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Sample records for oxide target elements

  1. OXIDATION OF TRANSURANIC ELEMENTS

    DOEpatents

    Moore, R.L.

    1959-02-17

    A method is reported for oxidizing neptunium or plutonium in the presence of cerous values without also oxidizing the cerous values. The method consists in treating an aqueous 1N nitric acid solution, containing such cerous values together with the trivalent transuranic elements, with a quantity of hydrogen peroxide stoichiometrically sufficient to oxidize the transuranic values to the hexavalent state, and digesting the solution at room temperature.

  2. Separation of transuranium elements from irradiated targets

    SciTech Connect

    Wham, R.M.; Benker, D.E.; Felker, L.K.; Chattin, F.R.

    1993-12-31

    Aluminum targets containing curium/americium oxide are irradiated to produce the transcurium actinides einsteinium, fermium, berkelium, and californium. Recovery of recycle curium/americium and the transcurium elements involves several chemical processing steps to selectively recover those elements and remove fission products. Chemical processing steps developed at the Radiochemical Engineering Development Center (REDC) include aluminum dejacketing, solvent extraction to remove bulk impurities, solvent extraction to remove plutonium, anion exchange to partition curium and transcurium elements from the rare earths, and a second anion exchange cycle to separate americium/curium from the transcurium elements.

  3. New functionalities in abundant element oxides: ubiquitous element strategy.

    PubMed

    Hosono, Hideo; Hayashi, Katsuro; Kamiya, Toshio; Atou, Toshiyuki; Susaki, Tomofumi

    2011-06-01

    While most ceramics are composed of ubiquitous elements (the ten most abundant elements within the Earth's crust), many advanced materials are based on rare elements. A 'rare-element crisis' is approaching owing to the imbalance between the limited supply of rare elements and the increasing demand. Therefore, we propose a 'ubiquitous element strategy' for materials research, which aims to apply abundant elements in a variety of innovative applications. Creation of innovative oxide materials and devices based on conventional ceramics is one specific challenge. This review describes the concept of ubiquitous element strategy and gives some highlights of our recent research on the synthesis of electronic, thermionic and structural materials using ubiquitous elements.

  4. Removable preheater elements improve oxide induction furnace

    NASA Technical Reports Server (NTRS)

    Leipold, M. H.

    1964-01-01

    Heat and corrosion resistant preheater elements are used in oxide induction furnaces to raise the temperature to the level for conducting electricity. These preheater elements are then removed and the induction coil energized.

  5. New functionalities in abundant element oxides: ubiquitous element strategy

    PubMed Central

    Hosono, Hideo; Hayashi, Katsuro; Kamiya, Toshio; Atou, Toshiyuki; Susaki, Tomofumi

    2011-01-01

    While most ceramics are composed of ubiquitous elements (the ten most abundant elements within the Earth's crust), many advanced materials are based on rare elements. A ‘rare-element crisis’ is approaching owing to the imbalance between the limited supply of rare elements and the increasing demand. Therefore, we propose a ‘ubiquitous element strategy’ for materials research, which aims to apply abundant elements in a variety of innovative applications. Creation of innovative oxide materials and devices based on conventional ceramics is one specific challenge. This review describes the concept of ubiquitous element strategy and gives some highlights of our recent research on the synthesis of electronic, thermionic and structural materials using ubiquitous elements. PMID:27877391

  6. Oxidation of hydrogen halides to elemental halogens

    DOEpatents

    Rohrmann, Charles A.; Fullam, Harold T.

    1985-01-01

    A process for oxidizing hydrogen halides having substantially no sulfur impurities by means of a catalytically active molten salt is disclosed. A mixture of the subject hydrogen halide and an oxygen bearing gas is contacted with a molten salt containing an oxidizing catalyst and alkali metal normal sulfates and pyrosulfates to produce an effluent gas stream rich in the elemental halogen and substantially free of sulfur oxide gases.

  7. Oxidative Stress: A Promising Target for Chemoprevention

    PubMed Central

    John, AM Sashi Papu; Ankem, Murali K; Damodaran, Chendil

    2016-01-01

    Cancer is a leading cause of death worldwide, and treating advanced stages of cancer remains clinically challenging. Epidemiological studies have shown that oxidants and free radicals induced DNA damage is one of the predominant causative factors for cancer pathogenesis. Hence, oxidants are attractive targets for chemoprevention as well as therapy. Dietary agents are known to exert an anti-oxidant property which is one of the most efficient preventive strategy in cancer progression. In this article, we highlight dietary agents can potentially target oxidative stress, in turn delaying, preventing, or treating cancer development. Some of these agents are currently in use in basic research, while some have been launched successfully into clinical trials. PMID:27088073

  8. Association of trace elements with iron oxides during rock weathering

    SciTech Connect

    Koons, R.D.; Helmke, P.A.; Jackson, M.L.

    1980-01-01

    The association of trace elements with Fe oxides during the early stages of rock weathering was determined by analysis of fresh diabase and granite rocks, their associated whole and size-separated saprolites, and goethite by neutron activation and X-ray fluorescence. The same elements are found to be associated with Fe oxides when the results are interpreted by analysis of correlation, by the distribution of elements in the various size fractions by the effects of removing free Fe oxides, and by direct analysis of geothite from the saprolite. The elements Co, Cr, Mn, Sc, Th, U, Zn, and the heavy rare-earth elements during the weathering of diabase, and As, Co, Cr, Sc, Th, U, Zn, and the heavy rare-earth elements during the weathering of granite are associated with Fe oxides. The concentrations of Mn are too low in this system to separate the effects of Mn oxides from those of Fe oxides.

  9. Recent developments in zinc oxide target chemistry

    SciTech Connect

    Heaton, R.C.; Taylor, W.A.; Phillips, D.R.; Jamriska, D.J. Sr.; Garcia, J.B.

    1994-04-01

    Zinc oxide targets irradiated with high energy protons at the Los Alamos Meson Physics Facility (LAMPF) contain a number of radioactive spallation products in quantities large enough to warrant recovery. This paper describes methods for recovering {sup 7}Be, {sup 46}Sc, and {sup 48}V from such targets and offers suggestions on possible ways to recover additional isotopes. The proposed methods are based on traditional precipitation and ion exchange techniques, are readily adaptable to hot cell use, and produce no hazardous waste components. The products are obtained in moderate to high yields and have excellent radiopurity.

  10. Commissioning a Rotating Target Wheel Assembly for Heavy Element Studies

    NASA Astrophysics Data System (ADS)

    Fields, L. D.; Bennett, M. E.; Mayorov, D. A.; Folden, C. M.

    2013-10-01

    The heaviest elements are produced artificially by fusing nuclei of light elements within an accelerator to form heavier nuclei. The most direct method to increase the production rate of nuclei is to increase the beam intensity, necessitating the use of a rotating target to minimize damage to the target by deposited heat. Such a target wheel was constructed for heavy element research at Texas A&M University, Cyclotron Institute, consisting of a wheel with three banana-shaped target cutouts. The target is designed to rotate at 1700 rpm, and a fiber optic cable provides a signal to trigger beam pulsing in order to avoid irradiating the spokes between target segments. Following minor mechanical modifications and construction of a dedicated electrical panel, the rotating target assembly was commissioned for a beam experiment. A 15 MeV/u beam of 20Ne was delivered from the K500 cyclotron and detected by a ruggedized silicon detector. The beam pulsing response time was characterized as a function of the rational frequency of the target wheel. Preliminary analysis suggests that the K500 is capable of pulsing at rates of up to 250 Hz, which is sufficient for planned future experiments. Funded by DOE and NSF-REU Program.

  11. Oxidation and methylation of dissolved elemental mercury by anaerobic bacteria

    NASA Astrophysics Data System (ADS)

    Hu, Haiyan; Lin, Hui; Zheng, Wang; Tomanicek, Stephen J.; Johs, Alexander; Feng, Xinbin; Elias, Dwayne A.; Liang, Liyuan; Gu, Baohua

    2013-09-01

    Methylmercury is a neurotoxin that poses significant health risks to humans. Some anaerobic sulphate- and iron-reducing bacteria can methylate oxidized forms of mercury, generating methylmercury. One strain of sulphate-reducing bacteria (Desulfovibrio desulphuricans ND132) can also methylate elemental mercury. The prevalence of this trait among different bacterial strains and species remains unclear, however. Here, we compare the ability of two strains of the sulphate-reducing bacterium Desulfovibrio and one strain of the iron-reducing bacterium Geobacter to oxidize and methylate elemental mercury in a series of laboratory incubations. Experiments were carried out under dark, anaerobic conditions, in the presence of environmentally relevant concentrations of elemental mercury. We report differences in the ability of these organisms to oxidize and methylate elemental mercury. In line with recent findings, we show that D.desulphuricans ND132 can both oxidize and methylate elemental mercury. We find that the rate of methylation of elemental mercury is about one-third the rate of methylation of oxidized mercury. We also show that Desulfovibrio alaskensis G20 can oxidize, but not methylate, elemental mercury. Geobacter sulphurreducens PCA is able to oxidize and methylate elemental mercury in the presence of cysteine. We suggest that the activity of methylating and non-methylating bacteria may together enhance the formation of methylmercury in anaerobic environments.

  12. Actinide targets for the synthesis of super-heavy elements

    SciTech Connect

    Roberto, J.; Alexander, Charles W.; Boll, Rose Ann; Ezold, Julie G.; Felker, Leslie Kevin; Rykaczewski, Krzysztof Piotr; Hogle, Susan L.

    2015-06-18

    Since 2000, six new super-heavy elements with atomic numbers 113 through 118 have been synthesized in hot fusion reactions of 48Ca beams on actinide targets. These target materials, including 242Pu, 244Pu, 243Am, 245Cm, 248Cm, 249Cf, and 249Bk, are available in very limited quantities and require specialized production and processing facilities resident in only a few research centers worldwide. This report describes the production and chemical processing of heavy actinide materials for super-heavy element research, current availabilities of these materials, and related target fabrication techniques. The impact of actinide materials in super-heavy element discovery is reviewed, and strategies for enhancing the production of rare actinides including 249Bk, 251Cf, and 254Es are described.

  13. Actinide targets for the synthesis of super-heavy elements

    DOE PAGES

    Roberto, J.; Alexander, Charles W.; Boll, Rose Ann; ...

    2015-06-18

    Since 2000, six new super-heavy elements with atomic numbers 113 through 118 have been synthesized in hot fusion reactions of 48Ca beams on actinide targets. These target materials, including 242Pu, 244Pu, 243Am, 245Cm, 248Cm, 249Cf, and 249Bk, are available in very limited quantities and require specialized production and processing facilities resident in only a few research centers worldwide. This report describes the production and chemical processing of heavy actinide materials for super-heavy element research, current availabilities of these materials, and related target fabrication techniques. The impact of actinide materials in super-heavy element discovery is reviewed, and strategies for enhancing themore » production of rare actinides including 249Bk, 251Cf, and 254Es are described.« less

  14. Actinide targets for the synthesis of super-heavy elements

    NASA Astrophysics Data System (ADS)

    Roberto, J. B.; Alexander, C. W.; Boll, R. A.; Burns, J. D.; Ezold, J. G.; Felker, L. K.; Hogle, S. L.; Rykaczewski, K. P.

    2015-12-01

    Since 2000, six new super-heavy elements with atomic numbers 113 through 118 have been synthesized in hot fusion reactions of 48Ca beams on actinide targets. These target materials, including 242Pu, 244Pu, 243Am, 245Cm, 248Cm, 249Cf, and 249Bk, are available in very limited quantities and require specialized production and processing facilities resident in only a few research centers worldwide. This report describes the production and chemical processing of heavy actinide materials for super-heavy element research, current availabilities of these materials, and related target fabrication techniques. The impact of actinide materials in super-heavy element discovery is reviewed, and strategies for enhancing the production of rare actinides including 249Bk, 251Cf, and 254Es are described.

  15. NOVEL OXIDANT FOR ELEMENTAL MERCURY CONTROL FROM FLUE GAS

    EPA Science Inventory

    A novel economical oxidant has been developed for elemental mercury (Hg(0)) removal from coal-fired boilers. The oxidant was rigorously tested in a lab-scale fixed-bed system with the Norit America's FGD activated carbon (DOE's benchmark sorbent) in a typical PRB subbituminous/l...

  16. Rosamines Targeting the Cancer Oxidative Phosphorylation Pathway

    PubMed Central

    Lim, Siang Hui; Wu, Liangxing; Kiew, Lik Voon; Chung, Lip Yong; Burgess, Kevin; Lee, Hong Boon

    2014-01-01

    Reprogramming of energy metabolism is pivotal to cancer, so mitochondria are potential targets for anticancer therapy. A prior study has demonstrated the anti-proliferative activity of a new class of mitochondria-targeting rosamines. This present study describes in vitro cytotoxicity of second-generation rosamine analogs, their mode of action, and their in vivo efficacies in a tumor allografted mouse model. Here, we showed that these compounds exhibited potent cytotoxicity (average IC50<0.5 µM), inhibited Complex II and ATP synthase activities of the mitochondrial oxidative phosphorylation pathway and induced loss of mitochondrial transmembrane potential. A NCI-60 cell lines screen further indicated that rosamine analogs 4 and 5 exhibited potent antiproliferative effects with Log10GI50 = −7 (GI50 = 0.1 µM) and were more effective against a colorectal cancer sub-panel than other cell lines. Preliminary in vivo studies on 4T1 murine breast cancer-bearing female BALB/c mice indicated that treatment with analog 5 in a single dosing of 5 mg/kg or a schedule dosing of 3 mg/kg once every 2 days for 6 times (q2d×6) exhibited only minimal induction of tumor growth delay. Our results suggest that rosamine analogs may be further developed as mitochondrial targeting agents. Without a doubt proper strategies need to be devised to enhance tumor uptake of rosamines, i.e. by integration to carrier molecules for better therapeutic outcome. PMID:24622277

  17. Extraction radiopolarography for determining the oxidation potentials of transplutonium elements

    SciTech Connect

    Kosyakov, V.N.; Yakovlev, N.G.; Vlasov, M.M.

    1987-03-01

    A method is described for determining the oxidation potentials for valency transitions in transplutonium elements (TPE), which is usable when the element is present in trace amounts. This is based on electrochemical oxidation or reduction of the TPE in combination with a solvent-extraction method of determining the concentration ratio for the oxidized and reduced forms. The method is applicable to determining the potential of almost any reversible reaction if the solvent-extraction parameters for the oxidized and reduced forms differ substantially, while the potential (with allowance for the extraction system) lies in a region accessible to electrochemical oxidation or reduction. Two forms of use are considered: with liquid extraction and with extraction chromatography. The method is demonstrated on the Bk(IV)/Bk(III) transition with di-2-ethylhexylphosphoric acid as extraction agent.

  18. The quantification of mixture stoichiometry when fuel molecules contain oxidizer elements or oxidizer molecules contain fuel elements.

    SciTech Connect

    Mueller, Charles J.

    2005-05-01

    The accurate quantification and control of mixture stoichiometry is critical in many applications using new combustion strategies and fuels (e.g., homogeneous charge compression ignition, gasoline direct injection, and oxygenated fuels). The parameter typically used to quantify mixture stoichiometry (i.e., the proximity of a reactant mixture to its stoichiometric condition) is the equivalence ratio, /gf. The traditional definition of /gf is based on the relative amounts of fuel and oxidizer molecules in a mixture. This definition provides an accurate measure of mixture stoichiometry when the fuel molecule does not contain oxidizer elements and when the oxidizer molecule does not contain fuel elements. However, the traditional definition of /gf leads to problems when the fuel molecule contains an oxidizer element, as is the case when an oxygenated fuel is used, or once reactions have started and the fuel has begun to oxidize. The problems arise because an oxidizer element in a fuel molecule is counted as part of the fuel, even though it acts as an oxidizer. Similarly, if an oxidizer molecule contains fuel elements, the fuel elements in the oxidizer molecule are misleadingly lumped in with the oxidizer in the traditional definition of /gf. In either case, use of the traditional definition of /gf to quantify the mixture stoichiometry can lead to significant errors. This paper introduces the oxygen equivalence ratio, /gf/gV, a parameter that properly characterizes the instantaneous mixture stoichiometry for a broader class of reactant mixtures than does /gf. Because it is an instantaneous measure of mixture stoichiometry,/gf/gV can be used to track the time-evolution of stoichiometry as a reaction progresses. The relationship between /gf/gV and /gf is shown. Errors are involved when the traditional definition of /gf is used as a measure of mixture stoichiometry with fuels that contain oxidizer elements or oxidizers that contain fuel elements; /gf/gV is used to quantify

  19. Type-dependent oxidative damage in frontotemporal lobar degeneration: cortical astrocytes are targets of oxidative damage.

    PubMed

    Martínez, Anna; Carmona, Margarita; Portero-Otin, Manuel; Naudí, Alba; Pamplona, Reinald; Ferrer, Isidre

    2008-12-01

    Oxidative injury and stress responses are common features of many neurodegenerative diseases. To assess oxidative stress responses in frontotemporal lobar degeneration (FTLD), we identified increased 4-hydroxynonenal (HNE) adducts using gel electrophoresis and Western blotting in frontal cortex samples in 6 of 6 cases of FTLD with the P301L mutation in the tau gene (FTLD-tau), in 3 of 10 cases with tau-negative ubiquitin-immunoreactive inclusions, and in 2 of 3 cases associated with motor neuron disease. Selectively increased lipoxidation-derived protein damage associated with altered membrane unsaturation and fatty acid profiles was verified by mass spectrometry in FTLD-tau and FTLD associated with motor neuron disease. All FTLD-tau and most cases with increased HNE-positive bands had marked astrocytosis as determined by glial fibrillary acidic protein (GFAP) immunohistochemistry and increased GFAP expression on Western blotting; 2 FTLD cases with tau-negative ubiquitin-immunoreactive inclusions and with increased GFAP expression did not have increased HNE adducts. Bidimensional gel electrophoresis, Western blotting, in-gel digestion, and mass spectrometry identified GFAP as a major target of lipoxidation in all positive cases; confocal microscopy revealed colocalization of HNE and GFAP in cortical astrocytes, superoxide dismutase 1 in astrocytes, and superoxide dismutase 2 in astrocytes and neurons in all FTLD types. Thus, in FTLD, there is variable disease-dependent oxidative damage that is prominent in FTLD-tau, astrocytes are targets of oxidative damage, and GFAP is a target of lipoxidation. Astrocytes are, therefore, crucial elements of oxidative stress responses in FTLD.

  20. NASA-SETI microwave observing project: Targeted Search Element (TSE)

    NASA Technical Reports Server (NTRS)

    Webster, L. D.

    1991-01-01

    The Targeted Search Element (TSE) performs one of two complimentary search strategies of the NASA-SETI Microwave Observing Project (MOP): the targeted search. The principle objective of the targeted search strategy is to scan the microwave window between the frequencies of one and three gigahertz for narrowband microwave emissions eminating from the direction of 773 specifically targeted stars. The scanning process is accomplished at a minimum resolution of one or two Hertz at very high sensitivity. Detectable signals will be of a continuous wave or pulsed form and may also drift in frequency. The TSE will possess extensive radio frequency interference (RFI) mitigation and verification capability as the majority of signals detected by the TSE will be of local origin. Any signal passing through RFI classification and classifiable as an extraterrestrial intelligence (ETI) candidate will be further validated at non-MOP observatories using established protocol. The targeted search will be conducted using the capability provided by the TSE. The TSE provides six Targeted Search Systems (TSS) which independently or cooperatively perform automated collection, analysis, storage, and archive of signal data. Data is collected in 10 megahertz chunks and signal processing is performed at a rate of 160 megabits per second. Signal data is obtained utilizing the largest radio telescopes available for the Targeted Search such as those at Arecibo and Nancay or at the dedicated NASA-SETI facility. This latter facility will allow continuous collection of data. The TSE also provides for TSS utilization planning, logistics, remote operation, and for off-line data analysis and permanent archive of both the Targeted Search and Sky Survey data.

  1. Oxidation and methylation of dissolved elemental mercury by anaerobic bacteria

    SciTech Connect

    Hu, Haiyan; Lin, Hui; Zheng, Wang; Tomanicek, Stephen J; Johs, Alexander; Feng, Xinbin; Elias, Dwayne A; Liang, Liyuan; Gu, Baohua

    2013-08-04

    Methylmercury is a neurotoxin that poses significant health risks to humans. Some anaerobic sulphate- and iron-reducing bacteria can methylate oxidized forms of mercury, generating methylmercury1-4. One strain of sulphate-reducing bacteria (Desulfovibrio desulfuricans ND132) can also methylate elemental mercury5. The prevalence of this trait among different bacterial strains and species remains unclear, however. Here, we compare the ability of two strains of the sulphate-reducing bacterium Desulfovibrio and one strain of the iron-reducing bacterium Geobacter to oxidise and methylate elemental mercury in a series of laboratory incubations. Experiments were carried out under dark, anaerobic conditions, in the presence of environmentally-relevant concentrations of elemental mercury. We report differences in the ability of these organisms to oxidise and methylate elemental mercury. In line with recent findings5, we show that Desulfovibrio desulfuricans ND132 can both oxidise and methylate elemental mercury. However, the rate of methylation of elemental mercury is only about one third the rate of methylation of oxidized mercury. We also show that Desulfovibrio alaskensis G20 can oxidise, but not methylate, elemental mercury. Geobacter sulfurreducens PCA is able to oxidise and methylate elemental mercury in the presence of cysteine. We suggest that the activity of methylating and non-methylating bacteria may together enhance the formation of methylmercury in anaerobic environments.

  2. Oxidative elemental cycling under the low O2 Eoarchean atmosphere.

    PubMed

    Frei, Robert; Crowe, Sean A; Bau, Michael; Polat, Ali; Fowle, David A; Døssing, Lasse N

    2016-02-11

    The Great Oxidation Event signals the first large-scale oxygenation of the atmosphere roughly 2.4 Gyr ago. Geochemical signals diagnostic of oxidative weathering, however, extend as far back as 3.3-2.9 Gyr ago. 3.8-3.7 Gyr old rocks from Isua, Greenland stand as a deep time outpost, recording information on Earth's earliest surface chemistry and the low oxygen primordial biosphere. Here we find fractionated Cr isotopes, relative to the igneous silicate Earth reservoir, in metamorphosed banded iron formations (BIFs) from Isua that indicate oxidative Cr cycling 3.8-3.7 Gyr ago. Elevated U/Th ratios in these BIFs relative to the contemporary crust, also signal oxidative mobilization of U. We suggest that reactive oxygen species were present in the Eoarchean surface environment, under a very low oxygen atmosphere, inducing oxidative elemental cycling during the deposition of the Isua BIFs and possibly supporting early aerobic biology.

  3. NOVEL OXIDANT FOR ELEMENTAL MERCURY CONTROL FROM FLUE GAS

    EPA Science Inventory

    The primary objective of this study is to develop and test advanced noncarbonaceous solid sorbent materials suitable for removing the elemental form of mercury from power plant emissions. An efficient and cost-effective novel Hg(0) oxidant was evaluated in a lab-scale fixed-bed ...

  4. A new method for oxidation of gaseous, elemental mercury.

    SciTech Connect

    Livengood, C. D.; Mendelsohn, M. H.

    1999-08-23

    Elemental mercury (Hg) is difficult to remove from flue-gas streams using existing wet-scrubber technology, primarily because of its limited volubility in water. We have proposed and tested a concept for enhancing gaseous Hg{sup 0}removal in wet scrubber systems by altering the chemical form of the Hg{sup 0} to a water-soluble oxidized species. Recently, we have discovered a new method for injection of the oxidizing species that dramatically improves reactant utilization and at the same time gives significant nitric oxide (NO) oxidation as well. Our method uses a diluted oxidizing solution containing chloric acid and sodium chlorate (sold commercially as NOXSORB{trademark}). When this solution is injected into a gas stream containing Hg{sup 0} at about 300 F, we found that nearly 100% of the Hg{sup 0} was removed from the gas phase and was recovered in liquid samples from the test system. At the same time, approximately 80% of the added NO was also removed (oxidized). The effect of sulfur dioxide (SO{sub 2}) on this method was also investigated, and it appears to decrease slightly the amount of Hg oxidized. We are currently testing the effect of variations in oxidizing solution concentration, SO{sub 2} concentration, NO concentration, and reaction time (residence time).

  5. Targets of oxidative stress in cardiovascular system.

    PubMed

    Chakraborti, T; Ghosh, S K; Michael, J R; Batabyal, S K; Chakraborti, S

    1998-10-01

    Although oxidants such as superoxide (O2.) and hydrogen peroxide (H2O2) play a role in host-mediated destruction of foreign pathogens yet excessive generation of oxidants may lead to a variety of pathological complications in the cardiovascular system. An important mechanism by which oxidants cause dysfunction of the cardiovascular system appears to be due to the increase in intracellular free Ca2+ concentration. Oxidants cause cellular Ca2+ mobilization by modulating activities of a variety of regulators such as Na+/H+ and Na+/Ca2+ exchangers, Na+/K+ ATPase and Ca2+ ATPase and Ca2+ channels that are associated with Ca2+ transport in the plasma membrane and the sarco(endo)plasmic reticular membrane of myocardial cells. Recent research have suggested that the increase in Ca2+ level by oxidants plays a pivotal role in inducing several protein kinases such as protein kinase C, tyrosine kinase and mitogen activated protein kinases. Oxidant-mediated alteration of different signal transduction systems and their interations eventually regulate a variety of pathological conditions such as atherosclerosis, apoptosis and necrosis in the myocardium.

  6. Chromatin landscape dictates HSF binding to target DNA elements.

    PubMed

    Guertin, Michael J; Lis, John T

    2010-09-09

    Sequence-specific transcription factors (TFs) are critical for specifying patterns and levels of gene expression, but target DNA elements are not sufficient to specify TF binding in vivo. In eukaryotes, the binding of a TF is in competition with a constellation of other proteins, including histones, which package DNA into nucleosomes. We used the ChIP-seq assay to examine the genome-wide distribution of Drosophila Heat Shock Factor (HSF), a TF whose binding activity is mediated by heat shock-induced trimerization. HSF binds to 464 sites after heat shock, the vast majority of which contain HSF Sequence-binding Elements (HSEs). HSF-bound sequence motifs represent only a small fraction of the total HSEs present in the genome. ModENCODE ChIP-chip datasets, generated during non-heat shock conditions, were used to show that inducibly bound HSE motifs are associated with histone acetylation, H3K4 trimethylation, RNA Polymerase II, and coactivators, compared to HSE motifs that remain HSF-free. Furthermore, directly changing the chromatin landscape, from an inactive to an active state, permits inducible HSF binding. There is a strong correlation of bound HSEs to active chromatin marks present prior to induced HSF binding, indicating that an HSE's residence in "active" chromatin is a primary determinant of whether HSF can bind following heat shock.

  7. Respirometric characterization of aerobic sulfide, thiosulfate and elemental sulfur oxidation by S-oxidizing biomass.

    PubMed

    Mora, Mabel; López, Luis R; Lafuente, Javier; Pérez, Julio; Kleerebezem, Robbert; van Loosdrecht, Mark C M; Gamisans, Xavier; Gabriel, David

    2016-02-01

    Respirometry was used to reveal the mechanisms involved in aerobic biological sulfide oxidation and to characterize the kinetics and stoichiometry of a microbial culture obtained from a desulfurizing biotrickling filter. Physical-chemical processes such as stripping and chemical oxidation of hydrogen sulfide were characterized since they contributed significantly to the conversions observed in respirometric tests. Mass transfer coefficient for hydrogen sulfide and the kinetic parameters for chemical oxidation of sulfide with oxygen were estimated. The stoichiometry of the process was determined and the different steps in the sulfide oxidation process were identified. The conversion scheme proposed includes intermediate production of elemental sulfur and thiosulfate and the subsequent oxidation of both compounds to sulfate. A kinetic model describing each of the reactions observed during sulfide oxidation was calibrated and validated. The product selectivity was found to be independent of the dissolved oxygen to hydrogen sulfide concentration ratio in the medium at sulfide concentrations ranging from 3 to 30 mg S L(-1). Sulfide was preferentially consumed (SOURmax = 49.2 mg DO g(-1) VSS min(-1)) and oxidized to elemental sulfur at dissolved oxygen concentrations above 0.8 mg DO L(-1). Substrate inhibition of sulfide oxidation was observed (K(i,S(2-))= 42.4 mg S L(-1)). Intracellular sulfur accumulation also affected negatively the sulfide oxidation rate. The maximum fraction of elemental sulfur accumulated inside cells was estimated (25.6% w/w) and a shrinking particle equation was included in the kinetic model to describe elemental sulfur oxidation. The microbial diversity obtained through pyrosequencing analysis revealed that Thiothrix sp. was the main species present in the culture (>95%).

  8. Modelling oxidation behaviour in operating defective nuclear reactor fuel elements

    NASA Astrophysics Data System (ADS)

    Higgs, Jamie D.

    CANDU nuclear reactors are powered by ceramic uranium dioxide (UO 2) fuel pellets encased in a zirconium-alloy sheath. Occasionally, holes develop in the sheath, allowing steam ingress into the fuel-to-sheath gap, thus exposing the fuel to an oxidizing environment. Oxidation of UO2 fuel may lead to a reduction of fuel thermal conductivity and melting point, both reducing the margin to prevent fuel centre-line melting during transient or even normal operating conditions. Along with increasing fuel temperature, fuel oxidation also enhances the release of radioactive fission products into the reactor coolant. For the first time, a mechanistic treatment has been considered to predict fuel oxidation behaviour in operating defective fuel elements by coupling fuel oxidation kinetics, interstitial oxygen diffusion and heat transfer with sheath oxidation and hydriding rates and gas phase transport in both the fuel-to-sheath gap and within the fuel cracks. The three highly non-linear phenomena (solid-state oxygen diffusion, gas-phase transport and heat transfer) coupled in this treatment were modelled using a finite element technique. The result is a numerical tool that can provide predictions of both the temperature and oxygen-to-uranium (O/U) ratio profile both radially and axially along the fuel element length. The two-dimensional (azimuthally-symmetric) model has been compared to oxygen profile measurements from commercial reactor defective fuel with operating linear power ratings ranging from 26 to 51 kW m-1. Model predictions agree well with experimental observations. Defect size, linear power rating and post-defect residence time (PDRT) appear to be the factors that most influence the extent and rate of fuel oxidation. Thermodynamic modelling of hyperstoichiometric fuel provided the boundary conditions for the fuel oxidation kinetics model. A refined thermodynamic treatment for hyperstoichiometric UO2 has been established. Neutron diffraction experiments at Los Alamos

  9. Dissolution of Neptunium Oxide in Unirradiated Mark 53 Targets

    SciTech Connect

    Rudisill, T.S.

    2002-06-07

    Nine unirradiated Mark 53 targets currently stored at the K-Reactor must be dissolved to allow recovery of the neptunium content. The Mark 53 targets are an aluminum clad neptunium oxide (NpO2)/aluminum metal cermet used for the production of plutonium-238. The targets will be dissolved in H-Canyon and blended with solutions generated from routine fuel dissolutions for purification by solvent extraction

  10. Oxidative elemental cycling under the low O2 Eoarchean atmosphere

    PubMed Central

    Frei, Robert; Crowe, Sean A.; Bau, Michael; Polat, Ali; Fowle, David A.; Døssing, Lasse N.

    2016-01-01

    The Great Oxidation Event signals the first large-scale oxygenation of the atmosphere roughly 2.4 Gyr ago. Geochemical signals diagnostic of oxidative weathering, however, extend as far back as 3.3–2.9 Gyr ago. 3.8–3.7 Gyr old rocks from Isua, Greenland stand as a deep time outpost, recording information on Earth’s earliest surface chemistry and the low oxygen primordial biosphere. Here we find fractionated Cr isotopes, relative to the igneous silicate Earth reservoir, in metamorphosed banded iron formations (BIFs) from Isua that indicate oxidative Cr cycling 3.8–3.7 Gyr ago. Elevated U/Th ratios in these BIFs relative to the contemporary crust, also signal oxidative mobilization of U. We suggest that reactive oxygen species were present in the Eoarchean surface environment, under a very low oxygen atmosphere, inducing oxidative elemental cycling during the deposition of the Isua BIFs and possibly supporting early aerobic biology. PMID:26864443

  11. Accumulation and oxidation of elemental mercury in tropical soils.

    PubMed

    Soares, Liliane Catone; Egreja Filho, Fernando Barboza; Linhares, Lucília Alves; Windmoller, Cláudia Carvalhinho; Yoshida, Maria Irene

    2015-09-01

    The role of chemical and mineralogical soil properties in the retention and oxidation of atmospheric mercury in tropical soils is discussed based on thermal desorption analysis. The retention of gaseous mercury by tropical soils varied greatly both quantitatively and qualitatively with soil type. The average natural mercury content of soils was 0.08 ± 0.06 μg g(-1) with a maximum of 0.215 ± 0.009 μg g(-1). After gaseous Hg(0) incubation experiments, mercury content of investigated soils ranged from 0.6 ± 0.2 to 735 ± 23 μg g(-1), with a mean value of 44 ± 146 μg g(-1). Comparatively, A horizon of almost all soil types adsorbed more mercury than B horizon from the same soil, which demonstrates the key role of organic matter in mercury adsorption. In addition to organic matter, pH and CEC also appear to be important soil characteristics for the adsorption of mercury. All thermograms showed Hg(2+) peaks, which were predominant in most of them, indicating that elemental mercury oxidized in tropical soils. After four months of incubation, the thermograms showed oxidation levels from 70% to 100%. As none of the samples presented only the Hg(0) peak, and the soils retained varying amounts of mercury despite exposure under the same incubation conditions, it became clear that oxidation occurred on soil surface. Organic matter seemed to play a key role in mercury oxidation through complexation/stabilization of the oxidized forms. The lower percentages of available mercury (extracted with KNO3) in A horizons when compared to B horizons support this idea.

  12. Local structures around the substituted elements in mixed layered oxides

    PubMed Central

    Akama, Shota; Kobayashi, Wataru; Amaha, Kaoru; Niwa, Hideharu; Nitani, Hiroaki; Moritomo, Yutaka

    2017-01-01

    The chemical substitution of a transition metal (M) is an effective method to improve the functionality of a material, such as its electrochemical, magnetic, and dielectric properties. The substitution, however, causes local lattice distortion because the difference in the ionic radius (r) modifies the local interatomic distances. Here, we systematically investigated the local structures in the pure (x = 0.0) and mixed (x = 0.05 or 0.1) layered oxides, Na(M1−xM′x)O2 (M and M′ are the majority and minority transition metals, respectively), by means of extended X-ray absorption fine structure (EXAFS) analysis. We found that the local interatomic distance (dM-O) around the minority element approaches that around the majority element to reduces the local lattice distortion. We further found that the valence of the minority Mn changes so that its ionic radius approaches that of the majority M. PMID:28252008

  13. Solid oxide fuel cell stacks using extruded honeycomb type elements

    NASA Astrophysics Data System (ADS)

    Wetzko, M.; Belzner, A.; Rohr, F. J.; Harbach, F.

    A solid oxide fuel cell (SOFC) stack concept is described which comprises "condensed-tubes" like extruded honeycomb sections of ceramic electrolyte (ZrO 2-based) and interconnectors of nickel sheet as key elements. According to this concept, well known and extensively tested construction principles can be realised in a low-cost production. The cells are self-supported with in-plane conduction. A demonstrator model stack of five honeycomb elements and six nickel sheet seals/interconnectors was built and operated for 860 h at 1000°C. Volumetric power densities of 160 kW/m 3 were obtained with H 2 vs. air, of close to 200 kW/m 3 with H 2 vs. O 2.

  14. Local structures around the substituted elements in mixed layered oxides

    NASA Astrophysics Data System (ADS)

    Akama, Shota; Kobayashi, Wataru; Amaha, Kaoru; Niwa, Hideharu; Nitani, Hiroaki; Moritomo, Yutaka

    2017-03-01

    The chemical substitution of a transition metal (M) is an effective method to improve the functionality of a material, such as its electrochemical, magnetic, and dielectric properties. The substitution, however, causes local lattice distortion because the difference in the ionic radius (r) modifies the local interatomic distances. Here, we systematically investigated the local structures in the pure (x = 0.0) and mixed (x = 0.05 or 0.1) layered oxides, Na(M1‑xM‧x)O2 (M and M‧ are the majority and minority transition metals, respectively), by means of extended X-ray absorption fine structure (EXAFS) analysis. We found that the local interatomic distance (dM-O) around the minority element approaches that around the majority element to reduces the local lattice distortion. We further found that the valence of the minority Mn changes so that its ionic radius approaches that of the majority M.

  15. Oxidation of elemental Hg in anthropogenic and marine airmasses

    NASA Astrophysics Data System (ADS)

    Timonen, H.; Ambrose, J. L.; Jaffe, D. A.

    2013-03-01

    Mercury (Hg) is a neurotoxin that bioaccumulates in the food chain. Mercury is emitted to the atmosphere primarily in its elemental form, which has a long lifetime allowing global transport. It is known that atmospheric oxidation of gaseous elemental mercury (GEM) generates reactive gaseous mercury (RGM) which plays an important role in the atmospheric mercury cycle by enhancing the rate of mercury deposition to ecosystems. However, the primary GEM oxidants, and the chemical composition of RGM are poorly known. Using speciated mercury measurements conducted at the Mt. Bachelor Observatory since 2005 we present two previously unidentified sources of RGM to the free troposphere (FT). Firstly, we observed elevated RGM concentrations, large RGM/GEM-ratios, and anti-correlation between RGM and GEM during Asian long-rang transport events, demonstrating that RGM is formed from GEM by in-situ oxidation in some anthropogenic pollution plumes in the FT. During the Asian pollution events the measured RGM/GEM-enhancement ratios reached peak values, up to ~0.20, which are significantly larger than ratios typically measured (RGM/GEM < 0.03) in the Asian source region. Secondly, we observed very high RGM levels - the highest reported in the FT - in clean air masses that were processed upwind of Mt. Bachelor Observatory over the Pacific Ocean. The high RGM concentrations (up to 700 pg m-3), high RGM/GEM-ratios (up to 1), and very low ozone levels during these events provide observational evidence indicating significant GEM oxidation in the lower FT in some conditions.

  16. Process for oxidation of hydrogen halides to elemental halogens

    DOEpatents

    Lyke, Stephen E.

    1992-01-01

    An improved process for generating an elemental halogen selected from chlorine, bromine or iodine, from a corresponding hydrogen halide by absorbing a molten salt mixture, which includes sulfur, alkali metals and oxygen with a sulfur to metal molar ratio between 0.9 and 1.1 and includes a dissolved oxygen compound capable of reacting with hydrogen halide to produce elemental halogen, into a porous, relatively inert substrate to produce a substrate-supported salt mixture. Thereafter, the substrate-supported salt mixture is contacted (stage 1) with a hydrogen halide while maintaining the substrate-supported salt mixture during the contacting at an elevated temperature sufficient to sustain a reaction between the oxygen compound and the hydrogen halide to produce a gaseous elemental halogen product. This is followed by purging the substrate-supported salt mixture with steam (stage 2) thereby recovering any unreacted hydrogen halide and additional elemental halogen for recycle to stage 1. The dissolved oxygen compound is regenerated in a high temperature (stage 3) and an optical intermediate temperature stage (stage 4) by contacting the substrate-supported salt mixture with a gas containing oxygen whereby the dissolved oxygen compound in the substrate-supported salt mixture is regenerated by being oxidized to a higher valence state.

  17. Stimulation of elemental mercury oxidation by SH compounds

    SciTech Connect

    Yamamoto, M.; Nakamura, K.; Yasutake, A.; Fujisaki, T.; Nakano, A.; Hou, H.

    1995-03-01

    Anthropogenic mercury pollution has been a serious environmental problem. The presence of mercury in the environment has received a great deal of attention due to its highly toxic nature and translocation through the food chain. Elemental mercury released into the Amazon River basin due to gold mining activities is roughly estimated at 130 tons per year. In fact, high levels of total mercury, mostly in the form of methylmercury, in fish collected from around the gold mining areas and high levels of methylmercury in the hair of humans living in fishing villages downstream of these areas have recently been documented. These results suggest that the reaction which converts the discharged elemental mercury into mercuric mercury is present in nature before the methylation of the generated mercuric mercury. Methylation and reduction of mercuric mercury and decomposition of organomercury have been extensively studied. However, little information is available concerning the conversion of elemental mercury in aquatic ecosystems. The purpose of this study was to clarify the mechanism of oxidation of elemental mercury to mercuric mercury in the aquatic environment. 11 refs., 4 figs.

  18. Targeting heavy rare earth elements in carbonatite complexes

    NASA Astrophysics Data System (ADS)

    Broom-Fendley, S.; Wall, F.; Gunn, A. G.; Dowman, E.

    2012-04-01

    The world's main sources of the rare earth elements (REE) are concentrated in carbonatite complexes. These have the advantages of high grade and tonnage, combined with low thorium contents, yet they are generally enriched in light rare earths (LREE). The heavy rare earths (HREE, which include Eu-Lu and Y) are more highly sought after because of their role in new and green technologies. HREE are predominantly extracted from ion-adsorption clays in China. These are small, low grade deposits, which are often illegally mined by artisans. Increased government control, environmental legislation and local demand for REE in China have led to high prices and global concerns about the security of supply of the HREE. Alternative sources of the HREE are poorly documented. We present a review of such targets, including: (1) 'abnormal' carbonatites; (2) areas around LREE-rich complexes such as breccia, fenite and latter stage veins; and (3) weathered carbonatites. At Lofdal, Namibia, carbonatite dykes contain xenotime-(Y) together with LREE minerals. The original chemistry of the carbonatite magma, coupled with late-stage magma and fluid evolution, seem to be controlling factors [1, 2]. The Khibina carbonatite, Kola Peninsula, Russia, is an example of where early LREE carbonatites become increasing HREE-enriched as magmas evolve to carbo-hydrothermal fluids [3]. Around carbonatite complexes in Malawi HREE enrichment can be found in breccia and in fenite. Breccia around Songwe shows areas with high Y/La ratios within the matrix caused by narrow zones of xenotime enrichment. Fenite around Kangankunde and Chilwa Island has higher HREE:LREE ratios than the carbonatite [4]. At weathered complexes, such as at Mount Weld in Western Australia, changes in both HREE concentration and LREE:HREE ratios are observed. In currently unworked sections of the deposit, the HREE mineral churchite (YPO4.H2O) has formed concentrations due to groundwater flow [5]. These areas of enrichment are

  19. Oxidant-induced DNA damage of target cells.

    PubMed Central

    Schraufstätter, I; Hyslop, P A; Jackson, J H; Cochrane, C G

    1988-01-01

    In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks. PMID:2843565

  20. Whole Genome Resequencing Reveals Natural Target Site Preferences of Transposable Elements in Drosophila melanogaster

    PubMed Central

    Linheiro, Raquel S.; Bergman, Casey M.

    2012-01-01

    Transposable elements are mobile DNA sequences that integrate into host genomes using diverse mechanisms with varying degrees of target site specificity. While the target site preferences of some engineered transposable elements are well studied, the natural target preferences of most transposable elements are poorly characterized. Using population genomic resequencing data from 166 strains of Drosophila melanogaster, we identified over 8,000 new insertion sites not present in the reference genome sequence that we used to decode the natural target preferences of 22 families of transposable element in this species. We found that terminal inverted repeat transposon and long terminal repeat retrotransposon families present clade-specific target site duplications and target site sequence motifs. Additionally, we found that the sequence motifs at transposable element target sites are always palindromes that extend beyond the target site duplication. Our results demonstrate the utility of population genomics data for high-throughput inference of transposable element targeting preferences in the wild and establish general rules for terminal inverted repeat transposon and long terminal repeat retrotransposon target site selection in eukaryotic genomes. PMID:22347367

  1. Oxidative Stress in Intracerebral Hemorrhage: Sources, Mechanisms, and Therapeutic Targets

    PubMed Central

    Hu, Xin; Tao, Chuanyuan; Gan, Qi; Zheng, Jun; Li, Hao; You, Chao

    2016-01-01

    Intracerebral hemorrhage (ICH) is associated with the highest mortality and morbidity despite only constituting approximately 10–15% of all strokes. Complex underlying mechanisms consisting of cytotoxic, excitotoxic, and inflammatory effects of intraparenchymal blood are responsible for its highly damaging effects. Oxidative stress (OS) also plays an important role in brain injury after ICH but attracts less attention than other factors. Increasing evidence has demonstrated that the metabolite axis of hemoglobin-heme-iron is the key contributor to oxidative brain damage after ICH, although other factors, such as neuroinflammation and prooxidases, are involved. This review will discuss the sources, possible molecular mechanisms, and potential therapeutic targets of OS in ICH. PMID:26843907

  2. Rare earth element partitioning between hydrous ferric oxides and acid mine water during iron oxidation

    USGS Publications Warehouse

    Verplanck, P.L.; Nordstrom, D.K.; Taylor, H.E.; Kimball, B.A.

    2004-01-01

    Ferrous iron rapidly oxidizes to Fe (III) and precipitates as hydrous Fe (III) oxides in acid mine waters. This study examines the effect of Fe precipitation on the rare earth element (REE) geochemistry of acid mine waters to determine the pH range over which REEs behave conservatively and the range over which attenuation and fractionation occur. Two field studies were designed to investigate REE attenuation during Fe oxidation in acidic, alpine surface waters. To complement these field studies, a suite of six acid mine waters with a pH range from 1.6 to 6.1 were collected and allowed to oxidize in the laboratory at ambient conditions to determine the partitioning of REEs during Fe oxidation and precipitation. Results from field experiments document that even with substantial Fe oxidation, the REEs remain dissolved in acid, sulfate waters with pH below 5.1. Between pH 5.1 and 6.6 the REEs partitioned to the solid phases in the water column, and heavy REEs were preferentially removed compared to light REEs. Laboratory experiments corroborated field data with the most solid-phase partitioning occurring in the waters with the highest pH. ?? 2004 Elsevier Ltd. All rights reserved.

  3. Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles

    PubMed Central

    Tefft, Brandon J.; Uthamaraj, Susheil; Harburn, J. Jonathan; Klabusay, Martin; Dragomir-Daescu, Dan; Sandhu, Gurpreet S.

    2015-01-01

    Targeted delivery of cells and therapeutic agents would benefit a wide range of biomedical applications by concentrating the therapeutic effect at the target site while minimizing deleterious effects to off-target sites. Magnetic cell targeting is an efficient, safe, and straightforward delivery technique. Superparamagnetic iron oxide nanoparticles (SPION) are biodegradable, biocompatible, and can be endocytosed into cells to render them responsive to magnetic fields. The synthesis process involves creating magnetite (Fe3O4) nanoparticles followed by high-speed emulsification to form a poly(lactic-co-glycolic acid) (PLGA) coating. The PLGA-magnetite SPIONs are approximately 120 nm in diameter including the approximately 10 nm diameter magnetite core. When placed in culture medium, SPIONs are naturally endocytosed by cells and stored as small clusters within cytoplasmic endosomes. These particles impart sufficient magnetic mass to the cells to allow for targeting within magnetic fields. Numerous cell sorting and targeting applications are enabled by rendering various cell types responsive to magnetic fields. SPIONs have a variety of other biomedical applications as well including use as a medical imaging contrast agent, targeted drug or gene delivery, diagnostic assays, and generation of local hyperthermia for tumor therapy or tissue soldering. PMID:26554870

  4. Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis

    PubMed Central

    Kimura, Atsuko; Namekata, Kazuhiko; Guo, Xiaoli; Noro, Takahiko; Harada, Chikako

    2017-01-01

    Glaucoma is a neurodegenerative disease of the eye and it is one of the leading causes of blindness. Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons, namely, the optic nerve, usually associated with elevated intraocular pressure (IOP). Current glaucoma therapies target reduction of IOP, but since RGC death is the cause of irreversible vision loss, neuroprotection may be an effective strategy for glaucoma treatment. One of the risk factors for glaucoma is increased oxidative stress, and drugs with antioxidative properties including valproic acid and spermidine, as well as inhibition of apoptosis signal-regulating kinase 1, an enzyme that is involved in oxidative stress, have been reported to prevent glaucomatous retinal degeneration in mouse models of glaucoma. Optic neuritis is a demyelinating inflammation of the optic nerve that presents with visual impairment and it is commonly associated with multiple sclerosis, a chronic demyelinating disease of the central nervous system. Although steroids are commonly used for treatment of optic neuritis, reduction of oxidative stress by approaches such as gene therapy is effective in ameliorating optic nerve demyelination in preclinical studies. In this review, we discuss oxidative stress as a therapeutic target for glaucoma and optic neuritis. PMID:28270908

  5. Genome-wide target site triplication of Alu elements in the human genome.

    PubMed

    Lee, Wooseok; Mun, Seyoung; Kang, Keunsoo; Hennighausen, Lothar; Han, Kyudong

    2015-05-01

    Alu elements are the most successful short interspersed elements in primate genomes and their retrotransposition is a major source of genomic expansion. Alu elements integrate into genomic regions through target-site primed reverse transcription, which generates target site duplications (TSDs). Unexpectedly, we have identified target site triplications (TSTs) at some loci, where two Alu elements in tandem share one direct repeat. Thus, the three copies of the repeat are present. We located 212 TST loci in the human genome and examined 25 putative human-specific TST loci using PCR validation. As a result, 12 human-specific TST loci were identified. These findings suggest that unequal homologous recombination between TSDs can lead to TST. Through this mechanism, the copy number of Alu elements could have increased in primate genomes without new Alu retrotransposition events. This study provides new insight into the augmentation of Alu elements in the primate genome.

  6. Do pharmacological approaches that prevent opioid tolerance target different elements in the same regulatory machinery?

    PubMed

    Garzón, Javier; Rodríguez-Muñoz, María; Sánchez-Blázquez, Pilar

    2008-06-01

    In the nervous system, the interaction of opioids like heroin and morphine with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of tolerance to these opioids, as well as physical dependence. Tolerance implies that higher doses of these drugs must be consumed in order to obtain an equivalent sensation, a situation that contributes notably to the social problems surrounding recreational opioid abuse. The mechanisms that promote opioid tolerance involve a series of adaptive changes in the MOR and in the post-receptor signalling elements. Pharmacological studies have consistently identified a number of signalling proteins relevant to morphine-induced tolerance, including the delta-opioid receptor (DOR), protein kinase C (PKC), protein kinase A (PKA), calcium/calmodulin-dependent kinase II (CaMKII), nitric oxide synthase (NOS), N-methyl-D-aspartate acid glutamate receptors (NMDAR), and regulators of G-signalling (RGS) proteins. Thus, it is feasible that these treatments which diminish morphine tolerance target distinct elements within the same regulatory machinery. In this scheme, the signals originated at the agonist-activated MORs would be recognised by elements such as the NMDARs, which in turn exert a negative feedback on MOR-evoked signalling. This process involves DOR regulation of MORs, MOR-induced activation of NMDARs (probably via the regulation of Src, recruiting PKC and Galpha subunits) and the NMDAR-mediated activation of CaMKII. The active CaMKII promotes the sequestering of morphine-activated Gbetagamma dimers by phosducin-like proteins (PhLP) and of Galpha subunits by RGS proteins and tolerance to opioids like morphine develops. Future efforts to study these phenomena should focus on fitting additional pieces into this puzzle in order to fully define the mechanism underlying the desensitization of MORs in neural cells.

  7. Dissolution of Neptunium Oxide in Unirradiated Mark 53 Targets

    SciTech Connect

    Rudisill, T.S.

    2002-12-06

    Nine unirradiated Mark 53 targets currently stored at the K-Reactor must be dissolved to allow recovery of the neptunium content. The Mark 53 targets are an aluminum clad, neptunium oxide (NpO2)/aluminum metal cermet used for the production of plutonium-238. The targets will be dissolved in H-Canyon and blended with solutions generated from routine fuel dissolutions for purification by solvent extraction. The increased neptunium concentration should not have a significant effect on the neptunium decontamination factor achieved by the 1st cycle of solvent extraction; however, the neptunium content of the uranium product (1CU) will likely increase in proportion to the increase in the neptunium feed concentration. The recovered neptunium will be combined with the existing inventory of neptunium solution currently stored in H-Canyon. The combined inventory will undergo subsequent purification and conversion to an oxide for shipment to the Oak Ridge National Laboratory where plutonium- 238 will be manufactured using the High Flux Isotope Reactor.

  8. Regulatory Elements in Vectors for Efficient Generation of Cell Lines Producing Target Proteins

    PubMed Central

    Maksimenko, O.; Gasanov, N. B.; Georgiev, P.

    2015-01-01

    To date, there has been an increasing number of drugs produced in mammalian cell cultures. In order to enhance the expression level and stability of target recombinant proteins in cell cultures, various regulatory elements with poorly studied mechanisms of action are used. In this review, we summarize and discuss the potential mechanisms of action of such regulatory elements. PMID:26483956

  9. [Element Sulfur Autotrophic Denitrification Combined Anaerobic Ammonia Oxidation].

    PubMed

    Zhou, Jian; Huang, Yong; Liu, Xin; Yuan, Yi; Li Xiang; Wangyan, De-qing; Ding, Liang; Shao, Jing-wei; Zhao, Rong

    2016-03-15

    A novel element sulfur autotrophic denitrification combined anaerobic ammonia oxidation process, reacted in CSTR, was used to investigate the sulfate production and alkalinity consumption during the whole process. The element sulfur dosage was 50 g · L⁻¹. The inoculation volume of ANAMMOX granular sludge was 100 g · L⁻¹. The agitation rate and environment reaction temperature of the CSTR were set to 120 r · min⁻¹ and 35°C ± 0.5°C, respectively. The pH of influent was maintained in range of 8. 0-8. 4. During the start-up stage of sulfur based autotrophic denitrification, the nitrogen removal loading rate could reach 0.56-0.71 kg · (m³ · d) ⁻¹ in the condition of 5.3 h hydrogen retention time and 200 mg · L⁻¹ nitrate nitrogen. After the addition of 60 mg · L⁻¹ ammonia nitrogen, Δn(SO₄²⁻):Δn(NO₃⁻) decreased from 1.21 ± 0.06 to 1.01 ± 0.10, Δ(IC): Δ(NO₃⁻-N) decreased from 0.72 ± 0.1 to 0.51 ± 0.11, and the effluent pH increased from 6.5 to 7.2. During the combined stage, the ammonia concentration of effluent was 10.1-19.2 mg · L⁻¹, and the nitrate-nitrogen removal loading rate could be maintained in range of 0.66-0.88 kg · (m³ · d)⁻¹. The Δn (NH₄⁺): Δn (NO₃⁻) ratio reached 0.43, and the NO₃⁻ removal rate was increased by 60% in the simultaneous ammonia and nitrate removal reaction under the condition of G(T) = 22-64 s⁻¹ and pH = 8.08, while improper conditions reduced the efficiency of simultaneous reaction.

  10. Periodic Table Target: A Game that Introduces the Biological Significance of Chemical Element Periodicity

    ERIC Educational Resources Information Center

    Sevcik, Richard S.; McGinty, Ragan L.; Schultz, Linda D.; Alexander, Susan V.

    2008-01-01

    Periodic Table Target, a game for middle school or high school students, familiarizes students with the form of the periodic table and the biological significance of different elements. The Periodic Table Target game board is constructed as a class project, and the game is played to reinforce the content. Students are assigned several elements…

  11. KINETICS OF DIRECT OXIDATION OF H2S IN COAL GAS TO ELEMENTAL SULFUR

    SciTech Connect

    K.C. Kwon

    2002-02-01

    Removal of hydrogen sulfide (H{sub 2}S) from coal gasifier gas and sulfur recovery are key steps in the development of Department of Energy's (DOE's) advanced Vision 21 plants that employ coal and natural gas and produce electric power and clean transportation fuels. These Vision 21 plants will require highly clean coal gas with H{sub 2}S below 1 ppm and negligible amounts of trace contaminants such as hydrogen chloride, ammonia, alkali, heavy metals, and particulate. The conventional method of sulfur removal and recovery employing amine, Claus, and tail-gas treatment is very expensive. A second generation approach developed under DOE's sponsorship employs hot-gas desulfurization (HGD) using regenerable metal oxide sorbents followed by Direct Sulfur Recovery Process (DSRP). However, this process sequence does not remove trace contaminants and is targeted primarily towards the development of advanced integrated gasification combined cycle (IGCC) plants that produce electricity (not both electricity and transportation fuels). There is an immediate as well as long-term need for the development of cleanup processes that produce highly clean coal gas for next generation Vision 21 plants. To this end, a novel process is now under development at Research Triangle Institute (RTI) in which the H{sub 2}S in coal gas is directly oxidized to elemental sulfur over a selective catalyst. Such a process is ideally suited for coal gas from commercial gasifiers with a quench system to remove essentially all the trace contaminants except H{sub 2}S. This direct oxidation process has the potential to produce a super clean coal gas more economically than both conventional amine-based processes and HGD/DSRP. The objective of this research is to support the near- and long-term DOE efforts to commercialize this direct oxidation technology. Specifically, we aim to: Measure the kinetics of direct oxidation of H{sub 2}S to elemental sulfur over selective catalysts in the presence of major

  12. Modification of surface oxide layers of titanium targets for increasing lifetime of neutron tubes

    SciTech Connect

    Zakharov, A. M. Dvoichenkova, O. A.; Evsin, A. E.

    2015-12-15

    The peculiarities of interaction of hydrogen ions with a titanium target and its surface oxide layer were studied. Two ways of modification of the surface oxide layers of titanium targets for increasing the lifetime of neutron tubes were proposed: (1) deposition of an yttrium oxide barrier layer on the target surface; (2) implementation of neutron tube work regime in which the target is irradiated with ions with energies lower than 1000 eV between high-energy ion irradiation pulses.

  13. Modification of surface oxide layers of titanium targets for increasing lifetime of neutron tubes

    NASA Astrophysics Data System (ADS)

    Zakharov, A. M.; Dvoichenkova, O. A.; Evsin, A. E.

    2015-12-01

    The peculiarities of interaction of hydrogen ions with a titanium target and its surface oxide layer were studied. Two ways of modification of the surface oxide layers of titanium targets for increasing the lifetime of neutron tubes were proposed: (1) deposition of an yttrium oxide barrier layer on the target surface; (2) implementation of neutron tube work regime in which the target is irradiated with ions with energies lower than 1000 eV between high-energy ion irradiation pulses.

  14. Transposable Element Targeting by piRNAs in Laurasiatherians with Distinct Transposable Element Histories

    PubMed Central

    Vandewege, Michael W.; Platt, Roy N.; Ray, David A.; Hoffmann, Federico G.

    2016-01-01

    PIWI proteins and PIWI-interacting RNAs (piRNAs) are part of a cellular pathway that has evolved to protect genomes against the proliferation of transposable elements (TEs). PIWIs and piRNAs assemble into complexes that are involved in epigenetic and post-transcriptional repression of TEs. Most of our understanding of the mechanisms of piRNA-mediated TE silencing comes from fruit fly and mouse models. However, even in these well-studied animals it is unclear how piRNA responses relate to variable TE expression and whether the strength of the piRNA response affects TE content over time. Here, we assessed the evolutionary interactions between TE and piRNAs in a statistical framework using three nonmodel laurasiatherian mammals as a study system: dog, horse, and a vesper bat. These three species diverged ∼80 million years ago and have distinct genomic TE contents. By comparing species with distinct TE landscapes, we aimed to identify clear relationships among TE content, expression, and piRNAs. We found that the TE subfamilies that are the most transcribed appear to elicit the strongest “ping-pong” response. This was most evident among long interspersed elements, but the relationships between expression and ping-pong pilRNA (piRNA-like) expression were more complex among SINEs. SINE transcripts were equally abundant in the dog and horse yet new SINE insertions were relatively rare in the horse genome, where we identified a stronger piRNA response. Our analyses suggest that the piRNA response can have a strong impact on the TE composition of a genome. However, our results also suggest that the presence of a robust piRNA response is apparently not sufficient to stop TE mobilization and accumulation. PMID:27060702

  15. Stoichiometry control of complex oxides by sequential pulsed-laser deposition from binary-oxide targets

    NASA Astrophysics Data System (ADS)

    Herklotz, A.; Dörr, K.; Ward, T. Z.; Eres, G.; Christen, H. M.; Biegalski, M. D.

    2015-03-01

    To have precise atomic layer control over interfaces, we examine the growth of complex oxides through the sequential deposition from binary targets by pulsed laser deposition. In situ reflection high-energy electron diffraction (RHEED) is used to control the growth and achieve films with excellent structural quality. The growth from binary oxide targets is fundamentally different from single target growth modes and shows more similarities to shuttered growth by molecular beam epitaxy. The RHEED intensity oscillations of non-stoichiometric growth are consistent with a model of island growth and accumulation of excess material on the surface that can be utilized to determine the correct stoichiometry for growth. Correct monolayer doses can be determined through an envelope frequency in the RHEED intensity oscillations. In order to demonstrate the ability of this growth technique to create complex heterostructures, the artificial n = 2 and 3 Srn+1TinO3n+1 Ruddlesden-Popper phases are grown with good long-range order. This method enables the precise unit-cell level control over the structure of perovskite-type oxides, and thus the growth of complex materials with improved structural quality and electronic functionality.

  16. Stoichiometry control of complex oxides by sequential pulsed-laser deposition from binary-oxide targets

    SciTech Connect

    Herklotz, A.; Dörr, Kathrin; Ward, T. Z.; Eres, G.; Christen, H. M.; Biegalski, Michael D.

    2015-04-03

    In this paper, to have precise atomic layer control over interfaces, we examine the growth of complex oxides through the sequential deposition from binary targets by pulsed laser deposition. In situ reflection high-energy electron diffraction (RHEED) is used to control the growth and achieve films with excellent structural quality. The growth from binary oxide targets is fundamentally different from single target growth modes and shows more similarities to shuttered growth by molecular beam epitaxy. The RHEED intensity oscillations of non-stoichiometric growth are consistent with a model of island growth and accumulation of excess material on the surface that can be utilized to determine the correct stoichiometry for growth. Correct monolayer doses can be determined through an envelope frequency in the RHEED intensity oscillations. In order to demonstrate the ability of this growth technique to create complex heterostructures, the artificial n = 2 and 3 Sr n +1Ti n O3 n +1 Ruddlesden-Popper phases are grown with good long-range order. Finally, this method enables the precise unit-cell level control over the structure of perovskite-type oxides, and thus the growth of complex materials with improved structural quality and electronic functionality.

  17. Stoichiometry control of complex oxides by sequential pulsed-laser deposition from binary-oxide targets

    DOE PAGES

    Herklotz, A.; Dörr, Kathrin; Ward, T. Z.; ...

    2015-04-03

    In this paper, to have precise atomic layer control over interfaces, we examine the growth of complex oxides through the sequential deposition from binary targets by pulsed laser deposition. In situ reflection high-energy electron diffraction (RHEED) is used to control the growth and achieve films with excellent structural quality. The growth from binary oxide targets is fundamentally different from single target growth modes and shows more similarities to shuttered growth by molecular beam epitaxy. The RHEED intensity oscillations of non-stoichiometric growth are consistent with a model of island growth and accumulation of excess material on the surface that can bemore » utilized to determine the correct stoichiometry for growth. Correct monolayer doses can be determined through an envelope frequency in the RHEED intensity oscillations. In order to demonstrate the ability of this growth technique to create complex heterostructures, the artificial n = 2 and 3 Sr n +1Ti n O3 n +1 Ruddlesden-Popper phases are grown with good long-range order. Finally, this method enables the precise unit-cell level control over the structure of perovskite-type oxides, and thus the growth of complex materials with improved structural quality and electronic functionality.« less

  18. Stoichiometry control of complex oxides by sequential pulsed-laser deposition from binary-oxide targets

    SciTech Connect

    Herklotz, A.; Dörr, K.; Ward, T. Z.; Eres, G.; Christen, H. M.; Biegalski, M. D.

    2015-03-30

    To have precise atomic layer control over interfaces, we examine the growth of complex oxides through the sequential deposition from binary targets by pulsed laser deposition. In situ reflection high-energy electron diffraction (RHEED) is used to control the growth and achieve films with excellent structural quality. The growth from binary oxide targets is fundamentally different from single target growth modes and shows more similarities to shuttered growth by molecular beam epitaxy. The RHEED intensity oscillations of non-stoichiometric growth are consistent with a model of island growth and accumulation of excess material on the surface that can be utilized to determine the correct stoichiometry for growth. Correct monolayer doses can be determined through an envelope frequency in the RHEED intensity oscillations. In order to demonstrate the ability of this growth technique to create complex heterostructures, the artificial n = 2 and 3 Sr{sub n+1}Ti{sub n}O{sub 3n+1} Ruddlesden-Popper phases are grown with good long-range order. This method enables the precise unit-cell level control over the structure of perovskite-type oxides, and thus the growth of complex materials with improved structural quality and electronic functionality.

  19. TRACE ELEMENT BINDING DURING STRUCTURAL TRANSFORMATION IN IRON OXIDES

    EPA Science Inventory

    Iron (hydr)oxides often control the mobility of inorganic contaminants in soils and sediments. A poorly ordered form of ferrihydrite is commonly produced during rapid oxidation of ferrous iron at sharp redox fronts encountered during discharge of anoxic/suboxic waters into terre...

  20. Two Maize Genes Are Each Targeted Predominantly by Distinct Classes of Mu Elements

    PubMed Central

    Hardeman, K. J.; Chandler, V. L.

    1993-01-01

    The Mutator transposable element system of maize has been used to isolate mutations at many different genes. Six different classes of Mu transposable elements have been identified. An important question is whether particular classes of Mu elements insert into different genes at equivalent frequencies. To begin to address this question, we used a small number of closely related Mutator plants to generate multiple independent mutations at two different genes. The overall mutation frequency was similar for the two genes. We then determined what types of Mu elements inserted into the genes. We found that each of the genes was preferentially targeted by a different class of Mu element, even when the two genes were mutated in the same plant. Possible explanations for these findings are discussed. These results have important implications for cloning Mu-tagged genes as other genes may also be resistant or susceptible to the insertion of particular classes of Mu elements. PMID:8307329

  1. Pulsed—Laser Deposition Of Oxide Thin Films And Laser—Induced Breakdown Spectroscopy Of Multi—Element Materials

    NASA Astrophysics Data System (ADS)

    Pedarnig, Johannes D.

    2010-10-01

    New results of the Linz group on pulsed—laser deposition (PLD) of oxide thin films and on laser—induced breakdown spectroscopy (LIBS) of multi-element materials are reported. High-Tc superconducting (HTS) films with enhanced critical current density Jc are produced by laser ablation of novel nano-composite ceramic targets. The targets contain insulating nano-particles that are embedded into the YBa2Cu3O7 matrix. Epitaxial double-layers of lithium-doped and aluminum-doped ZnO are deposited on r-cut sapphire substrates. Acoustic over-modes in the GHz range are excited by piezoelectric actuation of layers. Smooth films of rare-earth doped glass are produced by F2—laser ablation. The transport properties of HTS thin films are modified by light—ion irradiation. Thin film nano—patterning is achieved by masked ion beam irradiation. LIBS is employed to analyze trace elements in industrial iron oxide powder and reference polymer materials. Various trace elements of ppm concentration are measured in the UV/VIS and vacuum-UV spectral range. Quantitative LIBS analysis of major components in oxide materials is performed by calibration-free methods.

  2. The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that responds to oxidative stress by binding to the antioxidant response element (ARE) in the promoter of genes coding for antioxidant enzymes like NAD(P)H:quinone oxidoreductase 1 (NQO1) and proteins for glutathione synthesis. ...

  3. Selected attributes of polyphenols in targeting oxidative stress in cancer.

    PubMed

    Stepanic, Visnja; Gasparovic, Ana Cipak; Troselj, Koraljka Gall; Amic, Dragan; Zarkovic, Neven

    2015-01-01

    Various plant polyphenols have been recognized as redox active molecules. This review discusses some aspects of polyphenols' modes of redox action, corresponding structure-activity relationships and their potential to be applied as adjuvants to conventional cytostatic drugs. Polyphenols' antioxidative capacity has been discussed as the basis for targeting oxidative stress and, consequently, for their chemopreventive and anti-inflammatory activities, which may alleviate side-effects on normal cells arising from oxidative stress caused by cytostatics. Some polyphenols may scavenge various free radicals directly, and some of them are found to suppress free radical production through inhibiting NADPH oxidases and xanthine oxidase. Additionally, polyphenols may increase antioxidative defense in normal cells by increasing the activity of NRF2, transcription factor for many protective proteins. The activation of the NRF2-mediated signaling pathways in cancer cells results in chemoresistance. Luteolin, apigenin and chrysin reduce NRF2 expression and increase the chemosensitivity of cancer cells to cytostatic drugs. Their common 5,7-dihydroxy-4H-chromen-4-one moiety, may represent a starting pharmacophore model for designing novel, non-toxic compounds for overcoming chemoresistance. However, prooxidative activity of some polyphenols (quercetin, EGCG) may also provide a basis for their use as chemotherapeutic adjuvants since they may enhance cytotoxic effects of cytostatics selectively on cancer cells. However, considerable caution is needed in applying polyphenols to anticancer therapy, since their effects greatly depend on the applied dose, the cell type, exposure time and environmental conditions.

  4. Oxidative Stress and Liver Cancer: Etiology and Therapeutic Targets

    PubMed Central

    Wang, Zhanpeng; Li, Zhuonan; Ye, Yanshuo; Xie, Lijuan

    2016-01-01

    Accumulating evidence has indicated that oxidative stress (OS) is associated with the development of hepatocellular carcinoma (HCC). However, the mechanisms remain largely unknown. Normally, OS occurs when the body receives any danger signal—from either an internal or external source—and further induces DNA oxidative damage and abnormal protein expression, placing the body into a state of vulnerability to the development of various diseases such as cancer. There are many factors involved in liver carcinogenesis, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcohol abuse, and nonalcoholic fatty liver disease (NAFLD). The relationship between OS and HCC has recently been attracting increasing attention. Therefore, elucidation of the impact of OS on the development of liver carcinogenesis is very important for the prevention and treatment of liver cancer. This review focuses mainly on the relationship between OS and the development of HCC from the perspective of cellular and molecular mechanisms and the etiology and therapeutic targets of HCC. PMID:27957239

  5. Inducible nitric oxide synthase as a possible target in hypertension.

    PubMed

    Oliveira-Paula, Gustavo H; Lacchini, Riccardo; Tanus-Santos, Jose E

    2014-02-01

    Nitric oxide (NO) is an important vasodilator produced by vascular endothelium. Its enzymatic formation is derived from three different synthases: neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) synthases. While relatively small amounts of NO produced by eNOS are important to cardiovascular homeostasis, high NO levels produced associated with iNOS activity may have detrimental consequences to the cardiovascular system and contribute to hypertension. In this article, we reviewed current literature and found mounting evidence indicating that increased iNOS expression and activity contribute to the pathogenesis of hypertension and its complications. Excessive amounts of NO produced by iNOS up-regulation can react with superoxide anions forming peroxynitrite, thereby promoting nitrosative stress and endothelial dysfunction. In addition, abnormal iNOS activity can up-regulate arginase activity, allowing it to compete with eNOS for L-arginine, thereby resulting in reduced NO bioavailability. This may also lead to eNOS uncoupling with enhanced production of superoxide anions instead of NO. All these alterations mediated by iNOS apparently contribute to hypertension and its complications. We also reviewed current evidence showing the effects of iNOS inhibitors on different animal models of hypertension. iNOS inhibition apparently exerts antihypertensive effects, decreases oxidative and nitrosative stress, and improves vascular function. Together, these studies highlight the possibility that iNOS is a potential pharmacological target in hypertension.

  6. Kinetics of Direct Oxidation of H2S in Coal Gas to Elemental Sulfur

    SciTech Connect

    K.C. Kwon

    2005-11-01

    Removal of hydrogen sulfide (H{sub 2}S) from coal gasifier gas and sulfur recovery are key steps in the development of Department of Energy's (DOE's) advanced Vision 21 plants that produce electric power and clean transportation fuels with coal and natural gas. These Vision 21 plants will require highly clean coal gas with H{sub 2}S below 1 ppm and negligible amounts of trace contaminants such as hydrogen chloride, ammonia, alkali, heavy metals, and particulate. The conventional method of sulfur removal and recovery employing amine, Claus, and tail-gas treatment is very expensive. A second generation approach developed under DOE's sponsorship employs hot-gas desulfurization (HGD) using regenerable metal oxide sorbents followed by Direct Sulfur Recovery Process (DSRP). However, this process sequence does not remove trace contaminants and is targeted primarily towards the development of advanced integrated gasification combined cycle (IGCC) plants that produce electricity (not both electricity and transportation fuels). There is an immediate as well as long-term need for the development of cleanup processes that produce highly clean coal gas for next generation Vision 21 plants. To this end, a novel process is now under development at several research organizations in which the H{sub 2}S in coal gas is directly oxidized to elemental sulfur over a selective catalyst. Such a process is ideally suited for coal gas from commercial gasifiers with a quench system to remove essentially all the trace contaminants except H{sub 2}S. The direct oxidation of H{sub 2}S to elemental sulfur in the presence of SO{sub 2} is ideally suited for coal gas from commercial gasifiers with a quench system to remove essentially all the trace contaminants except H{sub 2}S. This direct oxidation process has the potential to produce a super clean coal gas more economically than both conventional amine-based processes and HGD/DSRP. The objectives of this research are to measure kinetics of direct

  7. Uranium fluoride and metallic uranium as target materials for heavy-element experiments at SHIP

    NASA Astrophysics Data System (ADS)

    Kindler, Birgit; Ackermann, Dieter; Hartmann, Willi; Heßberger, Fritz Peter; Hofmann, Sigurd; Hübner, Annett; Lommel, Bettina; Mann, Rido; Steiner, Jutta

    2008-06-01

    In this contribution we describe the production and application of uranium targets for synthesis of heavy elements. The targets are prepared from uranium fluoride (UF 4) and from metallic uranium with thin carbon foils as backing. Targets of UF 4 were produced by thermal evaporation in a similar way as the frequently applied targets out of Bi, Bi 2O 3, Pb, PbS, SmF 3, and NdF 3, prepared mostly from isotopically enriched material [Birgit Kindler, et al., Nucl. Instr. and Meth. A 561 (2006) 107; Bettina Lommel, et al., Nucl. Instr. and Meth. A 561 (2006) 100]. In order to use more intensive beams and to avoid scattering of the reaction products in the target, metallic uranium is favorable. However, evaporation of metallic uranium is not feasible at a sustainable yield. Therefore, we established magnetron sputtering of metallic uranium. We describe production and properties of these targets. First irradiation tests show promising results.

