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1.
  • Anghel, Clara, et al. (author)
  • Effects of Pt Surface Coverage on Oxidation of Zr and Other Materials
  • 2009
  • In: ZIRCONIUM IN THE NUCLEAR INDUSTRY. - 9780803145146 ; , s. 285-302
  • Conference paper (peer-reviewed)abstract
    • Certain elements, including noble metals, are identified to influence corrosion behavior of many metals in high-temperature water/steam and O-2. We have previously reported effects of porous Pt coatings on the thermal oxidation of Zr, Fe, Ni, Cr, and GaAs in O-2. Effects of Pt on oxidation of Zircaloy-2 in H2O have also been observed at temperatures near 400 degrees C. An enhanced oxidation rate is observed in all of the studied systems upon a sufficiently high surface Pt-particle density. Even more interesting, low Pt-particle density in most cases leads to a decreased oxidation rate. In the case of Zr and Zircaloy-2 the beneficial effect of Pt is stronger when hydrogen is present in the metal substrate and in the oxide layer. From O-18/SIMS experiments it is concluded that, for a sufficiently high Pt-particle density on the surface, enhanced transport of dissociated oxygen, On- (n=0; 2), towards the oxide/metal interface occurs in all of the studied systems. An oxygen spillover from Pt particles to the adjacent surface is a known phenomenon in catalysis and partly explains the results observed also in the current study of oxidation of Zr-based materials. Such a spillover involves a high surface diffusivity of dissociated oxygen, On-, which results in an increased gradient of On- across the oxide scale. In turn, the high oxygen gradient enhances the transport of oxygen towards the substrate/oxide-interface, This shows that not only diffusivity but also an effective activity of dissociated oxygen at the external oxide surface influences the oxidation rate. Naturally, the effects of Pt are maximized when small (nm-sized) and evenly distributed Pt particles are present on the surface. In our presentation a summary of obtained results of Pt additions on different materials will be given with suggested interpretations. Especially, the observed beneficial combination of Pt and hydrogen in the oxidation of Zr-based materials is discussed with a possible mechanistic explanation. Parallels are also drawn to the potential effect of Noble Metal Chemical Application (NMCA), used in a large traction of the U.S. BWRs, on the corrosion resistance of Zr-based claddings.
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2.
  • Anghel, Clara, et al. (author)
  • Effects of Pt surface coverage on oxidation of Zr and other materials
  • 2008
  • In: Journal of ASTM International. - 1546-962X. ; 5:2
  • Journal article (peer-reviewed)abstract
    • Certain elements, including noble metals, are identified to influence corrosion behavior of many metals in high-temperature water/steam and O 2. We have previously reported effects of porous Pt coatings on the thermal oxidation of Zr, Fe, Ni, Cr and GaAs in O2. Effects of Pt on oxidation of Zircaloy-2 In H2O have also been observed at temperatures near 400°C. An enhanced oxidation rate Is observed in all of the studied systems upon a sufficiently high surface Pt-particle density. Even more interesting, low Pt-particle density in most cases leads to a decreased oxidation rate. In the case of Zr and Zircaloy-2 the beneficial effect of Pt is stronger when hydrogen is present In the metal substrate and in the oxide layer. From 18O/SIMS experiments it is concluded that, for a sufficiently high Pt-particle density on the surface, enhanced transport of dissociated oxygen, On- (n=0; 2), towards the oxide/metal interface occurs in all of the studied systems. An oxygen spillover from Pt particles to the adjacent surface is a known phenomenon in catalysis and partly explains the results observed also in the current study of oxidation of Zr-based materials. Such a spillover involves a high surface diffusivity of dissociated oxygen, O n-, which results In an increased gradient of On- across the oxide scale. In turn, the high oxygen gradient enhances the transport of oxygen towards the substrate/oxide-interface. This shows that not only diffusivlty but also an effective activity of dissociated oxygen at the external oxide surface influences the oxidation rate. Naturally, the effects of Pt are maximized when small (nm-sized) and evenly distributed Pt particles are present on the surface. In our presentation a summary of obtained results of Pt additions on different materials will be given with suggested interpretations. Especially, the observed beneficial combination of Pt and hydrogen in the oxidation of Zr-based materials Is discussed with a possible mechanistic explanation. Parallels are also drawn to the potential effect of Noble Metal Chemical Application (NMCA), used in a large fraction of the U.S. BWRs, on the corrosion resistance of Zr-based claddings.
