin, but not in rhodopsins from cold-blooded animals, where physiological temperatures can vary considerably. Here, we characterize the rate of retinal release from light-activated rhodopsin in an ectotherm, zebrafish (Danio rerio), demonstrating in a fluorescence assay that this process occurs more than twice as fast as bovine rhodopsin at similar temperatures in 0.1% dodecyl maltoside. Using site-directed mutagenesis, we found that differences in retinal release rates can be attributed to a series of variable residues lining the retinal channel in three key structural motifs: an opening in metarhodopsin II between transmembrane helix 5 (TM5) and TM6, in TM3 near E122, and in the "retinal plug" formed by extracellular loop 2 (EL2). The majority of these sites are more proximal to the β-ionone ring of retinal than the Schiff base, indicating their influence on retinal release is more likely due to steric effects during retinal dissociation, rather than alterations to Schiff base stability. An Arrhenius plot of zebrafish rhodopsin was consistent with this model, inferring that the activation energy for Schiff base hydrolysis is similar to that of bovine rhodopsin. Functional variation at key sites identified in this study is consistent with the idea that retinal release might be an adaptive property of rhodopsin in vertebrates. Our study is one of the few investigating a nonmammalian rhodopsin, which will help establish a better understanding of the molecular mechanisms contributing to vision in cold-blooded vertebrates.

  1. Comparative Mutagenesis Studies of Retinal Release in Light-Activated Zebrafish Rhodopsin Using Fluorescence Spectroscopy.

    PubMed

    Morrow, J M; Chang, B S W

    2015-07-28

    Rhodopsin is the visual pigment responsible for initiating scotopic (dim-light) vision in vetebrates. Once activated by light, release of all-trans-retinal from rhodopsin involves hydrolysis of the Schiff base linkage, followed by dissociation of retinal from the protein moiety. This kinetic process has been well studied in model systems such as bovine rhodopsin, but not in rhodopsins from cold-blooded animals, where physiological temperatures can vary considerably. Here, we characterize the rate of retinal release from light-activated rhodopsin in an ectotherm, zebrafish (Danio rerio), demonstrating in a fluorescence assay that this process occurs more than twice as fast as bovine rhodopsin at similar temperatures in 0.1% dodecyl maltoside. Using site-directed mutagenesis, we found that differences in retinal release rates can be attributed to a series of variable residues lining the retinal channel in three key structural motifs: an opening in metarhodopsin II between transmembrane helix 5 (TM5) and TM6, in TM3 near E122, and in the "retinal plug" formed by extracellular loop 2 (EL2). The majority of these sites are more proximal to the β-ionone ring of retinal than the Schiff base, indicating their influence on retinal release is more likely due to steric effects during retinal dissociation, rather than alterations to Schiff base stability. An Arrhenius plot of zebrafish rhodopsin was consistent with this model, inferring that the activation energy for Schiff base hydrolysis is similar to that of bovine rhodopsin. Functional variation at key sites identified in this study is consistent with the idea that retinal release might be an adaptive property of rhodopsin in vertebrates. Our study is one of the few investigating a nonmammalian rhodopsin, which will help establish a better understanding of the molecular mechanisms contributing to vision in cold-blooded vertebrates. PMID:26098991

  2. Potential Impacts of Reductions in Refinery Activity on Northeast Petroleum Product Markets

    EIA Publications

    2012-01-01

    Potential Impacts of Reductions in Refinery Activity on Northeast Petroleum Product Markets is an update to a previous Energy Information Administration (EIA) report, Reductions in Northeast Refining Activity: Potential Implications for Petroleum Product Markets, released in December 2011. This update analyzes possible market responses and impacts in the event Sunoco's Philadelphia refinery closes this summer, in addition to the recently idled refineries on the East Coast and in the U.S. Virgin Islands.

  3. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity.

    PubMed

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections.

  4. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity

    PubMed Central

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  5. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity.

    PubMed

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  6. Fission product partitioning in aerosol release from simulated spent nuclear fuel

    NASA Astrophysics Data System (ADS)

    Di Lemma, F. G.; Colle, J. Y.; Rasmussen, G.; Konings, R. J. M.

    2015-10-01

    Aerosols created by the vaporization of simulated spent nuclear fuel (simfuel) were produced by laser heating techniques and characterised by a wide range of post-analyses. In particular attention has been focused on determining the fission product behaviour in the aerosols, in order to improve the evaluation of the source term and consequently the risk associated with release from spent fuel sabotage or accidents. Different simulated spent fuels were tested with burn-up up to 8 at. %. The results from the aerosol characterisation were compared with studies of the vaporization process by Knudsen Effusion Mass Spectrometry and thermochemical equilibrium calculations. These studies permit an understanding of the aerosol gaseous precursors and the gaseous reactions taking place during the aerosol formation process.

  7. Phospholipid Ozonation Products Activate the 5-Lipoxygenase Pathway in Macrophages.

    PubMed

    Zemski Berry, Karin A; Murphy, Robert C

    2016-08-15

    Ozone is a highly reactive environmental toxicant that can react with the double bonds of lipids in pulmonary surfactant. This study was undertaken to investigate the proinflammatory properties of the major lipid-ozone product in pulmonary surfactant, 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (16:0/9al-PC), with respect to eicosanoid production. A dose-dependent increase in the formation of 5-lipoxygenase (5-LO) products was observed in murine resident peritoneal macrophages (RPM) and alveolar macrophages (AM) upon treatment with 16:0/9al-PC. In contrast, the production of cyclooxygenase (COX) derived eicosanoids did not change from basal levels in the presence of 16:0/9al-PC. When 16:0/9al-PC and the TLR2 ligand, zymosan, were added to RPM or AM, an enhancement of 5-LO product formation along with a concomitant decrease in COX product formation was observed. Neither intracellular calcium levels nor arachidonic acid release was influenced by the addition of 16:0/9al-PC to RPM. Results from mitogen-activated protein kinase (MAPK) inhibitor studies and direct measurement of phosphorylation of MAPKs revealed that 16:0/9al-PC activates the p38 MAPK pathway in RPM, which results in the activation of 5-LO. Our results indicate that 16:0/9al-PC has a profound effect on the eicosanoid pathway, which may have implications in inflammatory pulmonary disease states where eicosanoids have been shown to play a role. PMID:27448436

  8. Maximum reasonable radioxenon releases from medical isotope production facilities and their effect on monitoring nuclear explosions.

    PubMed

    Bowyer, Theodore W; Kephart, Rosara; Eslinger, Paul W; Friese, Judah I; Miley, Harry S; Saey, Paul R J

    2013-01-01

    Fission gases such as (133)Xe are used extensively for monitoring the world for signs of nuclear testing in systems such as the International Monitoring System (IMS). These gases are also produced by nuclear reactors and by fission production of (99)Mo for medical use. Recently, medical isotope production facilities have been identified as the major contributor to the background of radioactive xenon isotopes (radioxenon) in the atmosphere (Stocki et al., 2005; Saey, 2009). These releases pose a potential future problem for monitoring nuclear explosions if not addressed. As a starting point, a maximum acceptable daily xenon emission rate was calculated, that is both scientifically defendable as not adversely affecting the IMS, but also consistent with what is possible to achieve in an operational environment. This study concludes that an emission of 5 × 10(9) Bq/day from a medical isotope production facility would be both an acceptable upper limit from the perspective of minimal impact to monitoring stations, but also appears to be an achievable limit for large isotope producers. PMID:22995862

  9. Maximum reasonable radioxenon releases from medical isotope production facilities and their effect on monitoring nuclear explosions.

    PubMed

    Bowyer, Theodore W; Kephart, Rosara; Eslinger, Paul W; Friese, Judah I; Miley, Harry S; Saey, Paul R J

    2013-01-01

    Fission gases such as (133)Xe are used extensively for monitoring the world for signs of nuclear testing in systems such as the International Monitoring System (IMS). These gases are also produced by nuclear reactors and by fission production of (99)Mo for medical use. Recently, medical isotope production facilities have been identified as the major contributor to the background of radioactive xenon isotopes (radioxenon) in the atmosphere (Stocki et al., 2005; Saey, 2009). These releases pose a potential future problem for monitoring nuclear explosions if not addressed. As a starting point, a maximum acceptable daily xenon emission rate was calculated, that is both scientifically defendable as not adversely affecting the IMS, but also consistent with what is possible to achieve in an operational environment. This study concludes that an emission of 5 × 10(9) Bq/day from a medical isotope production facility would be both an acceptable upper limit from the perspective of minimal impact to monitoring stations, but also appears to be an achievable limit for large isotope producers.

  10. Release of asbestos fibers from weathered and corroded asbestos cement products

    SciTech Connect

    Spurny, K.R.

    1989-02-01

    The controversy on whether weathered and corroded asbestos cement products are emitting biologically significant asbestos fiber concentrations in ambient air has not been resolved. Nor is it known if the weathered and corroded asbestos cement products release asbestos fibers which have the same carcinogenic potency as standard chrysotile. The purpose of this research project was to develop a method for sampling and measuring asbestos fiber emissions from solid planar surfaces (i.e., roofs and facades) consisting of asbestos cement products and to develop methods for studying the physical and chemical changes and the carcinogenic potency of the emitted fibers. Using this method asbestos fiber emissions in ambient air have been measured in the FRG during 1984/1986. The emissions of asbestos fibers longer than 5 microns were in the range 10(6) to 10(8) fibers/m2.hr. The ambient air concentrations of these asbestos fibers were for the most part less than 10(3) fibers/m3. It was shown that the emitted asbestos fibers were chemically changed and it was shown with animal experiments that their carcinogenic potency did not differ from the carcinogenicity of standard chrysotile fibers.

  11. A Conserved Hydrophobic Core in Gαi1 Regulates G Protein Activation and Release from Activated Receptor.

    PubMed

    Kaya, Ali I; Lokits, Alyssa D; Gilbert, James A; Iverson, T M; Meiler, Jens; Hamm, Heidi E

    2016-09-01

    G protein-coupled receptor-mediated heterotrimeric G protein activation is a major mode of signal transduction in the cell. Previously, we and other groups reported that the α5 helix of Gαi1, especially the hydrophobic interactions in this region, plays a key role during nucleotide release and G protein activation. To further investigate the effect of this hydrophobic core, we disrupted it in Gαi1 by inserting 4 alanine amino acids into the α5 helix between residues Gln(333) and Phe(334) (Ins4A). This extends the length of the α5 helix without disturbing the β6-α5 loop interactions. This mutant has high basal nucleotide exchange activity yet no receptor-mediated activation of nucleotide exchange. By using structural approaches, we show that this mutant loses critical hydrophobic interactions, leading to significant rearrangements of side chain residues His(57), Phe(189), Phe(191), and Phe(336); it also disturbs the rotation of the α5 helix and the π-π interaction between His(57) and Phe(189) In addition, the insertion mutant abolishes G protein release from the activated receptor after nucleotide binding. Our biochemical and computational data indicate that the interactions between α5, α1, and β2-β3 are not only vital for GDP release during G protein activation, but they are also necessary for proper GTP binding (or GDP rebinding). Thus, our studies suggest that this hydrophobic interface is critical for accurate rearrangement of the α5 helix for G protein release from the receptor after GTP binding.

  12. Synaptic GABA release prevents GABA transporter type-1 reversal during excessive network activity

    PubMed Central

    Savtchenko, Leonid; Megalogeni, Maria; Rusakov, Dmitri A.; Walker, Matthew C.; Pavlov, Ivan

    2015-01-01

    GABA transporters control extracellular GABA, which regulates the key aspects of neuronal and network behaviour. A prevailing view is that modest neuronal depolarization results in GABA transporter type-1 (GAT-1) reversal causing non-vesicular GABA release into the extracellular space during intense network activity. This has important implications for GABA uptake-targeting therapies. Here we combined a realistic kinetic model of GAT-1 with experimental measurements of tonic GABAA receptor currents in ex vivo hippocampal slices to examine GAT-1 operation under varying network conditions. Our simulations predict that synaptic GABA release during network activity robustly prevents GAT-1 reversal. We test this in the 0 Mg2+ model of epileptiform discharges using slices from healthy and chronically epileptic rats and find that epileptiform activity is associated with increased synaptic GABA release and is not accompanied by GAT-1 reversal. We conclude that sustained efflux of GABA through GAT-1 is unlikely to occur during physiological or pathological network activity. PMID:25798861

  13. Active bio-based food-packaging: Diffusion and release of active substances through and from cellulose nanofiber coating toward food-packaging design.

    PubMed

    Lavoine, Nathalie; Guillard, Valérie; Desloges, Isabelle; Gontard, Nathalie; Bras, Julien

    2016-09-20

    Cellulose nanofibers (CNFs) were recently investigated for the elaboration of new functional food-packaging materials. Their nanoporous network was especially of interest for controlling the release of active species. Qualitative release studies were conducted, but quantification of the diffusion phenomenon observed when the active species are released from and through CNF coating has not yet been studied. Therefore, this work aims to model CNF-coated paper substrates as controlled release system for food-packaging using release data obtained for two model molecules, namely caffeine and chlorhexidine digluconate. The applied mathematical model - derived from Fickian diffusion - was validated for caffeine only. When the active species chemically interacts with the release device, another model is required as a non-predominantly diffusion-controlled release was observed. From caffeine modeling data, a theoretical active food-packaging material was designed. The use of CNFs as barrier coating was proved to be the ideal material configuration that best meets specifications. PMID:27261728

  14. Active bio-based food-packaging: Diffusion and release of active substances through and from cellulose nanofiber coating toward food-packaging design.

    PubMed

    Lavoine, Nathalie; Guillard, Valérie; Desloges, Isabelle; Gontard, Nathalie; Bras, Julien

    2016-09-20

    Cellulose nanofibers (CNFs) were recently investigated for the elaboration of new functional food-packaging materials. Their nanoporous network was especially of interest for controlling the release of active species. Qualitative release studies were conducted, but quantification of the diffusion phenomenon observed when the active species are released from and through CNF coating has not yet been studied. Therefore, this work aims to model CNF-coated paper substrates as controlled release system for food-packaging using release data obtained for two model molecules, namely caffeine and chlorhexidine digluconate. The applied mathematical model - derived from Fickian diffusion - was validated for caffeine only. When the active species chemically interacts with the release device, another model is required as a non-predominantly diffusion-controlled release was observed. From caffeine modeling data, a theoretical active food-packaging material was designed. The use of CNFs as barrier coating was proved to be the ideal material configuration that best meets specifications.

  15. PFOS and PFC releases and associated pollution from a PFC production plant in Minnesota (USA).

    PubMed

    Oliaei, Fardin; Kriens, Don; Weber, Roland; Watson, Alan

    2013-04-01

    Perfluorooctane sulfonate (PFOS) and PFOS-related substances have been listed as persistent organic pollutants in the Stockholm Convention. From August 2012, Parties to the Convention needed to address the use, storage, and disposal of PFOS-including production sites and sites where PFOS wastes have been deposited-in their national implementation plans. The paper describes the pollution in Minnesota (USA) caused by the 3M Company at one of the largest per/polyfluorinated chemical (PFC) production facilities. From early 1950s until the end of 2002, when 3M terminated PFOS and perfluorooctanoic acid (PFOA) production, PFOS, PFOA, and other PFC production wastes were disposed around the plant and in local disposal sites. Discharges from the site and releases from deposits caused widespread contamination of ground and surface waters including local drinking water wells. Fish in the river downstream were contaminated with PFOS to levels that led to fish consumption advisories. Human exposures resulted from ingesting contaminated drinking water, requiring installation of water treatment facilities and alternate water supplies. The critical evaluation of the assessments done revealed a range of gaps in particular of human exposure where relevant exposure pathways including the entire exposure via food have not been taken into consideration. Currently, the exposure assessment of vulnerable groups such as children or Hmong minorities is inadequate and needs to be improved/validated by epidemiological studies. The assessment methodology described for this site may serve-with highlighted improvements-as a model for assessment of other PFOS/PFC production sites in the Stockholm Convention implementation.

  16. Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma.

    PubMed

    Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

    2016-05-01

    We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production.Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production.The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (β = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05).We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

  17. Retrieved Vertical Profiles of Latent Heat Release Using TRMM Rainfall Products

    NASA Technical Reports Server (NTRS)

    Tao, W.-K.; Lang, S.; Olson, W. S.; Meneghini, R.; Yang, S.; Simpson, J.; Kummerow, C.; Smith, E.

    2000-01-01

    This paper represents the first attempt to use TRMM rainfall information to estimate the four dimensional latent heating structure over the global tropics for February 1998. The mean latent heating profiles over six oceanic regions (TOGA COARE IFA, Central Pacific, S. Pacific Convergence Zone, East Pacific, Indian Ocean and Atlantic Ocean) and three continental regions (S. America, Central Africa and Australia) are estimated and studied. The heating profiles obtained from the results of diagnostic budget studies over a broad range of geographic locations are used to provide comparisons and indirect validation for the heating algorithm estimated heating profiles. Three different latent heating algorithms, the Goddard Convective-Stratiform (CSH) heating, the Goddard Profiling (GPROF) heating, and the Hydrometeor heating (HH) are used and their results are intercompared. The horizontal distribution or patterns of latent heat release from the three different heating retrieval methods are quite similar. They all can identify the areas of major convective activity (i.e., a well defined ITCZ in the Pacific, a distinct SPCZ) in the global tropics. The magnitude of their estimated latent heating release is also not in bad agreement with each other and with those determined from diagnostic budget studies. However, the major difference among these three heating retrieval algorithms is the altitude of the maximum heating level. The CSH algorithm estimated heating profiles only show one maximum heating level, and the level varies between convective activity from various geographic locations. These features are in good agreement with diagnostic budget studies. By contrast, two maximum heating levels were found using the GPROF heating and HH algorithms. The latent heating profiles estimated from all three methods can not show cooling between active convective events. We also examined the impact of different TMI (Multi-channel Passive Microwave Sensor) and PR (Precipitation Radar

  18. Combustion instability and active control: Alternative fuels, augmentors, and modeling heat release

    NASA Astrophysics Data System (ADS)

    Park, Sammy Ace

    Experimental and analytical studies were conducted to explore thermo-acoustic coupling during the onset of combustion instability in various air-breathing combustor configurations. These include a laboratory-scale 200-kW dump combustor and a 100-kW augmentor featuring a v-gutter flame holder. They were used to simulate main combustion chambers and afterburners in aero engines, respectively. The three primary themes of this work includes: 1) modeling heat release fluctuations for stability analysis, 2) conducting active combustion control with alternative fuels, and 3) demonstrating practical active control for augmentor instability suppression. The phenomenon of combustion instabilities remains an unsolved problem in propulsion engines, mainly because of the difficulty in predicting the fluctuating component of heat release without extensive testing. A hybrid model was developed to describe both the temporal and spatial variations in dynamic heat release, using a separation of variables approach that requires only a limited amount of experimental data. The use of sinusoidal basis functions further reduced the amount of data required. When the mean heat release behavior is known, the only experimental data needed for detailed stability analysis is one instantaneous picture of heat release at the peak pressure phase. This model was successfully tested in the dump combustor experiments, reproducing the correct sign of the overall Rayleigh index as well as the remarkably accurate spatial distribution pattern of fluctuating heat release. Active combustion control was explored for fuel-flexible combustor operation using twelve different jet fuels including bio-synthetic and Fischer-Tropsch types. Analysis done using an actuated spray combustion model revealed that the combustion response times of these fuels were similar. Combined with experimental spray characterizations, this suggested that controller performance should remain effective with various alternative fuels

  19. IMPACT OF OIL PRODUCTION RELEASES ON SOME SOIL CHEMICAL PROPERTIES AT THE OSPER SITES

    EPA Science Inventory

    Surface and soil core samples were collected at two field sites in an old oil production area near Skiatook Lake in Oklahoma. The soil samples were analyzed for nitrates, organic matter, total petroleum hydrocarbons, conductivity, chlorides and dehydrogenase activity. Low level...

  20. Production Of High Specific Activity Copper-67

    DOEpatents

    Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

    2003-10-28

    A process for the selective production and isolation of high specific activity Cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

  1. Production Of High Specific Activity Copper-67

    DOEpatents

    Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

    2002-12-03

    A process for the selective production and isolation of high specific activity cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

  2. Photothermally activated drug release from liposomes coupled to hollow gold nanoshells

    NASA Astrophysics Data System (ADS)

    Forbes, Natalie; Zasadzinski, Joseph A.

    2011-03-01

    Liposomes show great promise as intravenous drug delivery vehicles, but it is difficult to combine stability in the circulation, extended drug retention and rapid, targeted release at the site of interest. Accessorizing conventional and multicompartment liposomes with photo-activated hollow gold nanoshells (HGN) provides a convenient method to initiate drug release with spatial and temporal control. HGN efficiently absorb near infrared (NIR) light and rapidly convert the absorbed optical energy into heat. Femto- to nano-second NIR light pulses cause the HGNs to rapidly heat, creating large temperature gradients between the HGNs and surrounding fluid. The formation and collapse of unstable vapor bubbles transiently rupture liposome and other bilayer membranes to trigger contents release. Near-complete contents release occurs when the nanoshells are encapsulated within the liposome or tethered to the outer surface of the liposome, with no chemical damage to the contents. Release is achieved by focusing the laser beam at the target, eliminating the need for highly specific targeting ligands or antibodies. Although HGN heating can be intense, the overall energy input is small causing minimal heating of the surroundings. To ensure that drugs are retained within the liposomes until delivery in a physiological environment, we have made novel multicompartment carriers called vesosomes, which consist of an outer lipid bilayer shell that encloses and protects the drug-carrying liposomes. The second bilayer increases the serum half-life of ciprofloxacin from <10 minutes in liposomes to 6 hours in vesosomes and alters the release kinetics. The enhanced drug retention is due to the outer membrane preventing enzymes and proteins in the blood from breaking down the drug-carrying interior compartments.

  3. Mechanism of release of active alpha subunit from dimeric alpha beta avian myeloblastosis virus DNA polymerase.

    PubMed Central

    Papas, T S; Marciani, D J; Samuel, K; Chirikjian, J G

    1976-01-01

    Storage of the dimeric (alphabeta) form of avian myeloblastosis virus (AMV) DNA polymerase in glycerol resulted in the release of the smaller alpha subunit, as detected by glycerol gradient sedimentation. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of enzyme stored in glycerol showed the concomitant appearance of several polypeptides and a lowering in the level of both beta and alpha components. This reduction appears to be the result of cleavages introduced by traces of hydrolytic activity present in glycerol samples. An enhancement of alpha subunit released, as detected by activity profile, was also achieved upon direct but limited exposure of purified avian myeloblastosis virus DNA polymerase to carboxymethyl-cellulose-bound trypsin matrix. Electrophoretic analysis of digested enzyme revealed a progressive fragmentation, with simultaneous increase in the alpha subunit and decrease in the beta subunit. PMID:58080

  4. Effects of recasting on the amount of corrosion products released from two Ni-Cr base metal alloys.

    PubMed

    Ozdemir, S; Arikan, A

    1998-12-01

    The corrosion products released from two recast Ni-Cr base metal alloys Wirolloy and Wiron 99 were investigated. Cast samples were placed in Meyer's modified Fusayama solution for 2 months and in 0.1M Lactic acid 0.1M NaCl solution for 7 days. The release of Ni, Cr and Mo ions from both alloys was measured by using a flame model Atomic Absorption Spectrophotometer. A Scanning Electron Microscope was used to evaluate the surface morphology of the samples before and after corrosion tests. Release of Ni and Cr from Wirolloy samples immersed in 0.1M Lactic acid 0.1M NaCl solution were much higher than those of Wiron 99. The number of recastings was found to have negligible effect on surface texture and on the amount of corrosion products released. PMID:10596615

  5. Antimicrobial cathelicidin polypeptide CAP11 suppresses the production and release of septic mediators in D-galactosamine-sensitized endotoxin shock mice.

    PubMed

    Murakami, Taisuke; Obata, Toru; Kuwahara-Arai, Kyoko; Tamura, Hiroshi; Hiramatsu, Keiichi; Nagaoka, Isao

    2009-08-01

    Endotoxin shock is a severe systemic inflammatory response that is caused by the augmented production and release of septic mediators. Among them, inflammatory cytokines such as tumor necrosis factor-alpha, IL-1beta and IL-6 play a pivotal role. In addition, anandamide, an endogenous cannabinoid and high-mobility group box-1 (HMGB1), a non-histone chromosomal protein has recently been recognized as members of septic mediators. We previously reported that cationic antibacterial polypeptide of 11-kDa (CAP11), an antimicrobial cathelicidin peptide (originally isolated from guinea pig neutrophils), potently neutralizes the biological activity of LPS and protects mice from lethal endotoxin shock. In this study, to clarify the protective mechanism of CAP11 against endotoxin shock, we evaluated the effects of CAP11 on the production and release of septic mediators in vitro and in vivo using a murine macrophage cell line RAW264.7 and a D-galactosamine-sensitized murine endotoxin shock model. LPS stimulation induced the production of inflammatory cytokines and anandamide and release of HMGB1 from RAW264.7 cells. Importantly, CAP11 suppressed the LPS-induced production and release of these mediators by RAW264.7 cells. Moreover, LPS administration enhanced the serum levels of HMGB1, anandamide and inflammatory cytokines in the endotoxin shock model. Of note, CAP11 suppressed the LPS-induced increase of these mediators in sera, and LPS binding to CD14-positive cells (peritoneal macrophages), accompanied with the increase of survival rates. Together these observations suggest that the protective action of CAP11 on endotoxin shock may be explained by its suppressive effect on the production and release of septic mediators by CD14-positive cells possibly via the inhibition of LPS binding to the targets.