  8. Macrophage Migration Inhibitory Factor as an Emerging Drug Target to Regulate Antioxidant Response Element System

    PubMed Central

    Yukitake, Hiroshi; Takizawa, Masayuki

    2017-01-01

    Oxidative stress is involved in pathophysiology and pathological conditions of numerous human diseases. Thus, understanding the mechanisms underlying the redox homeostasis in cells and organs is valuable for discovery of therapeutic drugs for oxidative stress-related diseases. Recently, by applying chemical biology approach with an ARE activator, BTZO-1, we found macrophage migration inhibitory factor (MIF) as a new regulator of antioxidant response element- (ARE-) mediated gene transcription. BTZO-1 and its active derivatives bound to MIF and protected cells and organs from oxidative insults via ARE activation in animal models with oxidative stress such as ischemia/reperfusion injury, inflammatory bowel diseases, and septic shock. In this review, we briefly highlight key findings in understanding the MIF-ARE system. PMID:28191280

  9. Cytoplasmic intron sequence-retaining transcripts can be dendritically targeted via ID element retrotransposons.

    PubMed

    Buckley, Peter T; Lee, Miler T; Sul, Jai-Yoon; Miyashiro, Kevin Y; Bell, Thomas J; Fisher, Stephen A; Kim, Junhyong; Eberwine, James

    2011-03-10

    RNA precursors give rise to mRNA after splicing of intronic sequences traditionally thought to occur in the nucleus. Here, we show that intron sequences are retained in a number of dendritically-targeted mRNAs, by using microarray and Illumina sequencing of isolated dendritic mRNA as well as in situ hybridization. Many of the retained introns contain ID elements, a class of SINE retrotransposon. A portion of these SINEs confers dendritic targeting to exogenous and endogenous transcripts showing the necessity of ID-mediated mechanisms for the targeting of different transcripts to dendrites. ID elements are capable of selectively altering the distribution of endogenous proteins, providing a link between intronic SINEs and protein function. As such, the ID element represents a common dendritic targeting element found across multiple RNAs. Retention of intronic sequence is a more general phenomenon than previously thought and plays a functional role in the biology of the neuron, partly mediated by co-opted repetitive sequences.

  10. Oxidation state of multivalent elements in high-level nuclear waste glass

    SciTech Connect

    Reynolds, J.G.

    2007-07-01

    Nuclear waste contains many different elements that have more than one oxidation state. When the nuclear waste is treated by vitrification, the behavior of the element in the melter and resulting glass product depends on the stable oxidation state. The stable oxidation state in any medium can be calculated from the standard potential in that medium. Consequently, the standard potential of multi-valent elements has been measured in many silicate-melts, including ones relevant to nuclear waste treatment. In this study, the relationship between the standard potential in molten nuclear waste glass and the standard potential in water will be quantified so that the standard potential of elements that have not been measured in glass can be estimated. The regression equation was found to have an R{sup 2} statistic of 0.96 or 0.83 depending on the number of electrons transferred in the reaction. The Nernst equation was then used to calculate the oxidation state of other relevant multi-valent elements in nuclear waste glass from these standard potentials and the measured ferrous to ferric iron ratio. The calculated oxidation states were consistent with all oxidation state measurements available. The calculated oxidation states were used to rationalize the behavior of many of the multi-valent elements. For instance, chromium increases glass crystallization because it is in the trivalent-state, iodine volatilises from the melter because it is in the volatile zero-valent state, and the leaching behavior of arsenic is driven by its oxidation state. Thus, these thermodynamic calculations explain the behavior of many trace elements during the vitrification process. (authors)

  11. HEATS OF FORMATION OF GIBBSITE AND LIGHT ELEMENT DOUBLE OXIDES,

    DTIC Science & Technology

    The heat of formation of gibbsite , from alpha-alumina and water, has been redetermined by solution calorimetry in hydrofluoric acid at 75C. A value...calorimetry in hydrofluoric acid at 75C. In the case of the double oxides that contained alumina, gibbsite was used as a reference compound. (Author)

  12. Development of Low-Cost Manufacturing Processes for Planar, Multilayer Solid Oxide Fuel Cell Elements

    SciTech Connect

    Scott Swartz; Matthew Seabaugh; William Dawson; Tim Armstrong; Harlan Anderson; John Lannutti

    2001-09-30

    This report summarizes the results of Phase II of this program, 'Low-Cost Manufacturing Of Multilayer Ceramic Fuel Cells'. The objective of the program is to develop advanced ceramic manufacturing technologies for making planar solid oxide fuel cell (SOFC) components that are more economical and reliable for a variety of applications. Phase II development work focused on three distinct manufacturing approaches (or tracks) for planar solid oxide fuel cell elements. Two development tracks, led by NexTech Materials and Oak Ridge National Laboratory, involved co-sintering of planar SOFC elements of cathode-supported and anode-supported variations. A third development track, led by the University of Missouri-Rolla, focused on a revolutionary approach for reducing operating temperature of SOFCs by using spin-coating to deposit ultra-thin, nano-crystalline YSZ electrolyte films. The work in Phase II was supported by characterization work at Ohio State University. The primary technical accomplishments within each of the three development tracks are summarized. Track 1--NexTech's targeted manufacturing process for planar SOFC elements involves tape casting of porous electrode substrates, colloidal-spray deposition of YSZ electrolyte films, co-sintering of bi-layer elements, and screen printing of opposite electrode coatings. The bulk of NexTech's work focused on making cathode-supported elements, although the processes developed at NexTech also were applied to the fabrication of anode-supported cells. Primary accomplishments within this track are summarized below: (1) Scale up of lanthanum strontium manganite (LSM) cathode powder production process; (2) Development and scale-up of tape casting methods for cathode and anode substrates; (3) Development of automated ultrasonic-spray process for depositing YSZ films; (4) Successful co-sintering of flat bi-layer elements (both cathode and anode supported); (5) Development of anode and cathode screen-printing processes; and (6

  13. The importance of pressure and mass ratios when depositing multi-element oxide thin films by pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Ojeda-G-P, Alejandro; Schneider, Christof W.; Döbeli, Max; Lippert, Thomas; Wokaun, Alexander

    2016-12-01

    Angle-resolved thickness and compositional analyses of BaTiO3, CaTiO3, La0.4Ca0.6MnO3, EuAlO3, and LiMn2O4 were performed to study the influence of the background gas pressure when depositing multi-elemental oxide materials. With increasing gas pressure the typical forward directed deposition changes to a constant thickness at all angles. Compositional changes with respect to the target show dependencies on (in order of influence): target material, deposition pressure, and angular location (substrate size). A linear relationship was found between target mass-ratios and compositional deviations. This can lead to compositional deviations of up to 70% for large mass-ratios in certain pressure regimes.

  14. Fabrication of neptunium oxide targets for irradiation in FFTF

    SciTech Connect

    Blair, H.T.; Chidester, K.M.

    1993-07-01

    The feasibility of.fabdcating neptunium oxide into various target configurations for irradiation in FFTF to produce plutonium-238 was demonstrated by the Nuclear Fuels Technology group at Los Alamos. The configurations included cold-pressed and sintered pellets and wafers and powder encapsulated in 0.0025-cm thick molybdenum foil envelopes. NpO{sub 2} Pellets with a density of 86.5%TD and wafers that were approximately 2-cm diameter by 0.0229-cm thick were produced. Uranium dioxide wafers were fabricated without cracking and warping by assuring uniform distribution of powder in the die before pressing and by setting the pressed wafers on ceramic microspheres for sintering. Forming the powder into microspheres before pressing enabled uniform die filling. Radiation exposure measurements made during the NPO{sub 2} processing showed a maximum of 500 g/mo could be handled in the shielded gloveboxes at Los Alamos and still comply with the exposure limits set by DOE Radiological Control Manual, DOE-EH-0256T.

  15. Targets of uranium, plutonium, and curium for heavy-element research

    NASA Astrophysics Data System (ADS)

    Lobanov, Yu. V.; Buklanov, G. V.; Abdullin, F. Sh.; Polyakov, A. N.; Shirokovsky, I. V.; Tsyganov, Yu. S.; Utyonkov, V. K.

    1997-02-01

    The heavy-element research program of the Dubna gas-filled recoil separator requires the use of rather exotic, strongly radioactive targets which can withstand long-term, high-intensity heavy-ion bombardments. A number of targets with thicknesses of 0.1-0.8 mg/cm 2 deposited on various backings by different techniques such as electrospraying, mechanical painting with organic solutions, as well as molecular plating or electrodeposition from organic solutions were tested. The best results were obtained for electroplated targets deposited on 1.5 μm Ti backings. Isotopically enriched targets of 235,236,238U, 242,244Pu, and 248Cm mounted on rotating disks were irradiated by ions ranging from neon to argon with intensities up to 2 × 10 13pps delivered by the U400 cyclotron. During two months of irradiation the total beam dose of the 34S ions applied to the target of 244Pu reached 2.5 × 10 19. Collaborative Dubna-Livermore experiments were performed in 1993-1995 by employing the Dubna gas-filled recoil separator and resulted in the discovery of the new nuclides 262104, 265106, 266106, 267108, and 273110. The experiments aimed at the synthesis of element 114 are under preparation. Target fabrication methods and experimental results for nuclear physics studies at Coulomb energies are described.

  16. A versatile fluorescent biosensor based on target-responsive graphene oxide hydrogel for antibiotic detection.

    PubMed

    Tan, Bing; Zhao, Huimin; Du, Lei; Gan, Xiaorong; Quan, Xie

    2016-09-15

    A fluorescent sensing platform based on graphene oxide (GO) hydrogel was developed through a fast and facile gelation, immersion and fluorescence determination process, in which the adenosine and aptamer worked as the co-crosslinkers to connect the GO sheets and then form the three-dimensional (3D) macrostructures. The as-prepared hydrogel showed high mechanical strength and thermal stability. The optimal hydrogel had a linear response for oxytetracycline (OTC) of 25-1000μg/L and a limit of quantitation (LOQ) of 25μg/L. Moreover, together with the high affinity of the aptamer for its target, this assay exhibited excellent sensitivity and selectivity. According to its design principle, the as-designed hydrogel was also tested to possess the generic detection function for other molecules by simply replacing its recognition element, which is expected to lay a foundation to realize the assembly of functionalized hierarchical graphene-based materials for practical applications in analytical field.

  17. Intrinsic Bonding Defects in Transition Metal Elemental Oxides

    DTIC Science & Technology

    2006-01-01

    deposition, ALD. Spectroscopic studies have also been performed on nanocrystalline TiO2 , ZrO2, HfO2, and complex mixed oxides such as ZrTiO4, LaAlO3 and...5d-state and defect features are identified. Figure 2(b). SXPS valence band spectrum of TiO2 . 5d-state and defect features... TiO2 . 3d-state features are identified. Figure 4. Ti L3 edge XAS spectrum of TiO2 . Ti 3d J-T term split states are

  18. Kinetic Constant Variability in Bacterial Oxidation of Elemental Sulfur▿

    PubMed Central

    Pokorna, Blanka; Mandl, Martin; Borilova, Sarka; Ceskova, Pavla; Markova, Romana; Janiczek, Oldrich

    2007-01-01

    Wide ranges of growth yields on sulfur (from 2.4 × 1010 to 8.1 × 1011 cells g−1) and maximum sulfur oxidation rates (from 0.068 to 1.30 mmol liter−1 h−1) of an Acidithiobacillus ferrooxidans strain (CCM 4253) were observed in 73 batch cultures. No significant correlation between the constants was observed. Changes of the Michaelis constant for sulfur (from 0.46 to 15.5 mM) in resting cells were also noted. PMID:17449698

  19. Oxidation Resistance of Fe80Cr20 Alloys Treated by Rare Earth Element Ion Implantation

    NASA Astrophysics Data System (ADS)

    Sebayang, Darwin; Khaerudini, Deni S.; Saryanto, H.; Hasan, Sulaiman; Othman, M. A.; Untoro, Puji

    2011-10-01

    The oxidation behaviour of newly developed process of Fe80Cr20 alloy was studied as a function of temperature in the range 1173-1273 K for up to 100 h in flowing air, which corresponds to the Solid Oxide Fuel Cell (SOFC) environment operating conditions. The effects of rare earth element implantation and depth profile on the oxidation behaviour of specimens were analyzed based on oxide morphology and microstructure. Characterisation of the oxide phase products after oxidation was made by X-ray diffraction (XRD). The surface morphology of oxide scales was examined using the scanning electronic microscope (SEM) with energy-dispersive X-ray analysis (EDX). The rate constant of thermal oxidation was determined using Wagner method. Experimental results show that the specimens implanted with lanthanum have remarkably enhanced the oxidation resistance. The oxidation test indicates that the newly developed process of Fe80Cr20 implantation with lanthanum ions exhibit considerably greater improvement in the oxidation resistance compared to the specimens implanted with titanium. The newly developed process of Fe80Cr20 milled for 60h show better oxidation resistance compared to specimens milled for 40h.

  20. Targeting oxidative stress response by green tea polyphenols: clinical implications.

    PubMed

    Yiannakopoulou, Eugenia Ch

    2013-09-01

    Green tea polyphenols, the most interesting constituent of green tea leaves, have been shown to have both pro-oxidant and antioxidant properties. Both pro-oxidant and antioxidant properties are expected to contribute to modulation of oxidative stress response under ideal optimal dosage regimens. Exposure to a low concentration of a pro-oxidant prior to exposure to oxidative stress induces the expression of genes that code for proteins that induce adaptation in a subsequent oxidative stress. On the other hand, exposure to an antioxidant concurrently with exposure to the oxidative stress affords protection through free radical scavenging or through other indirect antioxidant mechanisms. In any case, the optimal conditions that afford protection from oxidative stress should be defined for any substance with redox properties. Green tea polyphenols, being naturally occurring substances, seem to be an ideal option for the modulation of oxidative stress response. This paper reviews available data on the pro-oxidant and antioxidant properties of green tea polyphenols focusing on their potential on the modulation of oxidative stress response.

  1. Distribution and speciation of trace elements in iron and manganese oxide cave deposits

    NASA Astrophysics Data System (ADS)

    Frierdich, Andrew J.; Catalano, Jeffrey G.

    2012-08-01

    Fe and Mn oxide minerals control the distribution and speciation of heavy metals and trace elements in soils and aquatic systems through chemical mechanisms involving adsorption, incorporation, and electron transfer. The Pautler Cave System in Southwest Illinois, an analog to other temperate carbonate-hosted karst systems, contains Fe and Mn oxide minerals that form in multiple depositional environments and have high concentrations of associated trace elements. Synchrotron-based micro-scanning X-ray fluorescence (μ-SXRF) shows unique spatial distributions of Fe, Mn, and trace elements in mineral samples. Profile maps of Mn oxide cave stream pebble coatings show Fe- and As-rich laminations, indicating dynamic redox conditions in the cave stream. μ-SXRF maps demonstrate that Ni, Cu, and Zn correlate primarily with Mn whereas As correlates with both Mn and Fe; As is more enriched in the Fe phase. Zn is concentrated in the periphery of Mn oxide stream pebble coatings, and may be an indication of recent anthropogenic surface activity. X-ray absorption fine structure spectroscopy measurements reveal that As(V) occurs as surface complexes on Mn and Fe oxides whereas Zn(II) associated with Mn oxides is adsorbed to the basal planes of phyllomanganates in a tetrahedral coordination. Co(III) and Se(IV) are also observed to be associated with Mn oxides. The observation of Fe, Mn, and trace element banding in Mn oxide cave stream pebble coatings suggests that these materials are sensitive to and document aqueous redox conditions, similar to ferromanganese nodules in soils and in marine and freshwater sediments. Furthermore, speciation and distribution measurements indicate that these minerals scavenge trace elements and limit the transport of micronutrients and contaminants in karst aquifer systems while also potentially recording changes in anthropogenic surface activity and land-use.

  2. Distribution and speciation of trace elements in iron and manganese oxide cave deposits

    SciTech Connect

    Frierdich, Andrew J.; Catalano, Jeffrey G.

    2012-10-24

    Fe and Mn oxide minerals control the distribution and speciation of heavy metals and trace elements in soils and aquatic systems through chemical mechanisms involving adsorption, incorporation, and electron transfer. The Pautler Cave System in Southwest Illinois, an analog to other temperate carbonate-hosted karst systems, contains Fe and Mn oxide minerals that form in multiple depositional environments and have high concentrations of associated trace elements. Synchrotron-based micro-scanning X-ray fluorescence ({mu}-SXRF) shows unique spatial distributions of Fe, Mn, and trace elements in mineral samples. Profile maps of Mn oxide cave stream pebble coatings show Fe- and As-rich laminations, indicating dynamic redox conditions in the cave stream. {mu}-SXRF maps demonstrate that Ni, Cu, and Zn correlate primarily with Mn whereas As correlates with both Mn and Fe; As is more enriched in the Fe phase. Zn is concentrated in the periphery of Mn oxide stream pebble coatings, and may be an indication of recent anthropogenic surface activity. X-ray absorption fine structure spectroscopy measurements reveal that As(V) occurs as surface complexes on Mn and Fe oxides whereas Zn(II) associated with Mn oxides is adsorbed to the basal planes of phyllomanganates in a tetrahedral coordination. Co(III) and Se(IV) are also observed to be associated with Mn oxides. The observation of Fe, Mn, and trace element banding in Mn oxide cave stream pebble coatings suggests that these materials are sensitive to and document aqueous redox conditions, similar to ferromanganese nodules in soils and in marine and freshwater sediments. Furthermore, speciation and distribution measurements indicate that these minerals scavenge trace elements and limit the transport of micronutrients and contaminants in karst aquifer systems while also potentially recording changes in anthropogenic surface activity and land-use.

  3. Vanadium oxide bronzes containing rare-earth elements

    SciTech Connect

    Volkov, V.L.; Zubkov, V.G.; Fedyukov, A.S.; Zainulin, Yu.G.

    1988-05-01

    We attempted to make phases having the general formula Ln/sub x/V/sub 2/O/sub 5/ (Ln = La, Eu, Yb) without success; the specimens usually consisted of three phases: the rare-earth orthovanadate LnVO/sub 4/, vanadium(V) oxide, and VO/sub 2/. To shift the process to give Ln/sub x/V/sub 2/O/sub 5/, heat treatment was applied to mixtures of the initial high-purity substances. The x-ray patterns were recorded with a DRON-UM1 apparatus with Cr K..cap alpha.. radiation and were processed by the Poroshok program. The IR spectra were recorded with UR-20 spectrometer with oil mulls.

  4. RCS Predictions From a Method of Moments and a Finite-Element Code for Several Targets

    DTIC Science & Technology

    2010-07-01

    01803 14. ABSTRACT This report presents results of radar cross section (RCS) calculations for several interesting targets using a method-of-moments...TERMS radar cross section, method of moments, finite element, modeling 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18... radar cross section (RCS) simulation that require an exact code for solution. In this report, we compare RCS calculations with two very different

  5. Targeting the Reversibly Oxidized Protein Tyrosine Phosphatase Superfamily

    PubMed Central

    Boivin, Benoit; Yang, Ming; Tonks, Nicholas K.

    2010-01-01

    Controlled production of reactive oxygen species leads to reversible oxidation of protein tyrosine phosphatases (PTPs) and has emerged as an important tier of regulation over phosphorylation-dependent signal transduction. We present a modified cysteinyl-labeling assay that detects reversible oxidation of members of each of the different PTP subclasses. Here, we describe the methods for enriching reversibly oxidized PTPs from complex protein extracts, illustrating the procedure in IMR90 fibroblasts. PMID:20807953

  6. Finite element analysis of the tetragonal to monoclinic phase transformation during oxidation of zirconium alloys

    NASA Astrophysics Data System (ADS)

    Platt, P.; Frankel, P.; Gass, M.; Howells, R.; Preuss, M.

    2014-11-01

    Corrosion is a key limiting factor in the degradation of zirconium alloys in light water reactors. Developing a mechanistic understanding of the corrosion process offers a route towards improving safety and efficiency as demand increases for higher burn-up of fuel. Oxides formed on zirconium alloys are composed of both monoclinic and meta-stable tetragonal phases, and are subject to a number of potential mechanical degradation mechanisms. The work presented investigates the link between the tetragonal to monoclinic oxide phase transformation and degradation of the protective character of the oxide layer. To achieve this, Abaqus finite element analysis of the oxide phase transformation has been carried out. Study of the change in transformation strain energy shows how relaxation of oxidation induced stress and fast fracture at the metal-oxide interface could destabilise the tetragonal phase. Central to this is the identification of the transformation variant most likely to form, and understanding why twinning of the transformed grain is likely to occur. Development of transformation strain tensors and analysis of the strain components allows some separation of dilatation and shear effects. Maximum principal stress is used as an indication of fracture in the surrounding oxide layer. Study of the stress distributions shows the way oxide fracture is likely to occur and the differing effects of dilatation and shape change. Comparison with literature provides qualitative validation of the finite element simulations.

  7. Potentially toxic element release by fenton oxidation of sewage sludge.

    PubMed

    Andrews, J P; Asaadi, M; Clarke, B; Ouki, S

    2006-01-01

    The presence, in sewage sludge, of excess levels of the potentially toxic elements (PTE) copper, zinc, chromium, cadmium, nickel, lead and mercury, could impact on our ability to recycle these residues in the future. Far stricter limits on the levels of PTEs are likely in proposed legislation. A method involving the dosing of Fenton's reagent, a mixture of ferrous iron and hydrogen peroxide, under acidic conditions was evaluated for its potential to reduce metal levels. The [Fe]:[H2O2] (w/w) ratio was found to give a good indication of the percentage copper and zinc elution obtainable. Sites with no iron dosing as part of wastewater treatment required extra iron to be added in order to initiate the Fenton's reaction. A significant reduction, in excess of 70%, of the copper and zinc was eluted from both raw primary and activated sludge solid fractions. Cadmium and nickel could be reduced to below detection limits but elution of mercury, lead and chromium was less than 40%. The iron catalyst concentration was found to be a crucial parameter. This process has the potential to reduce the heavy metal content of the sludge and allow the recycling of sludge to continue in a sustainable manner.

  8. Effects of point defect concentrations of the reactive element oxides on the oxidation kinetics of pure Ni and Ni-Cr alloys

    NASA Astrophysics Data System (ADS)

    Yan, Ruey-Fong

    The addition of some reactive element oxides, e.g. Ysb2Osb3 or ZrOsb2, has significant effects, e.g. improvement in scale adhesion and reduction in oxidation rate, on the oxidation behavior of chromia and alumina scale forming alloys at high temperatures. However, there is little agreement about how a small addition of an oxygen-active element can cause such profound effects. It was the goal of this project to study the growth kinetics of an oxide scale when different reactive-element oxides were added to pure Ni and Ni-Cr alloys and, consequently, to aid in clarifying the mechanism of reactive element effects. The oxidation kinetics were measured using a thermogravimetric analysis (TGA) method and the material characterization of oxide scale was conducted. The relationship between point defect structures and oxidation kinetics was discussed. The results in this research showed that Ysb2Osb3 and ZrOsb2 exhibited the reactive element effects on the oxidation behaviors of Ni and Ni-Cr alloys. In addition, the point defect concentrations of the reactive element oxide, Ysb2Osb3, were changed by doping of different valent oxides. The modification of point defect concentrations of the reactive element oxide dispersed phases did change the oxidation kinetics of the pure Ni and Ni-Cr alloys containing Ysb2Osb3. These results indicate that the transport properties of the reactive element oxide dispersed phases are one of the important factors in determining the growth rate of an oxide scale.

  9. Morpholino antisense oligonucleotides targeting intronic repressor Element1 improve phenotype in SMA mouse models.

    PubMed

    Osman, Erkan Y; Miller, Madeline R; Robbins, Kate L; Lombardi, Abby M; Atkinson, Arleigh K; Brehm, Amanda J; Lorson, Christian L

    2014-09-15

    Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of Survival Motor Neuron-1 (SMN1). In all SMA patients, a nearly identical copy gene called SMN2 is present, which produces low levels of functional protein owing to an alternative splicing event. To prevent exon-skipping, we have targeted an intronic repressor, Element1 (E1), located upstream of SMN2 exon 7 using Morpholino-based antisense oligonucleotides (E1(MO)-ASOs). A single intracerebroventricular injection in the relatively severe mouse model of SMA (SMNΔ7 mouse model) elicited a robust induction of SMN protein, and mean life span was extended from an average survival of 13 to 54 days following a single dose, consistent with large weight gains and a correction of the neuronal pathology. Additionally, E1(MO)-ASO treatment in an intermediate SMA mouse (SMN(RT) mouse model) significantly extended life span by ∼700% and weight gain was comparable with the unaffected animals. While a number of experimental therapeutics have targeted the ISS-N1 element of SMN2 pre-mRNA, the development of E1 ASOs provides a new molecular target for SMA therapeutics that dramatically extends survival in two important pre-clinical models of disease.

  10. Physical and chemical analysis of elemental sulfur formation during galena surface oxidation.

    PubMed

    Hampton, Marc A; Plackowski, Chris; Nguyen, Anh V

    2011-04-05

    The surface oxidation of sulfide minerals, such as galena (PbS), in aqueous solutions is of critical importance in a number of applications. A comprehensive understanding of the formation of oxidation species at the galena surface is still lacking. Much controversy over the nature of these oxidation products exists. A number of oxidation pathways have been proposed, and experimental evidence for the formation of elemental sulfur, metal polysulfides, and metal-deficient lead sulfides in acidic conditions has been shown and argued. This paper provides further insight into the electrochemical behavior of galena at pH 4.5. Utilizing a novel experimental system that combines in situ electrochemical control and AC mode atomic force microscopy (AFM) surface imaging, the formation and growth of nanoscopic domains on the galena surface are detected and examined at anodic potentials. AFM phase images indicate that these domains have different material properties to the underlying galena. Continued oxidation results in nanoscopic pitting and the formation of microscopic surface domains, which are confirmed to be elemental sulfur by Raman spectroscopy. Further clarification of the presence of elemental sulfur is provided by Cryo-XPS. Polysulfide and metal-deficient sulfide could not be detected within this system.

  11. URANIUM OXIDE-CONTAINING FUEL ELEMENT COMPOSITION AND METHOD OF MAKING SAME

    DOEpatents

    Handwerk, J.H.; Noland, R.A.; Walker, D.E.

    1957-09-10

    In the past, bodies formed of a mixture of uranium dioxide and aluminum powder have been used in fuel elements; however, these mixtures were found not to be suitable when exposed to temperatures of about 600 deg C, because at such high temperatures the fuel elements were distorted. If uranosic oxide, U/sub 3/O/sub 8/, is substituted for UO/sub 2/, the mechanical properties are not impaired when these materials are used at about 600 deg C and no distortion takes place. The uranosic oxide and aluminum, both in powder form, are first mixed, and after a homogeneous mixture has been obtained, are shaped into fuel elements by extrusion at elevated temperature. Magnesium powder may be used in place of the aluminum.

  12. Deubiquitinases as a signaling target of oxidative stress

    PubMed Central

    Cotto-Rios, Xiomaris M.; Békés, Miklos; Chapman, Jessica; Ueberheide, Beatrix; Huang, Tony T.

    2012-01-01

    SUMMARY Deubiquitinating enzymes (DUBs) constitute a large family of cysteine proteases that have broad impact on numerous biological and pathological processes, including the regulation of genomic stability. DUBs are often assembled onto multiprotein complexes to assist in their localization and substrate selection, yet it remains unclear how the enzymatic activity of DUBs is modulated by intracellular signals. Herein, we show that bursts of reactive oxygen species (ROS) reversibly inactivate DUBs through the oxidation of the catalytic cysteine residue. Importantly, USP1, a key regulator of genomic stability, is reversibly inactivated upon oxidative stress. This, in part, explains the rapid nature of PCNA monoubiquitination-dependent DNA damage tolerance in response to oxidative DNA damage in replicating cells. We propose that DUBs of the cysteine protease family act as ROS sensors in human cells and that ROS-mediated DUB inactivation is a critical mechanism for fine-tuning stress-activated signaling pathways. PMID:23219552

  13. The Application of Neutron Radioscopy to Lithium-Aluminum Alloy Target Elements

    DTIC Science & Technology

    1990-04-01

    MTL TR 90-18 AD 00 m THE APPLICATION OF NEUTRON * NRADIOSCOPY TO LITHIUM-ALUMINUM * ALLOY TARGET ELEMENTS JOHN J. ANTAL and ALFRED S. MAROTTA U.S...PERFORMING ORG. REPORT NUMBER 7. AUTHOR(S) 0. CONTRACT OR GRANT NUMBER(s) John J. Antal, Alfred S. Marotta, Saleem R. Salaymeh,* and Thomas P. Varallo...1 ATTN: Dr. G. Prather. Deputy for Science & Technology I ATTN: Dr. W. Rryzik I Sr. J. R. Sculley , SARD 1 0. Rose 1 Lt. Col. Louis M. Jackson

  14. Plant mitochondria: source and target for nitric oxide.

    PubMed

    Igamberdiev, Abir U; Ratcliffe, R George; Gupta, Kapuganti J

    2014-11-01

    Plant mitochondria generate nitric oxide (NO) under anoxia through the action of cytochrome c oxidase and other electron transport chain components on nitrite. This reductive mechanism operates under aerobic conditions at high electron transport rates. Indirect evidence also indicates that the oxidative pathway of NO production may be associated with mitochondria. We review the consequences of mitochondrial NO production, including the inhibition of oxygen uptake by cytochrome c oxidase, the inhibition of aconitase and succinate dehydrogenase, the induction of alternative oxidase, and the nitrosylation of several proteins, including glycine decarboxylase. The importance of these events in adaptation to abiotic and biotic stresses is discussed.

  15. Oxidation of dissolved elemental mercury by thiol compounds under anoxic conditions.

    PubMed

    Zheng, Wang; Lin, Hui; Mann, Benjamin F; Liang, Liyuan; Gu, Baohua

    2013-11-19

    Mercuric ion, Hg(2+), forms strong complexes with thiolate compounds that commonly dominate Hg(II) speciation in natural freshwater. However, reactions between dissolved aqueous elemental mercury (Hg(0)aq) and organic ligands in general, and thiol compounds in particular, are not well studied although these reactions likely affect Hg speciation and cycling in the environment. In this study, we compared the reaction rates between Hg(0)aq and a number of selected organic ligands with varying molecular structures and sulfur (S) oxidation states in dark, anoxic conditions to assess the role of these ligands in Hg(0)aq oxidation. Significant Hg(0)aq oxidation was observed with all thiols but not with ligands containing no S. Compounds with oxidized S (e.g., disulfide) exhibited little or no reactivity toward Hg(0)aq either at pH 7. The rate and extent of Hg(0)aq oxidation varied greatly depending on the chemical and structural properties of thiols, thiol/Hg ratios, and the presence or absence of electron acceptors. Smaller aliphatic thiols and higher thiol/Hg ratios resulted in higher Hg(0)aq oxidation rates than larger aromatic thiols at lower thiol/Hg ratios. The addition of electron acceptors (e.g., humic acid) also led to substantially increased Hg(0)aq oxidation. Our results suggest that thiol-induced oxidation of Hg(0)aq is important under anoxic conditions and can affect Hg redox transformation and bioavailability for microbial methylation.

  16. Trace element cycling through iron oxide minerals during redox-driven dynamic recrystallization

    SciTech Connect

    Frierdich, Andrew J.; Luo, Yun; Catalano, Jeffrey G.

    2011-11-17

    Microbially driven iron redox cycling in soil and sedimentary systems, including during diagenesis and fluid migration, may activate secondary abiotic reactions between aqueous Fe(II) and solid Fe(III) oxides. These reactions catalyze dynamic recrystallization of iron oxide minerals through localized and simultaneous oxidative adsorption of Fe(II) and reductive dissolution of Fe(III). Redox-active trace elements undergo speciation changes during this process, but the impact redox-driven recrystallization has on redox-inactive trace elements associated with iron oxides is uncertain. Here we demonstrate that Ni is cycled through the minerals goethite and hematite during redox-driven recrystallization. X-ray absorption spectroscopy demonstrates that during this process adsorbed Ni becomes progressively incorporated into the minerals. Kinetic studies using batch reactors containing aqueous Fe(II) and Ni preincorporated into iron oxides display substantial release of Ni to solution. We conclude that iron oxide recrystallization activated by aqueous Fe(II) induces cycling of Ni through the mineral structure, with adsorbed Ni overgrown in regions of Fe(II) oxidative adsorption and incorporated Ni released in regions of reductive dissolution of structural Fe(III). The redistribution of Ni among the mineral bulk, mineral surface, and aqueous solution appears to be thermodynamically controlled and catalyzed by Fe(II). Our work suggests that important proxies for ocean composition on the early Earth may be invalid, identifies new processes controlling micronutrient availability in soil, sedimentary, and aquatic ecosystems, and points toward a mechanism for trace element mobilization during diagenesis and enrichment in geologic fluids.

  17. Comparing targeted and non-targeted high-resolution mass spectrometric approaches for assessing advanced oxidation reactor performance.

    PubMed

    Parry, Emily; Young, Thomas M

    2016-11-01

    High resolution mass spectrometry (HR-MS) offers the opportunity to track large numbers of non-target analytes through water treatment processes, providing a more comprehensive view of reactor performance than targeted evaluation. Both approaches were used to evaluate the performance of a pilot scale advanced oxidation process (AOP) employing ultraviolet light and hydrogen peroxide (UV/H2O2) to treat municipal wastewater effluent. Twelve pharmaceuticals and personal care products were selected as target compounds and added to reactor influent. Target compound removal over a range of flow rates and hydrogen peroxide addition levels was assessed using a liquid chromatograph combined with a quadrupole time-of-flight mass spectrometer (LC-qTOF-MS). Target compound removals were used to determine hydroxyl radical concentrations and UV fluence under pilot scale conditions. The experiments were also analyzed using a nontarget approach, which identified "molecular features" in either reactor influent or effluent. Strong correlation (r = 0.94) was observed between target compound removals calculated using the targeted and non-targeted approaches across the range of reactor conditions tested. The two approaches also produced consistent rankings of the performance of the various reactor operating conditions, although the distribution of compound removal efficiencies was usually less favorable with the broader, nontarget approach. For example, in the UV only treatment 8.3% of target compounds and 2.2% of non-target compounds exhibited removals above 50%, while 100% of target compounds and 74% of non-target compounds exhibited removals above 50% in the best condition tested. These results suggest that HR-MS methods can provide more holistic evaluation of reactor performance, and may reduce biases caused by selection of a limited number of target compounds. HR-MS methods also offer insights into the composition of poorly removed compounds and the formation of transformation

  18. Nickel oxide and molybdenum oxide thin films for infrared imaging prepared by biased target ion-beam deposition

    NASA Astrophysics Data System (ADS)

    Jin, Yao; Saint John, David; Jackson, Tom N.; Horn, Mark W.

    2014-06-01

    Vanadium oxide (VOx) thin films have been intensively used as sensing materials for microbolometers. VOx thin films have good bolometric properties such as low resistivity, high negative temperature coefficient of resistivity (TCR) and low 1/f noise. However, the processing controllability of VOx fabrication is difficult due to the multiple valence states of vanadium. In this study, metal oxides such as nickel oxide (NiOx) and molybdenum oxide (MoOx) thin films have been investigated as possible new microbolometer sensing materials with improved process controllability. Nickel oxide and molybdenum oxide thin films were prepared by reactive sputtering of nickel and molybdenum metal targets in a biased target ion beam deposition tool. In this deposition system, the Ar+ ion energy (typically lower than 25 eV) and the target bias voltage can be independently controlled since ions are remotely generated. A residual gas analyzer (RGA) is used to precisely control the oxygen partial pressure. A real-time spectroscopic ellipsometry is used to monitor the evolution of microstructure and properties of deposited oxides during growth and post-deposition. The properties of deposited oxide thin films depend on processing parameters. The resistivity of the NiOx thin films is in the range of 0.5 to approximately 100 ohm-cm with a TCR from -2%/K to -3.3%/K, where the resistivity of MoOx is between 3 and 2000 ohm-cm with TCR from -2.1%/K to -3.2%/K. We also report on the thermal stability of these deposited oxide thin films.

  19. Influence of a reactive element oxide coating on the high temperature oxidation of chromia-former alloys

    NASA Astrophysics Data System (ADS)

    Chevalier, S.; Bonnet, G.; Colson, J. C.; Larpin, J. P.

    1998-10-01

    MOCVD technique was used to deposit Nd2O3 coatings on two chromia-formers alloys. Oxidation experiments were performed at 1000 circC under air at atmospheric pressure on uncoated alloys and Nd2O3-coated alloys. The beneficial effects generally ascribed to the reactive elements were confirmed: the oxidation rates were decreased and the adherence of the oxide scales was drastically improved. The reactive element was located at the top of the oxide scale after oxidation. X-ray diffraction measurements identified NdCrO3 as the phase containing the reactive element. This work is compared to a previous study [1] concerning the influence of Nd2O3 on the high temperature oxidation behaviour of a Ti-containing chromia-former alloy in the oxide scale of which a complex phase close to CeTi21O38 was characterized. La technique MOCVD a été utilisée afin de préparer des revêtements de Nd2O3 sur deux alliages chromino-formeurs. Des expériences d'oxydation ont été réalisées à 1000 circC sous air à la pression atmosphérique sur les alliages non revêtus et revêtus de Nd2O3. Les effets bénéfiques généralement attribués aux éléments réactifs ont été confirmés : les vitesses d'oxydation ont été diminuées et l'adhérence des couches d'oxyde a été fortement améliorée. L'élément réactif a été localisé au sommet de la couche d'oxyde. Des analyses par diffraction des rayons X ont permis d'identifier NdCrO3 comme étant la phase contenant l'élément réactif. Ce travail a été comparé avec une étude précédente [1] concernant le comportement en oxydation à haute température d'un acier chromino-formeur contenant du Ti et pour lequel une phase complexe proche de CeTi{21}O{38} avait été caractérisée.

  20. Microbially Induced Reductive Dissolution of Trace Element-Rich Lacustrine Iron-Oxides

    NASA Astrophysics Data System (ADS)

    Crowe, S. A.; Kulczykci, E.; O'Neill, A. H.; Roberts, J. A.; Fowle, D. A.

    2004-12-01

    Iron (oxy)hydroxides are ubiquitous components of surfacial materials and are often the dominant redox buffering solid phases in soils and sediments. As a result, the geochemical behavior of these minerals has a profound influence on the global biogeochemical cycling of trace elements, including heavy metals and arsenic (As), in addition to nutrients such as, sulfur (S), carbon (C), nitrogen (N), and phosphorus (P). Understanding the behavior of trace elements and nutrients during biological and abiotic processes that effect iron (Fe) mineral phase transformations is paramount for predicting their distribution, mobility, and bioavailability in the environment. To evaluate the impact of dissimilatory Fe-reduction (DIR) on trace element mobility we have conducted batch incubations of Fe-rich lateritic lacustrine sediments. In contrast to mid-latitude lakes where Fe (oxy)hydroxides constitute only a small fraction of the total sediment, tropical lake sediments have been known to comprise up to 40-60 wt. % Fe-oxides. Under suboxic and nonsulphidogenic conditions it is likely that DIR plays a prominent role in early diagenesis and therefore may exert control on the fate and distribution of many trace elements in this environment (e.g. Crowe et al. 2004). In batch incubations conducted in a minimal media of similar composition to typical freshwater the lacustrine Fe-oxides were reductively dissolved at a rate very similar to pure synthetic goethite of similar surface area (measured by N2-BET). This is in contrast to the slower rates previously observed for trace element substituted Fe-oxides. These slower rates have been attributed to surface passivation by secondary Al and Cr mineral precipitation. We propose that these passivation effects may be offset in minimal media incubations by enhanced microbial metabolism due the presence of nutrients (P, Co and other metals) in the lacustrine Fe-oxides. These nutrients became available with progressive reduction as the

  1. Alloying element's substitution in titanium alloy with improved oxidation resistance and enhanced magnetic properties

    NASA Astrophysics Data System (ADS)

    Yu, Ang-Yang; Wei, Hua; Hu, Qing-Miao; Yang, Rui

    2017-01-01

    First-principles method is used to characterize segregation and magnetic properties of alloyed Ti/TiO2interface. We calculate the segregation energy of the doped Ti/TiO2 interface to investigate alloying atom's distribution. The oxidation resistance of Ti/TiO2 interface is enhanced by elements Fe and Ni but reduced by element Co. Magnetism could be produced by alloying elements such as Co, Fe and Ni in the bulk of titanium and the surface of Ti at Ti/TiO2 interface. The presence of these alloying elements could transform the non-magnetic titanium alloys into magnetic systems. We have also calculated the temperature dependence of magnetic permeability for the doped and pure Ti/TiO2 interfaces. Alloying effects on the Curie temperature of the Ti/TiO2 interface have been elaborated.

  2. The {alpha}-induced thick-target {gamma}-ray yield from light elements

    SciTech Connect

    Heaton, R.K. |

    1994-10-01

    The {alpha}-induced thick-target {gamma}-ray yield from light elements has been measured in the energy range 5.6 MeV {le} E{sub {alpha}} {le} 10 MeV. The {gamma}-ray yield for > 2.1 MeV from thick targets of beryllium, boron nitride, sodium fluoride, magnesium, aluminum and silicon were measured using the {alpha}-particle beam from the Lawrence Berkeley Laboratories 88 in. cyclotron. The elemental yields from this experiment were used to construct the {alpha}-induced direct production {gamma}-ray spectrum from materials in the SNO detector, a large volume ultra-low background neutrino detector located in the Creighton mine near Sudbury, Canada. This background source was an order of magnitude lower than predicted by previous calculations. These measurements are in good agreement with theoretical calculations of this spectrum based on a statistical nuclear model of the reaction, with the gross high energy spectrum structure being reproduced to within a factor of two. Detailed comparison of experimental and theoretical excitation population distribution of several residual nuclei indicate the same level of agreement within experimental uncertainties.

  3. Isotopic and Elemental Compositions of Ar, Kr, and Xe in Bulk, Slow, and Fast Solar Wind Targets from Genesis

    NASA Astrophysics Data System (ADS)

    Vogel, N.; Baur, H.; Burnett, D. S.; Heber, V. S.; Wieler, R.

    2010-03-01

    We present new heavy noble gas isotopic and elemental data from GENESIS targets exposed to the bulk, the fast, and the slow solar wind. Implications on fractionation effects between the Sun and the Solar Wind will be discussed.

  4. Bone as target organ for metals: the case of f-elements.

    PubMed

    Vidaud, Claude; Bourgeois, Damien; Meyer, Daniel

    2012-06-18

    The skeleton is a target organ for most metals. This leads to their bioaccumulation, either as storage of useful oligoelements or as a protection against damage by toxic elements. The different events leading to their accumulation in this organ, under constant remodeling, are not fully understood, nor the full subsequent impact on bone metabolism. This lack of knowledge is particularly true for lanthanides and actinides, whose use has been increasing over recent decades. These metals, known as f-elements, present chemical similarities and differences. After a comparison of the biologically relevant physicochemical properties of lanthanides and actinides, and a brief reminder of the main events of bone metabolism, this review considers the results published over the past decade regarding the interaction between bones and f-elements. Emphasis will be given to the molecular events, which constitute the basis of the most recent toxicological studies in this domain but still need further investigation. Ionic exchanges with the inorganic matrix, interactions with bone proteins, and cellular mechanism disturbances are mainly considered in this review.

  5. Oxidation of dissolved elemental mercury by thiol compounds under anoxic conditions

    SciTech Connect

    Zheng, Wang; Lin, Hui; Mann, Benjamin F; Liang, Liyuan; Gu, Baohua

    2013-01-01

    Mercuric mercury, Hg(II), forms strong complexes with thiol compounds that commonly dominate Hg(II) speciation in natural freshwater. However, reactions between dissolved elemental Hg(0) and thiols are not well understood although these processes are likely to be important in determining Hg speciation and geochemical cycling in the environment. In this study, reaction rates and mechanisms between dissolved Hg(0) and a number of selected organic ligands with varying molecular structures and sulfur (S) oxidation states were determined to assess the role of these ligands in Hg(0) redox transformation. We found that all thiols caused oxidation of Hg(0) under anoxic conditions but, contrary to expectation, compounds with higher S-oxidation states (e.g., disulfide) than thiols exhibited little or no reactivity with Hg(0) at pH 7. The rate and extent of Hg(0) oxidation varied widely, with smaller aliphatic thiols showing the greatest degree of oxidation. The mechanism of the oxidation is attributed to a two-step process involving adsorption of Hg(0) to thiols followed by the charge transfer from Hg(0) to electron acceptors. These observations demonstrate a unique thiol-induced oxidation pathway of dissolved Hg(0), with important implications for the redox transformation, speciation, and bioavailability of Hg for microbial methylation in anoxic environments.

  6. Organotitanoxanes with unique structure among transition-element organometallic oxide derivatives.

    PubMed

    Buitrago, Olga; Mosquera, Marta E G; Jiménez, Gerardo; Cuenca, Tomás

    2008-05-19

    The synthesis of novel titanoxane compounds, [{(TiCl)(Ti)[mu-(eta(5)-C5Me4SiMe2O-kappaO)]2(mu-O)}2(mu-O)] (4) and [{Ti[mu-(eta(5)-C5Me4SiMe2O-kappaO)](mu-O)}6] (5), by controlled hydrolysis of a dinuclear titanium/oxo complex is described. Complexes 4 and 5 show unprecedented structural features for organometallic oxide derivatives of transition elements and represent unique fully characterized examples of tetra- and hexanuclear organo-transition-metal oxide compounds with an open-chain and a monocyclic structure, respectively.

  7. Paired hormone response elements predict caveolin-1 as a glucocorticoid target gene.

    PubMed

    van Batenburg, Marinus F; Li, Hualing; Polman, J Annelies; Lachize, Servane; Datson, Nicole A; Bussemaker, Harmen J; Meijer, Onno C

    2010-01-21

    Glucocorticoids act in part via glucocorticoid receptor binding to hormone response elements (HREs), but their direct target genes in vivo are still largely unknown. We developed the criterion that genomic occurrence of paired HREs at an inter-HRE distance less than 200 bp predicts hormone responsiveness, based on synergy of multiple HREs, and HRE information from known target genes. This criterion predicts a substantial number of novel responsive genes, when applied to genomic regions 10 kb upstream of genes. Multiple-tissue in situ hybridization showed that mRNA expression of 6 out of 10 selected genes was induced in a tissue-specific manner in mice treated with a single dose of corticosterone, with the spleen being the most responsive organ. Caveolin-1 was strongly responsive in several organs, and the HRE pair in its upstream region showed increased occupancy by glucocorticoid receptor in response to corticosterone. Our approach allowed for discovery of novel tissue specific glucocorticoid target genes, which may exemplify responses underlying the permissive actions of glucocorticoids.

  8. KINETICS OF DIRECT OXIDATION OF H2S IN COAL GAS TO ELEMENTAL SULFUR

    SciTech Connect

    K.C. Kwon

    2005-01-01

    The direct oxidation of H{sub 2}S to elemental sulfur in the presence of SO{sub 2} is ideally suited for coal gas from commercial gasifiers with a quench system to remove essentially all the trace contaminants except H{sub 2}S. This direct oxidation process has the potential to produce a super clean coal gas more economically than both conventional amine-based processes and the hot-gas desulfurization using regenerable metal oxide sorbents followed by Direct Sulfur Recovery Process. The objective of this research is to support the near- and long-term process development efforts to commercialize this direct oxidation technology. The objectives of this research are to measure kinetics of direct oxidation of H{sub 2}S to elemental sulfur in the presence of a simulated coal gas mixture containing SO{sub 2}, H{sub 2}, and moisture, using 160-{micro}m C-500-04 alumina catalyst particles and a micro bubble reactor, and to develop kinetic rate equations and model the direct oxidation process to assist in the design of large-scale plants. This heterogeneous catalytic reaction has gaseous reactants such as H{sub 2}S and SO{sub 2}. However, this heterogeneous catalytic reaction has heterogeneous products such as liquid elemental sulfur and steam. To achieve the above-mentioned objectives, experiments on conversion of hydrogen sulfide into liquid elemental sulfur were carried out for the space time range of 0.059-0.87 seconds at 125-155 C to evaluate effects of reaction temperature, H{sub 2}S concentration, reaction pressure, and catalyst loading on conversion of hydrogen sulfide into liquid elemental sulfur. Simulated coal gas mixtures consist of 62-78 v% hydrogen, 3,000-7,000-ppmv hydrogen sulfide, 1,500-3,500 ppmv sulfur dioxide, and 10 vol % moisture, and nitrogen as remainder. Volumetric feed rates of a simulated coal gas mixture to a micro bubble reactor are 50 cm{sup 3}/min at room temperature and atmospheric pressure. The temperature of the reactor is controlled in an

  9. KINETICS OF DIRECT OXIDATION OF H2S IN COAL GAS TO ELEMENTAL SULFUR

    SciTech Connect

    K.C. Kwon

    2004-01-01

    The direct oxidation of H{sub 2}S to elemental sulfur in the presence of SO{sub 2} is ideally suited for coal gas from commercial gasifiers with a quench system to remove essentially all the trace contaminants except H{sub 2}S. This direct oxidation process has the potential to produce a super clean coal gas more economically than both conventional amine-based processes and the hot-gas desulfurization using regenerable metal oxide sorbents followed by Direct Sulfur Recovery Process. The objective of this research is to support the near- and long-term process development efforts to commercialize this direct oxidation technology. The objectives of this research are to measure kinetics of direct oxidation of H{sub 2}S to elemental sulfur in the presence of a simulated coal gas mixture containing SO{sub 2}, H{sub 2}, and moisture, using 160-{micro}m C-500-04 alumina catalyst particles and a micro bubble reactor, and to develop kinetic rate equations and model the direct oxidation process to assist in the design of large-scale plants. This heterogeneous catalytic reaction has gaseous reactants such as H{sub 2}S and SO{sub 2}. However, this heterogeneous catalytic reaction has heterogeneous products such as liquid elemental sulfur and steam. To achieve the above-mentioned objectives, experiments on conversion of hydrogen sulfide into liquid elemental sulfur were carried out for the space time range of 1-6 milliseconds at 125-155 C to evaluate effects of reaction temperature, moisture concentration, reaction pressure on conversion of hydrogen sulfide into liquid elemental sulfur. Simulated coal gas mixtures consist of 70 v% hydrogen, 2,500-7,500-ppmv hydrogen sulfide, 1,250-3,750 ppmv sulfur dioxide, and 0-15 vol% moisture, and nitrogen as remainder. Volumetric feed rates of a simulated coal gas mixture to a micro bubble reactor are 100 cm{sup 3}/min at room temperature and atmospheric pressure. The temperature of the reactor is controlled in an oven at 125-155 C. The

  10. Oxidation of hydrogen halides to elemental halogens with catalytic molten salt mixtures

    DOEpatents

    Rohrmann, Charles A.

    1978-01-01

    A process for oxidizing hydrogen halides by means of a catalytically active molten salt is disclosed. The subject hydrogen halide is contacted with a molten salt containing an oxygen compound of vanadium and alkali metal sulfates and pyrosulfates to produce an effluent gas stream rich in the elemental halogen. The reduced vanadium which remains after this contacting is regenerated to the active higher valence state by contacting the spent molten salt with a stream of oxygen-bearing gas.

  11. Double-pulse laser-induced breakdown spectroscopy for trace element analysis in sintered iron oxide ceramics

    NASA Astrophysics Data System (ADS)

    Heilbrunner, H.; Huber, N.; Wolfmeir, H.; Arenholz, E.; Pedarnig, J. D.; Heitz, J.

    2012-01-01

    Double-pulse laser-induced breakdown spectroscopy (LIBS) is an emerging technique for accurate compositional analysis of many different materials. We present a systematic study of collinear double-pulse LIBS for analysis of the trace and side elements boron, manganese, copper, aluminum, titanium, silicon, chromium, nickel, potassium, and calcium in sintered iron oxide targets. The samples were ablated in air by single-pulse and double-pulse Nd:YAG laser radiation (6 ns pulse duration, laser wavelength of 532 nm) and spectra were recorded with an Echelle spectrometer equipped with an ICCD camera. We investigated the evolution of atomic and ionic line emission intensities for different interpulse delay times between the laser pulses (from 100 ns to 50 μs) and gate delays after the second laser pulse. We also varied the energy partition between the first and second laser pulse and the size of the irradiated spot at the sample surface. For the trace and side elements, we observed double-pulse LIBS signals that were enhanced as compared to single-pulse measurements depending on the interpulse delay time, the energy partition between the pulses, and the spot size. For the elements boron, copper, aluminum, titanium, chromium, potassium, and calcium limits of detection below 10 ppm were achieved.

  12. Comparison of the effect of insulating blockages on metal and oxide fuel elements

    SciTech Connect

    Tilbrook, R.W.; Dever, D.J.

    1988-01-01

    The safety philosophy of the new liquid-metal reactor (LMR) plant designs is oriented toward inherent protection against loss of coolable geometry and other entries to core disruption. One potential entry is via propagation of local faults. The basic event in all local sequences is cladding failure, irrespective of initiator. A model of a complete insulating blockage, i.e., total loss of heat transfer from the cladding surface due to any cause, was developed for a range of insulated arcs. The internal properties represented either metal or oxide fuels, both irradiated to a condition that closed the fuel-clad gap. The advantage of the high conductivity of the metal fuel is clearly evident; the maximum cladding temperatures are considerably lower than for the oxide elements with the same circumferential blockage extent. Also, the minimum cladding temperature at the opposite side of the element is higher for the metal fuel, thus providing more uniform heat rejection from the unblocked portion of the cladding. The cladding temperatures at the edge of the blockages for the oxide elements are directly proportional to the blockage angle, indicating that the cladding is the main path for heat rejection.

  13. Microbial oxidation of elemental selenium in soil slurries and bacterial cultures

    USGS Publications Warehouse

    Dowdle, P.R.; Oremland, R.S.

    1998-01-01

    The microbial oxidation of elemental selenium [Se(O)] was studied by employing 75Se(O) as a tracer. Live, oxic soil slurries demonstrated a linear production of mostly Se(IV), with the formation of smaller quantities of Se(VI). Production of both Se(IV) and Se(VI) was inhibited by autoclaving, formalin, antibiotics, azide, and 2,4-dinitrophenol, thereby indicating the involvement of microbes. Oxidation of Se(O) in slurries was enhanced by addition of acetate, glucose, or sulfide, which implied involvement of chemoheterotrophs as well as chemoautotrophic thiobacilli. Cultures of Thiobacillus ASN-1, Leptothrix MnB1, and a heterotrophic soil enrichment all oxidized Se(O) with Se(VI) observed as the major product rather than Se(IV). This indicated that microbial oxidation in soils is partly constrained by the adsorption of Se(IV) onto soil surfaces. Rate constants for unamended soil slurry Se(O) oxidation ranged from 0.0009 to 0.0117 day-1 which were 3-4 orders of magnitude lower than those reported for dissimilatory Se(VI) reduction in organic-rich, anoxic sediments.The microbial oxidation of elemental selenium [Se(0)] was studied by employing 75Se(0) as a tracer. Live, oxic soil slurries demonstrated a linear production of mostly Se(IV), with the formation of smaller quantities of Se(VI). Production of both Se(IV) and Se(VI) was inhibited by autoclaving, formalin, antibiotics, azide, and 2,4-dinitrophenol, thereby indicating the involvement of microbes. Oxidation of Se(O) in slurries was enhanced by addition of acetate, glucose, or sulfide, which implied involvement of chemoheterotrophs as well as chemoautotrophic thiobacilli. Cultures of Thiobacillus ASN-1, Leptothrix MnB1, and a heterotrophic soil enrichment all oxidized Se(O) with Se(VI) observed as the major product rather than Se(IV). This indicated that microbial oxidation in soils is partly constrained by the adsorption of Se(IV) onto soil surfaces. Rate constants for unamended soil slurry Se(O) oxidation

  14. Canine visceral leishmaniasis: relationships between oxidative stress, liver and kidney variables, trace elements, and clinical status.

    PubMed

    Heidarpour, M; Soltani, S; Mohri, M; Khoshnegah, J

    2012-10-01

    The aim of this study was to investigate the role of oxidative stress in the pathology of canine visceral leishmaniasis (CVL). We therefore studied the relationships between oxidative stress markers, liver and kidney variables, trace elements, and clinical status in dogs naturally infected with Leishmania infantum. Two groups of Leishmania-infected dogs [asymptomatic (AD, n = 14) and symptomatic (SD, n = 16)] were assessed and compared with a group of non-infected control dogs (CD, n = 30). A significant decrease (p < 0.001) in serum total antioxidant status (TAS) and albumin concentration (p < 0.05) and a significant increase in serum malondialdehyde (MDA) and blood urea nitrogen (BUN) concentrations (p < 0.001), in the SD group, were observed when compared to CD and AD groups. Dogs of the AD group presented a significant decrease in copper (p < 0.01) and zinc (p < 0.001) concentrations, when compared to CD group, while the SD group presented a significant decrease (p < 0.001) in copper and zinc concentrations, when compared to CD and AD groups. Oxidative stress markers (MDA and TAS) showed significant correlations (p < 0.001) with trace elements (copper and zinc) and liver (alanine aminotransferase) and kidney (BUN and creatinine) variables. The results of the present study revealed that symptomatic dogs showed more severe oxidative stress than asymptomatic and non-infected dogs and enhanced lipid peroxidation may be linked to liver and kidney damage in canine visceral leishmaniasis.

  15. Conversion of elemental mercury with a novel membrane delivery catalytic oxidation system (MDCOs).

    PubMed

    Guo, Yongfu; Yan, Naiqiang; Yang, Shijian; Qu, Zan; Wu, Zhongbiao; Liu, Yue; Liu, Ping; Jia, Jinping

    2011-01-15

    In order to overcome the shortcomings of the traditional catalytic oxidation (TCO) mode for the conversion of the trace level of elemental mercury (Hg(0)) in flue gas, we put forward a novel and unique assembly that integrated membrane delivery with catalytic oxidation systems (MDCOs), which combined the controlled delivery of oxidants with the catalytic oxidation of Hg(0). The results show that the demanded HCl for Hg(0) conversion in the MDCOs was less than 5% of that in the TCO mode, and over 90% of Hg(0) removal efficiency can be obtained in the MDCOs with less than 0.5 mg m(-3) of HCl escaped. Meanwhile, the inhibition of SO(2) to Hg(0) catalytic conversion in the MDCOs was also less significant than in the TCO. The MDCOs have high retainability for HCl, which is quite favorable to Hg(0) conversion and HCl utilization. The reaction mechanism on mercury conversion in the MDCOs is discussed. The MDCOs appear to be a promising method for emission control of elemental mercury.

  16. Superparamagnetic iron oxide nanoparticles (SPIONs) for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Garg, Vijayendra K.; Kuzmann, Erno; Sharma, Virender K.; Kumar, Arun; Oliveira, Aderbal C.

    2016-10-01

    Studies of superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively carried out. Since the earlier work on Mössbauer studies on SPIONs in 1970s, many biomedical applications and their uses in innovative methods to produce new materials with improved performance have appeared. Applications of SPIONs in environmental remediation are also forthcoming. Several different methods of synthesis and coating of the magnetic particles have been described in the literature, and Mössbauer spectroscopy has been an important tool in the characterization of these materials. It is quite possible that the interpretation of the Mössbauer spectra might not be entirely correct because the possible presence of maghemite in the end product of SPIONs might not have been taken into consideration. Nanotechnology is an emerging field that covers a wide range of new technologies under development in nanoscale (1 to 100 nano meters) to produce new products and methodology.

  17. Effects of antiepileptic drugs on antioxidant and oxidant molecular pathways: focus on trace elements.

    PubMed

    Nazıroğlu, Mustafa; Yürekli, Vedat Ali

    2013-07-01

    Current reports on trace elements, oxidative stress, and the effect of antiepileptic drugs are poor and controversial. We aimed to review effects of most common used antiepileptics on antioxidant, trace element, calcium ion (Ca(2+)) influx, and oxidant systems in human and experimental animal models. Observations of lower blood or tissue antioxidant levels in epileptic patients and animals compared to controls in recent publications may commonly support the proposed crucial role of antioxidants in the pathogenesis of epilepsy. Effects of old and new antiepileptics on reactive oxygen species (ROS) production in epilepsy are controversial. The old antiepileptic drugs like valproic acid, phenytoin, and carbamazepine induced ROS overproduction, while new epileptic drugs (e.g., topiramate and zonisamide) induced scavenger effects on over production of ROS in human and animals. Antioxidant trace element levels such as selenium, copper, and zinc were generally low in the blood of epileptic patients, indicating trace element deficiencies in the pathogenesis of epilepsy. Recent papers indicate that selenium with/without topiramate administration in human and animals decreased seizure levels, although antioxidant values were increased. Recent studies also reported that sustained depolarization of mitochondrial membranes, enhanced ROS production and Ca(2+) influx may be modulated by topiramate. In conclusion, there is a large number of recent studies about the role of antioxidants or neuroprotectants in clinical and experimental models of epilepsy. New antiepileptic drugs are more prone to restore antioxidant redox systems in brain and neurons.

  18. Caesium in high oxidation states and as a p-block element.

    PubMed

    Miao, Mao-sheng

    2013-10-01

    The periodicity of the elements and the non-reactivity of the inner-shell electrons are two related principles of chemistry, rooted in the atomic shell structure. Within compounds, Group I elements, for example, invariably assume the +1 oxidation state, and their chemical properties differ completely from those of the p-block elements. These general rules govern our understanding of chemical structures and reactions. Here, first-principles calculations show that, under pressure, caesium atoms can share their 5p electrons to become formally oxidized beyond the +1 state. In the presence of fluorine and under pressure, the formation of CsF(n) (n > 1) compounds containing neutral or ionic molecules is predicted. Their geometry and bonding resemble that of isoelectronic XeF(n) molecules, showing a caesium atom that behaves chemically like a p-block element under these conditions. The calculated stability of the CsF(n) compounds shows that the inner-shell electrons can become the main components of chemical bonds.

  19. Halbach arrays consisting of cubic elements optimised for high field gradients in magnetic drug targeting applications.

    PubMed

    Barnsley, Lester C; Carugo, Dario; Owen, Joshua; Stride, Eleanor

    2015-11-07

    A key challenge in the development of magnetic drug targeting (MDT) as a clinically relevant technique is designing systems that can apply sufficient magnetic force to actuate magnetic drug carriers at useful tissue depths. In this study an optimisation routine was developed to generate designs of Halbach arrays consisting of multiple layers of high grade, cubic, permanent magnet elements, configured to deliver the maximum pull or push force at a position of interest between 5 and 50 mm from the array, resulting in arrays capable of delivering useful magnetic forces to depths past 20 mm. The optimisation routine utilises a numerical model of the magnetic field and force generated by an arbitrary configuration of magnetic elements. Simulated field and force profiles of optimised arrays were evaluated, also taking into account the forces required for assembling the array in practice. The resultant selection for the array, consisting of two layers, was then constructed and characterised to verify the simulations. Finally the array was utilised in a set of in vitro experiments to demonstrate its capacity to separate and retain microbubbles loaded with magnetic nanoparticles against a constant flow. The optimised designs are presented as light-weight, inexpensive options for applying high-gradient, external magnetic fields in MDT applications.

  20. A P Element Chimera Containing Captured Genomic Sequences Was Recovered at the Vestigial Locus in Drosophila following Targeted Transposition

    PubMed Central

    Heslip, T. R.; Williams, J. A.; Bell, J. B.; Hodgetts, R. B.

    1992-01-01

    A P element carrying the Dopa decarboxylase gene, P[Ddc], was targeted into vg(21), a cryptic P element induced mutant allele of the vestigial (vg) locus. The resulting allele, vg(28w), contained the expected P[Ddc] plus an additional 9.5 kb of DNA, captured from elsewhere on chromosome II. Reversion of the vg(28w) mutant allele demonstrated that the entire insert can excise but cannot reinsert at an appreciable frequency. We explain the targeted transposition as the repair of a double stranded gap, created by the excision of the P element at vg(21), and suggest that the formation of chimeric elements may be an important component of P element dependent genomic instability. PMID:1325388

  1. Biodistribution of antibody-targeted and non-targeted iron oxide nanoparticles in a breast cancer mouse model

    NASA Astrophysics Data System (ADS)

    Tate, Jennifer A.; Kett, Warren; NDong, Christian; Griswold, Karl E.; Hoopes, P. Jack

    2013-02-01

    Iron oxide nanoparticle (IONP) hyperthermia is a novel therapeutic strategy currently under consideration for the treatment of various cancer types. Systemic delivery of IONP followed by non-invasive activation via a local alternating magnetic field (AMF) results in site-specific energy deposition in the IONP-containing tumor. Targeting IONP to the tumor using an antibody or antibody fragment conjugated to the surface may enhance the intratumoral deposition of IONP and is currently being pursued by many nanoparticle researchers. This strategy, however, is subject to a variety of restrictions in the in vivo environment, where other aspects of IONP design will strongly influence the biodistribution. In these studies, various targeted IONP are compared to non-targeted controls. IONP were injected into BT-474 tumor-bearing NSG mice and tissues harvested 24hrs post-injection. Results indicate no significant difference between the various targeted IONP and the non-targeted controls, suggesting the IONP were prohibitively-sized to incur tumor penetration. Additional strategies are currently being pursued in conjuncture with targeted particles to increase the intratumoral deposition.

  2. Target enrichment of ultraconserved elements from arthropods provides a genomic perspective on relationships among Hymenoptera.

    PubMed

    Faircloth, Brant C; Branstetter, Michael G; White, Noor D; Brady, Seán G

    2015-05-01

    Gaining a genomic perspective on phylogeny requires the collection of data from many putatively independent loci across the genome. Among insects, an increasingly common approach to collecting this class of data involves transcriptome sequencing, because few insects have high-quality genome sequences available; assembling new genomes remains a limiting factor; the transcribed portion of the genome is a reasonable, reduced subset of the genome to target; and the data collected from transcribed portions of the genome are similar in composition to the types of data with which biologists have traditionally worked (e.g. exons). However, molecular techniques requiring RNA as a template, including transcriptome sequencing, are limited to using very high-quality source materials, which are often unavailable from a large proportion of biologically important insect samples. Recent research suggests that DNA-based target enrichment of conserved genomic elements offers another path to collecting phylogenomic data across insect taxa, provided that conserved elements are present in and can be collected from insect genomes. Here, we identify a large set (n = 1510) of ultraconserved elements (UCEs) shared among the insect order Hymenoptera. We used in silico analyses to show that these loci accurately reconstruct relationships among genome-enabled hymenoptera, and we designed a set of RNA baits (n = 2749) for enriching these loci that researchers can use with DNA templates extracted from a variety of sources. We used our UCE bait set to enrich an average of 721 UCE loci from 30 hymenopteran taxa, and we used these UCE loci to reconstruct phylogenetic relationships spanning very old (≥220 Ma) to very young (≤1 Ma) divergences among hymenopteran lineages. In contrast to a recent study addressing hymenopteran phylogeny using transcriptome data, we found ants to be sister to all remaining aculeate lineages with complete support, although this result could be explained by

  3. MnOx/Graphene for the Catalytic Oxidation and Adsorption of Elemental Mercury.

    PubMed

    Xu, Haomiao; Qu, Zan; Zong, Chenxi; Huang, Wenjun; Quan, Fuquan; Yan, Naiqiang

    2015-06-02

    MnOx/graphene composites were prepared and employed to enhance the performance of manganese oxide (MnOx) for the capture of elemental mercury (Hg(0)) in flue gas. The composites were characterized using FT-IR, XPS, XRD, and TEM, and the results showed that the highly dispersed MnOx particles could be readily deposited on graphene nanosheets via hydrothermal process described here. Graphene appeared to be an ideal support for MnOx particles and electron transfer channels in the catalytic oxidation of Hg(0) at a high efficiency. Thus, MnOx/graphene-30% sorbents exhibited an Hg(0) removal efficiency of greater than 90% at 150 °C under 4% O2, compared with the 50% removal efficiency of pure MnOx. The mechanism of Hg(0) capture is discussed, and the main Hg(0) capture mechanisms of MnOx/graphene were catalytic oxidation and adsorption. Mn is the main active site for Hg(0) catalytic oxidation, during which high valence Mn (Mn(4+) or Mn(3+)) is converted to low valence Mn (Mn(3+) or Mn(2+)). Graphene enhanced the electrical conductivity of MnOx, which is beneficial for catalytic oxidation. Furthermore, MnOx/graphene exhibited an excellent regenerative ability, and is a promising sorbent for capturing Hg(0).

  4. Exogenous Nitric Oxide Suppresses in Vivo X-ray-Induced Targeted and Non-Targeted Effects in Zebrafish Embryos

    PubMed Central

    Kong, E.Y.; Yeung, W.K.; Chan, T.K.Y.; Cheng, S.H.; Yu, K.N.

    2016-01-01

    The present paper studied the X-ray-induced targeted effect in irradiated zebrafish embryos (Danio rerio), as well as a non-targeted effect in bystander naïve embryos partnered with irradiated embryos, and examined the influence of exogenous nitric oxide (NO) on these targeted and non-targeted effects. The exogenous NO was generated using an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). The targeted and non-targeted effects, as well as the toxicity of the SNAP, were assessed using the number of apoptotic events in the zebrafish embryos at 24 h post fertilization (hpf) revealed through acridine orange (AO) staining. SNAP with concentrations of 20 and 100 µM were first confirmed to have no significant toxicity on zebrafish embryos. The targeted effect was mitigated in zebrafish embryos if they were pretreated with 100 µM SNAP prior to irradiation with an X-ray dose of 75 mGy but was not alleviated in zebrafish embryos if they were pretreated with 20 µM SNAP. On the other hand, the non-targeted effect was eliminated in the bystander naïve zebrafish embryos if they were pretreated with 20 or 100 µM SNAP prior to partnering with zebrafish embryos having been subjected to irradiation with an X-ray dose of 75 mGy. These findings revealed the importance of NO in the protection against damages induced by ionizing radiations or by radiation-induced bystander signals, and could have important impacts on development of advanced cancer treatment strategies. PMID:27529238

  5. A possible aid in targeted insertion of large DNA elements by CRISPR/Cas in mouse zygotes.

    PubMed

    Nakao, Harumi; Harada, Takeshi; Nakao, Kazuki; Kiyonari, Hiroshi; Inoue, Kenichi; Furuta, Yasuhide; Aiba, Atsu

    2016-02-01

    The CRISPR/Cas system has rapidly emerged recently as a new tool for genome engineering, and is expected to allow for controlled manipulation of specific genomic elements in a variety of species. A number of recent studies have reported the use of CRISPR/Cas for gene disruption (knockout) or targeted insertion of foreign DNA elements (knock-in). Despite the ease of simple gene knockout and small insertions or nucleotide substitutions in mouse zygotes by the CRISPR/Cas system, targeted insertion of large DNA elements remains an apparent challenge. Here the generation of knock-in mice with successful targeted insertion of large donor DNA elements ranged from 3.0 to 7.1 kb at the ROSA26 locus using the CRISPR/Cas system was achieved. Multiple independent knock-in founder mice were obtained by injection of hCas9 mRNA/sgRNA/donor vector mixtures into the cytoplasm of C57BL/6N zygotes when the injected zygotes were treated with an inhibitor of actin polymerization, cytochalasin. Successful germ line transmission of three of these knock-in alleles was also confirmed. The results suggested that treatment of zygotes with actin polymerization inhibitors following microinjection could be a viable method to facilitate targeted insertion of large DNA elements by the CRISPR/Cas system, enabling targeted knock-in readily attainable in zygotes.

  6. Design and Fabrication of Oxygen/RP-2 Multi-Element Oxidizer-Rich Staged Combustion Thrust Chamber Injectors

    NASA Technical Reports Server (NTRS)

    Garcia, C. P.; Medina, C. R.; Protz, C. S.; Kenny, R. J.; Kelly, G. W.; Casiano, M. J.; Hulka, J. R.; Richardson, B. R.

    2016-01-01

    As part of the Combustion Stability Tool Development project funded by the Air Force Space and Missile Systems Center, the NASA Marshall Space Flight Center was contracted to assemble and hot-fire test a multi-element integrated test article demonstrating combustion characteristics of an oxygen/hydrocarbon propellant oxidizer-rich staged-combustion engine thrust chamber. Such a test article simulates flow through the main injectors of oxygen/kerosene oxidizer-rich staged combustion engines such as the Russian RD-180 or NK-33 engines, or future U.S.-built engine systems such as the Aerojet-Rocketdyne AR-1 engine or the Hydrocarbon Boost program demonstration engine. On the current project, several configurations of new main injectors were considered for the thrust chamber assembly of the integrated test article. All the injector elements were of the gas-centered swirl coaxial type, similar to those used on the Russian oxidizer-rich staged-combustion rocket engines. In such elements, oxidizer-rich combustion products from the preburner/turbine exhaust flow through a straight tube, and fuel exiting from the combustion chamber and nozzle regenerative cooling circuits is injected near the exit of the oxidizer tube through tangentially oriented orifices that impart a swirl motion such that the fuel flows along the wall of the oxidizer tube in a thin film. In some elements there is an orifice at the inlet to the oxidizer tube, and in some elements there is a sleeve or "shield" inside the oxidizer tube where the fuel enters. In the current project, several variations of element geometries were created, including element size (i.e., number of elements or pattern density), the distance from the exit of the sleeve to the injector face, the width of the gap between the oxidizer tube inner wall and the outer wall of the sleeve, and excluding the sleeve entirely. This paper discusses the design rationale for each of these element variations, including hydraulic, structural

  7. Direct chemiluminescence detection of nitric oxide in aqueous solutions using the natural nitric oxide target soluble guanylyl cyclase.