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3.
  • Anghel, Clara, et al. (author)
  • Gas-tight oxides – Reality or just a Hope
  • 2006
  • In: Materials Science Forum. - 0255-5476 .- 1662-9752. ; 522-523, s. 93-101
  • Journal article (peer-reviewed)abstract
    • A better understanding of the transport properties of gases in oxides is certainly very important in many applications. In the case of metals, a general protection measure against corrosion implies formation of a dense metal oxide scale. The scale should act as a barrier against gas transport and consequently it needs to be gas-tight. This is often assumed but rarely, if ever, confirmed. Hence there is a need for characterization of micro- and/or meso- pores formed especially during the early oxidation stage of metallic materials. This paper presents a novel and relatively straightforward method for characterization of gas release from an oxide previously equilibrated in a controlled atmosphere. The geometry of the sample is approximated to be a plate. The plate can be self-supporting or constitute a scale on a substrate. A mathematical model for calculation of diffusivity and gas content is given for this geometry. A desorption experiment, involving a mass spectrometer placed in ultra high vacuum, can be used to determine diffusivity and amount of gas released with aid of the mathematical model. The method is validated in measurements of diffusivity and solubility of He in quartz and applied in characterization of two Zr-oxides and one Fe oxide. From the outgassed amounts of water and nitrogen the H2O/N-2 molar ratio can be used to estimate an effective pore size in oxides.
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4.
  • Anghel, Clara, et al. (author)
  • Influence of Pt, Fe/Ni/Cr–containing intermetallics and deuterium on the oxidation of Zr-based materials
  • 2005
  • In: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 340:2-3, s. 271-283
  • Journal article (peer-reviewed)abstract
    • An in situ gas phase analysis technique and the 18O-SIMS technique are used to evaluate the transport of oxygen and hydrogen in oxidation of Zr-based materials. At 400 °C, it is found that oxygen dissociation efficiency decreases in the order: Pt > Zr2Fe > Zr2Ni > ZrCr2 Zircaloy-2. Two Zr-plates partly coated with 200 Å porous Pt, with and respectively without D in the substrate, were oxidized in two stages at 400 °C. SIMS depth profiles in the Pt area show that an enhanced oxidation takes place mainly by inward oxygen transport. A minimum in the oxide thickness was found near the Pt area on both Zr plates. Two Ar-filled Zircaloy-2 tubes with ZrSn liner were exposed at 370 °C to 22 mbar water, filled in from one side. Our experimental results suggest that a proper choice of the SPP composition and size distribution can lead to reduced hydrogen uptake during oxidation of Zr-based materials in water.
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5.
  • Anghel, Clara, 1971- (author)
  • Modified oxygen and hydrogen transport in Zr-based oxides
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • Most metals and alloys in the presence of oxygen and moisture will instantaneously react and form a thin (2-5 nm) surface oxide layer. For further reaction to occur, oxygen ions and/or metal cations often diffuse through the already formed oxide layer. The corrosion resistance of a metal in aggressive environments at high temperatures depends on the properties of the surface oxide scale. Zirconium-based alloys represent the main structural materials used in water-cooled nuclear reactors. For these materials, the formation of a thin, adherent oxide scale with long-term stability in high temperature water/steam under irradiation conditions, is crucial. In this thesis, the transport of oxygen and hydrogen through Zr-based oxide scales at relevant temperatures for the nuclear industry is investigated using isotopic gas mixtures and isotope-monitoring techniques such as Gas Phase Analysis and Secondary Ion Mass Spectrometry. Porosity development in the oxide scales generates easy diffusion pathways for molecules across the oxide layer during oxidation. A considerable contribution of molecular oxygen to total oxygen transport in zirconia has been observed at temperatures up to 800°C. A novel method for evaluation of the gas diffusion, gas concentration and effective pore size of oxide scales is presented in this thesis. Effective pore sizes in the nanometer range were found for pretransition oxides on Zircaloy-2. A mechanism for densification of oxide scales by obtaining a better balance between inward oxygen and outward metal transport is suggested. Outward Zr transport can be influenced by the presence of hydrogen in the oxide and/or metal substrate. Inward oxygen transport can be promoted by oxygen dissociating elements such as Fe-containing second phase particles. The results suggest furthermore that a proper choice of the second-phase particles composition and size distribution can lead to the formation of dense oxides, which are characterized by low oxygen and hydrogen uptake rates during oxidation. Hydrogen uptake in Zr-based materials during oxidation in high temperature water/steam can generate degradation due to the formation of brittle hydrides in the metal substrate. A promising method for the suppression of hydrogen uptake has been developed and is presented in this thesis.