  6. Isolation and characterization of two peptides with prolactin release-inhibiting activity from porcine hypothalami.

    PubMed Central

    Schally, A V; Guoth, J G; Redding, T W; Groot, K; Rodriguez, H; Szonyi, E; Stults, J; Nikolics, K

    1991-01-01

    Two peptides with in vitro prolactin release-inhibiting activity were purified from stalk median eminence (SME) fragments of 20,000 pig hypothalami. Monolayer cultures of rat anterior pituitary cells were incubated with aliquots of chromatographic fractions and the inhibition of release of prolactin in vitro was measured by RIA in order to monitor the purification. The hypothalamic tissue extract was separated into 11 fractions by high-performance aqueous size-exclusion chromatography with one fraction showing a 4-fold increase in prolactin release-inhibiting factor (PIF) activity. This material was further purified by semipreparative reversed-phase (RP) HPLC. This process resulted in the separation of two distinct fractions that showed high PIF activity. These were further purified by semipreparative and analytical RP-HPLC to apparent homogeneity as judged by the UV absorbance profiles. Neither of the two peptides showed cross-reactivity with gonadotropin releasing hormone-associated peptide or with somatostatin-14 antibodies. Protein sequence analysis revealed that one of the PIF peptides was Trp-Cys-Leu-Glu-Ser-Ser-Gln-Cys-Gln-Asp-Leu-Ser-Thr-Glu-Ser-Asn-Leu-Leu- Ala-Cys - Ile-Arg-Ala-Cys-Lys-Pro, identical to residues 27-52 of the N-terminal region of the proopiomelanocortin (POMC) precursor (corresponding to amino acids 1-26 of the 16-kDa fragment). The sequence of the other PIF was Ala-Ser-Asp-Arg-Ser-Asn-Ala-Thr-Leu-Leu-Asp-Gly-Pro-Ser-Gly-Ala-Leu-Leu- Leu-Arg - Leu-Val-Gln-Leu-Ala-Gly-Ala-Pro-Glu-Pro-Ala-Glu-Pro-Ala-Gln-Pro-Gly-Val- Tyr, representing residues 109-147 of the vasopressin-neurophysin precursor. Synthetic peptides corresponding to the N-terminal region of POMC had significant PIF activity in vitro. PMID:2023899

  7. Estimates of radioxenon released from Southern Hemisphere medical isotope production facilities using measured air concentrations and atmospheric transport modeling.

    PubMed

    Eslinger, Paul W; Friese, Judah I; Lowrey, Justin D; McIntyre, Justin I; Miley, Harry S; Schrom, Brian T

    2014-09-01

    The International Monitoring System (IMS) of the Comprehensive-Nuclear-Test-Ban-Treaty monitors the atmosphere for radioactive xenon leaking from underground nuclear explosions. Emissions from medical isotope production represent a challenging background signal when determining whether measured radioxenon in the atmosphere is associated with a nuclear explosion prohibited by the treaty. The Australian Nuclear Science and Technology Organisation (ANSTO) operates a reactor and medical isotope production facility in Lucas Heights, Australia. This study uses two years of release data from the ANSTO medical isotope production facility and (133)Xe data from three IMS sampling locations to estimate the annual releases of (133)Xe from medical isotope production facilities in Argentina, South Africa, and Indonesia. Atmospheric dilution factors derived from a global atmospheric transport model were used in an optimization scheme to estimate annual release values by facility. The annual releases of about 6.8 × 10(14) Bq from the ANSTO medical isotope production facility are in good agreement with the sampled concentrations at these three IMS sampling locations. Annual release estimates for the facility in South Africa vary from 2.2 × 10(16) to 2.4 × 10(16) Bq, estimates for the facility in Indonesia vary from 9.2 × 10(13) to 3.7 × 10(14) Bq and estimates for the facility in Argentina range from 4.5 × 10(12) to 9.5 × 10(12) Bq. PMID:24811887

  8. Protein kinase C activation and alpha 2-autoreceptor-modulated release of noradrenaline.

    PubMed Central

    Allgaier, C.; Hertting, G.; Huang, H. Y.; Jackisch, R.

    1987-01-01

    1 Effects of phorbol esters on the evoked noradrenaline release were studied in slices of the rabbit hippocampus, labelled with [3H]-noradrenaline, superfused continuously with a medium containing the reuptake inhibitor cocaine and stimulated electrically for 2 min (stimulation parameters: 2 ms, 24 mA, 5 V cm-1, 3 or 0.3 Hz). 2 The electrically-evoked overflow of [3H]-noradrenaline in the slices was increased in a concentration-dependent manner by the protein kinase C (PKC) activators 12-O-tetradecanoylphorbol 13-acetate (TPA) and 4 beta-phorbol 12,13-dibutyrate (4 beta-PDB). Phorbol esters, which do not activate PKC, 4-O-methyl-TPA and 4 alpha-PDB, showed no effect on neurotransmitter release. The effect of 4 beta-PDB was abolished in the presence of tetrodotoxin and in the absence of calcium. The PKC inhibitor polymyxin B inhibited the evoked noradrenaline release. 3 In the presence of 4 beta-PDB the inhibitory effects of the alpha 2-adrenoceptor agonist clonidine or the facilitatory effects of the alpha 2-adrenoceptor antagonist yohimbine seemed to be modified only by changes in the concentration of noradrenaline in the synaptic region. At a stimulation frequency of 3 Hz the inhibitory action of clonidine was reduced whereas the facilitatory effect of the yohimbine was even slightly enhanced by the phorbol ester. At 0.3 Hz and in the presence of 4 beta-PDB the effect of clonidine remained and that of yohimbine was strongly enhanced. 4 Pretreatment of the slices with islet-activating protein or N-ethylmaleimide significantly reduced the enhancement of noradrenaline release caused by 4 beta-PDB. It is possible that a regulatory N-protein is involved in steps following PKC activation. 5 These results suggest that PKC participates in the mechanism of action-potential-induced noradrenaline release from noradrenergic nerve terminals of the rabbit hippocampus and that effects on the autoinhibitory feedback system were not responsible for the 4 beta-PDB-induced increase

  9. Reduced phospholipase A2 activity is not accompanied by reduced arachidonic acid release.

    PubMed

    Goldberg, H; Maxwell, P; Hack, N; Skorecki, K

    1994-01-14

    Arachidonic acid release in cells highly over expressing cytosolic phospholipase A2 has been attributed to mitogen-activated protein kinase phosphorylation of cytosolic phospholipase A2 on serine-505. To investigate the role of cytosolic phospholipase A2 in cellular physiology, we attempted to inhibit cytosolic phospholipase A2 in the intact cell employing an antisense RNA strategy. Swiss 3T3 cells were stably transfected with an antisense cytosolic phospholipase A2 expression vector. A clone of cells with reduced immunodetectable cytosolic phospholipase A2, compared to a vector transfected cell line, was identified by Western blotting and a corresponding decrease in phospholipase A2 activity was confirmed by enzymatic assay in cell free extracts. However, arachidonic acid release from intact cells in response to agonists was not different between antisense and control cell lines. Thus, arachidonic acid release in intact cells with decreased cytosolic phospholipase A2 activity is likely to be modulated by rate limiting factors that are extrinsic to cytosolic phospholipase A2.

  10. Human mast cells produce and release the cytotoxic lymphocyte associated protease granzyme B upon activation.

    PubMed

    Strik, Merel C M; de Koning, Pieter J A; Kleijmeer, Monique J; Bladergroen, Bellinda A; Wolbink, Angela M; Griffith, Janice M; Wouters, Dorine; Fukuoka, Yoshihiro; Schwartz, Lawrence B; Hack, C Erik; van Ham, S Marieke; Kummer, J Alain

    2007-07-01

    Mast cells are widely distributed throughout the body and express effector functions in allergic reactions, inflammatory diseases, and host defense. Activation of mast cells results in exocytosis of preformed chemical mediators and leads to novel synthesis and secretion of lipid mediators and cytokines. Here, we show that human mast cells also express and release the cytotoxic lymphocyte-associated protease, granzyme B. Granzyme B was active and localized in cytoplasmic granules, morphologically resembling those present in cytotoxic lymphocytes. Expression and release of granzyme B by mast cell-lines HMC-1 and LAD 2 and by cord blood- and mature skin-derived human mast cells depended on the mode of activation of these cells. In mast cell lines and cord blood-derived mast cells, granzyme B expression was mainly induced by non-physiological stimuli (A23187/PMA, Compound 48/80) and substance P. In contrast, mature skin-derived mast cells only produced granzyme B upon IgE-dependent stimulation. We conclude that granzyme B is expressed and released by human mast cells upon physiologic stimulation. This suggests a role for granzyme B as a novel mediator in mast cell biology.

  11. Enhancement of GABA release through endogenous activation of axonal GABA(A) receptors in juvenile cerebellum.

    PubMed

    Trigo, Federico F; Chat, Mireille; Marty, Alain

    2007-11-14

    Recent evidence indicates the presence of presynaptic GABA(A) receptors (GABA(A)Rs) in the axon domain of several classes of central neurons, including cerebellar basket and stellate cells. Here, we investigate the possibility that these receptors could be activated in the absence of electrical or chemical stimulation. We find that low concentrations of GABA increase the frequency of miniature GABAergic synaptic currents. Submaximal concentrations of a GABA(A)R blocker, gabazine, decrease both the miniature current frequency and the probability of evoked GABA release. Zolpidem, an agonist of the benzodiazepine binding site, and NO-711 (1-[2-[[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride), a blocker of GABA uptake, both increase the frequency of miniature currents. These effects occur up to postnatal day 14, but not later. Immunohistochemistry indicates the presence of alpha1-containing GABA(A)Rs in interneuron presynaptic terminals with a similar age dependence. We conclude that, under resting conditions, axonal GABA(A)Rs are significantly activated, that this activation results in enhanced GABA release, and that it can be augmented by increasing the affinity of GABA(A)Rs or reducing GABA uptake. Our findings suggest the existence of a positive-feedback mechanism involving presynaptic GABA(A)Rs that maintains a high release rate and a high local GABA concentration in the immature cerebellar network.

  12. Smart magnetic poly(N-isopropylacrylamide) to control the release of bio-active molecules.

    PubMed

    Dionigi, Chiara; Lungaro, Lisa; Goranov, Vitaly; Riminucci, Alberto; Piñeiro-Redondo, Yolanda; Bañobre-López, Manuel; Rivas, José; Dediu, Valentin

    2014-10-01

    Thermo switchable magnetic hydrogels undoubtedly have a great potential for medical applications since they can behave as smart carriers able to transport bioactive molecules to a chosen part of the body and release them on demand via magneto-thermal activation. We report on the ability to modify the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAM) on demand from 32 °C to LCST ≥ 37 °C. This was achieved by the absorption of controlled amounts of magnetite nanoparticles on the polymer chains. We show, through the effect on cell viability, that the resulting magnetic PNIPAM is able to trap and to release bio-active molecules, such as cell growth factors. The activities of the released bio molecule are tested on human umbilical vein endothelial cells culture. We demonstrate that the LCST of the magnetic PNIPAM can be reached remotely via inductive heating with an alternating magnetic field. This approach on magnetic PNIPAM clearly supports appealing applications in safe biomedicine.

  13. Smart magnetic poly(N-isopropylacrylamide) to control the release of bio-active molecules.

    PubMed

    Dionigi, Chiara; Lungaro, Lisa; Goranov, Vitaly; Riminucci, Alberto; Piñeiro-Redondo, Yolanda; Bañobre-López, Manuel; Rivas, José; Dediu, Valentin

    2014-10-01

    Thermo switchable magnetic hydrogels undoubtedly have a great potential for medical applications since they can behave as smart carriers able to transport bioactive molecules to a chosen part of the body and release them on demand via magneto-thermal activation. We report on the ability to modify the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAM) on demand from 32 °C to LCST ≥ 37 °C. This was achieved by the absorption of controlled amounts of magnetite nanoparticles on the polymer chains. We show, through the effect on cell viability, that the resulting magnetic PNIPAM is able to trap and to release bio-active molecules, such as cell growth factors. The activities of the released bio molecule are tested on human umbilical vein endothelial cells culture. We demonstrate that the LCST of the magnetic PNIPAM can be reached remotely via inductive heating with an alternating magnetic field. This approach on magnetic PNIPAM clearly supports appealing applications in safe biomedicine. PMID:24477874

  14. Load release balance test under unstable conditions effectively discriminates between physically active and sedentary young adults.

    PubMed

    Zemková, E; Štefániková, G; Muyor, J M

    2016-08-01

    This study investigates test-retest reliability and diagnostic accuracy of the load release balance test under four varied conditions. Young, early and late middle-aged physically active and sedentary subjects performed the test over 2 testing sessions spaced 1week apart while standing on either (1) a stable or (2) an unstable surface with (3) eyes open (EO) and (4) eyes closed (EC), respectively. Results identified that test-retest reliability of parameters of the load release balance test was good to excellent, with high values of ICC (0.78-0.92) and low SEM (7.1%-10.7%). The peak and the time to peak posterior center of pressure (CoP) displacement were significantly lower in physically active as compared to sedentary young adults (21.6% and 21.0%) and early middle-aged adults (22.0% and 20.9%) while standing on a foam surface with EO, and in late middle-aged adults on both unstable (25.6% and 24.5%) and stable support surfaces with EO (20.4% and 20.0%). The area under the ROC curve >0.80 for these variables indicates good discriminatory accuracy. Thus, these variables of the load release balance test measured under unstable conditions have the ability to differentiate between groups of physically active and sedentary adults as early as from 19years of age. PMID:27203382

  15. Reactive oxygen species and p38 mitogen-activated protein kinase activate Bax to induce mitochondrial cytochrome c release and apoptosis in response to malonate.

    PubMed

    Gomez-Lazaro, M; Galindo, M F; Melero-Fernandez de Mera, R M; Fernandez-Gómez, F J; Concannon, C G; Segura, M F; Comella, J X; Prehn, J H M; Jordan, J

    2007-03-01

    Malonate, an inhibitor of mitochondrial complex II, is a widely used toxin to study neurodegeneration in Huntington's disease and ischemic stroke. We have shown previously that malonate increased reactive oxygen species (ROS) production in human SH-SY5Y neuroblastoma cells, leading to oxidative stress, cytochrome c release, and apoptotic cell death. Expression of a green fluorescent protein-Bax fusion protein in SH-SY5Y neuroblastoma cells demonstrated a Bax redistribution from the cytosol to mitochondria after 12 to 24 h of malonate treatment that coincided with mitochondrial potential collapse and chromatin condensation. Inhibition of Bax translocation using furosemide, as well as Bax gene deletion, afforded significant protection against malonate-induced apoptosis. Further experiments revealed that malonate induced a prominent increase in the level of activated p38 mitogen-activated protein (MAP) kinase and that treatment with the p38 MAP kinase inhibitor SKF86002 potently blocked malonate-induced Bax translocation and apoptosis. Treatment with vitamin E diminished ROS production, reduced the activation status of p38 MAP kinase, inhibited Bax translocation, and protected against malonate-induced apoptosis. Our data suggest that malonate-induced ROS production and subsequent p38 MAP kinase activation mediates the activation of the pro-apoptotic Bax protein to induce mitochondrial membrane permeabilization and neuronal apoptosis.

  16. Heparin-releasable lipase activity of rat adrenals, ovaries and testes.

    PubMed Central

    Jansen, H; De Greef, W J

    1981-01-01

    The presence of NaCl-resistant, neutral triacylglycerol hydrolase (lipase) activity in rat adrenal gland, ovary and testis was studied. Both adrenals and ovaries but not testes were found to contain such a lipase. The activity of the enzyme in the adrenal gland was lowered during cortisol treatment and hypothyroidism. An elevated adrenal lipase activity was found during hyperthyroidism. Pseudo-pregnant and lactating rats had higher ovarian lipase activities than cyclic rats. Ovarian lipase activity in lactating rats was positively correlated with the serum concentrations of progesterone and of 20 alpha-hydroxyprogesterone and negatively correlated with the high-density-lipoprotein non-esterified cholesterol concentration. The lipase activity of adrenals and of ovaries was largely releasable from these organs by heparin and could be inhibited by an antibody against heparin-releasable liver lipase. This indicated that the lipase is extracellularly located and is similar to 'liver' lipase. A possible role of this lipase in adrenals and ovaries is discussed. PMID:7317012

  17. Cellulase activity and dissolved organic carbon release from lignocellulose macrophyte-derived in four trophic conditions.

    PubMed

    Bottino, Flávia; Cunha-Santino, Marcela Bianchessi; Bianchini, Irineu

    2016-01-01

    Considering the importance of lignocellulose macrophyte-derived for the energy flux in aquatic ecosystems and the nutrient concentrations as a function of force which influences the decomposition process, this study aims to relate the enzymatic activity and lignocellulose hydrolysis in different trophic statuses. Water samples and two macrophyte species were collected from the littoral zone of a subtropical Brazilian Reservoir. A lignocellulosic matrix was obtained using aqueous extraction of dried plant material (≈40°C). Incubations for decomposition of the lignocellulosic matrix were prepared using lignocelluloses, inoculums and filtered water simulating different trophic statuses with the same N:P ratio. The particulate organic carbon and dissolved organic carbon (POC and DOC, respectively) were quantified, the cellulase enzymatic activity was measured by releasing reducing sugars and immobilized carbon was analyzed by filtration. During the cellulose degradation indicated by the cellulase activity, the dissolved organic carbon daily rate and enzyme activity increased. It was related to a fast hydrolysable fraction of cellulose that contributed to short-term carbon immobilization (ca. 10 days). After approximately 20 days, the dissolved organic carbon and enzyme activity were inversely correlated suggesting that the respiration of microorganisms was responsible for carbon mineralization. Cellulose was an important resource in low nutrient conditions (oligotrophic). However, the detritus quality played a major role in the lignocelluloses degradation (i.e., enzyme activity) and carbon release. PMID:26991278

  18. Evaluation of photodynamic activity, photostability and in vitro drug release of zinc phthalocyanine-loaded nanocapsules.

    PubMed

    de Souza, Thiane Deprá; Ziembowicz, Francieli Isa; Müller, Debora Friedrich; Lauermann, Sâmera Cristina; Kloster, Carmen Luisa; Santos, Roberto Christ Vianna; Lopes, Leonardo Quintana Soares; Ourique, Aline Ferreira; Machado, Giovanna; Villetti, Marcos Antonio

    2016-02-15

    Nanocapsule formulations containing zinc phthalocyanine (ZnPc) were investigated as drug delivery systems for use in photodynamic therapy (PDT). ZnPc loaded chitosan, PCL, and PCL coated with chitosan nanocapsules were prepared and characterized by means of their physicochemical properties, photodynamic activity, photostability and drug release profile. All formulations presented nanometric hydrodynamic radius, around 100 nm, low polydispersity index (0.08-0.24), slightly negative zeta potential for PCL nanoparticles and positive zeta potential for suspension containing chitosan. Encapsulation efficiencies were higher than 99%. The capacity of ZnPc loaded nanocapsules to produce cytotoxic singlet oxygen ((1)O2) by irradiation with red laser was monitored using 1.3-diphenylisobenzofuran as a probe. The singlet oxygen quantum yields (ΦΔ) for ZnPc loaded chitosan nanocapsules were high and similar to that of the standard (ZnPc in DMSO), displaying excellent ability to generate (1)O2. The photosensitizer loaded nanocapsules are photostable in the timescale usually utilized in PDT and only a small photobleaching event was observed when a light dose of 610J/cm(2) was applied. The in vitro drug release studies of ZnPc from all nanocapsules demonstrated a sustained release profile controlled by diffusion, without burst effect. The nature of the polymer and the core type of the nanocapsules regulated ZnPc release. Thus, the nanocapsules developed in this work are a promising strategy to be employed in PDT.

  19. Evaluation of photodynamic activity, photostability and in vitro drug release of zinc phthalocyanine-loaded nanocapsules.

    PubMed

    de Souza, Thiane Deprá; Ziembowicz, Francieli Isa; Müller, Debora Friedrich; Lauermann, Sâmera Cristina; Kloster, Carmen Luisa; Santos, Roberto Christ Vianna; Lopes, Leonardo Quintana Soares; Ourique, Aline Ferreira; Machado, Giovanna; Villetti, Marcos Antonio

    2016-02-15

    Nanocapsule formulations containing zinc phthalocyanine (ZnPc) were investigated as drug delivery systems for use in photodynamic therapy (PDT). ZnPc loaded chitosan, PCL, and PCL coated with chitosan nanocapsules were prepared and characterized by means of their physicochemical properties, photodynamic activity, photostability and drug release profile. All formulations presented nanometric hydrodynamic radius, around 100 nm, low polydispersity index (0.08-0.24), slightly negative zeta potential for PCL nanoparticles and positive zeta potential for suspension containing chitosan. Encapsulation efficiencies were higher than 99%. The capacity of ZnPc loaded nanocapsules to produce cytotoxic singlet oxygen ((1)O2) by irradiation with red laser was monitored using 1.3-diphenylisobenzofuran as a probe. The singlet oxygen quantum yields (ΦΔ) for ZnPc loaded chitosan nanocapsules were high and similar to that of the standard (ZnPc in DMSO), displaying excellent ability to generate (1)O2. The photosensitizer loaded nanocapsules are photostable in the timescale usually utilized in PDT and only a small photobleaching event was observed when a light dose of 610J/cm(2) was applied. The in vitro drug release studies of ZnPc from all nanocapsules demonstrated a sustained release profile controlled by diffusion, without burst effect. The nature of the polymer and the core type of the nanocapsules regulated ZnPc release. Thus, the nanocapsules developed in this work are a promising strategy to be employed in PDT. PMID:26678154

  20. Magnetic field activated drug release system based on magnetic PLGA microspheres for chemo-thermal therapy.

    PubMed

    Fang, Kun; Song, Lina; Gu, Zhuxiao; Yang, Fang; Zhang, Yu; Gu, Ning

    2015-12-01

    Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3 wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30 min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.

  1. A measurement of the efficiency of lithium vapor production in high altitude releases

    NASA Technical Reports Server (NTRS)

    Ledley, B. G.; Cheung, C. Y.; Manring, E.

    1985-01-01

    The masses of lithium vapor produced in two sounding rocket chemical releases were determined by comparing ground measurements of the irradiance and the brightness distribution of the sunlit releases with the results from a model calculation. The yields of the two releases, which had different compositions, were found to be approximately 5 and 15 percent of the available lithium.

  2. Saccharification of ozonated sugarcane bagasse using enzymes from Myceliophthora thermophila JCP 1-4 for sugars release and ethanol production.

    PubMed

    Pereira, Josiani de Cassia; Travaini, Rodolfo; Marques, Natalia Paganini; Bolado-Rodríguez, Silvia; Martins, Daniela Alonso Bocchini

    2016-03-01

    The saccharification of ozonated sugarcane bagasse (SCB) by enzymes from Myceliophthora thermophila JCP 1-4 was studied. Fungal enzymes provided slightly higher sugar release than commercial enzymes, working at 50°C. Sugar release increased with temperature increase. Kinetic studies showed remarkable glucose release (4.99 g/L, 3%w/w dry matter) at 60°C, 8 h of hydrolysis, using an enzyme load of 10 FPU (filter paper unit). FPase and β-glucosidase activities increased during saccharification (284% and 270%, respectively). No further significant improvement on glucose release was observed increasing the enzyme load above 7.5 FPU per g of cellulose. Higher dry matter contents increased sugars release, but not yields. The fermentation of hydrolysates by Saccharomyces cerevisiae provided glucose-to-ethanol conversions around to 63%. PMID:26773948

  3. Effect of composition on the physicochemical properties and active substance release from gelatin-alginate sponge.

    PubMed

    Haznar, Dorota; Pluta, Janusz

    2003-01-01

    The aim the study was physicochemically characterize and develop ability of the active substance (cefradine) from the implantable porous carriers. The drug delivery systems consisting of the gelatine and alginic acid sodium salt and glycerol (GL) or peanut oil (AO). Gelatin-alginate sponge was prepared by foamed components and next freeze-dried this foam. The composition of the sponges affected on the sorption ability and on the stability to proteolytic enzymes. Owing to porous structure obtained specific profile of active substance release.

  4. Land management as a factor controlling dissolved organic carbon release from upland peat soils 1: spatial variation in DOC productivity.

    PubMed

    Yallop, A R; Clutterbuck, B

    2009-06-01

    The importance of soil storage in global carbon cycling is well recognised and factors leading to increased losses from this pool may act as a positive feedback mechanism in global warming. Upland peat soils are usually assumed to serve as carbon sinks, there is however increasing evidence of carbon loss from upland peat soils, and DOC concentrations in UK rivers have increased markedly over the past three decades. A number of drivers for increasing DOC release from peat soils have been proposed although many of these would not explain fine-scale variations in DOC release observed in many catchments. We examined the effect of land use and management on DOC production in upland peat catchments at two spatial scales within the UK. DOC concentration was measured in streams draining 50 small-scale catchments (b3 km2) in three discrete regions of the south Pennines and one area in the North Yorkshire Moors. Annual mean DOC concentration was also derived from water colour data recorded at water treatment works for seven larger scale catchments (1.5-20 km2) in the south Pennines. Soil type and land use/management in all catchments were characterised from NSRI digital soil data and ortho-corrected colour aerial imagery. Of the factors assessed, representing all combinations of soil type and land use together with catchment slope and area, the proportion of exposed peat surface resulting from new heather burning was consistently identified as the most significant predictor of variation in DOC concentration. This relationship held across all blanket peat catchments and scales. We propose that management activities are driving changes in edaphic conditions in upland peat to those more favourable for aerobic microbial activity and thus enhance peat decomposition leading to increased losses of carbon from these environments.