    PubMed

    Woldman, Yakov Y; Sun, Jian; Zweier, Jay L; Khramtsov, Valery V

    2009-11-15

    Nitric oxide (NO) is a free radical involved in many physiological processes including regulation of blood pressure, immune response, and neurotransmission. However, the measurement of extremely low, in some cases subnanomolar, physiological concentrations of nitric oxide presents an analytical challenge. The purpose of this methods article is to introduce a new highly sensitive chemiluminescence approach to direct NO detection in aqueous solutions using a natural nitric oxide target, soluble guanylyl cyclase (sGC), which catalyzes the conversion of guanosine triphosphate to guanosine 3',5'-cyclic monophosphate and inorganic pyrophosphate. The suggested enzymatic assay uses the fact that the rate of the reaction increases by about 200 times when NO binds with sGC and, in so doing, provides a sensor for nitric oxide. Luminescence detection of the above reaction is accomplished by converting inorganic pyrophosphate into ATP with the help of ATP sulfurylase followed by light emission from the ATP-dependent luciferin-luciferase reaction. Detailed protocols for NO quantification in aqueous samples are provided. The examples of applications include measurement of NO generated by a nitric oxide donor (PAPA-NONOate), nitric oxide synthase, and NO gas dissolved in buffer. The method allows for the measurement of NO concentrations in the nanomolar range and NO generation rates as low as 100 pM/min.

  8. Impact of Seminal Chemical Elements on the Oxidative Balance in Bovine Seminal Plasma and Spermatozoa.

    PubMed

    Tvrdá, Eva; Lukáč, Norbert; Schneidgenová, Monika; Lukáčová, Jana; Szabó, Csaba; Goc, Zofia; Greń, Agnieszka; Massányi, Peter

    2013-01-01

    Mutual relationships between selected chemical elements (Na, K, Fe, Cu, Mg, and Zn), basic motility characteristics (motility and progressive motility), and markers of the oxidative balance (superoxide dismutase, catalase, glutathione, albumin, and malondialdehyde) were investigated in bovine seminal plasma and spermatozoa. Computer assisted sperm analysis was used to assess the motility parameters; mineral concentrations were determined by the voltammetric method and flame absorption spectrophotometry; antioxidants and malondialdehyde were evaluated by UV/VIS spectrophotometry. Concentrations of chemical elements in both seminal fractions were in the following descending order: Na > K > Zn > Mg > Fe > Cu. Higher amounts of all minerals and nonenzymatic antioxidants were detected in the seminal plasma (P < 0.01; P < 0.001), while higher MDA concentration and activity of enzymatic antioxidants were recorded in the cell lysates (P < 0.01; P < 0.001). Na, Fe, Cu, Mg, and Zn were positively correlated with the motility and antioxidant parameters (P < 0.05; P < 0.01; P < 0.001). Inversely, K exhibited the positive associations with malondialdehyde (P < 0.05). This study demonstrates that most chemical elements are integral components of bovine semen and are needed for the protection against oxidative stress development.

  9. Suppressing iron oxide nanoparticle toxicity by vascular targeted antioxidant polymer nanoparticles.

    PubMed

    Cochran, David B; Wattamwar, Paritosh P; Wydra, Robert; Hilt, J Zach; Anderson, Kimberly W; Eitel, Richard E; Dziubla, Thomas D

    2013-12-01

    The biomedical use of superparamagnetic iron oxide nanoparticles has been of continued interest in the literature and clinic. Their ability to be used as contrast agents for imaging and/or responsive agents for remote actuation makes them exciting materials for a wide range of clinical applications. Recently, however, concern has arisen regarding the potential health effects of these particles. Iron oxide toxicity has been demonstrated in in vivo and in vitro models, with oxidative stress being implicated as playing a key role in this pathology. One of the key cell types implicated in this injury is the vascular endothelial cells. Here, we report on the development of a targeted polymeric antioxidant, poly(trolox ester), nanoparticle that can suppress oxidative damage. As the polymer undergoes enzymatic hydrolysis, active trolox is locally released, providing a long term protection against pro-oxidant agents. In this work, poly(trolox) nanoparticles are targeted to platelet endothelial cell adhesion molecules (PECAM-1), which are able to bind to and internalize in endothelial cells and provide localized protection against the cytotoxicity caused by iron oxide nanoparticles. These results indicate the potential of using poly(trolox ester) as a means of mitigating iron oxide toxicity, potentially expanding the clinical use and relevance of these exciting systems.

  10. Identification of the RNA recognition element of the RBPMS family of RNA-binding proteins and their transcriptome-wide mRNA targets.

    PubMed

    Farazi, Thalia A; Leonhardt, Carl S; Mukherjee, Neelanjan; Mihailovic, Aleksandra; Li, Song; Max, Klaas E A; Meyer, Cindy; Yamaji, Masashi; Cekan, Pavol; Jacobs, Nicholas C; Gerstberger, Stefanie; Bognanni, Claudia; Larsson, Erik; Ohler, Uwe; Tuschl, Thomas

    2014-07-01

    Recent studies implicated the RNA-binding protein with multiple splicing (RBPMS) family of proteins in oocyte, retinal ganglion cell, heart, and gastrointestinal smooth muscle development. These RNA-binding proteins contain a single RNA recognition motif (RRM), and their targets and molecular function have not yet been identified. We defined transcriptome-wide RNA targets using photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) in HEK293 cells, revealing exonic mature and intronic pre-mRNA binding sites, in agreement with the nuclear and cytoplasmic localization of the proteins. Computational and biochemical approaches defined the RNA recognition element (RRE) as a tandem CAC trinucleotide motif separated by a variable spacer region. Similar to other mRNA-binding proteins, RBPMS family of proteins relocalized to cytoplasmic stress granules under oxidative stress conditions suggestive of a support function for mRNA localization in large and/or multinucleated cells where it is preferentially expressed.

  11. Effects of working pressure on physical properties of tungsten-oxide thin films sputtered from oxide target

    SciTech Connect

    Riech, I.; Acosta, M.; Pena, J. L.; Bartolo-Perez, P.

    2010-03-15

    Tungsten-oxide films were deposited on glass substrates from a metal-oxide target by nonreactive radio-frequency sputtering. The authors have studied the effect that changing Ar gas pressure has on the electrical, optical, and chemical composition in the thin films. Resistivity of WO{sub 3} changed ten orders of magnitude with working gas pressure values from 20 to 80 mTorr. Thin films deposited at 20 mTorr of Ar sputtering pressure showed lower resistivity and optical transmittance. X-ray photoelectron spectroscopy (XPS) measurements revealed similar chemical composition for all samples irrespective of Ar pressure used. However, XPS analyses of the evolution of W 4f and O 1s peaks indicated a mixture of oxides dependent on the Ar pressure used during deposition.

  12. Adsorption and oxidation of elemental mercury over Ce-MnOx/Ti-PILCs.

    PubMed

    He, Chuan; Shen, Boxiong; Chen, Jianhong; Cai, Ji

    2014-07-15

    A series of innovative Ce-Mn/Ti-pillared-clay (Ce-Mn/Ti-PILC) catalysts combining the advantages of PILCs and Ce-Mn were investigated for elemental mercury (Hg0) capture at 100-350 °C in the absence of HCl in the flue gas. The fresh and used catalysts were characterized by scanning electron microscopy (SEM), nitrogen adsorption-desorption, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The catalyst characterization indicated that the 6%Ce-6%MnOx/Ti-PILC catalyst possessed a large specific surface area and high dispersion of Ce and Mn on the surface. The experimental results indicated that the 6%Ce-6%MnOx/Ti-PILC catalyst exhibited high Hg0 capture (>90%) at 100-350 °C. During the first stage of the reaction, the main Hg0 capture mechanism for the catalyst was adsorption. As the reaction proceeded, the Hg0 oxidation ability was substantially enhanced. Both the hydroxyl oxygen and the lattice oxygen on the surface of the catalysts participated in Hg0 oxidation. At a low temperature (150 °C), the hydroxyl oxygen and lattice oxygen from Ce4+→Ce3+ and Mn3+→Mn2+ on the surface contributed to Hg0 oxidation. However, at a high temperature (250 °C), the hydroxyl oxygen and lattice oxygen from Mn4+→Mn3+ contributed to Hg0 oxidation. Hg0 oxidation was preferred at a high temperature. The 6%Ce-6%MnOx/Ti-PILC catalyst was demonstrated to a good Hg0 adsorbent and catalytic oxidant in the absence of HCl in the flue gas.

  13. Reactions of calcium orthosilicate and barium zirconate with oxides and sulfates of various elements

    NASA Technical Reports Server (NTRS)

    Zaplatynsky, I.

    1979-01-01

    Calcium orthosilicate and barium zirconate were evaluated as the insulation layer of thermal barrier coatings for air cooled gas turbine components. Their reactions with various oxides and sulfates were studied at 1100 C and 1300 C for times ranging up to 400 and 200 hours, respectively. These oxides and sulfates represent potential impurities or additives in gas turbine fuels and in turbine combustion air, as well as elements of potential bond coat alloys. The phase compositions of the reaction products were determined by X-ray diffraction analysis. BaZrO3 and 2CaO-SiO2 both reacted with P2O5, V2O5, Cr2O3, Al2O3, and SiO2. In addition, 2CaO-SiO2 reacted with Na2O, BaO, MgO, and CoO and BaZrO3 reacted with Fe2O3.

  14. Method for removing sulfur oxide from waste gases and recovering elemental sulfur

    DOEpatents

    Moore, Raymond H.

    1977-01-01

    A continuous catalytic fused salt extraction process is described for removing sulfur oxides from gaseous streams. The gaseous stream is contacted with a molten potassium sulfate salt mixture having a dissolved catalyst to oxidize sulfur dioxide to sulfur trioxide and molten potassium normal sulfate to solvate the sulfur trioxide to remove the sulfur trioxide from the gaseous stream. A portion of the sulfur trioxide loaded salt mixture is then dissociated to produce sulfur trioxide gas and thereby regenerate potassium normal sulfate. The evolved sulfur trioxide is reacted with hydrogen sulfide as in a Claus reactor to produce elemental sulfur. The process may be advantageously used to clean waste stack gas from industrial plants, such as copper smelters, where a supply of hydrogen sulfide is readily available.

  15. Phase transitions via selective elemental vacancy engineering in complex oxide thin films

    NASA Astrophysics Data System (ADS)

    Lee, Sang A.; Jeong, Hoidong; Woo, Sungmin; Hwang, Jae-Yeol; Choi, Si-Young; Kim, Sung-Dae; Choi, Minseok; Roh, Seulki; Yu, Hosung; Hwang, Jungseek; Kim, Sung Wng; Choi, Woo Seok

    2016-04-01

    Defect engineering has brought about a unique level of control for Si-based semiconductors, leading to the optimization of various opto-electronic properties and devices. With regard to perovskite transition metal oxides, O vacancies have been a key ingredient in defect engineering, as they play a central role in determining the crystal field and consequent electronic structure, leading to important electronic and magnetic phase transitions. Therefore, experimental approaches toward understanding the role of defects in complex oxides have been largely limited to controlling O vacancies. In this study, we report on the selective formation of different types of elemental vacancies and their individual roles in determining the atomic and electronic structures of perovskite SrTiO3 (STO) homoepitaxial thin films fabricated by pulsed laser epitaxy. Structural and electronic transitions have been achieved via selective control of the Sr and O vacancy concentrations, respectively, indicating a decoupling between the two phase transitions. In particular, O vacancies were responsible for metal-insulator transitions, but did not influence the Sr vacancy induced cubic-to-tetragonal structural transition in epitaxial STO thin film. The independent control of multiple phase transitions in complex oxides by exploiting selective vacancy engineering opens up an unprecedented opportunity toward understanding and customizing complex oxide thin films.

  16. Oxidation behavior of iron-chromium alloys at elevated temperatures: A reactive-element effect

    SciTech Connect

    Park, J.H.; Natesan, K.

    1992-03-01

    Oxidation tests were conducted on samples of Fe-25Cr, Fe-25Cr,-0.3-1.0Y, and Fe-25Cr-1Ce at temperatures of 700 to 1000{degrees}C and oxygen partial pressures of 1 to 20 atm for time periods of 19 to 160 h. In some tests, oxidized samples were quenched from test temperature to room temperature in {approximately}20 min to examine characteristics of the spallation scales. The results showed that the scales, even though of the same composition, spalled totally when developed on Fe-25Cr alloy, while those on Ce- and Y-containing alloys exhibited good scale adherence and no spallation. After removal of the spalled scales, specimens of Fe-25Cr alloy were reoxidized to gain insight into development and morphology of thermally grown scales and their spallation characteristics. The reoxidized samples formed complex scale layers that had iron oxide phase at the gas side of the interface; the scale layer was adherent and no spallation was noted. Experiments were conducted to evaluate the roles of alloy grain size and grain growth rate in development and spallation of oxide scales. Results showed that excessive alloy grain growth is the primary cause of spallation of thermally grown scales. Additions of reactive elements such as Y and Ce minimize alloy grain growth and thus improve the adhesion of scales to the substrate and virtually eliminate spallation.

  17. Phase transitions via selective elemental vacancy engineering in complex oxide thin films

    PubMed Central

    Lee, Sang A.; Jeong, Hoidong; Woo, Sungmin; Hwang, Jae-Yeol; Choi, Si-Young; Kim, Sung-Dae; Choi, Minseok; Roh, Seulki; Yu, Hosung; Hwang, Jungseek; Kim, Sung Wng; Choi, Woo Seok

    2016-01-01

    Defect engineering has brought about a unique level of control for Si-based semiconductors, leading to the optimization of various opto-electronic properties and devices. With regard to perovskite transition metal oxides, O vacancies have been a key ingredient in defect engineering, as they play a central role in determining the crystal field and consequent electronic structure, leading to important electronic and magnetic phase transitions. Therefore, experimental approaches toward understanding the role of defects in complex oxides have been largely limited to controlling O vacancies. In this study, we report on the selective formation of different types of elemental vacancies and their individual roles in determining the atomic and electronic structures of perovskite SrTiO3 (STO) homoepitaxial thin films fabricated by pulsed laser epitaxy. Structural and electronic transitions have been achieved via selective control of the Sr and O vacancy concentrations, respectively, indicating a decoupling between the two phase transitions. In particular, O vacancies were responsible for metal-insulator transitions, but did not influence the Sr vacancy induced cubic-to-tetragonal structural transition in epitaxial STO thin film. The independent control of multiple phase transitions in complex oxides by exploiting selective vacancy engineering opens up an unprecedented opportunity toward understanding and customizing complex oxide thin films. PMID:27033718

  18. Alterations of Bio-elements, Oxidative, and Inflammatory Status in the Zinc Deficiency Model in Rats.

    PubMed

    Doboszewska, Urszula; Szewczyk, Bernadeta; Sowa-Kućma, Magdalena; Noworyta-Sokołowska, Karolina; Misztak, Paulina; Gołębiowska, Joanna; Młyniec, Katarzyna; Ostachowicz, Beata; Krośniak, Mirosław; Wojtanowska-Krośniak, Agnieszka; Gołembiowska, Krystyna; Lankosz, Marek; Piekoszewski, Wojciech; Nowak, Gabriel

    2016-01-01

    Our previous study showed that dietary zinc restriction induces depression-like behavior with concomitant up-regulation of the N-methyl-D-aspartate receptor (NMDAR). Because metal ions, oxidative stress, and inflammation are involved in depression/NMDAR function, in the present study, bio-elements (zinc, copper, iron, magnesium, and calcium), oxidative (thiobarbituric acid-reactive substances; protein carbonyl content), and inflammatory (IL-1α, IL-1β) factors were measured in serum, hippocampus (Hp), and prefrontal cortex (PFC) of male Sprague-Dawley rats subjected to a zinc-adequate (ZnA) (50 mg Zn/kg) or a zinc-deficient (ZnD) (3 mg Zn/kg) diet for 4 or 6 weeks. Both periods of dietary zinc restriction reduced serum zinc and increased serum iron levels. At 4 weeks, lowered zinc level in the PFC and Hp as well as lowered iron level in the PFC of the ZnD rats was observed. At 6 weeks, however, iron level was increased in the PFC of these rats. Although at 6 weeks zinc level in the PFC did not differ between the ZnA and ZnD rats, extracellular zinc concentration after 100 mM KCl stimulation was reduced in the PFC of the ZnD rats and was accompanied by increased extracellular iron and glutamate levels (as measured by the in vivo microdialysis). The examined oxidative and inflammatory parameters were generally enhanced in the tissue of the ZnD animals. The obtained data suggest dynamic redistribution of bio-elements and enhancement of oxidative/inflammatory parameters after dietary zinc restriction, which may have a link with depression-like behavior/NMDAR function/neurodegeneration.

  19. Targeting multiple types of tumors using NKG2D-coated iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Wu, Ming-Ru; Cook, W. James; Zhang, Tong; Sentman, Charles L.

    2014-11-01

    Iron oxide nanoparticles (IONPs) hold great potential for cancer therapy. Actively targeting IONPs to tumor cells can further increase therapeutic efficacy and decrease off-target side effects. To target tumor cells, a natural killer (NK) cell activating receptor, NKG2D, was utilized to develop pan-tumor targeting IONPs. NKG2D ligands are expressed on many tumor types and its ligands are not found on most normal tissues under steady state conditions. The data showed that mouse and human fragment crystallizable (Fc)-fusion NKG2D (Fc-NKG2D) coated IONPs (NKG2D/NPs) can target multiple NKG2D ligand positive tumor types in vitro in a dose dependent manner by magnetic cell sorting. Tumor targeting effect was robust even under a very low tumor cell to normal cell ratio and targeting efficiency correlated with NKG2D ligand expression level on tumor cells. Furthermore, the magnetic separation platform utilized to test NKG2D/NP specificity has the potential to be developed into high throughput screening strategies to identify ideal fusion proteins or antibodies for targeting IONPs. In conclusion, NKG2D/NPs can be used to target multiple tumor types and magnetic separation platform can facilitate the proof-of-concept phase of tumor targeting IONP development.

  20. Qualification of high heat flux components: application to target elements of W7-X divertor

    NASA Astrophysics Data System (ADS)

    Missirlian, M.; Durocher, A.; Grosman, A.; Schlosser, J.; Boscary, J.; Escourbiac, F.; Cismondi, F.

    2007-03-01

    The development of actively cooled plasma-facing components (PFC) represents one of fusion's most challenging engineering efforts. In this frame, a high-quality bonding between the refractory armour and the heat sink is essential to ensure the heat removal capability and the thermal performances of PFC. Experience gained during manufacturing of Tore Supra actively cooled PFC led to the establishment of a qualification methodology and provided a large experience of acceptance criteria using an active infrared thermography (système d'acquisition de traitement infra-rouge, SATIR). This paper presents the application of this qualification process to the W7-X pre-series components, with the objective of assessing and defining workable acceptance criteria that enable reliable predictions of performance at the nominal heat flux requirements in W7-X. Finally, to check the reliability of the non-destructive examination (NDE) method by transient infrared thermography, the newly defined acceptance criteria were applied to W7-X pre-series target elements (batch #3). The SATIR results, benchmarked with HHF tests performed on the GLADIS ion beam facility were discussed to assess the ability to detect critical defects at the interface between tiles and heat sink.

  1. Expression of the Arabidopsis transposable element Tag1 is targeted to developing gametophytes.

    PubMed Central

    Galli, Mary; Theriault, Angie; Liu, Dong; Crawford, Nigel M

    2003-01-01

    The Arabidopsis transposon Tag1 undergoes late excision during vegetative and germinal development in plants containing 35S-Tag1-GUS constructs. To determine if transcriptional regulation can account for the developmental control of Tag1 excision, the transcriptional activity of Tag1 promoter-GUS fusion constructs of various lengths was examined in transgenic plants. All constructs showed expression in the reproductive organs of developing flowers but no expression in leaves. Expression was restricted to developing gametophytes in both male and female lineages. Quantitative RT-PCR analysis confirmed that Tag1 expression predominates in the reproductive organs of flower buds. These results are consistent with late germinal excision of Tag1, but they cannot explain the vegetative excision activity of Tag1 observed with 35S-Tag1-GUS constructs. To resolve this issue, Tag1 excision was reexamined using elements with no adjacent 35S promoter sequences. Tag1 excision in this context is restricted to germinal events with no detectable vegetative excision. If a 35S enhancer sequence is placed next to Tag1, vegetative excision is restored. These results indicate that the intrinsic activity of Tag1 is restricted to germinal excision due to targeted expression of the Tag1 transposase to developing gametophytes and that this activity is altered by the presence of adjacent enhancers or promoters. PMID:14704189

  2. Activity of a Py-Im polyamide targeted to the estrogen response element.

    PubMed

    Nickols, Nicholas G; Szablowski, Jerzy O; Hargrove, Amanda E; Li, Benjamin C; Raskatov, Jevgenij A; Dervan, Peter B

    2013-05-01

    Pyrrole-imidazole (Py-Im) polyamides are a class of programmable DNA minor groove binders capable of modulating the activity of DNA-binding proteins and affecting changes in gene expression. Estrogen receptor alpha (ERα) is a ligand-activated hormone receptor that binds as a homodimer to estrogen response elements (ERE) and is a driving oncogene in a majority of breast cancers. We tested a selection of structurally similar Py-Im polyamides with differing DNA sequence specificity for activity against 17β-estadiol (E2)-induced transcription and cytotoxicity in ERα positive, E2-stimulated T47DKBluc cells, which express luciferase under ERα control. The most active polyamide targeted the sequence 5'-WGGWCW-3' (W = A or T), which is the canonical ERE half site. Whole transcriptome analysis using RNA-Seq revealed that treatment of E2-stimulated breast cancer cells with this polyamide reduced the effects of E2 on the majority of those most strongly affected by E2 but had much less effect on the majority of E2-induced transcripts. In vivo, this polyamide circulated at detectable levels following subcutaneous injection and reduced levels of ER-driven luciferase expression in xenografted tumors in mice after subcutaneous compound administration without significant host toxicity.

  3. Nitric oxide and disorders of the erythrocyte: emerging roles and therapeutic targets.

    PubMed

    Maley, Jason H; Lasker, George F; Kadowitz, Philip J

    2010-12-01

    Nitric oxide (NO) plays an important role in states of erythrocyte dysfunction, including sickle cell disease (SCD), malaria, and banked blood preservation. By understanding the role of nitric oxide in these conditions, which are accompanied by hemolysis, vasoocclusion, and erythrocyte dysfunction, new therapeutic targets may be identified to treat complications of these disease states. Furthermore, the role of the erythrocyte in the controlled release of NO in hypoxic tissues is of particular interest, and two theories are discussed regarding this mechanism. In this article, the role of nitric oxide in erythrocyte function, sickle cell anemia, malaria, and damage to banked blood is reviewed, and the use of NO targeted therapies for erythrocyte disease states is discussed.

  4. Targeting oxidative stress attenuates malonic acid induced Huntington like behavioral and mitochondrial alterations in rats.

    PubMed

    Kalonia, Harikesh; Kumar, Puneet; Kumar, Anil

    2010-05-25

    Objective of the present study was to explore the possible role of oxidative stress in the malonic acid induced behavioral, biochemical and mitochondrial alterations in rats. In the present study, unilateral single injections of malonic acid at different doses (1.5, 3 and 6 micromol) were made into the ipsilateral striatum in rats. Behavioral parameters were accessed on 1st, 7th and 14th day post malonic acid administration. Oxidative stress parameters and mitochondrial enzyme functions were assessed on day 14 after behavioral observations. Ipsilateral striatal malonic acid (3 and 6 micromol) administration significantly reduced body weight, locomotor activity, motor coordination and caused oxidative damage (lipid peroxidation, nitrite, superoxide dismutase, catalase and glutathione) in the striatum as compared to sham treated animal. Mitochondrial enzyme complexes and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolinium bromide) activity were significantly inhibited by malonic acid. Vitamin E treatment (50 and 100 mg/kg, p.o.) significantly reversed the various behavioral, biochemical and mitochondrial alterations in malonic acid treated animals. Our findings show that targeting oxidative stress by vitamin E in malonic acid model, results in amelioration of behavioral and mitochondrial alterations are linked to inhibition of oxidative damage. Based upon these finding present study hypothesize that protection exerted by vitamin E on behavioral, mitochondrial markers indicates the possible preservation of the functional status of the striatal neurons by targeting the deleterious actions of oxidative stress.

  5. Elemental Metals or Oxides Distributed on a Carbon Substrate or Self-Supported and the Manufacturing Process Using Graphite Oxide as Template

    NASA Technical Reports Server (NTRS)

    Hung, Ching-Cheh (Inventor)

    1999-01-01

    A process for providing elemental metals or metal oxides distributed on a carbon substrate or self-supported utilizing graphite oxide as a precursor. The graphite oxide is exposed to one or more metal chlorides to form an intermediary product comprising carbon, metal, chloride, and oxygen. This intermediary product can be further processed by direct exposure to carbonate-solutions to form a second intermediary product comprising carbon, metal carbonate, and oxygen. Either intermediary product may be further processed: a) in air to produce metal oxide; b) in an inert environment to produce metal oxide on carbon substrate; c) in a reducing environment to produce elemental metal distributed on carbon substrate. The product generally takes the shape of the carbon precursor.

  6. Elemental Metals or Oxides Distributed on a Carbon Substrate or Self-Supported and the Manufacturing Process Using Graphite Oxide as Template

    NASA Technical Reports Server (NTRS)

    Hung, Ching-Chen (Inventor)

    1999-01-01

    A process for providing elemental metals or metal oxides distributed on a carbon substrate or self-supported utilizing graphite oxide as a percursor. The graphite oxide is exposed to one or more metal chlorides to form an intermediary product comprising carbon, metal, chloride, and oxygen. This intermediary product can be further processed by direct exposure to carbonate solutions to form a second intermediary product comprising carbon, metal carbonate, and oxygen. Either intermediary product may be further processed: a) in air to produce metal oxide; b) in an inert environment to produce metal oxide on carbon substrate; c) in a reducing environment to produce elemental metal distributed on carbon substrate. The product generally takes the shape of the carbon precursor.

  7. Brain oxidative stress as basic target of antioxidant traditional oriental medicines.

    PubMed

    Konishi, Tetsuya

    2009-04-01

    Prevention and amelioration of Mibyou (sub-healthy condition) is the critical target for disease prevention including age-related diseases and cancer although the Mibyou condition is not yet pathologically defined. Since the oxidative stress is an underlying basic etiology associated with many diseases and aging, the psychologically induced oxidative stress, especially in the brain was supposed as one of the pathology of Mibyou. Several traditional herbal prescriptions applied for the brain disorder were found effective to prevent cerebral oxidative stress induced by ischemia/reperfusion and also under psychological distress produced by whiskers cut in mice. Shengmai San comprising three herbs, Panax ginseng, Ophiopogon japonicus and Schisandra chinensis is a traditional herbal medicine formula having a long history of using as a remedy and clinical prescription to treat coronal heart diseases. Multifunctional aspect of traditional herbal prescription was discussed in terms of preventing oxidative injury in the brain using Shengmai San as a typical prescription.

  8. Long circulating reduced graphene oxide-iron oxide nanoparticles for efficient tumor targeting and multimodality imaging.

    PubMed

    Xu, Cheng; Shi, Sixiang; Feng, Liangzhu; Chen, Feng; Graves, Stephen A; Ehlerding, Emily B; Goel, Shreya; Sun, Haiyan; England, Christopher G; Nickles, Robert J; Liu, Zhuang; Wang, Taihong; Cai, Weibo

    2016-07-07

    Polyethylene glycol (PEG) surface modification is one of the most widely used approaches to improve the solubility of inorganic nanoparticles, prevent their aggregation and prolong their in vivo blood circulation half-life. Herein, we developed double-PEGylated biocompatible reduced graphene oxide nanosheets anchored with iron oxide nanoparticles (RGO-IONP-(1st)PEG-(2nd)PEG). The nanoconjugates exhibited a prolonged blood circulation half-life (∼27.7 h) and remarkable tumor accumulation (>11 %ID g(-1)) via an enhanced permeability and retention (EPR) effect. Due to the strong near-infrared absorbance and superparamagnetism of RGO-IONP-(1st)PEG-(2nd)PEG, multimodality imaging combining positron emission tomography (PET) imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging was successfully achieved. The promising results suggest the great potential of these nanoconjugates for multi-dimensional and more accurate tumor diagnosis and therapy in the future.

  9. Long circulating reduced graphene oxide-iron oxide nanoparticles for efficient tumor targeting and multimodality imaging

    NASA Astrophysics Data System (ADS)

    Xu, Cheng; Shi, Sixiang; Feng, Liangzhu; Chen, Feng; Graves, Stephen A.; Ehlerding, Emily B.; Goel, Shreya; Sun, Haiyan; England, Christopher G.; Nickles, Robert J.; Liu, Zhuang; Wang, Taihong; Cai, Weibo

    2016-06-01

    Polyethylene glycol (PEG) surface modification is one of the most widely used approaches to improve the solubility of inorganic nanoparticles, prevent their aggregation and prolong their in vivo blood circulation half-life. Herein, we developed double-PEGylated biocompatible reduced graphene oxide nanosheets anchored with iron oxide nanoparticles (RGO-IONP-1stPEG-2ndPEG). The nanoconjugates exhibited a prolonged blood circulation half-life (~27.7 h) and remarkable tumor accumulation (>11 %ID g-1) via an enhanced permeability and retention (EPR) effect. Due to the strong near-infrared absorbance and superparamagnetism of RGO-IONP-1stPEG-2ndPEG, multimodality imaging combining positron emission tomography (PET) imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging was successfully achieved. The promising results suggest the great potential of these nanoconjugates for multi-dimensional and more accurate tumor diagnosis and therapy in the future.

  10. Reactions of yttria-stabilized zirconia with oxides and sulfates of various elements

    NASA Technical Reports Server (NTRS)

    Zaplatynsky, I.

    1978-01-01

    The reactions between partially stabilized zirconia, containing 8 weight-percent yttria, and oxides and sulfates of various elements were studied at 1200, 1300, and 1400 C for times to 800, 400, and 200 hours, respectively. These oxides and sulfates represent impurities and additives potentially present in gas turbine fuels or impurities in the turbine combustion air as well as the elements of the substrate alloys in contact with zirconia. Based on the results, these compounds can be classified in four groups: (1) compounds which did not react with zirconia (Na2SO4, K2SO4, Cr2O3, Al2O3 and NiO); (2) compounds that reached completely with both zirconia phases (CaO, BaO, and BaSO4); (3) compounds that reacted preferentially with monoclinic zirconia (Na2O, K2O, CoO, Fe2O3, MgO, SiO2, and ZnO); and (4) compounds that reacted preferentially with cubic zirconia (V2O5, P2O5).

  11. Targeted mRNA oxidation regulates sunflower seed dormancy alleviation during dry after-ripening.

    PubMed

    Bazin, Jérémie; Langlade, Nicolas; Vincourt, Patrick; Arribat, Sandrine; Balzergue, Sandrine; El-Maarouf-Bouteau, Hayat; Bailly, Christophe

    2011-06-01

    After-ripening is the mechanism by which dormant seeds become nondormant during their dry storage after harvest. The absence of free water in mature seeds does not allow detectable metabolism; thus, the processes associated with dormancy release under these conditions are largely unknown. We show here that sunflower (Helianthus annuus) seed alleviation of dormancy during after-ripening is associated with mRNA oxidation and that this oxidation is prevented when seeds are maintained dormant. In vitro approaches demonstrate that mRNA oxidation results in artifacts in cDNA-amplified fragment length polymorphim analysis and alters protein translation. The oxidation of transcripts is not random but selective, and, using microarrays, we identified 24 stored mRNAs that became highly oxidized during after-ripening. Oxidized transcripts mainly correspond to genes involved in responses to stress and in cell signaling. Among them, protein phosphatase 2C PPH1, mitogen-activated protein kinase phosphatase 1, and phenyl ammonia lyase 1 were identified. We propose that targeted mRNA oxidation during dry after-ripening of dormant seeds could be a process that governs cell signaling toward germination in the early steps of seed imbibition.

  12. Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH)

    PubMed Central

    Takaki, Akinobu; Kawai, Daisuke; Yamamoto, Kazuhide

    2013-01-01

    Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease. PMID:24132155

  13. Molecular photoacoustic tomography of breast cancer using receptor targeted magnetic iron oxide nanoparticles as contrast agents.

    PubMed

    Xi, Lei; Grobmyer, Stephen R; Zhou, Guangyin; Qian, Weiping; Yang, Lily; Jiang, Huabei

    2014-06-01

    In this report, we present a breast imaging technique combining high-resolution near-infrared (NIR) light induced photoacoustic tomography (PAT) with NIR dye-labeled amino-terminal fragments of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (NIR830-ATF-IONP) for breast cancer imaging using an orthotopic mouse mammary tumor model. We show that accumulation of the targeted nanoparticles in the tumor led to photoacoustic contrast enhancement due to the high absorption of iron oxide nanoparticles (IONP). NIR fluorescence images were used to validate specific delivery of NIR830-ATF-IONP to mouse mammary tumors. We found that systemic delivery of the targeted IONP produced 4- and 10-fold enhancement in photoacoustic signals in the tumor, compared to the tumor of the mice that received non-targeted IONP or control mice. The use of targeted nanoparticles allowed imaging of tumors located as deep as 3.1 cm beneath the normal tissues. Our study indicates the potential of the combination of photoacoustic tomography and receptor-targeted NIR830-ATF-IONP as a clinical tool that can provide improved specificity and sensitivity for breast cancer detection.

  14. Characterization of Niobium Oxide Films Deposited by High Target Utilization Sputter Sources

    SciTech Connect

    Chow, R; Ellis, A D; Loomis, G E; Rana, S I

    2007-01-29

    High quality, refractory metal, oxide coatings are required in a variety of applications such as laser optics, micro-electronic insulating layers, nano-device structures, electro-optic multilayers, sensors and corrosion barriers. A common oxide deposition technique is reactive sputtering because the kinetic mechanism vaporizes almost any solid material in vacuum. Also, the sputtered molecules have higher energies than those generated from thermal evaporation, and so the condensates are smoother and denser than those from thermally-evaporated films. In the typical sputtering system, target erosion is a factor that drives machine availability. In some situations such as nano-layered capacitors, where the device's performance characteristics depends on thick layers, target life becomes a limiting factor on the maximizing device functionality. The keen interest to increase target utilization in sputtering has been addressed in a variety of ways such as target geometry, rotating magnets, and/or shaped magnet arrays. Also, a recent sputtering system has been developed that generates a high density plasma, directs the plasma beam towards the target in a uniform fashion, and erodes the target in a uniform fashion. The purpose of this paper is to characterize and compare niobia films deposited by two types of high target utilization sputtering sources, a rotating magnetron and a high density plasma source. The oxide of interest in this study is niobia because of its high refractive index. The quality of the niobia films were characterized spectroscopically in optical transmission, ellipsometrically, and chemical stoichiometry with X-ray photo-electron spectroscopy. The refractive index, extinction coefficients, Cauchy constants were derived from the ellipsometric modeling. The mechanical properties of coating density and stress are also determined.

  15. Speciation of adsorbed yttrium and rare earth elements on oxide surfaces

    NASA Astrophysics Data System (ADS)

    Piasecki, Wojciech; Sverjensky, Dimitri A.

    2008-08-01

    The distribution of yttrium and the rare earth elements (YREE) between natural waters and oxide mineral surfaces depends on adsorption reactions, which in turn depend on the specific way in which YREE are coordinated to mineral surfaces. Recent X-ray studies have established that Y 3+ is adsorbed to the rutile (1 1 0) surface as a distinctive tetranuclear species. However, the hydrolysis state of the adsorbed cation is not known from experiment. Previous surface complexation models of YREE adsorption have suggested two to four cation hydrolysis states coexisting on oxide surfaces. In the present study, we investigate the applicability of the X-ray results to rare earth elements and to several oxides in addition to rutile using the extended triple-layer surface complexation model. The reaction producing a hydrolyzed tetranuclear surface species 4>SOH+M+2HO=(>SOH)2_M(OH)2++4H was found to account for a significant fraction of the adsorbed Y 3+, La 3+, Nd 3+, Gd 3+, and Yb 3+ on rutile, hematite, alumina and silica over wide ranges of pH and ionic strength. Where adsorption data were available as a function of surface coverage for hematite and silica, an additional reaction involving a mononuclear species could be used to account for the higher surface coverages. However, it is also possible that some of the higher surface coverage data refer to surface precipitation rather than adsorption. The results of the present study provide an internally consistent basis for describing YREE adsorption which could be used to investigate more complex systems in which YREE compete both in aqueous solution and on mineral surfaces with alkaline earths and ligands such as carbonate, sulfate, chloride and organic species, in order to build a predictive adsorption model applicable to natural waters.

  16. Investigation of processes controlling summertime gaseous elemental mercury oxidation at midlatitudinal marine, coastal, and inland sites

    NASA Astrophysics Data System (ADS)

    Ye, Zhuyun; Mao, Huiting; Lin, Che-Jen; Kim, Su Youn

    2016-07-01

    A box model incorporating a state-of-the-art chemical mechanism for atmospheric mercury (Hg) cycling was developed to investigate the oxidation of gaseous elemental mercury (GEM) at three locations in the northeastern United States: Appledore Island (AI; marine), Thompson Farm (TF; coastal, rural), and Pack Monadnock (PM; inland, rural, elevated). The chemical mechanism in this box model included the most up-to-date Hg and halogen chemistry. As a result, the box model was able to simulate reasonably the observed diurnal cycles of gaseous oxidized mercury (GOM) and chemical speciation bearing distinct differences between the three sites. In agreement with observations, simulated GOM diurnal cycles at AI and TF showed significant daytime peaks in the afternoon and nighttime minimums compared to flat GOM diurnal cycles at PM. Moreover, significant differences in the magnitude of GOM diurnal amplitude (AI > TF > PM) were captured in modeled results. At the coastal and inland sites, GEM oxidation was predominated by O3 and OH, contributing 80-99 % of total GOM production during daytime. H2O2-initiated GEM oxidation was significant (˜ 33 % of the total GOM) at the inland site during nighttime. In the marine boundary layer (MBL) atmosphere, Br and BrO became dominant GEM oxidants, with mixing ratios reaching 0.1 and 1 pptv, respectively, and contributing ˜ 70 % of the total GOM production during midday, while O3 dominated GEM oxidation (50-90 % of GOM production) over the remaining day when Br and BrO mixing ratios were diminished. The majority of HgBr produced from GEM+Br was oxidized by NO2 and HO2 to form brominated GOM species. Relative humidity and products of the CH3O2+BrO reaction possibly significantly affected the mixing ratios of Br or BrO radicals and subsequently GOM formation. Gas-particle partitioning could potentially be important in the production of GOM as well as Br and BrO at the marine site.

  17. Formation of soluble mercury oxide coatings: Transformation of elemental mercury in soils

    DOE PAGES

    Miller, Carrie L.; Watson, David B.; Lester, Brian P.; ...

    2015-09-21

    In this study, the impact of mercury (Hg) on human and ecological health has been known for decades. Although a treaty signed in 2013 by 147 nations regulates future large-scale mercury emissions, legacy Hg contamination exists worldwide and small-scale releases will continue. The fate of elemental mercury, Hg(0), lost to the subsurface and its potential chemical transformation that can lead to changes in speciation and mobility are poorly understood. Here, we show that Hg(0) beads interact with soil or manganese oxide solids and X-ray spectroscopic analysis indicates that the soluble mercury coatings are HgO. Dissolution studies show that, after reactingmore » with a composite soil, >20 times more Hg is released into water from the coated beads than from a pure liquid mercury bead. An even larger, >700 times, release occurs from coated Hg(0) beads that have been reacted with manganese oxide, suggesting that manganese oxides are involved in the transformation of the Hg(0) beads and creation of the soluble mercury coatings. Although the coatings may inhibit Hg(0) evaporation, the high solubility of the coatings can enhance Hg(II) migration away from the Hg(0)-spill site and result in potential changes in mercury speciation in the soil and increased mercury mobility.« less

  18. Photochemical Oxidation of Dissolved Elemental Mercury by Carbonate Radicals in Water

    DOE PAGES

    He, Feng; Zhao, Weirong; Liang, Liyuan; ...

    2014-11-11

    Photochemical oxidation of dissolved elemental mercury [Hg(0)] affects mercury chemical speciation and its transfer at the water-air interface in the aquatic environment. The mechanisms and factors that control Hg(0) photooxidation, however, are not completely understood, especially in natural freshwaters containing dissolved organic matter (DOM) and carbonate. Here, we evaluate Hg(0) photooxidation rates affected by various reactive ionic species [e.g., DOM, CO32-, NO3-] and free radicals in a creek water and a phosphate buffer solution (pH=8) under simulated solar irradiation. We report a high Hg(0) photooxidation rate (k = 1.44 h-1) in the presence of both HCO32- and NO3-, whereas HCO32-,more » NO3-, or DOM alone increased the oxidation rate slightly (k = 0.1 0.17 h-1). Using scavengers and enhancers for singlet oxygen (1O2) and hydroxyl (HO∙ ) radicals, as well as electron paramagnetic resonance spectroscopy, we identify that carbonate radicals (CO3 ∙-) primarily drive the Hg(0) photooxidation, whereas addition of DOM resulted in a 2-fold decrease in Hg(0) oxidation. This study identifies an unrecognized pathway of Hg(0) photooxidation by CO3 ∙- radicals and the inhibitory effect of DOM, which could be important in assessing Hg transformation and fate in water containing carbonate such as hard water and seawater.« less

  19. Oxidation of elemental mercury by aqueous chlorine (HOCl/OCl-): Implications for tropospheric mercury chemistry

    NASA Astrophysics Data System (ADS)

    Lin, Che-Jen; Pehkonen, Simo O.

    1998-11-01

    The stoichiometry and kinetics of elemental mercury (Hg0) oxidation by aqueous chlorine (HOCl/OCl-) have been investigated. The stoichiometric ratio of Hg0 to HOCl/OCl- is found to be 1:1, the same as the electron transfer ratio. The rate constants of the oxidation are measured in a novel fashion by using chloramine (NH2Cl) as the free chlorine reservoir. The rate constants at room temperature (23°˜ 25°C) for the Hg0-HOCl and Hg0-OCl- are measured to be (2.09±0.06)×106 and (1.99±0.05)×106 M-1 s-1, respectively. Based on the solubility data of chlorine, the intrinsic Henry's law constant of chlorine is calculated to be 7.61×10-2 M atm-1 at 25°C. Model study using the kinetic data in this investigation shows that the oxidation of Hg0 by aqueous chlorine is an important pathway contributing dissolved divalent mercury (Hg(II)) in atmospheric water, especially at higher cloud water pH when solubility of chlorine is greatly increased and before sunrise when chlorine reaches its peak concentrations in the marine troposphere.

  20. Trace elements, oxidative stress and glycemic control in young people with type 1 diabetes mellitus.

    PubMed

    Lin, Ching-Chiang; Huang, Hsiu-Hua; Hu, Chiung-Wen; Chen, Bai-Hsiun; Chong, Inn-Wen; Chao, Yu-Ying; Huang, Yeou-Lih

    2014-01-01

    Trace elements and oxidative stress are associated with glycemic control and diabetic complications in type 1 diabetes mellitus. In this study, we analyzed the levels of serum copper, zinc, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and urinary MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in 33 type 1 diabetic patients with optimal and suboptimal glycemic control (HbA1C<9.0%) and 40 patients with poor glycemic control (HbA1C≥9%) and 27 age- and sex-matched non-diabetic controls to evaluate the differences between these markers in different glycemic control states. Diabetic patients, especially poor-glycemic-control subjects (HbA1C≥9%), exhibited significantly lower levels of serum zinc and increased levels of serum copper (and, therefore, increased serum copper-to-zinc ratios), serum SOD, blood MDA, and urinary MDA and 8-OHdG, relative to non-diabetic subjects. Furthermore, significant correlations existed in these patients between the serum copper, serum copper-to-zinc ratio, and urinary MDA (all p<0.001) and the levels of urinary 8-OHdG (p=0.007) and HbA1C. Our results suggest that high serum copper levels and oxidative stress correlate with glycemic control. Therefore, strict glycemic control, decreased oxidative stress, and a lower copper concentration might prevent diabetic complications in patients with type 1 diabetes mellitus.

  1. Formation of Soluble Mercury Oxide Coatings: Transformation of Elemental Mercury in Soils.

    PubMed

    Miller, Carrie L; Watson, David B; Lester, Brian P; Howe, Jane Y; Phillips, Debra H; He, Feng; Liang, Liyuan; Pierce, Eric M

    2015-10-20

    The impact of mercury (Hg) on human and ecological health has been known for decades. Although a treaty signed in 2013 by 147 nations regulates future large-scale mercury emissions, legacy Hg contamination exists worldwide and small-scale releases will continue. The fate of elemental mercury, Hg(0), lost to the subsurface and its potential chemical transformation that can lead to changes in speciation and mobility are poorly understood. Here, we show that Hg(0) beads interact with soil or manganese oxide solids and X-ray spectroscopic analysis indicates that the soluble mercury coatings are HgO. Dissolution studies show that, after reacting with a composite soil, >20 times more Hg is released into water from the coated beads than from a pure liquid mercury bead. An even larger, >700 times, release occurs from coated Hg(0) beads that have been reacted with manganese oxide, suggesting that manganese oxides are involved in the transformation of the Hg(0) beads and creation of the soluble mercury coatings. Although the coatings may inhibit Hg(0) evaporation, the high solubility of the coatings can enhance Hg(II) migration away from the Hg(0)-spill site and result in potential changes in mercury speciation in the soil and increased mercury mobility.

  2. Oxidative stress indicators and trace element concentrations in tissues of mako shark (Isurus oxyrinchus).

    PubMed

    Vélez-Alavez, Marcela; Labrada-Martagón, Vanessa; Méndez-Rodriguez, Lía C; Galván-Magaña, Felipe; Zenteno-Savín, Tania

    2013-08-01

    Liver, kidney and muscle from juvenile mako sharks (Isurus oxyrinchus) were collected in Baja California Sur. Lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) concentrations were determined by atomic absorption spectrophotometry. The production of superoxide radical (O2(•-)) was measured as an indicator of reactive oxygen species production; lipid peroxidation (TBARS) and protein carbonyl levels were quantified as indicators of oxidative damage, and the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) was assessed as indicator of antioxidant defenses. Two discriminant functions separated muscle from liver and kidney samples. Cd concentration was lower in muscle than in kidney (p<0.05) and Hg concentration was higher in muscle than in liver and kidney (p<0.05). Although GR and SOD activities were higher, oxidative damage (TBARS and carbonyl protein levels) was also higher in kidney (p<0.05). SOD activity, TBARS levels, and Cd and Hg concentration were the set of predictors with significant relevance during tissue discrimination. Tissue metabolism, physiology of the organisms and environmental factors may be related to the differences in trace elements and oxidative stress indicators found in muscle, liver and kidney of the mako shark.

  3. Formation of soluble mercury oxide coatings: Transformation of elemental mercury in soils

    SciTech Connect

    Miller, Carrie L.; Watson, David B.; Lester, Brian P.; Howe, Jane Y.; Phillips, Debra H.; He, Feng; Liang, Liyuan; Pierce, Eric M.

    2015-09-21

    In this study, the impact of mercury (Hg) on human and ecological health has been known for decades. Although a treaty signed in 2013 by 147 nations regulates future large-scale mercury emissions, legacy Hg contamination exists worldwide and small-scale releases will continue. The fate of elemental mercury, Hg(0), lost to the subsurface and its potential chemical transformation that can lead to changes in speciation and mobility are poorly understood. Here, we show that Hg(0) beads interact with soil or manganese oxide solids and X-ray spectroscopic analysis indicates that the soluble mercury coatings are HgO. Dissolution studies show that, after reacting with a composite soil, >20 times more Hg is released into water from the coated beads than from a pure liquid mercury bead. An even larger, >700 times, release occurs from coated Hg(0) beads that have been reacted with manganese oxide, suggesting that manganese oxides are involved in the transformation of the Hg(0) beads and creation of the soluble mercury coatings. Although the coatings may inhibit Hg(0) evaporation, the high solubility of the coatings can enhance Hg(II) migration away from the Hg(0)-spill site and result in potential changes in mercury speciation in the soil and increased mercury mobility.

  4. Mycobacteria Isolated from Angkor Monument Sandstones Grow Chemolithoautotrophically by Oxidizing Elemental Sulfur

    PubMed Central

    Kusumi, Asako; Li, Xian Shu; Katayama, Yoko

    2011-01-01

    To characterize sulfate-producing microorganisms from the deteriorated sandstones of Angkor monuments in Cambodia, strains of Mycobacterium spp. were isolated from most probable number-positive cultures. All five strains isolated were able to use both elemental sulfur (S0) for chemolithoautotrophic growth and organic substances for chemoorganoheterotrophic growth. Results of phylogenetic and phenotypic analyses indicated that all five isolates were rapid growers of the genus Mycobacterium and were most similar to Mycobacterium cosmeticum and Mycobacterium pallens. Chemolithoautotrophic growth was further examined in the representative strain THI503. When grown in mineral salts medium, strain THI503 oxidized S0 to thiosulfate and sulfate; oxidation was accompanied by a decrease in the pH of the medium from 4.7 to 3.6. The link between sulfur oxidation and energy metabolism was confirmed by an increase in ATP. Fluorescence microscopy of DAPI-stained cells revealed that strain THI503 adheres to and proliferates on the surface of sulfur particles. The flexible metabolic ability of facultative chemolithoautotrophs enables their survival in nutrient-limited sandstone environments. PMID:21747806

  5. A Topical Mitochondria-Targeted Redox-Cycling Nitroxide Mitigates Oxidative Stress-Induced Skin Damage.

    PubMed

    Brand, Rhonda M; Epperly, Michael W; Stottlemyer, J Mark; Skoda, Erin M; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E; Greenberger, Joel S; Falo, Louis D

    2017-03-01

    Skin is the largest human organ, and it provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation-induced skin damage ranges from photoaging and cutaneous carcinogenesis caused by UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation-induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species. Mitochondria are particularly susceptible to oxidative stress, and mitochondrial-dependent apoptosis plays a major role in radiation-induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent reactive oxygen species accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrially targeted antioxidant prevents and mitigates radiation-induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin's antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress.

  6. Fabrication of self-supported oxide targets by cationic adsorption in cellulosic membranes and thermal decomposition

    SciTech Connect

    Quinby, T.C.

    1983-01-01

    Techniques for producing relatively durable oxide films of various elements will be described. Areal densities of films produced to date have ranged from 150 ..mu..g/cm/sup 2/ to 2.5 mg/cm/sup 2/, and are virtually transparent. Films produced by this technique were weighed directly and mounted on frames. General parameters for use of this technique will be described.

  7. Protective Effects of Melatonin and Mitochondria-targeted Antioxidants Against Oxidative Stress: A Review.

    PubMed

    Ramis, M R; Esteban, S; Miralles, A; Tan, Dun-Xian; Reiter, R J

    2015-01-01

    Oxidative damage is related to aging and a wide range of human disorders. Mitochondria are in large part responsible for free radical production and they are also main targets of the attack of these toxic molecules. The resulting deleterious effects of the damage to mitochondria can be prevented by antioxidants. Melatonin is an endogenously-produced indoleamine that modulates numerous functions, including mitochondria-related functions; this result from its capacity to penetrate all morphophysiological barriers and to enter all subcellular compartments due to its amphiphilic nature. Furthermore, this indoleamine and its metabolites are powerful antioxidants and scavengers of free radicals, protecting cellular membranes, the electron transport chain and mitochondrial DNA from oxidative damage. These properties may make melatonin a potent protector against a variety of free radical-related diseases. By comparison, other conventional antioxidants have less efficacy due to their limited access to the mitochondria. In recent years, research has focused on the advancement of mitochondria-targeted antioxidants, such as MitoQ (composed by the lipophilic triphenylphosphonium cation conjugated to the endogenous antioxidant coenzyme Q10) and MitoE (composed by the triphenylphosphonium cation attached to the antioxidant α-tocopherol). Mitochondria-targeted antioxidants accumulate in several hundred-fold greater concentrations within mitochondria and protect these critical organelles from oxidative damage. Melatonin also seems to be a mitochondria-targeted antioxidant and has similar protective actions as the synthetic antioxidants. Further work is required to determine the therapeutic properties of these antioxidants in ameliorating diseases related to mitochondrial dysfunction.

  8. Identifying initial molecular targets of PDT: protein and lipid oxidation products

    NASA Astrophysics Data System (ADS)

    Oleinick, Nancy L.; Kim, Junhwan; Rodriguez, Myriam E.; Xue, Liang-yan; Kenney, Malcolm E.; Anderson, Vernon E.

    2009-06-01

    Photodynamic Therapy (PDT) generates singlet oxygen (1O2) which oxidizes biomolecules in the immediate vicinity of its formation. The phthalocyanine photosensitizer Pc 4 localizes to mitochondria and endoplasmic reticulum, and the primary targets of Pc 4-PDT are expected to be lipids and proteins of those membranes. The initial damage then causes apoptosis in cancer cells via the release of cytochrome c (Cyt-c) from mitochondria into the cytosol, followed by the activation of caspases. That damage also triggers the induction of autophagy, an attempt by the cells to eliminate damaged organelles, or when damage is too extensive, to promote cell death. Cyt-c is bound to the cytosolic side of the mitochondrial inner membrane through association with cardiolipin (CL), a phospholipid containing four unsaturated fatty acids and thus easily oxidized by 1O2 or by other oxidizing agents. Increasing evidence suggests that oxidation of CL loosens its association with Cyt-c, and that the peroxidase activity of Cyt-c can oxidize CL. In earlier studies of Cyt-c in homogeneous medium by MALDI-TOF-MS and LC-ESI-MS, we showed that 1O2 generated by Pc 4-PDT oxidized histidine, methionine, tryptophan, and unexpectedly phenylalanine but not tyrosine. Most of the oxidation products were known to be formed by other oxidizing agents, such as hydroxyl radical, superoxide radical anion, and peroxynitrite. However, two products of histidine were unique to 1O2 and may be useful for reporting the action of 1O2 in cells and tissues. These products, as well as CL oxidation products, have now been identified in liposomes and mitochondria after Pc 4-PDT. In mitochondria, the PDT dose-dependent oxidations can be related to specific changes in mitochondrial function, Bcl-2 photodamage, and Cyt-c release. Thus, the role of PDT-generated 1O2 in oxidizing Cyt-c and CL and the interplay between protein and lipid targets may be highly relevant to understanding one mechanism for cell killing by PDT.

  9. KINETICS OF DIRECT OXIDATION OF H2S IN COAL GAS TO ELEMENTAL SULFUR

    SciTech Connect

    K.C. Kwon

    2003-01-01

    The direct oxidation of H{sub 2}S to elemental sulfur in the presence of SO{sub 2} is ideally suited for coal gas from commercial gasifiers with a quench system to remove essentially all the trace contaminants except H{sub 2}S. This direct oxidation process has the potential to produce a super clean coal gas more economically than both conventional amine-based processes and HGD/DSRP. The objective of this research is to support the near- and long-term DOE efforts to commercialize this direct oxidation technology. The objectives of this research are to measure kinetics of direct oxidation of H{sub 2}S to elemental sulfur in the presence of a simulated coal gas mixture containing SO{sub 2}, H{sub 2}, and moisture, using 60-{micro}m C-500-04 alumina catalyst particles and a PFA differential fixed-bed micro reactor, and to develop kinetic rate equations and model the direct oxidation process to assist in the design of large-scale plants. To achieve the above-mentioned objectives, experiments on conversion of hydrogen sulfide into elemental sulfur were carried out for the space time range of 0.01-0.047 seconds at 125-155 C to evaluate effects of reaction temperatures, moisture concentrations, reaction pressures on conversion of hydrogen sulfide into elemental sulfur. Simulated coal gas mixtures consist of 61-89 v% hydrogen, 2,300-9,200-ppmv hydrogen sulfide, 1,600-4,900 ppmv sulfur dioxide, and 2.6-13.7 vol % moisture, and nitrogen as remainder. Volumetric feed rates of a simulated coal gas mixture to the reactor are 100-110 cm{sup 3}/min at room temperature and atmospheric pressure (SCCM). The temperature of the reactor is controlled in an oven at 125-155 C. The pressure of the reactor is maintained at 28-127 psia. The following results were obtained based on experimental data generated from the differential reactor system, and their interpretations, (1) Concentration of moisture and concentrations of both H{sub 2}S and SO{sub 2} appear to affect slightly reaction

  10. Periodontitis in Rats Induces Systemic Oxidative Stress That Is Controlled by Bone-Targeted Antiresorptives

    PubMed Central

    Oktay, Sehkar; Chukkapalli, Sasanka S.; Rivera-Kweh, Mercedes F.; Velsko, Irina M.; Holliday, L. Shannon; Kesavalu, Lakshmyya

    2015-01-01

    Background Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease–induced oxidative stress during oral infection. Methods Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bisenoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham-infected rats. Results Rats infected with the periodontal pathogens displayed a five-fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone-targeted antiresorptives bis-enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis-enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive. Conclusion To the best of the authors’ knowledge, this is the first study to demonstrate that the increased oxidative stress induced by periodontal infection in rats can be ameliorated by bone-targeted antiresorptives. PMID:25101489

  11. Adsorption and Catalytic Oxidation of Gaseous Elemental Mercury in Flue Gas over MnOx/Alumina

    SciTech Connect

    Qiao, S.H.; Chen, J.; Li, J.F.; Qu, Z.; Liu, P.; Yan, N.Q.; Jia, J.Q.

    2009-04-15

    MnOx/Al{sub 2}O{sub 3} catalysts (i.e., impregnating manganese oxide on alumina) were employed to remove elemental mercury (Hg{sup 0}) from flue gas. MnOx/Al{sub 2}O{sub 3} was found to have significant adsorption performance on capturing Hg{sup 0} in the absence of hydrogen chloride (HCl), and its favorable adsorption temperature was about 600 K. However, the catalytic oxidation of Hg{sup 0} became dominant when HCl or chlorine (Cl{sub 2}) was present in flue gas, and the removal efficiency of Hg{sup 0} was up to 90% with 20 ppm of HCl or 2 ppm of Cl{sub 2}. In addition, the catalysts with adsorbed mercury could be chemically regenerated by rinsing with HCl gas to strip off the adsorbed mercury in the form of HgCl{sub 2}. Sulfur dioxide displayed inhibition to the adsorption of Hg{sup 0} on the catalysts, but the inhibition was less to the catalytic oxidation of Hg{sup 0}, especially in the presence of Cl{sub 2}. The analysis results of XPS and pyrolysis-AAS indicated that the adsorbed mercury was mainly in the forms of mercuric oxide (Hg{sup 0}) and the weakly bonded speciation, and the ratio of them varied with the adsorption amount and manganese content on catalysts. The multifunctional performances of MnOx/Al{sub 2}O{sub 3} on the removal of Hg{sup 0} appeared to the promising in the industrial applications.

  12. Long interspersed nuclear element-1 hypomethylation and oxidative stress: correlation and bladder cancer diagnostic potential.

    PubMed

    Patchsung, Maturada; Boonla, Chanchai; Amnattrakul, Passakorn; Dissayabutra, Thasinas; Mutirangura, Apiwat; Tosukhowong, Piyaratana

    2012-01-01

    Although, increased oxidative stress and hypomethylation of long interspersed nuclear element-1 (LINE-1) associate with bladder cancer (BCa) development, the relationship between these alterations is unknown. We evaluated the oxidative stress and hypomethylation of the LINE-1 in 61 BCa patients and 45 normal individuals. To measure the methylation levels and to differentiate the LINE-1 loci into hypermethylated, partially methylated and hypomethylated, peripheral blood cells, urinary exfoliated cells and cancerous tissues were evaluated by combined bisulfite restriction analysis PCR. The urinary total antioxidant status (TAS) and plasma protein carbonyl content were determined. The LINE-1 methylation levels and patterns, especially hypomethylated loci, in the blood and urine cells of the BCa patients were different from the levels and patterns in the healthy controls. The urinary TAS was decreased, whereas the plasma protein carbonyl content was increased in the BCa patients relative to the controls. A positive correlation between the methylation of LINE-1 in the blood-derived DNA and urinary TAS was found in both the BCa and control groups. The urinary hypomethylated LINE-1 loci and the plasma protein carbonyl content provided the best diagnostic potential for BCa prediction. Based on post-diagnostic samples, the combination test improved the diagnostic power to a sensitivity of 96% and a specificity of 96%. In conclusion, decreased LINE-1 methylation is associated with increased oxidative stress both in healthy and BCa subjects across the various tissue types, implying a dose-response association. Increases in the LINE-1 hypomethylation levels and the number of hypomethylated loci in both the blood- and urine-derived cells and increase in the oxidative stress were found in the BCa patients. The combination test of the urinary hypomethylated LINE-1 loci and the plasma protein carbonyl content may be useful for BCa screening and monitoring of treatment.

  13. Mitochondrial targeting of bilirubin regulatory enzymes: An adaptive response to oxidative stress

    SciTech Connect

    Muhsain, Siti Nur Fadzilah; Lang, Matti A.; Abu-Bakar, A'edah

    2015-01-01

    The intracellular level of bilirubin (BR), an endogenous antioxidant that is cytotoxic at high concentrations, is tightly controlled within the optimal therapeutic range. We have recently described a concerted intracellular BR regulation by two microsomal enzymes: heme oxygenase 1 (HMOX1), essential for BR production and cytochrome P450 2A5 (CYP2A5), a BR oxidase. Herein, we describe targeting of these enzymes to hepatic mitochondria during oxidative stress. The kinetics of microsomal and mitochondrial BR oxidation were compared. Treatment of DBA/2J mice with 200 mg pyrazole/kg/day for 3 days increased hepatic intracellular protein carbonyl content and induced nucleo-translocation of Nrf2. HMOX1 and CYP2A5 proteins and activities were elevated in microsomes and mitoplasts but not the UGT1A1, a catalyst of BR glucuronidation. A CYP2A5 antibody inhibited 75% of microsomal BR oxidation. The inhibition was absent in control mitoplasts but elevated to 50% after treatment. An adrenodoxin reductase antibody did not inhibit microsomal BR oxidation but inhibited 50% of mitochondrial BR oxidation. Ascorbic acid inhibited 5% and 22% of the reaction in control and treated microsomes, respectively. In control mitoplasts the inhibition was 100%, which was reduced to 50% after treatment. Bilirubin affinity to mitochondrial and microsomal CYP2A5 enzyme is equally high. Lastly, the treatment neither released cytochrome c into cytoplasm nor dissipated membrane potential, indicating the absence of mitochondrial membrane damage. Collectively, the observations suggest that BR regulatory enzymes are recruited to mitochondria during oxidative stress and BR oxidation by mitochondrial CYP2A5 is supported by mitochondrial mono-oxygenase system. The induced recruitment potentially confers membrane protection. - Highlights: • Pyrazole induces oxidative stress in the mouse liver. • Pyrazole-induced oxidative stress induces mitochondrial targeting of key bilirubin regulatory enzymes, HMOX1

  14. Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

    SciTech Connect

    Cai, Wenqing; Zhang, Baoxin; Duan, Dongzhu; Wu, Jincai; Fang, Jianguo

    2012-08-01

    The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent signaling pathways. Curcumin, a naturally occurring pigment that gives a specific yellow color in curry food, is consumed in normal diet up to 100 mg per day. This molecule has also been used in traditional medicine for the treatment of a variety of diseases. Curcumin has numerous biological functions, and many of these functions are related to induction of oxidative stress. However, how curcumin elicits oxidative stress in cells is unclear. Our previous work has demonstrated the way by which curcumin interacts with recombinant TrxR1 and alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in vitro. Herein we reported that curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin-modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH to oxygen with the production of ROS. Also, curcumin can drastically down-regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which in turn remarkably decreases intracellular free thiols, shifting the intracellular redox balance to a more oxidative state, and subsequently induces DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to curcumin cytotoxicity, highlighting the physiological significance of targeting TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized prooxidant mechanism of curcumin in cells, and provide a deep insight in understanding how curcumin works in vivo. -- Highlights: ► Curcumin induces oxidative stress by targeting the thioredoxin system. ► Curcumin-modified TrxR quantitatively oxidizes NADPH to generate ROS. ► Knockdown of TrxR1 augments curcumin's cytotoxicity in HeLa cells. ► Curcumin

  15. 1,4-Dihydropyridine Derivatives: Dihydronicotinamide Analogues—Model Compounds Targeting Oxidative Stress

    PubMed Central

    Velena, Astrida; Zarkovic, Neven; Gall Troselj, Koraljka; Bisenieks, Egils; Krauze, Aivars; Poikans, Janis; Duburs, Gunars

    2016-01-01

    Many 1,4-dihydropyridines (DHPs) possess redox properties. In this review DHPs are surveyed as protectors against oxidative stress (OS) and related disorders, considering the DHPs as specific group of potential antioxidants with bioprotective capacities. They have several peculiarities related to antioxidant activity (AOA). Several commercially available calcium antagonist, 1,4-DHP drugs, their metabolites, and calcium agonists were shown to express AOA. Synthesis, hydrogen donor properties, AOA, and methods and approaches used to reveal biological activities of various groups of 1,4-DHPs are presented. Examples of DHPs antioxidant activities and protective effects of DHPs against OS induced damage in low density lipoproteins (LDL), mitochondria, microsomes, isolated cells, and cell cultures are highlighted. Comparison of the AOA of different DHPs and other antioxidants is also given. According to the data presented, the DHPs might be considered as bellwether among synthetic compounds targeting OS and potential pharmacological model compounds targeting oxidative stress important for medicinal chemistry. PMID:26881016

  16. 1,4-Dihydropyridine Derivatives: Dihydronicotinamide Analogues-Model Compounds Targeting Oxidative Stress.

    PubMed

    Velena, Astrida; Zarkovic, Neven; Gall Troselj, Koraljka; Bisenieks, Egils; Krauze, Aivars; Poikans, Janis; Duburs, Gunars

    2016-01-01

    Many 1,4-dihydropyridines (DHPs) possess redox properties. In this review DHPs are surveyed as protectors against oxidative stress (OS) and related disorders, considering the DHPs as specific group of potential antioxidants with bioprotective capacities. They have several peculiarities related to antioxidant activity (AOA). Several commercially available calcium antagonist, 1,4-DHP drugs, their metabolites, and calcium agonists were shown to express AOA. Synthesis, hydrogen donor properties, AOA, and methods and approaches used to reveal biological activities of various groups of 1,4-DHPs are presented. Examples of DHPs antioxidant activities and protective effects of DHPs against OS induced damage in low density lipoproteins (LDL), mitochondria, microsomes, isolated cells, and cell cultures are highlighted. Comparison of the AOA of different DHPs and other antioxidants is also given. According to the data presented, the DHPs might be considered as bellwether among synthetic compounds targeting OS and potential pharmacological model compounds targeting oxidative stress important for medicinal chemistry.

  17. High conservation of a 5' element required for RNA editing of a C target in chloroplast psbE transcripts.

    PubMed

    Hayes, Michael L; Hanson, Maureen R

    2008-09-01

    C-to-U editing modifies 30-40 distinct nucleotides within higher-plant chloroplast transcripts. Many C targets are located at the same position in homologous genes from different plants; these either could have emerged independently or could share a common origin. The 5' sequence GCCGUU, required for editing of C214 in tobacco psbE in vitro, is one of the few identified editing cis-elements. We investigated psbE sequences from many plant species to determine in what lineage(s) editing of psbE C214 emerged and whether the cis-element identified in tobacco is conserved in plants with a C214. The GCCGUU sequence is present at a high frequency in plants that carry a C214 in psbE. However, Sciadopitys verticillata (Pinophyta) edits C214 despite the presence of nucleotide differences compared to the conserved cis-element. The C214 site in psbE genes is represented in members of four branches of spermatophytes but not in gnetophytes, resulting in the parsimonious prediction that editing of psbE C214 was present in the ancestor of spermatophytes. Extracts from chloroplasts from a species that has a difference in the motif and lacks the C target are incapable of editing tobacco psbE C214 substrates, implying that the critical trans-acting protein factors were not retained without a C target. Because noncoding sequences are less constrained than coding regions, we analyzed sequences 5' to two C editing targets located within coding regions to search for possible editing-related conserved elements. Putative editing cis-elements were uncovered in the 5' UTRs near editing sites psbL C2 and ndhD C2.

  18. Elemental mercury oxidation and adsorption on magnesite powder modified by Mn at low temperature.

    PubMed

    Xu, Yalin; Zhong, Qin; Liu, Xinya

    2015-01-01

    Mn modified the commercial magnesite powder prepared by wet impregnation method has been shown to be effective for gas-phase elemental mercury (Hg(0)) removal at low temperatures. The prepared samples are characterized in detail across multiform techniques: XRF, BET, SEM-EDX, XRD, H2-TPR, and XPS, and all the results show that the amorphous MnO2 impregnated on magnesite powder improves the removal efficiency of Hg(0). Through further analysis by TG and in situ FTIR, the reasonable removal mechanism is also speculated. The results indicate that chemisorbed oxygen is an important reactant in the heterogeneous reaction, and gas-phase Hg(0) is adsorbed and then oxidized to solid MnHgO3 on the surface of the adsorbent.

  19. Targeting Transporters: Promoting Blood-Brain Barrier Repair in Response to Oxidative Stress Injury

    PubMed Central

    Ronaldson, Patrick T.; Davis, Thomas P.

    2015-01-01

    The blood-brain barrier (BBB) is a physical and biochemical barrier that precisely regulates the ability of endogenous and exogenous substances to accumulate within brain tissue. It possesses structural and biochemical features (i.e., tight junction and adherens junction protein complexes, influx and efflux transporters) that work in concert to control solute permeation. Oxidative stress, a critical component of several diseases including cerebral hypoxia/ischemia and peripheral inflammatory pain, can cause considerable injury to the BBB and lead to significant CNS pathology. This suggests a critical need for novel therapeutic approaches that can protect the BBB in diseases with an oxidative stress component. Recent studies have identified molecular targets (i.e., endogenous transporters, intracellular signaling systems) that can be exploited for optimization of endothelial drug delivery or for control of transport of endogenous substrates such as the antioxidant glutathione (GSH). In particular, targeting transporters offers a unique approach to protect BBB integrity by promoting repair of cell-cell interactions at the level of the brain microvascular endothelium. This review summarizes current knowledge in this area and emphasizes those targets that present considerable opportunity for providing BBB protection and/or promoting BBB repair in the setting of oxidative stress. PMID:25796436

  20. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

    PubMed Central

    Forte, Maurizio; Damato, Antonio; Ambrosio, Mariateresa; Puca, Annibale A.; Sciarretta, Sebastiano; Frati, Giacomo; Vecchione, Carmine

    2016-01-01

    Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases. PMID:27651855

  1. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases.

    PubMed

    Forte, Maurizio; Conti, Valeria; Damato, Antonio; Ambrosio, Mariateresa; Puca, Annibale A; Sciarretta, Sebastiano; Frati, Giacomo; Vecchione, Carmine; Carrizzo, Albino

    2016-01-01

    Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases.

  2. Exposure to PM2.5 in modern office buildings through elemental characterization and oxidative potential

    NASA Astrophysics Data System (ADS)

    Szigeti, Tamás; Kertész, Zsófia; Dunster, Christina; Kelly, Frank J.; Záray, Gyula; Mihucz, Victor G.

    2014-09-01

    Fifty samples of indoor and outdoor PM2.5 were collected onto quartz fiber and Teflon membrane filters in five office buildings equipped with heating, ventilation and air-conditioning system for 8 h daily in order to coincide with the work shift of employees. Samples were analyzed for i) mass concentration; ii) elemental concentration; and iii) oxidative potential (OP) through antioxidant depletion. The PM2.5 mass concentration exceeded the annual mean guideline of 10 μg m-3 WHO in 50% of the samples. Indoor and outdoor PM2.5 mass concentrations correlated almost linearly. Proton-induced X-ray emission (PIXE) spectrometry was used for the monitoring of 21 elements. Quantitative determination was achieved in the case of Teflon filters only for Al, Si, S, Cl, K, Ca, Ti, Cr, Mn, Fe and Zn at ng m-3 concentration level. Quartz fiber filters were less adequate for the PIXE measurements due to their greater thickness and filamentary structure. Ca, Cr, Zn and Ti had generally higher concentration (mg g-1) indoors. Indoor/outdoor (I/O) OP values were higher than one in 14% and 57% of the samples in the case of ascorbate and reduced glutathione (GSH), respectively. Spatial and temporal variations of OP were observed across the office buildings. The I/O ratios for OP, Cr and Zn concentrations in the case of GSH were higher for three buildings. Significant relationship was observed between GSH oxidation and Cr and Zn concentrations. Thus, employees were exposed to a higher extent to reactive oxygen species in three buildings.

  3. The impact of electrogenic sulfide oxidation on elemental cycling and solute fluxes in coastal sediment

    NASA Astrophysics Data System (ADS)

    Rao, Alexandra M. F.; Malkin, Sairah Y.; Hidalgo-Martinez, Silvia; Meysman, Filip J. R.

    2016-01-01

    Filamentous sulfide oxidizing cable bacteria are capable of linking the oxidation of free sulfide in deep anoxic layers of marine sediments to the reduction of oxygen or nitrate in surface sediments by conducting electrons over centimeter-scale distances. Previous studies have shown that this newly discovered microbial process, referred to as electrogenic sulfide oxidation (e-SOx), may alter elemental cycling in sediments, but the nature and rates of the resulting biogeochemical transformations and their influence on benthic-pelagic coupling remain largely unknown. Here we quantify changes in sediment geochemistry and solute fluxes at the sediment-water interface as e-SOx develops and declines over time in laboratory incubations of organic-rich sediments from a seasonally hypoxic coastal basin (Marine Lake Grevelingen, The Netherlands). Our results show that e-SOx enhanced sediment O2 consumption and acidified subsurface sediment, resulting in the dissolution of calcium carbonate and iron sulfide minerals in deeper sediment horizons and the associated accumulation of dissolved iron, manganese, and calcium in porewater. Remobilized Fe diffusing upward was reoxidized at the sediment-water interface, producing an amorphous Fe oxide crust, while dissolved Fe diffusing downward was reprecipitated in the form of FeS as it encountered the free sulfide horizon. The development of e-SOx enhanced the diffusive release of dissolved Mn at the sediment-water interface, capped the phosphate efflux, generated a buildup of organic matter in surface sediments, and strongly stimulated the release of alkalinity from the sediment. About 75% of this alkalinity production was associated with net CaCO3 dissolution, while the remaining 25% was attributed to a pumping mechanism that transfers alkalinity from anodic H2S oxidation (an alkalinity sink) in deeper sediments to cathodic O2 reduction (an alkalinity source) near the sediment-water interface. The resulting sediment alkalinity

  4. DSSylation, a novel protein modification targets proteins induced by oxidative stress, and facilitates their degradation in cells.