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6.
  • Belonoshko, Anatoly B., et al. (author)
  • Thermal regimes of passivative oxide film formation on Al surface : Theoretical and experimental study
  • 2006
  • In: Surface Science. - : Elsevier BV. - 0039-6028 .- 1879-2758. ; 600:20, s. 4796-4800
  • Journal article (peer-reviewed)abstract
    • We report results of ab initio molecular dynamics simulations of an Al surface exposed to an oxygen atmosphere. The results, supported by experiments performed in this study, demonstrate that the Al surface, by reacting with the oxygen molecules, can be heated above melting temperature and transformed into a liquid. This process is potentially capable of creating an amorphous corrosion scale which might possess an enhanced resistance to deterioration.
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7.
  • Cetinkaya, Cihan, et al. (author)
  • Combined IFN-gamma and retinoic acid treatment targets the N-Myc/Max/Mad1 network resulting in repression of N-Myc target genes in MYCN-amplified neuroblastoma cells
  • 2007
  • In: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 6:10, s. 2634-2641
  • Journal article (peer-reviewed)abstract
    • The MYCN protooncogene is involved in the control of cell proliferation, differentiation, and survival of neuroblasts. Deregulation of MYCN by gene amplification contributes to neuroblastoma development and is strongly correlated to advanced disease and poor outcome, emphasizing the urge for new therapeutic strategies targeting MYCN function. The transcription factor N-Myc, encoded by MYCN, regulates numerous genes together with its partner Max, which also functions as a cofactor for the Mad/Mnt family of Myc antagonists/transcriptional repressors. We and others have previously reported that IFN-gamma synergistically potentiates retinoic acid (RA)induced sympathetic differentiation and growth inhibition in neuroblastoma cells. This study shows that combined treatment of MYCN-amplified neuroblastorna cells with RA+IFN-gamma down-regulates N-Myc protein expression through increased protein turnover, up-regulates Mad1 mRNA and protein, and reduces N-Myc/Max heteroclimerization. This results in a shift of occupancy at the ornithine decarboxylase N-Myc/Mad1 target promoter in vivo from N-Myc/Max to Madl/Max predominance, correlating with histone H4 deacetylation, indicative of a chromatin structure typical of a transcriptionally repressed state. This is further supported by data showing that RA + IFN-gamma treatment strongly represses expression of N-Myc/Mad1 target genes ornithine decarboxylase and hTERT. Our results suggest that combined IFN-gamma and RA signaling can form a basis for new therapeutic strategies targeting N-Myc function for patients with high-risk, MYCN-amplified neuroblastoma.
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8.
  • Dong, Qian, et al. (author)
  • Does nitrogen transport in vitreous silica only take place in molecular form?
  • 2006
  • In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 100:10, s. 104904-
  • Journal article (peer-reviewed)abstract
    • It is generally believed that nitrogen transport in vitreous silica exclusively takes place in molecular form, although no evidence for this is found in the literature. Actually, an analysis of literature data of transport of nitrogen and noble gases in vitreous silica at 900 °C suggests it may not be the case. In order to clarify the operative species of nitrogen transport in this material, experiments of permeation and uptake/release have been performed with the use of gas phase analysis and isotopic labeling of nitrogen. By comparing the relative distributions of N2 14,14, N2 14,15, and N2 15,15 in exposure gas, permeated gas and released gas with distribution of equilibrated nitrogen molecules, the percentage of dissociated nitrogen in the transport has been evaluated at different temperatures. It has then been found that nitrogen undergoes dissociation not only on the surface of vitreous silica but also in its bulk and that the overall dissociation of nitrogen increases with temperature. It is concluded that nitrogen diffuses both in molecular and atomic forms with approximately 15% atomic nitrogen transport at 900 °C. The observed transport rates are explained by diffusion of molecular nitrogen combined with a retardation of dissociated nitrogen in reversible traps.
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9.