  5. Activation of the Tonic GABAC Receptor Current in Retinal Bipolar Cell Terminals by Nonvesicular GABA Release

    PubMed Central

    Jones, S. M.; Palmer, M. J.

    2009-01-01

    Within the second synaptic layer of the retina, bipolar cell (BC) output to ganglion cells is regulated by inhibitory input to BC axon terminals. GABAA receptors (GABAARs) mediate rapid synaptic currents in BC terminals, whereas GABAC receptors (GABACRs) mediate slow evoked currents and a tonic current, which is strongly regulated by GAT-1 GABA transporters. We have used voltage-clamp recordings from BC terminals in goldfish retinal slices to determine the source of GABA for activation of these currents. Inhibition of vesicular release with concanamycin A or tetanus toxin significantly inhibited GABAAR inhibitory postsynaptic currents and glutamate-evoked GABAAR and GABACR currents but did not reduce the tonic GABACR current, which was also not dependent on extracellular Ca2+. The tonic current was strongly potentiated by inhibition of GABA transaminase, under both normal and Ca2+-free conditions, and was activated by exogenous taurine; however inhibition of taurine transport had little effect. The tonic current was unaffected by GAT-2/3 inhibition and was potentiated by GAT-1 inhibition even in the absence of vesicular release, indicating that it is unlikely to be evoked by reversal of GABA transporters or by ambient GABA. In addition, GABA release does not appear to occur via hemichannels or P2X7 receptors. BC terminals therefore exhibit two forms of GABACR-mediated inhibition, activated by vesicular and by nonvesicular GABA release, which are likely to have distinct functions in visual signal processing. The tonic GABACR current in BC terminals exhibits similar properties to tonic GABAAR and glutamate receptor currents in the brain. PMID:19494193

  6. HTR 2014 Paper - Comparison of fission product release predictions using PARFUME with results from the AGR-1 safety tests

    SciTech Connect

    Blaise P. Collin

    2001-10-01

    Safety tests were conducted on fourteen fuel compacts from AGR-1, the first irradiation experiment of the Advanced Gas Reactor (AGR) Fuel Development and Qualification program, at temperatures ranging from 1600 to 1800°C to determine fission product release at temperatures that bound reactor accident conditions. The PARFUME (PARticle FUel ModEl) code was used to predict the release of fission products silver, cesium, strontium, and krypton from fuel compacts containing tristructural isotropic (TRISO) coated particles during the safety tests, and the predicted values were compared with experimental results. Preliminary comparisons between PARFUME predictions and post-irradiation examination (PIE) results of the safety tests show an overall over-prediction of the fractional release of these fission products, which is largely attributed to an over-estimation of the diffusivities used in the modeling of fission product transport in TRISO-coated particles. Correction factors to these diffusivities were assessed for silver and cesium in order to enable a better match between the modeling predictions and the safety testing results. In the case of strontium, correction factors could not be assessed because potential release during the safety tests could not be distinguished from matrix content released during irradiation. In the case of krypton, all the coating layers are partly retentive and the available data did not allow to determine their respective retention powers, hence preventing to derive any correction factors.

  7. Fission product release and microstructure changes of irradiated MOX fuel at high temperatures

    NASA Astrophysics Data System (ADS)

    Colle, J.-Y.; Hiernaut, J.-P.; Wiss, T.; Beneš, O.; Thiele, H.; Papaioannou, D.; Rondinella, V. V.; Sasahara, A.; Sonoda, T.; Konings, R. J. M.

    2013-11-01

    burnups correspond reasonably well with measurement of Walker et al. [11]. All those data are shown Fig. 2.Fragments of 2-8 mg were chosen for the experiments. Since these specimens are small compared to the drilled sample size and were taken randomly, the precise radial position could not be determined, in particular the specimens of sample type, A and B could be from close radial locations.Specimens from each drilled sample type were annealed up to complete vaporisation (˜2600 K) at a speed of about 10 K min-1 in a Knudsen effusion mass spectrometer (KEMS) described previously [13,14]. In addition to helium and to the FGs all the species present in the vapour between 83 and 300 a.m.u. were measured during the heating. Additionally, the 85Kr isotope was analysed in a cold trap by β and γ counting. The long-lived fission gas isotopes correspond to masses 131, 132, 134 and 136 for Xe and 83, 84, 85 and 86 for Kr. The absolute quantities of gas released from specimens of sample types A and B were also determined using the in-house built Q-GAMES (Quantitative gas measurement system), described in detail in [15].For each of the samples, fragments were also annealed and measured in the KEMS up to specific temperatures corresponding to different stages of the FGs or He release. These fragments were subsequently analysed by Scanning Electron Microscopy (SEM, Philips XL40) [16] in order to investigate the relationship between structural changes, burn-up, irradiation temperature and fission products release. SEM observations were also done on the samples before the KEMS experiments and the fracture surface appearance of the samples is shown in Fig. 3, revealing the presence of the high burnup structure (HBS) in the Pu-rich agglomerates.A summary of the 12 samples analysed by KEMS, SEM and Q-GAMES is given in Table 1. At 1300 K no clear change potentially related to gas release appears in the UM and PA. At 1450 K a beginning of grain boundaries opening can be observed as well as

  8. Novel bio-active lipid nanocarriers for the stabilization and sustained release of sitosterol

    NASA Astrophysics Data System (ADS)

    Lacatusu, I.; Badea, N.; Stan, R.; Meghea, A.

    2012-11-01

    In this work, new stable and efficiently bio-active lipid nanocarriers (NLCs) with antioxidant properties have been developed for the transport of active ingredients in food. The novel NLCs loaded with β-sitosterol/β-sitosterol and green tea extract (GTE) and prepared by a combination of natural oils (grape seed oil, fish oil and squalene) and biological lipids with food grade surfactants, were physico-chemically examined by DLS, TEM, electrokinetic potential, DSC and HPLC and found to have main diameters less than 200 nm, a spherical morphology, excellent physical stability, an imperfect crystalline lattice and high entrapment efficiency. The novel loaded-NLCs have demonstrated the potential to develop a high blocking action of chain reactions, trapping up to 92% of the free-oxygen radicals, as compared to the native β-sitosterol (AA%=36.5). Another advantage of this study is associated with the quality of bio-active NLCs based on grape seed oil and squalene to manifest a better sitosterol—sustained release behaviour as compared to their related nanoemulsions. By coupling both in vitro results, i.e. the enhanced antioxidant activity and superior release properties, this study emphasizes the sustainability of novel bio-active nanocarriers to gain specific bio-food features for development of functional foods with a high applicability spectrum.

  9. [Soil biological activities at maize seedling stage under application of slow/controlled release nitrogen fertilizers].

    PubMed

    Li, Dongpo; Wu, Zhijie; Chen, Lijun; Liang, Chenghua; Zhang, Lili; Wang, Weicheng; Yang, Defu

    2006-06-01

    With pot experiment and simulating field ecological environment, this paper studied the effects of different slow/ controlled release N fertilizers on the soil nitrate - reductase and urease activities and microbial biomass C and N at maize seedling stage. The results showed that granular urea amended with dicyandiamide (DCD) and N-(n-bultyl) thiophosphoric triamide (NBPT) induced the highest soil nitrate-reductase activity, granular urea brought about the highest soil urease activity and microbial biomass C and N, while starch acetate (SA)-coated granular urea, SA-coated granular urea amended with DCD, methyl methacrylate (MMA) -coated granular urea amended with DCD, and no N fertilization gave a higher soil urease activity. Soil microbial C and N had a similar variation trend after applying various kinds of test slow/controlled release N fertilizers, and were the lowest after applying SA-coated granular urea amended with DCD and NBPT. Coated granular urea amended with inhibitors had a stronger effect on soil biological activities than coated granular urea, and MMA-coating had a better effect than SA-coating. PMID:16964940

  10. [Soil biological activities at maize seedling stage under application of slow/controlled release nitrogen fertilizers].

    PubMed

    Li, Dongpo; Wu, Zhijie; Chen, Lijun; Liang, Chenghua; Zhang, Lili; Wang, Weicheng; Yang, Defu

    2006-06-01

    With pot experiment and simulating field ecological environment, this paper studied the effects of different slow/ controlled release N fertilizers on the soil nitrate - reductase and urease activities and microbial biomass C and N at maize seedling stage. The results showed that granular urea amended with dicyandiamide (DCD) and N-(n-bultyl) thiophosphoric triamide (NBPT) induced the highest soil nitrate-reductase activity, granular urea brought about the highest soil urease activity and microbial biomass C and N, while starch acetate (SA)-coated granular urea, SA-coated granular urea amended with DCD, methyl methacrylate (MMA) -coated granular urea amended with DCD, and no N fertilization gave a higher soil urease activity. Soil microbial C and N had a similar variation trend after applying various kinds of test slow/controlled release N fertilizers, and were the lowest after applying SA-coated granular urea amended with DCD and NBPT. Coated granular urea amended with inhibitors had a stronger effect on soil biological activities than coated granular urea, and MMA-coating had a better effect than SA-coating.

  11. Novel bio-active lipid nanocarriers for the stabilization and sustained release of sitosterol.

    PubMed

    Lacatusu, I; Badea, N; Stan, R; Meghea, A

    2012-11-16

    In this work, new stable and efficiently bio-active lipid nanocarriers (NLCs) with antioxidant properties have been developed for the transport of active ingredients in food. The novel NLCs loaded with β-sitosterol/β-sitosterol and green tea extract (GTE) and prepared by a combination of natural oils (grape seed oil, fish oil and squalene) and biological lipids with food grade surfactants, were physico-chemically examined by DLS, TEM, electrokinetic potential, DSC and HPLC and found to have main diameters less than 200 nm, a spherical morphology, excellent physical stability, an imperfect crystalline lattice and high entrapment efficiency. The novel loaded-NLCs have demonstrated the potential to develop a high blocking action of chain reactions, trapping up to 92% of the free-oxygen radicals, as compared to the native β-sitosterol (AA%=36.5). Another advantage of this study is associated with the quality of bio-active NLCs based on grape seed oil and squalene to manifest a better sitosterol-sustained release behaviour as compared to their related nanoemulsions. By coupling both in vitro results, i.e. the enhanced antioxidant activity and superior release properties, this study emphasizes the sustainability of novel bio-active nanocarriers to gain specific bio-food features for development of functional foods with a high applicability spectrum.

  12. The lectin ArtinM binds to mast cells inducing cell activation and mediator release.

    PubMed

    Barbosa-Lorenzi, Valéria Cintra; Buranello, Patrícia Andressa de Almeida; Roque-Barreira, Maria Cristina; Jamur, Maria Célia; Oliver, Constance; Pereira-da-Silva, Gabriela

    2011-12-16

    Mast cells are inflammatory cells that respond to signals of innate and adaptive immunity with immediate and delayed release of mediators. ArtinM, a lectin from Artocarpus integrifolia with immunomodulatory activities, is able to induce mast cell activation, but the mechanisms remain unknown. This study sought to further investigate the effects of the lectin on mast cells. We showed that ArtinM binds to mast cells, possibly to the high affinity receptor for immunoglobulin E (IgE) - FcεRI - and/or to IgE bound to FcεRI. Binding of the lectin resulted in protein tyrosine phosphorylation and release of the pre- and newly-formed mediators, β-hexosaminidase and LTB(4) by mast cells, activities that were potentiated in the presence of IgE. ArtinM also induced the activation of the transcription factors NFκB and NFAT, resulting in expression of some of their target genes such as IL-4 and TNF-α. In view of the established significance of mast cells in many immunological and inflammatory reactions, a better understanding of the mechanisms involved in mast cell activation by ArtinM is crucial to the pharmacological application of the lectin.

  13. Determination of the potential for release of mercury from combustion product amended soils: Part 1 - Simulations of beneficial use

    SciTech Connect

    Mae Sexauer Gustin; Jody Ericksen; George C. Fernandez

    2008-05-15

    This paper describes a project that assessed the potential for mercury (Hg) release to air and water from soil amended with combustion products to simulate beneficial use. Combustion products (ash) derived from wood, sewage sludge, subbituminous coal, and a subbituminous coal-petroleum coke mixture were added to soil as agricultural supplements, soil stabilizers, and to develop low permeability surfaces. Hg release was measured from the latter when intact and after it was broken up and mixed into the soil. Air-substrate Hg exchange was measured for all materials six times over 24 hr, providing data that reflected winter, spring, summer, and fall meteorological conditions. Dry deposition of atmospheric Hg and emission of Hg to the atmosphere were both found to be important fluxes. Measured differences in seasonal and diel (24 hr) fluxes demonstrated that to establish an annual estimate of air-substrate flux from these materials data on both of these time steps should be collected. Air-substrate exchange was highly correlated with soil and air temperature, as well as incident light. Hg releases to the atmosphere from coal and wood combustion product-amended soils to simulate an agricultural application were similar to that measured for the unamended soil, whereas releases to the air for the sludge-amended materials were higher. Hg released to soil solutions during the Synthetic Precipitation Leaching Procedure for ashamended materials was higher than that released from soil alone. On the basis of estimates of annual releases of Hg to the air from the materials used, emissions from coal and wood ash-amended soil to simulate an agricultural application could simply be re-emission of Hg deposited by wet processes from the atmosphere; however, releases from sludge-amended materials and those generated to simulate soil stabilization and disturbed low-permeability pads include Hg indigenous to the material. 37 refs., 5 figs., 4 tabs.

  14. Promising applications of cyclodextrins in food: Improvement of essential oils retention, controlled release and antiradical activity.

    PubMed

    Kfoury, Miriana; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

    2015-10-20

    Essential oils (EOs) are gaining great interest as alternatives for harmful synthetic food preservatives. Due to their volatile nature, they could be applied in food packaging to improve food quality and extend shelf-life. To provide long-term effects of EOs by increasing their retention and ensuring controlled release of their components, they could be encapsulated in cyclodextrins (CDs). Herein, the ability of six CDs to retain nine EOs and to bind their individual components was investigated. Retention capacities and binding abilities of CDs were assessed by static headspace-gas chromatography (SH-GC) using a new validated "rapid method". The ability of CDs to generate controlled release systems was examined by multiple headspace extraction (MHE). Finally, radical scavenging activity of free and encapsulated EOs was evaluated. The highest retention capacity toward the studied EOs was obtained for β-CD and its derivatives (69-78%). Also, β-CD and its derivatives showed, with one exception, the highest Kf values for all the studied guests. In addition, encapsulation in CDs reduced the releasing rate of EO components (from 1.43 to 2.43-fold for β-CD/Satureja montana EO used as a model). Furthermore, the inclusion complexes showed higher ABTS(+) scavenging capacity than the free EOs. Results confirmed the usefulness of CDs as encapsulant for EOs and should encourage their application in food and as part of active packaging systems. PMID:26256184

  15. Molecular Machines Regulating the Release Probability of Synaptic Vesicles at the Active Zone

    PubMed Central

    Körber, Christoph; Kuner, Thomas

    2016-01-01

    The fusion of synaptic vesicles (SVs) with the plasma membrane of the active zone (AZ) upon arrival of an action potential (AP) at the presynaptic compartment is a tightly regulated probabilistic process crucial for information transfer. The probability of a SV to release its transmitter content in response to an AP, termed release probability (Pr), is highly diverse both at the level of entire synapses and individual SVs at a given synapse. Differences in Pr exist between different types of synapses, between synapses of the same type, synapses originating from the same axon and even between different SV subpopulations within the same presynaptic terminal. The Pr of SVs at the AZ is set by a complex interplay of different presynaptic properties including the availability of release-ready SVs, the location of the SVs relative to the voltage-gated calcium channels (VGCCs) at the AZ, the magnitude of calcium influx upon arrival of the AP, the buffering of calcium ions as well as the identity and sensitivity of the calcium sensor. These properties are not only interconnected, but can also be regulated dynamically to match the requirements of activity patterns mediated by the synapse. Here, we review recent advances in identifying molecules and molecular machines taking part in the determination of vesicular Pr at the AZ. PMID:26973506

  16. Molecular Machines Regulating the Release Probability of Synaptic Vesicles at the Active Zone.

    PubMed

    Körber, Christoph; Kuner, Thomas

    2016-01-01

    The fusion of synaptic vesicles (SVs) with the plasma membrane of the active zone (AZ) upon arrival of an action potential (AP) at the presynaptic compartment is a tightly regulated probabilistic process crucial for information transfer. The probability of a SV to release its transmitter content in response to an AP, termed release probability (Pr), is highly diverse both at the level of entire synapses and individual SVs at a given synapse. Differences in Pr exist between different types of synapses, between synapses of the same type, synapses originating from the same axon and even between different SV subpopulations within the same presynaptic terminal. The Pr of SVs at the AZ is set by a complex interplay of different presynaptic properties including the availability of release-ready SVs, the location of the SVs relative to the voltage-gated calcium channels (VGCCs) at the AZ, the magnitude of calcium influx upon arrival of the AP, the buffering of calcium ions as well as the identity and sensitivity of the calcium sensor. These properties are not only interconnected, but can also be regulated dynamically to match the requirements of activity patterns mediated by the synapse. Here, we review recent advances in identifying molecules and molecular machines taking part in the determination of vesicular Pr at the AZ.

  17. Promising applications of cyclodextrins in food: Improvement of essential oils retention, controlled release and antiradical activity.

    PubMed

    Kfoury, Miriana; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

    2015-10-20

    Essential oils (EOs) are gaining great interest as alternatives for harmful synthetic food preservatives. Due to their volatile nature, they could be applied in food packaging to improve food quality and extend shelf-life. To provide long-term effects of EOs by increasing their retention and ensuring controlled release of their components, they could be encapsulated in cyclodextrins (CDs). Herein, the ability of six CDs to retain nine EOs and to bind their individual components was investigated. Retention capacities and binding abilities of CDs were assessed by static headspace-gas chromatography (SH-GC) using a new validated "rapid method". The ability of CDs to generate controlled release systems was examined by multiple headspace extraction (MHE). Finally, radical scavenging activity of free and encapsulated EOs was evaluated. The highest retention capacity toward the studied EOs was obtained for β-CD and its derivatives (69-78%). Also, β-CD and its derivatives showed, with one exception, the highest Kf values for all the studied guests. In addition, encapsulation in CDs reduced the releasing rate of EO components (from 1.43 to 2.43-fold for β-CD/Satureja montana EO used as a model). Furthermore, the inclusion complexes showed higher ABTS(+) scavenging capacity than the free EOs. Results confirmed the usefulness of CDs as encapsulant for EOs and should encourage their application in food and as part of active packaging systems.

  18. HTR-2014 Paper Comparison of fission product release predictions using PARFUME with results from the AGR-1 irradiation experiment

    SciTech Connect

    Blaise Collin

    2001-10-01

    The PARFUME (PARticle FUel ModEl) code was used to predict fission product release from tristructural isotropic (TRISO) coated fuel particles and compacts during the first irradiation experiment (AGR-1) of the Advanced Gas Reactor Fuel Development and Qualification program. The PARFUME model for the AGR-1 experiment used the fuel compact volume average temperature for each of the 620 days of irradiation to calculate the release of fission products silver, cesium, and strontium from a representative particle for a select number of AGR-1 compacts. Post-irradiation examination (PIE) measurements provided data on release of fission products from fuel compacts and fuel particles, and retention of fission products in the compacts outside of the SiC layer. PARFUME-predicted fractional release of these fission products was determined and compared to the PIE measurements. Results show an overall over-prediction of the fractional release of cesium by PARFUME. For particles with failed silicon carbide (SiC) layers, the over-prediction is by a factor of about two, corresponding to an over-estimation of the diffusivity in uranium oxycarbide (UCO) by a factor of about 100. For intact particles, whose release is much lower, the over-prediction is by an average of about an order of magnitude, which could additionally be attributed to an over-estimated diffusivity in SiC by about 30%. The release of strontium from intact particles is also over-estimated by PARFUME, which also points towards an over-estimated diffusivity of strontium in either SiC or UCO, or possibly both. The measured strontium fractional release from intact particles varied considerably from compact to compact, making it difficult to assess the effective over-estimation of the diffusivities. Furthermore, the release of strontium from particles with failed SiC is difficult to observe experimentally due to the release from intact particles, preventing any conclusions to be made on the accuracy or validity of the

  19. Encapsulation and controlled release of active DNA from uncrosslinked gelatin microspheres

    NASA Astrophysics Data System (ADS)

    Hardin, James Otey, IV

    This thesis work investigates the encapsulation of DNA in gelatin microspheres (GMS) and the subsequent temperature controlled release of the encapsulated DNA from these GMS. DNA-loaded GMS were then used as templates for colloidal satellite assemblies and the released DNA was shown to competitively displace the original partner strands of immobilized DNA on the surface of the assemblies. To support these investigations, hybridization of DNA at colloidal surfaces was also investigated using in situ measurements. DNA hybridization is of particular interest as means of controlling the functionality of colloidal structures because it is uniquely reversible and tunable as well as biocompatible. Gelatin was chosen as the encapsulation matrix for its superior biocompatibility, convenient gel to liquid phase transition at ˜35°C, and economical availability. This thesis is divided into five chapters. Chapter 1 covers the motivation of this work and provides a general background for the materials used. Chapter 2 details the synthesis of GMS and the use of these uncrosslinked GMS as controlled release matrices for active DNA. Bare GMS were not found to be able to inhibit DNA release on their own. With the addition of a polyelectrolyte bilayer, however, clear inhibition of DNA release at room temperature and permitted release at 37 °C was observed. Chapter 3 is an investigation of the thermodynamics and kinetics of primary and secondary DNA hybridization at colloidal surfaces. Flow cytometry was used to quantify the hybridization reaction in situ and compare it to more conventional measurement protocols involving washing steps. The post washing results illuminated the importance of the toehold region and demonstrated changes in kinetics with changing toehold length which are consistent with published solution studies of toehold-mediated strand displacement. The in situ studies enabled the measurement of primary hybridization rate as well as secondary hybridization rate

  20. The oxygen isotope composition of phosphate released from phytic acid by the activity of wheat and Aspergillus niger phytase

    NASA Astrophysics Data System (ADS)

    von Sperber, C.; Tamburini, F.; Brunner, B.; Bernasconi, S. M.; Frossard, E.

    2015-07-01

    Phosphorus (P) is an essential nutrient for living organisms. Under P-limiting conditions plants and microorganisms can exude extracellular phosphatases that release inorganic phosphate (Pi) from organic phosphorus compounds (Porg). Phytic acid (myo-inositol hexakisphosphate, IP6) is an important form of Porg in many soils. The enzymatic hydrolysis of IP6 by phytase yields available Pi and less phosphorylated inositol derivates as products. The hydrolysis of organic P compounds by phosphatases leaves an isotopic imprint on the oxygen isotope composition (δ18O) of released Pi, which might be used to trace P in the environment. This study aims at determining the effect of phytase on the oxygen isotope composition of released Pi. For this purpose, enzymatic assays with histidine acid phytases from wheat and Aspergillus niger were prepared using IP6, adenosine 5'-monophosphate (AMP) and glycerophosphate (GPO4) as substrates. For a comparison to the δ18O of Pi released by other extracellular enzymes, enzymatic assays with acid phosphatases from potato and wheat germ with IP6 as a substrate were prepared. During the hydrolysis of IP6 by phytase, four of the six Pi were released, and one oxygen atom from water was incorporated into each Pi. This incorporation of oxygen from water into Pi was subject to an apparent inverse isotopic fractionation (ϵ ~ 6 to 10 ‰), which was similar to that imparted by acid phosphatase from potato during the hydrolysis of IP6 (ϵ ~ 7 ‰), where less than three Pi were released. The incorporation of oxygen from water into Pi during the hydrolysis of AMP and GPO4 by phytase yielded a normal isotopic fractionation (ϵ ~ -12 ‰), similar to values reported for acid phosphatases from potato and wheat germ. We attribute this similarity in ϵ to the same amino acid sequence motif (RHGXRXP) at the active site of these enzymes, which leads to similar reaction mechanisms. We suggest that the striking

  1. The oxygen isotope composition of phosphate released from phytic acid by the activity of wheat and Aspergillus niger phytase

    NASA Astrophysics Data System (ADS)

    Sperber, C. v.; Tamburini, F.; Brunner, B.; Bernasconi, S. M.; Frossard, E.