    PubMed

    Zhang, Yinghao; Chang, Fang-Mei; Huang, Jianjun; Junco, Jacob J; Maffi, Shivani K; Pridgen, Hannah I; Catano, Gabriel; Dang, Hong; Ding, Xiang; Yang, Fuquan; Kim, Dae Joon; Slaga, Thomas J; He, Rongqiao; Wei, Sung-Jen

    2014-02-01

    Timely removal of oxidatively damaged proteins is critical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein modification that may play a role in targeting oxidized proteins and remove them. In this process, DSS1 (deleted in split hand/split foot 1), an evolutionally conserved small protein, is conjugated to proteins induced by oxidative stresses in vitro and in vivo, implying oxidized proteins are DSS1 clients. A subsequent ubiquitination targeting DSS1-protein adducts has been observed, suggesting the client proteins are degraded through the ubiquitin-proteasome pathway. The DSS1 attachment to its clients is evidenced to be an enzymatic process modulated by an unidentified ATPase. We name this novel protein modification as DSSylation, in which DSS1 plays as a modifier, whose attachment may render target proteins a signature leading to their subsequent ubiquitination, thereby recruits proteasome to degrade them.

  5. A novel pre-oxidation method for elemental mercury removal utilizing a complex vaporized absorbent.

    PubMed

    Zhao, Yi; Hao, Runlong; Guo, Qing

    2014-09-15

    A novel semi-dry integrative method for elemental mercury (Hg(0)) removal has been proposed in this paper, in which Hg(0) was initially pre-oxidized by a vaporized liquid-phase complex absorbent (LCA) composed of a Fenton reagent, peracetic acid (CH3COOOH) and sodium chloride (NaCl), after which Hg(2+) was absorbed by the resultant Ca(OH)2. The experimental results indicated that CH3COOOH and NaCl were the best additives for Hg(0) oxidation. Among the influencing factors, the pH of the LCA and the adding rate of the LCA significantly affected the Hg(0) removal. The coexisting gases, SO2 and NO, were characterized as either increasing or inhibiting in the removal process, depending on their concentrations. Under optimal reaction conditions, the efficiency for the single removal of Hg(0) was 91%. Under identical conditions, the efficiencies of the simultaneous removal of SO2, NO and Hg(0) were 100%, 79.5% and 80.4%, respectively. Finally, the reaction mechanism for the simultaneous removal of SO2, NO and Hg(0) was proposed based on the characteristics of the removal products as determined by X-ray diffraction (XRD), atomic fluorescence spectrometry (AFS), the analysis of the electrode potentials, and through data from related research references.

  6. A graphene oxide-based strand displacement amplification platform for ricin detection using aptamer as recognition element.

    PubMed

    Li, Chun Hong; Xiao, Xue; Tao, Jing; Wang, Dong Mei; Huang, Cheng Zhi; Zhen, Shu Jun

    2017-05-15

    The toxic plant protein ricin is a potential agent for criminal or bioterrorist attacks due to the wide availability and relative ease of preparation. Herein, we developed a novel strategy for the detection of ricin B-chain (RTB) based on isothermal strand-displacement polymerase reaction (ISDPR) by using aptamer as a recognition element and graphene oxide (GO) as a low background platform. In this method, ricin-binding aptamer (RBA) hybridized with a short blocker firstly, and then was immobilized on the surface of streptavidin-coated magnetic beads (MBs). The addition of RTB could release the blocker, which could hybridize with the dye-modified hairpin probe and trigger the ISDPR, resulting in high fluorescence intensity. In the absence of RTB, however, the fluorescence of the dye could be quenched strongly by GO, resulting in the extremely low background signal. Thus, RTB could be sensitively detected by the significantly increased fluorescence signal. The linear range of the current analytical system was from 0.75μg/mL to 100μg/mL and the limit of detection (3σ) was 0.6μg/mL. This method has been successfully utilized for the detection of both the RTB and the entire ricin toxin in real samples, and it could be generalized to any kind of target detection based on an appropriate aptamer.

  7. Rotating target wheel system for super-heavy element production at ATLAS

    NASA Astrophysics Data System (ADS)

    Greene, John P.; Heinz, Andreas; Falout, Joe; Janssens, Robert V. F.

    2004-03-01

    A new scattering chamber housing a large diameter rotating target wheel has been designed and constructed in front of the Fragment Mass Analyzer (FMA) for the production of very heavy nuclei ( Z>100) using beams from the Argonne Tandem Linear Accelerator System (ATLAS). In addition to the target and drive system, the chamber is extensively instrumented in order to monitor target performance and deterioration. Capabilities also exist to install rotating entrance and exit windows for gas cooling of the target within the scattering chamber. The design and initial tests are described.

  8. Effects of nanoparticle zinc oxide on emotional behavior and trace elements homeostasis in rat brain.

    PubMed

    Amara, Salem; Slama, Imen Ben; Omri, Karim; El Ghoul, Jaber; El Mir, Lassaad; Rhouma, Khemais Ben; Abdelmelek, Hafedh; Sakly, Mohsen

    2015-12-01

    Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain.

  9. DEVELOPMENT OF LOW-COST MANUFACTURING PROCESSES FOR PLANAR, MULTILAYER SOLID OXIDE FUEL CELL ELEMENTS

    SciTech Connect

    Scott Swartz; Matthew Seabaugh; William Dawson; Harlan Anderson; Tim Armstrong; Michael Cobb; Kirby Meacham; James Stephan; Russell Bennett; Bob Remick; Chuck Sishtla; Scott Barnett; John Lannutti

    2004-06-12

    This report summarizes the results of a four-year project, entitled, ''Low-Cost Manufacturing Of Multilayer Ceramic Fuel Cells'', jointly funded by the U.S. Department of Energy, the State of Ohio, and by project participants. The project was led by NexTech Materials, Ltd., with subcontracting support provided by University of Missouri-Rolla, Michael A. Cobb & Co., Advanced Materials Technologies, Inc., Edison Materials Technology Center, Gas Technology Institute, Northwestern University, and The Ohio State University. Oak Ridge National Laboratory, though not formally a subcontractor on the program, supported the effort with separate DOE funding. The objective of the program was to develop advanced manufacturing technologies for making solid oxide fuel cell components that are more economical and reliable for a variety of applications. The program was carried out in three phases. In the Phase I effort, several manufacturing approaches were considered and subjected to detailed assessments of manufacturability and development risk. Estimated manufacturing costs for 5-kW stacks were in the range of $139/kW to $179/kW. The risk assessment identified a number of technical issues that would need to be considered during development. Phase II development work focused on development of planar solid oxide fuel cell elements, using a number of ceramic manufacturing methods, including tape casting, colloidal-spray deposition, screen printing, spin-coating, and sintering. Several processes were successfully established for fabrication of anode-supported, thin-film electrolyte cells, with performance levels at or near the state-of-the-art. The work in Phase III involved scale-up of cell manufacturing methods, development of non-destructive evaluation methods, and comprehensive electrical and electrochemical testing of solid oxide fuel cell materials and components.

  10. Photochemical Oxidation of Dissolved Elemental Mercury by Carbonate Radicals in Water

    SciTech Connect

    He, Feng; Zhao, Weirong; Liang, Liyuan; Gu, Baohua

    2014-11-11

    Photochemical oxidation of dissolved elemental mercury [Hg(0)] affects mercury chemical speciation and its transfer at the water-air interface in the aquatic environment. The mechanisms and factors that control Hg(0) photooxidation, however, are not completely understood, especially in natural freshwaters containing dissolved organic matter (DOM) and carbonate. Here, we evaluate Hg(0) photooxidation rates affected by various reactive ionic species [e.g., DOM, CO32-, NO3-] and free radicals in a creek water and a phosphate buffer solution (pH=8) under simulated solar irradiation. We report a high Hg(0) photooxidation rate (k = 1.44 h-1) in the presence of both HCO32- and NO3-, whereas HCO32-, NO3-, or DOM alone increased the oxidation rate slightly (k = 0.1 0.17 h-1). Using scavengers and enhancers for singlet oxygen (1O2) and hydroxyl (HO ) radicals, as well as electron paramagnetic resonance spectroscopy, we identify that carbonate radicals (CO3 ∙-) primarily drive the Hg(0) photooxidation, whereas addition of DOM resulted in a 2-fold decrease in Hg(0) oxidation. This study identifies an unrecognized pathway of Hg(0) photooxidation by CO3 ∙- radicals and the inhibitory effect of DOM, which could be important in assessing Hg transformation and fate in water containing carbonate such as hard water and seawater.

  11. Sulfur-Oxidizing Bacteria Mediate Microbial Community Succession and Element Cycling in Launched Marine Sediment.

    PubMed

    Ihara, Hideyuki; Hori, Tomoyuki; Aoyagi, Tomo; Takasaki, Mitsuru; Katayama, Yoko

    2017-01-01

    A large amount of marine sediment was launched on land by the Great East Japan earthquake. Here, we employed both on-site and laboratory studies on the launched marine sediment to investigate the succession of microbial communities and its effects on geochemical properties of the sediment. Twenty-two-month on-site survey showed that microbial communities at the uppermost layer (0-2 mm depth) of the sediment changed significantly with time, whereas those at the deeper layer (20-40 mm depth) remained nearly unchanged and kept anaerobic microbial communities. Nine months after the incidence, various sulfur-oxidizing bacteria (SOB) prevailed in the uppermost layer, in which afterwards diverse chemoorganotrophic bacteria predominated. Geochemical analyses indicated that the concentration of metals other than Fe was lower in the uppermost layer than that in the deeper layer. Laboratory study was carried out by incubating the sediment for 57 days, and clearly indicated the dynamic transition of microbial communities in the uppermost layer exposed to atmosphere. SOB affiliated in the class Epsilonproteobacteria rapidly proliferated and dominated at the uppermost layer during the first 3 days, after that Fe(II)-oxidizing bacteria and chemoorganotrophic bacteria were sequentially dominant. Furthermore, the concentration of sulfate ion increased and the pH decreased. Consequently, SOB may have influenced the mobilization of heavy metals in the sediment by metal-bound sulfide oxidation and/or sediment acidification. These results demonstrate that SOB initiated the dynamic shift from the anaerobic to aerobic microbial communities, thereby playing a critical role in element cycling in the marine sediment.

  12. Sulfur-Oxidizing Bacteria Mediate Microbial Community Succession and Element Cycling in Launched Marine Sediment

    PubMed Central

    Ihara, Hideyuki; Hori, Tomoyuki; Aoyagi, Tomo; Takasaki, Mitsuru; Katayama, Yoko

    2017-01-01

    A large amount of marine sediment was launched on land by the Great East Japan earthquake. Here, we employed both on-site and laboratory studies on the launched marine sediment to investigate the succession of microbial communities and its effects on geochemical properties of the sediment. Twenty-two-month on-site survey showed that microbial communities at the uppermost layer (0–2 mm depth) of the sediment changed significantly with time, whereas those at the deeper layer (20–40 mm depth) remained nearly unchanged and kept anaerobic microbial communities. Nine months after the incidence, various sulfur-oxidizing bacteria (SOB) prevailed in the uppermost layer, in which afterwards diverse chemoorganotrophic bacteria predominated. Geochemical analyses indicated that the concentration of metals other than Fe was lower in the uppermost layer than that in the deeper layer. Laboratory study was carried out by incubating the sediment for 57 days, and clearly indicated the dynamic transition of microbial communities in the uppermost layer exposed to atmosphere. SOB affiliated in the class Epsilonproteobacteria rapidly proliferated and dominated at the uppermost layer during the first 3 days, after that Fe(II)-oxidizing bacteria and chemoorganotrophic bacteria were sequentially dominant. Furthermore, the concentration of sulfate ion increased and the pH decreased. Consequently, SOB may have influenced the mobilization of heavy metals in the sediment by metal-bound sulfide oxidation and/or sediment acidification. These results demonstrate that SOB initiated the dynamic shift from the anaerobic to aerobic microbial communities, thereby playing a critical role in element cycling in the marine sediment. PMID:28217124

  13. ICAM-1 targeted catalase encapsulated PLGA-b-PEG nanoparticles against vascular oxidative stress.

    PubMed

    Sari, Ece; Tunc-Sarisozen, Yeliz; Mutlu, Hulya; Shahbazi, Reza; Ucar, Gulberk; Ulubayram, Kezban

    2015-01-01

    Targeted delivery of therapeutics is the favourable idea, whereas it is possible to distribute the therapeutically active drug molecule only to the site of action. For this purpose, in this study, catalase encapsulated poly(D,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles were developed and an endothelial target molecule (anti-ICAM-1) was conjugated to this carrier system in order to decrease the oxidative stress level in the target site. According to the enzymatic activity results, initial catalase activity of nanoparticles was increased from 27.39 U/mg to up to 45.66 U/mg by adding 5 mg/mL bovine serum albumin (BSA). After 4 h, initial catalase activity was preserved up to 46.98% while free catalase retained less than 4% of its activity in proteolytic environment. Furthermore, FITC labelled anti-ICAM-1 targeted catalase encapsulated nanoparticles (anti-ICAM-1/CatNPs) were rapidly taken up by cultured endothelial cells and concomitantly endothelial cells were resistant to H2O2 induced oxidative impairment.

  14. Erlotinib-Conjugated Iron Oxide Nanoparticles as a Smart Cancer-Targeted Theranostic Probe for MRI

    NASA Astrophysics Data System (ADS)

    Ali, Ahmed Atef Ahmed; Hsu, Fei-Ting; Hsieh, Chia-Ling; Shiau, Chia-Yang; Chiang, Chiao-Hsi; Wei, Zung-Hang; Chen, Cheng-Yu; Huang, Hsu-Shan

    2016-11-01

    We designed and synthesized novel theranostic nanoparticles that showed the considerable potential for clinical use in targeted therapy, and non-invasive real-time monitoring of tumors by MRI. Our nanoparticles were ultra-small with superparamagnetic iron oxide cores, conjugated to erlotinib (FeDC-E NPs). Such smart targeted nanoparticles have the preference to release the drug intracellularly rather than into the bloodstream, and specifically recognize and kill cancer cells that overexpress EGFR while being non-toxic to EGFR-negative cells. MRI, transmission electron microscopy and Prussian blue staining results indicated that cellular uptake and intracellular accumulation of FeDC-E NPs in the EGFR overexpressing cells was significantly higher than those of the non-erlotinib-conjugated nanoparticles. FeDC-E NPs inhibited the EGFR–ERK–NF-κB signaling pathways, and subsequently suppressed the migration and invasion capabilities of the highly invasive and migrative CL1-5-F4 cancer cells. In vivo tumor xenograft experiments using BALB/c nude mice showed that FeDC-E NPs could effectively inhibit the growth of tumors. T2-weighted MRI images of the mice showed significant decrease in the normalized signal within the tumor post-treatment with FeDC-E NPs compared to the non-targeted control iron oxide nanoparticles. This is the first study to use erlotinib as a small-molecule targeting agent for nanoparticles.

  15. Erlotinib-Conjugated Iron Oxide Nanoparticles as a Smart Cancer-Targeted Theranostic Probe for MRI

    PubMed Central

    Ali, Ahmed Atef Ahmed; Hsu, Fei-Ting; Hsieh, Chia-Ling; Shiau, Chia-Yang; Chiang, Chiao-Hsi; Wei, Zung-Hang; Chen, Cheng-Yu; Huang, Hsu-Shan

    2016-01-01

    We designed and synthesized novel theranostic nanoparticles that showed the considerable potential for clinical use in targeted therapy, and non-invasive real-time monitoring of tumors by MRI. Our nanoparticles were ultra-small with superparamagnetic iron oxide cores, conjugated to erlotinib (FeDC-E NPs). Such smart targeted nanoparticles have the preference to release the drug intracellularly rather than into the bloodstream, and specifically recognize and kill cancer cells that overexpress EGFR while being non-toxic to EGFR-negative cells. MRI, transmission electron microscopy and Prussian blue staining results indicated that cellular uptake and intracellular accumulation of FeDC-E NPs in the EGFR overexpressing cells was significantly higher than those of the non-erlotinib-conjugated nanoparticles. FeDC-E NPs inhibited the EGFR–ERK–NF-κB signaling pathways, and subsequently suppressed the migration and invasion capabilities of the highly invasive and migrative CL1-5-F4 cancer cells. In vivo tumor xenograft experiments using BALB/c nude mice showed that FeDC-E NPs could effectively inhibit the growth of tumors. T2-weighted MRI images of the mice showed significant decrease in the normalized signal within the tumor post-treatment with FeDC-E NPs compared to the non-targeted control iron oxide nanoparticles. This is the first study to use erlotinib as a small-molecule targeting agent for nanoparticles. PMID:27833124

  16. Nuclear factor erythroid 2-related factor 2 signaling in Parkinson disease: a promising multi therapeutic target against oxidative stress, neuroinflammation and cell death.

    PubMed

    Kumar, Hemant; Koppula, Sushruta; Kim, In-Su; More, Sandeep Vasant; Kim, Byung-Wook; Choi, Dong-Kug

    2012-12-01

    Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder with increased oxidative stress as central component. Till date, treatments related to PD are based on restoring dopamine either by targeting neurotransmitter and/or at receptor levels. These therapeutic approaches try to repair damage but do not address the underlying processes such as oxidative stress and neuroinflammation that contribute to cell death. The central nervous system maintains a robust antioxidant defense mechanism consisting of several cytoprotective genes and enzymes whose expression is controlled by antioxidant response element (ARE) which further depends on activation of nuclear factor erythroid 2-related factor 2 (Nrf2). In response to oxidative or electrophilic stress transcription factor Nrf2 binds to ARE and rescues the cells from oxidative stress and neuroinflammation. Recently, Nrf2 has been utilized as a drug target and some agents are currently under clinical trial. Owing to the potential role of Nrf2 in counteracting oxidative stress and neuroinflammation seen in PD, here we have focused on the molecular mechanism of the Nrf2/ARE antioxidant defense pathway in PD. Further, we also summarize published reports on the potential inducers of Nrf2 that demonstrate neuroprotective effects in experimental models of PD with possible future strategies to increase the transcriptional level of Nrf2 as a therapeutic strategy to provide neuroprotection of damaged dopaminergic neurons in PD.

  17. An in silico strategy identified the target gene candidates regulated by dehydration responsive element binding proteins (DREBs) in Arabidopsis genome.

    PubMed

    Wang, Shichen; Yang, Shuo; Yin, Yuejia; Guo, Xiaosen; Wang, Shan; Hao, Dongyun

    2009-01-01

    Identification of downstream target genes of stress-relating transcription factors (TFs) is desirable in understanding cellular responses to various environmental stimuli. However, this has long been a difficult work for both experimental and computational practices. In this research, we presented a novel computational strategy which combined the analysis of the transcription factor binding site (TFBS) contexts and machine learning approach. Using this strategy, we conducted a genome-wide investigation into novel direct target genes of dehydration responsive element binding proteins (DREBs), the members of AP2-EREBPs transcription factor super family which is reported to be responsive to various abiotic stresses in Arabidopsis. The genome-wide searching yielded in total 474 target gene candidates. With reference to the microarray data for abiotic stresses-inducible gene expression profile, 268 target gene candidates out of the total 474 genes predicted, were induced during the 24-h exposure to abiotic stresses. This takes about 57% of total predicted targets. Furthermore, GO annotations revealed that these target genes are likely involved in protein amino acid phosphorylation, protein binding and Endomembrane sorting system. The results suggested that the predicted target gene candidates were adequate to meet the essential biological principle of stress-resistance in plants.

  18. Oxidative Stress: A New Target for Pancreatic Cancer Prognosis and Treatment

    PubMed Central

    Martinez-Useros, Javier; Li, Weiyao; Cabeza-Morales, Marticela; Garcia-Foncillas, Jesus

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumors, and its incidence is rising worldwide. Survival can be improved when tumors are detected at an early stage; however, this cancer is usually asymptomatic, and the disease only becomes apparent after metastasis. Several risk factors are associated to this disease. Chronic pancreatitis, diabetes, and some infectious disease are the most relevant risk factors. Incidence of PDAC has increased in the last decades. It is hypothesized it could be due to other acquired risk habits, like smoking, high alcohol intake, and obesity. Indeed, adipose tissue is a dynamic endocrine organ that secretes different pro-inflammatory cytokines, enzymes, and other factors that activate oxidative stress. Reactive oxygen species caused by oxidative stress, damage DNA, proteins, and lipids, and produce several toxic and high mutagenic metabolites that could modify tumor behavior, turning it into a malignant phenotype. Anti-oxidant compounds, like vitamins, are considered protective factors against cancer. Here, we review the literature on oxidative stress, the molecular pathways that activate or counteract oxidative stress, and potential treatment strategies that target reactive oxygen species suitable for this kind of cancer. PMID:28282928

  19. Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease.

    PubMed

    Ruiz, Stacey; Pergola, Pablo E; Zager, Richard A; Vaziri, Nosratola D

    2013-06-01

    Oxidative stress and inflammation are mediators in the development and progression of chronic kidney disease (CKD) and its complications, and they are inseparably linked as each begets and amplifies the other. CKD-associated oxidative stress is due to increased production of reactive oxygen species (ROS) and diminished antioxidant capacity. The latter is largely caused by impaired activation of Nrf2, the transcription factor that regulates genes encoding antioxidant and detoxifying molecules. Protective effects of Nrf2 are evidenced by amelioration of oxidative stress, inflammation, and kidney disease in response to natural Nrf2 activators in animal models, while Nrf2 deletion amplifies these pathogenic pathways and leads to autoimmune nephritis. Given the role of impaired Nrf2 activity in CKD-induced oxidative stress and inflammation, interventions aimed at restoring Nrf2 may be effective in retarding CKD progression. Clinical trials of the potent Nrf2 activator bardoxolone methyl showed significant improvement in renal function in CKD patients with type 2 diabetes. However, due to unforeseen complications the BEACON trial, which was designed to investigate the effect of this drug on time to end-stage renal disease or cardiovascular death in patients with advanced CKD, was prematurely terminated. This article provides an overview of the role of impaired Nrf2 activity in the pathogenesis of CKD-associated oxidative stress and inflammation and the potential utility of targeting Nrf2 in the treatment of CKD.

  20. Deciphering dynamic dose responses of natural promoters and single cis elements upon osmotic and oxidative stress in yeast.

    PubMed

    Dolz-Edo, Laura; Rienzo, Alessandro; Poveda-Huertes, Daniel; Pascual-Ahuir, Amparo; Proft, Markus

    2013-06-01

    Fine-tuned activation of gene expression in response to stress is the result of dynamic interactions of transcription factors with specific promoter binding sites. In the study described here we used a time-resolved luciferase reporter assay in living Saccharomyces cerevisiae yeast cells to gain insights into how osmotic and oxidative stress signals modulate gene expression in a dose-sensitive manner. Specifically, the dose-response behavior of four different natural promoters (GRE2, CTT1, SOD2, and CCP1) reveals differences in their sensitivity and dynamics in response to different salt and oxidative stimuli. Characteristic dose-response profiles were also obtained for artificial promoters driven by only one type of stress-regulated consensus element, such as the cyclic AMP-responsive element, stress response element, or AP-1 site. Oxidative and osmotic stress signals activate these elements separately and with different sensitivities through different signaling molecules. Combination of stress-activated cis elements does not, in general, enhance the absolute expression levels; however, specific combinations can increase the inducibility of the promoter in response to different stress doses. Finally, we show that the stress tolerance of the cell critically modulates the dynamics of its transcriptional response in the case of oxidative stress.

  1. Targeting NADPH Oxidase Decreases Oxidative Stress in the Transgenic Sickle Cell Mouse Penis

    PubMed Central

    Musicki, Biljana; Liu, Tongyun; Sezen, Sena F.; Burnett, Arthur L.

    2012-01-01

    Introduction Sickle cell disease (SCD) is a state of chronic vasculopathy characterized by endothelial dysfunction and increased oxidative stress, but the sources and mechanisms responsible for reactive oxygen species (ROS) production in the penis are unknown. Aims We evaluated whether SCD activates NADPH oxidase, induces endothelial nitric oxide synthase (eNOS) uncoupling, and decreases antioxidants in the SCD mouse penis. We further tested the hypothesis that targeting NADPH oxidase decreases oxidative stress in the SCD mouse penis. Methods SCD transgenic (sickle) mice were used as an animal model of SCD. Hemizygous (hemi) mice served as controls. Mice received an NADPH oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Penes were excised at baseline for molecular studies. Markers of oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NADPH oxidase subunits p67phox, p47phox, and gp91phox), and enzymatic antioxidants (superoxide dismutase [SOD]1, SOD2, catalase, and glutathione peroxidase-1 [GPx1]) were measured by Western blot in penes. Main Outcome Measures Sources of ROS, oxidative stress, and enzymatic antioxidants in the SCD penis. Results Relative to hemi mice, SCD increased (P < 0.05) protein expression of NADPH oxidase subunits p67phox, p47phox, and gp91phox, 4-HNE-modified proteins, induced eNOS uncoupling, and reduced Gpx1 expression in the penis. Apocynin treatment of sickle mice reversed (P < 0.05) the abnormalities in protein expressions of p47phox, gp91phox (but not p67phox) and 4-HNE, but only slightly (P > 0.05) prevented eNOS uncoupling in the penis. Apocynin treatment of hemi mice did not affect any of these parameters. Conclusion NADPH oxidase and eNOS uncoupling are sources of oxidative stress in the SCD penis; decreased GPx1 further contributes to oxidative stress. Inhibition of NADPH oxidase upregulation decreases oxidative stress, implying a major role for NADPH oxidase as a ROS source and a

  2. A specific Ce oxidation process during sorption of rare earth elements on biogenic Mn oxide produced by Acremonium sp. strain KR21-2

    NASA Astrophysics Data System (ADS)

    Tanaka, Kazuya; Tani, Yukinori; Takahashi, Yoshio; Tanimizu, Masaharu; Suzuki, Yoshinori; Kozai, Naofumi; Ohnuki, Toshihiko

    2010-10-01

    Sorption of rare earth elements (REEs) and Ce oxidation on natural and synthetic Mn oxides have been investigated by many researchers. Although Mn(II)-oxidizing microorganisms are thought to play an important role in the formation of Mn oxides in most natural environments, Ce oxidation by biogenic Mn oxide and the relevance of microorganisms to the Ce oxidation process have not been well understood. Therefore, in this study, we conducted sorption experiments of REEs on biogenic Mn oxide produced by Acremonium sp. strain KR21-2. The distribution coefficients, Kd(REE), between biogenic Mn oxide (plus hyphae) and 10 mmol/L NaCl solution showed a large positive Ce anomaly and convex tetrad effect variations at pH 3.8, which was consistent with previous works using synthetic Mn oxide. The positive Ce anomaly was caused by oxidation of Ce(III) to Ce(IV) by the biogenic Mn oxide, which was confirmed by analysis of the Ce L III-edge XANES spectra. With increasing pH, the positive Ce anomaly and convex tetrad effects became less pronounced. Furthermore, negative Ce anomalies were observed at a pH of more than 6.5, suggesting that Ce(IV) was stabilized in the solution (<0.2 μm) phase, although Ce(III) oxidation to Ce(IV) on the biogenic Mn oxide was confirmed by XANES analysis. It was demonstrated that no Ce(III) oxidation occurred during sorption on the hyphae of strain KR21-2 by the Kd(REE) patterns and XANES analysis. The analysis of size exclusion HPLC-ICP-MS showed that some fractions of REEs in the filtrates (<0.2 μm) after sorption experiments were bound to organic molecules (40 and <670 kDa fractions), which were possibly released from hyphae. A line of our data indicates that the negative Ce anomalies under circumneutral pH conditions arose from Ce(III) oxidation on the biogenic Mn oxide and subsequent complexation of Ce(IV) with organic ligands. The suppression of tetrad effects is also explained by the complexation of REEs with organic ligands. The results of

  3. Binding and Internalization of Iron Oxide Nanoparticles Targeted to Nuclear Oncoprotein

    PubMed Central

    Knight, Linda C.; Romano, Jan E.; Krynska, Barbara; Faro, Scott; Mohamed, Feroze B.; Gordon, Jennifer

    2013-01-01

    A targeted nanoconjugate is being developed for non-invasive detection of gene expression in cells expressing the JC virus oncoprotein, T-antigen, which has been associated with medulloblastoma and other cancers. JC virus T-antigen localizes predominantly to the nucleus via a classical monopartite nuclear localization signal (NLS). An antibody fragment which recognizes JC virus T-antigen was attached to cross-linked dextran coated iron oxide nanoparticles. Radiolabeled conjugates were added to mouse medulloblastoma cells expressing the target T-antigen to test their ability to bind to tumor cells and be internalized by the cells. All conjugates containing targeting antibody bound to cells and were internalized, with increasing levels over time. There was no difference in cell binding or internalization among conjugates containing 2, 4, 6 or 8 antibody fragments per nanoparticle. Conjugates with only nonspecific antibody on nanoparticles, or unconjugated nonspecific antibody, had significantly lower total binding and internalization than conjugates with targeting antibody. Unconjugated targeting antibody had equivalent or lower cell uptake compared with targeted nanoparticle conjugates. Specificity of uptake was demonstrated by >80% reduction of nanoconjugate uptake in the presence of 100 fold excess of unconjugated antibody. The presence of a membrane translocation peptide (Tat) on the nanoparticles in addition to targeting antibody did not improve nanoconjugate internalization over the internalization caused by the antibody alone. This antibody nanoconjugate demonstrates feasibility of targeting a nuclear protein and suggests that a minimum number of antibody fragments per nanoparticle are sufficient for achieving binding specificity and efficient uptake into living cells. PMID:23487404

  4. Targeted Nitric Oxide Delivery by Supramolecular Nanofibers for the Prevention of Restenosis After Arterial Injury

    PubMed Central

    Bahnson, Edward S.M.; Kassam, Hussein A.; Moyer, Tyson J.; Jiang, Wulin; Morgan, Courtney E.; Vercammen, Janet M.; Jiang, Qun; Flynn, Megan E.; Stupp, Samuel I.

    2016-01-01

    Abstract Aims: Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. We sought to develop and evaluate a systemically delivered nanostructure targeted to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues. Results: Structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescent detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl [SNO])-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation. Innovation: This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects. Conclusion: We successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases. Antioxid. Redox Signal. 27, 401–418. PMID:26593400

  5. Targeted nitric oxide delivery by supramolecular nanofibers for the prevention of restenosis after arterial injury

    SciTech Connect

    Bahnson, Edward S. M.; Kassam, Hussein A.; Moyer, Tyson J.; Jiang, Wulin; Morgan, Courtney E.; Vercammen, Janet M.; Jiang, Qun; Flynn, Megan E.; Stupp, Samuel I.; Kibbe, Melina R.

    2016-01-21

    Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. Here we sought to develop and evaluate a systemically delivered nanostructure targeted to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues. As a result, structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescent detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl [SNO])-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation. This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects. In conclusion, we successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases

  6. Targeted nitric oxide delivery by supramolecular nanofibers for the prevention of restenosis after arterial injury

    DOE PAGES

    Bahnson, Edward S. M.; Kassam, Hussein A.; Moyer, Tyson J.; ...

    2016-01-21

    Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. Here we sought to develop and evaluate a systemically delivered nanostructure targeted to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues. As a result, structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescentmore » detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl [SNO])-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation. This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects. In conclusion, we successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases« less

  7. Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes.

    PubMed

    Yang, Ji Hye; Shin, Bo Yeon; Han, Jae Yun; Kim, Mi Gwang; Wi, Ji Eun; Kim, Young Woo; Cho, Il Je; Kim, Sang Chan; Shin, Sang Mi; Ki, Sung Hwan

    2014-01-15

    Isorhamentin is a 3'-O-methylated metabolite of quercetin, and has been reported to have anti-inflammatory and anti-proliferative effects. However, the effects of isorhamnetin on Nrf2 activation and on the expressions of its downstream genes in hepatocytes have not been elucidated. Here, we investigated whether isorhamnetin has the ability to activate Nrf2 and induce phase II antioxidant enzyme expression, and to determine the protective role of isorhamnetin on oxidative injury in hepatocytes. In HepG2 cells, isorhamnetin increased the nuclear translocation of Nrf2 in a dose- and time-dependent manner, and consistently, increased antioxidant response element (ARE) reporter gene activity and the protein levels of hemeoxygenase (HO-1) and of glutamate cysteine ligase (GCL), which resulted in intracellular GSH level increases. The specific role of Nrf2 in isorhamnetin-induced Nrf2 target gene expression was verified using an ARE-deletion mutant plasmid and Nrf2-knockout MEF cells. Deletion of the ARE in the promoter region of the sestrin2 gene, which is recently identified as the Nrf2 target gene by us, abolished the ability of isorhamnetin to increase luciferase activity. In addition, Nrf2 deficiency completely blocked the ability of isorhamnetin to induce HO-1 and GCL. Furthermore, isorhamnetin pretreatment blocked t-BHP-induced ROS production and reversed GSH depletion by t-BHP and consequently, due to reduced ROS levels, decreased t-BHP-induced cell death. In addition isorhamnetin increased ERK1/2, PKCδ and AMPK phosphorylation. Finally, we showed that Nrf2 deficiency blocked the ability of isorhamnetin to protect cells from injury induced by t-BHP. Taken together, our results demonstrate that isorhamnetin is efficacious in protecting hepatocytes against oxidative stress by Nrf2 activation and in inducing the expressions of its downstream genes.

  8. Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes

    SciTech Connect

    Yang, Ji Hye; Shin, Bo Yeon; Han, Jae Yun; Kim, Mi Gwang; Wi, Ji Eun; Kim, Young Woo; Cho, Il Je; Kim, Sang Chan; Shin, Sang Mi; Ki, Sung Hwan

    2014-01-15

    Isorhamentin is a 3′-O-methylated metabolite of quercetin, and has been reported to have anti-inflammatory and anti-proliferative effects. However, the effects of isorhamnetin on Nrf2 activation and on the expressions of its downstream genes in hepatocytes have not been elucidated. Here, we investigated whether isorhamnetin has the ability to activate Nrf2 and induce phase II antioxidant enzyme expression, and to determine the protective role of isorhamnetin on oxidative injury in hepatocytes. In HepG2 cells, isorhamnetin increased the nuclear translocation of Nrf2 in a dose- and time-dependent manner, and consistently, increased antioxidant response element (ARE) reporter gene activity and the protein levels of hemeoxygenase (HO-1) and of glutamate cysteine ligase (GCL), which resulted in intracellular GSH level increases. The specific role of Nrf2 in isorhamnetin-induced Nrf2 target gene expression was verified using an ARE-deletion mutant plasmid and Nrf2-knockout MEF cells. Deletion of the ARE in the promoter region of the sestrin2 gene, which is recently identified as the Nrf2 target gene by us, abolished the ability of isorhamnetin to increase luciferase activity. In addition, Nrf2 deficiency completely blocked the ability of isorhamnetin to induce HO-1 and GCL. Furthermore, isorhamnetin pretreatment blocked t-BHP-induced ROS production and reversed GSH depletion by t-BHP and consequently, due to reduced ROS levels, decreased t-BHP-induced cell death. In addition isorhamnetin increased ERK1/2, PKCδ and AMPK phosphorylation. Finally, we showed that Nrf2 deficiency blocked the ability of isorhamnetin to protect cells from injury induced by t-BHP. Taken together, our results demonstrate that isorhamnetin is efficacious in protecting hepatocytes against oxidative stress by Nrf2 activation and in inducing the expressions of its downstream genes. - Highlights: • We investigated the effect of isorhamnetin on Nrf2 activation. • Isorhamnetin increased Nrf2

  9. Lactoferrin conjugated iron oxide nanoparticles for targeting brain glioma cells in magnetic particle imaging

    NASA Astrophysics Data System (ADS)

    Tomitaka, Asahi; Arami, Hamed; Gandhi, Sonu; Krishnan, Kannan M.

    2015-10-01

    Magnetic Particle Imaging (MPI) is a new real-time imaging modality, which promises high tracer mass sensitivity and spatial resolution directly generated from iron oxide nanoparticles. In this study, monodisperse iron oxide nanoparticles with median core diameters ranging from 14 to 26 nm were synthesized and their surface was conjugated with lactoferrin to convert them into brain glioma targeting agents. The conjugation was confirmed with the increase of the hydrodynamic diameters, change of zeta potential, and Bradford assay. Magnetic particle spectrometry (MPS), performed to evaluate the MPI performance of these nanoparticles, showed no change in signal after lactoferrin conjugation to nanoparticles for all core diameters, suggesting that the MPI signal is dominated by Néel relaxation and thus independent of hydrodynamic size difference or presence of coating molecules before and after conjugations. For this range of core sizes (14-26 nm), both MPS signal intensity and spatial resolution improved with increasing core diameter of nanoparticles. The lactoferrin conjugated iron oxide nanoparticles (Lf-IONPs) showed specific cellular internalization into C6 cells with a 5-fold increase in MPS signal compared to IONPs without lactoferrin, both after 24 h incubation. These results suggest that Lf-IONPs can be used as tracers for targeted brain glioma imaging using MPI.

  10. Vented target elements for use in an isotope-production reactor. [LMFBR

    DOEpatents

    Cawley, W.E.; Omberg, R.P.

    1982-08-19

    A method is described for producing tritium gas in a fast breeder reactor cooled with liquid metal. Lithium target material is placed in pins equipped with vents, and tritium gas is recovered from the coolant.

  11. Combining Hi-C data with phylogenetic correlation to predict the target genes of distal regulatory elements in human genome.

    PubMed

    Lu, Yulan; Zhou, Yuanpeng; Tian, Weidong

    2013-12-01

    Defining the target genes of distal regulatory elements (DREs), such as enhancer, repressors and insulators, is a challenging task. The recently developed Hi-C technology is designed to capture chromosome conformation structure by high-throughput sequencing, and can be potentially used to determine the target genes of DREs. However, Hi-C data are noisy, making it difficult to directly use Hi-C data to identify DRE-target gene relationships. In this study, we show that DREs-gene pairs that are confirmed by Hi-C data are strongly phylogenetic correlated, and have thus developed a method that combines Hi-C read counts with phylogenetic correlation to predict long-range DRE-target gene relationships. Analysis of predicted DRE-target gene pairs shows that genes regulated by large number of DREs tend to have essential functions, and genes regulated by the same DREs tend to be functionally related and co-expressed. In addition, we show with a couple of examples that the predicted target genes of DREs can help explain the causal roles of disease-associated single-nucleotide polymorphisms located in the DREs. As such, these predictions will be of importance not only for our understanding of the function of DREs but also for elucidating the causal roles of disease-associated noncoding single-nucleotide polymorphisms.

  12. Refinement of adsorptive coatings for fluorescent riboflavin-receptor-targeted iron oxide nanoparticles.

    PubMed

    Tsvetkova, Yoanna; Beztsinna, Nataliia; Jayapaul, Jabadurai; Weiler, Marek; Arns, Susanne; Shi, Yang; Lammers, Twan; Kiessling, Fabian

    2016-01-01

    Flavin mononucleotide (FMN) is a riboflavin derivative that can be exploited to target the riboflavin transporters (RFTs) and the riboflavin carrier protein (RCP) in cells with high metabolic activity. In this study we present the synthesis of different FMN-coated ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) and their efficiency as targeting contrast agents. Since FMN alone cannot stabilize the nanoparticles, we used adenosine phosphates--AMP, ADP and ATP--as spacers to obtain colloidally stable nanoparticles. Nucleotides with di- and triphosphate groups were intended to increase the USPIO charge and thus improve zeta potential and stability. However, all nanoparticles formed negatively charged clusters with similar properties in terms of zeta potential (-28 ± 2 mV), relaxivity (228-259 mM(-1) s(-1) at 3 T) and hydrodynamic radius (53-85 nm). Molecules with a higher number of phosphate groups, such as ADP and ATP, have a higher adsorption affinity towards iron oxide, which, instead of providing more charge, led to partial desorption and replacement of FMN. Hence, we obtained USPIOs carrying different amounts of targeting agent, which significantly influenced the nanoparticles' uptake. The nanoparticles' uptake by different cancer cells and HUVECs was evaluated photometrically and with MR relaxometry, showing that the cellular uptake of the USPIOs increases with the FMN amount on their surface. Thus, for USPIOs targeted with riboflavin derivatives the use of spacers with increasing numbers of phosphate groups does not improve either zeta potential or the particles' stability, but rather detaches the targeting moieties from their surface, leading to lower cellular uptake.

  13. Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

    NASA Astrophysics Data System (ADS)

    Huang, Ya-Shu; Lu, Yu-Jen; Chen, Jyh-Ping

    2017-04-01

    A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe3O4 magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which 60% of DOX was released at pH 5.4 and 10% was released at pH 7.4. In contrast, 90% CPT-11 was released at pH 5.4 and 70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy.

  14. Heavy-Ion Irradiation of Thulium(III) Oxide Targets Prepared by Polymer-Assisted Deposition

    SciTech Connect

    Garcia, Mitch A.; Ali, Mazhar N.; Chang, Noel N.; Parsons-Moss, Tashi; Ashby, Paul D.; Gates, Jacklyn M.; Stavsetra, Liv; Gregorich, Kenneth E.; Nitsche, Heino

    2008-09-15

    Thulium(III) oxide (Tm{sub 2}O{sub 3}) targets prepared by the polymer-assisted deposition (PAD) method were irradiated by heavy-ion beams to test the method's feasibility for nuclear science applications. Targets were prepared on silicon nitride backings (thickness of 1000 nm, 344 {micro}g/cm{sup 2}) and were irradiated with an {sup 40}Ar beam at laboratory frame energy of {approx}210 MeV (50 particle nA). The root mean squared (RMS) roughness prior to irradiation is 1.1 nm for a {approx}250 nm ({approx}220 {micro}g/cm{sup 2}) Tm{sub 2}O{sub 3} target, and an RMS roughness of 2.0 nm after irradiation was measured by atomic force microscopy (AFM). Scanning electron microscopy of the irradiated target reveals no significant differences in surface homogeneity when compared to imaging prior to irradiation. Target flaking was not observed from monitoring Rutherford scattered particles as a function of time.

  15. Mesoporous Silica Coated Polydopamine Functionalized Reduced Graphene Oxide for Synergistic Targeted Chemo-Photothermal Therapy.

    PubMed

    Shao, Leihou; Zhang, Ruirui; Lu, Jianqing; Zhao, Caiyan; Deng, Xiongwei; Wu, Yan

    2017-01-18

    The integration of different therapies into a single nanoplatform has shown great promise for synergistic tumor treatment. Herein, mesoporous silica (MS) coated polydopamine functionalized reduced graphene oxide (pRGO) further modified with hyaluronic acid (HA) (pRGO@MS-HA) has been utilized as a versatile nanoplatform for synergistic targeted chemo-photothermal therapy against cancer. A facile and green chemical method is adopted for the simultaneous reduction and noncovalent functionalization of graphene oxide (GO) by using mussel inspired dopamine (DA) to enhance biocompatibility and the photothermal effect. Then, it was coated with mesoporous silica (MS) (pRGO@MS) to enhance doxorubicin (DOX) loading and be further modified with the targeting moieties hyaluronic acid (HA). The pH-dependent and near-infrared (NIR) laser irradiation-triggered DOX release from pRGO@MS(DOX)-HA is observed, which could enhance the chemo-photothermal therapy effect. In vitro experimental results confirm that pRGO@MS(DOX)-HA exhibits good dispersibility, excellent photothermal property, remarkable tumor cell killing efficiency, and specificity to target tumor cells. In vivo antitumor experiments further demonstrated that pRGO@MS(DOX)-HA could exhibit an excellent synergistic antitumor efficacy, which is much more distinct than any monotherapy. This work presents a novel nanoplatform which could load chemotherapy drugs with high efficiency and be used as light-mediated photothermal cancer therapy agent.

  16. Electrospun metal oxide-TiO2 nanofibers for elemental mercury removal from flue gas.

    PubMed

    Yuan, Yuan; Zhao, Yongchun; Li, Hailong; Li, Yang; Gao, Xiang; Zheng, Chuguang; Zhang, Junying

    2012-08-15

    Nanofibers prepared by an electrospinning method were used to remove elemental mercury (Hg(0)) from simulated coal combustion flue gas. The nanofibers composed of different metal oxides (MO(x)) including CuO, In(2)O(3), V(2)O(5), WO(3) and Ag(2)O supported on TiO(2) have been characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), energy dispersing X-ray (EDX) and UV-vis spectra. The average diameters of these nanofibers were about 200nm. Compared to pure TiO(2), the UV-vis absorption intensity for MO(x)-TiO(2) increased significantly and the absorption bandwidth also expanded, especially for Ag(2)O-TiO(2) and V(2)O(5)-TiO(2). Hg(0) oxidation efficiencies over the MO(x)-TiO(2) nanofibers were tested under dark, visible light (vis) irradiation and UV irradiation, respectively. The results showed that WO(3) doped TiO(2) exhibited the highest Hg(0) removal efficiency of 100% under UV irradiation. Doping V(2)O(5) into TiO(2) enhanced Hg(0) removal efficiency greatly from 6% to 63% under visible light irradiation. Ag(2)O doped TiO(2) showed a steady Hg(0) removal efficiency of around 95% without any light due to the formation of silver amalgam. An extended experiment with 8 Hg(0) removal cycles showed that the MO(x)-TiO(2) nanofibers were stable for removing Hg(0) from flue gas. Factors responsible for the enhanced photocatalytic activities of the MO(x)-TiO(2) nanofibers were also discussed.

  17. The Thermodynamic Properties of the f-Elements and their Compounds. Part 2. The Lanthanide and Actinide Oxides

    SciTech Connect

    Konings, Rudy J. M. Beneš, Ondrej; Kovács, Attila; Manara, Dario; Sedmidubský, David; Gorokhov, Lev; Iorish, Vladimir S.; Yungman, Vladimir; Shenyavskaya, E.; Osina, E.

    2014-03-15

    A comprehensive review of the thermodynamic properties of the oxide compounds of the lanthanide and actinide elements is presented. The available literature data for the solid, liquid, and gaseous state have been analysed and recommended values are presented. In case experimental data are missing, estimates have been made based on the trends in the two series, which are extensively discussed.

  18. Treatment-Resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy

    PubMed Central

    Zorumski, Charles F.; Nagele, Peter; Mennerick, Steven; Conway, Charles R.

    2015-01-01

    Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15–30% of MDD patients. There has been recent interest in N-methyl-d-aspartate receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine’s utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant. PMID:26696909

  19. A multi-element screening method to identify metal targets for blood biomonitoring in green sea turtles (Chelonia mydas).

    PubMed

    Villa, C A; Finlayson, S; Limpus, C; Gaus, C

    2015-04-15

    Biomonitoring of blood is commonly used to identify and quantify occupational or environmental exposure to chemical contaminants. Increasingly, this technique has been applied to wildlife contaminant monitoring, including for green turtles, allowing for the non-lethal evaluation of chemical exposure in their nearshore environment. The sources, composition, bioavailability and toxicity of metals in the marine environment are, however, often unknown and influenced by numerous biotic and abiotic factors. These factors can vary considerably across time and space making the selection of the most informative elements for biomonitoring challenging. This study aimed to validate an ICP-MS multi-element screening method for green turtle blood in order to identify and facilitate prioritisation of target metals for subsequent fully quantitative analysis. Multi-element screening provided semiquantitative results for 70 elements, 28 of which were also determined through fully quantitative analysis. Of the 28 comparable elements, 23 of the semiquantitative results had an accuracy between 67% and 112% relative to the fully quantified values. In lieu of any available turtle certified reference materials (CRMs), we evaluated the use of human blood CRMs as a matrix surrogate for quality control, and compared two commonly used sample preparation methods for matrix related effects. The results demonstrate that human blood provides an appropriate matrix for use as a quality control material in the fully quantitative analysis of metals in turtle blood. An example for the application of this screening method is provided by comparing screening results from blood of green turtles foraging in an urban and rural region in Queensland, Australia. Potential targets for future metal biomonitoring in these regions were identified by this approach.

  20. Association of Serum Concentration of Different Trace Elements with Biomarkers of Systemic Oxidant Status in Dairy Cattle.

    PubMed

    Abuelo, Angel; Hernandez, Joaquín; Alves-Nores, Víctor; Benedito, José L; Castillo, Cristina

    2016-12-01

    There has been some recent criticism about the reliability of the assays commonly used to measure oxidant status in cattle, because some recent publications suggested that the concentration of different trace elements influences the results of these assays. The aim of this study was to test the correlation in 502 bovine serum samples between the concentration of several trace elements (Br, Co, Cr, Cu, Fe, I, Mn, Mo, Ni, Se, Sr, V and Zn) and markers of oxidant status (reactive oxygen species (ROS) and total serum antioxidant capacity (SAC)). The Oxidative Stress index (OSi) was also calculated as ROS/SAC. Some significant correlations were found, although weak (|ρ| < 0.50). Therefore, the relationships observed might be attributed to the different pro- and antioxidant effect of the different elements rather than to the assays detecting these elements instead of the oxidised molecules or total antioxidant potential, respectively. The OSi was poorly correlated (|ρ| ≤ 0.36) with the concentration of the studied trace elements, and therefore, its use is recommended to assess shifts in the systemic redox balance.

  1. Electrochemical and spectroscopic studies of some less stable oxidation states of selected lanthanide and actinide elements

    SciTech Connect

    Hobart, D. E.

    1981-06-01

    Simultaneous observation of electrochemical and spectroscopic properties (spectroelectrochemistry) at optically transparent electrodes (OTE's) was used to study some less stable oxidation states of selected lanthanide and actinide elements. Cyclic voltammetry at microelectrodes was used in conjunction with spectroelectrochemistry for the study of redox couples. Additional analytical techniques were used. The formal reduction potential (E/sup 0/') values of the M(III)/M(II) redox couples in 1 M KCl at pH 6 were -0.34 +- 0.01 V for Eu, -1.18 +- 0.01 V for Yb, and -1.50 +- 0.01 V for Sm. Spectropotentiostatic determination of E/sup 0/' for the Eu(III)/Eu(II) redox couple yielded a value of -0.391 +- 0.005 V. Spectropotentiostatic measurement of the Ce(IV)/Ce(III) redox couple in concentrated carbonate solution gave E/sup 0/' equal to 0.051 +- 0.005 V, which is about 1.7 V less positive than the E/sup 0/' value in noncomplexing solution. This same difference in potential was observed for the E/sup 0/' values of the Pr(IV)/Pr(III) and Tb(IV)/Tb(III) redox couples in carbonate solution, and thus Pr(IV) and Tb(IV) were stabilized in this medium. The U(VI)/U(V)/U(IV) and U(IV)/U(III) redox couples were studied in 1 M KCl at OTE's. Spectropotentiostatic measurement of the Np(VI)/Np(V) redox couple in 1 M HClO/sub 4/ gave an E/sup 0/' value of 1.140 +- 0.005 V. An E/sup 0/' value of 0.46 +- 0.01 V for the Np(VII)/Np(VI) couple was found by voltammetry. Oxidation of Am(III) was studied in concentrated carbonate solution, and a reversible cyclic voltammogram for the Am(IV)/Am(III) couple yielded E/sup 0/' = 0.92 +- 0.01 V in this medium; this value was used to estimate the standard reduction potential (E/sup 0/) of the couple as 2.62 +- 0.01 V. Attempts to oxidize Cm(III) in concentrated carbonate solution were not successful which suggests that the predicted E/sup 0/ value for the Cm(IV)/Cm(III) redox couple may be in error.

  2. Evaluation of BOC'S Lotox Process for the Oxidation of Elemental Mercury in Flue Gas from a Coal-Fired Boiler

    SciTech Connect

    Khalid Omar

    2008-04-30

    Linde's Low Temperature Oxidation (LoTOx{trademark}) process has been demonstrated successfully to remove more than 90% of the NOx emitted from coal-fired boilers. Preliminary findings have shown that the LoTOx{trademark} process can be as effective for mercury emissions control as well. In the LoTOx{trademark} system, ozone is injected into a reaction duct, where NO and NO{sub 2} in the flue gas are selectively oxidized at relatively low temperatures and converted to higher nitrogen oxides, which are highly water soluble. Elemental mercury in the flue gas also reacts with ozone to form oxidized mercury, which unlike elemental mercury is water-soluble. Nitrogen oxides and oxidized mercury in the reaction duct and residual ozone, if any, are effectively removed in a wet scrubber. Thus, LoTOx{trademark} appears to be a viable technology for multi-pollutant emission control. To prove the feasibility of mercury oxidation with ozone in support of marketing LoTOx{trademark} for multi-pollutant emission control, Linde has performed a series of bench-scale tests with simulated flue gas streams. However, in order to enable Linde to evaluate the performance of the process with a flue gas stream that is more representative of a coal-fired boiler; one of Linde's bench-scale LoTOx{trademark} units was installed at WRI's combustion test facility (CTF), where a slipstream of flue gas from the CTF was treated. The degree of mercury and NOx oxidation taking place in the LoTOx{trademark} unit was quantified as a function of ozone injection rates, reactor temperatures, residence time, and ranks of coals. The overall conclusions from these tests are: (1) over 80% reduction in elemental mercury and over 90% reduction of NOx can be achieved with an O{sub 3}/NO{sub X} molar ratio of less than two, (2) in most of the cases, a lower reactor temperature is preferred over a higher temperature due to ozone dissociation, however, the combination of both low residence time and high temperature

  3. Targeting Prostate Cancer Cells by Combined Oxidative Stress Induction and Androgen Receptor Antagonism

    DTIC Science & Technology

    2015-08-01

    Enzalutamide (Enz, MDV-3100) and EPI-001 derived hybrid drugs that target AR C-terminal ligand binding domain or N-terminal domain meanwhile inducing...oxidative stress. Five classes of hybrid drugs have been designed and synthesized, i.e. Enz-PL (e.g. compd 28), Enz-catechol (e.g., compds 29, 30), Enz...established in collaborator’s lab and will be used to study novel multifunctional hybrid drugs . Effects of Enz and piperlongumine (PL) on LAPC4 cell

  4. A targeted drug delivery system based on dopamine functionalized nano graphene oxide

    NASA Astrophysics Data System (ADS)

    Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

    2017-01-01

    The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

  5. Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy

    PubMed Central

    Huang, Peng; Xu, Cheng; Lin, Jing; Wang, Can; Wang, Xiansong; Zhang, Chunlei; Zhou, Xuejiao; Guo, Shouwu; Cui, Daxiang

    2011-01-01

    Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity. The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and π-π stacking. The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation. These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT. PMID:21562631

  6. Functionalized magnetic iron oxide/alginate core-shell nanoparticles for targeting hyperthermia

    PubMed Central

    Liao, Shih-Hsiang; Liu, Chia-Hung; Bastakoti, Bishnu Prasad; Suzuki, Norihiro; Chang, Yung; Yamauchi, Yusuke; Lin, Feng-Huei; Wu, Kevin C-W

    2015-01-01

    Hyperthermia is one of the promising treatments for cancer therapy. However, the development of a magnetic fluid agent that can selectively target a tumor and efficiently elevate temperature while exhibiting excellent biocompatibility still remains challenging. Here a new core-shell nanostructure consisting of inorganic iron oxide (Fe3O4) nanoparticles as the core, organic alginate as the shell, and cell-targeting ligands (ie, D-galactosamine) decorated on the outer surface (denoted as Fe3O4@Alg-GA nanoparticles) was prepared using a combination of a pre-gel method and coprecipitation in aqueous solution. After treatment with an AC magnetic field, the results indicate that Fe3O4@Alg-GA nanoparticles had excellent hyperthermic efficacy in a human hepatocellular carcinoma cell line (HepG2) owing to enhanced cellular uptake, and show great potential as therapeutic agents for future in vivo drug delivery systems. PMID:26005343

  7. Glycosaminoglycan-targeted iron oxide nanoparticles for magnetic resonance imaging of liver carcinoma.

    PubMed

    Yang, Rui-Meng; Fu, Chao-Ping; Li, Nan-Nan; Wang, Li; Xu, Xiang-Dong; Yang, Ding-Yan; Fang, Jin-Zhi; Jiang, Xin-Qing; Zhang, Li-Ming

    2014-12-01

    To develop an efficient probe for targeted magnetic resonance (MR) imaging of liver carcinoma, the surface modification of superparamagnetic iron oxide nanoparticles (SPIONs) was carried out by conjugating a naturally-occurring glycosaminoglycan with specific biological recognition to human hepatocellular liver carcinoma (HepG2) cells. These modified SPIOs have good water dispersibility, superparamagnetic property, cytocompatibility and high magnetic relaxivity for MR imaging. When incubated with HepG2 cells, they demonstrated significant cellular uptake and specific accumulation, as confirmed by Prussian blue staining and confocal microscopy. The in vitro MR imaging of HepG2 cells and in vivo MR imaging of HepG2 tumors confirmed their effectiveness for targeted MR imaging of liver carcinoma.

  8. Oxidative stress in muscular dystrophy: from generic evidence to specific sources and targets.

    PubMed

    Canton, Marcella; Menazza, Sara; Di Lisa, Fabio

    2014-02-01

    Muscular dystrophies (MDs) are a heterogeneous group of diseases that share a common end-point represented by muscular wasting. MDs are caused by mutations in a variety of genes encoding for different molecules, including extracellular matrix, transmembrane and membrane-associated proteins, cytoplasmic enzymes and nuclear proteins. However, it is still to be elucidated how genetic mutations can affect the molecular mechanisms underlying the contractile impairment occurring in these complex pathologies. The intracellular accumulation of reactive oxygen species (ROS) is widely accepted to play a key role in contractile derangements occurring in the different forms of MDs. However, scarce information is available concerning both the most relevant sources of ROS and their major molecular targets. This review focuses on (i) the sources of ROS, with a special emphasis on monoamine oxidase, a mitochondrial enzyme, and (ii) the targets of ROS, highlighting the relevance of the oxidative modification of myofilament proteins.

  9. Lactosylated poly(ethylene oxide)-poly(propylene oxide) block copolymers for potential active targeting: synthesis and physicochemical and self-aggregation characterization

    NASA Astrophysics Data System (ADS)

    Cuestas, María L.; Glisoni, Romina J.; Mathet, Verónica L.; Sosnik, Alejandro

    2013-01-01

    Aiming to develop polymeric self-assembly nanocarriers with potential applications in active drug targeting to the liver, linear and branched poly(ethylene oxide)-poly(propylene oxide) amphiphiles were conjugated to lactobionic acid (LA), a disaccharide of galactose and gluconic acid, by the conventional Steglich esterification reaction. The conjugation was confirmed by ATR/FT-IR, 1H-NMR, and 13C-NMR spectroscopy. Elemental analysis and MALDI-TOF mass spectrometry were employed to elucidate the conjugation extent and the final molecular weight, respectively. The critical micellar concentration (CMC), the size and size distribution and zeta potential of the pristine and modified polymeric micelles under different conditions of pH and temperature were characterized by dynamic light scattering (DLS). Conjugation with LA favored the micellization process, leading to a decrease of the CMC with respect to the pristine counterpart, this phenomenon being independent of the pH and the temperature. At 37 °C, micelles made of pristine copolymers showed a monomodal size distribution between 12.8 and 24.4 nm. Conversely, LA-conjugated micelles showed a bimodal size pattern that comprised a main fraction of relatively small size (11.6-22.2 nm) and a second one with remarkably larger sizes of up to 941.4 nm. The former corresponded to single micelles, while the latter would indicate a secondary aggregation phenomenon. The spherical morphology of LA-micelles was visualized by transmission electron microscopy (TEM). Finally, to assess the ability of the LA-conjugated micelles to interact with lectin-like receptors, samples were incubated with concanavalin A at 37 °C and the size and size distribution were monitored by DLS. Findings indicated that regardless of the relatively weak affinity of this vegetal lectin for galactose, micelles underwent agglutination probably through the interaction of a secondary site in the lectin with the gluconic acid unit of LA.

  10. Roles of Cationic and Elemental Calcium in the Electro-Reduction of Solid Metal Oxides in Molten Calcium Chloride

    NASA Astrophysics Data System (ADS)

    Qiu, Guohong; Jiang, Kai; Ma, Meng; Wang, Dihua; Jin, Xianbo; Chen, George Z.

    2007-06-01

    Previous work, mainly from this research group, is re-visited on electrochemical reduction of solid metal oxides, in the form of compacted powder, in molten CaCl2, aiming at further understanding of the roles of cationic and elemental calcium. The discussion focuses on six aspects: 1.) debate on two mechanisms proposed in the literature, i. e. electro-metallothermic reduction and electro-reduction (or electro-deoxidation), for the electrolytic removal of oxygen from solid metals or metal oxides in molten CaCl2; 2.) novel metallic cavity working electrodes for electrochemical investigations of compacted metal oxide powders in high temperature molten salts assisted by a quartz sealed Ag/AgCl reference electrode (650 ºC- 950 ºC); 3.) influence of elemental calcium on the background current observed during electrolysis of solid metal oxides in molten CaCl2; 4.) electrochemical insertion/ inclusion of cationic calcium into solid metal oxides; 5.) typical features of cyclic voltammetry and chronoamperometry (potentiostatic electrolysis) of metal oxide powders in molten CaCl2; and 6.) some kinetic considerations on the electrolytic removal of oxygen.

  11. Application of a sorbent trap system to gas-phase elemental and oxidized mercury analysis.

    PubMed

    Zhang, Zishuo; Eom, Yujin; Lee, Michelle J; Lee, Tai Gyu

    2016-07-01

    A sorbent trap that utilizes activated carbon (AC) as the solid trapping medium is a new technology for measuring total mercury (Hg) emissions from combustion facilities. In this study, sorbent trap technology was further developed, improved and evaluated at the laboratory scale. AC was impregnated with 5% aqua regia to enhance its Hg adsorption capacity. Sorbent traps spiked with an Hg standard solution were found to be reproducibly prepared and highly stable. The effect of the Hg concentration on the spiking efficiency was further investigated. The adsorption of elemental and oxidized Hg by the sorbent trap was studied under various experimental conditions (temperature, flow rate and inlet Hg concentration). The Hg concentration of the flue gas effluent from the sorbent trap was measured. In addition, the concentration of Hg adsorbed on the AC was determined by digesting the used AC with an acid according to US EPA method 3052 and then analyzing it with cold vapor atomic absorption spectrometry. Furthermore, the gas-phase Hg emissions from a combustion source were measured using the sorbent trap according to US EPA method 30B. The results showed that the sorbent trap could be used for Hg concentrations between 10.0 and 40.0 μg m(-3) and flow rates between 0.5 and 1.0 lpm with adsorption efficiencies greater than 90%.

  12. Review of behavior of mixed-oxide fuel elements in extended overpower transient tests in EBR-II

    SciTech Connect

    Tsai, H.; Neimark, L.A.; Nagai, S.; Nakae, N.

    1994-10-01

    From a series of five tests conducted in EBR-II, a substantial data base has been established on the performance of mixed-oxide fuel elements in a liquid-metal-cooled reactor under slow-ramp transient overpower conditions. Each test contained 19 preirradiated fuel elements with varying design and prior operating histories. Elements with aggressive design features, such as high fuel smear density and/or thin cladding, were included to accentuate transient effects. The ramp rates were either 0.1 or 10% {Delta}P/P/s and the overpowers ranged between {approx}60 and 100% of the elements` prior power ratings. Six elements breached during the tests, all with aggressive design parameters. The other elements, including all those with moderate design features for the reference or advanced long-life drivers for PNC`s prototype fast reactor Monju, maintained their cladding integrity during the tests. Posttest examination results indicated that fuel/cladding mechanical interaction (FCMI) was the most significant mechanism causing the cladding strain and breach. In contrast, pressure loading from the fission gas in the element plenum was less important, even in high-burnup elements. During an overpower transient, FCMI arises from fuel/cladding differential thermal expansion, transient fuel swelling, and, significantly, the gas pressure in the sealed central cavity of elements with substantial centerline fuel melting. Fuel performance data from these tests, including cladding breaching margin and transient cladding strain, are correlatable with fuel-element design and operating parameters. These correlations are being incorporated into fuel-element behavior codes. At the two tested ramp rates, fuel element behavior appears to be insensitive to transient ramp rate and there appears to be no particular vulnerability to slow ramp transients as previously perceived.

  13. Demystifying the secret mission of enhancers: linking distal regulatory elements to target genes

    PubMed Central

    Yao, Lijing; Berman, Benjamin P.; Farnham, Peggy J.

    2015-01-01

    Abstract Enhancers are short regulatory sequences bound by sequence-specific transcription factors and play a major role in the spatiotemporal specificity of gene expression patterns in development and disease. While it is now possible to identify enhancer regions genomewide in both cultured cells and primary tissues using epigenomic approaches, it has been more challenging to develop methods to understand the function of individual enhancers because enhancers are located far from the gene(s) that they regulate. However, it is essential to identify target genes of enhancers not only so that we can understand the role of enhancers in disease but also because this information will assist in the development of future therapeutic options. After reviewing models of enhancer function, we discuss recent methods for identifying target genes of enhancers. First, we describe chromatin structure-based approaches for directly mapping interactions between enhancers and promoters. Second, we describe the use of correlation-based approaches to link enhancer state with the activity of nearby promoters and/or gene expression. Third, we describe how to test the function of specific enhancers experimentally by perturbing enhancer–target relationships using high-throughput reporter assays and genome editing. Finally, we conclude by discussing as yet unanswered questions concerning how enhancers function, how target genes can be identified, and how to distinguish direct from indirect changes in gene expression mediated by individual enhancers. PMID:26446758

  14. Over Target Baseline: Lessons Learned from the NASA SLS Booster Element

    NASA Technical Reports Server (NTRS)

    Carroll, Truman J.

    2016-01-01

    Goal of the presentation is to teach, and then model, the steps necessary to implement an Over Target Baseline (OTB). More than a policy and procedure session, participants will learn from recent first hand experience the challenges and benefits that come from successfully executing an OTB.

  15. Downstream Regulatory Element Antagonist Modulator (DREAM), a target for anti-thrombotic agents.

    PubMed

    Cho, Jaehyung

    2017-03-01

    Circulating platelets participate in the process of numerous diseases including thrombosis, inflammation, and cancer. Thus, it is of great importance to understand the underlying mechanisms mediating platelet activation under disease conditions. Emerging evidence indicates that despite the lack of a nucleus, platelets possess molecules that are involved in gene transcription in nucleated cells. This review will summarize downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, and highlight recent findings suggesting its novel non-transcriptional role in hemostasis and thrombosis.

  16. Novel biomarkers of protein oxidation sites and degrees using horse cytochrome c as the target by mass spectrometry.

    PubMed

    Zong, Wansong; Liu, Rutao; Guo, Changying; Sun, Feng

    2011-05-01

    Biomarkers held both incredible application and significant challenge in probing the oxidation mechanisms of proteins under oxidative stress. Here, mass spectrometry (MS) coupled with liquid chromatography (LC) was applied to establish a new pipeline to probe the oxidation sites and degrees of horse cytochrome c (HCC) with its oxidative products serving as the biomarkers. Samples of native and UV/H(2)O(2) oxidized HCCs were digested by trypsin and subjected to biomarker discovery using LC/MS and tandem mass spectrometry (MS/MS). Experiment results proved that the main oxidation sites were located at Cys(14), Cys(17), Met(65) and Met(80) residues in peptides C(14)AQC(heme)HTVEK(22), C(14)AQCHTVEK(22), E(60)ETLMEYLENPKK(73), M(80)IFAGIK(86) and M(80)IFAGIKK(87). Quantitative analysis on the oxidized peptides showed the oxidation degrees of target sites had positive correlations with extended oxidation dose and controlled by residues types and their accessibility to solvent molecules. Being able to provide plentiful information for the oxidation sites and oxidation degrees, the identified oxidized products were feasibility biomarkers for HCC oxidation, compared with the conventional protein carbonyl assay.

  17. Selective Targeting of Heme Protein in Cytochrome P450 and Nitric Oxide Synthase by Diphenyleneiodonium.

    PubMed

    Szilagyi, John T; Mishin, Vladimir; Heck, Diane E; Jan, Yi-Hua; Aleksunes, Lauren M; Richardson, Jason R; Heindel, Ned D; Laskin, Debra L; Laskin, Jeffrey D

    2016-05-01

    Cytochrome P450 (CYP) enzymes mediate mixed-function oxidation reactions important in drug metabolism. The aromatic heterocyclic cation, diphenyleneiodonium (DPI), binds flavin in cytochrome P450 reductase and inhibits CYP-mediated activity. DPI also inhibits CYP by directly interacting with heme. Herein, we report that DPI effectively inhibits a number of CYP-related monooxygenase reactions including NADPH oxidase, a microsomal enzyme activity that generates hydrogen peroxide in the absence of metabolizing substrates. Inhibition of monooxygenase by DPI was time and concentration dependent with IC50's ranging from 0.06 to 1.9 μM. Higher (4.6-23.9 μM), but not lower (0.06-1.9 μM), concentrations of DPI inhibited electron flow via cytochrome P450 reductase, as measured by its ability to reduce cytochrome c and mediate quinone redox cycling. Similar results were observed with inducible nitric oxide synthase (iNOS), an enzyme containing a C-terminal reductase domain homologous to cytochrome P450 reductase that mediates reduction of cytochrome c, and an N-terminal heme-thiolate oxygenase domain mediating nitric oxide production. Significantly greater concentrations of DPI were required to inhibit cytochrome c reduction by iNOS (IC50 = 3.5 µM) than nitric oxide production (IC50 = 0.16 µM). Difference spectra of liver microsomes, recombinant CYPs, and iNOS demonstrated that DPI altered heme-carbon monoxide interactions. In the presence of NADPH, DPI treatment of microsomes and iNOS yielded a type II spectral shift. These data indicate that DPI interacts with both flavin and heme in CYPs and iNOS. Increased sensitivity for inhibition of CYP-mediated metabolism and nitric oxide production by iNOS indicates that DPI targets heme moieties within the enzymes.

  18. Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI

    PubMed Central

    Tarin, Carlos; Carril, Monica; Martin-Ventura, Jose Luis; Markuerkiaga, Irati; Padro, Daniel; Llamas-Granda, Patricia; Moreno, Juan Antonio; García, Isabel; Genicio, Nuria; Plaza-Garcia, Sandra; Blanco-Colio, Luis Miguel; Penades, Soledad; Egido, Jesus

    2015-01-01

    CD163 is a membrane receptor expressed by macrophage lineage. Studies performed in atherosclerosis have shown that CD163 expression is increased at inflammatory sites, pointing at the presence of intraplaque hemorrhagic sites or asymptomatic plaques. Hence, imaging of CD163 expressing macrophages is an interesting strategy in order to detect atherosclerotic plaques. We have prepared a targeted probe based on gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody for the specific detection of CD163 by MRI. Firstly, the specificity of the targeted probe was validated in vitro by incubation of the probe with CD163(+) or (−) macrophages. The probe was able to selectively detect CD163(+) macrophages both in human and murine cells. Subsequently, the targeted probe was injected in 16 weeks old apoE deficient mice developing atherosclerotic lesions and the pararenal abdominal aorta was imaged by MRI. The accumulation of probe in the site of interest increased over time and the signal intensity decreased significantly 48 hours after the injection. Hence, we have developed a highly sensitive targeted probe capable of detecting CD163-expressing macrophages that could provide useful information about the state of the atheromatous lesions. PMID:26616677

  19. Manganese G8 Dendrimers Targeted to Oxidation-Specific Epitopes: In vivo MR imaging of Atherosclerosis

    PubMed Central

    Nguyen, Tuyen H.; Bryant, Henry; Shapsa, Ari; Street, Hannah; Mani, Venkatesh; Fayad, Zahi A.; Frank, Joseph A.; Tsimikas, Sotirios; Briley-Saebo, Karen C.

    2014-01-01

    Objective To determine if manganese (Mn) G8 dendrimers targeted to oxidation-specific epitopes (OSE) allow for in vivo detection of atherosclerotic lesions. Background OSE have been identified as key factors in atherosclerotic plaque progression and destabilization. Mn offers a potentially clinically translatable alternative to gadolinium-based agents when bioretention and potential toxicity of gadolinium is anticipated. However, to be effective, high payloads of Mn must accumulate intracellularly in macrophages. It was hypothesized that G8 dendrimers targeted to OSE may allow delivery of high Mn payloads, thereby enabling in vivo detection of macrophage rich plaques. Methods G8 dendrimers were modified to allow conjugation with MnDTPA (758 Mn ion) and the antibody MDA2 that is targeted to malondialdehyde (MDA)-lysine epitopes. Both the untargeted and targeted G8 dendrimers were characterized and their in vivo efficacy evaluated in apoE-/- mice over a 96-hour time period after bolus administration of a 0.05 mmol Mn/kg dose using a clinical MR system (3 Tesla). Results Significant enhancement (normalized enhancement >60%, p=0.0013) of atherosclerotic lesions was observed within a 72-hour time period following administration of the targeted dendrimers. The presence of Mn within atherosclerotic lesions was confirmed using spectroscopic methods (>8 μg Mn/g). Limited signal attenuation (<18%) and Mn deposition (< 1 μg Mn/g) was observed in the arterial wall following injection of the untargeted material. Conclusions This study demonstrates that manganese labeled dendrimers, allowing a high Mn payload, targeted to OSE may allow in vivo image of atherosclerotic lesions. PMID:24610640

  20. Study of uranium oxide milling in order to obtain nanostructured UCx target

    NASA Astrophysics Data System (ADS)

    Guillot, Julien; Tusseau-Nenez, Sandrine; Roussière, Brigitte; Barré-Boscher, Nicole; Brisset, François; Mhamed, Maher Cheikh; Lau, Christophe; Nowak, Sophie

    2016-05-01

    A R&D program is developed at the ALTO facility to provide new beams of exotic neutron-rich nuclei, as intense as possible. In the framework of European projects, it has been shown that the use of refractory targets with nanometric structure allows us to obtain beams of nuclei unreachable until now. The first parameter to be controlled in the processing to obtain targets with a homogeneous nanostructure is the grinding of uranium dioxide, down to 100 nm grain size. In this study, dry and wet grinding routes are studied and the powders are analyzed in terms of phase stabilization, specific surface area and grain morphology. It appears that the grinding, as well dry as wet, leads to the decrease of the particle size. The oxidation of UO2 is observed whatever the grinding. However, the dry grinding is the most efficient and leads to the oxidation of UO2 into U4O9 and U3O7 whose quantities increase with the grinding time while crystallite sizes decrease.