  • Dong, Q., et al. (author)
  • Platinum-catalyzed high temperature oxidation of metals
  • 2007
  • In: Corrosion Science. - : Elsevier BV. - 0010-938X .- 1879-0496. ; 49:8, s. 3348-3360
  • Journal article (peer-reviewed)abstract
    • Samples of At, Cr, Ni, and Zr were sputter-coated with porous Pt-films with a particle size of 20-30 nm. Thermal oxidation of these samples was studied by gas phase analysis (GPA) and secondary ion mass spectrometry (SIMS). SIMS analysis on partly Pt-coated samples of At, Cr, Ni, and Zr at different oxide depths in areas with Pt and in areas away from Pt indicates an enhanced inward oxide growth in the Pt area and mm-ranged distance from Pt-area. Weight gain measurements on Pt-coated Ni samples show a reduced or increased oxidation rate depending on the amount of porous Pt-coating. Pt has two effects on the thermal oxidation of metals and the overall effect of Pt on the oxidation of metals depends on the mechanism of oxide growth in the absence of Pt.
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10.
  • Dong, Qian, 1973- (author)
  • Transport in Oxides Studied by Gas Phase Analysis
  • 2007
  • Doctoral thesis (other academic/artistic)abstract
    • The transport in oxides is studied by the use of gas phase analysis (GPA). An experimental method to identify transported species of gases and their contribution to the overall transport of gases in oxides and an experimental method to evaluate the parameters diffusivity, concentration, permeability of gases in oxides and effective pore size in oxides are developed, respectively. Pt has two effects on the thermal oxidation of metals. One is to enhance the oxidation of metals which takes place at the oxide-metal interface by promoting a high concentration gradient of dissociated oxygen across the oxide layer. The other effect is to suppress the oxidation of metals by decreasing the contact area between metal and oxygen. The overall effect of Pt on the oxidation of metals depends on the mechanism of oxide growth in the absence of Pt. It is suggested that an appropriate amount of Pt coating induces a balanced oxide growth resulting from stoichimetrical inward oxygen flux to outward metal flux, which leads to a reduced oxidation rate. The diffusion of diatomic gases in oxides such as vitreous silica and yttria stabilized zirconia (YSZ) takes place in both molecular and dissociated (atomic or/and ionic) form. The fraction of transport of molecular species decreases with temperatures, and the fraction of transport of dissociated species increases with temperatures. Measured permeabilities of diatomic gases in vitreous silica are higher than the expected permeabilities of their molecules, which are explained by diffusion of molecules combined with a retardation of dissociated species in reversible traps. The diffusion of hydrogen in vitreous silica is concentration dependent and increases with local concentration. Transport paths are shared among transported species and gases at all temperatures in YSZ. Helium shares transport path with molecular oxygen and nitrogen at low temperatures; whereas helium shares transport path with dissociated oxygen and also dissociated nitrogen at high temperatures.
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11.
  • Hultquist, Gunnar B., et al. (author)
  • Detection of hydrogen in corrosion of copper in pure water
  • 2008
  • In: Int. Corros. Congr.: Corros. Control Serv. Soc.. - 9781615674251 ; , s. 2378-2386
  • Conference paper (peer-reviewed)abstract
    • Copper is generally assumed to be immune to corrosion by water itself. However, this is not supported by any scientific experimental evidence. Corrosion results from 15 years of exposure are presented here. A transition from O 2-consuming to H 2-evolving copper corrosion is concluded, which implies that copper can corrode by water itself. The complex corrosion product contains hydrogen. We have also measured a hydrogen uptake in the copper metal as a result of metallic copper corrosion by water which implies a sample thickness dependence on hydrogen uptake. The results are described in terms of autoionisation of water which offers an explanation why copper corrosion can take place in pure O 2-free water.
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12.