    2015-03-01

    Phosphorus (P) is an essential nutrient for living organisms. Under P-limiting conditions plants and microorganisms can exude extracellular phosphatases that release inorganic phosphate (Pi) from organic phosphorus compounds (Porg). Phytic acid (IP6) is an important form of Porg in many soils. The enzymatic hydrolysis of IP6 by phytase yields plant available inorganic phosphate (Pi) and less phosphorylated inositol derivates as products. The hydrolysis of organic P-compounds by phosphatases leaves an isotopic imprint on the oxygen isotope composition (δ18O) of released Pi, which might be used to trace P in the environment. This study aims at determining the effect of phytase on the oxygen isotope composition of released Pi. For this purpose, enzymatic assays with histidine acid phytases from wheat and Aspergillus niger were prepared using IP6, adenosine 5'monophosphate (AMP) and glycerophosphate (GPO4) as substrates. For a comparison to the δ18O of Pi released by other extracellular enzymes, enzymatic assays with acid phosphatases from potato and wheat germ with IP6 as substrate were prepared. During the hydrolysis of IP6 by phytase, four Pi are released, and one oxygen atom from water is incorporated into each Pi. This incorporation of oxygen from water into Pi is subject to an apparent inverse isotopic fractionation (ϵ ∼ 6 to 10‰), which is similar to that imparted by acid phosphatase from potato during the hydrolysis of IP6 (ϵ ∼ 7‰) where less than three Pi are released. The incorporation of oxygen from water into Pi during the hydrolysis of AMP and GPO4 by phytase yielded a normal isotopic fractionation (ϵ ∼ -12‰), again similar to values reported for acid phosphatases from potato and wheat germ. We attribute this similarity in ɛ to the same amino acid sequence motif (RHGXRXP) at the active site of these enzymes, which leads to similar reaction mechanisms. We suggest that the striking substrate-dependency of

  2. Meteorite organics in planetary environments: hydrothermal release, surface activity, and microbial utilization.

    PubMed

    Mautner, M N; Leonard, R L; Deamer, D W

    1995-01-01

    Up to 50% of the organics in the Murchison meteorite, possibly including some of the polymer, is released in high temperature and pressure aqueous environments, to 350 degrees C and 250 bar, that simulate submarine volcanic, hydrothermal or impact-induced conditions. Meteorite organics of prebiotic significance, such as nonanoic acid, glycine, and pyrene survive the hydrothermal conditions. The released material is surface active with surface pressures up to 19.8 x 10(-3) N m-1, and exhibits an extended surface tension isotherm which suggests a mixture of amphiphilic components. One component, nonanoic acid, is shown to form vesicles. The materials extracted under mild conditions, at 120 degrees C, are nutrients for the humic acid bacterium Pseudomonas maltophilia and efficient nutrients for the oligotroph Flavobacterium oryzihabitans, demonstrating the capability of microorganisms to metabolize extraterrestrial organics.

  3. RIM-binding protein, a central part of the active zone, is essential for neurotransmitter release.

    PubMed

    Liu, Karen S Y; Siebert, Matthias; Mertel, Sara; Knoche, Elena; Wegener, Stephanie; Wichmann, Carolin; Matkovic, Tanja; Muhammad, Karzan; Depner, Harald; Mettke, Christoph; Bückers, Johanna; Hell, Stefan W; Müller, Martin; Davis, Graeme W; Schmitz, Dietmar; Sigrist, Stephan J

    2011-12-16

    The molecular machinery mediating the fusion of synaptic vesicles (SVs) at presynaptic active zone (AZ) membranes has been studied in detail, and several essential components have been identified. AZ-associated protein scaffolds are viewed as only modulatory for transmission. We discovered that Drosophila Rab3-interacting molecule (RIM)-binding protein (DRBP) is essential not only for the integrity of the AZ scaffold but also for exocytotic neurotransmitter release. Two-color stimulated emission depletion microscopy showed that DRBP surrounds the central Ca(2+) channel field. In drbp mutants, Ca(2+) channel clustering and Ca(2+) influx were impaired, and synaptic release probability was drastically reduced. Our data identify RBP family proteins as prime effectors of the AZ scaffold that are essential for the coupling of SVs, Ca(2+) channels, and the SV fusion machinery. PMID:22174254

  4. Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue.

    PubMed

    Binder, Waltraud; Mousa, Shaaban A; Sitte, Nicolle; Kaiser, Myriam; Stein, Christoph; Schäfer, Michael

    2004-07-01

    Stress induces analgesia by mechanisms within and outside the brain. Here we show that the sympathetic nervous system is an essential trigger of intrinsic opioid analgesia within peripheral injured tissue. Noradrenaline, injected directly into inflamed hind paws of male Wistar rats, produced dose-dependent antinociception, reversible by alpha(1)-, alpha(2)- and beta(2)-antagonists. alpha(1)-, alpha(2)- and beta(2)-adrenergic receptors were demonstrated on beta-endorphin-containing immune cells and noradrenaline induced adrenergic receptor-specific release of beta-endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by micro - and delta-opioid antagonists as well as by anti-beta-endorphin. Stress-induced peripheral analgesia was abolished by chemical sympathectomy and by adrenergic antagonists. These findings indicate that sympathetic neuron-derived noradrenaline stimulates adrenergic receptors on inflammatory cells to release beta-endorphin, which induces analgesia via activation of peripheral opioid receptors. PMID:15245482

  5. Meteorite organics in planetary environments: hydrothermal release, surface activity, and microbial utilization.

    PubMed

    Mautner, M N; Leonard, R L; Deamer, D W

    1995-01-01

    Up to 50% of the organics in the Murchison meteorite, possibly including some of the polymer, is released in high temperature and pressure aqueous environments, to 350 degrees C and 250 bar, that simulate submarine volcanic, hydrothermal or impact-induced conditions. Meteorite organics of prebiotic significance, such as nonanoic acid, glycine, and pyrene survive the hydrothermal conditions. The released material is surface active with surface pressures up to 19.8 x 10(-3) N m-1, and exhibits an extended surface tension isotherm which suggests a mixture of amphiphilic components. One component, nonanoic acid, is shown to form vesicles. The materials extracted under mild conditions, at 120 degrees C, are nutrients for the humic acid bacterium Pseudomonas maltophilia and efficient nutrients for the oligotroph Flavobacterium oryzihabitans, demonstrating the capability of microorganisms to metabolize extraterrestrial organics. PMID:11538427

  6. Meteorite organics in planetary environments: hydrothermal release, surface activity, and microbial utilization

    NASA Astrophysics Data System (ADS)

    Mautner, Michael N.; Leonard, Robert L.; Deamer, David W.

    1995-02-01

    Up to 50% of the organics in the Murchison meteorite, possibly including some of the polymer, is released in high temperature and pressure aqueous environments, to 350°C and 250 bar, that simulate submarine volcanic, hydrothermal or impact-induced conditions. Meteorite organics of prebiotic significance, such as nonanoic acid, glycine, and pyrene survive the hydrothermal conditions. The released material is surface active with surface pressures up to 19.8 × 10 -3 N m -1, and exhibits an extended surface tension isotherm which suggests a mixture of amphiphilic components. One component, nonanoic acid, is shown to form vesicles. The materials extracted under mild conditions, at 120°C, are nutrients for the humic acid bacterium Pseudomonas maltophilia and efficient nutrients for the oligotroph Flavobacterium oryzihabitans, demonstrating the capability of micro-organisms to metabolize extraterrestrial organics.

  7. Meteorite organics in planetary environments: hydrothermal release, surface activity, and microbial utilization

    NASA Technical Reports Server (NTRS)

    Mautner, M. N.; Leonard, R. L.; Deamer, D. W.

    1995-01-01

    Up to 50% of the organics in the Murchison meteorite, possibly including some of the polymer, is released in high temperature and pressure aqueous environments, to 350 degrees C and 250 bar, that simulate submarine volcanic, hydrothermal or impact-induced conditions. Meteorite organics of prebiotic significance, such as nonanoic acid, glycine, and pyrene survive the hydrothermal conditions. The released material is surface active with surface pressures up to 19.8 x 10(-3) N m-1, and exhibits an extended surface tension isotherm which suggests a mixture of amphiphilic components. One component, nonanoic acid, is shown to form vesicles. The materials extracted under mild conditions, at 120 degrees C, are nutrients for the humic acid bacterium Pseudomonas maltophilia and efficient nutrients for the oligotroph Flavobacterium oryzihabitans, demonstrating the capability of microorganisms to metabolize extraterrestrial organics.

  8. Identification of the growth hormone-releasing hormone analogue [Pro1, Val14]-hGHRH with an incomplete C-term amidation in a confiscated product.

    PubMed

    Esposito, Simone; Deventer, Koen; Van Eenoo, Peter

    2014-01-01

    In this work, a modified version of the 44 amino acid human growth hormone-releasing hormone (hGHRH(1-44)) containing an N-terminal proline extension, a valine residue in position 14, and a C-terminus amidation (sequence: PYADAIFTNSYRKVVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2 ) has been identified in a confiscated product by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Investigation of the product suggests also an incomplete C-term amidation. Similarly to other hGHRH analogues, available in black markets, this peptide can potentially be used as performance-enhancing drug due to its growth hormone releasing activity and therefore it should be considered as a prohibited substance in sport. Additionally, the presence of partially amidated molecule reveals the poor pharmaceutical quality of the preparation, an aspect which represents a big concern for public health as well.

  9. Anticancer drug released from near IR-activated prodrug overcomes spatiotemporal limits of singlet oxygen.

    PubMed

    Rajaputra, Pallavi; Bio, Moses; Nkepang, Gregory; Thapa, Pritam; Woo, Sukyung; You, Youngjae

    2016-04-01

    Photodynamic therapy (PDT) is a cancer treatment modality where photosensitizer (PS) is activated by visible and near IR light to produce singlet oxygen ((1)O2). However, (1)O2 has a short lifetime (<40 ns) and cannot diffuse (<20 nm) beyond the cell diameter (e.g., ∼ 1800 nm). Thus, (1)O2 damage is both spatially and temporally limited and does not produce bystander effect. In a heterogeneous tumor, cells escaping (1)O2 damage can regrow after PDT treatment. To overcome these limitations, we developed a prodrug concept (PS-L-D) composed of a photosensitizer (PS), an anti-cancer drug (D), and an (1)O2-cleavable linker (L). Upon illumination of the prodrug, (1)O2 is generated, which damages the tumor and also releases anticancer drug. The locally released drug could cause spatially broader and temporally sustained damage, killing the surviving cancer cells after the PDT damage. In our previous report, we presented the superior activity of our prodrug of CA4 (combretastatin A-4), Pc-(L-CA4)2, compared to its non-cleavable analog, Pc-(NCL-CA4)2, that produced only PDT effects. Here, we provide clear evidence demonstrating that the released anticancer drug, CA4, indeed damages the surviving cancer cells over and beyond the spatial and temporal limits of (1)O2. In the limited light illumination experiment, cells in the entire well were killed due to the effect of released anti-cancer drug, whereas only a partial damage was observed in the pseudo-prodrug treated wells. A time-dependent cell survival study showed more cell death in the prodrug-treated cells due to the sustained damage by the released CA4. Cell cycle analysis and microscopic imaging data demonstrated the typical damage patterns by CA4 in the prodrug treated cells. A time-dependent histological study showed that prodrug-treated tumors lacked mitotic bodies, and the prodrug caused broader and sustained tumor size reduction compared to those seen in the tumors treated with the pseudo-prodrug. This data

  10. Rac1-mediated NADPH oxidase release of O2- regulates epithelial sodium channel activity in the alveolar epithelium.

    PubMed

    Takemura, Yoshizumi; Goodson, Preston; Bao, Hui Fang; Jain, Lucky; Helms, My N

    2010-04-01

    We examine whether alveolar cells can control release of O(2)(-) through regulated NADPH oxidase (NOX) 2 (NOX2) activity to maintain lung fluid homeostasis. Using FACS to purify alveolar epithelial cells, we show that type 1 cells robustly express each of the critical NOX components that catalyze the production of O(2)(-) (NOX2 or gp91(phox), p22(phox), p67(phox), p47(phox), and p40(phox) subunits) as well as Rac1 at substantially higher levels than type 2 cells. Immunohistochemical labeling of lung tissue shows that Rac1 expression is cytoplasmic and resides near the apical surface of type 1 cells, whereas NOX2 coimmunoprecipitates with epithelial sodium channel (ENaC). Since Rac1 is a known regulator of NOX2, and hence O(2)(-) release, we tested whether inhibition or activation of Rac1 influenced ENaC activity. Indeed, 1 microM NSC23766 inhibition of Rac1 decreased O(2)(-) output in lung cells and significantly decreased ENaC activity from 0.87 +/- 0.16 to 0.52 +/- 0.16 [mean number of channels (N) and single-channel open probability (P(o)) (NP(o)) +/- SE, n = 6; P < 0.05] in type 2 cells. NSC23766 (10 microM) decreased ENaC NP(o) from 1.16 +/- 0.27 to 0.38 +/- 0.10 (n = 6 in type 1 cells). Conversely, 10 ng/ml EGF (a known stimulator of both Rac1 and O(2)(-) release) increased ENaC NP(o) values in both type 1 and 2 cells. NP(o) values increased from 0.48 +/- 0.21 to 0.91 +/- 0.28 in type 2 cells (P < 0.05; n = 10). In type 1 cells, ENaC activity also significantly increased from 0.40 +/- 0.15 to 0.60 +/- 0.23 following EGF treatment (n = 7). Sequestering O(2)(-) using 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) compound prevented EGF activation of ENaC in both type 1 and 2 cells. In conclusion, we report that Rac1-mediated NOX2 activity is an important component in O(2)(-) regulation of ENaC.

  11. TRPA1 and TRPV4 activation in human odontoblasts stimulates ATP release.

    PubMed

    Egbuniwe, O; Grover, S; Duggal, A K; Mavroudis, A; Yazdi, M; Renton, T; Di Silvio, L; Grant, A D

    2014-09-01

    The mechanism of pain in dentine hypersensitivity is poorly understood but proposed to result from the activation of dental sensory neurons in response to dentinal fluid movements. Odontoblasts have been suggested to contribute to thermal and mechanosensation in the tooth via expression of transient receptor potential (TRP) channels. However, a mechanism by which odontoblasts could modulate neuronal activity has not been demonstrated. In this study, we investigated functional TRP channel expression in human odontoblast-like cells and measured ATP release in response to TRP channel activation. Human immortalized dental pulp cells were driven toward an odontoblast phenotype by culture in conditioned media. Functional expression of TRP channels was determined with reverse transcription polymerase chain reaction and ratiometric calcium imaging with Fura-2. ATP release was measured using a luciferin-luciferase assay. Expression of mRNA for TRPA1, TRPV1, and TRPV4 but not TRPM8 was detected in odontoblasts by reverse transcription polymerase chain reaction. Expression of TRPV4 protein was detected by Western blotting and immunocytochemistry. The TRPA1 agonists allyl isothiocyanate and cinnamaldehyde and the TRPV4 agonist GSK1016790A caused a concentration-dependent increase in intracellular Ca(2+) concentration that was inhibited by the selective antagonists HC030031, AP18, and HC067047, respectively. In contrast, exposure to the TRPV1 agonist capsaicin or the TRPM8 agonist icilin had no effect on intracellular Ca(2+) concentration. Treatment with allyl isothiocyanate, cinnamaldehyde, or GSK1016790A caused an increase in ATP concentration in culture medium that was abolished by preincubation with TRP channel antagonists. These data demonstrate that activation of TRPA1 and TRPV4 channels in human odontoblast-like cells can stimulate ATP release. We were unable to confirm the presence of thermosensitive TRPV1 and TRPM8 that has previously been reported in odontoblasts

  12. TRPA1 and TRPV4 Activation in Human Odontoblasts Stimulates ATP Release

    PubMed Central

    Egbuniwe, O.; Grover, S.; Duggal, A.K.; Mavroudis, A.; Yazdi, M.; Renton, T.; Di Silvio, L.; Grant, A.D.

    2014-01-01

    The mechanism of pain in dentine hypersensitivity is poorly understood but proposed to result from the activation of dental sensory neurons in response to dentinal fluid movements. Odontoblasts have been suggested to contribute to thermal and mechanosensation in the tooth via expression of transient receptor potential (TRP) channels. However, a mechanism by which odontoblasts could modulate neuronal activity has not been demonstrated. In this study, we investigated functional TRP channel expression in human odontoblast-like cells and measured ATP release in response to TRP channel activation. Human immortalized dental pulp cells were driven toward an odontoblast phenotype by culture in conditioned media. Functional expression of TRP channels was determined with reverse transcription polymerase chain reaction and ratiometric calcium imaging with Fura-2. ATP release was measured using a luciferin-luciferase assay. Expression of mRNA for TRPA1, TRPV1, and TRPV4 but not TRPM8 was detected in odontoblasts by reverse transcription polymerase chain reaction. Expression of TRPV4 protein was detected by Western blotting and immunocytochemistry. The TRPA1 agonists allyl isothiocyanate and cinnamaldehyde and the TRPV4 agonist GSK1016790A caused a concentration-dependent increase in intracellular Ca2+ concentration that was inhibited by the selective antagonists HC030031, AP18, and HC067047, respectively. In contrast, exposure to the TRPV1 agonist capsaicin or the TRPM8 agonist icilin had no effect on intracellular Ca2+ concentration. Treatment with allyl isothiocyanate, cinnamaldehyde, or GSK1016790A caused an increase in ATP concentration in culture medium that was abolished by preincubation with TRP channel antagonists. These data demonstrate that activation of TRPA1 and TRPV4 channels in human odontoblast-like cells can stimulate ATP release. We were unable to confirm the presence of thermosensitive TRPV1 and TRPM8 that has previously been reported in odontoblasts. PMID

  13. Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase

    PubMed Central

    Berthier, Christine; Kutchukian, Candice; Bouvard, Clément; Okamura, Yasushi

    2015-01-01

    Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P2 in Ca2+ homeostasis and excitation–contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein–tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca2+ transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca2+ release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP–expressing fibers challenged by 5-s-long depolarizing pulses, the Ca2+ level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP–expressing fibers showed a reversible depression of Ca2+ release during trains, with the peak Ca2+ transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP–expressing fibers. Cav1.1 Ca2+ channel–mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ1PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule–bound PLCδ1PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers

  14. Product-specific validation of a serological potency test for release of Leptospira vaccines in the European Union.

    PubMed

    Stirling, Catrina; Novokova, Viera

    2013-09-01

    Historically in the European Union, all Leptospira vaccines were released using the European Pharmacopoeia (Ph. Eur.) hamster potency assay. Recently, there has been a shift toward alternatives that offer either refinement of testing or replacement of animals for product release. This is being driven by animal welfare concerns but also by a drive to have more consistent, cheaper, and faster batch release tests. This publication discusses one such example of a multicomponent canine vaccine that includes three Leptospira serovars and has recently been registered in the European Union. The potency release test is a refinement because it uses rabbit serology rather than hamster challenge. This publication covers the principles of the test method, challenges faced during its development and registration, and discussion about benefits and limitations of this method. It concludes with a view of how the use of serology testing could fit into an overall strategy to move to fully in vitro testing by adopting a consistency approach.

  15. Product-specific validation of a serological potency test for release of Leptospira vaccines in the European Union.

    PubMed

    Stirling, Catrina; Novokova, Viera

    2013-09-01

    Historically in the European Union, all Leptospira vaccines were released using the European Pharmacopoeia (Ph. Eur.) hamster potency assay. Recently, there has been a shift toward alternatives that offer either refinement of testing or replacement of animals for product release. This is being driven by animal welfare concerns but also by a drive to have more consistent, cheaper, and faster batch release tests. This publication discusses one such example of a multicomponent canine vaccine that includes three Leptospira serovars and has recently been registered in the European Union. The potency release test is a refinement because it uses rabbit serology rather than hamster challenge. This publication covers the principles of the test method, challenges faced during its development and registration, and discussion about benefits and limitations of this method. It concludes with a view of how the use of serology testing could fit into an overall strategy to move to fully in vitro testing by adopting a consistency approach. PMID:23849308

  16. Activation of AMPA receptor promotes TNF-α release via the ROS-cSrc-NFκB signaling cascade in RAW264.7 macrophages

    SciTech Connect

    Cheng, Xiu-Li; Ding, Fan; Li, Hui; Tan, Xiao-Qiu; Liu, Xiao; Cao, Ji-Min; Gao, Xue

    2015-05-29

    The relationship between glutamate signaling and inflammation has not been well defined. This study aimed to investigate the role of AMPA receptor (AMPAR) in the expression and release of tumor necrosis factor-alpha (TNF-α) from macrophages and the underlying mechanisms. A series of approaches, including confocal microscopy, immunofluorescency, flow cytometry, ELISA and Western blotting, were used to estimate the expression of AMPAR and downstream signaling molecules, TNF-α release and reactive oxygen species (ROS) generation in the macrophage-like RAW264.7 cells. The results demonstrated that AMPAR was expressed in RAW264.7 cells. AMPA significantly enhanced TNF-α release from RAW264.7 cells, and this effect was abolished by CNQX (AMPAR antagonist). AMPA also induced elevation of ROS production, phosphorylation of c-Src and activation of nuclear factor (NF)-κB in RAW264.7 cells. Blocking c-Src by PP2, scavenging ROS by glutathione (GSH) or inhibiting NF-κB activation by pyrrolidine dithiocarbamate (PDTC) decreased TNF-α production from RAW264.7 cells. We concluded that AMPA promotes TNF-α release in RAW264.7 macrophages likely through the following signaling cascade: AMPAR activation → ROS generation → c-Src phosphorylation → NF-κB activation → TNF-α elevation. The study suggests that AMPAR may participate in macrophage activation and inflammation. - Highlights: • AMPAR is expressed in RAW264.7 macrophages and is upregulated by AMPA stimulation. • Activation of AMPAR stimulates TNF-α release in macrophages through the ROS-cSrc-NFκB signaling cascade. • Macrophage AMPAR signaling may play an important role in inflammation.

  17. Cell death, BAX activation, and HMGB1 release during infection with Chlamydia.

    PubMed

    Jungas, Thomas; Verbeke, Philippe; Darville, Toni; Ojcius, David M

    2004-11-01

    Infection by a number of Chlamydia species leads to resistance of the host cell to apoptosis, followed by induction of host-cell death. In a population of infected cells that displays protection against staurosporine-induced apoptosis among the adherent cells, we find that cells that had been recovered from the supernatant share characteristics of both apoptosis and necrosis, as assayed by the propidium iodide (PI)-annexin V double-labeling technique. Cell death was observed in both an epithelial cell line and primary fibroblasts, although the primary cells had a higher propensity to die through apoptosis than the immortalized cell line. Staurosporine-mediated activation of the pro-apoptotic BCL-2 family member, BAX, was inhibited in the epithelial cell line infected for 32 h with the lymphogranuloma venereum (LGV/L2) but not the murine pneumonitis (MoPn) strain of C. trachomatis, but inhibition of staurosporine-mediated BAX activation disappeared after 48 h of infection with the LGV/L2 strain. Conversely, infection with MoPn (C. muridarum) but not LGV/L2 led to BAX activation after 72 h, as previously reported for shorter (48 h) infection with the guinea pig inclusion conjunctivitis (GPIC) serovar of C. psittaci (C. caviae). These results suggest that the ability to inhibit staurosporine-mediated BAX activation or to activate BAX due to the infection itself may vary as a function of the chlamydial strain. Interestingly, both the epithelial cells and the fibroblasts also released high mobility group box 1 protein (HMGB1) during infection, although much less HMGB1 was released from fibroblasts, consistent with the higher level of apoptosis observed in the primary cells. HMGB1 is released preferentially by necrotic or permeabilized viable cells, but not apoptotic cells. In the extracellular space, HMGB1 promotes inflammation through interaction with specific cell-surface receptors. Higher levels of HMGB1 were also measured in the genital-tract secretions of mice

  18. Hydrological controls on dissolved organic carbon production and release from UK peatlands

    NASA Astrophysics Data System (ADS)

    Fenner, Nathalie; Freeman, Chris; Worrall, Fred

    Long-term increases in dissolved organic carbon (DOC) release from peatlands to British aquatic ecosystems are widely acknowledged, and are now confirmed to occur in a wide variety of boreal and subboreal settings. Depth to water table is probably the single most important hydrological factor governing that DOC generation and will modulate the response of the system to other environmental factors (such as warming and rising atmospheric carbon dioxide) in a changing climate. Many workers have attempted to attribute the rising DOC trend to a single "universal" driving variable. However, two fundamental problems prevent this: (1) universal theories, i.e., climate change theories that can account for rising trends in diverse catchment types, seem insufficient to account for the large observed increases, and (2) regional theories cannot account for the trend in all catchment types. Here it is suggested that multiple and possibly different drivers can modify DOC exports at four stages, namely, production, diffusion, solubility, and transport, with hydrology undoubtedly having a direct or indirect role in all the potential drivers considered here. These mechanisms, and the interactions between them, need to be more fully understood if we are to predict the response of the United Kingdom and global peatland carbon stores to environmental changes. Moreover, if we are to attempt to ameliorate rising DOC, we will need to fully appreciate the implications of restoration of drained peatlands and land management practices, to ensure that carbon losses are reduced on various temporal scales. These are research topics that remain in their infancy.