  1. Targeting neuronal nitric oxide synthase as a valuable strategy for the therapy of neurological disorders

    PubMed Central

    Maccallini, Cristina; Amoroso, Rosa

    2016-01-01

    The management of neurological disorders have huge and increasing human and economic costs. Despite this, there is a scarcity of effective therapeutics, and there is an extreme urgency for new and real treatments. In this short review we analyze some promising advancements in the search of new bioactive molecules targeting neuronal nitric oxide synthase (nNOS), an enzyme deputed to the biosynthesis of nitric oxide (NO). In different conditions of neuronal damages, this molecule is overproduced, contributing to the pathogenesis and progression of neuronal diseases. Two main approaches to modulate nNOS are discussed: a first one consisting in the direct inhibition of the enzyme by means of small organic molecules, which can be also active against other different targets involved in such diseases. A second section is dedicated to molecules able to prevent the formation of the ternary complex N-methyl-D-aspartate (NMDA)-type glutamate receptors, postsynaptic density-95 (PSD95) protein-nNOS, which is necessary to activate the latter for the biosynthesis of NO. PMID:28123402

  2. Targeting a Regulatory Element in Human Thymidylate Synthase mRNA

    PubMed Central

    Brunn, Nicholas D.; Sega, Emily Garcia; Kao, Melody B.

    2013-01-01

    Thymidylate synthase (TS) is a key enzyme in the biosynthesis of thymidine. TS inhibitors, which are used in cancer chemotherapy, suffer from resistance development in tumors through upregulation of TS expression. Autoregulatory translation control has been implicated with TS overexpression. TS binding at its own mRNA, which leads to sequestration of the start codon, is abolished when the enzyme forms an inhibitor complex, thereby relieving translation suppression. We have used the protein binding site from the TS mRNA in the context of a bicistronic expression system to validate targeting the regulatory motif with stabilizing ligands that prevent ribosomal initiation. Stabilization of the RNA by mutations, which were studied as surrogates of ligand binding, suppresses translation of the TS protein. Compounds that stabilize the TS binding RNA motif and thereby inhibit ribosomal initiation might be used in combination with existing TS enzyme-targeting drugs to overcome resistance development during chemotherapy. PMID:23143777

  3. Ambient air particles: effects on cellular oxidant radical generation in relation to particulate elemental chemistry.

    PubMed

    Prahalad, A K; Soukup, J M; Inmon, J; Willis, R; Ghio, A J; Becker, S; Gallagher, J E

    1999-07-15

    Epidemiologic studies have reported causal relationships between exposures to high concentrations of ambient air particles (AAP) and increased morbidity in individuals with underlying respiratory problems. Polymorphonuclear leukocytes (PMN) are frequently present in the airways of individuals exposed to particles. Upon particulate stimulation the PMN may release reactive oxygen species (ROS), which can result in tissue damage and injury. In this study a wide range of AAP samples from divergent sources (1, natural dust; 2, oil fly ash; 2, coal fly ash; 5, ambient air; and 1, carbon black) were analyzed for elemental content and solubility in relation to their ability to generate ROS. Elemental analyses were carried out in AAP and dH(2)O-washed AAP using energy dispersive x-ray fluorescence (XRF). Percent of sample mass accounted for by XRF-detectable elements was 1.2% (carbon black); 22-29% (natural dust and ambient air particles); 13-22% (oil fly ash particles); 28-49% (coal fly ash particles). The major proportion of elements in most of these particles were aluminosilicates and insoluble iron, except oil-derived fly ash particles in which soluble vanadium and nickel were in highest concentrations, consistent with particle acidity as measured in the supernatants. Human blood-derived monocytes and PMN were exposed to AAP and dH(2)O-washed particles, and generation of ROS was determined using luminol-enhanced chemiluminescence (LCL) assay. All the particles induced chemiluminescence response in the cells, except carbon black. The oxidant response of monocytes induced by AAP (with the exception of oil fly ash particles) was less than the response elicited by PMN. The LCL response of PMN in general increased with all washed particles, with oil fly ash (OFA) and one urban air particle showing statistically significant (p < 0. 05) differences between dH(2)O-washed and unwashed particles. The LCL activity in PMN induced by both particles and dH(2)O-washed particles was

  4. Catalytic oxidation of elemental mercury over the modified catalyst Mn/alpha-Al2O3 at lower temperatures.

    PubMed

    Li, Jianfeng; Yan, Naiqiang; Qu, Zan; Qiao, Shaohua; Yang, Shijian; Guo, Yongfu; Liu, Ping; Jia, Jinping

    2010-01-01

    In order to facilitate the removal of elemental mercury (Hg(0)) from coal-fired flue gas, catalytic oxidation of Hg(0) with manganese oxides supported on inert alumina (alpha-Al2O3) was investigated at lower temperatures (373-473 K). To improve the catalytic activity and the sulfur-tolerance of the catalysts at lower temperatures, several metal elements were employed as dopants to modify the catalyst of Mn/alpha-Al2O3. The best performance among the tested elements was achieved with molybdenum (Mo) as the dopant in the catalysts. It can work even better than the noble metal catalyst Pd/alpha-Al2O3. Additionally, the Mo doped catalyst displayed excellent sulfur-tolerance performance at lower temperatures, and the catalytic oxidation efficiency for Mo(0.03)-Mn/alpha-Al2O3 was over 95% in the presence of 500 ppm SO2 versus only about 48% for the unmodified catalyst. The apparent catalytic reaction rate constant increased by approximately 5.5 times at 423 K. In addition, the possible mechanisms involved in Hg(0) oxidation and the reaction with the Mo modified catalyst have been discussed.

  5. Behaviors of trace elements in Neoarchean and Paleoproterozoic paleosols: Implications for atmospheric oxygen evolution and continental oxidative weathering

    NASA Astrophysics Data System (ADS)

    Murakami, Takashi; Matsuura, Kei; Kanzaki, Yoshiki

    2016-11-01

    The behaviors of redox-sensitive and/or bio-essential trace elements in Neoarchean and Paleoproterozoic paleosols (ancient weathering profiles) were investigated to better understand atmospheric oxygen evolution. The loss or retention of individual trace elements in the paleosols can show how continental oxidative weathering, and thus atmospheric oxygen evolution, took place against age mainly due to their various redox potentials. The V, Cr, Ni, Cu, Zn and Mo concentrations of two Paleoproterozoic paleosols were measured by inductively coupled plasma optical emission spectrometry and mass spectrometry, and those, as well as Co, W and U concentrations, of nine Neoarchean and Paleoproterozoic paleosols were obtained from the literature. The trace element behaviors were constrained by their degrees of loss or retention in the paleosols. We applied two methods to the estimation: (i) retention fraction of element M (a mass ratio of element M of paleosol to parent rock using immobile elements such as Ti) and (ii) element-element (in particular, Si-element) correlations at different profile depths of a paleosol. There are two distinct groups in trace element behavior in the Neoarchean and Paleoproterozoic paleosols: Co, Ni, Zn and W were lost from weathering profiles until the early Paleoproterozoic but retained in the middle and late Paleoproterozoic, while V, Cr, Cu, Mo and U were retained in the profiles until the early Paleoproterozoic or slightly later but lost from the profiles in the middle and late Paleoproterozoic. More precisely, the timings of such loss and retention were different between trace elements during the Paleoproterozoic. The characteristics of these changes from retention to loss or from loss to retention indicate that the changes occurred and lasted throughout the Paleoproterozoic. The trace element behaviors, accordingly, suggest that continental weathering became oxidative progressively with age during almost the whole Paleoproterozoic, and thus

  6. Autoregulation of fos: the dyad symmetry element as the major target of repression.

    PubMed Central

    König, H; Ponta, H; Rahmsdorf, U; Büscher, M; Schönthal, A; Rahmsdorf, H J; Herrlich, P

    1989-01-01

    Fos and Jun co-operatively repress the fos promoter. Removal of all putative Fos/Jun binding sites from the fos promoter neither obliterates the repression by Fos/Jun in transient cotransfection experiments in NIH3T3 cells nor the turn-off kinetics of serum-induced fos expression in stably transfected NIH3T3 cells. The dyad symmetry element (DSE) suffices to subject a promoter to this type of repression. However, one of the putative Fos/Jun binding sites (-292 to -299 and thus located immediately adjacent to the DSE), determines the very low level of basal expression. Images PMID:2511006

  7. Mitochondria are an early target of oxidative modifications in senescing legume nodules.

    PubMed

    Matamoros, Manuel A; Fernández-García, Nieves; Wienkoop, Stefanie; Loscos, Jorge; Saiz, Ana; Becana, Manuel

    2013-02-01

    Legume nodule senescence is a poorly understood process involving a decrease in N(2) fixation and an increase in proteolytic activity. Some physiological changes during nodule aging have been reported, but scarce information is available at the subcellular level. Biochemical, immunological and proteomic approaches were used to provide insight into the effects of aging on the mitochondria and cytosol of nodule host cells. In the mitochondria, the oxidative modification of lipids and proteins was associated with a marked decline in glutathione, a reduced capacity to regenerate ascorbate, and upregulation of alternative oxidase and manganese superoxide dismutase. In the cytosol, there were consistent reductions in the protein concentrations of carbon metabolism enzymes, inhibition of protein synthesis and increase in serine proteinase activity, disorganization of cytoskeleton, and a sharp reduction of cytosolic proteins, but no detectable accumulation of oxidized molecules. We conclude that nodule mitochondria are an early target of oxidative modifications and a likely source of redox signals. Alternative oxidase and manganese superoxide dismutase may play important roles in controlling ROS concentrations and the redox state of mitochondria. The finding that specific methionine residues of a cytosolic glutamine synthetase isoform are sulfoxidized suggests a regulatory role of this enzyme in senescing nodules.

  8. Uranium and minor-element partitioning in Fe-Ti oxides and zircon from partially melted granodiorite, Crater Lake, Oregon

    SciTech Connect

    La Tourrette, T.Z.; Burnett, D.S. ); Bacon C.R. )

    1991-02-01

    Crystal-liquid partitioning in Fe-Ti oxides and zircon was studied in partially melted granodiorite blocks ejected during the climactic eruption of Mt. Mazama (Crater Lake), Oregon. The blocks, which contain up to 33% rhyolite glass (75 wt% SiO{sub 2}), are interpreted to be portions of the magma chamber walls that were torn off during eruption. The glass is clear and well homogenized for all measured elements except Zr. Results for Fe-Ti oxides give D{sub U}{sup oxide/liq} {approx} 0.1. Partitioning of Mg, Mn, Al, Si, V, and Cr in Fe-Ti oxides indicates that grains surrounded by glass are modestly well equilibrated with the melt for many of the minor elements, while those that are inclusions in relict plagioclase are not. Uranium and ytterbium inhomogeneities in zircons indicate that the zircons have only partially equilibrated with the melt and that uranium appears to have been diffusing out of the zircons have only partially equilibrated with the melt and that uranium appears to have been diffusing out of the zircons faster that the zircons were dissolving. Based on the authors measurements and given their low abundances in most rocks, Fe-Ti oxides probably do not play a major role in U-Th fractional during partial melting. The partial melts were undersaturated with zircon and apatite, but both phases are present in the authors samples. This demonstrates an actual case of nonequilibrium source retention of accessory phases, which in general could be an important trace element fractionation mechanism. Their results do not support the hypothesis that liquid structure is the dominant factor controlling trace-element partitioning in high-silica rhyolites.

  9. Folatereceptor targeted, carboxymethyl chitosan functionalized iron oxide nanoparticles: a novel ultradispersed nanoconjugates for bimodal imaging

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Dipsikha; Das, Manasmita; Mishra, Debashis; Banerjee, Indranil; Sahu, Sumanta K.; Maiti, Tapas K.; Pramanik, Panchanan

    2011-04-01

    This article delineates the design and synthesis of a novel, bio-functionalized, magneto-fluorescent multifunctional nanoparticles suitable for cancer-specific targeting, detection and imaging. Biocompatible, hydrophilic, magneto-fluorescent nanoparticles with surface-pendant amine, carboxyl and aldehyde groups were designed using o-carboxymethyl chitosan (OCMC). The free aminegroups of OCMC stabilized magnetite nanoparticles on the surface allow for the covalent attachment of a fluorescent dye such as rhodamine isothiocyanate (RITC) with the aim to develop a magneto-fluorescent nanoprobe for optical imaging. In order to impart specific cancer cell targeting properties, folic acid and its aminated derivative was conjugated onto these magneto-fluorescent nanoparticles using different pendant groups (-NH2, -COOH, -CHO). These newly synthesized iron-oxide folate nanoconjugates (FA-RITC-OCMC-SPIONs) showed excellent dispersibility, biocompatibility and good hydrodynamic sizes under physiological conditions which were extensively studied by a variety of complementary techniques. The cellular internalization efficacy of these folate-targeted and its non-targeted counterparts were studied using a folate-overexpressed (HeLa) and a normal (L929fibroblast) cells by fluorescence microscopy and magnetically activated cell sorting (MACS). Cell-uptake behaviors of nanoparticles clearly demonstrate that cancer cells over-expressing the human folatereceptor internalized a higher level of these nanoparticle-folate conjugates than normal cells. These folate targeted nanoparticles possess specific magnetic properties in the presence of an external magnetic field and the potential of these nanoconjugates as T2-weighted negative contrast MR imaging agent were evaluated in folate-overexpressed HeLa and normal L929fibroblastcells.

  10. Targeted Iron-Oxide Nanoparticle for Photodynamic Therapy and Imaging of Head and Neck Cancer

    PubMed Central

    2015-01-01

    Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin β1. Then the PDT drug Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs demonstrated significantly greater inhibition of tumor growth than nontargeted IO-Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs have great potential to serve as both a magnetic resonance imaging (MRI) agent and PDT drug in the clinic. PMID:24923902

  11. Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer.

    PubMed

    Wang, Dongsheng; Fei, Baowei; Halig, Luma V; Qin, Xulei; Hu, Zhongliang; Xu, Hong; Wang, Yongqiang Andrew; Chen, Zhengjia; Kim, Sungjin; Shin, Dong M; Chen, Zhuo Georgia

    2014-07-22

    Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin β1. Then the PDT drug Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs demonstrated significantly greater inhibition of tumor growth than nontargeted IO-Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs have great potential to serve as both a magnetic resonance imaging (MRI) agent and PDT drug in the clinic.

  12. Uranium and other trace elements' distribution in Korean granite: implications for the influence of iron oxides on uranium migration.

    PubMed

    Lee, Seung Yeop; Baik, Min Hoon

    2009-06-01

    To understand trace radionuclide (uranium) migration occurring in rocks, a granitic batholith located at the Korea Atomic Energy Research Institute (KAERI) site was selected and investigated. The rock samples obtained from this site were examined using mineralogical methods, including scanning electron microscopy (SEM) and electron probe microanalysis (EPMA). The changes in the distribution pattern of uranium (U) and small amounts of trace elements, and the mineralogical textures affected by weathering, were examined. Based on the element distribution analyses, it was found that Fe2+ released from fresh biotite is oxidized in short geological time, forming amorphous iron oxides, such as ferrihydrite, around silicate minerals. In that case, the amorphous ferrihydrite does not show distinct adsorption for U. However, as it gradually crystallizes to goethite or hematite, the most U-rich phases were found to be associated with the secondary iron oxides having granular forms. This evidence suggests that the geological subsurface environment is favorable for the crystallized iron oxides to keep their structures more stable for a long time as compared with the amorphous phases. There is a possibility that the long residence of U which is in contact with the stable crystalline phases of iron may finally lead to the partial sequestration of U in their structure. Consequently, it seems that Fe-oxide crystallization can be a dominating mechanism for U uptake and controls long-term U transport in granites with low U contents.

  13. Major Element Analysis of the Target Rocks at Meteor Crater, Arizona

    NASA Technical Reports Server (NTRS)

    See, Thomas H.; Hoerz, Friedrich; Mittlefehldt, David W.; Varley, Laura; Mertzman, Stan; Roddy, David

    2002-01-01

    We collected approximately 400 rock chips in continuous vertical profile at Meteor Crater, Arizona, representing, from bottom to top, the Coconino, Toroweap, Kaibab, and Moenkopi Formations to support ongoing compositional analyses of the impact melts and their stratigraphic source depth(s) and other studies at Meteor Crater that depend on the composition of the target rocks. These rock chips were subsequently pooled into 23 samples for compositional analysis by XRF (x ray fluorescence) methods, each sample reflecting a specific stratigraphic "subsection" approximately 5-10 in thick. We determined the modal abundance of quartz, dolomite, and calcite for the entire Kaibab Formation at vertical resolutions of 1-2 meters. The Coconino Formation composes the lower half of the crater cavity. It is an exceptionally pure sandstone. The Toroweap is only two inches thick and compositionally similar to Coconino, therefore, it is not a good compositional marker horizon. The Kaibab Formation is approximately 80 in thick. XRD (x ray diffraction) studies show that the Kaibab Formation is dominated by dolomite and quartz, albeit in highly variable proportions; calcite is a minor phase at best. The Kaibab at Meteor Crater is therefore a sandy dolomite rather than a limestone, consistent with pronounced facies changes in the Permian of SE Arizona over short vertical and horizontal distances. The Moenkopi forms the 12 in thick cap rock and has the highest Al2O3 and FeO concentrations of all target rocks. With several examples, we illustrate how this systematic compositional and modal characterization of the target ideologies may contribute to an understanding of Meteor Crater, such as the depth of its melt zone, and to impact cratering in general, such as the liberation of CO2 from shocked carbonates.

  14. Recent Advances in Superparamagnetic Iron Oxide Nanoparticles for Cellular Imaging and Targeted Therapy Research

    PubMed Central

    Wang, Yi-Xiang J.; Xuan, Shouhu; Port, Marc; Idee, Jean-Marc

    2013-01-01

    Advances of nanotechnology have led to the development of nanomaterials with both potential diagnostic and therapeutic applications. Among them, superparamagnetic iron oxide (SPIO) nanoparticles have received particular attention. Over the past decade, various SPIOs with unique physicochemical and biological properties have been designed by modifying the particle structure, size and coating. This article reviews the recent advances in preparing SPIOs with novel properties, the way these physicochemical properties of SPIOs influence their interaction with cells, and the development of SPIOs in liver and lymph nodes magnetic resonance imaging (MRI) contrast. Cellular uptake of SPIO can be exploited in a variety of potential clinical applications, including stem cell and inflammation cell tracking and intra-cellular drug delivery to cancerous cells which offers higher intra-cellular concentration. When SPIOs are used as carrier vehicle, additional advantages can be achieved including magnetic targeting and hyperthermia options, as well as monitoring with MRI. Other potential applications of SPIO include magnetofection and gene delivery, targeted retention of labeled stem cells, sentinel lymph nodes mapping, and magnetic force targeting and cell orientation for tissue engineering. PMID:23621536

  15. Anti-HER2/neu peptide-conjugated iron oxide nanoparticles for targeted delivery of paclitaxel to breast cancer cells

    NASA Astrophysics Data System (ADS)

    Mu, Qingxin; Kievit, Forrest M.; Kant, Rajeev J.; Lin, Guanyou; Jeon, Mike; Zhang, Miqin

    2015-10-01

    Nanoparticles (NPs) for targeted therapy are required to have appropriate size, stability, drug loading and release profiles, and efficient targeting ligands. However, many of the existing NPs such as albumin, liposomes, polymers, gold NPs, etc. encounter size limit, toxicity and stability issues when loaded with drugs, fluorophores, and targeting ligands. Furthermore, antibodies are bulky and this can greatly affect the physicochemical properties of the NPs, whereas many small molecule-based targeting ligands lack specificity. Here, we report the utilization of biocompatible, biodegradable, small (~30 nm) and stable iron oxide NPs (IONPs) for targeted delivery of paclitaxel (PTX) to HER2/neu positive breast cancer cells using an anti-HER2/neu peptide (AHNP) targeting ligand. We demonstrate the uniform size and high stability of these NPs in biological medium, their effective tumour targeting in live mice, as well as their efficient cellular targeting and selective killing in human HER2/neu-positive breast cancer cells.Nanoparticles (NPs) for targeted therapy are required to have appropriate size, stability, drug loading and release profiles, and efficient targeting ligands. However, many of the existing NPs such as albumin, liposomes, polymers, gold NPs, etc. encounter size limit, toxicity and stability issues when loaded with drugs, fluorophores, and targeting ligands. Furthermore, antibodies are bulky and this can greatly affect the physicochemical properties of the NPs, whereas many small molecule-based targeting ligands lack specificity. Here, we report the utilization of biocompatible, biodegradable, small (~30 nm) and stable iron oxide NPs (IONPs) for targeted delivery of paclitaxel (PTX) to HER2/neu positive breast cancer cells using an anti-HER2/neu peptide (AHNP) targeting ligand. We demonstrate the uniform size and high stability of these NPs in biological medium, their effective tumour targeting in live mice, as well as their efficient cellular

  16. Mineralized iron oxidizing bacteria from hydrothermal vents: targeting biosignatures on Mars

    NASA Astrophysics Data System (ADS)

    Leveille, R. J.

    2010-12-01

    formation of an iron oxyhydroxide precipitate, either in direct association with the cells or within the growth medium, were observed. Preliminary analyses suggest that these precipitates are different from abiotic precipitates. Continuing work includes high-resolution TEM observations of cultured organisms and biogenic iron minerals, Raman and reflectance spectroscopy of precipitates, examination of seafloor incubation experiments, and bioreactor silicification experiments in order to better understand the Fe-Si fossilization process. Microaerophilic iron oxidation could have existed on the early Earth in environments containing small amounts of oxygen produced either by locally-concentrated photosynthetic microorganisms (e.g., cyanobacteria) or by chemical reactions. By analogy, similar subsurface or near-surface microaerophilic environments could have existed on Mars in the past, including in low-temperature hydrothermal systems. The distinctive morphologies and Fe-Si mineralization patterns of iron oxidizing bacteria could be a useful biosignature to search for on Mars. Deposits and features similar to those described here could be identified on Mars with existing technologies, and thus hydrothermal systems represent an attractive target for future surface and sample return missions.

  17. Scavenger receptor A gene regulatory elements target gene expression to macrophages and to foam cells of atherosclerotic lesions.

    PubMed Central

    Horvai, A; Palinski, W; Wu, H; Moulton, K S; Kalla, K; Glass, C K

    1995-01-01

    Transcription of the macrophage scavenger receptor A gene is markedly upregulated during monocyte to macrophage differentiation. In these studies, we demonstrate that 291 bp of the proximal scavenger receptor promoter, in concert with a 400-bp upstream enhancer element, is sufficient to direct macrophage-specific expression of a human growth hormone reporter in transgenic mice. These regulatory elements, which contain binding sites for PU.1, AP-1, and cooperating ets-domain transcription factors, are also sufficient to mediate regulation of transgene expression during the in vitro differentiation of bone marrow progenitor cells in response to macrophage colony-stimulating factor. Mutation of the PU.1 binding site within the scavenger receptor promoter severely impairs transgene expression, consistent with a crucial role of PU.1 in regulating the expression of the scavenger receptor gene. The ability of the scavenger receptor promoter and enhancer to target gene expression to macrophages in vivo, including foam cells of atherosclerotic lesions, suggests that these regulatory elements will be of general utility in the study of macrophage differentiation and function by permitting specific modifications of macrophage gene expression. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7777517

  18. Targeting the (3.8-4.0 Ga) Impactors: Siderophile Element Signatures of Lunar Impact Melts

    NASA Astrophysics Data System (ADS)

    Bennett, V.; Norman, M.; Ryder, G.

    2001-12-01

    Significant gaps remain in our understanding of the early impact history of the Earth and Moon, and their influence on geologic and biologic development. Outstanding controversies include whether or not the Moon, and by inference the early Earth, was hit by an unusually heavy "terminal cataclysm" of collisions during the period 3.8 to 4.0 Ga, and the number of large impact events represented by lunar samples. Coincidentally or not, the large nearside lunar basins are almost identical in age with the oldest terrestrial rocks, and are therefore relevant for consideration of the possible role of impacts in shaping the terrestrial continents and early life environments. To improve our understanding of the impact history of the Moon and to provide new information about the types of planetesimals that were involved in the early impact history of the inner Solar System, we measured the concentrations of highly siderophile elements (HSE: Re, Ir, Pt, Pd, Ru) in a suite of Apollo 17 impact melt breccias using high precision ID-ICPMS methods. These breccias all have poikilitic textures, relatively mafic bulk compositions, and high levels of incompatible trace elements and all likely represent ejecta from the Serenitatis basin. Ar-Ar ages are consistent with the formation of these breccias in a single impact event at 3893 +/- 9 Ma. HSE from 11 representative samples have W-shaped patterns on CI-normalized diagrams, with enrichments in Re, Ru and Pd relative to Ir and Pt, and absolute abundances ranging from \\sim0.5 to 4% of CI reference values. Stronger depletions of Ir and Pt relative to Re, Ru, and Pd are correlated with decreasing HSE concentrations. The samples with the highest HSE concentrations have patterns that are identical to those of EH chondrites, but the patterns become increasingly less diagnostic of meteorite group with decreasing concentrations. The systematic variation of HSE patterns with decreasing concentration suggests that simple chemical fingerprints of

  19. Receptor-targeted, drug-loaded, functionalized graphene oxides for chemotherapy and photothermal therapy

    PubMed Central

    Thapa, Raj Kumar; Choi, Ju Yeon; Poudel, Bijay Kumar; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2016-01-01

    Cancer is one of the leading causes of death worldwide. Although different chemotherapeutic agents have been developed to treat cancers, their use can be limited by low cellular uptake, drug resistance, and side effects. Hence, targeted drug delivery systems are continually being developed in order to improve the efficacy of chemotherapeutic agents. The main aim of this study was to prepare folic acid (FA)-conjugated polyvinyl pyrrolidone-functionalized graphene oxides (GO) (FA-GO) for targeted delivery of sorafenib (SF). GO were prepared using a modified Hummer’s method and subsequently altered to prepare FA-GO and SF-loaded FA-GO (FA-GO/SF). Characterization of GO derivatives was done using ultraviolet/visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, atomic force microscopy, zeta potential measurements, and determination of in vitro drug release. Hemolytic toxicity, in vitro cytotoxicity, cellular uptake, and apoptotic effects of FA-GO/SF were also investigated. The results revealed that GO was successfully synthesized and that further transformation to FA-GO improved the stability and SF drug-loading capacity. In addition, the enhanced SF release under acidic conditions suggested possible benefits for cancer treatment. Conjugation of FA within the FA-GO/SF delivery system enabled targeted delivery of SF to cancer cells expressing high levels of FA receptors, thus increasing the cellular uptake and apoptotic effects of SF. Furthermore, the photothermal effect achieved by exposure of GO to near-infrared irradiation enhanced the anticancer effects of FA-GO/SF. Taken together, FA-GO/SF is a potential carrier for targeted delivery of chemotherapeutic agents in cancer. PMID:27358565

  20. Uranium and minor-element partitioning in Fe-Ti oxides and zircon from partially melted granodiorite, Crater Lake, Oregon

    USGS Publications Warehouse

    Tourrette, T.Z.L.; Burnett, D.S.; Bacon, C.R.

    1991-01-01

    Crystal-liquid partitioning in Fe-Ti oxides and zircon was studied in partially melted granodiorite blocks ejected during the climactic eruption of Mt. Mazama (Crater Lake), Oregon. The blocks, which contain up to 33% rhyolite glass (75 wt% SiO2), are interpreted to be portions of the magma chamber walls that were torn off during eruption. The glass is clear and well homogenized for all measured elements except Zr. Results for Fe-Ti oxides give DUoxide/liq ??? 0.1. Partitioning of Mg, Mn, Al, Si, V, and Cr in Fe-Ti oxides indicates that grains surrounded by glass are moderately well equilibrated with the melt for many of the minor elements, while those that are inclusions in relict plagioclase are not. Uranium and ytterbium inhomogeneities in zircons indicate that the zircons have only partially equilibrated with the melt and that uranium appears to have been diffusing out of the zircons faster than the zircons were dissolving. Minimum U, Y, and P concentrations in zircons give maximum DUzrc/liq = 13,DYzrc/liq = 23, and DPzrc/liq = 1, but these are considerably lower than reported by other workers for U and Y. Based on our measurements and given their low abundances in most rocks, Fe-Ti oxides probably do not play a major role in U-Th fractionation during partial melting. The partial melts were undersaturated with zircon and apatite, but both phases are present in our samples. This demonstrates an actual case of non-equilibrium source retention of accessory phases, which in general could be an important trace-element fractionation mechanism. Our results do not support the hypothesis that liquid structure is the dominant factor controlling trace-element partitioning in high-silica rhyolites. Rough calculations based on Zr gradients in the glass indicate that the samples could have been partially molten for 800 to 8000 years. ?? 1991.

  1. Kinetics of Cyclic Oxidation and Cracking and Finite Element Analysis of MA956 and Sapphire/MA956 Composite System

    NASA Technical Reports Server (NTRS)

    Lee, Kang N.; Arya, Vinod K.; Halford, Gary R.; Barrett, Charles A.

    1996-01-01

    Sapphire fiber-reinforced MA956 composites hold promise for significant weight savings and increased high-temperature structural capability, as compared to unreinforced MA956. As part of an overall assessment of the high-temperature characteristics of this material system, cyclic oxidation behavior was studied at 1093 C and 1204 C. Initially, both sets of coupons exhibited parabolic oxidation kinetics. Later, monolithic MA956 exhibited spallation and a linear weight loss, whereas the composite showed a linear weight gain without spallation. Weight loss of the monolithic MA956 resulted from the linking of a multiplicity of randomly oriented and closely spaced surface cracks that facilitated ready spallation. By contrast, cracking of the composite's oxide layer was nonintersecting and aligned nominally parallel with the orientation of the subsurface reinforcing fibers. Oxidative lifetime of monolithic MA956 was projected from the observed oxidation kinetics. Linear elastic, finite element continuum, and micromechanics analyses were performed on coupons of the monolithic and composite materials. Results of the analyses qualitatively agreed well with the observed oxide cracking and spallation behavior of both the MA956 and the Sapphire/MA956 composite coupons.

  2. Red Fluorescent Zinc Oxide Nanoparticle: A Novel Platform for Cancer Targeting

    PubMed Central

    Hong, Hao; Wang, Fei; Zhang, Yin; Graves, Stephen A.; Eddine, Savo Bou Zein; Yang, Yunan; Theuer, Charles P.; Nickles, Robert J.; Wang, Xudong; Cai, Weibo

    2015-01-01

    Multifunctional zinc oxide (ZnO) nanoparticles (NPs) with well-integrated multimodality imaging capacities have generated increasing research interest in the last decade. However, limited progress has been made in developing ZnO NP-based multimodality tumor-imaging agents. Here we developed novel red fluorescent ZnO NPs and described the successful conjugation of 64Cu (t1/2 = 12.7 h) and TRC105, a chimeric monoclonal antibody against CD105, to these ZnO NPs via well-developed surface engineering procedures. The produced dual-modality ZnO NPs were readily applicable for positron emission tomography (PET) imaging and fluorescence imaging of the tumor vasculature. Their pharmacokinetics and tumor-targeting efficacy/specificity in mice bearing murine breast 4T1 tumor were thoroughly investigated. ZnO NPs with dual-modality imaging properties can serve as an attractive candidate for future cancer theranostics. PMID:25607242

  3. Pharmaceutical formulation of HSA hybrid coated iron oxide nanoparticles for magnetic drug targeting.

    PubMed

    Zaloga, Jan; Pöttler, Marina; Leitinger, Gerd; Friedrich, Ralf P; Almer, Gunter; Lyer, Stefan; Baum, Eva; Tietze, Rainer; Heimke-Brinck, Ralph; Mangge, Harald; Dörje, Frank; Lee, Geoffrey; Alexiou, Christoph

    2016-04-01

    In this work we present a new formulation of superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic drug targeting. The particles were reproducibly synthesized from current good manufacturing practice (cGMP) - grade substances. They were surface coated using fatty acids as anchoring molecules for human serum albumin. We comprehensively characterized the physicochemical core-shell structure of the particles using sophisticated methods. We investigated biocompatibility and cellular uptake of the particles using an established flow cytometric method in combination with microwave-plasma assisted atomic emission spectroscopy (MP-AES). The cytotoxic drug mitoxantrone was adsorbed on the protein shell and we showed that even in complex media it is slowly released with a close to zero order kinetics. We also describe an in vitro proof-of-concept assay in which we clearly showed that local enrichment of this SPION-drug conjugate with a magnet allows site-specific therapeutic effects.

  4. Mitochondria are selective targets for the protective effects of heat shock against oxidative injury.

    PubMed Central

    Polla, B S; Kantengwa, S; François, D; Salvioli, S; Franceschi, C; Marsac, C; Cossarizza, A

    1996-01-01

    Heat shock (HS) proteins (HSPs) induce protection against a number of stresses distinct from HS, including reactive oxygen species. In the human premonocytic line U937, we investigated in whole cells the effects of preexposure to HS and exposure to hydrogen peroxide (H2O2) on mitochondrial membrane potential, mass, and ultrastructure. HS prevented H2O2-induced alterations in mitochondrial membrane potential and cristae formation while increasing expression of HSPs and the protein product of bcl-2. Protection correlated best with the expression of the 70-kDa HSP, hsp70. We propose that mitochondria represent a selective target for HS-mediated protection against oxidative injury. Images Fig. 3 PMID:8692837

  5. Water based suspensions of iron oxide obtained by laser target evaporation for biomedical applications

    NASA Astrophysics Data System (ADS)

    Novoselova, I. P.; Safronov, A. P.; Samatov, O. M.; Beketov, I. V.; Medvedev, A. I.; Kurlyandskaya, G. V.

    2016-10-01

    In this work spherical magnetic nanoparticles (MNPs) of iron oxide were obtained by laser target evaporation technique (LTE). Water based suspensions were prepared on the basis of obtained MNPs and their properties were also studied including inductive heat capacity. Their structure and properties were studied by a number of techniques including magnetometry and heat capacity measurements. Magnetic induction heating experiment show the specific loss power (SLP) value in the narrow range from 1.30 to 1.45 W/g for all samples under consideration when using alternating magnetic field of 1.7 kA/m and frequency of 210 kHz. These parameters insure that LTE MNPs are interesting materials promising for magnetic fluid hyperthermia.

  6. Properties of electrochromic nickel-vanadium oxide films sputter-deposited from nonmagnetic alloy target

    NASA Astrophysics Data System (ADS)

    Avendano, Esteban; Azens, Andris; Niklasson, Gunnar A.

    2001-11-01

    In this study we investigate the structure, composition, diffusion coefficient, and electrochromic properties of nickel-vanadium oxide films as a function of deposition conditions. Polycrystalline films have been deposited by DC magnetron sputtering from a nonmagnetic target of Ni0.93V0.07 in an atmosphere of O2/Ar and Ar/O2/H2, with the gas flow ratios varied systematically to cover the range from nearly-metallic to overoxidized films. The results contradict the usual view that films deposited in O2/Ar are dark brown in their as-deposited state. While such films can easily be deposited, the optimum electrochromic properties have been observed at O2/Ar ratios giving nearly transparent films. Addition of hydrogen to the sputtering atmosphere improved cycling stability of the films. The diffusion coefficient has been determined by the Galvanostatic Intermittent Titration Technique (GITT).

  7. Solvent-Free Click-Mechanochemistry for the Preparation of Cancer Cell Targeting Graphene Oxide

    PubMed Central

    2015-01-01

    Polyethylene glycol-functionalized nanographene oxide (PEGylated n-GO) was synthesized from alkyne-modified n-GO, using solvent-free click-mechanochemistry, i.e., copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC). The modified n-GO was subsequently conjugated to a mucin 1 receptor immunoglobulin G antibody (anti-MUC1 IgG) via thiol–ene coupling reaction. n-GO derivatives were characterized with Fourier-transformed infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), Bradford assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and atomic force microscopy (AFM). Cell targeting was confirmed in vitro in MDA-MB-231 cells, either expressing or lacking MUC1 receptors, using flow cytometry, confocal laser scanning microscopy (CLSM) and multiphoton (MP) fluorescence microscopy. Biocompatibility was assessed using the modified lactate dehydrongenase (mLDH) assay. PMID:26278410

  8. CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic resonance imaging.

    PubMed

    Gallo, Juan; Kamaly, Nazila; Lavdas, Ioannis; Stevens, Elizabeth; Nguyen, Quang-De; Wylezinska-Arridge, Marzena; Aboagye, Eric O; Long, Nicholas J

    2014-09-01

    MRI offers high spatial resolution with excellent tissue penetration but it has limited sensitivity and the commonly administered contrast agents lack specificity. In this study, two sets of iron oxide nanoparticles (IONPs) were synthesized that were designed to selectively undergo copper-free click conjugation upon sensing of matrix metalloproteinase (MMP) enzymes, thereby leading to a self-assembled superparamagnetic nanocluster network with T2 signal enhancement properties. For this purpose, IONPs with bioorthogonal azide and alkyne surfaces masked by polyethylene glycol (PEG) layers tethered to CXCR4-targeted peptide ligands were synthesized and characterized. The IONPs were tested in vitro and T2 signal enhancements of around 160 % were measured when the IONPs were incubated with cells expressing MMP2/9 and CXCR4. Simultaneous systemic administration of the bioorthogonal IONPs in tumor-bearing mice demonstrated the signal-enhancing ability of these 'smart' self-assembling nanomaterials.

  9. Structural elements in the oxidation process of a single cobalt layer on Ir(100)-(1×1)

    NASA Astrophysics Data System (ADS)

    Gubo, Matthias; Ebensperger, Christina; Meyer, Wolfgang; Hammer, Lutz; Heinz, Klaus

    2011-02-01

    The ordered phases developing in sequence by oxidation of a single monolayer of cobalt deposited on Ir(100)-(1×1) were investigated by low-energy electron diffraction (LEED), scanning tunneling microscopy, and thermal desorption spectroscopy. It turns out that the structural elements of the different phases observed for increasing oxygen content and analyzed by quantitative LEED are pyramids based on squares or triangles made up by cobalt species and oxygen on top. The Co-O bond lengths are smaller than in the bulk of cobalt oxide owing to the reduced coordination of oxygen. For O:Co ratios of r=1/4, 1/2, and 5/8, the bonding of the oxide to the iridium substrate is merely by the cobalt species, and at r=1 it is via both Co and O.

  10. Key Elements of and Materials Performance Targets for Highly Insulating Window Frames

    SciTech Connect

    Gustavsen, Arild; Grynning, Steinar; Arasteh, Dariush; Jelle, Bjorn Petter; Goudey, Howdy

    2011-03-28

    The thermal performance of windows is important for energy efficient buildings. Windows typically account for about 30-50 percent of the transmission losses though the building envelope, even if their area fraction of the envelope is far less. The reason for this can be found by comparing the thermal transmittance (U-factor) of windows to the U-factor of their opaque counterparts (wall, roof and floor constructions). In well insulated buildings the U-factor of walls, roofs an floors can be between 0.1-0.2 W/(m2K). The best windows have U-values of about 0.7-1.0. It is therefore obvious that the U-factor of windows needs to be reduced, even though looking at the whole energy balance for windows (i.e. solar gains minus transmission losses) makes the picture more complex.In high performance windows the frame design and material use is of utmost importance, as the frame performance is usually the limiting factor for reducing the total window U-factor further. This paper describes simulation studies analyzing the effects on frame and edge-of-glass U-factors of different surface emissivities as well as frame material and spacer conductivities. The goal of this work is to define materials research targets for window frame components that will result in better frame thermal performance than is exhibited by the best products available on the market today.

  11. Process and apparatus for generating elemental sulfur and re-usable metal oxide from spent metal sulfide sorbents

    DOEpatents

    Ayala, Raul E.; Gal, Eli

    1995-01-01

    A process and apparatus for generating elemental sulfur and re-usable metal oxide from spent metal-sulfur compound. Spent metal-sulfur compound is regenerated to re-usable metal oxide by moving a bed of spent metal-sulfur compound progressively through a single regeneration vessel having a first and second regeneration stage and a third cooling and purging stage. The regeneration is carried out and elemental sulfur is generated in the first stage by introducing a first gas of sulfur dioxide which contains oxygen at a concentration less than the stoichiometric amount required for complete oxidation of the spent metal-sulfur compound. A second gas containing sulfur dioxide and excess oxygen at a concentration sufficient for complete oxidation of the partially spent metal-sulfur compound, is introduced into the second regeneration stage. Gaseous sulfur formed in the first regeneration stage is removed prior to introducing the second gas into the second regeneration stage. An oxygen-containing gas is introduced into the third cooling and purging stage. Except for the gaseous sulfur removed from the first stage, the combined gases derived from the regeneration stages which are generally rich in sulfur dioxide and lean in oxygen, are removed from the regenerator as an off-gas and recycled as the first and second gas into the regenerator. Oxygen concentration is controlled by adding air, oxygen-enriched air or pure oxygen to the recycled off-gas.

  12. Comparative proteomic analysis of sulfur-oxidizing Acidithiobacillus ferrooxidans CCM 4253 cultures having lost the ability to couple anaerobic elemental sulfur oxidation with ferric iron reduction.

    PubMed

    Kucera, Jiri; Sedo, Ondrej; Potesil, David; Janiczek, Oldrich; Zdrahal, Zbynek; Mandl, Martin

    2016-09-01

    In extremely acidic environments, ferric iron can be a thermodynamically favorable electron acceptor during elemental sulfur oxidation by some Acidithiobacillus spp. under anoxic conditions. Quantitative 2D-PAGE proteomic analysis of a resting cell suspension of a sulfur-grown Acidithiobacillus ferrooxidans CCM 4253 subculture that had lost its iron-reducing activity revealed 147 protein spots that were downregulated relative to an iron-reducing resting cell suspension of the antecedent sulfur-oxidizing culture and 111 that were upregulated. Tandem mass spectrometric analysis of strongly downregulated spots identified several physiologically important proteins that apparently play roles in ferrous iron oxidation, including the outer membrane cytochrome Cyc2 and rusticyanin. Other strongly repressed proteins were associated with sulfur metabolism, including heterodisulfide reductase, thiosulfate:quinone oxidoreductase and sulfide:quinone reductase. Transcript-level analyses revealed additional downregulation of other respiratory genes. Components of the iron-oxidizing system thus apparently play central roles in anaerobic sulfur oxidation coupled with ferric iron reduction in the studied microbial strain.

  13. Elemental Mercury Oxidation over Fe-Ti-Mn Spinel: Performance, Mechanism, and Reaction Kinetics.

    PubMed

    Xiong, Shangchao; Xiao, Xin; Huang, Nan; Dang, Hao; Liao, Yong; Zou, Sijie; Yang, Shijian

    2017-01-03

    The design of a high-performance catalyst for Hg(0) oxidation and predicting the extent of Hg(0) oxidation are both extremely limited due to the uncertainties of the reaction mechanism and the reaction kinetics. In this work, Fe-Ti-Mn spinel was developed as a high-performance catalyst for Hg(0) oxidation, and the reaction mechanism and the reaction kinetics of Hg(0) oxidation over Fe-Ti-Mn spinel were studied. The reaction orders of Hg(0) oxidation over Fe-Ti-Mn spinel with respect to gaseous Hg(0) concentration and gaseous HCl concentration were approximately 1 and 0, respectively. Therefore, Hg(0) oxidation over Fe-Ti-Mn spinel mainly followed the Eley-Rideal mechanism (i.e., the reaction of gaseous Hg(0) with adsorbed HCl), and the rate of Hg(0) oxidation mainly depended on Cl(•) concentration on the surface. As H2O, SO2, and NO not only inhibited Cl(•) formation on the surface but also interfered with the interface reaction between gaseous Hg(0) and Cl(•) on the surface, Hg(0) oxidation over Fe-Ti-Mn spinel was obviously inhibited in the presence of H2O, SO2, and NO. Furthermore, the extent of Hg(0) oxidation over Fe-Ti-Mn spinel can be predicted according to the kinetic parameter kE-R, and the predicted result was consistent with the experimental result.

  14. Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage.

    PubMed

    Schürmann, Nura; Forrer, Pascal; Casse, Olivier; Li, Jiagui; Felmy, Boas; Burgener, Anne-Valérie; Ehrenfeuchter, Nikolaus; Hardt, Wolf-Dietrich; Recher, Mike; Hess, Christoph; Tschan-Plessl, Astrid; Khanna, Nina; Bumann, Dirk

    2017-01-23

    Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible H2O2 at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0.1 μm. Myeloperoxidase-deficient neutrophils were predicted to accumulate large quantities of H2O2 that still effectively kill Salmonella, but most H2O2 would leak from the phagosome. Salmonella stimulation of neutrophils from normal and myeloperoxidase-deficient human donors experimentally confirmed an inverse relationship between myeloperoxidase activity and extracellular H2O2 release. Myeloperoxidase-deficient mice infected with Salmonella had elevated hydrogen peroxide tissue levels and exacerbated oxidative damage of host lipids and DNA, despite almost normal Salmonella control. These data show that myeloperoxidase has a major function in mitigating collateral tissue damage during antimicrobial oxidative bursts, by converting diffusible long-lived H2O2 into highly reactive, microbicidal and locally confined HOCl at pathogen surfaces.

  15. Studying the buckling and vibration characteristics of single-walled zinc oxide nanotubes using a nanoscale finite element model

    NASA Astrophysics Data System (ADS)

    Ansari, R.; Rouhi, S.; Mirnezhad, M.; Sadeghiyeh, F.

    2013-09-01

    The free vibration and axial buckling of achiral zinc oxide nanotubes (ZnONTs) are studied in this paper based on a three-dimensional finite-element model in which bonds are modeled using beam elements and mass elements are placed at the joints of beams instead of atoms. To determine the mechanical properties of the nanotubes, a linkage is established between molecular mechanics and density functional theory. The fundamental frequency and critical buckling load of ZnONTs with different geometries, chiralities and boundary conditions are calculated. It is shown that zigzag nanotubes are more stable than armchair ones. Investigating the effect of aspect ratio on the critical force shows that longer nanotubes are less stable. Also, it is indicated that increasing the length of the nanotubes will result in decreasing the frequency. Moreover, as the aspect ratio increases, the effect of end conditions diminishes.

  16. High specificity targeting and detection of human neuroblastoma using multifunctional anti-GD2 iron-oxide nanoparticles

    PubMed Central

    Baiu, Dana C.; Artz, Nathan S.; McElreath, Meghan R.; Menapace, Bryan D.; Hernando, Diego; Reeder, Scott B.; Grüttner, Cordula; Otto, Mario

    2015-01-01

    Aim To develop biocompatible, tumor-specific multifunctional iron oxide nanoconstructs targeting neuroblastoma, an aggressive pediatric malignancy. Materials & methods Clinical-grade humanized monoclonal antibody (hu14.18K322A), designed to target GD2 antigen on neuroblastoma with reduced non-specific immune interactions, was conjugated to hydroxyethyl starch-coated iron oxide nanoparticles. Targeting capability in vitro and in vivo was assessed by immunofluorescence, electron microscopy, analytical spectrophotometry, histochemistry and magnetic resonance R2* relaxometry. Results The biocompatible nanoconstructs demonstrated high tumor-specificity in vitro and in vivo, and low background uptake in a mouse flank xenograft model. Specific accumulation in tumors enabled particle visualization and quantification by magnetic resonance R2* mapping. Conclusions Our findings support the further development towards clinical application of this anti-GD2 iron-oxide nanoconstruct as diagnostic and therapeutic scaffold for neuroblastoma and potentially other GD2 positive malignancies. PMID:26420448

  17. Hyaluronic Acid Modified Tantalum Oxide Nanoparticles Conjugating Doxorubicin for Targeted Cancer Theranostics.

    PubMed

    Jin, Yushen; Ma, Xibo; Feng, Shanshan; Liang, Xiao; Dai, Zhifei; Tian, Jie; Yue, Xiuli

    2015-12-16

    Theranostic tantalum oxide nanoparticles (TaOxNPs) of about 40 nm were successfully developed by conjugating functional molecules including polyethylene glycol (PEG), near-infrared (NIR) fluorescent dye, doxorubicin (DOX), and hyaluronic acid (HA) onto the surface of the nanoparticles (TaOx@Cy7-DOX-PEG-HA NPs) for actively targeting delivery, pH-responsive drug release, and NIR fluorescence/X-ray CT bimodal imaging. The obtained nanoagent exhibits good biocompatibility, high cumulative release rate in the acidic microenvironments, long blood circulation time, and superior tumor-targeting ability. Both in vitro and in vivo experiments show that it can serve as an excellent contrast agent to simultaneously enhance fluorescence imaging and CT imaging greatly. Most importantly, such a nanoagent could enhance the therapeutic efficacy of the tumor greatly and the tumor growth inhibition was evaluated to be 87.5%. In a word, multifunctional TaOx@Cy7-DOX-PEG-HA NPs can serve as a theranostic nanomedicine for fluorescence/X-ray CT bimodal imaging, remote-controlled therapeutics, enabling personalized detection, and treatment of cancer with high efficacy.

  18. Mitochondrial Oxidative Damage in Aging and Alzheimer's Disease: Implications for Mitochondrially Targeted Antioxidant Therapeutics

    PubMed Central

    Reddy, P. Hemachandra

    2006-01-01

    The overall aim of this article is to review current therapeutic strategies for treating AD, with a focus on mitochondrially targeted antioxidant treatments. Recent advances in molecular, cellular, and animal model studies of AD have revealed that amyloid precursor protein derivatives, including amyloid beta (Aβ) monomers and oligomers, are likely key factors in tau hyperphosphorylation, mitochondrial oxidative damage, inflammatory changes, and synaptic failure in the brain tissue of AD patients. Several therapeutic strategies have been developed to treat AD, including anti-inflammatory, antioxidant, and antiamyloid approaches. Among these, mitochondrial antioxidant therapy has been found to be the most efficacious in reducing pathological changes and in not producing adverse effects; thus, mitochondrial antioxidant therapy is promising as a treatment for AD patients. However, a major limitation in applying mitochondrial antioxidants to AD treatment has been the inability of researchers to enhance antioxidant levels in mitochondria. Recently, however, there has been a breakthrough. Researchers have recently been able to promote the entry of certain antioxidants—including MitoQ, MitoVitE, MitoPBN, MitoPeroxidase, and amino acid and peptide-based SS tetrapeptides—into mitochondria, several hundred-fold more than do natural antioxidants. Once in the mitochondria, they rapidly neutralize free radicals and decrease mitochondrial toxicity. Thus, mitochondrially targeted antioxidants are promising candidates for treating AD patients. PMID:17047303

  19. Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview

    PubMed Central

    2011-01-01

    Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with multiple genetic aberrations. Several molecular pathways involved in the regulation of proliferation and cell death are implicated in the hepatocarcinogenesis. The major etiological factors for HCC are both hepatitis B virus (HBV) and hepatitis C virus infection (HCV). Continuous oxidative stress, which results from the generation of reactive oxygen species (ROS) by environmental factors or cellular mitochondrial dysfunction, has recently been associated with hepatocarcinogenesis. On the other hand, a distinctive pathological hallmark of HCC is a dramatic down-regulation of oxido-reductive enzymes that constitute the most important free radical scavenger systems represented by catalase, superoxide dismutase and glutathione peroxidase. The multikinase inhibitor sorafenib represents the most promising target agent that has undergone extensive investigation up to phase III clinical trials in patients with advanced HCC. The combination with other target-based agents could potentiate the clinical benefits obtained by sorafenib alone. In fact, a phase II multicenter study has demonstrated that the combination between sorafenib and octreotide LAR (So.LAR protocol) was active and well tolerated in advanced HCC patients. The detection of molecular factors predictive of response to anti-cancer agents such as sorafenib and the identification of mechanisms of resistance to anti-cancer agents may probably represent the direction to improve the treatment of HCC. PMID:21985599

  20. Silver nanoparticle-embedded graphene oxide-methotrexate for targeted cancer treatment.

    PubMed

    Thapa, Raj Kumar; Kim, Jae Hee; Jeong, Jee-Heon; Shin, Beom Soo; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2017-05-01

    Combination therapies are widely investigated cancer treatment modalities. Carbon based systems such as graphene oxide (GO), plasmonic nanoparticles such as silver nanoparticles (AgNPs), and the folate analog, methotrexate (MTX), have been separately studied for their potential anticancer effects. In this study, we combined these systems to develop AgNPs-embedded GO with conjugated MTX (MTX-GO/AgNPs) and studied their folate receptor-targeted anticancer effects. Results revealed successful formation of AgNPs on GO along with MTX conjugation as suggested by UV/visible, TEM, AFM, FTIR, and XRD analysis. Folate receptor-positive MCF-7 cells were more prone to cytotoxic effects of MTX-GO/AgNPs compared to folate receptor-negative HepG2 cells. Folic acid analog MTX interacts with folate receptors expressed in MCF-7 cells, improving cellular uptake and subsequent anticancer effects of the system. Importantly, AgNPs enhanced the total ROS production within the treated cells leading to improve cellular apoptosis, as evidenced by western blot. Moreover, near infrared (NIR)-induced photothermal effects of GO improved the anticancer activity of the system. Therefore, the combinational therapy system MTX-GO/AgNPs can be potentially applied for effective folate receptor-targeted treatment of cancers.

  1. Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs

    PubMed Central

    Dumkova, Jana; Vrlikova, Lucie; Vecera, Zbynek; Putnova, Barbora; Docekal, Bohumil; Mikuska, Pavel; Fictum, Petr; Hampl, Ales; Buchtova, Marcela

    2016-01-01

    The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level. PMID:27271611

  2. Carboxymethyl chitosan-mediated synthesis of hyaluronic acid-targeted graphene oxide for cancer drug delivery.

    PubMed

    Yang, Huihui; Bremner, David H; Tao, Lei; Li, Heyu; Hu, Juan; Zhu, Limin

    2016-01-01

    In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release, a new drug carrier was developed. Graphene oxide (GO) was first modified with carboxymethyl chitosan (CMC), followed by conjugation of hyaluronic acid (HA) and fluorescein isothiocyanate (FI). The resulting GO-CMC-FI-HA conjugate was characterized and used as a carrier to encapsulate the anticancer drug doxorubicin (DOX) to study in vitro release behavior. The drug loading capacity is as high as 95% and the drug release rate under tumor cell microenvironment of pH 5.8 is significantly higher than that under physiological conditions of pH 7.4. Cell uptake studies show that the GO-CMC-FI-HA/DOX complex can specifically target cancer cells, which are over-expressing CD44 receptors and effectively inhibit their growth. The above results suggest that the functionalized graphene-based material has potential applications for targeted delivery and controlled release of anticancer drugs.

  3. A graphene oxide based smart drug delivery system for tumor mitochondria-targeting photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wei, Yanchun; Zhou, Feifan; Zhang, Da; Chen, Qun; Xing, Da

    2016-02-01

    Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in organic and aqueous environments, respectively. The PPa-NGO-mAb assembly is able to effectively target the αvβ3-positive tumor cells with surface ligand and receptor recognition; once endocytosized by the cells, they are observed escaping from lysosomes and subsequently transferring to the mitochondria. In the mitochondria, the `on' state PPa-NGO-mAb performs its effective phototoxicity to kill cells. The biological and physical dual selections and on/off control of PPa-NGO-mAb significantly enhance mitochondria-mediated apoptosis of PDT. This smart system offers a potential alternative to drug delivery systems for cancer therapy.Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in

  4. Nox2 as a potential target of mitochondrial superoxide and its role in endothelial oxidative stress

    PubMed Central

    Nazarewicz, Rafal R.; Bikineyeva, Alfiya; Dikalov, Sergey I.

    2013-01-01

    Superoxide (O2·−) production by the NADPH oxidases is implicated in the pathogenesis of many cardiovascular diseases, including hypertension. We have previously shown that activation of NADPH oxidases increases mitochondrial O2·− which is inhibited by the ATP-sensitive K+ channel (mitoKATP) inhibitor 5-hydroxydecanoic acid and that scavenging of mitochondrial or cytoplasmic O2·− inhibits hypertension. We hypothesized that mitoKATP-mediated mitochondrial O2·− potentiates cytoplasmic O2·− by stimulation of NADPH oxidases. In this work we studied Nox isoforms as a potential target of mitochondrial O2·−. We tested contribution of reverse electron transfer (RET) from complex II to complex I in mitochondrial O2·− production and NADPH oxidase activation in human aortic endothelial cells. Activation of mitoKATP with low dose of diazoxide (100 nM) decreased mitochondrial membrane potential (tetramethylrhodamine methyl ester probe) and increased production of mitochondrial and cytoplasmic O2·− measured by site-specific probes and mitoSOX. Inhibition of RET with complex II inhibitor (malonate) or complex I inhibitor (rotenone) attenuated the production of mitochondrial and cytoplasmic O2·−. Supplementation with a mitochondria-targeted SOD mimetic (mitoTEMPO) or a mitochondria-targeted glutathione peroxidase mimetic (mitoEbselen) inhibited production of mitochondrial and cytoplasmic O2·−. Inhibition of Nox2 (gp91ds) or Nox2 depletion with small interfering RNA but not Nox1, Nox4, or Nox5 abolished diazoxide-induced O2·− production in the cytoplasm. Treatment of angiotensin II-infused mice with RET inhibitor dihydroethidium (malate) significantly reduced blood pressure. Our study suggests that mitoKATP-mediated mitochondrial O2·− stimulates cytoplasmic Nox2, contributing to the development of endothelial oxidative stress and hypertension. PMID:23955717

  5. Significance of RuO2 modified SCR catalyst for elemental mercury oxidation in coal-fired flue gas.

    PubMed

    Yan, Naiqiang; Chen, Wanmiao; Chen, Jie; Qu, Zan; Guo, Yongfu; Yang, Shijian; Jia, Jinping

    2011-07-01

    Catalytic conversion of elemental mercury (Hg(0)) to its oxidized form has been considered as an effective way to enhance mercury removal from coal-fired power plants. In order to make good use of the existing selective catalytic reduction of NO(x) (SCR) catalysts as a cobenefit of Hg(0) conversion at lower level HCl in flue gas, various catalysts supported on titanium dioxide (TiO(2)) and commercial SCR catalysts were investigated at various cases. Among the tested catalysts, ruthenium oxides (RuO(2)) not only showed rather high catalytic activity on Hg(0) oxidation by itself, but also appeared to be well cooperative with the commercial SCR catalyst for Hg(0) conversion. In addition, the modified SCR catalyst with RuO(2) displayed an excellent tolerance to SO(2) and ammonia without any distinct negative effects on NO(x) reduction and SO(2) conversion. The demanded HCl concentration for Hg(0) oxidation can be reduced dramatically, and Hg(0) oxidation efficiency over RuO(2) doped SCR catalyst was over 90% even at about 5 ppm HCl in the simulated gases. Ru modified SCR catalyst shows a promising prospect for the cobenefit of mercury emission control.

  6. Performance evaluation of non-thermal plasma injection for elemental mercury oxidation in a simulated flue gas.

    PubMed

    An, Jiutao; Shang, Kefeng; Lu, Na; Jiang, Yuze; Wang, Tiecheng; Li, Jie; Wu, Yan

    2014-03-15

    The use of non-thermal plasma (NTP) injection approach to oxidize elemental mercury (Hg(0)) in simulated flue gas at 110°C was studied, where a surface discharge plasma reactor (SDPR) inserted in the simulated flue duct was used to generate and inject active species into the flue gas. Approximately 81% of the Hg(0) was oxidized and 20.5μgkJ(-1) of energy yield was obtained at a rate of 3.9JL(-1). A maximal Hg(0) oxidation efficiency was found with a change in the NTP injection air flow rate. A high Hg(0) oxidation efficiency was observed in the mixed flue gas that included O2, H2O, SO2, NO and HCl. Chemical and physical processes (e.g., ozone, N2 metastable states and UV-light) were found to contribute to Hg(0) oxidation, with ozone playing a dominant role. The deposited mercury species on the internal surface of the flue duct was analyzed using X-ray photoelectron spectroscopy (XPS) and electronic probe microanalysis (EPMA), and the deposit was identified as HgO. The mercury species is thought to primarily exist in the form of HgO(s) by adhering to the suspended aerosols in the gas-phase.

  7. Promoter G-quadruplex sequences are targets for base oxidation and strand cleavage during hypoxia-induced transcription.

    PubMed

    Clark, David W; Phang, Tzu; Edwards, Michael G; Geraci, Mark W; Gillespie, Mark N

    2012-07-01

    The G-quadruplex, a non-B DNA motif that forms in certain G-rich sequences, is often located near transcription start sites in growth regulatory genes. Multiple lines of evidence show that reactive oxygen species generated as second messengers during physiologic signaling target specific DNA sequences for oxidative base modifications. Because guanine repeats are uniquely sensitive to oxidative damage, and G4 sequences are known "hot spots" for genetic mutation and DNA translocation, we hypothesized that G4 sequences are targeted for oxidative base modifications in hypoxic signaling. Approximately 25% of hypoxia-regulated genes in pulmonary artery endothelial cells harbored G4 sequences within their promoters. Chromatin immunoprecipitation showed that common base oxidation product 8-oxoguanine was selectively introduced into G4s, in promoters of hypoxia up-, down-, and nonregulated genes. Additionally, base excision DNA repair (BER) enzymes were recruited, and transient strand breaks formed in these sequences. Transcription factor Sp1, constitutively bound to G4 sequences in normoxia, was evicted as 8-oxoguanine accumulated during hypoxic exposure. Blocking hypoxia-induced oxidant production prevented both base modifications and decreased Sp1 binding. These findings suggest that oxidant stress in hypoxia causes oxidative base modifications, recruitment of BER enzymes, and transient strand breaks in G4 promoter sequences potentially altering G4 integrity and function.

  8. A novel target-specific gene delivery system combining baculovirus and sequence-specific long interspersed nuclear elements.

    PubMed

    Kawashima, Tomoko; Osanai, Mizuko; Futahashi, Ryo; Kojima, Tetsuya; Fujiwara, Haruhiko

    2007-07-01

    Transposable elements are valuable for somatic and germ-line transformation. However, long interspersed nuclear elements (LINEs) have not been used because of poor information on the transposition mechanism. We have developed a novel gene delivery system combining baculovirus AcNPV and two silkworm LINEs, SART1 and R1, which integrate into specific sequences of telomeric repeats and 28S ribosomal DNA, respectively. When two LINEs containing the enhanced green fluorescent protein gene recombined into AcNPV were infected into fifth instar larvae of the silkworm, we observed target-specific retrotransposition of LINEs at 72h post-infection, using polymerase chain reaction amplification and sequencing. Telomere- and 28S rDNA-specific transposition occurred in all nine tissues tested, including the ovary and testis. This is the first demonstration of site-specific gene delivery in living larvae. Insertion efficiencies were dependent on the virus titer for injection and the host strains of Bombyx mori. Using this system, we successfully detected the intergeneration transmission of retrotransposed sequences. In addition, AcNPV-mediated SART1 also transposed into telomere of another lepidopteran, Orgyia recens, suggesting that this system is useful for a wide variety of AcNPV-infectious insects. Site-specific gene delivery by virus-mediated LINE will be a potential gene therapy tool to avoid harmful unexpected insertions.

  9. Increasing prevalence of ciprofloxacin-resistant food-borne Salmonella strains harboring multiple PMQR elements but not target gene mutations

    PubMed Central

    Lin, Dachuan; Chen, Kaichao; Wai-Chi Chan, Edward; Chen, Sheng

    2015-01-01

    Fluoroquinolone resistance in Salmonella has become increasingly prevalent in recent years. To probe the molecular basis of this phenomenon, the genetic and phenotypic features of fluoroquinolone resistant Salmonella strains isolated from food samples were characterized. Among the 82 Salmonella strains tested, resistance rate of the three front line antibiotics of ceftriaxone, ciprofloxacin and azithromycin was 10%, 39% and 25% respectively, which is significantly higher than that reported in other countries. Ciprofloxacin resistant strains typically exhibited cross-resistance to multiple antibiotics including ceftriaxone, primarily due to the presence of multiple PMQR genes and the blaCTX-M-65, blaCTX-M-55 blaCMY-2 and blaCMY-72 elements. The prevalence rate of the oqxAB and aac(6’)-Ib-cr genes were 91% and 75% respectively, followed by qnrS (66%), qnrB (16%) and qnrD (3%). The most common PMQR combination observable was aac(6’)-Ib-cr-oqxAB-qnrS2, which accounted for 50% of the ciprofloxacin resistant strains. Interestingly, such isolates contained either no target mutations or only a single gyrA mutation. Conjugation and hybridization experiments suggested that most PMQR genes were located either in the chromosome or a non-transferrable plasmid. To summarize, findings in this work suggested that PMQRs greatly facilitate development of fluoroquinolone resistance in Salmonella by abolishing the requirement of target gene mutations. PMID:26435519

  10. Rational Design of Iron Oxide Nanoparticles as Targeted Nanomedicines for Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Kievit, Forrest M.

    2011-07-01

    Nanotechnology provides a flexible platform for the development of effective therapeutic nanomaterials that can interact specifically with a target in a biological system and provoke a desired biological response. Of the nanomaterials studied, superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as one of top candidates for cancer therapy due to their intrinsic superparamagnetism that enables non-invasive magnetic resonance imaging (MRI) and biodegradability favorable for in vivo application. This dissertation is aimed at development of SPION-based nanomedicines to overcome the current limitations in cancer therapy. These limitations include non-specificity of therapy which can harm healthy tissue, the difficulty in delivering nucleic acids for gene therapy, the formation of drug resistance, and the inability to detect and treat micrometastases. First, a SPION-based non-viral gene delivery vehicle was developed through functionalization of the SPION core with a co-polymer designed to provide stable binding of DNA and low toxicity which showed excellent gene delivery in vitro and in vivo. This SPION-based non-viral gene delivery vehicle was then activated with a targeting agent to improve gene delivery throughout a xenograft tumor of brain cancer. It was found that targeting did not promote the accumulation of SPIONs at the tumor site, but rather improved the distribution of SPIONs throughout the tumor so a higher proportion of cells received treatment. Next, the high surface area of SPIONs was utilized for loading large amounts of drug which was shown to overcome the multidrug resistance acquired by many cancer cells. Drug bound to SPIONs showed significantly higher multidrug resistant cell uptake as compared to free drug which translated into improved cell kill. Also, an antibody activated SPION was developed and was shown to be able to target micrometastases in a transgenic animal model of metastatic breast cancer. These SPION-based nanomedicines

  11. Demethyleneberberine, a natural mitochondria-targeted antioxidant, inhibits mitochondrial dysfunction, oxidative stress, and steatosis in alcoholic liver disease mouse model.

    PubMed

    Zhang, Pengcheng; Qiang, Xiaoyan; Zhang, Miao; Ma, Dongshen; Zhao, Zheng; Zhou, Cuisong; Liu, Xie; Li, Ruiyan; Chen, Huan; Zhang, Yubin

    2015-01-01

    Excessive alcohol consumption induces oxidative stress and lipid accumulation in the liver. Mitochondria have long been recognized as the key target for alcoholic liver disease (ALD). Recently, the artificial mitochondria-targeted antioxidant MitoQ has been used to treat ALD effectively in mice. Here, we introduce the natural mitochondria-targeted antioxidant demethyleneberberine (DMB), which has been found in Chinese herb Cortex Phellodendri chinensis. The protective effect of DMB on ALD was evaluated with HepG2 cells and acutely/chronically ethanol-fed mice, mimicking two common patterns of drinking in human. The results showed that DMB, which is composed of a potential antioxidant structure, could penetrate the membrane of mitochondria and accumulate in mitochondria either in vitro or in vivo. Consequently, the acute drinking-caused oxidative stress and mitochondrial dysfunction were significantly ameliorated by DMB. Moreover, we also found that DMB suppressed CYP2E1, hypoxia inducible factor α, and inducible nitric oxide synthase, which contributed to oxidative stress and restored sirtuin 1/AMP-activated protein kinase/peroxisome proliferator-activated receptor-γ coactivator-1α pathway-associated fatty acid oxidation in chronic ethanol-fed mice, which in turn ameliorated lipid peroxidation and macrosteatosis in the liver. Taking these findings together, DMB could serve as a novel and potential therapy for ALD in human beings.

  12. Targeted fluorescence imaging enhanced by 2D materials: a comparison between 2D MoS2 and graphene oxide.

    PubMed

    Xie, Donghao; Ji, Ding-Kun; Zhang, Yue; Cao, Jun; Zheng, Hu; Liu, Lin; Zang, Yi; Li, Jia; Chen, Guo-Rong; James, Tony D; He, Xiao-Peng

    2016-08-04

    Here we demonstrate that 2D MoS2 can enhance the receptor-targeting and imaging ability of a fluorophore-labelled ligand. The 2D MoS2 has an enhanced working concentration range when compared with graphene oxide, resulting in the improved imaging of both cell and tissue samples.

  13. Folic acid-conjugated iron oxide porous nanorods loaded with doxorubicin for targeted drug delivery.

    PubMed

    Yu, Ping; Xia, Xi-Ming; Wu, Ming; Cui, Can; Zhang, Yang; Liu, Lei; Wu, Bo; Wang, Cai-Xia; Zhang, Liu-Jie; Zhou, Xiang; Zhuo, Ren-Xi; Huang, Shi-Wen

    2014-08-01

    Iron oxide porous nanorods (IOPNR) with lengths ranging from 40nm to 60nm and pore diameters ranging from 5nm to 10nm were prepared, and further modified with NH2-PEG-FA (FA-PEG-IOPNR) for ligand targeting and modified with NH2-PEG-OCH3 (PEG-IOPNR) as a control. Instead of chemical bonding, doxorubicin (DOX), a low water solubility anticancer drug, was loaded in the pores of the modified IOPNR because of their porous structure and high porosity. The release of DOX in acidic PBS solution (pH 5.3) was faster than that in neutral (pH 7.4) solution. The analysis results from TEM, inductively coupled plasma emission spectroscopy, confocal laser scanning microscopy, and flow cytometry analyses indicated that the presence of FA on the surface of the nanorods increase the cellular uptake of nanorods in the case of HeLa cells, a folate receptor (FR)-positive cell line. In contrast, for COS 7 cells, a FR-negative cell line, FA ligand on the surface of the nanorods showed no effect on the cellular uptake. MTT assay indicated that the cytotoxicity of DOX loaded in FA-PEG-IOPNR to HeLa cells was higher than that of DOX in PEG-IOPNR. In the case of COS 7 cells, no significant difference between the cytotoxicity of DOX loaded in FA-PEG-IOPNR and PEG-IOPNR was found. These results suggested that FA-PEG-IOPNR had the potential for target delivery of chemotherapeutic into cancer cells.

  14. The lectin-like oxidized LDL receptor-1: a new potential molecular target in colorectal cancer

    PubMed Central

    Murdocca, Michela; Mango, Ruggiero; Pucci, Sabina; Biocca, Silvia; Testa, Barbara; Capuano, Rosamaria; Paolesse, Roberto; Sanchez, Massimo; Orlandi, Augusto; di Natale, Corrado; Novelli, Giuseppe; Sangiuolo, Federica

    2016-01-01

    The identification of new biomarkers and targets for tailored therapy in human colorectal cancer (CRC) onset and progression is an interesting challenge. CRC tissue produces an excess of ox-LDL, suggesting a close correlation between lipid dysfunction and malignant transformation. Lectin-like oxidized LDL receptor-1 (LOX-1) is involved in several mechanisms closely linked to tumorigenesis. Here we report a tumor specific LOX-1 overexpression in human colon cancers: LOX-1 results strongly increased in the 72% of carcinomas (P<0.001), and strongly overexpressed in 90% of highly aggressive and metastatic tumours (P<0.001), as compared to normal mucosa. Moreover LOX-1 results modulated since the early stage of the disease (adenomas vs normal mucosa; P<0.001) suggesting an involvement in tumor insurgence and progression. The in vitro knockdown of LOX-1 in DLD-1 and HCT-8 colon cancer cells by siRNA and anti-LOX-1 antibody triggers to an impaired proliferation rate and affects the maintenance of cell growth and tumorigenicity. The wound-healing assay reveals an evident impairment in closing the scratch. Lastly knockdown of LOX-1 delineates a specific pattern of volatile compounds characterized by the presence of a butyrate derivative, suggesting a potential role of LOX-1 in tumor-specific epigenetic regulation in neoplastic cells. The role of LOX-1 as a novel biomarker and molecular target represents a concrete opportunity to improve current therapeutic strategies for CRC. In addition, the innovative application of a technology focused to the identification of LOX-1 driven volatiles specific to colorectal cancer provides a promising diagnostic tool for CRC screening and for monitoring the response to therapy. PMID:26895376

  15. Hot-Fire Test Results of Liquid Oxygen/RP-2 Multi-Element Oxidizer-Rich Preburners

    NASA Technical Reports Server (NTRS)

    Protz, C. S.; Garcia, C. P.; Casiano, M. J.; Parton, J. A.; Hulka, J. R.