  • Hultquist, Gunnar, et al. (author)
  • Catalysed self-cleaning of air on the earth's surface
  • 2006
  • In: Journal of Atmospheric Chemistry. - : Springer Science and Business Media LLC. - 0167-7764 .- 1573-0662. ; 55:2, s. 131-146
  • Journal article (peer-reviewed)abstract
    • Generally, it is assumed that UV-light, high temperature or reactive molecules like O-3 and OH are needed to activate gas reactions in air. In consequence, the catalytic activity on natural materials such as sand and soil on the earth's surface is assumed to be insignificant. We have measured O-2-dissociation rates on natural quartz sand at 40 degrees C and compared these with O-2-dissociation rates near 500 degrees C on materials with well-known catalytic activity. In terms of probabilities for dissociation of impinging O-2-molecules the measured rates are in the 10(-12)-10(-4) range. We have also measured dissociation rates of H-2 and N-2, water-formation from H-2 and O-2 mixtures, exchange of N between N-2, NO (x) and a breakdown of HNO3, NO2 and CH4 on natural quartz sand at 40 degrees C. The measured rates together with an effective global land area have been used to estimate the impact of thermodynamically driven reactions on the earth's surface on the global atmospheric budgets of H-2, NO2 and CH4. The experimental data on natural quartz sand together with data from equilibrium calculations of air suggest that an expected increase in anthropogenic supply of air pollutants, such as NO (x) or other reactive nitrogen compounds, hydrogen and methane, will be counter-acted by catalysis on the earth's surface. On the other hand, at Polar Regions and boreal forests where the reactive nitrogen concentration is below equilibrium, the same catalytic effect activates formation of bio-available nitrogen compounds from N-2, O-2 and H2O.
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13.
  • Hultquist, Gunnar, et al. (author)
  • Effects of hydrogen on the corrosion resistance of metallic materials and semiconductors
  • 2006
  • In: High-Temperature Oxidation And Corrosion 2005. - 087849409X ; , s. 139-146
  • Conference paper (peer-reviewed)abstract
    • For long time it is known that protons in aqueous solutions have a detrimental effect on metallic materials. Relatively recently, it has also been observed in aqueous solution that the pitting corrosion resistance of Cr, stainless steel 304 and 310 decreases and the anodic dissolution rate increases due to the presence of hydrogen in the metal. In gas phase a high oxidation rate has been observed for hydrogen containing Cr and Fe. Hydrogen in the substrate can also enhance the oxidation of Fe in SS 316 and As in GaAs. All these results suggest enhanced dissolution in aqueous solution and enhanced oxide growth at the oxide/gas interface in gas phase oxidation due to hydrogen promoted outward-transport of substrate components. A possible mechanism for such out-transport is an increased metal ion diffusivity in the metal-oxide due to a high abundance of metal ion vacancies generated by hydrogen. In contrast to all the above examples, also positive effects of hydrogen have been identified under certain conditions. In an attempt to understand both the negative and the positive effects the concept of a beneficial, balanced oxide growth is used. In this concept a certain amount of hydrogen can be beneficial in the oxidation by improving the balance between oxygen-ion and metalion transport, leading to more dense and protective oxides. Depending on the temperature, H(2) in air is considered as either a sink or a source for hydrogen in materials.
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14.
  • Hultquist, Gunnar, et al. (author)
  • Effects of O-2 dissociation on a porous platinum coating in the thermal oxidation of GaAs
  • 2006
  • In: Journal of the Electrochemical Society. - : The Electrochemical Society. - 0013-4651 .- 1945-7111. ; 153:2, s. G182-G186
  • Journal article (peer-reviewed)abstract
    • A 20-30-nm-thick porous Pt layer has been sputter-coated on a portion of a GaAs sample and subsequently the sample was oxidized at 500 degrees C in O-16(2) followed by O-18-enriched O-2. The oxide formed was characterized by Auger electron spectroscopy, secondary ion mass spectrometry, and X-ray photoelectron spectroscopy, all with a lateral resolution of about 100 mu m. Away from the Pt area, a mm-ranged gradually decreasing degree of As oxidation was observed in the outermost oxide layer. In the Pt area, Ga was preferentially oxidized at the oxide/substrate interface producing a five to seven times thicker oxide than in an area without the influence of Pt. A strongly enhanced dissociation rate of O-2 on Pt particles and a subsequent O spillover to adjacent oxide explain the experimental observations. The mm-ranged spillover is believed to take place via fast lateral surface diffusion and results in the observed variation of oxidized As at the gas/oxide interface. In the Pt area, a high concentration gradient of dissociated oxygen across the oxide layer supplies a high flux of dissociated oxygen to the GaAs substrate where Ga is preferentially oxidized. The results clearly demonstrate that both a surface reaction and solid-state diffusion influence the oxidation rate. A localized high effective oxygen (O) activity that spills over to a nearby oxide area is believed to be a general phenomenon that is operating in oxides where a dissociating element such as Pt is present at O-2/oxide interfaces.