  19. Anaphylactic release of a prekallikrein activator from human lung in vitro.

    PubMed Central

    Meier, H L; Kaplan, A P; Lichtenstein, L M; Revak, S; Cochrane, C G; Newball, H H

    1983-01-01

    We have demonstrated the in vitro IgE-mediated release of a prekallikrein activator from human lung. The lung prekallikrein activator was partially purified by sequential chromatography on sulfopropyl-Sephadex, DEAE-Sephacel, and Sepharose 6B. Purified human prekallikrein was converted to its active form (kallikrein) by the lung protease. The generated kallikrein was shown to be biologically active; that is, it generates bradykinin from purified human high-molecular weight kininogen and also cleaves benzoyl-propyl-phenyl-arginyl-p-nitroanilide, a known synthetic substrate of kallikrein. The lung prekallikrein activator differs from the known physiologic activators of prekallikrein (the activated forms of Hageman factor) with respect to: (a) size (it has a mol wt of approximately 175,000); (b) synthetic substrate specificity (D-propyl/phenyl/arginyl-p-nitroanilide is a substrate for the activated forms of Hageman factor, but not the lung protease); (c) antigenic specificity (an anti-Hageman factor immunoadsorbent column did not remove significant amounts of the lung protease, while it removed most of the activity of activated Hageman factor fragments); and (d) inhibition profile (the lung proteases was not inhibited by corn trypsin inhibitor). This prekallikrein activator provides a physiologic mechanism by which prekallikrein can be directly activated during IgE-mediated reactions of the lung. While the role of this lung prekallikrein activator in immediate hypersensitivity reactions and in other inflammatory processes is not clear, it does represent a first and important interface between IgE-mediated reactions and the Hageman factor-dependent pathways of the inflammatory response. Images FIGURE 6 PMID:6192147

  20. Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

    PubMed

    Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C; Salgado, Humberto

    2016-01-01

    Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented-in order of decreasing affinity for the catecholamine-by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing-in turn-a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a large

  1. Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

    PubMed Central

    Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C.; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C.; Salgado, Humberto

    2016-01-01

    Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented—in order of decreasing affinity for the catecholamine—by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing—in turn—a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a

  2. Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

    PubMed Central

    Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C.; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C.; Salgado, Humberto

    2016-01-01

    Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented—in order of decreasing affinity for the catecholamine—by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing—in turn—a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a

  3. Rapid estimation of sugar release from winter wheat straw during bioethanol production using FTIR-photoacoustic spectroscopy

    SciTech Connect

    Bekiaris, Georgios; Lindedam, Jane; Peltre, Clément; Decker, Stephen R.; Turner, Geoffrey B.; Magid, Jakob; Bruun, Sander

    2015-06-18

    Complexity and high cost are the main limitations for high-throughput screening methods for the estimation of the sugar release from plant materials during bioethanol production. In addition, it is important that we improve our understanding of the mechanisms by which different chemical components are affecting the degradability of plant material. In this study, Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) was combined with advanced chemometrics to develop calibration models predicting the amount of sugars released after pretreatment and enzymatic hydrolysis of wheat straw during bioethanol production, and the spectra were analysed to identify components associated with recalcitrance. A total of 1122 wheat straw samples from nine different locations in Denmark and one location in the United Kingdom, spanning a large variation in genetic material and environmental conditions during growth, were analysed. The FTIR-PAS spectra of non-pretreated wheat straw were correlated with the measured sugar release, determined by a high-throughput pretreatment and enzymatic hydrolysis (HTPH) assay. A partial least square regression (PLSR) calibration model predicting the glucose and xylose release was developed. The interpretation of the regression coefficients revealed a positive correlation between the released glucose and xylose with easily hydrolysable compounds, such as amorphous cellulose and hemicellulose. Additionally, we observed a negative correlation with crystalline cellulose and lignin, which inhibits cellulose and hemicellulose hydrolysis. FTIR-PAS was used as a reliable method for the rapid estimation of sugar release during bioethanol production. The spectra revealed that lignin inhibited the hydrolysis of polysaccharides into monomers, while the crystallinity of cellulose retarded its hydrolysis into glucose. Amorphous cellulose and xylans were found to contribute significantly to the released amounts of glucose and xylose, respectively.

  4. Rapid estimation of sugar release from winter wheat straw during bioethanol production using FTIR-photoacoustic spectroscopy

    DOE PAGES

    Bekiaris, Georgios; Lindedam, Jane; Peltre, Clément; Decker, Stephen R.; Turner, Geoffrey B.; Magid, Jakob; Bruun, Sander

    2015-06-18

    Complexity and high cost are the main limitations for high-throughput screening methods for the estimation of the sugar release from plant materials during bioethanol production. In addition, it is important that we improve our understanding of the mechanisms by which different chemical components are affecting the degradability of plant material. In this study, Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) was combined with advanced chemometrics to develop calibration models predicting the amount of sugars released after pretreatment and enzymatic hydrolysis of wheat straw during bioethanol production, and the spectra were analysed to identify components associated with recalcitrance. A total of 1122more » wheat straw samples from nine different locations in Denmark and one location in the United Kingdom, spanning a large variation in genetic material and environmental conditions during growth, were analysed. The FTIR-PAS spectra of non-pretreated wheat straw were correlated with the measured sugar release, determined by a high-throughput pretreatment and enzymatic hydrolysis (HTPH) assay. A partial least square regression (PLSR) calibration model predicting the glucose and xylose release was developed. The interpretation of the regression coefficients revealed a positive correlation between the released glucose and xylose with easily hydrolysable compounds, such as amorphous cellulose and hemicellulose. Additionally, we observed a negative correlation with crystalline cellulose and lignin, which inhibits cellulose and hemicellulose hydrolysis. FTIR-PAS was used as a reliable method for the rapid estimation of sugar release during bioethanol production. The spectra revealed that lignin inhibited the hydrolysis of polysaccharides into monomers, while the crystallinity of cellulose retarded its hydrolysis into glucose. Amorphous cellulose and xylans were found to contribute significantly to the released amounts of glucose and xylose

  5. Production of high specific activity silicon-32

    SciTech Connect

    Phillips, D.R.; Brzezinski, M.A.

    1998-12-31

    This is the final report of a three-year, Laboratory Directed Research and Development Project (LDRD) at Los Alamos National Laboratory (LANL). There were two primary objectives for the work performed under this project. The first was to take advantage of capabilities and facilities at Los Alamos to produce the radionuclide {sup 32}Si in unusually high specific activity. The second was to combine the radioanalytical expertise at Los Alamos with the expertise at the University of California to develop methods for the application of {sup 32}Si in biological oceanographic research related to global climate modeling. The first objective was met by developing targetry for proton spallation production of {sup 32}Si in KCl targets and chemistry for its recovery in very high specific activity. The second objective was met by developing a validated field-useable, radioanalytical technique, based upon gas-flow proportional counting, to measure the dynamics of silicon uptake by naturally occurring diatoms.

  6. Responses of ram lambs to active immunization against testosterone and luteinizing hormone-releasing hormone.

    PubMed

    Schanbacher, B D

    1982-03-01

    Active immunization of young ram lambs against testosterone and luteinizing hormone-releasing hormone (LHRH) was shown to block the growth attributes characteristic of intact ram lambs. Testosterone and LHRH-immunized lambs grew at a slower rate and converted feed to live weight gain less efficiently than albumin-immunized controls. Lambs immunized against testosterone and LHRH had high antibody titers for their respective antigens. Moreover, testosterone-immunized lambs had high serum concentrations of luteinizing hormone (LH) and testosterone, whereas LHRH-immunized lambs had low to nondetectable serum concentrations of these hormones. Release of LH and testosterone following the intravenous administration of LHRH (250 ng) was absent in LHRH-immunized lambs, but quantitatively similar for intact and albumin-immunized control lambs. Testosterone-immunized lambs responded as did conventional castrates with a large LH release, but testosterone concentrations were unchanged. These findings are discussed relative to the integrity of the hypothalamic-pituitary-testicular endocrine axis and the importance of gonadotropin support for normal testicular development. These data show that LHRH immunoneutralization effectively retards testicular development and produces a castration effect in young ram lambs.

  7. Transcription termination factor rho prefers catalytically active elongation complexes for releasing RNA.

    PubMed

    Dutta, Dipak; Chalissery, Jisha; Sen, Ranjan

    2008-07-18

    RNA polymerase pauses at different DNA sequences during transcription elongation, and this pausing is associated with distinct conformational state(s) of the elongation complex (EC). Transcription termination by the termination factor Rho, an RNA-dependent molecular motor, requires pausing of the EC in the termination zone of Rho-dependent terminators. We hypothesized that the conformational state(s) of the EC associated with this pausing would influence the action of Rho. Analyses of the pausing behavior of the EC at the termination points of two well known Rho-dependent terminators revealed that Rho prefers actively transcribing complexes for termination. RNA release kinetics from stalled ECs showed that the rate of RNA release by Rho was reduced if the EC was irreversibly backtracked, if its RNA exit channel was modified by an RNA hairpin, or the bridge helix/trigger loop movement in its active site was perturbed. These defects were overcome significantly by enhancing the rate of ATP hydrolysis either by increasing the concentration of ATP or by using a Rho mutant with higher ATPase activity. We propose that the force generated from ATP hydrolysis of Rho is the key factor in dislodging the EC through its molecular motor action, and this process is facilitated when the EC is in a catalytically competent state, undergoing rapid "Brownian ratchet" motion.

  8. A correlation between antioxidant activity and metabolite release during the blanching of Chrysanthemum coronarium L.

    PubMed

    Kim, Jiyoung; Choi, Jung Nam; Ku, Kang Mo; Kang, Daejung; Kim, Jong Sang; Park, Jung Han Yoon; Lee, Choong Hwan

    2011-01-01

    Liquid chromatography tandem mass spectrometry (LCMS/MS)-based metabolite profiling was applied to elucidate the correlation between metabolite release and antioxidant activity during water blanching of Chrysanthemum coronarium L. (CC). Some major metabolites showing differences between fresh CC and blanched CC (BCC) were selected by principal component analysis (PCA) and partial least-square discriminate analysis (PLS-DA) loading plots, and were identified as dicaffeoylquinic acid (DCQA), succinoyl-DCQA, and acetylmycosinol. By PLS regression analysis of the correlation between antioxidant components and effects, candidate antioxidative metabolites were predicted due to strong positive correlations with DCQA and succinoyl-DCQA, and by a relatively weak positive correlation with acetylmycosinol.

  9. Novel lead structures and activation mechanisms for CO-releasing molecules (CORMs)

    PubMed Central

    Schatzschneider, U

    2015-01-01

    Carbon monoxide (CO) is an endogenous small signalling molecule in the human body, produced by the action of haem oxygenase on haem. Since it is very difficult to apply safely as a gas, solid storage and delivery forms for CO are now explored. Most of these CO-releasing molecules (CORMs) are based on the inactivation of the CO by coordinating it to a transition metal centre in a prodrug approach. After a brief look at the potential cellular target structures of CO, an overview of the design principles and activation mechanisms for CO release from a metal coordination sphere is given. Endogenous and exogenous triggers discussed include ligand exchange reactions with medium, enzymatically-induced CO release and photoactivated liberation of CO. Furthermore, the attachment of CORMs to hard and soft nanomaterials to confer additional target specificity to such systems is critically assessed. A survey of analytical methods for the study of the stoichiometry and kinetics of CO release, as well as the tracking of CO in living systems by using fluorescent probes, concludes this review. CORMs are very valuable tools for studying CO bioactivity and might lead to new drug candidates; however, in the design of future generations of CORMs, particular attention has to be paid to their drug-likeness and the tuning of the peripheral ‘drug sphere’ for specific biomedical applications. Further progress in this field will thus critically depend on a close interaction between synthetic chemists and researchers exploring the physiological effects and therapeutic applications of CO. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 PMID:24628281

  10. Modified hydrotalcite-like compounds as active fillers of biodegradable polymers for drug release and food packaging applications.

    PubMed

    Costantino, Umberto; Nocchetti, Morena; Tammaro, Loredana; Vittoria, Vittoria

    2012-11-01

    This review treats the recent patents and related literature, mainly from the Authors laboratories, on biomedical and food packaging applications of nano-composites constituted of biodegradable polymers filled with micro or nano crystals of organically modified Layered Double Hydroxides of Hydrotalcite type. After a brief outline of the chemical and structural aspects of Hydrotalcite-like compounds (HTlc) and of their manipulation via intercalation of functional molecular anions to obtain materials for numerous, sometime unexpected applications, the review approaches the theme in three separated parts. Part 1 deals with the synthetic method used to prepare the pristine Mg-Al and Zn-Al HTlc and with the procedures of their functionalization with anti-inflammatory (diclofenac), antibacterial (chloramphenicol hemisuccinate), antifibrinolytic (tranexamic acid) drugs and with benzoates with antimicrobial activity. Procedures used to form (nano) composites of polycaprolactone, used as an example of biodegradable polymer, and functionalized HTlc are also reported. Part 2 discusses a patent and related papers on the preparation and biomedical use of a controlled delivery system of the above mentioned pharmacologically active substances. After an introduction dealing with the recent progress in the field of local drug delivery systems, the chemical and structural aspects of the patented system constituted of a biodegradable polymer and HTlc loaded with the active substances will be presented together with an extensive discussion of the drug release in physiological medium. Part 3 deals with a recent patent and related papers on chemical, structural and release property of antimicrobial species of polymeric films containing antimicrobial loaded HTlc able to act as active packaging for food products prolonging their shelf life.

  11. Formation and Release Behavior of Iron Corrosion Products under the Influence of Bacterial Communities in a Simulated Water Distribution System

    EPA Science Inventory

    Understanding the effects of biofilm on the iron corrosion, iron release and associated corrosion by-products is critical for maintaining the water quality and the integrity of drinking water distribution system (DWDS). In this work, iron corrosion experiments under sterilized a...

  12. Ca2+-Activated K+ Channels in Gonadotropin-Releasing Hormone-Stimulated Mouse Gonadotrophs

    PubMed Central

    Waring, Dennis W.; Turgeon, Judith L.

    2009-01-01

    GnRH receptor activation elicits release of intracellular Ca2+, which leads to secretion and also activates Ca2+-activated ion channels underlying membrane voltage changes. The predominant Ca2+-activated ion channels in rat and mouse gonadotrophs are Ca2+-activated K+ channels. To establish the temporal relationship between GnRH-induced changes in intracellular [Ca2+] ([Ca2+]i) and membrane current (Im), and to identify specific Ca2+-activated K+ channels linking GnRH-induced increase in [Ca2+]i to changes in plasma membrane electrical activity, we used single female mouse gonadotrophs in the perforated patch configuration of the patch-clamp technique, which preserves signaling pathways. Simultaneous measurement of [Ca2+]i and Im in voltage-clamped gonadotrophs revealed that GnRH stimulates an increase in [Ca2+]i that precedes outward Im, and that activates two kinetically distinct currents identified, using specific toxin inhibitors, as small conductance Ca2+-activated K+ (SK) current (ISK) and large (big) conductance voltage- and Ca2+-activated K+ (BK) current (IBK). We show that the apamin-sensitive current has an IC50 of 69 pM, consistent with the SK2 channel subtype and confirmed by immunocytochemistry. The magnitude of the SK current response to GnRH was attenuated by 17β-estradiol (E2) pretreatment. Iberiotoxin, an inhibitor of BK channels, completely blocked the residual apamin-insensitive outward Im, substantiating that IBK is a component of the GnRH-induced outward Im. In contrast to its suppression of ISK, E2 pretreatment augmented peak IBK. SK or BK channel inhibition modulated GnRH-stimulated LH secretion, implicating a role for these channels in gonadotroph function. In summary, in mouse gonadotrophs the GnRH-stimulated increase in [Ca2+]i activates ISK and IBK, which are differentially regulated by E2 and which may be targets for E2 positive feedback in LH secretion. PMID:19106218

  13. Activation of A(1) adenosine or mGlu3 metabotropic glutamate receptors enhances the release of nerve growth factor and S-100beta protein from cultured astrocytes.

    PubMed

    Ciccarelli, R; Di Iorio, P; Bruno, V; Battaglia, G; D'Alimonte, I; D'Onofrio, M; Nicoletti, F; Caciagli, F

    1999-09-01

    Pharmacological activation of A(1) adenosine receptor with 2-chloro-N6-cyclopentyladenosine (CCPA) or mGlu3 metabotropic glutamate receptors with (2S,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl)glycine (DCG-IV) or aminopyrrolidine-2R, 4R-dicarboxylate (2R,4R-APDC) enhanced the release of nerve growth factor (NGF) or S-100beta protein from rat cultured astrocytes. Stimulation of release by CCPA and DCG-IV or 2R,4R-APDC was inhibited by the A(1) adenosine receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine and by the mGlu2/3 receptor antagonist (2S,1'S, 2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-4), respectively. Time-course studies revealed a profound difference between the release of S-100beta protein and the release of NGF in response to extracellular signals. Stimulation of S-100beta protein exhibited rapid kinetics, peaking after 1 h of drug treatment, whereas the enhancement of NGF release was much slower, requiring at least 6 h of A(1) adenosine or mGlu3 receptor activation. In addition, stimulation of NGF but not S-100beta release was substantially reduced in cultures treated with the protein synthesis inhibitor cycloheximide. In addition, a 6-8 h treatment of cultured astrocytes with A(1) or mGlu3 receptor agonists increased the levels of both NGF mRNA and NGF-like immunoreactive proteins, including NGF prohormone. We conclude that activation of A(1) adenosine or mGlu3 receptors produces pleiotropic effects in astrocytes, stimulating the synthesis and/or the release of protein factors. Astrocytes may therefore become targets for drugs that stimulate the local production of neurotrophic factors in the CNS, and this may provide the basis for a novel therapeutic strategy in chronic neurodegenerative disorders. PMID:10457374

  14. Actinide, Activation Product and Fission Product Decay Data for Reactor-based Applications

    SciTech Connect

    Perry, R.J.; Dean, C.J.; Nichols, A.L.

    2014-06-15

    The UK Activation Product Decay Data Library was first released in September 1977 as UK-PADD1, to be followed by regular improvements on an almost yearly basis up to the assembly of UKPADD6.12 in March 2013. Similarly, the UK Heavy Element and Actinide Decay Data Library followed in December 1981 as UKHEDD1, with the implementation of various modifications leading to UKHEDD2.6, February 2008. Both the data content and evaluation procedures are defined, and the most recent evaluations are described in terms of specific radionuclides and the resulting consistency of their recommended decay-data files. New versions of the UKPADD and UKHEDD libraries are regularly submitted to the NEA Data Bank for possible inclusion in the JEFF library.

  15. Monocyte Caspase-1 Is Released in a Stable, Active High Molecular Weight Complex Distinct from the Unstable Cell Lysate-Activated Caspase-1

    PubMed Central

    Shamaa, Obada R.; Mitra, Srabani; Gavrilin, Mikhail A.; Wewers, Mark D.

    2015-01-01

    Mononuclear phagocytes utilize caspase-1 activation as a means to respond to danger signals. Although caspase-1 was discovered using highly concentrated cell extracts that spontaneously activate caspase-1, it is now clear that in live cell models caspase-1 activation occurs in the process of its cellular release and is not an intracellular event. Therefore, we compared the characteristics of caspase-1 activation in the cell lysate model to that of caspase-1 that is released in response to exogenous inflammasome activation. Whereas both models generated active caspase-1, the cell-lysate induced caspase-1 required highly concentrated cell lysates and had a short half-life (~15 min) whereas, the activation induced released caspase-1 required 2–3 log fold fewer cells and was stable for greater than 12 h. Both forms were able to cleave proIL-1beta but unexpectedly, the released activity was unable to be immunodepleted by caspase-1 antibodies. Size exclusion chromatography identified two antigenic forms of p20 caspase-1 in the activation induced released caspase-1: one at the predicted size of tetrameric, p20/p10 caspase-1 and the other at >200 kDa. However, only the high molecular weight form had stable functional activity. These results suggest that released caspase-1 exists in a unique complex that is functionally stable and protected from immunodepletion whereas cell-extract generated active caspase-1 is rapidly inhibited in the cytosolic milieu. PMID:26599267

  16. Chlorotriazine herbicides and metabolites activate an ACTH-dependent release of corticosterone in male Wistar rats.

    PubMed

    Laws, Susan C; Hotchkiss, Michelle; Ferrell, Janet; Jayaraman, Saro; Mills, Lesley; Modic, Walker; Tinfo, Nicole; Fraites, Melanie; Stoker, Tammy; Cooper, Ralph

    2009-11-01

    Previously, we reported that atrazine (ATR) alters steroidogenesis in male Wistar rats resulting in elevated serum corticosterone (CORT), progesterone, and estrogens. The increase in CORT indicated that this chlorotriazine herbicide may alter the hypothalamic-pituitary-adrenal axis. This study characterizes the temporal changes in adrenocorticotropic hormone (ACTH), CORT, and P4 in male Wistar rats following a single dose of ATR (0, 5, 50, 100, and 200 mg/kg), simazine (SIM; 188 mg/kg), propazine (PRO; 213 mg/kg), or primary metabolites, deisopropylatrazine (DIA; 4, 10, 40, 80, and 160 mg/kg), deethylatrazine (DEA; 173 mg/kg), and diamino-s-chlorotriazine (DACT; 3.37, 33.7, 67.5, and 135 mg/kg). The maximum dose for each chemical was the molar equivalent of ATR (200 mg/kg). Significant increases in plasma ACTH were observed within 15 min, following exposure to ATR, SIM, PRO, DIA, or DEA. Dose-dependent elevations in CORT and progesterone were also observed at 15 and 30 min post-dosing with these compounds indicating an activation of adrenal steroidogenesis. Measurement of the plasma concentrations of the parent compounds and metabolites confirmed that ATR, SIM, and PRO are rapidly metabolized to DACT. Although DACT had only minimal effects on ACTH and steroid release, dosing with this metabolite resulted in plasma DACT concentrations that were 60-fold greater than that observed following an equimolar dose of ATR and eightfold greater than equimolar doses of DIA or DEA, indicating that DACT is not likely the primary inducer of ACTH release. Thus, the rapid release of ACTH and subsequent activation of adrenal steroidogenesis following a single exposure to ATR, SIM, PRO, DIA, or DEA may reflect chlorotriazine-induced changes at the level of the brain and/or pituitary.

  17. Light-controlled active release of photocaged ciprofloxacin for lipopolysaccharide-targeted drug delivery using dendrimer conjugates.

    PubMed

    Wong, Pamela T; Tang, Shengzhuang; Mukherjee, Jhindan; Tang, Kenny; Gam, Kristina; Isham, Danielle; Murat, Claire; Sun, Rachel; Baker, James R; Choi, Seok Ki

    2016-08-16

    We report an active delivery mechanism targeted specifically to Gram(-) bacteria based on the photochemical release of photocaged ciprofloxacin carried by a cell wall-targeted dendrimer nanoconjugate. PMID:27476878

  18. Cytidine deaminase activity in synovial fluid of patients with rheumatoid arthritis: relation to lactoferrin, acidosis, and cartilage proteoglycan release.

    PubMed Central

    Månsson, B; Geborek, P; Saxne, T; Björnsson, S

    1990-01-01

    It is claimed that cytidine deaminase activity reflects local granulocyte turnover or activity in the synovial fluid of patients with rheumatoid arthritis, but cytidine deaminase is not a granulocyte specific enzyme. Lactoferrin is a granulocyte specific protein that is released from the secondary granulae during activation. We measured cytidine deaminase activity and lactoferrin concentrations in 33 rheumatic synovial fluid samples. Cytidine deaminase activity and lactoferrin concentrations correlated closely, indicating that both analyses reflect similar events in the joint-that is, result in their release from granulocytes. Cytidine deaminase activity and granulocyte concentrations correlated less closely, suggesting that there are additional factors besides the cell number which contribute to this release. Joint acidosis may be one such factor, as pH and cytidine deaminase activity correlated inversely. There was no association with synovial fluid proteoglycan concentrations, a marker of cartilage degradation. PMID:2396864

  19. Activation of histamine H3 receptors inhibits carrier-mediated norepinephrine release in a human model of protracted myocardial ischemia.

    PubMed

    Hatta, E; Yasuda, K; Levi, R

    1997-11-01

    During protracted myocardial ischemia, ATP depletion promotes Na+ accumulation in sympathetic terminals and prevents vesicular storage of norepinephrine (NE). This forces the reversal of the neuronal uptake1 transporter, and NE is massively released (carrier-mediated release). We had shown that histamine H3 receptors (H3Rs) modulate ischemic NE release in animals. We have now used a human model of protracted myocardial ischemia to investigate whether H3Rs may control carrier-mediated NE release. Surgical specimens of human atrium were incubated in anoxic conditions. NE release increased approximately 7-fold within 70 min of anoxia. This release was carrier mediated because it was Ca++ independent and inhibited by the uptake1 inhibitor desipramine. Furthermore, the Na+/H+ exchanger (NHE) inhibitors ethyl-isopropyl-amiloride and HOE 642, and the Na+ channel blocker tetrodotoxin inhibited NE release, whereas the Na+ channel activator aconitine potentiated it. The selective H3R agonist imetit decreased NE release, an effect that was blocked by each of the H3R antagonists thioperamide and clobenpropit. Notably, imetit acted synergistically with ethyl-isopropyl-amiloride, HOE 642 and tetrodotoxin to reduce anoxic NE release. Thus, activation of H3R appears to result in an inhibition of both NHE- and voltage-dependent Na+ channels. Most importantly, endogenous histamine was released from the anoxic human heart, and thioperamide and clobenpropit each alone increased NE release, indicating that H3R become activated in myocardial ischemia. Our findings indicate that H3Rs are likely to mitigate sympathetic overactivity in the ischemic human heart and suggest new therapeutic strategies to alleviate dysfunctions associated with myocardial ischemia.

  20. Effects of Globally Waste-Disturbing Activities on Gas Generation, Retention, and Release in Hanford Waste Tanks

    SciTech Connect

    Stewart, Charles W.; Huckaby, James L.; Meyer, Perry A.