    2016-01-01

    As part of the Combustion Stability Tool Development project funded by the Air Force Space and Missile Systems Center, the NASA Marshall Space Flight Center was contracted to assemble and hot-fire test a multi-element integrated test article demonstrating combustion characteristics of an oxygen/hydrocarbon propellant oxidizer-rich staged-combustion engine thrust chamber. Such a test article simulates flow through the main injectors of oxygen/kerosene oxidizer-rich staged combustion engines such as the Russian RD-180 or NK-33 engines, or future U.S.-built engine systems such as the Aerojet-Rocketdyne AR-1 engine or the Hydrocarbon Boost program demonstration engine. To supply the oxidizer-rich combustion products to the main injector of the integrated test article, existing subscale preburner injectors from a previous NASA-funded oxidizer-rich staged combustion engine development program were utilized. For the integrated test article, existing and newly designed and fabricated inter-connecting hot gas duct hardware were used to supply the oxidizer-rich combustion products to the oxidizer circuit of the main injector of the thrust chamber. However, before one of the preburners was used in the integrated test article, it was first hot-fire tested at length to prove it could provide the hot exhaust gas mean temperature, thermal uniformity and combustion stability necessary to perform in the integrated test article experiment. This paper presents results from hot-fire testing of several preburner injectors in a representative combustion chamber with a sonic throat. Hydraulic, combustion performance, exhaust gas thermal uniformity, and combustion stability data are presented. Results from combustion stability modeling of these test results are described in a companion paper at this JANNAF conference, while hot-fire test results of the preburner injector in the integrated test article are described in another companion paper.

  16. Induction of the mammalian stress response gene GADD153 by oxidative stress: role of AP-1 element.

    PubMed Central

    Guyton, K Z; Xu, Q; Holbrook, N J

    1996-01-01

    GADD153 is a CCAAT/enhancer-binding-protein-related gene that may function to control cellular growth in response to stress signals. In this study, a variety of oxidant treatments were shown to stimulate endogenous GADD153 mRNA expression and to transcriptionally activate a GADD153 promoter-reporter gene construct in transfected HeLa cells. Both commonalities and distinctions in the induction of GADD153 by H2O2 and the thiol-reactive compound arsenite were demonstrated. GADD153 mRNA induction by both H2O2 and arsenite was potentiated by GSH depletion, and completely inhibited by N-acetyl-cysteine. o-Phenanthroline and mannitol blocked GADD153 induction by H2O2, indicating that iron-generated hydroxyl radical mediates this induction. Concordantly, GSH peroxidase overexpression in WI38 cells attenuated GADD153 mRNA induction by H2O2. However, GADD153 induction by arsenite was only modestly reduced in the same cells, suggesting a lesser contribution of peroxides to gene activation by arsenite. We also demonstrated that oxidative stress participates in the induction of GADD153 by UVC (254 nm) irradiation. Finally, both promoter-deletion analysis and point mutation of the AP-1 site in an otherwise intact promoter support a significant role for AP-1 in transcriptional activation of GADD153 by UVC or oxidant treatment. Indeed, exposure of cells to oxidants or UVC stimulated binding of Fos and Jun to the GADD153 AP-1 element. Together, these results demonstrate that both free-radical generation and thiol modification can transcriptionally activate GADD153, and that AP-1 is critical to oxidative regulation of this gene. This study further supports a role for the GADD153 gene product in the cellular response to oxidant injury. PMID:8670069

  17. Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w.

    PubMed

    Wang, Jian-Xun; Gao, Jie; Ding, Su-Ling; Wang, Kun; Jiao, Jian-Qin; Wang, Yin; Sun, Teng; Zhou, Lu-Yu; Long, Bo; Zhang, Xiao-Jie; Li, Qian; Liu, Jin-Ping; Feng, Chang; Liu, Jia; Gong, Ying; Zhou, Zhixia; Li, Pei-Feng

    2015-07-02

    MicroRNAs (miRNAs) are small non-coding RNAs, and they bind to complementary sequences in the three prime untranslated regions (3' UTRs) of target mRNA transcripts, thereby inhibiting mRNA translation or promoting mRNA degradation. Excessive reactive oxygen species (ROS) can cause cell-damaging effects through oxidative modification of macromolecules leading to their inappropriate functions. Such oxidative modification is related to cancers, aging, and neurodegenerative and cardiovascular diseases. Here we report that miRNAs can be oxidatively modified by ROS. We identified that miR-184 upon oxidative modification associates with the 3' UTRs of Bcl-xL and Bcl-w that are not its native targets. The mismatch of oxidized miR-184 with Bcl-xL and Bcl-w is involved in the initiation of apoptosis in the study with rat heart cell line H9c2 and mouse models. Our results reveal a model of ROS in regulating cellular events by oxidatively modifying miRNA.

  18. Is Nitrate radical a major oxidant of elemental mercury in the atmosphere?

    NASA Astrophysics Data System (ADS)

    Luria, M.; Obrist, D.; Peleg, M.; Matveev, V.; Tas, E.

    2012-12-01

    Nitrate radicals (NO3) play a major role in the nighttime atmospheric oxidation of VOC. The radicals are produced throughout the reaction between O3 and NO2 and are removed via a sequence of homogeneous and heterogeneous reactions. Nitrate radicals reach significant levels only at night and mostly under conditions of low humidity (Asaf et al, 2009, 2010 and references therein). Because of its very high photolysis rate, daytime levels are extremely low, and thus are insignificant in atmospheric oxidation processes. The reaction of Hg with NO3 has not been sufficiently investigated; a value of 4x10-15 cm3 molec-1 s-1 (Sommar et al 1997) is most commonly used. Its importance for the atmospheric mercury chemistry was discussed by Mao el al., (2008) who examined the potential oxidation of mercury by the most common atmospheric oxidants applying the best available rate coefficients. According to their report, the uncertainty in the oxidation capacity of O3 is very large (a factor of 20). If the lower limit is applied, as suggested by Calvert and Lindberg (2005), oxidation by O3 is nearly negligible and, NO3 radicals, at typical nighttime levels, are responsible for the bulk of the Hg oxidation. Obviously this is true in the absence of reactive halogen compounds (RHC, Peleg et al., 2008). The most common method of measuring nitrate radicals is the differential optical absorption system (DOAS) technique. In a recent study performed at an urban semi arid site (Jerusalem, Israel; Asaf et al., 2009, 2010) it was found that nitrate levels could reach levels of up to 800 ppt, significantly higher than ever reported in the past. They further demonstrated that under the conditions prevailed; nitrate radicals are at least as important as the hydroxyl radicals in the overall oxidation capacity of VOC in the atmosphere. Side by side measurements of Nitrate radicals using the DOAS technique and speciated mercury compounds (Total, Particulate and Reactive gaseous) were performed

  19. Electronic devices containing switchably conductive silicon oxides as a switching element and methods for production and use thereof

    DOEpatents

    Tour, James M.; Yao, Jun; Natelson, Douglas; Zhong, Lin; He, Tao

    2015-09-08

    In various embodiments, electronic devices containing switchably conductive silicon oxide as a switching element are described herein. The electronic devices are two-terminal devices containing a first electrical contact and a second electrical contact in which at least one of the first electrical contact or the second electrical contact is deposed on a substrate to define a gap region therebetween. A switching layer containing a switchably conductive silicon oxide resides in the gap region between the first electrical contact and the second electrical contact. The electronic devices exhibit hysteretic current versus voltage properties, enabling their use in switching and memory applications. Methods for configuring, operating and constructing the electronic devices are also presented herein.

  20. Electronic devices containing switchably conductive silicon oxides as a switching element and methods for production and use thereof

    DOEpatents

    Tour, James M; Yao, Jun; Natelson, Douglas; Zhong, Lin; He, Tao

    2013-11-26

    In various embodiments, electronic devices containing switchably conductive silicon oxide as a switching element are described herein. The electronic devices are two-terminal devices containing a first electrical contact and a second electrical contact in which at least one of the first electrical contact or the second electrical contact is deposed on a substrate to define a gap region therebetween. A switching layer containing a switchably conductive silicon oxide resides in the the gap region between the first electical contact and the second electrical contact. The electronic devices exhibit hysteretic current versus voltage properties, enabling their use in switching and memory applications. Methods for configuring, operating and constructing the electronic devices are also presented herein.

  1. The effect of oxidant addition on ferrous iron removal from multi-element acidic sulphate solutions

    NASA Astrophysics Data System (ADS)

    Mbedzi, Ndishavhelafhi; Ibana, Don; Dyer, Laurence; Browner, Richard

    2017-01-01

    This study was an investigation on the hydrolytic precipitation of iron from simulated pregnant leach solution (PLS) of nickel laterite atmospheric leaching. The effect of equilibrium pH, temperature and the addition of oxidant on total iron (ferrous (Fe (II)) and ferric (Fe (III)), aluminium and chromium removal was investigated together with the associated nickel and cobalt losses to the precipitate. Systematic variations of the experimental variables revealed ≥99% of the ferric iron can be removed from solution at conditions similar to those used in standard partial neutralisation in zinc and nickel production, pH of 2.5 and temperature less than 100 °C with minimal losses (<0.5%) of both nickel and cobalt. Temperature variation from 55 to 90 °C had no significant effect on the magnitude of Fe (III) precipitation but led to a significant increase in aluminium removal from 67% to 95% and improved the filterability of the precipitates. There was no ferrous iron precipitation even at a pH of 3.75 in the absence of an oxidant with its removal (98%) achieved by oxidative precipitation with oxygen gas at pH 3.5. Unlike Fe (III) precipitation, the operating temperature significantly affects oxidative precipitation of Fe (II). Hence, in practical application, the hydrolytic precipitation and oxidation to remove iron must be operated at 85 °C to ensure both ferrous and ferric iron are precipitated.

  2. Recovery of elemental sulphur from anaerobic effluents through the biological oxidation of sulphides.

    PubMed

    de Sousa, José Tavares; Lima, Jéssyca de Freitas; da Silva, Valquíria Cordeiro; Leite, Valderi Duarte; Lopes, Wilton Silva

    2017-03-01

    The aim of the present study was to evaluate the biological oxidation of sulphide in two different UASB reactors by assessing the occurrence of oxidized forms of sulphur in the effluents and the amount of S(0) that could be recovered in the process. The bioreactors employed were an anaerobic hybrid (AH) reactor employing porous polyurethane foam as support media and a micro-aerated UASB reactor equipped with an aeration device above the digestion zone. The AH reactor produced a final effluent containing low concentrations of S(2-) (3.87% of total sulphur load). It was achieved due to a complete oxidation of 56.1% of total sulphur. The partial biological oxidation that occurred in the AH reactor allowed the recovery of 30% of the sulphur load as S(0). The effluent from the micro-aerated UASB reactor contained 5% of the sulphur load in the form of S(2-), while 20.9% was present as dissolved SO4(2-) and 46% was precipitated as S(0). It is concluded that the AH reactor or micro-aeration carried out above the digestion zone of the UASB reactor favoured the biological oxidation of S(2-) and the release of odourless effluents. Both technologies represent feasible and low-cost alternatives for the anaerobic treatment of domestic sewage.

  3. On the Highest Oxidation States of Metal Elements in MO4 Molecules (M = Fe, Ru, Os, Hs, Sm, and Pu).

    PubMed

    Huang, Wei; Xu, Wen-Hua; Schwarz, W H E; Li, Jun

    2016-05-02

    Metal tetraoxygen molecules (MO4, M = Fe, Ru, Os, Hs, Sm, Pu) of all metal atoms M with eight valence electrons are theoretically studied using density functional and correlated wave function approaches. The heavier d-block elements Ru, Os, Hs are confirmed to form stable tetraoxides of Td symmetry in (1)A1 electronic states with empty metal d(0) valence shell and closed-shell O(2-) ligands, while the 3d-, 4f-, and 5f-elements Fe, Sm, and Pu prefer partial occupation of their valence shells and peroxide or superoxide ligands at lower symmetry structures with various spin couplings. The different geometric and electronic structures and chemical bonding types of the six iso-stoichiometric species are explained in terms of atomic orbital energies and orbital radii. The variations found here contribute to our general understanding of the periodic trends of oxidation states across the periodic table.

  4. The cyclic oxidation resistance at 1200 C of beta-NiAl, FeAl, and CoAl alloys with selected third element additions

    NASA Technical Reports Server (NTRS)

    Barrett, C. A.; Titran, R. H.

    1992-01-01

    The intermetallic compounds Beta-NiAl, FeAl, and CoAl were tested in cyclic oxidation with selected third element alloy additions. Tests in static air for 200 1-hr cycles at 1200 C indicated by specific weight change/time data and x-ray diffraction analysis that the 5 at percent alloy additions did not significantly improve the oxidation resistance over the alumina forming baseline alloys without the additions. Many of the alloy additions were actually deleterious. Ta and Nb were the only alloy additions that actually altered the nature of the oxide(s) formed and still maintained the oxidation resistance of the protective alumina scale.

  5. Targeting of pollen tubes to ovules is dependent on nitric oxide (NO) signaling.

    PubMed

    Prado, Ana Margarida; Colaço, Renato; Moreno, Nuno; Silva, Ana Catarina; Feijó, José A

    2008-07-01

    The guidance signals that drive pollen tube navigation inside the pistil and micropyle targeting are still, to a great extent, unknown. Previous studies in vitro showed that nitric oxide (NO) works as a negative chemotropic cue for pollen tube growth in lily (Lilium longiflorum). Furthermore, Arabidopsis thaliana Atnos1 mutant plants, which show defective NO production, have reduced fertility. Here, we focus in the role of NO in the process of pollen-pistil communication, using Arabidopsis in-vivo and lily semi-vivo assays. Cross-pollination between wild-type and Atnos1 plants shows that the mutation affects the pistil tissues in a way that is compatible with abnormal pollen tube guidance. Moreover, DAF-2DA staining for NO in kanadi floral mutants showed the presence of NO in an asymmetric restricted area around the micropyle. The pollen-pistil interaction transcriptome indicates a time-course-specific modulation of transcripts of AtNOS1 and two Nitrate Reductases (nr1 and nr2), which collectively are thought to trigger a putative NO signaling pathway. Semi-vivo assays with isolated ovules and lily pollen further showed that NO is necessary for micropyle targeting to occur. This evidence is supported by CPTIO treatment with subsequent formation of balloon tips in pollen tubes facing ovules. Activation of calcium influx in pollen tubes partially rescued normal pollen tube morphology, suggesting that this pathway is also dependent on Ca(2+) signaling. A role of NO in modulating Ca(2+) signaling was further substantiated by direct imaging the cytosolic free Ca(2+) concentration during NO-induced re-orientation, where two peaks of Ca(2+) occur-one during the slowdown/stop response, the second during re-orientation and growth resumption. Taken together, these results provide evidence for the participation of NO signaling events during pollen-pistil interaction. Of special relevance, NO seems to directly affect the targeting of pollen tubes to the ovule's micropyle by

  6. Red fluorescent zinc oxide nanoparticle: A novel platform for cancer targeting

    SciTech Connect

    Hong, Hao; Wang, Fei; Zhang, Yin; Graves, Stephen A.; Eddine, Savo Bou Zein; Yang, Yunan; Theuer, Charles P.; Nickles, Robert J.; Wang, Xudong; Cai, Weibo

    2015-01-21

    Multifunctional zinc oxide (ZnO) nanoparticles (NPs) with well-integrated multimodality imaging capacities have generated increasing research interest in the past decade. However, limited progress has been made in developing ZnO NP-based multimodality tumor-imaging agents. In this paper, we developed novel red fluorescent ZnO NPs and described the successful conjugation of 64Cu (t1/2 = 12.7 h) and TRC105, a chimeric monoclonal antibody against CD105, to these ZnO NPs via well-developed surface engineering procedures. The produced dual-modality ZnO NPs were readily applicable for positron emission tomography (PET) imaging and fluorescence imaging of the tumor vasculature. Their pharmacokinetics and tumor-targeting efficacy/specificity in mice bearing murine breast 4T1 tumor were thoroughly investigated. In conclusion, ZnO NPs with dual-modality imaging properties can serve as an attractive candidate for future cancer theranostics.

  7. Facile synthesis of manganese ferrite/graphene oxide nanocomposites for controlled targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Wang, Guangshuo; Ma, Yingying; Zhang, Lina; Mu, Jingbo; Zhang, Zhixiao; Zhang, Xiaoliang; Che, Hongwei; Bai, Yongmei; Hou, Junxian

    2016-03-01

    In this study, manganese ferrite/graphene oxide (MnFe2O4/GO) nanocomposites as controlled targeted drug delivery were prepared by a facile sonochemical method. It was found that GO nanosheets were fully exfoliated and decorated with MnFe2O4 nanoparticles having diameters of 5-13 nm. The field-dependent magnetization curve indicated superparamagnetic behavior of the obtained MnFe2O4/GO with saturation magnetization of 34.9 emu/g at room temperature. The in vitro cytotoxicity testing exhibited negligible cytotoxicity of as-prepared MnFe2O4/GO even at the concentration as high as 150 μg/mL. Doxorubicin hydrochloride (DOX) as an anti-tumor model drug was utilized to explore the application potential of MnFe2O4/GO for controlled drug delivery. The drug loading capacity of this nanocarrier was as high as 0.97 mg/mg and the drug release behavior showed a sustained and pH-responsive way.

  8. MiR-590-5p Inhibits Oxidized- LDL Induced Angiogenesis by Targeting LOX-1.

    PubMed

    Dai, Yao; Zhang, Zhigao; Cao, Yongxiang; Mehta, Jawahar L; Li, Jun

    2016-03-02

    Oxidized low-density lipoprotein (ox-LDL) is, at least in part, responsible for angiogenesis in atherosclerotic regions. This effect of ox-LDL has been shown to be mediated through a specific receptor LOX-1. Here we describe the effect of miR-590-5p on ox-LDL-mediated angiogenesis in in vitro and in vivo settings. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-590-5p mimic or inhibitor followed by treatment with ox-LDL. In other experiments, Marigel plugs were inserted in the mice subcutaneous space. Both in vitro and in vivo studies showed that miR-590-5p mimic (100 nM) inhibited the ox-LDL-mediated angiogenesis (capillary tube formation, cell proliferation and migration as well as pro-angiogenic signals- ROS, MAPKs, pro-inflammatory cytokines and adhesion-related proteins). Of note, miR-590-5p inhibitor (200 nM) had the opposite effects. The inhibitory effect of miR-590-5p on angiogenesis was mediated by inhibition of LOX-1 at translational level. The inhibition of LOX-1 by miR-590-5p was confirmed by luciferase assay. In conclusion, we show that MiR-590-5p inhibits angiogenesis by targeting LOX-1 and suppressing redox-sensitive signals.

  9. Indium oxide-based transparent conductive films deposited by reactive sputtering using alloy targets

    NASA Astrophysics Data System (ADS)

    Miyazaki, Yusuke; Maruyama, Eri; Jia, Junjun; Machinaga, Hironobu; Shigesato, Yuzo

    2017-04-01

    High-quality transparent conductive oxide (TCO) films, Sn-doped In2O3 (ITO) and In2O3–ZnO (IZO), were successfully deposited on either synthetic silica or polyethylene terephthalate (PET) substrates in the “transition region” by reactive dc magnetron sputtering using In–Zn and In–Sn alloy targets, respectively, with a specially designed plasma emission feedback system. The composition, crystallinity, surface morphology, and electrical and optical properties of the films were analyzed. All of the IZO films were amorphous, whereas the ITO films were polycrystalline over a wide range of deposition conditions. The minimum resistivities of the IZO and ITO films deposited on the heated PET substrates at 150 °C were 3.3 × 10‑4 and 5.4 × 10‑4 Ω·cm, respectively. By applying rf bias to unheated PET substrates, ITO films with a resistivity of 4.4 × 10‑4 Ω·cm were deposited at a dc self-bias voltage of ‑60 V.

  10. Dephosphorylation of receptor tyrosine kinases as target of regulation by radiation, oxidants or alkylating agents.

    PubMed Central

    Knebel, A; Rahmsdorf, H J; Ullrich, A; Herrlich, P

    1996-01-01

    Several non-physiologic agents such as radiation, oxidants and alkylating agents induce ligand-independent activation of numerous receptor tyrosine kinases (RTKs) and of protein tyrosine kinases at the inner side of the plasma membrane (e.g. Dévary et al., 1992; Sachsenmaier et al., 1994; Schieven et al., 1994; Coffer et al., 1995). Here we show additional evidence for the activation of epidermal growth factor receptor (EGFR), and we show activation of v-ErbB, ErbB2 and platelet-derived growth factor receptor. As a common principle of action the inducing agents such as UVC, UVB, UVA, hydrogen peroxide and iodoacetamide inhibit receptor tyrosine dephosphorylation in a thiol-sensitive and, with the exception of the SH-alkylating agent, reversible manner. EGFR dephosphorylation can also be modulated by these non-physiologic agents in isolated plasma membranes in the presence of Triton X-100. Further, substrate (EGFR) and phosphatase have been separated: a membrane preparation of cells that have been treated with epidermal growth factor (EGF) and whose dephosphorylating enzymes have been permanently destroyed by iodoacetamide can be mixed with a membrane preparation from untreated cells which re-establishes EGFR dephosphorylation. This dephosphorylation can be modulated in vitro by UV and thiol agents. We conclude that RTKs exhibit significant spontaneous protein kinase activity; several adverse agents target (an) essential SH-group(s) carried by (a) membrane-bound protein tyrosine phosphatase(s). Images PMID:8895576

  11. Targeting nasopharyngeal carcinoma by artesunate through inhibiting Akt/mTOR and inducing oxidative stress.

    PubMed

    Li, Qin; Ni, Wei; Deng, Zhifeng; Liu, Minghe; She, Lazhi; Xie, Qiong

    2017-01-11

    Drug repurposing has become an alternative therapeutic strategy for cancer treatment given the known pharmacokinetics and toxicity. The inhibitory effects of artesunate have been reported in various cancers. In this work, we investigated the effects of artesunate in nasopharyngeal carcinoma (NPC). We demonstrate that artesunate significantly inhibits proliferation via arresting NPC cells at G2/M phase. It also induces apoptosis through caspase-dependent and mitochondria-independent pathways in multiple NPC cell lines. The combination of artesunate and cisplatin is synergistic in targeting NPC cells in in vitro cellular culture system and in vivo xenograft tumor models. Artesunate inhibits phosphorylation of essential molecules involved in Akt/mTOR pathway in NPC cells, such as Akt, mTOR, and 4EBP1, and its inhibitory effects are partially abolished by overexpression of constitutively active Akt. In addition, artesunate also induces mitochondrial dysfunction and oxidative stress via inhibiting mitochondrial respiration, increasing levels of mitochondrial superoxide and cellular reactive oxygen species (ROS), leading to decreased ATP levels. Two ROS scavengers partially abolish the inhibitory effects of artesunate in NPC cells. These data suggest that both inhibition of Akt/mTOR pathway and induction of ROS are required for the action of artesunate in NPC cells. Our work demonstrates that artesunate is a potential candidate for NPC treatment. Our work also highlights the critical roles of Akt/mTOR pathway and mitochondrial function in NPC cells.

  12. Superparamagnetic Iron Oxide Nanoparticles Coated with Galactose-Carrying Polymer for Hepatocyte Targeting

    PubMed Central

    Yoo, Mi Kyong; Kim, In Yong; Kim, Eun Mi; Jeong, Hwan-Jeong; Lee, Chang-Moon; Jeong, Yong Yeon; Akaike, Toshihiro; Cho, Chong Su

    2007-01-01

    Our goal is to develop the functionalized superparamagnetic iron oxide nanoparticles (SPIONs) demonstrating the capacities to be delivered in liver specifically and to be dispersed in physiological environment stably. For this purpose, SPIONs were coated with polyvinylbenzyl-O-β-D-galactopyranosyl-D-gluconamide (PVLA) having galactose moieties to be recognized by asialoglycoprotein receptors (ASGP-R) on hepatocytes. For use as a control, we also prepared SPIONs coordinated with 2-pyrrolidone. The sizes, size distribution, structure, and coating of the nanoparticles were characterized by transmission electron microscopy (TEM), electrophoretic light scattering spectrophotometer (ELS), X-ray diffractometer (XRD), and Fourier transform infrared (FT-IR), respectively. Intracellular uptake of the PVLA-coated SPIONs was visualized by confocal laser scanning microscopy, and their hepatocyte-specific delivery was also investigated through magnetic resonance (MR) images of rat liver. MRI experimental results indicated that the PVLA-coated SPIONs possess the more specific accumulation property in liver compared with control, which suggests their potential utility as liver-targeting MRI contrast agent. PMID:18317519

  13. MiR-590-5p Inhibits Oxidized- LDL Induced Angiogenesis by Targeting LOX-1

    PubMed Central

    Dai, Yao; Zhang, Zhigao; Cao, Yongxiang; Mehta, Jawahar L.; Li, Jun

    2016-01-01

    Oxidized low-density lipoprotein (ox-LDL) is, at least in part, responsible for angiogenesis in atherosclerotic regions. This effect of ox-LDL has been shown to be mediated through a specific receptor LOX-1. Here we describe the effect of miR-590-5p on ox-LDL-mediated angiogenesis in in vitro and in vivo settings. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-590-5p mimic or inhibitor followed by treatment with ox-LDL. In other experiments, Marigel plugs were inserted in the mice subcutaneous space. Both in vitro and in vivo studies showed that miR-590-5p mimic (100 nM) inhibited the ox-LDL-mediated angiogenesis (capillary tube formation, cell proliferation and migration as well as pro-angiogenic signals- ROS, MAPKs, pro-inflammatory cytokines and adhesion-related proteins). Of note, miR-590-5p inhibitor (200 nM) had the opposite effects. The inhibitory effect of miR-590-5p on angiogenesis was mediated by inhibition of LOX-1 at translational level. The inhibition of LOX-1 by miR-590-5p was confirmed by luciferase assay. In conclusion, we show that MiR-590-5p inhibits angiogenesis by targeting LOX-1 and suppressing redox-sensitive signals. PMID:26932825

  14. Magnetic Resonance Imaging of Atherosclerosis Using CD81-Targeted Microparticles of Iron Oxide in Mice

    PubMed Central

    Yan, Fei; Yang, Wei; Li, Xiang; Liu, Hongmei; Nan, Xiang; Xie, Lisi; Zhou, Dongliang; Xie, Guoxi; Wu, Junru; Qiu, Bensheng; Liu, Xin; Zheng, Hairong

    2015-01-01

    The goal of this study is to investigate the feasibility of using CD81- (Cluster of Differentiation 81 protein-) targeted microparticles of iron oxide (CD81-MPIO) for magnetic resonance imaging (MRI) of the murine atherosclerosis. CD81-MPIO and IgG- (Immunoglobulin G-) MPIO were prepared by covalently conjugating, respectively, with anti-CD81 monoclonal and IgG antibodies to the surface of the tosyl activated MPIO. The relevant binding capability of the MPIO was examined by incubating them with murine bEnd.3 cells stimulated with phenazine methosulfate (PMS) and its effect in shortening T2 relaxation time was also examined. MRI in apolipoprotein E-deficient mice was studied in vivo. Our results show that CD81-MPIO, but not IgG-MPIO, can bind to the PMS-stimulated bEnd.3 cells. The T2 relaxation time was significantly shortened for stimulated bEnd.3 cells when compared with IgG-MPIO. In vivo MRI in apolipoprotein E-deficient mice showed highly conspicuous areas of low signal after CD81-MPIO injection. Quantitative analysis of the area of CD81-MPIO contrast effects showed 8.96- and 6.98-fold increase in comparison with IgG-MPIO or plain MPIO, respectively (P < 0.01). Histological assay confirmed the expression of CD81 and CD81-MPIO binding onto atherosclerotic lesions. In conclusion, CD81-MPIO allows molecular assessment of murine atherosclerotic lesions by magnetic resonance imaging. PMID:26266263

  15. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis

    PubMed Central

    Cassano, Paolo; Petrie, Samuel R.; Hamblin, Michael R.; Henderson, Theodore A.; Iosifescu, Dan V.

    2016-01-01

    Abstract. We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: “near-infrared radiation,” “NIR,” “low-level light therapy,” “low-level laser therapy,” or “LLLT” plus “depression.” We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD. PMID:26989758

  16. Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy.

    PubMed

    Dilnawaz, Fahima; Singh, Abhalaxmi; Mohanty, Chandana; Sahoo, Sanjeeb K

    2010-05-01

    The primary inadequacy of chemotherapeutic drugs is their relative non-specificity and potential side effects to the healthy tissues. To overcome this, drug loaded multifunctional magnetic nanoparticles are conceptualized. We report here an aqueous based formulation of glycerol monooleate coated magnetic nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor necrosis factor alpha assay, confocal microscopy. High entrapment efficiency approximately 95% and sustained release of encapsulated drugs for more than two weeks under in vitro conditions was achieved for different anticancer drugs (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not affect the magnetization properties of the iron oxide core as confirmed by magnetization study. Additionally the MNPs were functionalized with carboxylic groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary conjugation of amines. For targeted therapy, HER2 antibody was conjugated to GMO-MNPs and showed enhanced uptake in human breast carcinoma cell line (MCF-7). The IC(50) doses revealed potential antiproliferative effect in MCF-7. Therefore, antibody conjugated GMO-MNPs could be used as potential drug carrier for the active therapeutic aspects in cancer therapy.

  17. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.

    PubMed

    Cassano, Paolo; Petrie, Samuel R; Hamblin, Michael R; Henderson, Theodore A; Iosifescu, Dan V

    2016-07-01

    We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

  18. Red fluorescent zinc oxide nanoparticle: A novel platform for cancer targeting

    DOE PAGES

    Hong, Hao; Wang, Fei; Zhang, Yin; ...

    2015-01-21

    Multifunctional zinc oxide (ZnO) nanoparticles (NPs) with well-integrated multimodality imaging capacities have generated increasing research interest in the past decade. However, limited progress has been made in developing ZnO NP-based multimodality tumor-imaging agents. In this paper, we developed novel red fluorescent ZnO NPs and described the successful conjugation of 64Cu (t1/2 = 12.7 h) and TRC105, a chimeric monoclonal antibody against CD105, to these ZnO NPs via well-developed surface engineering procedures. The produced dual-modality ZnO NPs were readily applicable for positron emission tomography (PET) imaging and fluorescence imaging of the tumor vasculature. Their pharmacokinetics and tumor-targeting efficacy/specificity in mice bearingmore » murine breast 4T1 tumor were thoroughly investigated. In conclusion, ZnO NPs with dual-modality imaging properties can serve as an attractive candidate for future cancer theranostics.« less

  19. Trace elements profile is associated with insulin resistance syndrome and oxidative damage in thyroid disorders: Manganese and selenium interest in Algerian participants with dysthyroidism.

    PubMed

    Maouche, Naima; Meskine, Djamila; Alamir, Barkahoum; Koceir, Elhadj-Ahmed

    2015-10-01

    The relationship between dysthyroidism and antioxidant trace elements (ATE) status is very subtle during oxidative stress (OS). This relationship is mediated by thyroid hormone (TH) disorder, insulin resistance syndrome (IRS) and inflammation. The aim of this study was to investigate ATE such as selenium (Se), manganese (Mn), zinc (Zn) and copper (Cu) status on thyroid dysfunction, and their interaction with antioxidant enzyme activities, mainly, superoxide dismutase (SOD) and glutathione peroxidase (GPx), TH profile (TSH, T(3), T(4)) and IRS clusters. The study was undertaken on 220 Algerian adults (30-50 years), including 157 women and 63 men who were divided to 4 groups: subclinical hypothyroidism (n = 50), overt hypothyroidism (n = 60), Graves's disease hyperthyroidism (n = 60) and euthyroid controls (n = 50). The IRS was confirmed according to NCEP (National Cholesterol Education Program). Insulin resistance was evaluated by HOMA-IR model. Trace elements were determined by the Flame Atomic Absorption Spectrometry (Flame-AAS) technique. The antioxidant enzymes activity and metabolic parameters were determined by biochemical methods. The TH profile and anti-Thyroperoxidase Antibodies (anti-TPO-Ab) were evaluated by radioimmunoassay. Results showed that the plasma manganese levels were significantly increased in all dysthyroidism groups (p ≤ 0.01). However, the plasma copper and zinc concentrations were maintained normal or not very disturbed vs control group. In contrast, the plasma selenium levels were highly decreased (p ≤ 0.001) and positively correlated with depletion of glutathione peroxidase activity; and associated both with anti-TPO-Ab overexpression and fulminant HS-CRP levels. This study confirms the oxidative stress-inflammation relationship in the dysthyroidism. The thyroid follicles antioxidant protection appears preserved in the cytosol (Cu/Zn-SOD), while it is altered in the mitochondria (Mn-SOD), which gives this cell organelle, a status of

  20. Proceedings of transuranium elements

    SciTech Connect

    Not Available

    1992-01-01

    The identification of the first synthetic elements was established by chemical evidence. Conclusive proof of the synthesis of the first artificial element, technetium, was published in 1937 by Perrier and Segre. An essential aspect of their achievement was the prediction of the chemical properties of element 43, which had been missing from the periodic table and which was expected to have properties similar to those of manganese and rhenium. The discovery of other artificial elements, astatine and francium, was facilitated in 1939-1940 by the prediction of their chemical properties. A little more than 50 years ago, in the spring of 1940, Edwin McMillan and Philip Abelson synthesized element 93, neptunium, and confirmed its uniqueness by chemical means. On August 30, 1940, Glenn Seaborg, Arthur Wahl, and the late Joseph Kennedy began their neutron irradiations of uranium nitrate hexahydrate. A few months later they synthesized element 94, later named plutonium, by observing the alpha particles emitted from uranium oxide targets that had been bombarded with deuterons. Shortly thereafter they proved that is was the second transuranium element by establishing its unique oxidation-reduction behavior. The symposium honored the scientists and engineers whose vision and dedication led to the discovery of the transuranium elements and to the understanding of the influence of 5f electrons on their electronic structure and bonding. This volume represents a record of papers presented at the symposium.

  1. An estrogen-responsive element-targeted histone deacetylase enzyme has an antiestrogen activity that differs from that of hydroxytamoxifen.

    PubMed

    Demirpence, Ediz; Semlali, Abdelhabib; Oliva, Joan; Balaguer, Patrick; Badia, Eric; Duchesne, Marie-Josèphe; Nicolas, Jean-Claude; Pons, Michel

    2002-11-15

    We showed previously that prolonged treatment of a MCF-7-derived cell line with hydroxytamoxifen (OHT) induces the irreversible silencing of some estrogen-responsive genes, whereas OHT-resistant cell growth appears simultaneously (E. Badia et al., Cancer Res., 60: 4130-4138, 2000). Based on the hypothesis that particular gene silencings could be involved in triggering the resistance phenomenon, we focused our study on the mechanism of OHT-induced silencing. More precisely, we wished to determine to what extent the recruited histone deacetylase (HDAC) activity, which is known to be involved in the repressive effect induced by antagonist ligands of nuclear receptors, could participate in various aspects of OHT effects, particularly in gene silencing. A fusion protein (HDAC-EG) of human HDAC1 fused with the estrogen receptor DNA-binding domain and the glucocorticoid receptor ligand-binding domain allowed targeting of chimeric HDAC1 activity on estrogen-responsive elements (EREs) in the presence of glucocorticoid ligands. When HDAC-EG was transiently expressed in HeLa cells together with estrogen receptor, an antiestrogen-like effect was obtained on an ERE-controlled luciferase reporter gene in the presence of agonist or antagonist glucocorticoids. In MCF-7-derived cells stably expressing HDAC-EG and an estrogen-regulated luciferase, liganded HDAC-EG again produced an antiestrogenic effect on expression of natural estrogen-regulated genes such as pS2, progesterone receptor, and cathepsin D and cell growth together with chimeric luciferase gene expression. However, a prolonged HDAC-EG-mediated antiestrogen effect did not lead to irreversible luciferase gene silencing, as OHT does. It nevertheless accelerated the OHT-driven phenomenon. The antiestrogen effect of OHT thus differs from that of an ERE-targeted HDAC1 activity that might participate in irreversible silencing but is not sufficient to trigger it.

  2. Oxidized As (V) in fore-arc mantle serpentinites: Transfer of fluid-soluble elements from slabs to arc magmas

    NASA Astrophysics Data System (ADS)

    Hattori, K. H.; Takahashi, Y.; Guillot, S.; Johanson, B.

    2004-12-01

    Fluids released from subducting slabs and sediments hydrate the overlying peridotites in mantle wedges. Such hydrated peridotites (serpentinites) are enriched in fluid-soluble elements, although insoluble elements show the refractory geochemical signature. The enrichment pattern of serpentinites is similar to that of arc magmas (Hattori & Guillot, 2003 in Geology). Arsenic is one of the most enriched soluble elements, reaching greater than 1000 times of the primitive mantle value. We examined the speciation and occurrence of As in serpentinites to understand how such a highly mobile element can be transferred from subducting slabs to arc magmas via mantle wedges. Our study used serpentinites associated with the Tso Morari eclogitic rocks in the Indus Suture Zone of Himalaya. They represent the hydrated peridotites at the base of mantle wedge beneath the margin of Eurasia and were exhumed from the depth of about 100 km during the active subduction of the Indian continental margin. The serpentinites are made up of antigorite, chromite, minor talc. It contains As ranging from 6 to 275 ppm and S up to 51 ppm, but most have S below detection limit, 4 ppm. X-ray absorption spectroscopy data show that As is mostly As(V) and combined with oxygen, although Minute grains of As-bearing sulphides and arsenides are identified in samples. The fractions of As(V), calculated from the X-ray absorption near-edge structure, are greater in samples with higher As contents. High proportion of As(V) in the fore-arc mantle serpentinites contasts with high As(III) in the serpentinite at the base of the Nidar ophiolite. The source of As (V) in the serpentinites is most likely As adsorped on Fe- and Mn-oxides in subducted sediments and slabs. It was released during the subduction of slab and sediments at low temperatures, \\< 350° C, and shallow depths, \\< 25 km. Continuous flux of water from slabs at the base of the mantle wedge likely maintained As in oxidized condition. Arsenic in the

  3. Glioma-targeted superparamagnetic iron oxide nanoparticles as drug-carrying vehicles for theranostic effects

    NASA Astrophysics Data System (ADS)

    Xu, He-Lin; Mao, Kai-Li; Huang, Yin-Ping; Yang, Jing-Jing; Xu, Jie; Chen, Pian-Pian; Fan, Zi-Liang; Zou, Shuang; Gao, Zheng-Zheng; Yin, Jia-Yu; Xiao, Jian; Lu, Cui-Tao; Zhang, Bao-Lin; Zhao, Ying-Zheng

    2016-07-01

    Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug-carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX. DOX-loaded multifunctional nanoparticles (DOX@Ps 80-SPIONs) with a Dh of 58.0 nm, a zeta potential of 28.0 mV, and a drug loading content of 29.3% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 24.1 emu g-1. The cellular uptake of DOX@Ps 80-SPIONs by C6 cells under a magnetic field was significantly enhanced over that of free DOX in solution, resulting in stronger in vitro cytotoxicity. The real-time therapeutic outcome of DOX@Ps 80-SPIONs was easily monitored by MRI. Furthermore, the negative contrast enhancement effect of the nanoparticles was confirmed in glioma-bearing rats. Prussian blue staining and ex vivo DOX fluorescence assays showed that the magnetic Ps 80-SPIONs and encapsulated DOX were delivered to gliomas by imposing external magnetic fields, indicating effective magnetic targeting. Due to magnetic targeting and Ps 80-mediated endocytosis, DOX@Ps 80-SPIONs in the presence of a magnetic field led to the complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism of DOX@Ps 80-SPIONs acted by inducing apoptosis through the caspase-3 pathway. Finally, DOX@Ps 80-SPIONs' safety at therapeutic dosage was verified using pathological HE assays of the heart, liver, spleen, lung and kidney. Multifunctional SPIONs could be used as potential carriers for the

  4. Folic acid-grafted bovine serum albumin decorated graphene oxide: An efficient drug carrier for targeted cancer therapy.

    PubMed

    Ma, Naxin; Liu, Jing; He, Wenxiu; Li, Zhonghao; Luan, Yuxia; Song, Yunmei; Garg, Sanjay

    2017-03-15

    Targeting drug carrier systems based on graphene oxide (GO) are of great interest, since it can selectively deliver anticancer drugs to tumor cells, and enhance therapeutic activities with minimized side effects. However, direct grafting target molecules on GO usually results in aggregation of physiological fluid, limiting its biomedical applications. Here, we propose a new strategy to construct targeting GO drug carrier using folic acid grafted bovine serum albumin (FA-BSA) as both the stabilizer and targeting agent. FA-BSA decorated graphene oxide-based nanocomposite (FA-BSA/GO) was fabricated by the physical adsorption of FA-BSA on GO, which was developed as a targeting drug delivery carrier. FA-BSA/GO as the drug carrier was associated with anticancer drug doxorubicin (DOX) through π-π and hydrogen-bond interactions, resulting in high drug loading (up to 437.43μgDOX/mgFA-BSA/GO). FA-BSA/GO/DOX systems demonstrated pH responsive and sustained drug release. The hemolysis ratio of FA-BSA/GO was less than 5%, demonstrating its safety as drug carrier for intravenous injection. Moreover, in vitro cell cytotoxicity and cellular uptake analysis suggested that the constructed FA-BSA/GO/DOX nanohybrids could significantly enhance the anticancer activity. The present work has confirmed the potential for fabrication of highly stable and dispersible GO-based targeting delivery systems for efficient cancer therapy.

  5. Respiratory Ammonification of Nitrate Coupled to Anaerobic Oxidation of Elemental Sulfur in Deep-Sea Autotrophic Thermophilic Bacteria

    PubMed Central

    Slobodkina, Galina B.; Mardanov, Andrey V.; Ravin, Nikolai V.; Frolova, Anastasia A.; Chernyh, Nikolay A.; Bonch-Osmolovskaya, Elizaveta A.; Slobodkin, Alexander I.

    2017-01-01

    Respiratory ammonification of nitrate is the microbial process that determines the retention of nitrogen in an ecosystem. To date, sulfur-dependent dissimilatory nitrate reduction to ammonium has been demonstrated only with sulfide as an electron donor. We detected a novel pathway that couples the sulfur and nitrogen cycles. Thermophilic anaerobic bacteria Thermosulfurimonas dismutans and Dissulfuribacter thermophilus, isolated from deep-sea hydrothermal vents, grew autotrophically with elemental sulfur as an electron donor and nitrate as an electron acceptor producing sulfate and ammonium. The genomes of both bacteria contain a gene cluster that encodes a putative nitrate ammonification enzyme system. Nitrate reduction occurs via a Nap-type complex. The reduction of produced nitrite to ammonium does not proceed via the canonical Nrf system because nitrite reductase NrfA is absent in the genomes of both microorganisms. The genome of D. thermophilus encodes a complete sulfate reduction pathway, while the Sox sulfur oxidation system is missing, as shown previously for T. dismutans. Thus, in high-temperature environments, nitrate ammonification with elemental sulfur may represent an unrecognized route of primary biomass production. Moreover, the anaerobic oxidation of sulfur compounds coupled to growth has not previously been demonstrated for the members of Thermodesulfobacteria or Deltaproteobacteria, which were considered exclusively as participants of the reductive branch of the sulfur cycle. PMID:28194142

  6. Spectroscopic Studies of Band Edge Electronic States in Elemental High-k Oxide Dielectrics on Si and Ge Substrates

    SciTech Connect

    Lucovsky, G.; Seo, H.; Fleming, L. B.; Ulrich, M. D.; Luening, J.

    2007-09-26

    This paper uses X-ray absorption spectroscopy, and vacuum ultra-violet spectroscopic ellipsometry to distinguish between i) non-crystallinity, and ii) nano-crystallinity in transition metal (TM) elemental oxides. Near edge X-ray absorption spectroscopy is used to distinguish between two different scales of nano-crystalline order. The observation of band edge Jahn-Teller splittings in anti-bonding states with TM p-character correlate with the observation of nano-crystalline-order that can be detected by X-ray diffraction, and establish a length scale for order, {lambda}{sub s}>3 to 4 nm, The suppression of J-T splittings, and a spectral broadening is associated with reduced nano-crystalline order that can be detected by atomic-scale imaging and/or extended X-ray absorption spectroscopy for {lambda}{sub s}<{approx}2.5 nm. These different states of nano-crystalline grain-size order for addressed in elemental transition metal oxides on both Si and Ge substrates.

  7. Gene expression promoted by the SV40 DNA targeting sequence and the hypoxia-responsive element under normoxia and hypoxia.

    PubMed

    Sacramento, C B; Moraes, J Z; Denapolis, P M A; Han, S W

    2010-08-01

    The main objective of the present study was to find suitable DNA-targeting sequences (DTS) for the construction of plasmid vectors to be used to treat ischemic diseases. The well-known Simian virus 40 nuclear DTS (SV40-DTS) and hypoxia-responsive element (HRE) sequences were used to construct plasmid vectors to express the human vascular endothelial growth factor gene (hVEGF). The rate of plasmid nuclear transport and consequent gene expression under normoxia (20% O2) and hypoxia (less than 5% O2) were determined. Plasmids containing the SV40-DTS or HRE sequences were constructed and used to transfect the A293T cell line (a human embryonic kidney cell line) in vitro and mouse skeletal muscle cells in vivo. Plasmid transport to the nucleus was monitored by real-time PCR, and the expression level of the hVEGF gene was measured by ELISA. The in vitro nuclear transport efficiency of the SV40-DTS plasmid was about 50% lower under hypoxia, while the HRE plasmid was about 50% higher under hypoxia. Quantitation of reporter gene expression in vitro and in vivo, under hypoxia and normoxia, confirmed that the SV40-DTS plasmid functioned better under normoxia, while the HRE plasmid was superior under hypoxia. These results indicate that the efficiency of gene expression by plasmids containing DNA binding sequences is affected by the concentration of oxygen in the medium.

  8. Stimulatory Effect of Xenobiotics on Oxidative Electron Transport of Chemolithotrophic Nitrifying Bacteria Used as Biosensing Element

    PubMed Central

    Woznica, Andrzej; Nowak, Agnieszka; Ziemski, Przemyslaw; Kwasniewski, Mirosław; Bernas, Tytus

    2013-01-01

    Electron transport chain (ETCh) of ammonium (AOB) and nitrite oxidizing bacteria (NOB) participates in oxidation of ammonium to nitrate (nitrification). Operation of ETCh may be perturbed by a range of water-soluble xenobiotics. Therefore, consortia of nitrifying bacteria may be used as a biosensor to detect water contamination. A surprising feature of this system is an increase of oxygen consumption, detected in the presence of certain inhibitors of ETCh. Thus, to shed light on the mechanism of this effect (and other differences between inhibitors) we monitored separately respiration of the bacteria of the first (AOB - Nitrosomonas) and second (NOB -Nitrobacter) stages of nitrification. Furthermore, we measured plasma membrane potential and the level of reduction of NAD(P)H. We propose a novel model of ETCh in NOB to explain the role of reverse electron transport in the stimulation of oxygen consumption (previously attributed to hormesis). PMID:23326438

  9. Oxidation of elemental mercury by chlorine: Gas phase, Surface,and Photo-induced reaction pathways

    SciTech Connect

    Yan, Nai-Qiang; Liu, Shou-Heng; Chang, Shih-Ger

    2004-10-22

    Accurate oxidation rate constants of mercury gas are needed for determining its dispersion and lifetime in the atmosphere. They would also help in developing a technology for the control of mercury emissions from coal-fired power plants. However, it is difficult to establish the accurate rate constants primarily due to the fact that mercury easily adsorbs on solid surface and its reactions can be catalyzed by the surface. We have demonstrated a procedure that allows the determination of gas phase, surface-induced, and photo-induced contributions in the kinetic study of the oxidation of mercury by chlorine gas. The kinetics was studied using reactors with various surface to volume ratios. The effect of the surface and the photo irradiation on the reaction was taken into consideration. The pressure dependent study revealed that the gas phase oxidation was a three-body collision process. The third order rate constant was determined to be 7.5({+-}0.2) x 10{sup -39} mL{sup 2} molecules{sup -2}s{sup -1} with N{sub 2} as the third body at 297 {+-} 1 K. The surface induced reaction on quartz window was second order and the rate constant was 2.7 x 10{sup -17} mL{sup 2} molecules{sup -1} cm{sup -2} sec. Meanwhile, the 253.7 nm photon employed for mercury detection was found to accelerate the reaction. The utilization efficiency of 253.7 nm photon for Hg{sup 0} oxidation was 6.7 x 10{sup -4} molecules photon{sup -1} under the conditions employed in this study.

  10. Energy Transfer between Post-Transition Elements & Rare Earths in Oxide & Chalcogenide Glasses.

    DTIC Science & Technology

    1979-08-27

    narrow- 37 line excitation F. Optical transitions of Sm3+ in oxide glasses 41 G. Energy transfer from U i+ to Sm3+ in phosphate glass 45 H. Transition...probabilities of europium(III) in zirconium 50 and beryllium fluoride glasses, phosphate glass and pentaphosphate crystals I. Multiphonon relaxation in...in phosphate , borate, germa- nate and tellurite glasses. The level fluorescent lifetime was derived from these rates and from the calculated radiative

  11. Enhancing the Oxidation Performance of Wrought Ni-Base Superalloy by Minor Additions of Active Elements

    NASA Astrophysics Data System (ADS)

    Tawancy, H. M.

    2016-12-01

    We show that the oxidation performance of Cr2O3-forming superalloy based upon the Ni-Cr-W system is significantly improved by the presence of minor concentrations of La, Si and Mn, which outweigh the detrimental effect of high W concentration in the alloy. Although Cr2O3 is known to transform into volatile CrO3 at temperatures ≥950 °C, the respective protection is extended to temperatures reaching 1150 °C, which has also been correlated with the beneficial effects of La, Si and Mn. During high-temperature oxidation, an inner protective La- and Si-modified layer of α-Cr2O3 in contact with the superalloy substrate is developed and shielded by an outermost layer of MnCr2O4. The distribution of La and Si in the inner oxide layer has been characterized down to the scale of transmission electron microscopy, and the possible mechanisms underlying their beneficial effects are elucidated.

  12. The synergistic effect of folate and RGD dual ligand of nanographene oxide on tumor targeting and photothermal therapy in vivo

    NASA Astrophysics Data System (ADS)

    Jang, Cheol; Lee, Jong Hyun; Sahu, Abhishek; Tae, Giyoong

    2015-11-01

    Effective delivery of nanoparticles to the target site is necessary for successful biomedical applications. Inefficient targeting is a major concern for nanomedicines in cancer therapy. Conjugation of multiple targeting ligands to the nanoparticle surface might further enhance the targeting efficiency by a co-operative effect of individual ligands. In this study, a dual ligand targeting nanographene oxide (nGO) was developed by non-covalent interaction with folate and cRGD functionalized pluronic, which allowed precise control of ligand number on the nGO surface and ensured stability under physiological conditions. The tumor targeting abilities of single and dual ligand decorated nGOs were evaluated in vitro by using KB cells, over-expressing folate and integrin αvβ3 receptors. In vitro cellular uptake analysis by flow cytometry and confocal laser scanning microscopy showed enhanced uptake of dual ligand modified nGO compared to any of the single ligand modified nGOs. The cellular uptake of dual targeted cRGD-FA-nGO was increased by 1.9 and 2.4 folds compared to single targeted cRGD-nGO or FA-nGO, respectively. The in vivo biodistribution experiment in a mouse xenograft model also confirmed the synergistic targeting effect of cRGD and folate dual functionalized nGO. A significantly higher tumor accumulation of cRGD-FA-nGO was observed compared to cRGD-nGO or FA-nGO. The higher tumor accumulation of dual targeted nGO resulted in complete ablation of tumor tissue through an enhanced photothermal effect by NIR laser irradiation. Therefore, co-functionalization of a nanoparticle by cRGD and folate is a potentially useful way to enhance the tumor targeting efficacy.Effective delivery of nanoparticles to the target site is necessary for successful biomedical applications. Inefficient targeting is a major concern for nanomedicines in cancer therapy. Conjugation of multiple targeting ligands to the nanoparticle surface might further enhance the targeting efficiency by a

  13. In Vivo Molecular MRI Imaging of Prostate Cancer by Targeting PSMA with Polypeptide-Labeled Superparamagnetic Iron Oxide Nanoparticles

    PubMed Central

    Zhu, Yunkai; Sun, Ying; Chen, Yaqing; Liu, Weiyong; Jiang, Jun; Guan, Wenbin; Zhang, Zhongyang; Duan, Yourong

    2015-01-01

    The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa. PMID:25927579

  14. Inhibitory effects and oxidative target site of dibutyl phthalate on Karenia brevis.

    PubMed

    Li, Feng-min; Wu, Miao; Yao, Yuan; Zheng, Xiang; Zhao, Jian; Wang, Zhen-yu; Xing, Bao-shan

    2015-08-01

    The inhibitory action and possible damage mechanism of dibutyl phthalate (DBP) on the red tide algae Karenia brevis were investigated. The results showed that the algae experienced oxidative stress after exposure to 5mgL(-1) DBP. Malondialdehyde (MDA) peaked after 72h, with a value approximately 2.3 times higher than that observed for untreated cells. The superoxide dismutase (SOD) and catalase (CAT) activities significantly increased as an adaptive reaction after 48h. DBP induced the overproduction of reactive oxygen species (ROS), the OH concentration showed a peak of 33UmL(-1) at 48h, and the highest H2O2 content was approximately 250nmol/10(7) cells at 72h; these latter two values were 2.5 and 4.4 times higher than observed for the control, respectively. TEM images showed that a number of small vacuoles or apical tubers were commonly found around the cell membrane, and the membrane structure was ultimately disintegrated. Further experiments were carried out to locate the original ROS production sites following DBP exposure. The activity of CuZn-SOD (a mainly cytosolic isoform, with some also found in chloroplasts) under DBP exposure was approximately 2.5 times higher than the control, whereas the Mn-SOD (mitochondrial isoform) activity was significantly inhibited. No significant difference was observed in the activity of Fe-SOD (chloroplastic isoform). In addition, dicumarol (an inhibitor of the electron transport chain in the plasma membrane) stimulated DBP-induced ROS production, whereas rotenone (an inhibitor of the mitochondria electron transport chain complex I) decreased DBP-induced ROS production. These results suggested that mitochondria could be the main target sites for DBP attack.

  15. Synthesis and f-element ligation properties of NCMPO-decorated pyridine N-oxide platforms

    SciTech Connect

    Ouizem, Sabrina; Rosario-Amorin, Daniel; Dickie, D. A.; Paine, Robert T.; De Bettencourt-Dias, Ana; Hay, Benjamin; Podair, Julien; Delmau, Laetitia Helene

    2014-01-01

    Stepwise syntheses of 2-{[2-(diphenylphosphoryl)acetamido]methyl}pyridine 1-oxide, 2-[Ph2P(O)CH2C(O)N(H)CH2]C5H4NO (6), 2-{[2-(diphenylphosphoryl)acetamido]methyl}-6-[(diphenylphosphoryl)methyl]pyridine 1-oxide, 2-[Ph2P(O)CH2C(O)N(H)CH2]-6-[Ph2P(O)CH2]C5H3NO (7) and 2,6-bis{[2-(diphenylphosphoryl)acetamido]methyl}pyridine 1-oxide, 2,6-[Ph2P(O)CH2C(O)N(H)CH2]2C5H3NO (8), are reported along with spectroscopic characterization data and single crystal X-ray diffraction structure determination for 6 2H2O, 7 and 2,6-[Ph2P(O)CH2C(O)N(H)CH2]2C5H3N MeOH 18 MeOH, the pyridine precursor of 8. Molecular mechanics computations indicate that 6, 7 and 8 should experience minimal steric hindrance to donor group reorganization that would permit tridentate, tetradentate and pentadentate docking structures for the respective ligands on lanthanide cations. However, crystal structure determination for the lanthanide complexes, {[Yb(6)(NO3)3] (MeOH)}n, {[Lu(6)(NO3)3] (MeOH)}n, [Er(6)2(H2O)2](NO3)3 (H2O)4}n, {[La(13)(NO3)3(MeOH)] (MeOH)}n, {[Eu(7)(NO3)2(EtOAc)0.5(H2O)0.5](NO3)}2 MeOH and [Dy3(7)4(NO3)4(H2O)2](NO3)5 (MeOH)5 (H2O)2 reveal solid-state structures with mixed chelating/bridging ligand:Ln(III) interactions that employ lower than the maximal denticity. The binding of 6 and 7 with Eu(III) in the solid state and in MeOH solutions is also accessed by emission spectroscopy. The acid dependence for solvent extractions with 6 and 7 in 1,2-dichloroethane for Eu(III) and Am(III) in nitric acid solutions is described and compared with the behavior of n-octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (OPhDiBCMPO, 1b) and 2-[(diphenyl)phosphinoylmethyl]pyridine N-oxide (DPhNOPO, 4a).

  16. Trace element and isotope studies in oxide/phosphate/silicate inclusions of iron meteorites

    NASA Technical Reports Server (NTRS)

    Olsen, Edward J.

    1996-01-01

    Under the above grant research was funded in the following areas: 1. Pallasites: Rare earth element measurements in phosphates to determine if all pallasites fit into only two trace element groups. This work has been completed. 2. HIAB irons: To complete work on the only known silicate inclusion in a IIIAB iron meteorite. This work has been completed. 3. IIIAB irons: To continue the search for Cr-53 excesses in IIIAB iron meteorite phosphates. A part of this work has been completed 4. IIIAB irons: To complete the identification of the phosphate minerals in IIIAB iron meteorites and try to determine the phase relations and chemical history of trace element distributions during the core formation process. Work on this has been largely completed and preliminary results have been reported. The final work is being assessed prior to preparation of a manuscript for publication. 5. IIE irons: To complete work on the unique silicate assemblage in the IIE iron meteorite. Work on this was completed and a paper published. 6. Ungrouped irons: A partially devitrified silicate glass inclusion has been found in the ungrouped iron meteorite. Preliminary work on this has been reported. All the work on this has been now completed and a manuscript has been prepared and submitted for publication.

  17. Intracellular repair of oxidation-damaged α-synuclein fails to target C-terminal modification sites

    PubMed Central

    Binolfi, Andres; Limatola, Antonio; Verzini, Silvia; Kosten, Jonas; Theillet, Francois-Xavier; May Rose, Honor; Bekei, Beata; Stuiver, Marchel; van Rossum, Marleen; Selenko, Philipp

    2016-01-01

    Cellular oxidative stress serves as a common denominator in many neurodegenerative disorders, including Parkinson's disease. Here we use in-cell NMR spectroscopy to study the fate of the oxidation-damaged Parkinson's disease protein alpha-synuclein (α-Syn) in non-neuronal and neuronal mammalian cells. Specifically, we deliver methionine-oxidized, isotope-enriched α-Syn into cultured cells and follow intracellular protein repair by endogenous enzymes at atomic resolution. We show that N-terminal α-Syn methionines Met1 and Met5 are processed in a stepwise manner, with Met5 being exclusively repaired before Met1. By contrast, C-terminal methionines Met116 and Met127 remain oxidized and are not targeted by cellular enzymes. In turn, persisting oxidative damage in the C-terminus of α-Syn diminishes phosphorylation of Tyr125 by Fyn kinase, which ablates the necessary priming event for Ser129 modification by CK1. These results establish that oxidative stress can lead to the accumulation of chemically and functionally altered α-Syn in cells. PMID:26807843

  18. Can the Isolated-Elements Strategy Be Improved by Targeting Points of High Cognitive Load for Additional Practice?

    ERIC Educational Resources Information Center

    Ayres, Paul

    2013-01-01

    Reducing problem complexity by isolating elements has been shown to be an effective instructional strategy. Novices, in particular, benefit from learning from worked examples that contain partially interacting elements rather than worked examples that provide full interacting elements. This study investigated whether the isolating-elements…

  19. Photoexcited Individual Nanowires: Key Elements in Room Temperature Detection of Oxidizing Gases

    SciTech Connect

    Prades, J. D.; Jimenez-Diaz, R.; Manzanares, M.; Andreu, T.; Cirera, A.; Romano-Rodriguez, A.; Morante, J. R.

    2009-05-23

    Illuminating metal oxide semiconductors with ultra-violet light is a feasible alternative to activate chemical reactions at their surface and thus, using them as gas sensors without the necessity of heating them. Here, the response at room temperature of individual single-crystalline SnO{sub 2} nanowires towards NO{sub 2} is studied in detail. The results reveal that similar responses to those obtained with thermally activated sensors can be achieved by choosing the optimal illumination conditions. This finding paves the way to the development of conductometric gas sensors operated at room temperature. The power consumption in these devices is in range with conventional micromachined sensors.

  20. STUDY OF BINARY OXIDES OF URANIUM AND RARE-EARTH ELEMENTS

    DTIC Science & Technology

    The formation of fluorite-type phases was investigated in R2O3- U3O8 - O2 systems (where R-La, Sm, Dy, Yb) annealed for 66-85 hr at 1200C, and the...coulometric analysis at a controlled potential. X-ray phase analysis was carried out by using the powder method with RKD-57 and RKU-86 cameras. The degree of...stability of the hexavalent state of uranium at high temperatures. Contrary to expectations, the solubility of rare earth oxides in U3O8 was found to be very low (less than 1.5 mol % of RO1.5).

  1. Mitochondria-Targeted Antioxidants and Uncouplers of Oxidative Phosphorylation in Treatment of the Systemic Inflammatory Response Syndrome (SIRS).

    PubMed

    Zakharova, Vlada V; Pletjushkina, Olga Yu; Zinovkin, Roman A; Popova, Ekaterina N; Chernyak, Boris V

    2017-05-01

    Systemic inflammatory response syndrome (SIRS) development is accompanied by mitochondrial dysfunction and excessive ROS production. Mitochondrial dysfunctions also occur in many SIRS-related diseases and may be critical for their pathogenesis; therefore, a use of mitochondria-targeted drugs is a promising trend in SIRS research and therapy. Here, we review recent studies concerning the application of the mitochondria-targeted antioxidants and uncouplers of oxidative phosphorylation in animal models of SIRS and related diseases. We propose that a new class of uncouplers of oxidative phosphorylation, lipophilic cations could be a base for a new generation of drugs for SIRS treatment. J. Cell. Physiol. 232: 904-912, 2017. © 2016 Wiley Periodicals, Inc.

  2. Nitric oxide as a target of complementary and alternative medicines to prevent and treat inflammation and cancer

    PubMed Central

    Hofseth, Lorne J.

    2009-01-01

    Nitric oxide (NO) and associated reactive nitrogen species (RNS) are involved in many physiological functions. There has been an ongoing debate to whether RNS can inhibit or perpetuate chronic inflammation and associated carcinogenesis. Although the final outcome depends on the genetic make-up of its target, the surrounding microenvironment, the activity and localization of nitric oxide synthase (NOS) isoforms, and overall levels of NO/RNS, evidence is accumulating that in general, RNS drive inflammation and cancers associated with inflammation. To this end, many complementary and alternative medicines (CAMs) that work in chemoprevention associated with chronic inflammation, are inhibitors of excessive NO observed in inflammatory conditions. Here we review recent literature outlining a role of NO/RNS in chronic inflammation and cancer, and point toward NO as one of several targets for the success of CAMs in treating chronic inflammation and cancer associated with this inflammation. PMID:18440130

  3. Assessing the physiological concentration and targets of nitric oxide in brain tissue

    PubMed Central

    Hall, Catherine N; Attwell, David

    2008-01-01

    Low nanomolar concentrations of nitric oxide activate guanylyl cyclase to produce cGMP, which has diverse physiological effects. Higher concentrations inhibit mitochondrial respiration at cytochrome c oxidase and this has been proposed to be important physiologically, increasing oxygen permeation into tissue (by reducing the oxygen use of cells near blood vessels), activating AMP kinase, and regulating the relationship between cerebral blood flow and oxygen use. It is unclear, however, whether nitric oxide can accumulate physiologically to concentrations at which inhibition of respiration occurs. In rat cerebellar slices, we activated nitric oxide production from each isoform of nitric oxide synthase. Only activation of inducible nitric oxide synthase, which is expressed pathologically, caused any significant inhibition of respiration. Modelling oxygen and nitric oxide concentrations predicted that, in vivo, physiological nitric oxide levels are too low to affect respiration. Even pathologically, the nitric oxide concentration may only rise to 2.5 nm, producing a 1.5% inhibition of respiration. Thus, under physiological conditions, nitric oxide signals do not inhibit respiration but are well-tuned to the dynamic range of guanylyl cyclase activation. PMID:18535091

  4. Supported transition-metal oxide catalysts for reduction of sulfur dioxide with hydrogen to elemental sulfur.

    PubMed

    Chen, Chun-Liang; Wang, Ching-Huei; Weng, Hung-Shan

    2004-08-01

    This work is for the purpose to find a high performance catalyst for the catalytic reduction of SO2 with H2 as a reducing agent. NiO/gamma-Al2O3 catalyst was found to be the most active catalyst among the seven gamma-Al2O3-supported metal-oxide catalysts tested. With NiO as the active species, of the supports tested, gamma-Al2O3 was the most suitable one and the optimal Ni content was 16 wt%. Using this NiO/gamma-Al2O3 catalyst, we found that the optimal feed ratio of H2/SO2 is 2:1 and the catalyst presulfided with H2 + H2S exhibits a higher performance than that pretreated with H2 or He. XRD patterns reveal that the nickel oxide experienced a transformation to Ni3S2 and NiS, and then to NiS2, the most active nickel sulfide, during the reaction process. The reason for the highest catalyst activity of 16 wt% Ni was attributed to the largest amount of NiS2. Water vapor in the feed gas reactant caused inhibition of catalyst activity, whereas H2S promoted the reduction of SO2. These phenomena were rationalized with the aid of Claus reaction.

  5. Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore

    PubMed Central

    Marquardt, Joseph R.; Perkins, Jennifer L.; Beuoy, Kyle J.; Fisk, Harold A.

    2016-01-01

    Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus. PMID:27339139

  6. Joint Recovery of f-Elements Using Solvent Based on Carbamoyl-phosphine Oxides Heading Toward ORGA-Process

    SciTech Connect

    Ozawa, M.; Babain, V.; Shadrin, A.; Strelkov, S.; Kiseleva, R.; Murzin, A.

    2007-07-01

    Development of the recovery system which allows realizing joint recovery of all the actinides from the HLW is one of the relevant questions in radiochemistry. Carbamoyl-phosphine oxides (CMPO) were proposed and studied as extractant for rare-earth and transplutonium elements (RE and TPE) recovery from HLW with high acidity, for example TRUEX- and SETFICS-process. Organic system CMPO with TBP in kerosene is usually used as a solvent. However, low solubility of actinide adducts with CMPO results in third phase formation when the actinides concentration in organic phase is high. Application of fluorinated polar diluents increases the solubility of CMPO adducts with actinides in organic phase. It was shown that solvent based on carbamoyl-phosphonate in fluorinated polar diluents allows to recover both uranium and minor actinides concurrently, and there was no precipitation or third phase formation even at high uranium concentration in organic phase. The f-elements joint recovery process based on this solvent was proposed. Solvent containing octyl-phenyl-N,N-di-isobutyl-carbamoyl-methylene-phosphine oxide (O{phi}D[iB]CMPO) in polar diluent meta-nitro-benzo-trifluoride (fluoro-pole-732) was screened out for these studies. And, combined use of them with TBP modifier allows to provide uranium and europium (americium) high recovery characteristics concurrently with an opportunity of attainment of f-elements high concentration in organic phase. As it was indicated, precipitates or third phase was absent even when uranium content in organic phase was 100 g/l. Recovery efficiency to europium remained sufficiently high for its effective recovery. Organic phase saturation about 100% from theoretical attains in europium recovery with this system. Increasing of (O{phi}D[iB]CMPO) concentration in recovery system from 0.2 to 0.8 M results in europium content increasing in organic phase, but no third phase formation is observed. The highest possible europium content in organic phase

  7. Sputtering deposition of Al-doped zinc oxide thin films using mixed powder targets

    NASA Astrophysics Data System (ADS)

    Ohshima, Tamiko; Maeda, Takashi; Tanaka, Yuki; Kawasaki, Hiroharu; Yagyu, Yoshihito; Ihara, Takeshi; Suda, Yoshiaki

    2016-01-01

    Sputtering deposition generally uses high-density bulk targets. Such a fabrication process has various problems including deterioration of the material during heating and difficulty in mixing a large number of materials in precise proportions. However, these problems can be solved by using a powder target. In this study, we prepared Al-doped ZnO (AZO) as transparent conductive thin films by radio-frequency magnetron sputtering with powder and bulk targets. Both the powder and bulk targets formed crystalline structures. The ZnO (002) peak was observed in the X-ray diffraction measurements. The mean transparency and resistivity of the films prepared with the powder target were 82% and 0.548 Ω · cm, respectively. The deposition rate with the powder target was lower than that with the bulk target.

  8. Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells.

    PubMed

    Kim, Seok-Jo; Cheresh, Paul; Williams, David; Cheng, Yuan; Ridge, Karen; Schumacker, Paul T; Weitzman, Sigmund; Bohr, Vilhelm A; Kamp, David W

    2014-02-28

    Mitochondria-targeted human 8-oxoguanine DNA glycosylase (mt-hOgg1) and aconitase-2 (Aco-2) each reduce oxidant-induced alveolar epithelial cell (AEC) apoptosis, but it is unclear whether protection occurs by preventing AEC mitochondrial DNA (mtDNA) damage. Using quantitative PCR-based measurements of mitochondrial and nuclear DNA damage, mtDNA damage was preferentially noted in AEC after exposure to oxidative stress (e.g. amosite asbestos (5-25 μg/cm(2)) or H2O2 (100-250 μM)) for 24 h. Overexpression of wild-type mt-hOgg1 or mt-long α/β 317-323 hOgg1 mutant incapable of DNA repair (mt-hOgg1-Mut) each blocked A549 cell oxidant-induced mtDNA damage, mitochondrial p53 translocation, and intrinsic apoptosis as assessed by DNA fragmentation and cleaved caspase-9. In contrast, compared with controls, knockdown of Ogg1 (using Ogg1 shRNA in A549 cells or primary alveolar type 2 cells from ogg1(-/-) mice) augmented mtDNA lesions and intrinsic apoptosis at base line, and these effects were increased further after exposure to oxidative stress. Notably, overexpression of Aco-2 reduced oxidant-induced mtDNA lesions, mitochondrial p53 translocation, and apoptosis, whereas siRNA for Aco-2 (siAco-2) enhanced mtDNA damage, mitochondrial p53 translocation, and apoptosis. Finally, siAco-2 attenuated the protective effects of mt-hOgg1-Mut but not wild-type mt-hOgg1 against oxidant-induced mtDNA damage and apoptosis. Collectively, these data demonstrate a novel role for mt-hOgg1 and Aco-2 in preserving AEC mtDNA integrity, thereby preventing oxidant-induced mitochondrial dysfunction, p53 mitochondrial translocation, and intrinsic apoptosis. Furthermore, mt-hOgg1 chaperoning of Aco-2 in preventing oxidant-mediated mtDNA damage and apoptosis may afford an innovative target for the molecular events underlying oxidant-induced toxicity.

  9. Methods for both coating a substrate with aluminum oxide and infusing the substrate with elemental aluminum

    SciTech Connect

    Choi, Jung-Pyung; Weil, Kenneth Scott

    2016-11-01

    Methods of aluminizing the surface of a metal substrate. The methods of the present invention do not require establishment of a vacuum or a reducing atmosphere, as is typically necessary. Accordingly, aluminization can occur in the presence of oxygen, which greatly simplifies and reduces processing costs by allowing deposition of the aluminum coating to be performed, for example, in air. Embodiments of the present invention can be characterized by applying a slurry that includes a binder and powder granules containing aluminum to the metal substrate surface. Then, in a combined step, a portion of the aluminum is diffused into the substrate and a portion of the aluminum is oxidized by heating the slurry to a temperature greater than the melting point of the aluminum in an oxygen-containing atmosphere.

  10. Probing the density of states of two-level tunneling systems in silicon oxide films using superconducting lumped element resonators

    SciTech Connect

    Skacel, S. T.; Kaiser, Ch.; Wuensch, S.; Siegel, M.; Rotzinger, H.; Lukashenko, A.; Jerger, M.; Weiss, G.; Ustinov, A. V.

    2015-01-12

    We have investigated dielectric losses in amorphous silicon oxide (a-SiO) thin films under operating conditions of superconducting qubits (mK temperatures and low microwave powers). For this purpose, we have developed a broadband measurement setup employing multiplexed lumped element resonators using a broadband power combiner and a low-noise amplifier. The measured temperature and power dependences of the dielectric losses are in good agreement with those predicted for atomic two-level tunneling systems (TLS). By measuring the losses at different frequencies, we found that the TLS density of states is energy dependent. This had not been seen previously in loss measurements. These results contribute to a better understanding of decoherence effects in superconducting qubits and suggest a possibility to minimize TLS-related decoherence by reducing the qubit operation frequency.

  11. Comparative Finite Element Analysis of the Stress-Strain States in Three Different Bonded Solid Oxide Fuel Cell Seal Designs

    SciTech Connect

    Weil, K. Scott; Koeppel, Brian J.

    2008-05-15

    One of the critical issues in designing and fabricating a high performance planar solid oxide fuel cell (pSOFC) stack is the development of the appropriate materials and techniques for hermetically sealing the metal and ceramic components. We are currently developing a foil-based approach that appears to offer good hermeticity and mechanical integrity, while minimizing the generation of interfacial stresses in either of the joint substrate materials, particulary the ceramic cell. Prior experimental work conducted on small-scale samples demonstrated the viability of the concept. Here we present recent results from computational analyses undertaken to investigate potential issues associated with scaling up the seal to full-scale pSOFC stack dimensions/geometry. Here we employ finite element modeling to assess the potential thermal cycling performance of this design, specifically as it pertains to sealing components with vastly different thermal expansion properties.

  12. rapid separation of higher actinide elements by cocrystallization using lower oxidation states

    SciTech Connect

    Kamenskaya, A.N.; Konovalova, N.A.; Kulyukhin, S.A.; Mikheev, N.B.

    1986-07-01

    An express method has been developed for the separation of higher actinides based on their cocrystallization with alkali metal halides. By carrying out reduction with the dichlorides of europium, ytterbium, and samarium it was possible to separate mendelevium from fermium, einsteinium, and californium, fermium from einsteinium and californium, and californium with einsteinium from trivalent actinides in turn. A practically complete purification from lanthanides was achieved in this way. Separation was carried in aqueous ethanol solutions by cocrystallization with NaCl resulting from salting out with ethanol. The purification coefficient of actinides from accompanying elements was 10/sup 3/ to 10/sup 4/. The yield on separation was about 90%. The duration of the separation process was 3-5 min.

  13. Magnetic Targeting of Novel Heparinized Iron Oxide Nanoparticles Evaluated in a 9L-glioma mouse model

    PubMed Central

    Zhang, Jian; Shin, Meong Cheol; Yang, Victor C.