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15.
  • Hultquist, Gunnar, et al. (author)
  • Water Corrodes Copper
  • 2009
  • In: Catalysis Letters. - : Springer Science and Business Media LLC. - 1011-372X .- 1572-879X. ; 132:3-4, s. 311-316
  • Journal article (peer-reviewed)abstract
    • According to a current concept, copper canisters of thickness 0.05 m will be safe for nuclear waste containment for 100,000 years. We show that more than 1 m copper thickness might be required for 100,000 years durability based on water exposures of copper for 20 h, 7 weeks, 15 years, and 333 years. An observed evolution of hydrogen which involves heterogeneous catalysis of molecular hydrogen, first principles simulations, thermodynamic considerations and corrosion product characterization provide further evidence that water corrodes copper resulting in the formation of a copper hydroxide. These findings cast additional doubt on copper for nuclear waste containment and other important applications.
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16.
  • Rundgren, John, et al. (author)
  • Concentration-dependent diffusion of hydrogen in vitreous silica
  • 2006
  • In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 100:10, s. 104902-1-104902-5
  • Journal article (peer-reviewed)abstract
    • We report diffusion experiments where hydrogen permeates through a 1 mm wall of vitreous silica at 550 °C with applied gas pressures of 70, 460, 840, and 1200 mbars. For each pressure, and at steady state, the flux and the amount of hydrogen in the material are measured. Within the experimental accuracy we find that the flux is proportional to the pressure and that the hydrogen amount increases with a falling gradient with respect to pressure. The result is a relationship between flux and mean concentration. A careful evaluation of the flux versus concentration relationship by means of the steady-state diffusion equation shows that the hydrogen diffusivity in the silica wall is concentration dependent and increases linearly with local concentration.
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17.
  • Szakalos, Peter, et al. (author)
  • Corrosion of copper by water
  • 2007
  • In: Electrochemical and solid-state letters. - : The Electrochemical Society. - 1099-0062 .- 1944-8775. ; 10:11, s. C63-C67
  • Journal article (peer-reviewed)abstract
    • We have studied copper corrosion in a system comprised of deionized water, absolute pressure gauges, and a palladium membrane. A transition from O-2-consuming to H-2-evolving copper corrosion is observed, which indicates that copper can corrode by water itself. The equilibrium hydrogen pressure in corrosion of copper by water at 73 degrees C exceeds the steady-state atmospheric hydrogen pressure (5 x 10(-7) bar) by a factor of about 2000. The growth of a hydrogen-containing corrosion product in O-2-free water is controlled by the hydrogen removal from the corroding surface. The results are discussed in the perspective of conventional potential-pH diagram for copper.
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18.
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19.
  • Wu, Siqin, et al. (author)
  • TGF-beta enforces senescence in Myc-transformed hematopoietic tumor cells through induction of Mad1 and repression of Myc activity
  • 2009
  • In: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 315:18, s. 3099-3111
  • Journal article (peer-reviewed)abstract
    • Inhibition of tumor growth factor (TGF)-beta-mediated cell cycle exit is considered an important tumorigenic function of Myc oncoproteins. Here we found that TGF-beta1 enforced G(1) cell cycle arrest and cellular senescence in human U-937 myeloid tumor cells ectopically expressing v-Myc, which contains a stabilizing mutation frequently found in lymphomas. This correlated with induced expression of the Myc antagonist Mad1, resulting in replacement of Myc for Mad1 at target promoters, reduced histone acetylation and strong repression of Myc-driven transcription. The latter was partially reversed by histone deacetylase (HDAC) inhibitors, consistent with involvement of Mad1. Importantly, knockdown of MAD1 expression prevented TGF-beta1-induced senescence, underscoring that Mad1 is a crucial component of this process. Enforced Mad1 expression sensitized U-937-myc cells to TGF-beta and restored phorbol ester-induced cell cycle exit, but could not alone induce G(1) arrest, suggesting that Mad1 is required but not sufficient for cellular senescence. Our results thus demonstrate that TGF-beta can override Myc activity despite a stabilizing cancer mutation and induce senescence in myeloid tumor cells, at least in part by induction of Mad1. TGF-beta-induced senescence, or signals mimicking this pathway, could therefore potentially be explored as a therapeutic principle for treating hematopoietic and other tumors with deregulated MYC expression.
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