    2002-12-18

    Various operations are authorized in Hanford single- and double-shell tanks that disturb all or a large fraction of the waste. These globally waste-disturbing activities have the potential to release a large fraction of the retained flammable gas and to affect future gas generation, retention, and release behavior. This report presents analyses of the expected flammable gas release mechanisms and the potential release rates and volumes resulting from these activities. The background of the flammable gas safety issue at Hanford is summarized, as is the current understanding of gas generation, retention, and release phenomena. Considerations for gas monitoring and assessment of the potential for changes in tank classification and steady-state flammability are given.

  1. Molecular organization and assembly of the presynaptic active zone of neurotransmitter release.

    PubMed

    Fejtova, Anna; Gundelfinger, Eckart D

    2006-01-01

    At chemical synapses, neurotransmitter is released at a restricted region of the presynaptic plasma membrane, called the active zone. At the active zone, a matrix of proteins is assembled, which is termed the presynaptic grid or cytomatrix at the active zone (CAZ). Components of the CAZ are thought to localize and organize the synaptic vesicle cycle, a series of membrane trafficking events underlying regulated neurotransmitter exocytosis. This review is focused on a set of specific proteins involved in the structural and functional organization of the CAZ. These include the multi-domain Rab3-effector proteins RIM1alpha and RIM2alpha; Bassoon and Piccolo, two multi-domain CAZ scaffolding proteins of enormous size; as well as members of the CAST/ERC family of CAZ-specific structural proteins. Studies on ribbon synapses of retinal photoreceptor cells have fostered understanding the molecular design of the CAZ. In addition, the analysis of the delivery pathways for Bassoon and Piccolo to presynaptic sites during development has produced new insights into assembly mechanisms of brain synapses during development. Based on these studies, the active zone transport vesicle hypothesis was formulated, which postulates that active zones, at least in part, are pre-assembled in neuronal cell bodies and transported as so-called Piccolo-Bassoon transport vesicles (PTVs) to sites of synaptogenesis. Several PTVs can fuse on demand with the presynaptic membrane to rapidly form an active zone.

  2. Release of butylated hydroxytoluene from an active film packaging to Asadero cheese and its effect on oxidation and odor stability.

    PubMed

    Soto-Cantú, C D; Graciano-Verdugo, A Z; Peralta, E; Islas-Rubio, A R; González-Córdova, A; González-León, A; Soto-Valdez, H

    2008-01-01

    Antioxidant active packaging consisting of coextruded films made of low density polyethylene (LDPE) added with 0, 8, and 14 mg/g of butylated hydroxytoluene (BHT) and polyamide 6/66 were fabricated. The release of BHT from the films to Asadero cheese was determined. Most of the BHT was diffused from the LDPE layer to the cheese during the first 20 d of storage at 5 degrees C. Diffusion coefficient for the diffusion of BHT from the films 8 and 14 to the cheese was calculated as 6.24E-12 and 6.26E-12 cm2/s, respectively. The release of BHT from the film added with 8 mg/g of the antioxidant in the LDPE layer complied with the legal limit established for food products. However, the film added with 14 mg/g of the antioxidant exceeded that limit. The film added with 8 mg/g of BHT maintained the same levels of oxidized odor from 20 to 100 d of storage.

  3. Novel biologically active series of N-acetylglucosamine derivatives for the suppressive activities on GAG release.

    PubMed

    Cao, Tingting; Li, Yong; Jiang, Lijuan; Yuan, Li; Dong, Lin; Li, Ying; Yin, Shufan

    2016-10-01

    (d)-Glucosamine and other nutritional supplements have emerged as safe alternative therapies for osteoarthritis, a chronic and degenerative articular joint disease. N-acetyl-(d)-glucosamine, a compound that can be modified at the N position, is considered to improve the oral bioavailability of (d)-glucosamine and has been proven to possess greater in vitro chondroprotective activity compared with the parent agent. In this study, to further utilize these properties, we focus on the modification of the N position with a benzenesulfonyl and different isoxazole formyl groups. Among these compounds, the 3-(2-chlorobenzene)-5-methyl-isoxazole formyl chloride and p-methoxybenzenesulfonyl chloride modifying structures proved to be the most active of the series and efficiently processed the chondrocytes in vitro. These novel N-position substitution compounds may represent promising leads for osteoarthritis drug development. PMID:27454655

  4. Release of surfactant cargo from interfacially-active halloysite clay nanotubes for oil spill remediation.

    PubMed

    Owoseni, Olasehinde; Nyankson, Emmanuel; Zhang, Yueheng; Adams, Samantha J; He, Jibao; McPherson, Gary L; Bose, Arijit; Gupta, Ram B; John, Vijay T

    2014-11-18

    Naturally occurring halloysite clay nanotubes are effective in stabilizing oil-in-water emulsions and can serve as interfacially-active vehicles for delivering oil spill treating agents. Halloysite nanotubes adsorb at the oil-water interface and stabilize oil-in-water emulsions that are stable for months. Cryo-scanning electron microscopy (Cryo-SEM) imaging of the oil-in-water emulsions shows that these nanotubes assemble in a side-on orientation at the oil-water interface and form networks on the interface through end-to-end linkages. For application in the treatment of marine oil spills, halloysite nanotubes were successfully loaded with surfactants and utilized as an interfacially-active vehicle for the delivery of surfactant cargo. The adsorption of surfactant molecules at the interface serves to lower the interfacial tension while the adsorption of particles provides a steric barrier to drop coalescence. Pendant drop tensiometry was used to characterize the dynamic reduction in interfacial tension resulting from the release of dioctyl sulfosuccinate sodium salt (DOSS) from halloysite nanotubes. At appropriate surfactant compositions and loadings in halloysite nanotubes, the crude oil-saline water interfacial tension is effectively lowered to levels appropriate for the dispersion of oil. This work indicates a novel concept of integrating particle stabilization of emulsions together with the release of chemical surfactants from the particles for the development of an alternative, cheaper, and environmentally-benign technology for oil spill remediation.

  5. Mesoporous silica coatings for cephalosporin active release at the bone-implant interface

    NASA Astrophysics Data System (ADS)

    Rădulescu, Dragoş; Voicu, Georgeta; Oprea, Alexandra Elena; Andronescu, Ecaterina; Grumezescu, Valentina; Holban, Alina Maria; Vasile, Bogdan Stefan; Surdu, Adrian Vasile; Grumezescu, Alexandru Mihai; Socol, Gabriel; Mogoantă, Laurenţiu; Mogoşanu, George Dan; Balaure, Paul Cătălin; Rădulescu, Radu; Chifiriuc, Mariana Carmen

    2016-06-01

    In this study, we investigated the potential of MAPLE-deposited coatings mesoporous silica nanoparticles (MSNs) to release Zinforo (ceftarolinum fosmil) in biologically active form. The MSNs were prepared by using a classic procedure with cetyltrimethylammonium bromide as sacrificial template and tetraethylorthosilicate as the monomer. The Brunauer-Emmett-Teller (BET) and transmission electron microscopy (TEM) analyses revealed network-forming granules with diameters under 100 nm and an average pore diameter of 2.33 nm. The deposited films were characterized by SEM, TEM, XRD and IR. Microbiological analyses performed on ceftaroline-loaded films demonstrated that the antibiotic was released in an active form, decreasing the microbial adherence rate and colonization of the surface. Moreover, the in vitro and in vivo assays proved the excellent biodistribution and biocompatibility of the prepared systems. Our results suggest that the obtained bioactive coatings possess a significant potential for the design of drug delivery systems and antibacterial medical-use surfaces, with great applications in bone implantology.

  6. Release of surfactant cargo from interfacially-active halloysite clay nanotubes for oil spill remediation.

    PubMed

    Owoseni, Olasehinde; Nyankson, Emmanuel; Zhang, Yueheng; Adams, Samantha J; He, Jibao; McPherson, Gary L; Bose, Arijit; Gupta, Ram B; John, Vijay T

    2014-11-18

    Naturally occurring halloysite clay nanotubes are effective in stabilizing oil-in-water emulsions and can serve as interfacially-active vehicles for delivering oil spill treating agents. Halloysite nanotubes adsorb at the oil-water interface and stabilize oil-in-water emulsions that are stable for months. Cryo-scanning electron microscopy (Cryo-SEM) imaging of the oil-in-water emulsions shows that these nanotubes assemble in a side-on orientation at the oil-water interface and form networks on the interface through end-to-end linkages. For application in the treatment of marine oil spills, halloysite nanotubes were successfully loaded with surfactants and utilized as an interfacially-active vehicle for the delivery of surfactant cargo. The adsorption of surfactant molecules at the interface serves to lower the interfacial tension while the adsorption of particles provides a steric barrier to drop coalescence. Pendant drop tensiometry was used to characterize the dynamic reduction in interfacial tension resulting from the release of dioctyl sulfosuccinate sodium salt (DOSS) from halloysite nanotubes. At appropriate surfactant compositions and loadings in halloysite nanotubes, the crude oil-saline water interfacial tension is effectively lowered to levels appropriate for the dispersion of oil. This work indicates a novel concept of integrating particle stabilization of emulsions together with the release of chemical surfactants from the particles for the development of an alternative, cheaper, and environmentally-benign technology for oil spill remediation. PMID:25346266

  7. Bruchpilot and Synaptotagmin collaborate to drive rapid glutamate release and active zone differentiation.

    PubMed

    Paul, Mila M; Pauli, Martin; Ehmann, Nadine; Hallermann, Stefan; Sauer, Markus; Kittel, Robert J; Heckmann, Manfred

    2015-01-01

    The active zone (AZ) protein Bruchpilot (Brp) is essential for rapid glutamate release at Drosophila melanogaster neuromuscular junctions (NMJs). Quantal time course and measurements of action potential-waveform suggest that presynaptic fusion mechanisms are altered in brp null mutants (brp(69) ). This could account for their increased evoked excitatory postsynaptic current (EPSC) delay and rise time (by about 1 ms). To test the mechanism of release protraction at brp(69) AZs, we performed knock-down of Synaptotagmin-1 (Syt) via RNAi (syt(KD) ) in wildtype (wt), brp(69) and rab3 null mutants (rab3(rup) ), where Brp is concentrated at a small number of AZs. At wt and rab3(rup) synapses, syt(KD) lowered EPSC amplitude while increasing rise time and delay, consistent with the role of Syt as a release sensor. In contrast, syt(KD) did not alter EPSC amplitude at brp(69) synapses, but shortened delay and rise time. In fact, following syt(KD) , these kinetic properties were strikingly similar in wt and brp(69) , which supports the notion that Syt protracts release at brp(69) synapses. To gain insight into this surprising role of Syt at brp(69) AZs, we analyzed the structural and functional differentiation of synaptic boutons at the NMJ. At 'tonic' type Ib motor neurons, distal boutons contain more AZs, more Brp proteins per AZ and show elevated and accelerated glutamate release compared to proximal boutons. The functional differentiation between proximal and distal boutons is Brp-dependent and reduced after syt(KD) . Notably, syt(KD) boutons are smaller, contain fewer Brp positive AZs and these are of similar number in proximal and distal boutons. In addition, super-resolution imaging via dSTORM revealed that syt(KD) increases the number and alters the spatial distribution of Brp molecules at AZs, while the gradient of Brp proteins per AZ is diminished. In summary, these data demonstrate that normal structural and functional differentiation of Drosophila AZs requires

  8. Bruchpilot and Synaptotagmin collaborate to drive rapid glutamate release and active zone differentiation

    PubMed Central

    Paul, Mila M.; Pauli, Martin; Ehmann, Nadine; Hallermann, Stefan; Sauer, Markus; Kittel, Robert J.; Heckmann, Manfred

    2015-01-01

    The active zone (AZ) protein Bruchpilot (Brp) is essential for rapid glutamate release at Drosophila melanogaster neuromuscular junctions (NMJs). Quantal time course and measurements of action potential-waveform suggest that presynaptic fusion mechanisms are altered in brp null mutants (brp69). This could account for their increased evoked excitatory postsynaptic current (EPSC) delay and rise time (by about 1 ms). To test the mechanism of release protraction at brp69 AZs, we performed knock-down of Synaptotagmin-1 (Syt) via RNAi (sytKD) in wildtype (wt), brp69 and rab3 null mutants (rab3rup), where Brp is concentrated at a small number of AZs. At wt and rab3rup synapses, sytKD lowered EPSC amplitude while increasing rise time and delay, consistent with the role of Syt as a release sensor. In contrast, sytKD did not alter EPSC amplitude at brp69 synapses, but shortened delay and rise time. In fact, following sytKD, these kinetic properties were strikingly similar in wt and brp69, which supports the notion that Syt protracts release at brp69synapses. To gain insight into this surprising role of Syt at brp69 AZs, we analyzed the structural and functional differentiation of synaptic boutons at the NMJ. At ‘tonic’ type Ib motor neurons, distal boutons contain more AZs, more Brp proteins per AZ and show elevated and accelerated glutamate release compared to proximal boutons. The functional differentiation between proximal and distal boutons is Brp-dependent and reduced after sytKD. Notably, sytKD boutons are smaller, contain fewer Brp positive AZs and these are of similar number in proximal and distal boutons. In addition, super-resolution imaging via dSTORM revealed that sytKD increases the number and alters the spatial distribution of Brp molecules at AZs, while the gradient of Brp proteins per AZ is diminished. In summary, these data demonstrate that normal structural and functional differentiation of Drosophila AZs requires concerted action of Brp and Syt. PMID

  9. dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration.

    PubMed

    Nelson, Amanda M; Reddy, Sashank K; Ratliff, Tabetha S; Hossain, M Zulfiquer; Katseff, Adiya S; Zhu, Amadeus S; Chang, Emily; Resnik, Sydney R; Page, Carly; Kim, Dongwon; Whittam, Alexander J; Miller, Lloyd S; Garza, Luis A

    2015-08-01

    Regeneration of skin and hair follicles after wounding--a process known as wound-induced hair neogenesis (WIHN)--is a rare example of adult organogenesis in mammals. As such, WIHN provides a unique model system for deciphering mechanisms underlying mammalian regeneration. Here, we show that dsRNA, which is released from damaged skin, activates Toll-Like Receptor 3 (TLR3) and its downstream effectors IL-6 and STAT3 to promote hair follicle regeneration. Conversely, TLR3-deficient animals fail to initiate WIHN. TLR3 activation promotes expression of hair follicle stem cell markers and induces elements of the core hair morphogenetic program, including ectodysplasin A receptor (EDAR) and the Wnt and Shh pathways. Our results therefore show that dsRNA and TLR3 link the earliest events of mammalian skin wounding to regeneration and suggest potential therapeutic approaches for promoting hair neogenesis.

  10. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

    SciTech Connect

    Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.; Liu Tao; Yue, H.-Y.; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-02-20

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na{sup +}-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  11. Free radical-mediated platelet activation by hemoglobin released from red blood cells.

    PubMed

    Iuliano, L; Violi, F; Pedersen, J Z; Praticò, D; Rotilio, G; Balsano, F

    1992-12-01

    It is known that the rate of thrombus formation depends on interaction between platelets and erythrocytes, but the mechanism of this process has remained obscure. We here show that nanomolar levels of hemoglobin released from damaged red blood cells can induce platelet aggregation. The molecular mechanism is not receptor-based, but involves oxidation of oxyhemoglobin by platelet-derived hydrogen peroxide, with subsequent generation of a small unknown free radical species, detected by ESR spectroscopy. Methemoglobin and carbon monoxide-treated hemoglobin are unable to cause platelet activation or radical formation. The aggregation of platelets induced by hemoglobin is completely blocked by catalase or radical scavengers. These findings indicate a role for a novel extracellular free radical second messenger in the activation of platelets.

  12. Curdlan in fibers as carriers of tetracycline hydrochloride: Controlled release and antibacterial activity.

    PubMed

    El-Naggar, Mehrez E; Abdelgawad, Abdelrahman M; Salas, Carlos; Rojas, Orlando J

    2016-12-10

    Curdlan (CURD) and polyethylene oxide were used to synthesize nanofibers as carriers of hydro soluble tetracycline hydrochloride (TCH). The viscosity, surface tension and conductivity of the precursor multicomponent aqueous solutions were determined and adjusted to produce defect-free fiber webs. Except for a slight increase in diameter, the addition of TCH did not affect the original morphology of the CURD/PEO nanofibers, as determined by FE-SEM imaging. However, the thermal stability of the system was enhanced (TGA and DSC). Moreover, water resistance, as measured with 24-h immersion tests, was observed upon crosslinking with glutaraldehyde. In-vitro activity measurements indicated a sustained and controlled TCH time-release pattern and excellent antibacterial activity against E. coli, as assessed by UV-vis spectroscopy and viable cell counting, respectively. Overall, we propose nanofibers based on CURD as promising platforms for scaffolds for wound dressing and drug delivery. PMID:27577910

  13. Thimerosal compromises human dendritic cell maturation, IL-12 production, chemokine release, and T-helper polarization

    PubMed Central

    Loison, Emily; Gougeon, Marie-Lise

    2014-01-01

    Thimerosal is a preservative used in multidose vials of vaccine formulations to prevent bacterial and fungal contamination. We recently reported that nanomolar concentrations of thimerosal induce cell cycle arrest of human T cells activated via the TCR and inhibition of proinflammatory cytokine production, thus interfering with T-cell functions. Given the essential role of dendritic cells (DCs) in T-cell polarization and vaccine immunity, we studied the influence of non-toxic concentrations of thimerosal on DC maturation and functions. Ex-vivo exposure of human monocyte-derived DCs to nanomolar concentrations of thimerosal prevented LPS-induced DC maturation, as evidenced by the inhibition of morphological changes and a decreased expression of the maturation markers CD86 and HLA-DR. In addition thimerosal dampened their proinflammatory response, in particular the production of the Th1 polarizing cytokine IL-12, as well as TNF-α and IL-6. DC-dependent T helper polarization was altered, leading to a decreased production of IFN-γ IP10 and GM-CSF and increased levels of IL-8, IL-9, and MIP-1α. Although multi-dose vials of vaccines containing thimerosal remain important for vaccine delivery, our results alert about the ex-vivo immunomodulatory effects of thimerosal on DCs, a key player for the induction of an adaptive response PMID:25424939

  14. Fate of corrosion products released from stainless steel in marine sediments and seawater. Part 2. Sequim Bay clayey silt

    SciTech Connect

    Schmidt, R.L.

    1982-04-01

    This report describes laboratory experiments in which neutron-activated 347 stainless steel specimens were exposed to clayey silt from Sequim Bay, Washington. The properties and trace metal geochemistry of the sediment and the amounts of corrosion products that were released under oxic and reduced conditions and their distribution among different chemical fractions of the sediment are discussed. The distributions of Cr, Mn, Fe, Ni and Cu among different chemical forms in the Sequim Bay sediment show that DTPA removed <10% of extractable Cr, Fe and Mn, approx. 20% of extractable Ni and approx. 30% of extractable Cu. The inorganic fraction (material soluble in 2.5% acetic acid) accounted for approx. 30% of total extractable Mn and approx. 10% or less of Cr, Fe, Ni and Cu. Major portions of Cr and Cu, and a large amount of Fe were in the organic fraction. Extractable Mn, Fe and Ni were associated with hydrous oxides likely as coatings on the mineral substrate of the sediment. No Co was detectable in any of the extracts. (PSB)

  15. Influence of local anesthetics upon human polymorphonuclear leukocyte function in vitro. Reduction of lysosomal enzyme release and superoxide anion production.

    PubMed

    Goldstein, I M; Lind, S; Hoffstein, S; Weissmann, G

    1977-08-01

    Cationic local anesthetics have been reported to influence cellular responses to surface stimuli by interfering with the function of microtubules and microfilaments. Since unimpaired microtubule and microfilament functions are required by human polymorphonuclear leukocytes in order to respond normally to surface stimulation, we have studied effects of the local anesthetic, tetracaine on the function and morphology of these cells in vitro. Tetracaine (0.25--1.0 mM) significantly reduced extracellular release of the lysosomal enzymes, beta-glucuronidase and lysozyme from polymorphonuclear leukocytes exposed to serum-treated zymosan (a particulate stimulus), zymosan-treated serum (a soluble stimulus), and to the surface-active lectin, concanavalin A. Tetracaine also significantly reduced superoixde anion production (superoxide dismutase-inhibitable cytochrome c reduction) by these cells. Tetrancaine was not cytotoxic and its effects could be reversed completely by washing cells once with buffer. Electron microscope examination of tetracaine-treated cells revealed marked alterations of surface membranes. Microtubules and microfilaments appeared normal in "resting" polymorphonuclear leukocytes, but the increase in microtubules normally observed in stimulated cells was not seen after tetracaine treatment. These results suggest that tetracaine interferes with those interactions between immune reactants and the polymorphonuclear leukocyte cell surface which provoke exocytosis and increased oxidative metabolism.

  16. Leveraging electrokinetics for the active control of dendritic fullerene-1 release across a nanochannel membrane

    NASA Astrophysics Data System (ADS)

    Bruno, Giacomo; Geninatti, Thomas; Hood, R. Lyle; Fine, Daniel; Scorrano, Giovanni; Schmulen, Jeffrey; Hosali, Sharath; Ferrari, Mauro; Grattoni, Alessandro

    2015-03-01

    General adoption of advanced treatment protocols such as chronotherapy will hinge on progress in drug delivery technologies that provide precise temporal control of therapeutic release. Such innovation is also crucial to future medicine approaches such as telemedicine. Here we present a nanofluidic membrane technology capable of achieving active and tunable control of molecular transport through nanofluidic channels. Control was achieved through application of an electric field between two platinum electrodes positioned on either surface of a 5.7 nm nanochannel membrane designed for zero-order drug delivery. Two electrode configurations were tested: laser-cut foils and electron beam deposited thin-films, configurations capable of operating at low voltage (<=1.5 V), and power (100 nW). Temporal, reproducible tuning and interruption of dendritic fullerene 1 (DF-1) transport was demonstrated over multi-day release experiments. Conductance tests showed limiting currents in the low applied potential range, implying ionic concentration polarization (ICP) at the interface between the membrane's micro- and nanochannels, even in concentrated solutions (<=1 M NaCl). The ability of this nanotechnology platform to facilitate controlled delivery of molecules and particles has broad applicability to next-generation therapeutics for numerous pathologies, including autoimmune diseases, circadian dysfunction, pain, and stress, among others.General adoption of advanced treatment protocols such as chronotherapy will hinge on progress in drug delivery technologies that provide precise temporal control of therapeutic release. Such innovation is also crucial to future medicine approaches such as telemedicine. Here we present a nanofluidic membrane technology capable of achieving active and tunable control of molecular transport through nanofluidic channels. Control was achieved through application of an electric field between two platinum electrodes positioned on either surface of a 5

  17. Production of high specific activity silicon-32

    DOEpatents

    Phillips, Dennis R.; Brzezinski, Mark A.

    1994-01-01

    A process for preparation of silicon-32 is provide and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution to from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidization state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  18. Monascus secondary metabolites: production and biological activity.

    PubMed

    Patakova, Petra

    2013-02-01

    The genus Monascus, comprising nine species, can reproduce either vegetatively with filaments and conidia or sexually by the formation of ascospores. The most well-known species of genus Monascus, namely, M. purpureus, M. ruber and M. pilosus, are often used for rice fermentation to produce red yeast rice, a special product used either for food coloring or as a food supplement with positive effects on human health. The colored appearance (red, orange or yellow) of Monascus-fermented substrates is produced by a mixture of oligoketide pigments that are synthesized by a combination of polyketide and fatty acid synthases. The major pigments consist of pairs of yellow (ankaflavin and monascin), orange (rubropunctatin and monascorubrin) and red (rubropunctamine and monascorubramine) compounds; however, more than 20 other colored products have recently been isolated from fermented rice or culture media. In addition to pigments, a group of monacolin substances and the mycotoxin citrinin can be produced by Monascus. Various non-specific biological activities (antimicrobial, antitumor, immunomodulative and others) of these pigmented compounds are, at least partly, ascribed to their reaction with amino group-containing compounds, i.e. amino acids, proteins or nucleic acids. Monacolins, in the form of β-hydroxy acids, inhibit hydroxymethylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis in animals and humans.

  19. Cofactor-Mediated Conformational Dynamics Promote Product Release From Escherichia coli Dihydrofolate Reductase via an Allosteric Pathway

    PubMed Central

    2016-01-01

    The enzyme dihydrofolate reductase (DHFR, E) from Escherichia coli is a paradigm for the role of protein dynamics in enzyme catalysis. Previous studies have shown that the enzyme progresses through the kinetic cycle by modulating the dynamic conformational landscape in the presence of substrate dihydrofolate (DHF), product tetrahydrofolate (THF), and cofactor (NADPH or NADP+). This study focuses on the quantitative description of the relationship between protein fluctuations and product release, the rate-limiting step of DHFR catalysis. NMR relaxation dispersion measurements of millisecond time scale motions for the E:THF:NADP+ and E:THF:NADPH complexes of wild-type and the Leu28Phe (L28F) point mutant reveal conformational exchange between an occluded ground state and a low population of a closed state. The backbone structures of the occluded ground states of the wild-type and mutant proteins are very similar, but the rates of exchange with the closed excited states are very different. Integrated analysis of relaxation dispersion data and THF dissociation rates measured by stopped-flow spectroscopy shows that product release can occur by two pathways. The intrinsic pathway consists of spontaneous product dissociation and occurs for all THF-bound complexes of DHFR. The allosteric pathway features cofactor-assisted product release from the closed excited state and is utilized only in the E:THF:NADPH complexes. The L28F mutation alters the partitioning between the pathways and results in increased flux through the intrinsic pathway relative to the wild-type enzyme. This repartitioning could represent a general mechanism to explain changes in product release rates in other E. coli DHFR mutants. PMID:26147643

  20. Silver nanoparticles temporarily retard NO2 - production without significantly affecting N2 O release by Nitrosomonas europaea.