    2013-01-01

    Purpose A novel PEGylated and heparinized magnetic iron oxide nano-platform (DNPH) was synthesized for simultaneous magnetic resonance imaging (MRI) and tumor targeting. Methods Starch-coated magnetic iron oxide nanoparticles (“D”) were crosslinked, aminated (DN) and then simultaneously PEGylated and heparinized with different feed ratios of PEG and heparin (DNPH1-4). DNPH products were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and superconducting quantum interference device (SQUID). The magentic targeting of DNPH3, with appropriate amounts of conjugated PEG and heparin, in a mouse 9L-glioma subcutaneous tumor model was confirmed by magnetic resonance imaging (MRI)/electron spin resonance (ESR). Results DNPH3 showed long circulating properties in vivo (half-life > 8 h, more than 60-fold longer than that of parent D) and low reticuloendothelial system (RES) recognition in liver and spleen. Protamine, a model cationic protein, was efficiently loaded onto DNPH3 with a maxium loading content of 26.4 μg/mg Fe. Magnetic capture of DNPH3 in tumor site with optimized conditions (I.D. of 12 mg/kg, targeting time of 45 min) was up to 29.42 μg Fe/g tissue (12.26% I.D./g tissue). Conclusion DNPH3 showed the potential to be used as a platform for cationic proteins for simultaneous tumor targeting and imaging. PMID:24065589

  14. Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach

    NASA Astrophysics Data System (ADS)

    Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Gerdil, Adèle; Diemer, Hélène; Proamer, Fabienne; Collin-Faure, Véronique; Habert, Aurélie; Strub, Jean-Marc; Hanau, Daniel; Herlin, Nathalie; Carrière, Marie; van Dorsselaer, Alain; Rabilloud, Thierry

    2014-05-01

    Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate catabolism and proteasome are critical determinants of sensitivity to zinc, which also induces DNA damage. Conversely, glutathione levels and phagocytosis appear unaffected at moderately toxic zinc concentrations.Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate

  15. CeO2-TiO2 catalysts for catalytic oxidation of elemental mercury in low-rank coal combustion flue gas.

    PubMed

    Li, Hailong; Wu, Chang-Yu; Li, Ying; Zhang, Junying

    2011-09-01

    CeO(2)-TiO(2) (CeTi) catalysts synthesized by an ultrasound-assisted impregnation method were employed to oxidize elemental mercury (Hg(0)) in simulated low-rank (sub-bituminous and lignite) coal combustion flue gas. The CeTi catalysts with a CeO(2)/TiO(2) weight ratio of 1-2 exhibited high Hg(0) oxidation activity from 150 to 250 °C. The high concentrations of surface cerium and oxygen were responsible for their superior performance. Hg(0) oxidation over CeTi catalysts was proposed to follow the Langmuir-Hinshelwood mechanism whereby reactive species from adsorbed flue gas components react with adjacently adsorbed Hg(0). In the presence of O(2), a promotional effect of HCl, NO, and SO(2) on Hg(0) oxidation was observed. Without O(2), HCl and NO still promoted Hg(0) oxidation due to the surface oxygen, while SO(2) inhibited Hg(0) adsorption and subsequent oxidation. Water vapor also inhibited Hg(0) oxidation. HCl was the most effective flue gas component responsible for Hg(0) oxidation. However, the combination of SO(2) and NO without HCl also resulted in high Hg(0) oxidation efficiency. This superior oxidation capability is advantageous to Hg(0) oxidation in low-rank coal combustion flue gas with low HCl concentration.

  16. Unbalanced Oxidant-Antioxidant Status: A Potential Therapeutic Target for Coronary Chronic Total Occlusion in Very Old Patients

    PubMed Central

    2016-01-01

    Unbalanced oxidant and antioxidant status played an important role in myocardial infarction. The present study was a clinical trial combined preclinically with targeted agent against cardiovascular injuries and ischemia in vivo model. We tried to confirm the association of unbalanced oxidant and antioxidant status with coronary chronic total occlusion (CTO) in 399 very old patients (80~89 years) and investigated the potential therapeutic value of purified polysaccharide from endothelium corneum gigeriae galli (PECGGp). We analyzed levels of circulating superoxide dismutase 3 (SOD3), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), and malondialdehyde (MDA) in very old patients with coronary CTO. Levels of SOD3, NO, eNOS, and MDA in the cardiac tissue were measured in myocardial infarction rats. Levels of SOD3, eNOS, and NO were lowered (p < 0.001) and levels of MDA were increased (p < 0.001). PECGGp treatment increased levels of SOD3, eNOS, and NO (p < 0.01) in cardiac tissue, while decreasing levels of MDA (p < 0.01). PECGGp may suppress unbalanced oxidant and antioxidant status in infarcted myocardium by inhibiting levels of MDA and elevating NO, eNOS, and SOD3 levels. PECGGp could be considered as a potential therapeutic agent for coronary CTO in very old patients. PMID:28044093

  17. A simplified procedure for semi-targeted lipidomic analysis of oxidized phosphatidylcholines induced by UVA irradiation.

    PubMed

    Gruber, Florian; Bicker, Wolfgang; Oskolkova, Olga V; Tschachler, Erwin; Bochkov, Valery N

    2012-06-01

    Oxidized phospholipids (OxPLs) are increasingly recognized as signaling mediators that are not only markers of oxidative stress but are also "makers" of pathology relevant to disease pathogenesis. Understanding the biological role of individual molecular species of OxPLs requires the knowledge of their concentration kinetics in cells and tissues. In this work, we describe a straightforward "fingerprinting" procedure for analysis of a broad spectrum of molecular species generated by oxidation of the four most abundant species of polyunsaturated phosphatidylcholines (OxPCs). The approach is based on liquid-liquid extraction followed by reversed-phase HPLC coupled to electrospray ionization MS/MS. More than 500 peaks corresponding in retention properties to polar and oxidized PCs were detected within 8 min at 99 m/z precursor values using a single diagnostic product ion in extracts from human dermal fibroblasts. Two hundred seventeen of these peaks were fluence-dependently and statistically significantly increased upon exposure of cells to UVA irradiation, suggesting that these are genuine oxidized or oxidatively fragmented species. This method of semitargeted lipidomic analysis may serve as a simple first step for characterization of specific "signatures" of OxPCs produced by different types of oxidative stress in order to select the most informative peaks for identification of their molecular structure and biological role.

  18. Immunohistochemical Study of Nrf2-Antioxidant Response Element as Indicator of Oxidative Stress Induced by Cadmium in Developing Rats

    PubMed Central

    Montes, Sergio; Juárez-Rebollar, Daniel; Nava-Ruíz, Concepción; Sánchez-García, Aurora; Heras-Romero, Yesica; Rios, Camilo; Méndez-Armenta, Marisela

    2015-01-01

    In developing animals, Cadmium (Cd) induces toxicity to many organs including brain. Reactive oxygen species (ROS) are often implicated in Cd-inducedtoxicity and it has been clearly demonstrated that oxidative stress interferes with the expression of genes as well as transcriptional factors such as Nrf2-dependent Antioxidant Response Element (Nrf2-ARE). Cd-generated oxidative stress and elevated Nrf2 activity have been reported in vitro and in situ cells. In this study we evaluated the morphological changes and the expression pattern of Nrf2 and correlated them with the Cd concentrations in different ages of developing rats in heart, lung, kidney, liver, and brain. The Cd content in different organs of rats treated with the metal was increased in all ages assayed. Comparatively, lower Cd brain levels were found in rats intoxicated at the age of 12 days, then pups treated at 5, 10, or 15 days old, at the same metal dose. No evident changes, as a consequence of cadmium exposure, were evident in the morphological analysis in any of the ages assayed. However, Nrf2-ARE immunoreactivity was observed in 15-day-old rats exposed to Cd. Our results support that fully developed blood-brain barrier is an important protector against Cd entrance to brain and that Nrf2 increased expression is a part of protective mechanism against cadmium-induced toxicity. PMID:26101558

  19. heterogeneous equilibration between solid and liquid phases in research on the lower oxidation states of the actinide elements

    SciTech Connect

    Mikheev, N.B.; Kamenskaya, A.N.; Konovalova, N.A.; Kulyukhin, S.A.; Rumer, I.A.

    1986-07-01

    Measurements have been made on the cocrystallization of Fe/sup 2 +/ and Md/sup +/ with NaCl and KCl in water-ethanol solutions in the presence of divalent lanthanides. A thermodynamic consideration showed that mendelevium is reduced to the 1+ oxidation state at the Eu/sup 2 +/ potential and cocrystallizes with KCl and NaCl isomorphously. Fermium in the same medium is reduced by Sm/sup 2 +/ only to the 2/sup +/ oxidation state and forms anomalous mixed crystals AMC with KCl, with the cocrystallization coefficient increasing linearly with (Cl/sup -/). These relationships show that Md/sup +/ and Fm/sup 2 +/ do not form stable chloride, complexes, and in that respect they are analogs of the alkali and alkaline-earth elements. The cocrystallization of Md/sup +/ with SmF/sub 2/ and YbF/sub 2/ shows that AMC are formed as when Ag/sup +/ cocrystallizes with SrF/sub 2/.

  20. Health Risks of Space Exploration: Targeted and Nontargeted Oxidative Injury by High-Charge and High-Energy Particles

    PubMed Central

    Li, Min; Gonon, Géraldine; Buonanno, Manuela; Autsavapromporn, Narongchai; de Toledo, Sonia M.; Pain, Debkumar

    2014-01-01

    Abstract Significance: During deep space travel, astronauts are often exposed to high atomic number (Z) and high-energy (E) (high charge and high energy [HZE]) particles. On interaction with cells, these particles cause severe oxidative injury and result in unique biological responses. When cell populations are exposed to low fluences of HZE particles, a significant fraction of the cells are not traversed by a primary radiation track, and yet, oxidative stress induced in the targeted cells may spread to nearby bystander cells. The long-term effects are more complex because the oxidative effects persist in progeny of the targeted and affected bystander cells, which promote genomic instability and may increase the risk of age-related cancer and degenerative diseases. Recent Advances: Greater understanding of the spatial and temporal features of reactive oxygen species bursts along the tracks of HZE particles, and the availability of facilities that can simulate exposure to space radiations have supported the characterization of oxidative stress from targeted and nontargeted effects. Critical Issues: The significance of secondary radiations generated from the interaction of the primary HZE particles with biological material and the mitigating effects of antioxidants on various cellular injuries are central to understanding nontargeted effects and alleviating tissue injury. Future Directions: Elucidation of the mechanisms underlying the cellular responses to HZE particles, particularly under reduced gravity and situations of exposure to additional radiations, such as protons, should be useful in reducing the uncertainty associated with current models for predicting long-term health risks of space radiation. These studies are also relevant to hadron therapy of cancer. Antioxid. Redox Signal. 20, 1501–1523. PMID:24111926

  1. Production and nature of highly luminescent spark- processed porous oxides of silicon and other elements

    NASA Astrophysics Data System (ADS)

    Stora, Michael Emery

    2000-09-01

    Spark-processed silicon (sp-Si) is a novel nano-porous material with unique optical and magnetic properties. Sp- Si exhibits two broad, intense, room-temperature photoluminescence (PL) bands, which are located near 370 nm and 530 nm when excited by 325 nm UV light. These are known as the UV/blue band and the green band, respectively. In addition, a number of other elements have been show to exhibit significant PL when spark- processed. Several PL spectroscopic methods were used to characterize sp-Si and other spark-processed materials. These included continuous-wave PL (CWPL), time-resolved PL (TRPL), PL excitation spectroscopy (PLE), and temperature-dependent PL measurements. In addition scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and secondary-ion mass spectroscopy (SIMS) were utilized. The influences of the chemical, physical, electrical, and temporal processing parameters on the PL of sp-Si and other spark-processed elements were extensively explored and characterized. Both PL bands of sp-Si as well as similar bands in sp-Ge, sp-Al, and sp-Ta were found to be strongly dependent on the presence of nitrogen in the processing ambient. The PL of sp-Si and several other spark-processed materials was found to exhibit extremely fast sub-10 ps lifetimes. Longer-lived components attributed to trapping and evidence of competition between the two PL bands of sp-Si indicate charge transfer between separate absorption and emission mechanisms. A model for the PL mechanisms of sp-Si is proposed. This model explains the observed properties of both PL bands of sp-Si and may be extended to other spark-processed materials. Absorption of UV light is attributed to a stable version of a normally metastable defect found in silica, and many other materials, known as the self- trapped exciton (STE). The rapid melting and solidification during spark-processing is believed to ``quench-in'' this defect. PL emission is the result of charge transfer

  2. Oxidative stress-induced posttranslational modification of proteins as a target of functional food.

    PubMed

    Naito, Yuji; Yoshikawa, Toshikazu

    2009-01-01

    In lifestyle-related diseases including metabolic syndrome, atherosclerosis, and cancer, oxidative stress is indicated by several markers, among which are lipid peroxides, aldehydes, and nitrotyrosine. We hypothesized that identification of proteins that are posttranslationally modified due to oxidative stress would lead to a greater understanding of some of the potential molecular mechanisms involved in degeneration and inflammation in these disorders. Proteomics is an emerging method for identification of proteins and their modification residues, and its application to food factor science is just beginning. Especially, we can obtain several monoclonal antibodies to detect specifically oxidized proteins, which can be applied to analysis by immunostaining or immunoblot. In this review, we present the use of these monoclonal antibodies in several diseases, from which new insights have emerged into mechanisms of metabolism and inflammation in these disorders that are associated with oxidative stress.

  3. Neuroinflammation and Oxidative Stress in Diabetic Neuropathy: Futuristic Strategies Based on These Targets

    PubMed Central

    Sandireddy, Reddemma; Yerra, Veera Ganesh; Areti, Aparna; Komirishetty, Prashanth

    2014-01-01

    In Diabetes, the chronic hyperglycemia and associated complications affecting peripheral nerves are one of the most commonly occurring microvascular complications with an overall prevalence of 50–60%. Among the vascular complications of diabetes, diabetic neuropathy is the most painful and disabling, fatal complication affecting the quality of life in patients. Several theories of etiologies surfaced down the lane, amongst which the oxidative stress mediated damage in neurons and surrounding glial cell has gained attention as one of the vital mechanisms in the pathogenesis of neuropathy. Mitochondria induced ROS and other oxidants are responsible for altering the balance between oxidants and innate antioxidant defence of the body. Oxidative-nitrosative stress not only activates the major pathways namely, polyol pathway flux, advanced glycation end products formation, activation of protein kinase C, and overactivity of the hexosamine pathway, but also initiates and amplifies neuroinflammation. The cross talk between oxidative stress and inflammation is due to the activation of NF-κB and AP-1 and inhibition of Nrf2, peroxynitrite mediate endothelial dysfunction, altered NO levels, and macrophage migration. These all culminate in the production of proinflammatory cytokines which are responsible for nerve tissue damage and debilitating neuropathies. This review focuses on the relationship between oxidative stress and neuroinflammation in the development and progression of diabetic neuropathy. PMID:24883061

  4. Hypoxia. 1. Intracellular sensors for oxygen and oxidative stress: novel therapeutic targets.

    PubMed

    Miyata, Toshio; Takizawa, Shunya; van Ypersele de Strihou, Charles

    2011-02-01

    A variety of human disorders, e.g., ischemic heart disease, stroke, kidney disease, eventually share the deleterious consequences of a common, hypoxic and oxidative stress pathway. In this review, we utilize recent information on the cellular defense mechanisms against hypoxia and oxidative stress with the hope to propose new therapeutic tools. The hypoxia-inducible factor (HIF) is a key player as it activates a broad range of genes protecting cells against hypoxia. Its level is determined by its degradation rate by intracellular oxygen sensors prolyl hydroxylases (PHDs). There are three different PHD isoforms (PHD1-3). Small molecule PHD inhibitors improve hypoxic injury in experimental animals but, unfortunately, may induce adverse effects associated with PHD2 inhibition, e.g., angiogenesis. As yet, no inhibitor specific for a distinct PHD isoform is currently available. Still, the specific disruption of the PHD1 gene is known to induce hypoxic tolerance, without angiogenesis and erythrocytosis, by reprogramming basal oxygen metabolism with an attendant decreased oxidative stress in hypoxic mitochondria. A specific PHD1 inhibitor might therefore offer a novel therapy against hypoxia. The nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulates the basal and inducible expression of numerous antioxidant stress genes. Disruption of its gene exacerbates oxidative tissue injury. Nrf2 activity is modulated by Kelch-like ECH-associated protein 1 (Keap1), an intracellular sensor for oxidative stress. Inhibitors of Keap 1 may prove therapeutic against oxidative tissue injury.

  5. THE PROTEIN TARGETING FACTOR GET3 FUNCTIONS AS AN ATP-INDEPENDENT CHAPERONE UNDER OXIDATIVE STRESS CONDITIONS

    PubMed Central

    Voth, Wilhelm; Schick, Markus; Gates, Stephanie; Li, Sheng; Vilardi, Fabio; Gostimskaya, Irina; Southworth, Daniel R.; Schwappach, Blanche; Jakob, Ursula

    2014-01-01

    Summary Exposure of cells to reactive oxygen species (ROS) causes a rapid and significant drop in intracellular ATP-levels. This energy depletion negatively affects ATP-dependent chaperone systems, making ROS-mediated protein unfolding and aggregation a potentially very challenging problem. Here we show that Get3, a protein involved in ATP-dependent targeting of tail-anchored (TA) proteins under non-stress conditions, turns into an effective ATP-in dependent chaperone when oxidized. Activation of Get3’s chaperone function, which is a fully reversible process, involves disulfide bond formation, metal release and its conversion into distinct, higher oligomeric structures. Mutational studies demonstrate that the chaperone activity of Get3 is functionally distinct from and likely mutually exclusive with its targeting function, and responsible for the oxidative stress sensitive phenotype that has long been noted for yeast cells lacking functional Get3. These results provide convincing evidence that Get3 functions as a redox regulated chaperone, effectively protecting eukaryotic cells against oxidative protein damage. PMID:25242142

  6. Differentially expressed miRNAs in sepsis-induced acute kidney injury target oxidative stress and mitochondrial dysfunction pathways

    PubMed Central

    Ge, Qin-Min; Huang, Chun-Mei; Zhu, Xiang-Yang; Bian, Fan; Pan, Shu-Ming

    2017-01-01

    Objective To identify specific miRNAs involved in sepsis-induced AKI and to explore their targeting pathways. Methods The expression profiles of miRNAs in serum from patients with sepsis-induced AKI (n = 6), sepsis-non AKI (n = 6), and healthy volunteers (n = 3) were investigated by microarray assay and validated by quantitative PCR (qPCR). The targets of the differentially expressed miRNAs were predicted by Target Scan, mirbase and Miranda. Then the significant functions and involvement in signaling pathways of gene ontology (GO) and KEGG pathways were analyzed. Furthermore, eight miRNAs were randomly selected out of the differentially expressed miRNAs for further testing by qPCR. Results qPCR analysis confirmed that the expressions levels of hsa-miR-23a-3p, hsa-miR-4456, hsa-miR-142-5p, hsa-miR-22-3p and hsa-miR-191-5p were significantly lower in patients with sepsis compared with the healthy volunteers, while hsa-miR-4270, hsa-miR-4321, hsa-miR-3165 were higher in the sepsis patients. Statistically, miR-4321; miR-4270 were significantly upregulated in the sepsis-induced AKI compared with sepsis-non AKI, while only miR-4321 significantly overexpressed in the sepsis groups compared with control groups. GO analysis showed that biological processes regulated by the predicted target genes included diverse terms. They were related to kidney development, regulation of nitrogen compound metabolic process, regulation of cellular metabolic process, cellular response to oxidative stress, mitochondrial outer membrane permeabilization, etc. Pathway analysis showed that several significant pathways of the predicted target genes related to oxidative stress. miR-4321 was involved in regulating AKT1, mTOR and NOX5 expression while miR-4270 was involved in regulating PPARGC1A, AKT3, NOX5, PIK3C3, WNT1 expression. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in oxidative stress and mitochondrial dysfunction. Conclusion This study

  7. A Method to Site-Specifically Identify and Quantitate Carbonyl End Products of Protein Oxidation Using Oxidation-Dependent Element Coded Affinity Tags (O-ECAT) and NanoLiquid Chromatography Fourier Transform Mass Spectrometry

    SciTech Connect

    Lee, S; Young, N L; Whetstone, P A; Cheal, S M; Benner, W H; Lebrilla, C B; Meares, C F

    2005-08-25

    Protein oxidation is linked to cellular stress, aging, and disease. Protein oxidations that result in reactive species are of particular interest, since these reactive oxidation products may react with other proteins or biomolecules in an unmediated and irreversible fashion, providing a potential marker for a variety of disease mechanisms. We have developed a novel system to identify and quantitate, relative to other states, the sites of oxidation on a given protein. A specially designed Oxidation-dependent carbonyl-specific Element-Coded Affinity Mass Tag (O-ECAT), AOD, ((S)-2-(4-(2-aminooxy)-acetamido)-benzyl)-1, 4, 7, 10-tetraazacyclododecane-N, N', N'', N'''-tetraacetic acid, is used to covalently tag the residues of a protein oxidized to aldehyde or keto end products. After proteolysis, the resulting AOD-tagged peptides are affinity purified, and analyzed by nanoLC-FTICR-MS, which provides high specificity in extracting co-eluting AOD mass pairs with a unique mass difference and affords relative quantitation based on isotopic ratios. Using this methodology, we have mapped the surface oxidation sites on a model protein, recombinant human serum albumin (rHSA) in its native form (as purchased) and after FeEDTA oxidation. A variety of modified amino acid residues including lysine, arginine, proline, histidine, threonine, aspartic and glutamic acids, were found to be oxidized to aldehyde and keto end products. The sensitivity of this methodology is shown by the number of peptides identified, twenty peptides on the native protein and twenty-nine after surface oxidation using FeEDTA and ascorbate. All identified peptides map to the surface of the HSA crystal structure validating this method for identifying oxidized amino acids on protein surfaces. In relative quantitation experiments between FeEDTA oxidation and native protein oxidation, identified sites showed different relative propensities towards oxidation independent of amino acid residue. We expect to extend

  8. Catalytic performance and deactivation of precipitated iron catalyst for selective oxidation of hydrogen sulfide to elemental sulfur in the waste gas streams from coal gasification

    SciTech Connect

    Mashapa, T.N.; Rademan, J.D.; van Vuuren, M.J.J.

    2007-09-15

    The selective oxidation of hydrogen sulfide to elemental sulfur, using a commercial, precipitated silica promoted ferric oxide based catalyst, was investigated in laboratory and pilot-plant reactors. Low levels of hydrogen sulfide (1-3 vol%) can be readily removed, but a continuous slow decrease in catalyst activity was apparent. X-ray photoelectron spectroscopy showed that the loss of activity was due to the formation of ferrous sulfate, which is known to be less active than the ferric oxide. In addition, studies using a model feed showed that the propene and HCN impurities in the plant feed stocks also act as potent catalyst poisons.

  9. An aptamer-targeting photoresponsive drug delivery system using ``off-on'' graphene oxide wrapped mesoporous silica nanoparticles

    NASA Astrophysics Data System (ADS)

    Tang, Yuxia; Hu, Hao; Zhang, Molly Gu; Song, Jibin; Nie, Liming; Wang, Shouju; Niu, Gang; Huang, Peng; Lu, Guangming; Chen, Xiaoyuan

    2015-03-01

    We have developed a novel aptamer-targeting photoresponsive drug delivery system by non-covalent assembly of a Cy5.5-AS1411 aptamer conjugate on the surface of graphene oxide wrapped doxorubicin (Dox)-loaded mesoporous silica nanoparticles (MSN-Dox@GO-Apt) for light-mediated drug release and aptamer-targeted cancer therapy. The two ``off-on'' switches of the MSN-Dox@GO-Apt were controlled by aptamer targeting and light triggering, respectively. The Cy5.5-AS1411 ligand provides MSN-Dox@GO-Apt with nucleolin specific targeting and real-time indicator abilities by ``off-on'' Cy5.5 fluorescence recovery. The GO acts as a gatekeeper to prevent the loaded Dox from leaking in the absence of laser irradiation, and to control the Dox release in response to laser irradiation. When the GO wrapping falls off upon laser irradiation, the ``off-on'' photoresponsive drug delivery system is activated, thus inducing chemotherapy. Interestingly, with an increase in laser power, the synergism of chemotherapy and photothermal therapy in a single MSN-Dox@GO-Apt platform led to much more effective cancer cell killing than monotherapies, providing a new approach for treatment against cancer.We have developed a novel aptamer-targeting photoresponsive drug delivery system by non-covalent assembly of a Cy5.5-AS1411 aptamer conjugate on the surface of graphene oxide wrapped doxorubicin (Dox)-loaded mesoporous silica nanoparticles (MSN-Dox@GO-Apt) for light-mediated drug release and aptamer-targeted cancer therapy. The two ``off-on'' switches of the MSN-Dox@GO-Apt were controlled by aptamer targeting and light triggering, respectively. The Cy5.5-AS1411 ligand provides MSN-Dox@GO-Apt with nucleolin specific targeting and real-time indicator abilities by ``off-on'' Cy5.5 fluorescence recovery. The GO acts as a gatekeeper to prevent the loaded Dox from leaking in the absence of laser irradiation, and to control the Dox release in response to laser irradiation. When the GO wrapping falls off upon

  10. Vanadium oxide thin films produced by magnetron sputtering from a V2O5 target at room temperature

    NASA Astrophysics Data System (ADS)

    de Castro, Marcelo S. B.; Ferreira, Carlos L.; de Avillez, Roberto R.

    2013-09-01

    Vanadium oxide thin films were grown by RF magnetron sputtering from a V2O5 target at room temperature, an alternative route of production of vanadium oxide thin films for infrared detector applications. The films were deposited on glass substrates, in an argon-oxygen atmosphere with an oxygen partial pressure from nominal 0% to 20% of the total pressure. X-ray diffraction (XRD) and X-ray photon spectroscopy (XPS) analyses showed that the films were a mixture of several vanadium oxides (V2O5, VO2, V5O9 and V2O3), which resulted in different colors, from yellow to black, depending on composition. The electrical resistivity varied from 1 mΩ cm to more than 500 Ω cm and the thermal coefficient of resistance (TCR), varied from -0.02 to -2.51% K-1. Computational thermodynamics was used to simulate the phase diagram of the vanadium-oxygen system. Even if plasma processes are far from equilibrium, this diagram provides the range of oxygen pressures that lead to the growth of different vanadium oxide phases. These conditions were used in the present work.

  11. Local delivery of nitric oxide: targeted delivery of therapeutics to bone and connective tissues

    PubMed Central

    Nichols, Scott P.; Storm, Wesley L.; Koh, Ahyeon; Schoenfisch, Mark H.

    2012-01-01

    Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair. PMID:22433782

  12. Protective effect of mitochondria‑targeted peptide MTP‑131 against oxidative stress‑induced apoptosis in RGC‑5 cells.

    PubMed

    Chen, Min; Liu, Bingqian; Ma, Jian; Ge, Jian; Wang, Kaijun

    2017-04-01

    The retina of the human eye is extremely vulnerable to oxidative damage. Previous studies have demonstrated that oxidative stress is the predominant mechanism associated with the pathogenesis of age‑related macular degeneration, diabetic retinopathy, glaucoma and retinitis pigmentosa. MTP‑131, a novel mitochondria‑targeted peptide, has been demonstrated to specifically concentrate in the inner mitochondria membrane and to exhibit remarkable antioxidant effects both in vitro and in animal models. In the present study, the protective effect of MTP‑131 was evaluated in response to hydrogen peroxide (H2O2)‑induced oxidative damage in a retinal ganglion cell line, RGC‑5. Cell viability was measured by lactate dehydrogenase (LDH) assay. Changes of mitochondrial membrane potential and generation of intracellular reactive oxygen species (ROS) were measured by flow cytometry and confocal microscopy, respectively. Annexin V‑fluorescein isothiocyanate/propidium iodide staining was used for assessment of apoptosis. Release of cytochrome c was analyzed by confocal microscopy. Pretreatment of cells with MTP‑131 inhibited H2O2‑induced cytotoxicity and reduced LDH release in a dose‑dependent manner, compared with cells treated with H2O2 alone. Mitochondrial depolarization and ROS generation were also prevented by MTP‑131 pretreatment. In addition, MTP‑131 pretreatment inhibited cytochrome c release from mitochondria to cytoplasm, and significantly reduced apoptosis in RGC‑5 cells, compared with cells treated with H2O2 alone. In conclusion, mitochondria‑targeted peptide MTP‑131 exhibited a protective effect against oxidative stress‑induced apoptosis in RGC‑5 cells, which may provide a novel approach for the treatment of age‑associated retinal diseases.

  13. VEGF-loaded graphene oxide as theranostics for multi-modality imaging-monitored targeting therapeutic angiogenesis of ischemic muscle

    NASA Astrophysics Data System (ADS)

    Sun, Zhongchan; Huang, Peng; Tong, Guang; Lin, Jing; Jin, Albert; Rong, Pengfei; Zhu, Lei; Nie, Liming; Niu, Gang; Cao, Feng; Chen, Xiaoyuan

    2013-07-01

    Herein we report the design and synthesis of multifunctional VEGF-loaded IR800-conjugated graphene oxide (GO-IR800-VEGF) for multi-modality imaging-monitored therapeutic angiogenesis of ischemic muscle. The as-prepared GO-IR800-VEGF positively targets VEGF receptors, maintains an elevated level of VEGF in ischemic tissues for a prolonged time, and finally leads to remarkable therapeutic angiogenesis of ischemic muscle. Although more efforts are required to further understand the in vivo behaviors and the long-term toxicology of GO, our work demonstrates the success of using GO for efficient VEGF delivery in vivo by intravenous administration and suggests the great promise of using graphene oxide in theranostic applications for treating ischemic disease.Herein we report the design and synthesis of multifunctional VEGF-loaded IR800-conjugated graphene oxide (GO-IR800-VEGF) for multi-modality imaging-monitored therapeutic angiogenesis of ischemic muscle. The as-prepared GO-IR800-VEGF positively targets VEGF receptors, maintains an elevated level of VEGF in ischemic tissues for a prolonged time, and finally leads to remarkable therapeutic angiogenesis of ischemic muscle. Although more efforts are required to further understand the in vivo behaviors and the long-term toxicology of GO, our work demonstrates the success of using GO for efficient VEGF delivery in vivo by intravenous administration and suggests the great promise of using graphene oxide in theranostic applications for treating ischemic disease. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr01573d

  14. Oxidation of elemental mercury by modified spent TiO2-based SCR-DeNOx catalysts in simulated coal-fired flue gas.

    PubMed

    Zhao, Lingkui; Li, Caiting; Zhang, Xunan; Zeng, Guangming; Zhang, Jie; Xie, Yin'e

    2016-01-01

    In order to reduce the costs, the recycle of spent TiO2-based SCR-DeNOx catalysts were employed as a potential catalytic support material for elemental mercury (Hg(0)) oxidation in simulated coal-fired flue gas. The catalytic mechanism for simultaneous removal of Hg(0) and NO was also investigated. The catalysts were characterized by Brunauer-Emmett-Teller (BET), scanning electron microscope (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) method. Results indicated that spent TiO2-based SCR-DeNOx catalyst supported Ce-Mn mixed oxides catalyst (CeMn/SCR1) was highly active for Hg(0) oxidation at low temperatures. The Ce1.00Mn/SCR1 performed the best catalytic activities, and approximately 92.80% mercury oxidation efficiency was obtained at 150 °C. The inhibition effect of NH3 on Hg(0) oxidation was confirmed in that NH3 consumed the surface oxygen. Moreover, H2O inhibited Hg(0) oxidation while SO2 had a promotional effect with the aid of O2. The XPS results illustrated that the surface oxygen was responsible for Hg(0) oxidation and NO conversion. Besides, the Hg(0) oxidation and NO conversion were thought to be aided by synergistic effect between the manganese and cerium oxides.

  15. Identification of the mismatch repair genes PMS2 and MLH1 as p53 target genes by using serial analysis of binding elements

    PubMed Central

    Chen, Jiguo; Sadowski, Ivan

    2005-01-01

    The ability to determine the global location of transcription factor binding sites in vivo is important for a comprehensive understanding of gene regulation in human cells. We have developed a technology, called serial analysis of binding elements (SABE), involving subtractive hybridization of chromatin immunoprecipitation-enriched DNA fragments followed by the generation and analysis of concatamerized sequence tags. We applied the SABE technology to search for p53 target genes in the human genome, and have identified several previously described p53 targets in addition to numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron. These two genes may serve as a sensor in DNA repair mechanisms and a critical determinant for the decision between cell-cycle arrest and apoptosis. These results also demonstrate the potential for use of SABE as a broadly applicable means to globally identify regulatory elements for human transcription factors in vivo. PMID:15781865

  16. Doxorubicin loaded PEG-b-poly(4-vinylbenzylphosphonate) coated magnetic iron oxide nanoparticles for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Hałupka-Bryl, Magdalena; Bednarowicz, Magdalena; Dobosz, Bernadeta; Krzyminiewski, Ryszard; Zalewski, Tomasz; Wereszczyńska, Beata; Nowaczyk, Grzegorz; Jarek, Marcin; Nagasaki, Yukio

    2015-06-01

    Due to their unique physical properties, superparamagnetic iron oxide nanoparticles are increasingly used in medical applications. They are very useful carriers for delivering antitumor drugs in targeted cancer treatment. Magnetic nanoparticles with chemiotherapeutic were synthesized by coprecipitation method followed by coating with biocompatible polymer. The aim of this work is to characterize physical and magnetic properties of synthesized nanoparicles. Characterization was carried out using EPR, HRTEM, X-ray diffraction, SQUID and NMR methods. The present findings show that synthesized nanosystem is promising tool for potential magnetic drug delivery.

  17. Platinum-group element geochemistry of the Zhuqing Fe-Ti-V oxide ore-bearing mafic intrusions in western Yangtze Block, SW China: control of platinum-group elements by magnetite

    NASA Astrophysics Data System (ADS)

    Fan, Hong-Peng; Zhu, Wei-Guang; Zhong, Hong; Bai, Zhong-Jie; He, De-Feng; Ye, Xian-Tao; Chen, Cai-Jie; Cao, Chong-Yong

    2014-06-01

    Platinum-group element (PGE) geochemistry combined with elemental geochemistry and magnetite compositions are reported for the Mesoproterozoic Zhuqing Fe-Ti-V oxide ore-bearing mafic intrusions in the western Yangtze Block, SW China. All the Zhuqing gabbros display extremely low concentrations of chalcophile elements and PGEs. The oxide-rich gabbros contain relatively higher contents of Cr, Ni, Ir, Ru, Rh, and lower contents of Pt and Pd than the oxide-poor gabbros. The abundances of whole-rock concentrations of Ni, Ir, Ru, and Rh correlate well with V contents in the Zhuqing gabbros, implying that the distributions of these elements are controlled by magnetite. The fractionation between Ir-Ru-Rh and Pt-Pd in the Zhuqing gabbros is mainly attributed to fractional crystallization of chromite and magnetite, whereas Ru anomalies are mainly due to variable degrees of compatibility of PGE in magnetite. The order of relative incompatibility of PGEs is calculated to be Pd < Pt < Rh < Ir < Ru. The very low PGE contents and Cu/Zr ratios and high Cu/Pd ratios suggest initially S-saturated magma parents that were highly depleted in PGE, which mainly formed due to low degrees of partial melting leaving sulfides concentrating PGEs behind in the mantle. Moreover, the low MgO, Ni, Ir and Ru contents and high Cu/Ni and Pd/Ir ratios for the gabbros suggest a highly evolved parental magma. Fe-Ti oxides fractionally crystallized from the highly evolved magma and subsequently settled in the lower sections of the magma chamber, where they concentrated and formed Fe-Ti-V oxide ore layers at the base of the lower and upper cycles. Multiple episodes of magma replenishment in the magma chamber may have been involved in the formation of the Zhuqing intrusions.

  18. piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells.

    PubMed

    Pezic, Dubravka; Manakov, Sergei A; Sachidanandam, Ravi; Aravin, Alexei A

    2014-07-01

    Transposable elements (TEs) occupy a large fraction of metazoan genomes and pose a constant threat to genomic integrity. This threat is particularly critical in germ cells, as changes in the genome that are induced by TEs will be transmitted to the next generation. Small noncoding piwi-interacting RNAs (piRNAs) recognize and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown. Here we show that in addition to DNA methylation, the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in germ cells. piRNA-dependent chromatin repression targets exclusively full-length elements of actively transposing LINE families, demonstrating the remarkable ability of the piRNA pathway to recognize active elements among the large number of genomic transposon fragments.

  19. International Experience with Key Program Elements of IndustrialEnergy Efficiency or Greenhouse Gas Emissions Reduction Target-SettingPrograms

    SciTech Connect

    Price, Lynn; Galitsky, Christina; Kramer, Klaas Jan

    2008-02-02

    Target-setting agreements, also known as voluntary ornegotiated agreements, have been used by a number of governments as amechanism for promoting energy efficiency within the industrial sector. Arecent survey of such target-setting agreement programs identified 23energy efficiency or GHG emissions reduction voluntary agreement programsin 18 countries. International best practice related to target-settingagreement programs calls for establishment of a coordinated set ofpolicies that provide strong economic incentives as well as technical andfinancial support to participating industries. The key program elementsof a target-setting program are the target-setting process,identification of energy-saving technologies and measures usingenergy-energy efficiency guidebooks and benchmarking as well as byconducting energy-efficiency audits, development of an energy-savingsaction plan, development and implementation of energy managementprotocols, development of incentives and supporting policies, monitoringprogress toward targets, and program evaluation. This report firstprovides a description of three key target-setting agreement programs andthen describes international experience with the key program elementsthat comprise such programs using information from the three keytarget-setting programs as well as from other international programsrelated to industrial energy efficiency or GHG emissionsreductions.

  20. Evaluation of trace elements, oxidant/antioxidant status, vitamin C and β-carotene in dogs with dermatophytosis.

    PubMed

    Beigh, S A; Soodan, J S; Singh, R; Khan, A M; Dar, M A

    2014-06-01

    The aim of the study was to determine zinc, copper and iron levels, erythrocyte oxidant/antioxidant status, vitamin C and β-carotene in dogs with dermatophytosis. A total of 23 dogs with clinically established diagnosis of dermatophytosis by trichogram and positive fungal culture and six dogs as control were included in this study. On cultural examination 52.17% fungal isolates were found to be Microsporum canis, 30.43% were Trichophyton mentagrophytes and 17.39% were M. gypseum. In comparison to healthy control, the dogs with dermatophytosis had significantly lower levels of zinc (P < 0.01), copper (P < 0.05), β-carotene and vitamin C levels (P < 0.05) and activities of superoxide dismutase (SOD) (P < 0.05) and catalase (P < 0.01), whereas the iron (P < 0.05) and malondialdehyde (MDA) (P < 0.01) levels were significantly increased. On correlation analysis, SOD activity was observed to be positively correlated (P < 0.05) with zinc and copper in both healthy and dermatophytosis affected dogs. In dermatophytosis affected dogs the MDA levels were negatively correlated (P < 0.05) with iron, β-carotene levels and the activities of antioxidant enzymes; SOD and catalase. Our results demonstrated that dermatophytosis in dogs is associated with significant alteration in oxidant/antioxidant balance and trace elements. It might be secondary consequence of dermatophytosis infection or contributing factor in its pathogenesis.

  1. Neodymium isotopic study of rare earth element sources and mobility in hydrothermal Fe oxide (Fe-P-REE) systems

    SciTech Connect

    Gleason, J.D.; Marikos, M.A.; Barton, M.D.; Johnson, D.A.

    2000-03-01

    Rare earth element (REE)-enriched, igneous-related hydrothermal Fe-oxide hosted (Fe-P-REE) systems from four areas in North America have been analyzed for their neodymium iosotopic composition to constrain REE sources and mobility in these systems. The Nd isotopic results evidence a common pattern of REE concentration from igneous sources despite large differences in age (Proterozoic to Tertiary), tectonic setting (subduction vs. intraplate), and magmatic style (mafic vs. felsic). In the Middle Proterozoic St. Francois Mountains terrane of southeastern Missouri, {epsilon}{sub Nd} for Fe-P-REE (apatite, monazite, xenotime) deposits ranges from +3.5 to +5.1, similar to associated felsic to intermediate igneous rocks of the same age ({epsilon}{sub Nd} = +2.6 to +6.2). At the mid-Jurassic Humboldt mafic complex in western Nevada, {epsilon}{sub Nd} for Fe-P-REE (apatite) mineralization varies between +1.1 and +2.4, similar to associated mafic igneous rocks ({minus}1.0 to +3.5). In the nearby Cortez Mountains in central Nevada, mid-Jurassic felsic volcanic and plutonic rocks ({epsilon}{sub Nd} = {minus}2.0 to {minus}4.4) are associated with Fe-P-REE (apatite-monazite) mineralization having similar {epsilon}{sub Nd}({minus}1.7 to {minus}2.4). At Cerro de Mercado, Durango, Mexico, all assemblages analyzed in this Tertiary rhyolite-hosted Fe oxide deposit have identical isotopic compositions with {epsilon}{sub Nd} = {minus}2.5. These data are consistent with coeval igneous host rocks being the primary source of REE in all four regions, and are inconsistent with a significant contribution of REE from other sources. Interpretations of the origin of these hydrothermal systems and their concomitant REE mobility must account for nonspecialized igneous sources and varied tectonic settings.

  2. Targeting the oxidative stress response system of fungi with safe, redox-potent chemosensitizing agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One mode of action of the antimycotics amphotericin B (AMB) or itraconazole (ITZ) against filamentous fungi involves cellular oxidative stress response. Aspergillus fumigatus sakA', a mitogen-activated protein kinase (MAPK) gene deletion mutant in the antioxidation system, was more sensitive to AMB ...

  3. Nitric oxide inhibits c-Jun DNA binding by specifically targeted S-glutathionylation.

    PubMed

    Klatt, P; Molina, E P; Lamas, S

    1999-05-28

    This study addresses potential molecular mechanisms underlying the inhibition of the transcription factor c-Jun by nitric oxide. We show that in the presence of the physiological sulfhydryl glutathione nitric oxide modifies the two cysteine residues contained in the DNA binding module of c-Jun in a selective and distinct way. Although nitric oxide induced the formation of an intermolecular disulfide bridge between cysteine residues in the leucine zipper site of c-Jun monomers, this same radical directed the covalent incorporation of stoichiometric amounts of glutathione to a single conserved cysteine residue in the DNA-binding site of the protein. We found that covalent dimerization of c-Jun apparently did not affect its DNA binding activity, whereas the formation of a mixed disulfide with glutathione correlated well with the inhibition of transcription factor binding to DNA. Furthermore, we provide experimental evidence that nitric oxide-induced S-glutathionylation and inhibition of c-Jun involves the formation of S-nitrosoglutathione. In conclusion, our results support the reversible formation of a mixed disulfide between glutathione and c-Jun as a potential mechanism by which nitrosative stress may be transduced into a functional response at the level of transcription.

  4. INTERACTION OF LASER RADIATION WITH MATTER. LASER PLASMA: Laser plume spectroscopy. 2. Graphite yttrium-stabilised and zirconium oxide targets

    NASA Astrophysics Data System (ADS)

    Osipov, V. V.; Solomonov, V. I.; Platonov, V. V.; Snigireva, O. A.; Ivanov, M. G.; Lisenkov, V. V.

    2005-07-01

    Spectral and kinetic properties of a plume formed in the vicinity of a graphite and a pressed yttrium-stabilised zirconium oxide (YSZ) powder targets irradiated in air by a 10.6-μm pulsed CO2 laser with a peak power of 1.5-9 kW at room temperature are studied. The plume propagated at right angles to the target surface and at an angle of 45° to the laser radiation. The spectral and kinetic characteristics of its luminescence were measured discretely along the entire length of the plume. It is shown that the YSZ plume as well as the graphite plume is a flux of nonequilibrium gaseous plasma at a temperature of about 4.7-3.1 kK, in which a luminescence of YO and ZrO radicals is excited.

  5. Production of transuranium elements

    SciTech Connect

    Wham, R.M.; Chattin, F.R.; Knauer, J.B.

    1993-12-31

    The Radiochemical Engineering Development Center (REDC) has the programmatic responsibility for the Department of Energy`s Transuranium Element Program. Principle elements from the program are einsteinium, berkelium, and fermium. Targets containing curium oxide mixed with aluminum powder are fabricated by the REDC and irradiated in the Oak Ridge National Laboratory (ORNL) High Flux Isotope Reactor. Following an irradiation period of 6-12 months, targets are returned to the REDC for chemical processing. Processing operations consists of aluminum dejacketing in a caustic-nitrate solution, filtration, acid dissolution, solvent extraction, anion exchange, and finally a cation exchange to recover the actinides. The processing operations take place in heavily shielded hot cell facilities and all operations are carried out remotely. The chemistry for the separations has been well established over the 26-yr. operating life of the facility.

  6. Influence of Minor Alloying Elements on Selective Oxidation and Reactive Wetting of CMnSi TRIP Steel during Hot Dip Galvanizing

    NASA Astrophysics Data System (ADS)

    Cho, Lawrence; Kim, Myung Soo; Kim, Young Ha; De Cooman, Bruno C.

    2014-09-01

    The influence of the addition of minor alloying elements on the selective oxidation and the reactive wetting of CMnSi transformation-induced plasticity (TRIP) steels was studied by means of galvanizing simulator tests. Five TRIP steels containing small alloying additions of Cr, Ni, Ti, Cu, and Sn were investigated. After intercritical annealing (IA) at 1093 K (820 °C) in a N2 + 5 pct H2 gas atmosphere with a dew point of 213 K (-60 °C), two types of oxides were formed on the strip surface: Mn-rich xMnO·SiO2 ( x > 1.5) and Si-rich xMnO·SiO2 ( x < 0.3) oxides. The addition of the minor alloying elements changed the morphology of the Si-rich oxides from a continuous film to discrete islands and this improved the wettability by molten Zn. The improved wetting effect of the minor alloying elements was attributed to an increased area fraction of the surface where the oxides were thinner, enabling a direct unhindered reaction between Fe and the Al in the liquid Zn and the formation of the inhibition layer during the hot dip galvanizing. The addition of a small amount of Sn is shown to significantly decrease the density of Zn-coating defects on CMnSi TRIP steels.

  7. Comparison of PCR assays targeting the multi-copy targets B1 gene and 529 bp repetitive element for detection of Toxoplasma gondii in swine muscle.

    PubMed

    Veronesi, Fabrizia; Santoro, Azzurra; Milardi, Giovanni Luigi; Diaferia, Manuela; Branciari, Raffaella; Miraglia, Dino; Cioffi, Attilia; Gabrielli, Simona; Ranucci, David

    2017-05-01

    The comparison of the sensitivities of two molecular assays designed to target the multi-copy sequences of the Toxoplasma gondii genomic B1 region and 529 bp-RE respectively, in detecting T. gondii in swine muscle was assessed. Diaphragm pillars were obtained from 498 slaughtered pigs managed in intensive farms in Central Italy. Genomic DNA was extracted from the tissues and T. gondii-B1 and 529 bp-RE sequences were amplified by specific PCR protocols. Toxoplasma gondii DNA was detected in 165 samples (33.13%). There was a good correlation (κ = 0.77) between the results obtained targeting the two different genetic markers, however the 529 bp RE-PCR assay overall detected a significantly higher (P < 0.05) number of T. gondii-positive samples (150 samples) than the B1-PCR protocol (134). Our results show that: i) standardized B1 and 529 bp-RE PCRs applied to muscle tissues can detect a high rate of T. gondii-infection; ii) a multi-target PCR approach is recommended for the accurate diagnosis of infection in swine and can also be used in food testing.

  8. Proteome targets of ubiquitin-like samp1ylation are associated with sulfur metabolism and oxidative stress in Haloferax volcanii

    PubMed Central

    Dantuluri, Swathi; Wu, Yifei; Hepowit, Nathaniel L.; Chen, Hui; Chen, Sixue; Maupin-Furlow, Julie A.

    2017-01-01

    Small archeal modifier proteins (SAMPs) are related to ubiquitin in tertiary structure and in their isopeptide linkage to substrate proteins. SAMPs also function in sulfur mobilization to form biomolecules such as molybdopterin and thiolated tRNA. While SAMP1 is essential for anaerobic growth and covalently attached to lysine residues of its molybdopterin synthase partner MoaE (K240 and K247), the full diversity of proteins modified by samp1ylation is not known. Here, we expand the knowledge of proteins isopeptide linked to SAMP1. LC-MS/MS analysis of -Gly-Gly signatures derived from SAMP1 S85R conjugates cleaved with trypsin was used to detect sites of sampylation (23 lysine residues) that mapped to 11 target proteins. Many of the identified target proteins were associated with sulfur metabolism and oxidative stress including MoaE, SAMP-activating E1 enzyme (UbaA), methionine sulfoxide reductase homologs (MsrA and MsrB), and the Fe-S assembly protein SufB. Several proteins were found to have multiple sites of samp1ylation, and the isopeptide linkage at SAMP3 lysines (K18, K55, and K62) revealed hetero-SAMP chain topologies. Follow-up affinity purification of selected protein targets (UbaA and MoaE) confirmed the LC-MS/MS results. 3D homology modeling suggested sampy1ylation is autoregulatory in inhibiting the activity of its protein partners (UbaA and MoaE), while occurring on the surface of some protein targets, such as SufB and MsrA/B. Overall, we provide evidence that SAMP1 is a ubiquitin-like protein modifier that is relatively specific in tagging its protein partners as well as proteins associated with oxidative stress response. PMID:26841191

  9. Buried targets in layered media: A combined finite element/physical acoustics model and comparison to data on a half buried 2:1 cylinder.

    PubMed

    Williams, Kevin L

    2016-12-01

    Previously, a combined finite element/physical acoustics model for proud targets [K. L. Williams, S. G. Kargl, E. I. Thorsos, D. S. Burnett, J. L. Lopes, M. Zampolli, and P. L. Marston, J. Acoust. Soc. Am. 127, 3356-3371 (2010)] was compared to both higher fidelity finite element models and to experimental data for a proud 2:1 aluminum cylinder. Here that expression is generalized to address the case of a target buried in a layered media. The result is compared to data acquired for the same 2:1 cylinder but half buried in a mud layer that covers the sand sediment (considered here as infinite in extent below the mud layer). The generalized expression reduces to both the previous proud result and to the result for a target buried in an infinite medium under the appropriate limiting conditions. The model/data comparisons shown include both the previous proud model and data results along with the ones for the half buried cylinder. The comparison quantifies the reduction in target strength as a function of frequency in the half buried case relative to the proud case.

  10. Protein S-thiolation targets glycolysis and protein synthesis in response to oxidative stress in the yeast Saccharomyces cerevisiae.

    PubMed Central

    Shenton, Daniel; Grant, Chris M

    2003-01-01

    The irreversible oxidation of cysteine residues can be prevented by protein S-thiolation, a process by which protein SH groups form mixed disulphides with low-molecular-mass thiols such as glutathione. We report here the target proteins which are modified in yeast cells in response to H(2)O(2). In particular, a range of glycolytic and related enzymes (Tdh3, Eno2, Adh1, Tpi1, Ald6 and Fba1), as well as translation factors (Tef2, Tef5, Nip1 and Rps5) are identified. The oxidative stress conditions used to induce S-thiolation are shown to inhibit GAPDH (glyceraldehyde-3-phosphate dehydrogenase), enolase and alcohol dehydrogenase activities, whereas they have no effect on aldolase, triose phosphate isomerase or aldehyde dehydrogenase activities. The inhibition of GAPDH, enolase and alcohol dehydrogenase is readily reversible once the oxidant is removed. In addition, we show that peroxide stress has little or no effect on glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase, the enzymes that catalyse NADPH production via the pentose phosphate pathway. Thus the inhibition of glycolytic flux is proposed to result in glucose equivalents entering the pentose phosphate pathway for the generation of NADPH. Radiolabelling is used to confirm that peroxide stress results in a rapid and reversible inhibition of protein synthesis. Furthermore, we show that glycolytic enzyme activities and protein synthesis are irreversibly inhibited in a mutant that lacks glutathione, and hence cannot modify proteins by S-thiolation. In summary, protein S-thiolation appears to serve an adaptive function during exposure to an oxidative stress by reprogramming metabolism and protecting protein synthesis against irreversible oxidation. PMID:12755685

  11. Modulation of Methuselah Expression Targeted to Drosophila Insulin-producing Cells Extends Life and Enhances Oxidative Stress Resistance

    PubMed Central

    Gimenez, Luis E. D.; Ghildyal, Parakashtha; Fischer, Kathleen E.; Hu, Hongxiang; Ja, William W.; Eaton, Benjamin A.; Wu, Yimin; Austad, Steven N.; Ranjan, Ravi

    2013-01-01

    Ubiquitously reduced signaling via Methuselah (MTH), a G-protein coupled receptor (GPCR) required for neurosecretion, has previously been reported to extend life and enhance stress resistance in flies. Whether these effects are due to reduced MTH signaling only in specific tissue(s) and through with signaling effects reduced MTH might produce these phenotypes remains unknown. We determined that reduced expression of mth targeted only to the insulin-producing cells (IPCs) of the fly brain was sufficient to extend life and enhance oxidative stress resistance. Paradoxically, we discovered that overexpression of mth targeted to the same cells has similar phenotypic effects to reduced expression due to MTH’s interaction with β-arrestin, which uncouples GPCRs from their G-proteins. We confirmed the functional relationship between MTH and β-arrestin by finding that IPC-targeted overexpression of β-arrestin alone mimics the longevity phenotype of reduced MTH signaling. As reduced MTH signaling also inhibits insulin secretion from the IPCs, the most parsimonious mechanistic explanation for its longevity and stress resistance enhancement might be through reduced insulin/IGF signaling (IIS). However, examination of phenotypic features of long-lived IPC-mth modulated flies as well as several downstream IIS targets implicates enhanced activity of the JNK stress resistance pathway more directly than insulin signaling in the longevity and stress resistance phenotypes. PMID:23121290

  12. Polyvalent Folate-Dendrimer-Coated Iron Oxide Theranostic Nanoparticles for Simultaneous Magnetic Resonance Imaging and Precise Cancer Cell Targeting.

    PubMed

    Luong, Duy; Sau, Samaresh; Kesharwani, Prashant; Iyer, Arun K

    2017-03-09

    The low therapeutic index of conventional chemotherapy and poor prognosis of patients diagnosed with metastatic cancers are prompting clinicians to adopt newer strategies to simultaneously detect cancer lesions at an early stage and to precisely deliver anticancer drugs to tumor sites. In this study, we employed a novel strategy to engineer a polyvalent theranostic nanocarrier consisting of superparamagnetic iron oxide nanoparticle core (SPIONs) decorated with folic acid-polyamidoamine dendrimers surface (FA-PAMAM). In addition, a highly potent hydrophobic anticancer agent 3,4-difluorobenzylidene-curcumin (CDF) was coloaded in the FA-PAMAM dendrimer to increase its solubility and assess its therapeutic potentials. The resulting targeted nanoparticles (SPIONs@FA-PAMAM-CDF) exhibited high MR contrast. When tested on folate receptor overexpressing ovarian (SKOV3) and cervical (HeLa) cancer cells, the CDF loaded targeted nanoformulations showed higher accumulation with a better anticancer activity as compared to the nontargeted counterparts, possibly due to multivalent folate receptor binding interaction with cells overexpressing the target. The results were corroborated by observation of a larger population of cells undergoing apoptosis due to upregulation of tumor suppressor phosphatase and tensis homologue (PTEN), caspase 3, and inhibition of NF-κB in groups treated with the targeted formulations, which further confirmed the ability of the multivalent theranostic nanoparticles for simultaneous imaging and therapy of cancers.

  13. Elemental and Isotopic Analysis of Uranium Oxide an NIST Glass Standards by FEMTOSECOND-LA-ICP-MIC-MS

    SciTech Connect

    Ebert, Chris; Zamzow, Daniel S.; McBay, Eddie H.; Bostick, Debra A.; Bajic, Stanley J.; Baldwin, David P.; Houk, R.S.

    2009-06-01

    The objective of this work was to test and demonstrate the analytical figures of merit of a femtosecond-laser ablation (fs-LA) system coupled with an inductively coupled plasma-multi-ion collector-mass spectrometer (ICP-MIC-MS). The mobile fs-LA sampling system was designed and assembled at Ames Laboratory and shipped to Oak Ridge National Laboratory (ORNL), where it was integrated with an ICP-MIC-MS. The test period of the integrated systems was February 2-6, 2009. Spatially-resolved analysis of particulate samples is accomplished by 100-shot laser ablation using a fs-pulsewidth laser and monitoring selected isotopes in the resulting ICP-MS transient signal. The capability of performing high sensitivity, spatially resolved, isotopic analyses with high accuracy and precision and with virtually no sample preparation makes fs-LA-ICP-MIC-MS valuable for the measurement of actinide isotopes at low concentrations in very small samples for nonproliferation purposes. Femtosecond-LA has been shown to generate particles from the sample that are more representative of the bulk composition, thereby minimizing weaknesses encountered in previous work using nanosecond-LA (ns-LA). The improvement of fs- over ns-LA sampling arises from the different mechanisms for transfer of energy into the sample in these two laser pulse-length regimes. The shorter duration fs-LA pulses induce less heating and cause less damage to the sample than the longer ns pulses. This results in better stoichiometric sampling (i.e., a closer correlation between the composition of the ablated particles and that of the original solid sample), which improves accuracy for both intra- and inter-elemental analysis. The primary samples analyzed in this work are (a) solid uranium oxide powdered samples having different {sup 235}U to {sup 238}U concentration ratios, and (b) glass reference materials (NIST 610, 612, 614, and 616). Solid uranium oxide samples containing {sup 235}U in depleted, natural, and enriched

  14. Oxidative stress indicators and trace elements in the blue shark (Prionace glauca) off the east coast of the Mexican Pacific Ocean.

    PubMed

    Barrera-García, Angélica; O'Hara, Todd; Galván-Magaña, Felipe; Méndez-Rodríguez, Lía C; Castellini, J Margaret; Zenteno-Savín, Tania

    2012-08-01

    Trace element concentrations and oxidative stress indicators (including production of reactive oxygen species (ROS), antioxidant enzyme activities and oxidative damage) were measured in muscle of blue sharks collected along the west coast of Baja California Sur to determine potential differences by sex and maturity cohorts. Mercury (Hg) concentration in muscle samples from larger sharks (>200 cm LT) exceeded the permissible limit (>1 ppm wet weight) for human consumption set by numerous international agencies. Significant differences were found in Hg concentrations (mature>immature; males>females), and in protein carbonyl concentrations (male>female); however, except for carbonyl protein levels, no significant differences by sex or maturity stage were found in the oxidative stress indicators. Differences between sexes and maturity stages in trace element concentration and carbonyl protein levels in blue shark muscle may be related to variations in diet within different cohorts.

  15. Regional framework and geology of iron oxide-apatite-rare earth element and iron oxide-copper-gold deposits of the Mesoproterozoic St. Francois Mountains Terrane, southeast Missouri

    USGS Publications Warehouse

    Day, Warren C.; Slack, John F.; Ayuso, Robert A.; Seeger, Cheryl M.

    2016-01-01

    This paper provides an overview on the genesis of Mesoproterozoic igneous rocks and associated iron oxide ± apatite (IOA) ± rare earth element, iron oxide-copper-gold (IOCG), and iron-rich sedimentary deposits in the St. Francois Mountains terrane of southeast Missouri, USA. The St. Francois Mountains terrane lies along the southeastern margin of Laurentia as part of the eastern granite-rhyolite province. The province formed during two major pulses of igneous activity: (1) an older early Mesoproterozoic (ca. 1.50–1.44 Ga) episode of volcanism and granite plutonism, and (2) a younger middle Mesoproterozoic (ca. 1.33–1.30 Ga) episode of bimodal gabbro and granite plutonism. The volcanic rocks are predominantly high-silica rhyolite pyroclastic flows, volcanogenic breccias, and associated volcanogenic sediments with lesser amounts of basaltic to andesitic volcanic and associated subvolcanic intrusive rocks. The iron oxide deposits are all hosted in the early Mesoproterozoic volcanic and volcaniclastic sequences. Previous studies have characterized the St. Francois Mountains terrane as a classic, A-type within-plate granitic terrane. However, our new whole-rock geochemical data indicate that the felsic volcanic rocks are effusive derivatives from multicomponent source types, having compositional similarities to A-type within-plate granites as well as to S- and I-type granites generated in an arc setting. In addition, the volcanic-hosted IOA and IOCG deposits occur within bimodal volcanic sequences, some of which have volcanic arc geochemical affinities, suggesting an extensional tectonic setting during volcanism prior to emplacement of the ore-forming systems.The Missouri iron orebodies are magmatic-related hydrothermal deposits that, when considered in aggregate, display a vertical zonation from high-temperature, magmatic ± hydrothermal IOA deposits emplaced at moderate depths (~1–2 km), to magnetite-dominant IOA veins and IOCG deposits emplaced at shallow

  16. What controls the oxidative ratio of UK peats? A multi-site study of elemental CHNO concentrations in peat cores

    NASA Astrophysics Data System (ADS)

    Clay, Gareth; Worrall, Fred; Masiello, Carrie

    2013-04-01

    The oxidative ratio (OR) is the amount of CO2 sequestered in the terrestrial biosphere for each mol of O2 produced. The OR governs the effectiveness of a terrestrial biome to mitigate the impact of anthropogenic CO2 emissions and it has been used to calculate the balance of terrestrial and oceanic carbon sinks across the globe. However, few studies have investigated the controls of the variability in OR. What factors affect OR - climate? Soil type? Vegetation type? N deposition? Land use? Land use change? Small shifts in OR could have important implications in the global partitioning of CO2 between the atmosphere, biosphere, and oceans. This study looks at peat soils from a series of sites representing a climatic transect across the UK. Duplicate peat cores were taken, along with samples of above-ground vegetation and litter, from sites in northern Scotland (Forsinard), southern Scotland (Auchencorth), northern England (Moor House; Thorne Moor) through the Welsh borders (Whixhall Moss) and Somerset levels (Westhay Moor) to Dartmoor and Bodmin Moor in the south west of England. Sub-samples of the cores were analysed for their CHNO concentrations using a Costech ECS 4010 Elemental combustion system. Using the method of Masiello et al. (2008), OR values could be calculated from these elemental concentrations. Results show that OR values of UK peats varied between 0.82 and 1.27 with a median value of 1.08 which is within the range of world soils. There were significant differences in OR of the peat between sites with the data falling into two broad groupings - Group 1: Forsinard, Auchencorth, Dartmoor and Bodmin Moor; Group 2: Moor House, Thorne Moor, Westhay Moor, Whixhall Moss. Whilst there were significant changes (p < 0.05) in elemental ratios with increasing peat depth (increasing C:N ratio and decreasing O:C ratio) there was no significant difference overall in OR with depth. This paper will explore some of the possible controlling factors on these ratios. Local

  17. Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy.

    PubMed

    Tassa, Carlos; Shaw, Stanley Y; Weissleder, Ralph

    2011-10-18

    Advances in our understanding of the genetic basis of disease susceptibility coupled with prominent successes for molecular targeted therapies have resulted in an emerging strategy of personalized medicine. This approach envisions risk stratification and therapeutic selection based on an individual's genetic makeup and physiologic state (the latter assessed through cellular or molecular phenotypes). Molecularly targeted nanoparticles can play a key role in this vision through noninvasive assessments of molecular processes and specific cell populations in vivo, sensitive molecular diagnostics, and targeted delivery of therapeutics. A superparamagnetic iron oxide nanoparticle with a cross-linked dextran coating, or CLIO, is a powerful and illustrative nanoparticle platform for these applications. These structures and their derivatives support diagnostic imaging by magnetic resonance (MRI), optical, and positron emission tomography (PET) modalities and constitute a versatile platform for conjugation to targeting ligands. A variety of conjugation methods exist to couple the dextran surface to different functional groups; in addition, a robust bioorthogonal [4 + 2] cycloaddition reaction between 1,2,4,5-tetrazene (Tz) and trans-cyclooctene (TCO) can conjugate nanoparticles to targeting ligands or label pretargeted cells. The ready availability of conjugation methods has given rise to the synthesis of libraries of small molecule modified nanoparticles, which can then be screened for nanoparticles with specificity for a specific cell type. Since most nanoparticles display their targeting ligands in a multivalent manner, a detailed understanding of the kinetics and affinity of a nanoparticle's interaction with its target (as determined by surface plasmon resonance) can yield functionally important insights into nanoparticle design. In this Account, we review applications of the CLIO platform in several areas relevant to the mission of personalized medicine. We demonstrate

  18. Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting.

    PubMed

    Cole, Adam J; David, Allan E; Wang, Jianxin; Galbán, Craig J; Hill, Hannah L; Yang, Victor C

    2011-03-01

    While successful magnetic tumor targeting of iron oxide nanoparticles has been achieved in a number of models, the rapid blood clearance of magnetically suitable particles by the reticuloendothelial system (RES) limits their availability for targeting. This work aimed to develop a long-circulating magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor exposure via the circulation and, thus, potentially enhanced magnetic tumor targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 & D20) were similar in size (140-190 nm) and relative PEG labeling (1.5% of surface amines - A5/D5, 0.4% - A20/D20), with all PEG-MNPs possessing magnetization properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in RES simulations in vitro to predict long-circulating character. D5 and D20 performed best showing sustained size stability in cell culture medium at 37 °C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when compared to previously targeted, unmodified starch MNPs (D). Observations in vitro were validated in vivo, with D5 (7.29 h) and D20 (11.75 h) showing much longer half-lives than D (0.12 h). Improved plasma stability enhanced tumor MNP exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC(0-∞). Sustained tumor exposure over 24 h was visually confirmed in a 9L-glioma rat model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate that a polyethylene glycol modified, cross-linked starch-coated MNP is a promising platform for enhanced magnetic tumor targeting, warranting further study in tumor models.

  19. Cerebral Small Vessel Disease: Targeting Oxidative Stress as a Novel Therapeutic Strategy?

    PubMed Central

    De Silva, T. Michael; Miller, Alyson A.

    2016-01-01

    Cerebral small vessel disease (SVD) is a major contributor to stroke, and a leading cause of cognitive impairment and dementia. Despite the devastating effects of cerebral SVD, the pathogenesis of cerebral SVD is still not completely understood. Moreover, there are no specific pharmacological strategies for its prevention or treatment. Cerebral SVD is characterized by marked functional and structural abnormalities of the cerebral microcirculation. The clinical manifestations of these pathological changes include lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. The main purpose of this review is to discuss evidence implicating oxidative stress in the arteriopathy of both non-amyloid and amyloid (cerebral amyloid angiopathy) forms of cerebral SVD and its most important risk factors (hypertension and aging), as well as its contribution to cerebral SVD-related brain injury and cognitive impairment. We also highlight current evidence of the involvement of the NADPH oxidases in the development of oxidative stress, enzymes that are a major source of reactive oxygen species in the cerebral vasculature. Lastly, we discuss potential pharmacological strategies for oxidative stress in cerebral SVD, including some of the historical and emerging NADPH oxidase inhibitors. PMID:27014073

  20. Oxidative Stress Is a Central Target for Physical Exercise Neuroprotection Against Pathological Brain Aging.

    PubMed

    García-Mesa, Yoelvis; Colie, Sandra; Corpas, Rubén; Cristòfol, Rosa; Comellas, Francesc; Nebreda, Angel R; Giménez-Llort, Lydia; Sanfeliu, Coral

    2016-01-01

    Physical exercise is suggested for preventing or delaying senescence and Alzheimer's disease (AD). We have examined its therapeutic value in the advanced stage of AD-like pathology in 3xTg-AD female mice through voluntary wheel running from 12 to 15 months of age. Mice submitted to exercise showed improved body fitness, immunorejuvenation, improvement of behavior and cognition, and reduced amyloid and tau pathology. Brain tissue analysis of aged 3xTg-AD mice showed high levels of oxidative damage. However, this damage was decreased by physical exercise through regulation of redox homeostasis. Network analyses showed that oxidative stress was a central event, which correlated with AD-like pathology and the AD-related behaviors of anxiety, apathy, and cognitive loss. This study corroborates the importance of redox mechanisms in the neuroprotective effect of physical exercise, and supports the theory of the crucial role of oxidative stress in the switch from normal brain aging to pathological aging and AD.

  1. Facing-target mid-frequency magnetron reactive sputtered hafnium oxide film: Morphology and electrical properties

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Xu, Jun; Wang, You-Nian; Choi, Chi Kyu; Zhou, Da-Yu

    2016-03-01

    Amorphous hafnium dioxide (HfO2) film was prepared on Si (100) by facing-target mid-frequency reactive magnetron sputtering under different oxygen/argon gas ratio at room temperature with high purity Hf target. 3D surface profiler results showed that the deposition rates of HfO2 thin film under different O2/Ar gas ratio remain unchanged, indicating that the facing target midfrequency magnetron sputtering system provides effective approach to eliminate target poisoning phenomenon which is generally occurred in reactive sputtering procedure. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) demonstrated that the gradual reduction of oxygen vacancy concentration and the densification of deposited film structure with the increase of oxygen/argon (O2/Ar) gas flow ratio. Atomic force microscopy (AFM) analysis suggested that the surface of the as-deposited HfO2 thin film tends to be smoother, the root-meansquare roughness (RMS) reduced from 0.876 nm to 0.333 nm while O2/Ar gas flow ratio increased from 1/4 to 1/1. Current-Voltage measurements of MOS capacitor based on Au/HfO2/Si structure indicated that the leakage current density of HfO2 thin films decreased by increasing of oxygen partial pressure, which resulted in the variations of pore size and oxygen vacancy concentration in deposited thin films. Based on the above characterization results the leakage current mechanism for all samples was discussed systematically.

  2. Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions

    PubMed Central

    Kagan, Valerian E.; Wipf, Peter; Stoyanovsky, Detcho; Greenberger, Joel S.; Borisenko, Grigory; Belikova, Natalia A.; Yanamala, Naveena; Samhan Arias, Alejandro K.; Tungekar, Muhammad A.; Jiang, Jianfei; Tyurina, Yulia Y.; Ji, Jing; Klein-Seetharaman, Judith; Pitt, Bruce R.; Shvedova, Anna A; Bayır, Hülya

    2009-01-01

    Effective regulation of highly compartmentalized production of reactive oxygen species and peroxidation reactions in mitochondria requires targeting of small molecule antioxidants and antioxidant enzymes into the organelles. This review describes recently developed approaches to mitochondrial targeting of small biologically active molecules based on: (i) preferential accumulation in mitochondria because of their hydrophobicity and positive charge (hydrophobic cations), (ii) binding with high affinity to an intra-mitochondrial constituent, and (iii) metabolic conversions by specific mitochondrial enzymes to reveal an active entity. In addition, targeted delivery of antioxidant enzymes via expression of leader-sequences directing the proteins into mitochondria is considered. Examples of successful antioxidant and anti-apoptotic protection based on the ability of targeted cargoes to inhibit cytochrome c-catalyzed peroxidation of a mitochondria-specific phospholipid cardiolipin, in vitro and in vivo are presented. Particular emphasis is placed on the employment of triphenylphosphonium- and hemi-gramicidin S-moieties as two effective vehicles for mitochondrial delivery of antioxidants. PMID:19716396

  3. Preparation of 152Gd targets from a small quantity of gadolinium oxide in a pyrochemical reaction

    NASA Astrophysics Data System (ADS)

    Lipski, A. R.

    1995-02-01

    A simple method utilizing small amounts (< 5 mg) of isotopically enriched material for the production of gadolinium targets is discussed. An electrostatically focused e-gun is used in the procedure in which 152Gd 2O 3 powder undergoes reduction-distillation and deposition onto an Fe foil.

  4. Förster resonance energy transfer-based sensor targeting endoplasmic reticulum reveals highly oxidative environment

    PubMed Central

    Kolossov, Vladimir L; Leslie, Matthew T; Chatterjee, Abhishek; Sheehan, Bridget M; Kenis, Paul J A; Gaskins, H Rex

    2012-01-01

    The glutathione thiol/disulfide couple is the major redox buffer in the endoplasmic reticulum (ER); however, mechanisms by which it contributes to the tightly regulated redox environment of this intracellular organelle are poorly understood. The recent development of genetically encoded, ratiometric, single green fluorescent protein-based redox-sensitive (roGFP) sensors adjusted for more oxidative environments enables non-invasive measurement of the ER redox environment in living cells. In turn, Förster resonance energy transfer (FRET) sensors based on two fluorophore probes represent an alternative strategy for ratiometric signal acquisition. In previous work, we described the FRET-based redox sensor CY-RL7 with a relatively high midpoint redox potential of −143 mV, which is required for monitoring glutathione potentials in the comparatively high oxidative environment of the ER. Here, the efficacy of the CY-RL7 probe was ascertained in the cytosol and ER of live cells with fluorescence microscopy and flow cytometry. The sensor was found to be fully reduced at steady state in the cytosol and became fully oxidized in response to treatment with 1-chloro-2,4-dinitrobenzene, a depletor of reduced glutathione (GSH). In contrast, the probe was strongly oxidized (88%) upon expression in the ER of cultured cells. We also examined the responsiveness of the ER sensor to perturbations in cellular glutathione homeostasis. We observed that the reductive level of the FRET sensor was increased two-fold to about 28% in cells pretreated with N-acetylcysteine, a substrate for GSH synthesis. Finally, we evaluated the responsiveness of CY-RL7 and roGFP1-iL to various perturbations of cellular glutathione homeostasis to address the divergence in the specificity of these two probes. Together, the present data generated with genetically encoded green fluorescent protein (GFP)-based glutathione probes highlight the complexity of the ER redox environment and indicate that the ER

  5. Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

    PubMed Central

    Uchiyama, Mayara Klimuk; Toma, Sergio Hiroshi; Rodrigues, Stephen Fernandes; Shimada, Ana Lucia Borges; Loiola, Rodrigo Azevedo; Cervantes Rodríguez, Hernán Joel; Oliveira, Pedro Vitoriano; Luz, Maciel Santos; Rabbani, Said Rahnamaye; Toma, Henrique Eisi; Poliselli Farsky, Sandra Helena; Araki, Koiti

    2015-01-01

    Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM−1s−1 in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics. PMID:26251595

  6. Arsenite Targets the Zinc Finger Domains of Tet Proteins and Inhibits Tet-Mediated Oxidation of 5-Methylcytosine.

    PubMed

    Liu, Shuo; Jiang, Ji; Li, Lin; Amato, Nicholas J; Wang, Zi; Wang, Yinsheng

    2015-10-06

    Arsenic toxicity is a serious public health problem worldwide that brings more than 100 million people into the risk of arsenic exposure from groundwater and food contamination. Although there is accumulating evidence linking arsenic exposure with aberrant cytosine methylation in the global genome or at specific genomic loci, very few have investigated the impact of arsenic on the oxidation of 5-methylcytosine (5-mC) mediated by the Ten-eleven translocation (Tet) family of proteins. Owing to the high binding affinity of As(III) toward cysteine residues, we reasoned that the highly conserved C3H-type zinc fingers situated in Tet proteins may constitute potential targets for arsenic binding. Herein, we found that arsenite could bind directly to the zinc fingers of Tet proteins in vitro and in cells, and this interaction substantially impaired the catalytic efficiency of Tet proteins in oxidizing 5-mC to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC). Treatments with arsenite also led to a dose-dependent decrease in the level of 5-hmC, but not 5-mC, in DNA isolated from HEK293T cells overexpressing the catalytic domain of any of the three Tet proteins and from mouse embryonic stem cells. Together, our study unveiled, for the first time, that arsenite could alter epigenetic signaling by targeting the zinc fingers of Tet proteins and perturbing the Tet-mediated oxidation of 5-mC in vitro and in cells. Our results offer important mechanistic understanding of arsenic epigenotoxicity and carcinogenesis in mammalian systems and may lead to novel approaches for the chemoprevention of arsenic toxicity.