    PubMed

    Michels, Camila; Yang, Yu; Moreira Soares, Hugo; Alvarez, Pedro J J

    2015-10-01

    Nitrifying bacteria are highly susceptible to silver nanoparticles (AgNPs). However, the effect of sublethal exposure to AgNPs after their release of nitrogenous compounds of environmental concern (e.g., the greenhouse gas nitrous oxide [N2 O] and the common water pollutant nitrite [NO2 -]) has not been systematically investigated. The present study reports the effect of AgNPs (and potentially released silver ions [Ag(+) ]) on NO2 - and N2 O production by Nitrosomonas europaea, and on the transcription of the associated genes. The release of NO2 - was more negatively affected than the production of N2 O. For example, exposure to AgNPs at 0.075 mg/L temporarily enhanced N2 O production (by 12%) without affecting nitrite release, whereas higher AgNP concentrations (>0.25 mg/L) inhibited NO2 - release (by >12%) but not N2 O production. Transcriptomic analyses corroborated these trends; AgNPs at 0.075 mg/L increased the expression of the nitric oxide reductase gene (norQ) associated with N2 O production (by 5.3-fold to 12.8-fold), whereas both 0.075 mg/L of Ag(+) and 0.75 mg/L of AgNPs down-regulated the ammonia monooxygenase gene (amoA2; by 0.08-fold to 0.15-fold and 0.32-fold to 0.64-fold, respectively), the nitrite reductase gene (nirK; by 0.01-fold to 0.02-fold and 0.22-fold to 0.44-fold, respectively), and norQ (by 0.11-fold to 0.15-fold and 0.32-fold to 0.57-fold, respectively). These results suggest that AgNP release to sewage treatment plants and land application of AgNP-containing biosolids should be minimized because of their potential temporary stimulation of N2 O release and interference with nitrification. Environ Toxicol Chem 2015;34:2231-2235. © 2015 SETAC. PMID:26010547

  1. Optimising aroma quality in curry sauce products using in vivo aroma release measurements.

    PubMed

    Hatakeyama, Jun; Davidson, James M; Kant, Avinash; Koizumi, Takeshi; Hayakawa, Fumiyo; Taylor, Andrew J

    2014-08-15

    Reducing fat content in foods to meet consumers' preferences and to address the obesity issue is a key task for food manufacturers but simply reducing fat content affects aroma quality adversely. Measuring the aroma release from regular and low-fat samples during eating to rebalance the aroma release has proved successful in model systems. Here, the reformulation of the spice content in a low fat curry sauce is described. Volatile markers of the key spices (coriander, cumin and turmeric) were selected and used to measure aroma release in regular (10 g oil/100 g) and low (2.5 or 5 g oil/100 g) fat sauces. Regression models were used to adjust the ingredient formulation so that the aroma release profiles in vivo were the same for the regular and reduced oil curry sauces and sensory analysis showed no significant difference between these samples. Despite the complexity of spice aromas, rebalancing was successful.

  2. Neutron activation-based gamma scintigraphy in pharmacoscintigraphic evaluation of an Egalet constant-release drug delivery system.

    PubMed

    Marvola, Janne; Kanerva, Hanna; Slot, Lillian; Lipponen, Maija; Kekki, Tommi; Hietanen, Heikki; Mykkänen, Sirpa; Ariniemi, Kari; Lindevall, Kai; Marvola, Martti

    2004-08-20

    This paper is a report from a pharmacoscintigraphic study with an Egalet constant-release system containing caffeine and natural abundance samarium oxide. First the formulation was tested in vitro to clarify integrity during irradiation in the nuclear reactor. Then six healthy male volunteers were enrolled into the in vivo study. The in vitro release of caffeine obeyed all the time linear zero-order kinetics. The in vivo release of radioactive Sm2O3 consisted of three consequent linear phases with different slopes. The release rate was fastest while the product was in the small intestine and slowest when the product was in the descending colon. In terms of the bioavailability of caffeine, the most important factor seemed to be the residence time in the ascending and transverse colon. A long residence time in these sections led to high AUC values for caffeine. PMID:15288338

  3. Neutron activation-based gamma scintigraphy in pharmacoscintigraphic evaluation of an Egalet constant-release drug delivery system.

    PubMed

    Marvola, Janne; Kanerva, Hanna; Slot, Lillian; Lipponen, Maija; Kekki, Tommi; Hietanen, Heikki; Mykkänen, Sirpa; Ariniemi, Kari; Lindevall, Kai; Marvola, Martti

    2004-08-20

    This paper is a report from a pharmacoscintigraphic study with an Egalet constant-release system containing caffeine and natural abundance samarium oxide. First the formulation was tested in vitro to clarify integrity during irradiation in the nuclear reactor. Then six healthy male volunteers were enrolled into the in vivo study. The in vitro release of caffeine obeyed all the time linear zero-order kinetics. The in vivo release of radioactive Sm2O3 consisted of three consequent linear phases with different slopes. The release rate was fastest while the product was in the small intestine and slowest when the product was in the descending colon. In terms of the bioavailability of caffeine, the most important factor seemed to be the residence time in the ascending and transverse colon. A long residence time in these sections led to high AUC values for caffeine.

  4. Selected demonstration and educational products/activities

    SciTech Connect

    Williams, R.J.; Mann, H.C.

    1992-07-01

    The information in this paper was assembled for several informal presentations to a variety of visitor groups during the summer of 1992. A number of staff members at TVA`s National Fertilizer and Environmental Research Center (NFERC) found it useful as a quick overview for their use and for their sharing with external colleagues and customers. The paper is not meant to be an exhaustive list or explanation of all products and services available from NFERC. However, the authors believe it will give a flavor and tenor of some of the ongoing activities of the Center, especially those activities relating to the retail fertilizer dealer. Programs over the years have focused on key aspects of nutrient efficiency and management. TVA is uniquely positioned to assist the fertilizer industry and US agriculture in protecting the environment from potential adverse environmental impacts of agriculture, especially for fertilizer and the attendant agrichemicals. TVA has the technical base and an ongoing working relationship with the fertilizer industry in technology development and introduction. Dealer education is very important in TVA programs in two aspects: (1) education for the dealer in meeting new environmental stewardship challenges from an operational perspective; and (2) education for the dealer in meeting the site-specific information needs of the farmer.

  5. Release of nitric oxide during the T cell-independent pathway of macrophage activation

    SciTech Connect

    Beckerman, K.P.; Rogers, H.W.; Corbett, J.A.; Schreiber, R.D.; McDaniel, M.L.; Unanue, E.R. )

    1993-02-01

    Immunodeficient mice are remarkably resistant to Listeria monocytogenes (LM) infection. The authors examined the role that nitric oxide (NO) plays in the CB-17/lcr SCID (SCID) response to LM. SCID spleen cells produced large quantities of NO (as measured by nitrite formation) when incubated in the presence of heat-killed LM. NO produced large quantities of nitrite in response to LM, but only in the presence of IFN-[gamma]. The production of NO induced by LM was not affected by neutralizing antibodies to TNF or IL-1. The production of NO was inhibited by addition of either of two inhibitors of NO synthase, N[sup G]-monomethyl arginine, or aminoguanidine. In a different situation, NK cells that were stimulated by TNF and Listeria products to release IFN-[gamma] did not produce NO. Macrophages cultured with IFN-[gamma] killed live LM. This increased killing of LM was significantly inhibited by amino-guanidine. In vivo, administration of aminoguanidine resulted in a marked increase in the mortality and spleen bacterial loads of LM-infected SCID or immunocompetent control mice. It is concluded that NO is a critical effector molecule of T cell-independent natural resistence of LM as studied in the SCID mouse, and that the NO-mediated response is essential for both SCID and immunocompetent host to survive after LM infection. 37 refs., 7 figs.

  6. Production of activated carbon from TCR char

    NASA Astrophysics Data System (ADS)

    Stenzel, Fabian; Heberlein, Markus; Klinner, Tobias; Hornung, Andreas

    2016-04-01

    The utilization of char for adsorptive purposes is known since the 18th century. At that time the char was made of wood or bones and used for decoloration of fluids. In the 20th century the production of activated carbon in an industrial scale was started. The today's raw materials for activated carbon production are hard coal, peat, wood or coconut shells. All these materials entail costs especially the latter. Thus, the utilization of carbon rich residues (biomass) is an interesting economic opportunity because it is available for no costs or even can create income. The char is produced by thermo-catalytic reforming (TCR®). This process is a combination of an intermediate pyrolysis and subsequently a reforming step. During the pyrolysis step the material is decomposed in a vapor and a solid carbon enriched phase. In the second step the vapor and the solid phase get in an intensive contact and the quality of both materials is improved via the reforming process. Subsequently, the condensables are precipitated from the vapor phase and a permanent gas as well as oil is obtained. Both are suitable for heat and power production which is a clear advantage of the TCR® process. The obtained biochar from the TCR® process has special properties. This material has a very low hydrogen and oxygen content. Its stability is comparable to hard coal or anthracite. Therefore it consists almost only of carbon and ash. The latter depends from input material. Furthermore the surface structure and area can be influenced during the reforming step. Depending from temperature and residence time the number of micro pores and the surface area can be increased. Preliminary investigations with methylene blue solution have shown that a TCR® char made of digestate from anaerobic digestion has adsorptive properties. The decoloration of the solution was achieved. A further influencing factor of the adsorption performance is the particle size. Based on the results of the preliminary tests a

  7. Calcium-mediated release of glucanase activity from cortical granules of sea urchin eggs.

    PubMed

    Moy, G W; Kopf, G S; Gache, C; Vacquier, V D

    1983-12-01

    Confluent monolayers of sea urchin eggs were bonded to culture dishes coated with protamine sulfate. The cytoplasm was then sheared away by a jet of isosmotic buffer. About 326,000 circular fragments of individual egg cortices (430 micrograms protein) remained bound to each dish. The fragments are composed of cortical granules (CG), plasma membrane, and vitelline layer. A single dish contains 7.7 X 10(8) CG and is referred to as a CG lawn (CGL). Ca2+-EGTA buffers of estimated free-Ca2+ concentrations (0.06-25.7 microM) were applied to CGL and samples removed and assayed for the CG marker enzyme exo-beta (1 leads to 3)-glucanohydrolase (glucanase). Estimated free-Ca2+ concentrations above 2.75 microM caused the total release of the glucanase to the supernatant within 4 min. The half-maximal rate of appearance of glucanase occurred in 2.5 microM Ca2+. At all Ca2+ concentrations tested, the appearance of enzyme activity exhibited sigmoidal kinetics. The visual disappearance of CG correlated with the appearance of glucanase in the Ca2+ buffer. In response to Ca2+ the CG probably lyse, fuse with adjacent CG, or fuse with the underlying plasma membrane. The calmodulin antagonist trifluoperazine inhibited Ca2+-mediated glucanase release from CGL (I50 8 microM). The sensitivity of the CGL to Ca2+ in the 1-10 microM range is rapidly lost during incubation of CGL in the isolation buffer. ATP and low temperature retard the rate of loss of Ca2+ sensitivity. These secretory granules are a model for studying the mechanism of Ca2+-induced secretion. In addition, they contain structural proteins and enzymes which function in the fertilization process. CGL preparations should be useful in studies dealing with the processing of CG components after their release in response to micromolar concentrations of Ca2+.

  8. Waste Form Release Data Package for the 2001 Immobilized Low-Activity Waste Performance Assessment

    SciTech Connect

    McGrail, B. Peter; Icenhower, Jonathan P.; Martin, Paul F.; Schaef, Herbert T.; O'Hara, Matthew J.; Rodriguez, Eugenio; Steele, Jackie L.

    2001-02-01

    This data package documents the experimentally derived input data on the representative waste glasses LAWABP1 and HLP-31 that will be used for simulations of the immobilized lowactivity waste disposal system with the Subsurface Transport Over Reactive Multiphases (STORM) code. The STORM code will be used to provide the near-field radionuclide release source term for a performance assessment to be issued in March of 2001. Documented in this data package are data related to 1) kinetic rate law parameters for glass dissolution, 2) alkali-H ion exchange rate, 3) chemical reaction network of secondary phases that form in accelerated weathering tests, and 4) thermodynamic equilibrium constants assigned to these secondary phases. The kinetic rate law and Na+-H+ ion exchange rate were determined from single-pass flow-through experiments. Pressurized unsaturated flow and vapor hydration experiments were used for accelerated weathering or aging of the glasses. The majority of the thermodynamic data were extracted from the thermodynamic database package shipped with the geochemical code EQ3/6. However, several secondary reaction products identified from laboratory tests with prototypical LAW glasses were not included in this database, nor are the thermodynamic data available in the open literature. One of these phases, herschelite, was determined to have a potentially significant impact on the release calculations and so a solubility product was estimated using a polymer structure model developed for zeolites. Although this data package is relatively complete, final selection of ILAW glass compositions has not been done by the waste treatment plant contractor. Consequently, revisions to this data package to address new ILAW glass formulations are to be regularly expected.

  9. The number and organization of Ca2+ channels in the active zone shapes neurotransmitter release from Schaffer collateral synapses

    PubMed Central

    Scimemi, Annalisa; Diamond, Jeffrey S.

    2013-01-01

    Fast synaptic transmission requires tight co-localization of Ca2+ channels and neurotransmitter vesicles. It is generally thought that Ca2+ channels are expressed abundantly in presynaptic active zones, that vesicles within the same active zone have similar release properties and that significant vesicle depletion only occurs at synapses with high release probability. Here we show, at excitatory CA3→CA1 synapses in mouse hippocampus, that release from individual vesicles is generally triggered by only one Ca2+ channel and that only few functional Ca2+ channels may be spread in the active zone at variable distances to neighboring neurotransmitter vesicles. Using morphologically realistic Monte Carlo simulations, we show that this arrangement leads to a widely heterogeneous distribution of release probability across the vesicles docked at the active zone, and that depletion of the vesicles closest to Ca2+ channels can account for the Ca2+-dependence of short term plasticity at these synapses. These findings challenge the prevailing view that efficient synaptic transmission requires numerous presynaptic Ca2+ channels in the active zone, and indicate that the relative arrangement of Ca2+ channels and vesicles contributes to the heterogeneity of release probability within and across synapses and to vesicle depletion at small central synapses with low average release probability. PMID:23238730

  10. The tumour necrosis factor superfamily ligand APRIL (TNFSF13) is released upon platelet activation and expressed in atherosclerosis.

    PubMed

    Sandberg, Wiggo J; Otterdal, Kari; Gullestad, Lars; Halvorsen, Bente; Ragnarsson, Asgrimur; Frøland, Stig S; Damås, Jan K; Oie, Erik; Aukrust, Pål; Hansson, Göran K; Yndestad, Arne

    2009-10-01

    Activated platelets release a wide range of inflammatory mediators, including members of the tumour necrosis factor (TNF) superfamily (e.g. CD40 ligand [CD40L] and LIGHT). Such platelet-mediated inflammation could be involved in atherogenesis and plaque destabilisation. In the present study we investigated whether APRIL, another member of the TNF superfamily that has been detected in megakaryocytes, could be released from platelets upon activation. The release of APRIL was studied in thrombin receptor (SFLLRN) activated platelets, and the expression of APRIL was examined in plasma and within the atherosclerotic lesion in patients with carotid and coronary atherosclerosis. Upon SFLLRN activation, there was a gradual release of APRIL, reaching maximum after 90 minutes. While this pattern is similar to that of CD40L and LIGHT, the release of APRIL was quite differently regulated. Thus, prostaglandin E1, but not inhibitors of metal-dependent proteases and actin polymerisation or the lack of GP IIb/IIIa, blocks APRIL release in activated platelets. With relevance to atherogenesis, we found that patients with coronary artery disease (n=80) had raised plasma levels of APRIL as compared with controls (n=20), and APRIL immunoreactivity was detected in aggregated platelets within the ruptured plaque in patients with myocardial infarction and within macrophages in symptomatic carotid plaques. In conclusion, activated platelets release significant amounts of APRIL in a long-lasting manner, differently regulated than the gradual release of other platelet-derived TNF superfamily ligands. The enhanced expression of APRIL in atherosclerotic disorders, both systemically and within the lesion, may suggest a potential involvement of APRIL in atherogenesis. PMID:19806256

  11. Release of soluble protein from peanut (Arachis hypogaea, Leguminosae) and its adsorption by activated charcoal.

    PubMed

    Kopper, Randall; Van, Trang; Kim, Ara; Helm, Ricki

    2011-01-12

    Peanut (Arachis hypogaea, Leguminosae) allergy is a major cause of food-induced anaphylaxis. The potential use of activated charcoal (AC) to adsorb and reduce the bioavailability of peanut protein allergens for use in the moderation of hypersensitivity reactions was investigated. The rate and extent of protein release from peanut and the adsorption of the solubilized protein by AC was determined under physiological pH values and confirmed in vivo using a porcine animal model system. Peanut proteins were adsorbed with equal efficiency at pH 2 and 7 and are completely removed from solution by an AC/protein ratio of approximately 80:1. This suggests that AC can bind protein under gastric (pH 2) or intestinal (pH 7) conditions. The rapid adsorption of soluble peanut allergens and the continuous binding of allergens released from peanut particulate material suggest the potential efficacy of using AC for gastric decontamination and possible elimination of a biphasic allergic reaction.

  12. Leveraging electrokinetics for the active control of dendritic fullerene-1 release across a nanochannel membrane

    PubMed Central

    Bruno, Giacomo; Geninatti, Thomas; Hood, R. Lyle; Fine, Daniel; Scorrano, Giovanni; Schmulen, Jeffrey; Hosali, Sharath; Ferrari, Mauro; Grattoni, Alessandro

    2015-01-01

    General adoption of advanced treatment protocols such as chronotherapy will hinge on progress in drug delivery technologies that provide precise temporal control of therapeutic release. Such innovation is also crucial to future medicine approaches such as telemedicine. Here we present a nanofluidic membrane technology capable of achieving active and tunable control of molecular transport through nanofluidic channels. Control was achieved through application of an electric field between two platinum electrodes positioned on either surface of a 5.7 nm nanochannel membrane designed for zero-order drug delivery. Two electrode configurations were tested: laser-cut foils and electron beam deposited thin-films, configurations capable of operating at low voltage (≤1.5 V), and power (100 nW). Temporal, reproducible tuning and interruption of dendritic fullerene 1 (DF-1) transport was demonstrated over multi-day release experiments. Conductance tests showed limiting currents in the low applied potential range, implying ionic concentration polarization (ICP) at the interface between the membrane’s micro- and nanochannels, even in concentrated solutions (≤ 1 M NaCl). The ability of this nanotechnology platform to facilitate controlled delivery of molecules and particles has broad applicability to next-generation therapeutics for numerous pathologies, including autoimmune diseases, circadian dysfunction, pain, and stress, among others. PMID:25707848

  13. Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release.

    PubMed

    Gao, Chunyan; Ji, Shuting; Dong, Weijun; Qi, Yushan; Song, Wen; Cui, Debin; Shi, Jialan

    2015-11-01

    Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients). Phosphatidylserine (PS) exposure of RBCs and their microparticles (MPs) release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca(2+) ([Ca(2+)]) with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca(2+)]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process. PMID:26516916

  14. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent.

    PubMed

    Hussein, Mohd Zobir; Al Ali, Samer Hasan; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2011-01-01

    An ellagic acid (EA)-zinc layered hydroxide (ZLH) nanohybrid (EAN) was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO) as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8' position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host-guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA.

  15. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent

    PubMed Central

    Hussein, Mohd Zobir; Al Ali, Samer Hasan; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2011-01-01

    An ellagic acid (EA)–zinc layered hydroxide (ZLH) nanohybrid (EAN) was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO) as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8′ position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host–guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA. PMID:21796241

  16. Anion-activated, thermoreversible gelation system for the capture, release, and visual monitoring of CO2

    PubMed Central

    Zhang, Xin; Lee, Songyi; Liu, Yifan; Lee, Minji; Yin, Jun; Sessler, Jonathan L.; Yoon, Juyoung

    2014-01-01

    Carbon dioxide (CO2) is an important green house gas. This is providing an incentive to develop new strategies to detect and capture CO2. Achieving both functions within a single molecular system represents an unmet challenge in terms of molecular design and could translate into enhanced ease of use. Here, we report an anion-activated chemosensor system, NAP-chol 1, that permits dissolved CO2 to be detected in organic media via simple color changes or through ratiometric differences in fluorescence intensity. NAP-chol 1 also acts as a super gelator for DMSO. The resulting gel is transformed into a homogeneous solution upon exposure to fluoride anions. Bubbling with CO2 regenerates the gel. Subsequent flushing with N2 or heating serves to release the CO2 and reform the sol form. This series of transformations is reversible and can be followed by easy-to-discern color changes. Thus, NAP-chol 1 allows for the capture and release of CO2 gas while acting as a three mode sensing system. In particular, it permits CO2 to be detected through reversible sol-gel transitions, simple changes in color, or ratiometric monitoring of the differences in the fluorescence features. PMID:24699626

  17. Anion-activated, thermoreversible gelation system for the capture, release, and visual monitoring of CO2

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Lee, Songyi; Liu, Yifan; Lee, Minji; Yin, Jun; Sessler, Jonathan L.; Yoon, Juyoung

    2014-04-01

    Carbon dioxide (CO2) is an important green house gas. This is providing an incentive to develop new strategies to detect and capture CO2. Achieving both functions within a single molecular system represents an unmet challenge in terms of molecular design and could translate into enhanced ease of use. Here, we report an anion-activated chemosensor system, NAP-chol 1, that permits dissolved CO2 to be detected in organic media via simple color changes or through ratiometric differences in fluorescence intensity. NAP-chol 1 also acts as a super gelator for DMSO. The resulting gel is transformed into a homogeneous solution upon exposure to fluoride anions. Bubbling with CO2 regenerates the gel. Subsequent flushing with N2 or heating serves to release the CO2 and reform the sol form. This series of transformations is reversible and can be followed by easy-to-discern color changes. Thus, NAP-chol 1 allows for the capture and release of CO2 gas while acting as a three mode sensing system. In particular, it permits CO2 to be detected through reversible sol-gel transitions, simple changes in color, or ratiometric monitoring of the differences in the fluorescence features.

  18. Anion-activated, thermoreversible gelation system for the capture, release, and visual monitoring of CO2.

    PubMed

    Zhang, Xin; Lee, Songyi; Liu, Yifan; Lee, Minji; Yin, Jun; Sessler, Jonathan L; Yoon, Juyoung

    2014-04-04

    Carbon dioxide (CO2) is an important green house gas. This is providing an incentive to develop new strategies to detect and capture CO2. Achieving both functions within a single molecular system represents an unmet challenge in terms of molecular design and could translate into enhanced ease of use. Here, we report an anion-activated chemosensor system, NAP-chol 1, that permits dissolved CO2 to be detected in organic media via simple color changes or through ratiometric differences in fluorescence intensity. NAP-chol 1 also acts as a super gelator for DMSO. The resulting gel is transformed into a homogeneous solution upon exposure to fluoride anions. Bubbling with CO2 regenerates the gel. Subsequent flushing with N2 or heating serves to release the CO2 and reform the sol form. This series of transformations is reversible and can be followed by easy-to-discern color changes. Thus, NAP-chol 1 allows for the capture and release of CO2 gas while acting as a three mode sensing system. In particular, it permits CO2 to be detected through reversible sol-gel transitions, simple changes in color, or ratiometric monitoring of the differences in the fluorescence features.

  19. Light- and pH-activated intracellular drug release from polymeric mesoporous silica nanoparticles.

    PubMed

    Tian, Ye; Kong, Yi; Li, Xiaojian; Wu, Jun; Ko, Alex C-T; Xing, Malcolm

    2015-10-01

    Surface modified mesoporous silica nanoparticles (MSNs) with reduced toxicity were prepared for light and pH dual triggerable drug delivery system. Both 413 nm light and acidic environment can activate the drug release process, improving the pharmacological action. By applying rhodamine B (RhB) as a model drug, the accumulative RhB release is as high as 95% in pH 5.0 and in irradiation of 413 nm light, compared to only 55% in pH 7.4 and in dark. The anti-cancer drug camptothecin (CPT) loaded nanoparticles can kill cancer cells with IC₅₀ value of 0.02 μg mL(-1) in exposure of 413 nm light, which is much lower than free CPT (about 0.1 μg mL(-1)). Multimodal nonlinear optical imaging microscopy (NLOM) was employed to acquire in vitro coherent anti-Stokes Raman (CARS) and two-photon excited fluorescence (TPEF) images of live MCF-7 cells and showed that the nanoparticles can be taken up by breast tumor cell MCF-7 with high efficiency, indicating its great potential for anti-cancer drug delivery system. PMID:26188470

  20. Leveraging electrokinetics for the active control of dendritic fullerene-1 release across a nanochannel membrane.

    PubMed

    Bruno, Giacomo; Geninatti, Thomas; Hood, R Lyle; Fine, Daniel; Scorrano, Giovanni; Schmulen, Jeffrey; Hosali, Sharath; Ferrari, Mauro; Grattoni, Alessandro

    2015-03-12

    General adoption of advanced treatment protocols such as chronotherapy will hinge on progress in drug delivery technologies that provide precise temporal control of therapeutic release. Such innovation is also crucial to future medicine approaches such as telemedicine. Here we present a nanofluidic membrane technology capable of achieving active and tunable control of molecular transport through nanofluidic channels. Control was achieved through application of an electric field between two platinum electrodes positioned on either surface of a 5.7 nm nanochannel membrane designed for zero-order drug delivery. Two electrode configurations were tested: laser-cut foils and electron beam deposited thin-films, configurations capable of operating at low voltage (≤1.5 V), and power (100 nW). Temporal, reproducible tuning and interruption of dendritic fullerene 1 (DF-1) transport was demonstrated over multi-day release experiments. Conductance tests showed limiting currents in the low applied potential range, implying ionic concentration polarization (ICP) at the interface between the membrane's micro- and nanochannels, even in concentrated solutions (≤1 M NaCl). The ability of this nanotechnology platform to facilitate controlled delivery of molecules and particles has broad applicability to next-generation therapeutics for numerous pathologies, including autoimmune diseases, circadian dysfunction, pain, and stress, among others.

  1. Probabilistic secretion of quanta: spontaneous release at active zones of varicosities, boutons, and endplates.

    PubMed Central

    Bennett, M R; Gibson, W G; Robinson, J

    1995-01-01

    The amplitude-frequency histogram of spontaneous miniature endplate potentials follows a Gaussian distribution at mature endplates. This distribution gives the mean and variance of the quantum of transmitter. According to the vesicle hypothesis, this quantum is due to exocytosis of the contents of a single synaptic vesicle. Multimodal amplitude-frequency histograms are observed in varying degrees at developing endplates and at peripheral and central synapses, each of which has a specific active zone structure. These multimodal histograms may be due to the near synchronous exocytosis of more than one vesicle. In the present work, a theoretical treatment is given of the rise of intraterminal calcium after the stochastic opening of a calcium channel within a particular active zone geometry. The stochastic interaction of this calcium with the vesicle-associated proteins involved in exocytosis is then used to calculate the probability of quantal secretions from one or several vesicles at each active zone type. It is shown that this procedure can account for multiquantal spontaneous release that may occur at varicosities and boutons, compared with that at the active zones of motor nerve terminals. PMID:7669909

  2. Readily releasable vesicles recycle at the active zone of hippocampal synapses.

    PubMed

    Schikorski, Thomas

    2014-04-01

    During the synaptic vesicle cycle, synaptic vesicles fuse with the plasma membrane and recycle for repeated exo/endocytic events. By using activity-dependent N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino) styryl) pyridinium dibromide dye uptake combined with fast (<1 s) microwave-assisted fixation followed by photoconversion and ultrastructural 3D analysis, we tracked endocytic vesicles over time, "frame by frame." The first retrieved synaptic vesicles appeared 4 s after stimulation, and these endocytic vesicles were located just above the active zone. Second, the retrieved vesicles did not show any sign of a protein coat, and coated pits were not detected. Between 10 and 30 s, large labeled vesicles appeared that had up to 5 times the size of an individual synaptic vesicle. Starting at around 20 s, these large labeled vesicles decreased in number in favor of labeled synaptic vesicles, and after 30 s, labeled vesicles redocked at the active zone. The data suggest that readily releasable vesicles are retrieved as noncoated vesicles at the active zone.

  3. Evaluation of the Microbicidal Activity and Cytokines/Chemokines Profile Released by Neutrophils from HTLV-1-Infected Individuals

    PubMed Central

    Bezerra, Caroline A.; Cardoso, Thiago M.; Giudice, Angela; Porto, Aurélia F.; Santos, Silvane B.; Carvalho, Edgar M.; Bacellar, Olívia

    2011-01-01

    Human T cell lymphotropic virus type-1 (HTLV-1) induces activation and spontaneous proliferation of T cells with production of type-1 pro-inflammatory cytokines. It modifies the immune response to other antigens and increases susceptibility to infectious diseases. However, little is known about innate immunity in HTLV-1 infection. HTLV-1-infected individuals have higher spontaneous neutrophil activation than HTLV-1-seronegative individuals, as shown by the nitroblue tetrazolium (NBT) assay. This study was conducted to evaluate neutrophil function in HTLV-1-infected individuals. Participants in the study included 18 HTLV-1-infected individuals and 14 HTLV-1-seronegative controls. We evaluated the ability of neutrophils (PMNs) to control a parasite infection, to produce peroxynitrite, cytokines and chemokines and to express activation markers in cultures when stimulated with LPS or infected with Leishmania. When compared with the control group, there was no difference in the percentage of PMNs infected with Leishmania or in the number of amastigotes/100 PMNs in HTLV-1-infected individuals. The microbicidal activity of the PMNs and the levels of CXCL8 and CCL4 released by these cells did not show a difference between HTLV-1-infected individuals and the control group. In both the HTLV-1 group and the control group, infection with Leishmania or stimulation of PMNs led to cellular activation. These observations suggest that neutrophils from HTLV-1-infected individuals have preserved their ability to become activated and to produce chemokines and peroxynitrite after stimulation and that the susceptibility to infection by intracellular Leishmania amazonensis in HTLV-1-infected individuals does not depend on impairment of neutrophil function. PMID:21595736

  4. Endogenous released ascorbic acid suppresses ethanol-induced hydroxyl radical production in rat striatum.

    PubMed

    Huang, Mei; Liu, Wen; Li, Qiang; Wu, Chun Fu

    2002-07-19

    Previous studies have shown that acute systemic administration of ethanol induced ascorbic acid release in the striatum. However, the pharmacological implications of ethanol-induced striatal ascorbic acid release are unclear. In the present study, ethanol-induced extracellular changes of ascorbic acid and hydroxyl radical levels were detected in rat striatum by using brain microdialysis coupled to high-performance liquid chromatography with electrochemical detection. It was found that both in male and female rats, ethanol (3.0 g/kg, i.p.) increased striatal ascorbic acid release in the first 60 min after ethanol administration. Meanwhile, the extracellular hydroxyl radical levels, detected as 2,3- and 2,5-DHBA, were significantly decreased. However, when the ascorbic acid levels returned to the baseline, hydroxyl radical levels rebounded. Administration of DL-fenfluramine (20 mg/kg, i.p.) had no effect on the basal levels of ascorbic acid and hydroxyl radical, but significantly blocked ethanol-induced ascorbic acid release and increased hydroxyl radical levels significantly. Exogenous administration of ascorbic acid (20 mg/kg, s.c.) increased the extracellular levels of ascorbic acid in the striatum, and inhibited the increase of 2,3- and 2,5-DHBA in DL-fenfluramine plus ethanol group. These results provide first evidence that release of endogenous ascorbic acid in the striatum plays an important role in preventing oxidative stress by trapping hydroxyl radical in the central nervous system.

  5. 31 CFR 593.412 - Release of any round log or timber product originating in Liberia from a bonded warehouse or...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Release of any round log or timber... Interpretations § 593.412 Release of any round log or timber product originating in Liberia from a bonded... from a bonded warehouse or foreign trade zone of any round log or timber product originating in...

  6. 31 CFR 593.412 - Release of any round log or timber product originating in Liberia from a bonded warehouse or...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Release of any round log or timber... Interpretations § 593.412 Release of any round log or timber product originating in Liberia from a bonded... from a bonded warehouse or foreign trade zone of any round log or timber product originating in...

  7. Fractionation and characterization of the immunosuppressive substance in crude extracellular products released by Streptococcus intermedius.

    PubMed Central

    Arala-Chaves, M P; Porto, M T; Arnaud, P; Saraiva, M J; Geada, H; Patrick, C C; Fudenberg, H H

    1981-01-01

    The noncytotoxic immunosuppressive substance detected in crude extracellular products of Streptococcus intermedius (CEP-SI) was fractionated by two steps of preparative isoelectric focusing in sucrose gradients using ampholytes of pH range from 3.5 to 6 and 4 to 5, respectively. The in vitro and in vivo suppressor effects of the most highly purified fraction of CEP-Si, designated fraction 3' (F3'EP-Si), corresponded well with those of the original CEP-Si. F3'EP-Si was sensitive to the effects of alpha, gamma, and delta chymotrypsin, trypsin, and heating. It contained approximately 1% of the total amount of protein found in the original CEP-Si, corresponding to a single band on analytical isoelectric focusing, stainable by Coomassie Blue and of isoelectric point of 4.25. The absorption spectrum of F3'EP-Si had a maximum at 260 nm but its biological activity was resistant to deoxyribonuclease and ribonuclease A and it did not contain material stainable by methylene blue. It was also resistant to neuraminidase and did not contain material stainable by periodic acid schiff. We conclude that the substance responsible for the suppressor activity of CEP-Si is a protein of molecular weight approximately 90,000, which adheres to Sephadex of cellulose acetate and forms complexes with other, nonactive constituents of CEP-Si. Images PMID:6454698

  8. Newly Released TRMM Version 7 Products, GPCP Version 2.2 Precipitation Dataset and Data Services at NASA GES DISC

    NASA Astrophysics Data System (ADS)

    Ostrenga, D.; Liu, Z.; Teng, W. L.; Trivedi, B.; Kempler, S.

    2011-12-01

    The NASA Goddard Earth Sciences Data and Information Services Center (GES DISC) is home of global precipitation product archives, in particular, the Tropical Rainfall Measuring Mission (TRMM) products. TRMM is a joint U.S.-Japan satellite mission to monitor tropical and subtropical (40deg S - 40deg N) precipitation and to estimate its associated latent heating. The TRMM satellite provides the first detailed and comprehensive dataset on the four dimensional distribution of rainfall and latent heating over vastly undersampled tropical and subtropical oceans and continents. The TRMM satellite was launched on November 27, 1997. TRMM data products are archived at and distributed by GES DISC. The newly released TRMM Version 7 consists of several changes including new parameters, new products, meta data, data structures, etc. For example, hydrometeor profiles in 2A12 now have 28 layers (14 in V6). New parameters have been added to several popular Level-3 products, such as, 3B42, 3B43. Version 2.2 of the Global Precipitation Climatology Project (GPCP) dataset has been added to the TRMM Online Visualization and Analysis System (TOVAS; URL: http://disc2.nascom.nasa.gov/Giovanni/tovas/), allowing online analysis and visualization without downloading data and software. The GPCP dataset extends back to 1979. Results of basic intercomparison between the new and the previous versions of both TRMM and GPCP will be presented to help understand changes in data product characteristics. To facilitate data and information access and support precipitation research and applications, we have developed a Precipitation Data and Information Services Center (PDISC; URL: http://disc.gsfc.nasa.gov/precipitation). In addition to TRMM, PDISC provides current and past observational precipitation data. Users can access precipitation data archives consisting of both remote sensing and in-situ observations. Users can use these data products to conduct a wide variety of activities, including case

  9. The characterization of anti-T. cruzi activity relationships between ferrocenyl, cyrhetrenyl complexes and ROS release.

    PubMed

    Echeverría, César; Romero, Valentina; Arancibia, Rodrigo; Klahn, Hugo; Montorfano, Ignacio; Armisen, Ricardo; Borgna, Vincenzo; Simon, Felipe; Ramirez-Tagle, Rodrigo

    2016-08-01

    Trypanosoma cruzi (T. cruzi) is the parasite that causes Chagas disease. Nifurtimox is the most used drug against the T. cruzi, this drug increases intermediaries nitro group, being mainly responsible for the high toxicity component, for this reason it is important to study new organic compounds and thus improve therapeutic strategies against Chagas disease. The electronic effects of ferrocenyl and cyrhetrenyl fragments were investigated by DFT calculation. A close correlation was found between HOMO-LUMO gap of nitro radical NO 2 (-) with the experimental reduction potential found for nitro group and IC50 of two forms the T. cruzi (epimastigote and trypomastigote). The IC50 on human hepatoma cells is higher for both compounds compared to IC50 demonstrated in the two forms the T. cruzi, and additionally show reactive oxygen species release. The information obtained in this paper could generate two new drugs with anti-T. cruzi activity, but additional studies are needed.

  10. Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells

    PubMed Central

    Duregotti, Elisa; Negro, Samuele; Scorzeto, Michele; Zornetta, Irene; Dickinson, Bryan C.; Chang, Christopher J.; Montecucco, Cesare; Rigoni, Michela

    2015-01-01

    An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann cells, Schwann cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases. PMID:25605902

  11. The characterization of anti-T. cruzi activity relationships between ferrocenyl, cyrhetrenyl complexes and ROS release.

    PubMed

    Echeverría, César; Romero, Valentina; Arancibia, Rodrigo; Klahn, Hugo; Montorfano, Ignacio; Armisen, Ricardo; Borgna, Vincenzo; Simon, Felipe; Ramirez-Tagle, Rodrigo

    2016-08-01

    Trypanosoma cruzi (T. cruzi) is the parasite that causes Chagas disease. Nifurtimox is the most used drug against the T. cruzi, this drug increases intermediaries nitro group, being mainly responsible for the high toxicity component, for this reason it is important to study new organic compounds and thus improve therapeutic strategies against Chagas disease. The electronic effects of ferrocenyl and cyrhetrenyl fragments were investigated by DFT calculation. A close correlation was found between HOMO-LUMO gap of nitro radical NO 2 (-) with the experimental reduction potential found for nitro group and IC50 of two forms the T. cruzi (epimastigote and trypomastigote). The IC50 on human hepatoma cells is higher for both compounds compared to IC50 demonstrated in the two forms the T. cruzi, and additionally show reactive oxygen species release. The information obtained in this paper could generate two new drugs with anti-T. cruzi activity, but additional studies are needed. PMID:27460450

  12. MELCOR 1.8.5 modeling aspects of fission product release, transport and deposition an assessment with recommendations.

    SciTech Connect

    Gauntt, Randall O.

    2010-04-01

    The Phebus and VERCORS data have played an important role in contemporary understanding and modeling of fission product release and transport from damaged light water reactor fuel. The data from these test programs have allowed improvement of MELCOR modeling of release and transport processes for both low enrichment uranium fuel as well as high burnup and mixed oxide (MOX) fuels. This paper discusses the synthesis of these findings in the MELCOR severe accident code. Based on recent assessments of MELCOR 1.8.5 fission product release modeling against the Phebus FPT-1 test and on observations from the ISP-46 exercise, modifications to the default MELCOR 1.8.5 release models are recommended. The assessments identified an alternative set of Booth diffusion parameters recommended by ORNL (ORNL-Booth), which produced significantly improved release predictions for cesium and other fission product groups. Some adjustments to the scaling factors in the ORNL-Booth model were made for selected fission product groups, including UO{sub 2}, Mo and Ru in order to obtain better comparisons with the FPT-1 data. The adjusted model, referred to as 'Modified ORNL-Booth,' was subsequently compared to original ORNL VI fission product release experiments and to more recently performed French VERCORS tests, and the comparisons was as favorable or better than the original CORSOR-M MELCOR default release model. These modified ORNL-Booth parameters, input to MELCOR 1.8.5 as 'sensitivity coefficients' (i.e. user input that over-rides the code defaults) are recommended for the interim period until improved release models can be implemented into MELCOR. For the case of ruthenium release in air-oxidizing conditions, some additional modifications to the Ru class vapor pressure are recommended based on estimates of the RuO{sub 2} vapor pressure over mildly hyperstoichiometric UO{sub 2}. The increased vapor pressure for this class significantly increases the net transport of Ru from the fuel to

  13. Fission product release and microstructure changes during laboratory annealing of a very high burn-up fuel specimen

    NASA Astrophysics Data System (ADS)

    Hiernaut, J.-P.; Wiss, T.; Colle, J.-Y.; Thiele, H.; Walker, C. T.; Goll, W.; Konings, R. J. M.

    2008-07-01

    A commercial PWR fuel sample with a local burn-up of about 240 MWd/kgHM was annealed in a Knudsen cell mass spectrometer system with a heating rate of 10 K/min up to 2750 K at which temperature the sample was completely vaporized. The release of fission gases and fission products was studied as a function of temperature. In one of the runs the heating was interrupted successively at 900, 1500 and 1860 K and at each step a small fragment of the sample was examined by SEM and analysed by energy dispersive electron probe microanalysis. The release behaviour of volatile, gaseous and other less volatile fission products is presented and analysed with the EFFUS program and related to the structural changes of the fuel.

  14. Caseinophosphopeptides released after tryptic hydrolysis versus simulated gastrointestinal digestion of a casein-derived by-product.

    PubMed

    Cruz-Huerta, E; García-Nebot, M J; Miralles, B; Recio, I; Amigo, L

    2015-02-01

    The production of caseinophosphopeptides from a casein-derived by-product generated during the manufacture of a functional ingredient based on antihypertensive peptides was attempted. The casein by-product was submitted to tryptic hydrolysis for 30, 60 and 120min and further precipitated with calcium chloride and ethanol at pH 4.0, 6.0 and 8.0. Identification and semi quantification of the derived products by tandem mass spectrometry revealed some qualitative and quantitative changes in the released caseinophosphopeptides over time at the different precipitation pHs. The by-product was also subjected to simulated gastrointestinal digestion. Comparison of the resulting peptides showed large sequence homology in the phosphopeptides released by tryptic hydrolysis and simulated gastrointestinal digestion. Some regions, specifically αS1-CN 43-59, αS1-CN 60-74, β-CN 1-25 and β-CN 30-50 showed resistance to both tryptic hydrolysis and simulated digestion. The results of the present study suggest that this casein-derived by-product can be used as a source of CPPs.

  15. Novel analytical method to measure formaldehyde release from heated hair straightening cosmetic products: Impact on risk assessment.

    PubMed

    Galli, Corrado Lodovico; Bettin, Federico; Metra, Pierre; Fidente, Paola; De Dominicis, Emiliano; Marinovich, Marina

    2015-08-01

    Hair straightening cosmetic products may contain formaldehyde (FA). In Europe, FA is permitted for use in personal care products at concentrations ⩽ 0.2g/100g. According to the Cosmetic Ingredient Review (CIR) Expert Panel products are safe when formalin (a 37% saturated solution of FA in water) concentration does not exceed 0.2g/100g (0.074 g/100g calculated as FA). The official method of reference does not discriminate between "free" FA and FA released into the air after heating FA donors. The method presented here captures and collects the FA released into the air from heated cosmetic products by derivatization with 2,4-dinitrophenylhydrazine and final analysis by UPLC/DAD instrument. Reliable data in terms of linearity, recovery, repeatability and sensitivity are obtained. On a total of 72 market cosmetic products analyzed, 42% showed FA concentrations very close to or above the threshold value (0.074 g/100g calculated as FA) suggested by the Cosmetic Ingredient Review committee, whereas 11 products, negative using the official method of reference, were close to or above the threshold value (0.074 g/100g calculated as FA). This may pose a health problem for occasional users and professional hair stylists.

  16. Release of ethanol to the atmosphere during use of consumer cleaning products

    SciTech Connect

    Wooley, J.; Nazaroff, W.W. ); Hodgson, A.T. )

    1990-08-01

    Liquid laundry and hand dish washing detergents contain volatile organic compounds, including ethanol, that may be liberated during use and contribute to photochemical air pollution. In this study, the release of ethanol to the atmosphere during simulated household use of liquid detergents was measured. Three replicate experiments, plus a blank, were conducted in a 20-m{sup 3} environmental chamber for each of four conditions: typical dish washing (DT), high-release dish washing (DH), typical laundry (LT), and high-release laundry (LH). Average amounts of ethanol transferred to the atmosphere per use (and the fraction of ethanol used so liberated) were 32 mg (0.038) for DT, 100 mg (0.049) for DH, 18 mg (0.002) for LT, and 110 mg (0.011) for LH. Thus, a large fraction of the ethanol added to wash solutions with liquid detergents is discharged to the sewer rather than transferred to the atmosphere during use.

  17. Assessment of Heat Resistance of Bacterial Spores from Food Product Isolates by Fluorescence Monitoring of Dipicolinic Acid Release

    PubMed Central

    Kort, Remco; O'Brien, Andrea C.; van Stokkum, Ivo H. M.; Oomes, Suus J. C. M.; Crielaard, Wim; Hellingwerf, Klaas J.; Brul, Stanley

    2005-01-01

    This study is aimed at the development and application of a convenient and rapid optical assay to monitor the wet-heat resistance of bacterial endospores occurring in food samples. We tested the feasibility of measuring the release of the abundant spore component dipicolinic acid (DPA) as a probe for heat inactivation. Spores were isolated from the laboratory type strain Bacillus subtilis 168 and from two food product isolates, Bacillus subtilis A163 and Bacillus sporothermodurans IC4. Spores from the lab strain appeared much less heat resistant than those from the two food product isolates. The decimal reduction times (D values) for spores from strains 168, A163, and IC4 recovered on Trypticase soy agar were 1.4, 0.7, and 0.3 min at 105°C, 120°C, and 131°C, respectively. The estimated Z values were 6.3°C, 6.1°C, and 9.7°C, respectively. The extent of DPA release from the three spore crops was monitored as a function of incubation time and temperature. DPA concentrations were determined by measuring the emission at 545 nm of the fluorescent terbium-DPA complex in a microtiter plate fluorometer. We defined spore heat resistance as the critical DPA release temperature (Tc), the temperature at which half the DPA content has been released within a fixed incubation time. We found Tc values for spores from Bacillus strains 168, A163, and IC4 of 108°C, 121°C, and 131°C, respectively. On the basis of these observations, we developed a quantitative model that describes the time and temperature dependence of the experimentally determined extent of DPA release and spore inactivation. The model predicts a DPA release rate profile for each inactivated spore. In addition, it uncovers remarkable differences in the values for the temperature dependence parameters for the rate of spore inactivation, DPA release duration, and DPA release delay. PMID:16000762

  18. Involvement of nitric oxide through endocannabinoids release in microglia activation during the course of CNS regeneration in the medicinal leech.

    PubMed

    Arafah, Karim; Croix, Dominique; Vizioli, Jacopo; Desmons, Annie; Fournier, Isabelle; Salzet, Michel

    2013-04-01

    The medicinal leech is notable for its capacity to regenerate its central nervous system (CNS) following mechanical trauma. Using an electrochemical nitric oxide (NO)-selective electrode to measure NO levels, we found that the time course of NO release in the injured leech CNS is partially under the control of endocannabinoids, namely, N-arachidonyl ethanolamide (AEA) and 2-arachidonyl glycerol (2-AG). Relative quantification of these endocannabinoids was performed by stable isotope dilution (2AGd8 and AAEd8) coupled to mass spectrometry in course of regeneration process or adenosine triphosphate (ATP) treatment. Data show that 2-AG levels rose to a maximum about 30 min after injury or ATP treatment, and returned to baseline levels 4 h after injury. In same conditions, AEA levels also rapidly (within 5 min) dropped after injury or ATP treatment to the nerve cord, but did not fully return to baseline levels within 4 h of injury. In correlation with these data, chemoattraction activities of endocannabinoids on isolated leech microglial cells have been shown in vitro and in vivo reflecting that control over NO production is accompanied by the controlled chemoattraction of microglia directed from the periphery to the lesion site for neuronal repair purposes. Taken together, our results show that in the leech, after injury concurrent with ATP production, purinergic receptor activation, NO production, microglia recruitment, and accumulation to lesion site, a fine imbalance occurs in the endocannabinoid system. These events can bring explanations about the ability of the leech CNS to regenerate after a trauma and the key role of endocannabinoids in this phenomenon. PMID:23355252

  19. Release of LHRH-activity from human fetal membranes upon exposure to PGE/sub 2/, oxytocin and isoproterenol

    SciTech Connect

    Poisner, A.M.; Poisner, R.; Becca, C.R.; Conn, P.M.

    1986-03-01

    The authors have previously reported that superfused chorion laeve (fetal membranes) release LHRH-like immunoreactivity upon exposure to angiotensin II. They have now studied the effects of other agonists on the release of LHRH-activity and something of its chemical nature. Fetal membranes were obtained from placentas delivered by cesarean section, the amnion stripped from the chorion, and the chorion superfused in an Amicon thin-channel device with the maternal surface facing up. The whole device was submerged in a 37 C water bath and perfused with a modified Locke's solution at 0.4 - 1.0 ml/min. LHRH-activity was measured by radioimmunoassay using three different antisera against LHRH. The release of LHRH-activity was stimulated by 6-10 min exposure to PGE/sub 2/, oxytocin, and isoproterenol. Extracts of chorion were studied using gel filtration on Sephacryl S-200 and ultrafiltration with Amicon PM-10 filters. The bulk of the LHRH-activity appeared as a higher molecular weight form (about 70,000 daltons). Since oxytocin has been reported to release PGE/sub 2/ from chorion, it may release LHRH-activity by virtue of liberating endogenous PGE/sub 2/. The chemical nature of the LHRH-activity is presently under investigation.

  20. Formation and release behavior of iron corrosion products under the influence of bacterial communities in a simulated water distribution system.

    PubMed

    Sun, Huifang; Shi, Baoyou; Lytle, Darren A; Bai, Yaohui; Wang, Dongsheng

    2014-03-0