  7. The effect of mechanical properties of iron oxide nanoparticle-loaded functional nano-carrier on tumor targeting and imaging.

    PubMed

    Choi, Won Il; Kim, Ja-Young; Heo, Seon U; Jeong, Yong Yeon; Kim, Young Ha; Tae, Giyoong

    2012-09-10

    To achieve a sufficient targeting efficiency and prolonged half-life in-vivo, the physicochemical parameters including size and surface chemistry of therapeutic and imaging agents should be controlled. In this study, we prepared an iron oxide nanoparticle (IONP)-loaded, functional nano-carrier with different loading contents to modulate the mechanical properties of the system, and compared the characteristics of tumor targeting and imaging in terms of loading contents of IONP. As a functional nano-carrier, chitosan-conjugated, Pluronic-based nano-carrier with useful properties such as long blood circulation, good tumor targeting, and easy loading of macromolecules was used. IONPs were efficiently encapsulated into the nano-carrier (high loading efficiency over 95%) and the mechanical properties of the IONP-loaded nano-carrier were controlled by varying the loading amount of IONP. The IONP-loaded nano-carrier with the higher loading content of IONP (40 wt.%) was significantly more rigid (over 2×) than those with lower loading contents of IONP (5 and 15 wt.%). Although the nano-carrier with the higher loading content of IONP showed more enhanced MR contrast effect with higher T(2) relaxivity and higher intracellular uptake in vitro, characteristics of in-vivo tumor targeting and MR cancer imaging were not good compared to that of the nano-carrrier with the lower loading contents of IONP. Since different loading contents did not affect other characteristics of the system (size, surface chemistry, and surface charge), the present result suggests that the mechanical properties (strength/flexibility) of nano-systems are also important factors to be controlled for targeted delivery and imaging.

  8. Photoresponsive fluorescent reduced graphene oxide by spiropyran conjugated hyaluronic acid for in vivo imaging and target delivery.

    PubMed

    Nahain, Abdullah-Al; Lee, Jung-Eun; Jeong, Ji Hoon; Park, Sung Young

    2013-11-11

    This present article demonstrates the strategy to prepare photoresponsive reduced graphene oxide with mussel inspired adhesive material dopamine (DN) and photochromic dye spiropyran (SP) conjugated to the backbone of the targeting ligand hyaluronic acid (HA; HA-SP). Graphene oxide (GO) was reduced by prepared HA-SP accepting the advantages of catechol chemistry under mildly alkaline condition enabling to achieve functionalized graphene (rGO/HA-SP) as fluorescent nanoparticles. Due to containing HA, rGO/HA-SP can bind to the CD44 cell receptors. The prepared rGO/HA-SP is able to retain its photochromic features and can be converted to merocyanine (MC) form upon irradiation with UV light (wavelength: 365 nm) displaying purple color. Photochromic behavior of rGO/HA-SP was monitored by UV-vis and fluorescence spectroscopy. In vitro fluorescence behavior, examined by confocal laser scanning microscope (CLSM), of rGO/HA-SP in cancerous A549 cell lines assured that efficient delivery of rGO/HA-SP was gained due to HA as targeting ligand. In this work, we have shown that in vivo fluorescence image of spiropyran is possible by administrating MC form solution of rGO/HA-SP using Balb/C mice as in vivo modal. Accumulation of rGO/HA-SP in tumor tissue from biodistribution analysis strongly supports the specific delivery of prepared graphene to the target destination. The well tuned drug release manner from the surface of rGO/HA-SP strongly recommends the developed material not only as fluorescent probe for diagnosis but also as a drug carrier in drug delivery system.

  9. Silibinin inhibits aberrant lipid metabolism, proliferation and emergence of androgen-independence in prostate cancer cells via primarily targeting the sterol response element binding protein 1.

    PubMed

    Nambiar, Dhanya K; Deep, Gagan; Singh, Rana P; Agarwal, Chapla; Agarwal, Rajesh

    2014-10-30

    Prostate cancer (PCA) kills thousands of men every year, demanding additional approaches to better understand and target this malignancy. Recently, critical role of aberrant lipogenesis is highlighted in prostate carcinogenesis, offering a unique opportunity to target it to reduce PCA. Here, we evaluated efficacy and associated mechanisms of silibinin in inhibiting lipid metabolism in PCA cells. At physiologically achievable levels in human, silibinin strongly reduced lipid and cholesterol accumulation specifically in human PCA cells but not in non-neoplastic prostate epithelial PWR-1E cells. Silibinin also decreased nuclear protein levels of sterol regulatory element binding protein 1 and 2 (SREBP1/2) and their target genes only in PCA cells. Mechanistically, silibinin activated AMPK, thereby increasing SREBP1 phosphorylation and inhibiting its nuclear translocation; AMPK inhibition reversed silibinin-mediated decrease in nuclear SREBP1 and lipid accumulation. Additionally, specific SREBP inhibitor fatostatin and stable overexpression of SREBP1 further confirmed the central role of SREBP1 in silibinin-mediated inhibition of PCA cell proliferation and lipid accumulation and cell cycle arrest. Importantly, silibinin also inhibited synthetic androgen R1881-induced lipid accumulation and completely abrogated the development of androgen-independent LNCaP cell clones via targeting SREBP1/2. Together, these mechanistic studies suggest that silibinin would be effective against PCA by targeting critical aberrant lipogenesis.

  10. CstF-64 and 3′-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα

    PubMed Central

    Kandala, Divya T.; Mohan, Nimmy; A, Vivekanand; AP, Sudheesh; G, Reshmi; Laishram, Rakesh S.

    2016-01-01

    Almost all eukaryotic mRNAs have a poly (A) tail at the 3′-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3′-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3′-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3′-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation. PMID:26496945

  11. CstF-64 and 3'-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα.

    PubMed

    Kandala, Divya T; Mohan, Nimmy; A, Vivekanand; A P, Sudheesh; G, Reshmi; Laishram, Rakesh S

    2016-01-29

    Almost all eukaryotic mRNAs have a poly (A) tail at the 3'-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3'-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3'-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3'-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation.

  12. Improved Yields of Iodine-124 from the Enriched Tellurium-124 Dioxide/Aluminum Oxide Target

    NASA Astrophysics Data System (ADS)

    Finn, R. D.; Qiao, J.; Nacca, A.; Sheh, Y.; Lom, C.; Balatoni, J.; Cai, S.; Bornmann, W.; Pentlow, K.

    2003-08-01

    The escalating clinical application of Positron Emission Tomography results from the novel radiotracers which are available to monitor specific biochemical or physiologic processes. Future developments of the technique will require an increasing availability of additional unique radioligands and radionuclides. Iodine-124, a radionuclide whose potential for both diagnostic and therapeutic applications is widely recognized, has been prepared at Memorial Sloan-Kettering Cancer Center on a weekly basis for several years (1). With its characteristic 4.18 day half life and complex decay scheme (2) which includes positron emission (22.0 ± 0.5%) and electron capture (78 ± 0.5%), this radionuclide has been shown to be appropriate for radiotracers describing slow physiologic processes with the clearance of non-specific radioactivity. The refinements and modifications being engineered into the cyclotron target system to increase the absolute yield of recoverable radioactivity from each irradiation and its chemical processing of the reusable solid target matrix are described..

  13. Improved Yields of Iodine-124 from the Enriched Tellurium-124 Dioxide/Aluminum Oxide Target

    SciTech Connect

    Finn, R.D.; Qiao, J.; Nacca, A.; Sheh, Y.; Lom, C.; Balatoni, J.; Cai, S.; Bornmann, W.; Pentlow, K.

    2003-08-26

    The escalating clinical application of Positron Emission Tomography results from the novel radiotracers which are available to monitor specific biochemical or physiologic processes. Future developments of the technique will require an increasing availability of additional unique radioligands and radionuclides. Iodine-124, a radionuclide whose potential for both diagnostic and therapeutic applications is widely recognized, has been prepared at Memorial Sloan-Kettering Cancer Center on a weekly basis for several years (1). With its characteristic 4.18 day half life and complex decay scheme (2) which includes positron emission (22.0 {+-} 0.5%) and electron capture (78 {+-} 0.5%), this radionuclide has been shown to be appropriate for radiotracers describing slow physiologic processes with the clearance of non-specific radioactivity. The refinements and modifications being engineered into the cyclotron target system to increase the absolute yield of recoverable radioactivity from each irradiation and its chemical processing of the reusable solid target matrix are described.

  14. The microstructure, mechanical and electrical properties of Niobium pentoxide-doped Titanium oxide ceramic targets

    NASA Astrophysics Data System (ADS)

    Ling, Qi; Xu, TingTing; Wu, LianZi; Peng, Wei; Zhu, ZuoXiang; Xie, ShengHui; Yang, HaiPeng; Gao, JiHua; Gao, Ling; Yang, HaiTao

    2017-03-01

    Nb2O5 doped TiO2 (NTO) ceramic targets were prepared by sintering in Ar at l350 °C for 2 hours. The morphologies structures, densification behavior, mechanical and electrical properties of the sintered ceramic targets with different doping concentration were investigated. The results show that the Nb2O5 content of increase from 0 wt% to 10 wt% not only enhance the densification but promote the grain growth. The morphologies, compositions, microstructure, and chemical states were characterized by SEM and XRD. The relative density, grain size and resistivity of 7.5 wt% content sintered at 1350 °C in Ar were 94.5%, 13.76 μm, and 7.8×10‑2 Ω·cm, respectively.

  15. RGD-functionalized ultrasmall iron oxide nanoparticles for targeted T1-weighted MR imaging of gliomas

    NASA Astrophysics Data System (ADS)

    Luo, Yu; Yang, Jia; Yan, Yu; Li, Jingchao; Shen, Mingwu; Zhang, Guixiang; Mignani, Serge; Shi, Xiangyang

    2015-08-01

    We report a convenient approach to prepare ultrasmall Fe3O4 nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe3O4 NPs were prepared by a solvothermal route. Then, the carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe3O4-PEG-RGD) was fully characterized using different techniques. We show that these Fe3O4-PEG-RGD particles with a size of 2.7 nm are water-dispersible, stable, cytocompatible and hemocompatible in a given concentration range, and display targeting specificity to glioma cells overexpressing αvβ3 integrin in vitro. With the relatively high r1 relaxivity (r1 = 1.4 mM-1 s-1), the Fe3O4-PEG-RGD particles can be used as an efficient nanoprobe for targeted T1-weighted positive MR imaging of glioma cells in vitro and the xenografted tumor model in vivo via an active RGD-mediated targeting pathway. The developed RGD-functionalized Fe3O4 NPs may hold great promise to be used as a nanoprobe for targeted T1-weighted MR imaging of different αvβ3 integrin-overexpressing cancer cells or biological systems.We report a convenient approach to prepare ultrasmall Fe3O4 nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe3O4 NPs were prepared by a solvothermal route. Then, the carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe3O4-PEG-RGD) was fully characterized using different techniques. We show that these Fe3O4-PEG-RGD particles with a size of 2.7 nm are water-dispersible, stable, cytocompatible and hemocompatible in a given concentration

  16. A comparison of an optimised sequential extraction procedure and dilute acid leaching of elements in anoxic sediments, including the effects of oxidation on sediment metal partitioning.

    PubMed

    Larner, Bronwyn L; Palmer, Anne S; Seen, Andrew J; Townsend, Ashley T

    2008-02-11

    The effect of oxidation of anoxic sediment upon the extraction of 13 elements (Cd, Sn, Sb, Pb, Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As) using the optimised Community Bureau of Reference of the European Commission (BCR) sequential extraction procedure and a dilute acid partial extraction procedure (4h, 1 molL(-1) HCl) was investigated. Elements commonly associated with the sulfidic phase, Cd, Cu, Pb, Zn and Fe exhibited the most significant changes under the BCR sequential extraction procedure. Cd, Cu, Zn, and to a lesser extent Pb, were redistributed into the weak acid extractable fraction upon oxidation of the anoxic sediment and Fe was redistributed into the reducible fraction as expected, but an increase was also observed in the residual Fe. For the HCl partial extraction, sediments with moderate acid volatile sulfide (AVS) levels (1-100 micromolg(-1)) showed no significant difference in element partitioning following oxidation, whilst sediments containing high AVS levels (>100 micromolg(-1)) were significantly different with elevated concentrations of Cu and Sn noted in the partial extract following oxidation of the sediment. Comparison of the labile metals released using the BCR sequential extraction procedure (SigmaSteps 1-3) to labile metals extracted using the dilute HCl partial extraction showed that no method was consistently more aggressive than the other, with the HCl partial extraction extracting more Sn and Sb from the anoxic sediment than the BCR procedure, whilst the BCR procedure extracted more Cr, Co, Cu and As than the HCl extraction.

  17. Antisense targeting of 3' end elements involved in DUX4 mRNA processing is an efficient therapeutic strategy for facioscapulohumeral dystrophy: a new gene-silencing approach.

    PubMed

    Marsollier, Anne-Charlotte; Ciszewski, Lukasz; Mariot, Virginie; Popplewell, Linda; Voit, Thomas; Dickson, George; Dumonceaux, Julie

    2016-04-15

    Defects in mRNA 3'end formation have been described to alter transcription termination, transport of the mRNA from the nucleus to the cytoplasm, stability of the mRNA and translation efficiency. Therefore, inhibition of polyadenylation may lead to gene silencing. Here, we choose facioscapulohumeral dystrophy (FSHD) as a model to determine whether or not targeting key 3' end elements involved in mRNA processing using antisense oligonucleotide drugs can be used as a strategy for gene silencing within a potentially therapeutic context. FSHD is a gain-of-function disease characterized by the aberrant expression of the Double homeobox 4 (DUX4) transcription factor leading to altered pathogenic deregulation of multiple genes in muscles. Here, we demonstrate that targeting either the mRNA polyadenylation signal and/or cleavage site is an efficient strategy to down-regulate DUX4 expression and to decrease the abnormally high-pathological expression of genes downstream of DUX4. We conclude that targeting key functional 3' end elements involved in pre-mRNA to mRNA maturation with antisense drugs can lead to efficient gene silencing and is thus a potentially effective therapeutic strategy for at least FSHD. Moreover, polyadenylation is a crucial step in the maturation of almost all eukaryotic mRNAs, and thus all mRNAs are virtually eligible for this antisense-mediated knockdown strategy.

  18. Remote magnetic targeting of iron oxide nanoparticles for cardiovascular diagnosis and therapeutic drug delivery: where are we now?

    PubMed

    Bietenbeck, Michael; Florian, Anca; Faber, Cornelius; Sechtem, Udo; Yilmaz, Ali

    2016-01-01

    Magnetic resonance imaging (MRI) allows for an accurate assessment of both functional and structural cardiac parameters, and thereby appropriate diagnosis and validation of cardiovascular diseases. The diagnostic yield of cardiovascular MRI examinations is often increased by the use of contrast agents that are almost exclusively based on gadolinium compounds. Another clinically approved contrast medium is composed of superparamagnetic iron oxide nanoparticles (IONs). These particles may expand the field of contrast-enhanced cardiovascular MRI as recently shown in clinical studies focusing on acute myocardial infarction (AMI) and atherosclerosis. Furthermore, IONs open up new research opportunities such as remote magnetic drug targeting (MDT). The approach of MDT relies on the coupling of bioactive molecules and magnetic nanoparticles to form an injectable complex. This complex, in turn, can be attracted to and retained at a desired target inside the body with the help of applied magnetic fields. In comparison to common systemic drug applications, MDT techniques promise both higher concentrations at the target site and lower concentrations elsewhere in the body. Moreover, concurrent or subsequent MRI can be used for noninvasive monitoring of drug distribution and successful delivery to the desired organ in vivo. This review does not only illustrate the basic conceptual and biophysical principles of IONs, but also focuses on new research activities and achievements in the cardiovascular field, mainly in the management of AMI. Based on the presentation of successful MDT applications in preclinical models of AMI, novel approaches and the translational potential of MDT are discussed.

  19. Design of multifunctional magnetic iron oxide nanoparticles/mitoxantrone-loaded liposomes for both magnetic resonance imaging and targeted cancer therapy.

    PubMed

    He, Yingna; Zhang, Linhua; Zhu, Dunwan; Song, Cunxian

    2014-01-01

    Tumor-targeting multifunctional liposomes simultaneously loaded with magnetic iron oxide nanoparticles (MIONs) as a magnetic resonance imaging (MRI) contrast agent and anticancer drug, mitoxantrone (Mit), were developed for targeted cancer therapy and ultrasensitive MRI. The gonadorelin-functionalized MION/Mit-loaded liposome (Mit-GML) showed significantly increased uptake in luteinizing hormone-releasing hormone (LHRH) receptor overexpressing MCF-7 (Michigan Cancer Foundation-7) breast cancer cells over a gonadorelin-free MION/Mit-loaded liposome (Mit-ML) control, as well as in an LHRH receptor low-expressing Sloan-Kettering HER2 3+ Ovarian Cancer (SK-OV-3) cell control, thereby leading to high cytotoxicity against the MCF-7 human breast tumor cell line. The Mit-GML formulation was more effective and less toxic than equimolar doses of free Mit or Mit-ML in the treatment of LHRH receptors overexpressing MCF-7 breast cancer xenografts in mice. Furthermore, the Mit-GML demonstrated much higher T2 enhancement than did Mit-ML controls in vivo. Collectively, the study indicates that the integrated diagnostic and therapeutic design of Mit-GML nanomedicine potentially allows for the image-guided, target-specific treatment of cancer.

  20. High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging.

    PubMed

    Xiao, Yunbin; Lin, Zuan Tao; Chen, Yanmei; Wang, He; Deng, Ya Li; Le, D Elizabeth; Bin, Jianguo; Li, Meiyu; Liao, Yulin; Liu, Yili; Jiang, Gangbiao; Bin, Jianping

    2015-01-01

    Magnetic resonance imaging (MRI) contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs) encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS) micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm) and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors.

  1. Deposition and characterization of titania-silica optical multilayers by asymmetric bipolar pulsed dc sputtering of oxide targets

    NASA Astrophysics Data System (ADS)

    Sagdeo, P. R.; Shinde, D. D.; Misal, J. S.; Kamble, N. M.; Tokas, R. B.; Biswas, A.; Poswal, A. K.; Thakur, S.; Bhattacharyya, D.; Sahoo, N. K.; Sabharwal, S. C.

    2010-02-01

    Titania-silica (TiO2/SiO2) optical multilayer structures have been conventionally deposited by reactive sputtering of metallic targets. In order to overcome the problems of arcing, target poisoning and low deposition rates encountered there, the application of oxide targets was investigated in this work with asymmetric bipolar pulsed dc magnetron sputtering. In order to evaluate the usefulness of this deposition methodology, an electric field optimized Fabry Perot mirror for He-Cd laser (λ = 441.6 nm) spectroscopy was deposited and characterized. For comparison, this mirror was also deposited by the reactive electron beam (EB) evaporation technique. The mirrors developed by the two complementary techniques were investigated for their microstructural and optical reflection properties invoking atomic force microscopy, ellipsometry, grazing incidence reflectometry and spectrophotometry. From these measurements the layer geometry, optical constants, mass density, topography, surface and interface roughness and disorder parameters were evaluated. The microstructural properties and spectral functional characteristics of the pulsed dc sputtered multilayer mirror were found to be distinctively superior to the EB deposited mirror. The knowledge gathered during this study has been utilized to develop a 21-layer high-pass edge filter for radio photoluminescence dosimetry.

  2. Remote magnetic targeting of iron oxide nanoparticles for cardiovascular diagnosis and therapeutic drug delivery: where are we now?

    PubMed Central

    Bietenbeck, Michael; Florian, Anca; Faber, Cornelius; Sechtem, Udo; Yilmaz, Ali

    2016-01-01

    Magnetic resonance imaging (MRI) allows for an accurate assessment of both functional and structural cardiac parameters, and thereby appropriate diagnosis and validation of cardiovascular diseases. The diagnostic yield of cardiovascular MRI examinations is often increased by the use of contrast agents that are almost exclusively based on gadolinium compounds. Another clinically approved contrast medium is composed of superparamagnetic iron oxide nanoparticles (IONs). These particles may expand the field of contrast-enhanced cardiovascular MRI as recently shown in clinical studies focusing on acute myocardial infarction (AMI) and atherosclerosis. Furthermore, IONs open up new research opportunities such as remote magnetic drug targeting (MDT). The approach of MDT relies on the coupling of bioactive molecules and magnetic nanoparticles to form an injectable complex. This complex, in turn, can be attracted to and retained at a desired target inside the body with the help of applied magnetic fields. In comparison to common systemic drug applications, MDT techniques promise both higher concentrations at the target site and lower concentrations elsewhere in the body. Moreover, concurrent or subsequent MRI can be used for noninvasive monitoring of drug distribution and successful delivery to the desired organ in vivo. This review does not only illustrate the basic conceptual and biophysical principles of IONs, but also focuses on new research activities and achievements in the cardiovascular field, mainly in the management of AMI. Based on the presentation of successful MDT applications in preclinical models of AMI, novel approaches and the translational potential of MDT are discussed. PMID:27486321

  3. Nanoimmunoliposome Delivery of Superparamagnetic Iron Oxide Markedly Enhances Targeting and Uptake in Human Cancer Cells In Vitro and In Vivo

    PubMed Central

    Yang, Chengli; Rait, Antonina; Pirollo, Kathleen F.; Dagata, John A.; Farkas, Natalia; Chang, Esther H.

    2008-01-01

    To circumvent the problem of reduction of the supermagnetic properties of superparamagnetic iron oxide (SPIO) nanoparticles after chemical modification to conjugate targeting molecules, we have adapted a tumor-targeting nanoimmunoliposome platform technology (scL) to encapsulate and deliver SPIO (scL-SPIO) in vitro and in vivo without chemical modification. Scanning probe microscopy, confocal microscopy, and Prussian blue staining were employed to analyze the scL-SPIO nanoparticles and assess intracellular uptake and distribution of SPIO in vitro. In vivo targeting and tumor-specific uptake of scL-SPIO was examined using fluorescent-labeled SPIO. We demonstrated that SPIO encapsulation in the scL complex results in approximately an 11 fold increase in SPIO uptake in human cancer cells in vitro, with distribution to cytoplasm and nucleus. Moreover, the scL nanocomplex specifically and efficiently delivered SPIO into tumor cells after systemic administration, demonstrating the potential of this approach to enhance local tumor concentration and the utility of SPIO for clinical applications. PMID:18676207

  4. Magnetic tumor targeting of β-glucosidase immobilized iron oxide nanoparticles.

    PubMed

    Zhou, Jie; Zhang, Jian; David, Allan E; Yang, Victor C

    2013-09-20

    Directed enzyme/prodrug therapy (DEPT) has promising application for cancer therapy. However, most current DEPT strategies face shortcomings such as the loss of enzyme activity during preparation, low delivery and transduction efficiency in vivo and difficultly of monitoring. In this study, a novel magnetic directed enzyme/prodrug therapy (MDEPT) was set up by conjugating β-glucosidase (β-Glu) to aminated, starch-coated, iron oxide magnetic iron oxide nanoparticles (MNPs), abbreviated as β-Glu-MNP, using glutaraldehyde as the crosslinker. This β-Glu-MNP was then characterized in detail by size distribution, zeta potential, FTIR spectra, TEM, SQUID and magnetophoretic mobility analysis. Compared to free enzyme, the conjugated β-Glu on MNPs retained 85.54% ± 6.9% relative activity and showed much better temperature stability. The animal study results showed that β-Glu-MNP displays preferable pharmacokinetics characteristics in relation to MNPs. With an adscititious magnetic field on the surface of a tumor, a significant quantity of β-Glu-MNP was selectively delivered into a subcutaneous tumor of a glioma-bearing mouse. Remarkably, the enzyme activity of the delivered β-Glu in tumor lesions showed as high as 20.123±5.022 mU g(-1) tissue with 2.14 of tumor/non-tumor β-Glu activity.

  5. Magnetic tumor targeting of β-Glucosidase immobilized iron oxide nanoparticles

    PubMed Central

    Zhou, Jie; Zhang, Jian; David, Allan E.; Yang, Victor C.

    2014-01-01

    Directed enzyme/prodrug therapy (DEPT) has promising application for cancer therapy. However, most current DEPT strategies face shortcomings such as the loss of enzyme activity during preparation, low delivery and transduction efficiency in vivo, difficult to be monitored. In current study, a novel magnetic directed enzyme/prodrug therapy (MDEPT) was set up by conjugating β-Glucosidase (β-Glu) to aminated, starch-coated, iron oxide magnetic iron oxide nanoparticles (MNP), abbreviated as β-Glu-MNP, using glutaraldehyde as the crosslinker. This β-Glu-MNP was then characterized in detail by size distribution, zeta potential, FTIR spectra, TEM, SQUID and magnetophoretic mobility analysis. Compared to free enzyme, the conjugated β-Glu on MNP remained 85.54%±6.9% relative activity and showed much better temperature stability. relative activity and showed much better temperature stability. The animal study results showed that β-Glu-MNP display preferable pharmacokinetics characteristic in relation to MNP. With adscititious magnetic field on the surface of tumor, a significant quantity of β-Glu-MNP was selectively delivered into a subcutaneous tumor of glioma-bearing mice. Remarkably, the enzyme activity of the delivered β-Glu in tumor lesions showed as high as 20.123 ± 5.022 mU/g tissue with 2.14 of tumor/non-turmor of β-Glu activity. PMID:23974977

  6. Mitochondrial Dysfunction and Oxidative Stress in Asthma: Implications for Mitochondria-Targeted Antioxidant Therapeutics

    PubMed Central

    Reddy, P. Hemachandra

    2011-01-01

    Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Genetic studies have revealed that multiple loci are involved in the etiology of asthma. Recent cellular, molecular, and animal-model studies have revealed several cellular events that are involved in the progression of asthma, including: increased Th2 cytokines leading to the recruitment of inflammatory cells to the airway, and an increase in the production of reactive oxygen species and mitochondrial dysfunction in the activated inflammatory cells, leading to tissue injury in the bronchial epithelium. Further, aging and animal model studies have revealed that mitochondrial dysfunction and oxidative stress are involved and play a large role in asthma. Recent studies using experimental allergic asthmatic mouse models and peripheral cells and tissues from asthmatic humans have revealed antioxidants as promising treatments for people with asthma. This article summarizes the latest research findings on the involvement of inflammatory changes, and mitochondrial dysfunction/oxidative stress in the development and progression of asthma. This article also addresses the relationship between aging and age-related immunity in triggering asthma, the antioxidant therapeutic strategies in treating people with asthma. PMID:21461182

  7. Magnetic tumor targeting of β-glucosidase immobilized iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Zhou, Jie; Zhang, Jian; David, Allan E.; Yang, Victor C.

    2013-09-01

    Directed enzyme/prodrug therapy (DEPT) has promising application for cancer therapy. However, most current DEPT strategies face shortcomings such as the loss of enzyme activity during preparation, low delivery and transduction efficiency in vivo and difficultly of monitoring. In this study, a novel magnetic directed enzyme/prodrug therapy (MDEPT) was set up by conjugating β-glucosidase (β-Glu) to aminated, starch-coated, iron oxide magnetic iron oxide nanoparticles (MNPs), abbreviated as β-Glu-MNP, using glutaraldehyde as the crosslinker. This β-Glu-MNP was then characterized in detail by size distribution, zeta potential, FTIR spectra, TEM, SQUID and magnetophoretic mobility analysis. Compared to free enzyme, the conjugated β-Glu on MNPs retained 85.54% ± 6.9% relative activity and showed much better temperature stability. The animal study results showed that β-Glu-MNP displays preferable pharmacokinetics characteristics in relation to MNPs. With an adscititious magnetic field on the surface of a tumor, a significant quantity of β-Glu-MNP was selectively delivered into a subcutaneous tumor of a glioma-bearing mouse. Remarkably, the enzyme activity of the delivered β-Glu in tumor lesions showed as high as 20.123±5.022 mU g-1 tissue with 2.14 of tumor/non-tumor β-Glu activity.

  8. Elements of the nitric oxide/cGMP pathway expressed in cerebellar granule cells: biochemical and functional characterisation.

    PubMed

    Jurado, Sandra; Sánchez-Prieto, José; Torres, Magdalena

    2004-11-01

    It is known that the nitric oxide (NO)/cGMP pathway affects neuronal development and the expression of the different proteins is developmentally dependent in several brain areas. However, so far there are no data on the expression of the proteins involved in this signalling system during the development of the cerebellar granule cell, one of the most widely used models of neuronal development. This study was accordingly designed to analyse the developmental regulation of neuronal nitric oxide synthase (nNOS), soluble guanylyl cyclase subunits (alpha1, alpha2 and beta1) and cGMP-dependent protein kinases (cGK I and cGK II) in cerebellar granule cells through real time-polymerase chain reaction (RT-PCR) and Western blotting. We were able to detect guanylyl cyclase subunits and cGK I and cGK II in cerebellar granule cells at every stage of development examined (cells freshly isolated from 7-day-old rat pups, and cells cultured for 7 days or 14 days). Expression levels, nevertheless, varied significantly at each stage. nNOS, alpha2 and beta1 and cGK II levels increased during granule cell development, while alpha1 and cGK I showed an opposite behaviour pattern; the levels of these latter proteins diminished as the cells matured. The functionality of this pathway was assessed by stimulating cells kept in culture for 7 days with DEA/NO or with N-methyl-D-aspartate (NMDA). Cells responded by increasing intracellular cGMP and activating cGMP-dependent protein kinase activity, which effectively phosphorylated two well-known substrates of this activity, the vasodilator stimulated phosphoprotein (VASP) and the cAMP response element binding protein (CREB). In summary, through both functional and biochemical tests, this is the first demonstration of a complete NO/cGMP signalling transduction pathway in cerebellar granule cells. Our results also indicate the developmental regulation of the proteins in this system.

  9. Reduction of Matrix-Induced Oxide Interferences on Rare Earth Elements and Platinum Using a Desolvating Nebulizer System with Quadrupole Inductively Coupled Plasma Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Smith, F.

    2013-12-01

    This paper will examine the use of a specialized low-flow desolvating nebulizer system for reduction of oxide mass spectral interferences that can occur in quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS). This nebulizer system uses an inert low-flow nebulizer (100 microliters/min) coupled to an inert, heated membrane desolvator for efficient water vapor removal before sample aerosol injection to the Q-ICP-MS instrument. Water vapor from conventional nebulizer / spray chamber systems used with Q-ICP-MS can cause numerous mass spectral interferences. One general example is metal oxides formed from the combination of oxygen (from injected water) with sample matrix components. Two specific examples of metal oxide interferences will be investigated with and without membrane desolvation: Ba and Ce oxides on several low-mass rare earth elements (Sm, Eu, and Gd) and Hf oxides on platinum. Rare earth elements are critically important components of modern electronics (ex. magnets, lasers, cell phones, computers) and platinum is a widely used catalyst. Figures of merit for both a conventional nebulizer/spray chamber and the desolvating nebulizer systems will include operating conditions, interference intensities and reduction factors, background equivalent concentrations (BECs), and instrument detection limits (IDLs).

  10. High temperature oxidation behavior of gamma-nickel+gamma'-nickel aluminum alloys and coatings modified with platinum and reactive elements

    NASA Astrophysics Data System (ADS)

    Mu, Nan

    Materials for high-pressure turbine blades must be able to operate in the high-temperature gases (above 1000°C) emerging from the combustion chamber. Accordingly, the development of nickel-based superalloys has been constantly motivated by the need to have improved engine efficiency, reliability and service lifetime under the harsh conditions imposed by the turbine environment. However, the melting point of nickel (1455°C) provides a natural ceiling for the temperature capability of nickel-based superalloys. Thus, surface-engineered turbine components with modified diffusion coatings and overlay coatings are used. Theses coatings are capable of forming a compact and adherent oxide scale, which greatly impedes the further transport of reactants between the high-temperature gases and the underlying metal and thus reducing attack by the atmosphere. Typically, these coatings contain beta-NiAl as a principal constituent phase in order to have sufficient aluminum content to form an Al2O3 scale at elevated temperatures. The drawbacks to the currently-used beta-based coatings, such as phase instabilities, associated stresses induced by such phase instabilities, and extensive coating/substrate interdiffusion, are major motivations in this study to seek next-generation coatings. The high-temperature oxidation resistance of novel Pt+Hf-modified gamma-Ni+gamma'-Ni 3Al-based alloys and coatings were investigated in this study. Both early-stage and 4-days isothermal oxidation behavior of single-phase gamma-Ni and gamma'-Ni3Al alloys were assessed by examining the weight changes, oxide-scale structures, and elemental concentration profiles through the scales and subsurface alloy regions. It was found that Pt promotes Al 2O3 formation by suppressing the NiO growth on both gamma-Ni and gamma'-Ni3Al single-phase alloys. This effect increases with increasing Pt content. Moreover, Pt exhibits this effect even at lower temperatures (˜970°C) in the very early stage of oxidation. It

  11. Determination of rare earth elements in high purity rare earth oxides by liquid chromatography, thermionic mass spectrometry and combined liquid chromatography/thermionic mass spectrometry

    NASA Astrophysics Data System (ADS)

    Stijfhoorn, D. E.; Stray, H.; Hjelmseth, H.

    1993-03-01

    A high-performance liquid Chromatographie (HPLC) method for the determination of rare earth elements in rocks has been modified and used for the determination of rare earth elements (REE) in high purity rare earth oxides. The detection limit was 1-1.5 ng or 2-3 mg/kg when a solution corresponding to 0.5 mg of the rare earth oxide was injected. The REE determination was also carried out by adding a mixture of selected REE isotopes to the sample and analysing the collected HPLC-fractions by mass spectrometry (MS) using a thermionic source. Since the matrix element was not collected, interference from this element during the mass spectrometric analysis was avoided. Detection limits as low as 0.5 mg/kg could then be obtained. Detection limits as low as 0.05 mg/kg were possible by MS without HPLC-pre-separation, but this approach could only be used for those elements that were not affected by the matrix. Commercial samples of high purity Nd 2O 3, Gd 2O 3 and Dy 2O 3 were analysed in this study, and a comparison of results obtained by HPLC, combined HPLC/MS and direct MS are presented.

  12. Comparative finite element analysis of the stress-strain states in three different bonded solid oxide fuel cell seal designs

    NASA Astrophysics Data System (ADS)

    Weil, K. S.; Koeppel, B. J.

    One of the critical issues in designing and fabricating a high performance planar solid oxide fuel cell (pSOFC) stack is the development of the appropriate materials and techniques for hermetically sealing the metal and ceramic components. A second critical issue is ensuring that the brittle ceramic cell constituents, i.e. the electrodes and electrolyte, exhibit high mechanical reliability by mitigating potential sources of thermal-mechanically induced stresses that can lead to fracture during operation and/or shutdown. A foil-based sealing approach is currently being developed that appears to offer good hermeticity and mechanical integrity, while minimizing the generation of high stresses in either of the joint's substrate materials. Based on the concept's viability, demonstrated in prior experimental work, numerical analyses were conducted to evaluate the behavior and benefits of the seal in a configuration prototypic of current pSOFC stack designs. This paper presents recent results from finite element (FE) simulations of a planar cell using the foil-based seal, along with companion analyses of the more conventionally employed glass-ceramic and brazed joints. The stresses and deformations of the components were evaluated at isothermal operating and shutdown temperatures. The results indicate that the foil seal is able to accommodate a significant degree of thermal mismatch strain between the metallic support structure and the ceramic cell via elastic deformations of the foil and plasticity in the foil-to-cell braze layer. Consequently the cell stresses in this type of seal are predicted to be much lower than those in the glass-ceramic and brazed designs, which is expected to lead to improved stack reliability. This ability to accommodate large thermal strain mismatches allows the design requirement of thermal expansion matching between ceramic and metal stack components to be relaxed and expands the list of candidate materials that can be considered for the

  13. [The link between trace elements and metabolic syndrome/oxidative stress in essential hypertension with or without type 2 diabetes].

    PubMed

    Gouaref, Ines; Bellahsene, Zina; Zekri, Samia; Alamir, Barkahoum; Koceir, Elhadj-Ahmed

    2016-01-01

    The relationship between trace elements (TE) and essential hypertension (EH) is subtle and complex. This relationship is mediated by endothelial dysfunction, insulin resistance, oxidative stress (OS) and athero-inflammatory state. The aim of this study was to examine the TE impact; particularly selenium (Se), zinc (Zn), copper (Cu) and manganese (Mn) as predictive type 2 diabetes biomarkers in a hypertensive subject. The study was undertaken on 400 adult patients (40-60 years), who were divided in 4 groups: hypertensive (H), type 2 diabetes (T2D), hypertensive-diabetic (HD) and healthy group. Patients were phenotyped regarding their metabolic syndrome profile using the NCEP/ATPIII criteria. Hypertension was defined as systolic (SBP) and diastolic (DBP) blood pressure ≥ 140/90 mmHg, respectively. The SBP and DBP measurements by electronic blood pressure using Omron 705 CP(®) type. Insulin resistance was assessed by Homa-IR model. Metabolic and inflammatory parameters were determined by Cobas Integra(®); the TE investigated by mass spectrometric atomic absorption; the OS markers evaluated by Randox kits. Serum Se concentrations are reduced in all groups, concomitantly with a marked depletion GPx activity in the HD group. However, Zn levels were decreased than in H and HD groups, but unchanged in T2D group. In contrast, Mn levels are increased in all groups; whereas the Cu levels increased only in H and HD groups, concomitantly with cytosolic SOD-Cu/Zn and mitochondrial SOD-Mn depletion. The Zn/Cu ratio decreases significantly in hypertensive group but not in diabetics groups. It appears that Zn/Cu ratio reflects the transition from hypertension phase to hypertension associated with T2D. Ultimately, TE plays an important role in the hypertension pathophysiology and can be considered as predictive T2D biomarkers in hypertensive patients.

  14. Design of a Novel Integration-deficient Lentivector Technology That Incorporates Genetic and Posttranslational Elements to Target Human Dendritic Cells

    PubMed Central

    Tareen, Semih U; Kelley-Clarke, Brenna; Nicolai, Christopher J; Cassiano, Linda A; Nelson, Lisa T; Slough, Megan M; Vin, Chintan D; Odegard, Jared M; Sloan, Derek D; Van Hoeven, Neal; Allen, James M; Dubensky, Thomas W; Robbins, Scott H

    2014-01-01

    As sentinels of the immune system, dendritic cells (DCs) play an essential role in regulating cellular immune responses. One of the main challenges of developing DC-targeted therapies includes the delivery of antigen to DCs in order to promote the activation of antigen-specific effector CD8 T cells. With the goal of creating antigen-directed immunotherapeutics that can be safely administered directly to patients, Immune Design has developed a platform of novel integration-deficient lentiviral vectors that target and deliver antigen-encoding nucleic acids to human DCs. This platform, termed ID-VP02, utilizes a novel genetic variant of a Sindbis virus envelope glycoprotein with posttranslational carbohydrate modifications in combination with Vpx, a SIVmac viral accessory protein, to achieve efficient targeting and transduction of human DCs. In addition, ID-VP02 incorporates safety features in its design that include two redundant mechanisms to render ID-VP02 integration-deficient. Here, we describe the characteristics that allow ID-VP02 to specifically transduce human DCs, and the advances that ID-VP02 brings to conventional third-generation lentiviral vector design as well as demonstrate upstream production yields that will enable manufacturing feasibility studies to be conducted. PMID:24419083

  15. Oxidized macrophage migration inhibitory factor is a potential new tissue marker and drug target in cancer

    PubMed Central

    Schinagl, Alexander; Thiele, Michael; Douillard, Patrice; Völkel, Dirk; Kenner, Lukas; Kazemi, Zahra; Freissmuth, Michael; Scheiflinger, Friedrich; Kerschbaumer, Randolf J.

    2016-01-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which was shown to be upregulated in cancers and to exhibit tumor promoting properties. Unlike other cytokines, MIF is ubiquitously present in the circulation and tissue of healthy subjects. We recently described a previously unrecognized, disease-related isoform of MIF, designated oxMIF, which is present in the circulation of patients with different inflammatory diseases. In this article, we report that oxMIF is also linked to different solid tumors as it is specifically expressed in tumor tissue from patients with colorectal, pancreatic, ovarian and lung cancer. Furthermore, oxMIF can be specifically targeted by a subset of phage display-derived fully human, monoclonal anti-MIF antibodies (mAbs) that were shown to neutralize pro-tumorigenic activities of MIF in vivo. We further demonstrate that anti-oxMIF mAbs sensitize human cancer cell lines (LNCaP, PC3, A2780 and A2780ADR) to the action of cytotoxic drugs (mitoxantrone, cisplatin and doxorubicin) in vitro and in an A2780 xenograft mouse model of ovarian cancer. We conclude that oxMIF is the disease related isoform of MIF in solid tumors and a potential new diagnostic marker and drug target in cancer. PMID:27636991

  16. Core-shell composite particles composed of biodegradable polymer particles and magnetic iron oxide nanoparticles for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Oka, Chiemi; Ushimaru, Kazunori; Horiishi, Nanao; Tsuge, Takeharu; Kitamoto, Yoshitaka

    2015-05-01

    Core-shell composite particles with biodegradability and superparamagnetic behavior were prepared using a Pickering emulsion for targeted drug delivery based on magnetic guidance. The composite particles were composed of a core of biodegradable polymer and a shell of assembled magnetic iron oxide nanoparticles. It was found that the dispersibility of the nanoparticles is crucial for controlling the core-shell structure. The addition of a small amount of dispersant into the nanoparticle's suspension could improve the dispersibility and led to the formation of composite particles with a thin magnetic shell covering a polymeric core. The composite particles were also fabricated with a model drug loaded into the core, which was released via hydrolysis of the core under strong alkaline conditions. Because the core can also be biodegraded by lipase, this result suggests that the slow release of the drug from the composite particles should occur inside the body.

  17. Bimodal-hybrid heterocyclic amine targeting oxidative pathways and copper mis-regulation in Alzheimer’s disease

    PubMed Central

    Gonzalez, Paulina; da Costa, Viviana C.P.; Hyde, Kimberly; Wu, Qiong; Annunziata, Onofrio; Rizo, Josep; Akkaraju, Giridhar; Green, Kayla N.

    2014-01-01

    Oxidative stress resulting from metal-ion misregulation plays a role in the development of Alzheimer’s disease (AD). This process includes the production of tissue-damaging reactive oxygen species and amyloid aggregates. Herein we describe the synthesis, characterization and protective capacity of the small molecule, lipoic cyclen, which has been designed to target molecular features of AD. This construct utilizes the biologically compatible and naturally occurring lipoic acid as a foundation for engendering low cellular toxicity in multiple cell lines, radical scavenging capacity, tuning the metal affinity of the parent cyclen, and results in an unexpected affinity for amyloid without inducing aggregation. The hybrid construct thereby shows protection against cell death induced by amyloid aggregates and copper ions. These results provide evidence for the rational design methods used to produce this fused molecule as a potential strategy for the development of lead compounds for the treatment of neurodegenerative disorders. PMID:25144522

  18. Impaired ovulation in mice with targeted deletion of the neuronal isoform of nitric oxide synthase.

    PubMed Central

    Klein, S. L.; Carnovale, D.; Burnett, A. L.; Wallach, E. E.; Zacur, H. A.; Crone, J. K.; Dawson, V. L.; Nelson, R. J.; Dawson, T. M.

    1998-01-01

    BACKGROUND: Nitric oxide (NO) plays an important role in numerous reproductive processes. To date, most studies have assessed the role of NO by using nonspecific pharmacological inhibitors of the precursor to NO, nitric oxide synthase (NOS). These pharmacological NOS inhibitors suppress all isoforms of NOS; thus, the precise contribution of each isoform to female reproductive physiology is unknown. The purpose of this study was to determine the specific role of neuronal NOS (nNOS) in the regulation of ovulation in female mice lacking the gene that encodes for nNOS (nNOS-/-). MATERIALS AND METHODS: Ovulation was assessed in wild-type (WT) and nNOS-/- female mice by examining the number of ovarian rupture sites and number of oocytes recovered from the oviducts following mating or exposure to exogenous gonadotropins (i.e., 5 IU pregnant mares serum gonadotropin [PMSG] and 5 IU human chorionic gonadotropin [hCG]). Ovulatory efficiency was determined as the number of ovulated oocytes per number of ovarian rupture sites. To examine whether ovulatory deficits in nNOS-/- mice were due to alternations in central mechanisms, plasma luteinizing hormone (LH) concentrations were assessed in WT and nNOS-/- mice that were challenged with 25 ng of gonadotropin-releasing hormone (GnRH). To determine whether ovulatory deficits in nNOS-/- mice were due to local ovulation processes, nerves innervating the reproductive tract of WT and nNOS-/- females were examined for the presence of nNOS protein. RESULTS: There were substantial fertility deficits in nNOS-/- female mice; the nNOS-/- mice had fewer oocytes in their oviducts following spontaneous and gonadotropin-stimulated ovulation. Pituitary responsiveness to exogenous GnRH challenge was intact in nNOS-/- mice. Dense nNOS protein staining was observed in nerves innervating the reproductive tracts of WT mice. CONCLUSIONS: The reproductive deficits in nNOS-/- females are most likely due to alternations in the transfer of oocytes from

  19. Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application

    NASA Astrophysics Data System (ADS)

    Hao, Yongwei; Wang, Lei; Zhang, Bingxiang; Zhao, Hongjuan; Niu, Mengya; Hu, Yujie; Zheng, Cuixia; Zhang, Hongling; Chang, Junbiao; Zhang, Zhenzhong; Zhang, Yun

    2016-01-01

    It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r 1 was 2.26 mM-1 s-1 at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.

  20. NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea

    PubMed Central

    Honkura, Yohei; Matsuo, Hirotaka; Murakami, Shohei; Sakiyama, Masayuki; Mizutari, Kunio; Shiotani, Akihiro; Yamamoto, Masayuki; Morita, Ichiro; Shinomiya, Nariyoshi; Kawase, Tetsuaki; Katori, Yukio; Motohashi, Hozumi

    2016-01-01

    Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2–/– mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2–/– mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2–/– mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention. PMID:26776972

  1. The HK2 Dependent "Warburg Effect" and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate.

    PubMed

    Lis, Paweł; Dyląg, Mariusz; Niedźwiecka, Katarzyna; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

    2016-12-15

    This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the "Warburg" and "Crabtree" effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the "Warburg effect" and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the "Warburg effect", and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the "Warburg effect", i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as "multiple myeloma". Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development.

  2. NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea.

    PubMed

    Honkura, Yohei; Matsuo, Hirotaka; Murakami, Shohei; Sakiyama, Masayuki; Mizutari, Kunio; Shiotani, Akihiro; Yamamoto, Masayuki; Morita, Ichiro; Shinomiya, Nariyoshi; Kawase, Tetsuaki; Katori, Yukio; Motohashi, Hozumi

    2016-01-18

    Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2(-/-) mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2(-/-) mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2(-/-) mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention.

  3. Oxidative Stress and Mitochondrial Dysfunction across Broad-Ranging Pathologies: Toward Mitochondria-Targeted Clinical Strategies

    PubMed Central

    d'Ischia, Marco; Gadaleta, Maria Nicola; Pallardó, Federico V.; Petrović, Sandra; Tiano, Luca; Zatterale, Adriana

    2014-01-01

    Beyond the disorders recognized as mitochondrial diseases, abnormalities in function and/or ultrastructure of mitochondria have been reported in several unrelated pathologies. These encompass ageing, malformations, and a number of genetic or acquired diseases, as diabetes and cardiologic, haematologic, organ-specific (e.g., eye or liver), neurologic and psychiatric, autoimmune, and dermatologic disorders. The mechanistic grounds for mitochondrial dysfunction (MDF) along with the occurrence of oxidative stress (OS) have been investigated within the pathogenesis of individual disorders or in groups of interrelated disorders. We attempt to review broad-ranging pathologies that involve mitochondrial-specific deficiencies or rely on cytosol-derived prooxidant states or on autoimmune-induced mitochondrial damage. The established knowledge in these subjects warrants studies aimed at elucidating several open questions that are highlighted in the present review. The relevance of OS and MDF in different pathologies may establish the grounds for chemoprevention trials aimed at compensating OS/MDF by means of antioxidants and mitochondrial nutrients. PMID:24876913

  4. Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein.

    PubMed

    Thakkar, Shraddha; Wang, Xianwei; Khaidakov, Magomed; Dai, Yao; Gokulan, Kuppan; Mehta, Jawahar L; Varughese, Kottayil I

    2015-11-18

    Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential.

  5. One-pot synthesis of dextran decorated reduced graphene oxide nanoparticles for targeted photo-chemotherapy.

    PubMed

    Hu, Yanfang; He, Liang; Ding, Jianxun; Sun, Diankui; Chen, Li; Chen, Xuesi

    2016-06-25

    Graphene-based nanocarriers show great potential in photo-chemotherapy, however, to prepare desired reduced graphene oxide (rGO) nanoparticles in a facile way is still a challenge. Herein, a novel strategy has been presented to prepare rGO nanoparticle using dextran (Dex) as a reducing agent. In this strategy, Dex was directly conjugated on rGO by hydrogen bond and then self-assemble to form rGO/Dex nanoparticles. After decorated by dextran, rGO-based nanoparticles not only show excellent biocompatibility but also can load anticancer drug for photo-chemotherapy. The data of fourier transform infrared (FT-IR) analysis, Raman spectrum analysis, thermos-gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), the transmission electron microscope (TEM) image and dynamic light scattering (DLS) measurements powerfully proved that the stable rGO-based nanoparticles with desired nanosize have been successfully prepared. To verify the photo-chemotherapy, anticancer drug, doxorubicin (DOX), has been loaded on rGO/Dex nanoparticles (rGO/DOX/Dex). And RGD, a kind of oligopeptide which can improve the intracellular uptake by αvβ3 recognition, also has been introduced (rGO/DOX/RDex). Compared with single chemotherapy, rGO/DOX/Dex and rGO/DOX/RDex combining the local specific chemotherapy and external near-infrared (NIR) photo-thermal therapy show higher therapeutic efficacy, endowing the desired rGO-based nanoparticle with great potential for cancer treatments.

  6. Multifunctional Nanographene Oxide for Targeted Gene-Mediated Thermochemotherapy of Drug-resistant Tumour

    PubMed Central

    Zeng, Yiping; Yang, Zhangyou; Li, Hong; Hao, Yuhui; Liu, Cong; Zhu, Lin; Liu, Jing; Lu, Binghui; Li, Rong

    2017-01-01

    Drug resistance remains a major challenge for anticancer treatment, and one of the major mechanisms of drug resistance is the overexpression of drug efflux transporters in cancer. A new approach for defeating drug resistance is the use of a co-delivery strategy that utilizes small interfering RNA (siRNA) to silence the expression of efflux transporters together with a suitable anticancer drug for drug-resistant cells. In this work, multifunctional graphene capable of integrating multiple functions in one system was employed as a novel co-delivery system for siRNA and doxorubicin (Dox), as well as for the controlled release of intracellular pH-triggered and heat-triggered Dox. Additionally, it was used as a synergistic therapy based on the photothermal effect of graphene oxide (GO) under near-infrared (NIR) irradiation and the chemotherapeutic effect of Dox. The nanocomplex exhibited high drug and siRNA loading. Furthermore, the dual delivery of siRNA and Dox by folic acid (FA)-conjugated polyethylenimine-modified PEGylated nanographene (PPG-FA/siRNA/Dox) exhibited a satisfactory gene silencing effect as well as efficient intracellular delivery of Dox. Thus, Dox could access the nucleus and induce greater cytotoxicity compared with siRNA-absent delivery systems. Significantly, under irradiation, the combined treatment showed more synergistic effect for overcoming drug resistance compared with chemotherapy effect alone. PMID:28272412

  7. Structure-based Design Targeted at LOX-1, a Receptor for Oxidized Low-Density Lipoprotein

    NASA Astrophysics Data System (ADS)

    Thakkar, Shraddha; Wang, Xianwei; Khaidakov, Magomed; Dai, Yao; Gokulan, Kuppan; Mehta, Jawahar L.; Varughese, Kottayil I.

    2015-11-01

    Atherosclerosis related cardiovascular diseases continue to be the primary cause of mortality in developed countries. The elevated level of low density lipoprotein (LDL) is generally considered to be the driver of atherosclerosis, but recent years have seen a shift in this perception in that the vascular plaque buildup is mainly caused by oxidized LDL (ox-LDL) rather than native-LDL. The scavenger receptor LOX-1 found in endothelial cells binds and internalizes ox-LDL which leads to the initiation of plaque formation in arteries. Using virtual screening techniques, we identified a few potential small molecule inhibitors of LOX-1 and tested their inhibitory potential using differential scanning fluorimetry and various cellular assays. Two of these molecules significantly reduced the uptake of ox-LDL by human endothelial cells, LOX-1 transcription and the activation of ERK1/2 and p38 MAPKs in human endothelial cells. In addition, these molecules suppressed ox-LDL-induced VCAM-1 expression and monocyte adhesion onto human endothelial cells demonstrating their therapeutic potential.

  8. Multifunctionalized iron oxide nanoparticles for selective targeting of pancreatic cancer cells.

    PubMed

    Trabulo, Sara; Aires, Antonio; Aicher, Alexandra; Heeschen, Christopher; Cortajarena, Aitziber L

    2017-02-01

    Nanomedicine nowadays offers novel solutions in cancer therapy by introducing multimodal treatments in one single formulation. In addition, nanoparticles act as nanocarriers changing the solubility, biodistribution and efficiency of the therapeutic molecules, thus generating more efficient treatments and reducing their side effects. To apply these novel therapeutic approaches, efforts are focused on the multi-functionalization of the nanoparticles and will open up new avenues to advanced combinational therapies. Pancreatic ductal adenocarcinoma (PDAC) is a cancer with unmet medical needs. Abundant expression of the anti-phagocytosis signal CD47 has also been observed on pancreatic cancer cells, in particular a subset of cancer stem cells (CSCs) responsible for resistance to standard therapy and metastatic potential. CD47 receptor is found on pancreatic cancer and highly expressed on CSCs, but not on normal pancreas. Inhibiting CD47 using monoclonal antibodies has been shown as an effective strategy to treat PDAC in vivo. However, CD47 inhibition effectively slowed tumor growth only in combination with Gemcitabine or Abraxane. In this work, we present the generation of multifunctionalized iron oxide magnetic nanoparticles (MNPs) that include the anti-CD47 antibody and the chemotherapeutic drug Gemcitabine in a single formulation. We demonstrate the in vitro efficacy of the formulation against CD47-positive pancreatic cancer cells. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

  9. Targeted Herceptin-dextran iron oxide nanoparticles for noninvasive imaging of HER2/neu receptors using MRI.

    PubMed

    Chen, Ting-Jung; Cheng, Tsan-Hwang; Chen, Chiao-Yun; Hsu, Sodio C N; Cheng, Tian-Lu; Liu, Gin-Chung; Wang, Yun-Ming

    2009-02-01

    A novel magnetic resonance imaging (MRI) contrast agent containing Herceptin is reported. The surfaces of superparamagnetic iron oxide nanoparticles were modified with dextran and conjugated with Herceptin (Herceptin-nanoparticles) to improve their dispersion, magnetization, and targeting of the specific receptors on cells. From analytical results, we found that Herceptin-nanoparticles were well dispersed in solutions of various pH range, and had no hysteresis, high saturation magnetization (80 emu/g), and low cytotoxicity to a variety of cells. Notably, the magnetic resonance enhancements for the different breast cancer cell lines (BT-474, SKBR-3, MDA-MB-231, and MCF-7) are proportional to the HER2/neu expression level in vitro. When Herceptin-nanoparticles were administered to mice bearing breast tumor allograft by intravenous injection, the tumor site was detected in T (2)-weighted magnetic resonance images as a 45% enhancement drop, indicating a high level of accumulation of the contrast agent within the tumor sites. Therefore, targeting of cancer cells was observed by in vitro and in vivo MRI studies using Herceptin-nanoparticles contrast agent. In addition, Herceptin-nanoparticles enhancing the magnetic resonance signal intensity were sufficient to detect the cell lines with a low level of HER2/neu expression.

  10. Multifunctional pH-sensitive superparamagnetic iron-oxide nanocomposites for targeted drug delivery and MR imaging.

    PubMed

    Zhu, Lijuan; Wang, Dali; Wei, Xuan; Zhu, Xinyuan; Li, Jianqi; Tu, Chunlai; Su, Yue; Wu, Jieli; Zhu, Bangshang; Yan, Deyue

    2013-08-10

    A multifunctional pH-sensitive superparamagnetic iron-oxide (SPIO) nanocomposite system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. Small-size SPIO nanoparticles were chemically bonded with antitumor drug doxorubicin (DOX) and biocompatible poly(ethylene glycol) (PEG) through pH-sensitive acylhydrazone linkages, resulting in the formation of SPIO nanocomposites with magnetic targeting and pH-sensitive properties. These DOX-conjugated SPIO nanocomposites exhibited not only good stability in aqueous solution but also high saturation magnetizations. Under an acidic environment, the DOX was quickly released from the SPIO nanocomposites due to the cleavage of pH-sensitive acylhydrazone linkages. With the help of magnetic field, the DOX-conjugated SPIO nanocomposites showed high cellular uptake, indicating their magnetic targeting property. Comparing to free DOX, the DOX-conjugated SPIO nanocomposites showed better antitumor effect under magnetic field. At the same time, the relaxivity value of these SPIO nanocomposites was higher than 146s(-1)mM(-1) Fe, leading to ~4 times enhancement compared to that of free SPIO nanoparticles. As a negative contrast agent, these SPIO nanocomposites illustrated high resolution in MRI diagnosis of tumor-bearing mice. All of these results confirm that these pH-sensitive SPIO nanocomposites are promising hybrid materials for synergistic MRI diagnosis and tumor therapy.

  11. Targeted Mesoporous Iron Oxide Nanoparticles-Encapsulated Perfluorohexane and a Hydrophobic Drug for Deep Tumor Penetration and Therapy

    PubMed Central

    Su, Yu-Lin; Fang, Jen-Hung; Liao, Chia-Ying; Lin, Chein-Ting; Li, Yun-Ting; Hu, Shang-Hsiu

    2015-01-01

    A magneto-responsive energy/drug carrier that enhances deep tumor penetration with a porous nano-composite is constructed by using a tumor-targeted lactoferrin (Lf) bio-gate as a cap on mesoporous iron oxide nanoparticles (MIONs). With a large payload of a gas-generated molecule, perfluorohexane (PFH), and a hydrophobic anti-cancer drug, paclitaxel (PTX), Lf-MIONs can simultaneously perform bursting gas generation and on-demand drug release upon high-frequency magnetic field (MF) exposure. Biocompatible PFH was chosen and encapsulated in MIONs due to its favorable phase transition temperature (56 °C) and its hydrophobicity. After a short-duration MF treatment induces heat generation, the local pressure increase via the gasifying of the PFH embedded in MION can substantially rupture the three-dimensional tumor spheroids in vitro as well as enhance drug and carrier penetration. As the MF treatment duration increases, Lf-MIONs entering the tumor spheroids provide an intense heat and burst-like drug release, leading to superior drug delivery and deep tumor thermo-chemo-therapy. With their high efficiency for targeting tumors, Lf-MIONs/PTX-PFH suppressed subcutaneous tumors in 16 days after a single MF exposure. This work presents the first study of using MF-induced PFH gasification as a deep tumor-penetrating agent for drug delivery. PMID:26379789

  12. First-principles studies of the influences mechanism of Y, Hf elements on the high temperature oxidation of γ-TiAl alloys

    NASA Astrophysics Data System (ADS)

    Zhang, G. Y.; Liu, C. M.; Fang, G. L.

    2017-01-01

    The influences mechanisms of Y, Hf elements on the high temperature oxidation of γ-TiAl alloys were studied by using a first-principle plane wave pseudopotential method within the density functional theory. It is shown that Y, Hf atoms segregate to the γ-TiAl surface by substituting Ti atoms, and Y atom is easier to segregate than Hf. Y, Hf atoms segregated at γ-TiAl surface decrease the adhesion of O and γ-TiAl surface, which decreases the oxidation rate of γ-TiAl alloys and thereby hinders the growth of oxide films. The electron structure calculations suggest that the interaction between O and Ti, Al, Y, Hf atom exists both ionic and covalent binding characteristics, the decrease of the adhesion of O and γ-TiAl surface with the doped Y, Hf is mainly attributed to the weaken covalent interactions. As a result, the results obtained by first principles can make us get a deeper understanding of the mechanism of the segregation of Y, Hf to the γ-TiAl surface and the influence mechanism of surface active elements Y, Hf on the initial oxidation of γ-TiAl alloys.

  13. Neuronal Nicotinic Receptors as New Targets for Amphetamine-Induced Oxidative Damage and Neurotoxicity

    PubMed Central

    Pubill, David; Garcia-Ratés, Sara; Camarasa, Jordi; Escubedo, Elena

    2011-01-01

    Amphetamine derivatives such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) are widely abused drugs in a recreational context. This has led to concern because of the evidence that they are neurotoxic in animal models and cognitive impairments have been described in heavy abusers. The main targets of these drugs are plasmalemmal and vesicular monoamine transporters, leading to reverse transport and increased monoamine efflux to the synapse. As far as neurotoxicity is concerned, increased reactive oxygen species (ROS) production seems to be one of the main causes. Recent research has demonstrated that blockade of α7 nicotinic acetylcholine receptors (nAChR) inhibits METH- and MDMA-induced ROS production in striatal synaptosomes which is dependent on calcium and on NO-synthase activation. Moreover, α7 nAChR antagonists (methyllycaconitine and memantine) attenuated in vivo the neurotoxicity induced by METH and MDMA, and memantine prevented the cognitive impairment induced by these drugs. Radioligand binding experiments demonstrated that both drugs have affinity to α7 and heteromeric nAChR, with MDMA showing lower Ki values, while fluorescence calcium experiments indicated that MDMA behaves as a partial agonist on α7 and as an antagonist on heteromeric nAChR. Sustained Ca increase led to calpain and caspase-3 activation. In addition, modulatory effects of MDMA on α7 and heteromeric nAChR populations have been found.

  14. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.

    PubMed

    Ariza, Ana Carolina; Deen, Peter Meinardus T; Robben, Joris Hubertus

    2012-01-01

    The succinate receptor (also known as GPR91) is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina, and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity, and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin-angiotensin system, starts to unfold: the succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients.

  15. The Succinate Receptor as a Novel Therapeutic Target for Oxidative and Metabolic Stress-Related Conditions

    PubMed Central

    Ariza, Ana Carolina; Deen, Peter Meinardus T.; Robben, Joris Hubertus

    2012-01-01

    The succinate receptor (also known as GPR91) is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina, and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity, and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin–angiotensin system, starts to unfold: the succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients. PMID:22649411

  16. The Core Promoter and Redox-sensitive Cis-elements as Key Targets for Inactivation of the Lysyl Oxidase Gene by Cadmium

    PubMed Central

    Li, Jianmin; Cheng, Guang; Zheng, Maoguen; Zhao, Yinzhi; Zhou, Jing; Li, Wande

    2015-01-01

    Exposure of humans to cadmium (Cd) either from environmental contamination or from cigarette smoke, often induces lung emphysema and cancers. Lysyl oxidase (LOX), a copper-dependent enzyme essential for crosslinking of the extracellular matrix, displays antagonistic effects on emphysema and cancer pathogenesis. Our previous studies showed down-regulation of LOX in Cd-resistant (CdR) rat fetal lung fibroblasts (RFL6) derived from parental cells via long-term Cd exposure. The cloned rat LOX gene promoter −804/−1 (relative to ATG) with the maximal promoter activity contains the Inr-DPE core promoter, putative NFI binding sites, metal response elements (MRE) and antioxidant response elements (ARE). ChIP assays reported here further characterize the rat LOX gene promoter in response to Cd. CdR cells exhibited enhanced methylation of CpG at the LOX core promoter region and reduced activities of the NFI binding sites and MRE, but increased activity of the ARE in a dose-dependent manner. The collective effect of Cd on the LOX promoter is trans-inhibition of the LOX gene as shown by suppression of histone H3 acetylation in the LOX core promoter region. Thus, the LOX core promoter and redox-sensitive cis-elements are key Cd targets for down-regulation of LOX relevant to mechanisms for Cd-induced emphysema and lung cancers. PMID:25741534

  17. Goat red blood cells as precursor for iron oxide nanocrystal synthesis to develop nuclear targeted lung cancer therapy

    SciTech Connect

    Sreevani, Vellingiri; Shanthi, Krishnamurthy; Kannan, Soundarapandian

    2013-09-01

    Graphical abstract: - Highlights: • Molecular approach of synthesis of Fe{sub 2}O{sub 3}-NC using goat blood as a bio-precursor. • The method is simple, efficient and environment friendly. • Synthesized nanocrystals were characterized by UV–vis spectroscopy, XRD, SEM, TEM, DLS and EDS. • Nanocrystals exhibited potent cytotoxicity against A549 cancer cell. • Nuclear targeting with expression of caspase-3, caspase-7 and Bcl-2 in A549 cancer cells. - Abstract: In this study, we synthesised iron oxide nanocrystals (Fe{sub 2}O{sub 3}-NC) from goat blood (bio-precursor) using red blood cells (RBC) lysis method (a molecular level approach) for the first time. The formation of Fe{sub 2}O{sub 3}-NC was achieved through a single-phase chemical reduction method. The size distribution of Fe{sub 2}O{sub 3}-NC falls between 20–30 nm for pellet and 100–200 nm for lysate and were found to be crystalline. Fe{sub 2}O{sub 3}-NC demonstrated significant cytotoxicity on A549. We report the direct visualization of interactions between Fe{sub 2}O{sub 3}-NC and the cancer cell nucleus. The active transport of Fe{sub 2}O{sub 3}-NC to the nucleus induces major changes to nuclear phenotype via nuclear envelope invaginations. We further examined the root cause for the involvement of Fe{sub 2}O{sub 3}-NC on the expression of caspase-3, caspase-7 and Bcl-2 in A549 cancer cells. This functional proteomic analysis clearly implies that the lung cancer cell proliferation is perfectly targeted by the biosynthesised Fe{sub 2}O{sub 3}-NC which could provide new insight for nuclear-targeted cancer therapy.

  18. Role of manganese oxides in the exposure of mute swans (Cygnus olor) to Pb and other elements in the Chesapeake Bay, USA.

    PubMed

    Beyer, W Nelson; Day, Daniel

    2004-05-01

    The aims of this study are to estimate exposure of waterfowl to elements in contaminated sediments in the Chesapeake Bay and to consider the potential role of Mn in influencing bioavailability and exposure. Metal concentrations were measured in livers and digesta taken from mute swans living on the Aberdeen Proving Ground, whose sediment had elevated concentrations of Cu, S, Se, Zn, As, Co, Cr, Hg and Pb. Concentrations of only the first four of these elements were elevated in swan digesta. None of the concentrations detected in the digesta or livers of the swans was considered toxic, although the concentrations of Cu and Se were high compared to concentrations of these elements reported in other waterfowl. Lead was found to be scavenged by Mn and Fe oxides from the water and deposited on the surface of vegetation at a reference site. Under some environmental chemical conditions, this is an important route of exposure to Pb in waterfowl, not previously recognized.

  19. Tumorigenesis by Meis1 overexpression is accompanied by a change of DNA target-sequence specificity which allows binding to the AP-1 element

    PubMed Central

    Dardaei, Leila; Penkov, Dmitry; Mathiasen, Lisa; Bora, Pranami; Morelli, Marco J.; Blasi, Francesco

    2015-01-01

    Meis1 overexpression induces tumorigenicity but its activity is inhibited by Prep1 tumor suppressor. Why does overexpression of Meis1 cause cancer and how does Prep1 inhibit? Tumor profiling and ChIP-sequencing data in a genetically-defined set of cell lines show that: 1) The number of Meis1 and Prep1 DNA binding sites increases linearly with their concentration resulting in a strong increase of “extra” target genes. 2) At high concentration, Meis1 DNA target specificity changes such that the most enriched consensus becomes that of the AP-1 regulatory element, whereas the specific OCTA consensus is not enriched because diluted within the many extra binding sites. 3) Prep1 inhibits Meis1 tumorigenesis preventing the binding to many of the “extra” genes containing AP-1 sites. 4) The overexpression of Prep1, but not of Meis1, changes the functional genomic distribution of the binding sites, increasing seven fold the number of its “enhancer” and decreasing its “promoter” targets. 5) A specific Meis1 “oncogenic” and Prep1 “tumor suppressing” signature has been identified selecting from the pool of genes bound by each protein those whose expression was modified uniquely by the “tumor-inducing” Meis1 or tumor-inhibiting Prep1 overexpression. In both signatures, the enriched gene categories are the same and are involved in signal transduction. However, Meis1 targets stimulatory genes while Prep1 targets genes that inhibit the tumorigenic signaling pathways. PMID:26259236

  20. Detection of Toxoplasma gondii in faeces of privately owned cats using two PCR assays targeting the B1 gene and the 529-bp repetitive element.

    PubMed

    Veronesi, Fabrizia; Santoro, Azzurra; Milardi, Giovanni L; Diaferia, Manuela; Morganti, Giulia; Ranucci, David; Gabrielli, Simona

    2017-03-01

    Toxoplasma gondii infection is a worldwide parasitic zoonosis with a high-health risk for humans. The key epidemiological role played by felids is related to oocyst shedding. The present study compared two amplification protocols for the molecular diagnosis of Toxoplasma infection in owned cats. A total of 78 owned cats referred to an Italian university-teaching hospital and exposed to various T. gondii-associated risk factors were sampled for blood and faeces. Faecal specimens were processed by flotation and tested using 2 copro-PCRs targeting the widely used B1 gene and the 529-bp repetitive element (RE). The sera were tested by the indirect immunofluorescent antibody test (IFAT) for the detection of immunoglobulins against T. gondii. Sixteen faeces (20.52%) tested positive for T. gondii DNA; 12 samples were positive only at B1-PCR, two at 529-bp RE-PCR and two at both genetic targets (overall agreement = 82.11%). The amplicons obtained were sequenced, and the Basic Local Alignment Search Tool analysis showed a high homology with the T. gondii strains available in reference databases. Two stool samples were microscopically positive for T. gondii-like oocysts and also tested positive by both B1 and 529-bp RE-PCRs. Thirty-three (42.3%) sera tested positive for antibodies; of which, seven were found to have T. gondii DNA-positive results using the B1 genetic target (overall agreement = 57.77%). The amplification sets targeting B1 and 529-bp RE showed substantially different yields. Further research is needed to better understand the significance and the sensitivities of using these multi-copy-targeted molecular methods from cat faeces before being used for routine diagnosis.

  1. Iron sulfide attenuates the methanogenic toxicity of elemental copper and zinc oxide nanoparticles and their soluble metal ion analogs.

    PubMed

    Gonzalez-Estrella, Jorge; Gallagher, Sara; Sierra-Alvarez, Reyes; Field, Jim A

    2016-04-01

    Elemental copper (Cu(0)) and zinc oxide (ZnO) nanoparticle (NP) toxicity to methanogens has been attributed to the release of soluble metal ions. Iron sulfide (FeS) partially controls the soluble concentration of heavy metals and their toxicity in aquatic environments. Heavy metals displace the Fe from FeS forming poorly soluble metal sulfides in the FeS matrix. Therefore, FeS may be expected to attenuate the NP toxicity. This work assessed FeS as an attenuator of the methanogenic toxicity of Cu(0) and ZnO NPs and their soluble salt analogs. The toxicity attenuation capacity of fine (25-75μm) and coarse (500 to 1200μm) preparations of FeS (FeS-f and FeS-c respectively) was tested in the presence of highly inhibitory concentrations of CuCl2, ZnCl2 Cu(0) and ZnO NPs. FeS-f attenuated methanogenic toxicity better than FeS-c. The results revealed that 2.5× less FeS-f than FeS-c was required to recover the methanogenic activity to 50% (activity normalized to uninhibited controls). The results also indicated that a molar FeS-f/Cu(0) NP, FeS-f/ZnO NP, FeS-f/ZnCl2, and FeS-f/CuCl2 ratio of 2.14, 2.14, 4.28, and 8.56 respectively, was necessary to recover the methanogenic activity to >75%. Displacement experiments demonstrated that CuCl2 and ZnCl2 partially displaced Fe from FeS. As a whole, the results indicate that not all the sulfide in FeS was readily av