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Sample records for air-pollution-control apc residues

  1. Production of geopolymers using glass produced from DC plasma treatment of air pollution control (APC) residues.

    PubMed

    Kourti, Ioanna; Rani, D Amutha; Deegan, D; Boccaccini, A R; Cheeseman, C R

    2010-04-15

    Air pollution control (APC) residues are the hazardous waste produced from cleaning gaseous emissions at energy-from-waste (EfW) facilities processing municipal solid waste (MSW). APC residues have been blended with glass-forming additives and treated using DC plasma technology to produce a high calcium alumino-silicate glass. This research has investigated the optimisation and properties of geopolymers prepared from this glass. Work has shown that high strength geopolymers can be formed and that the NaOH concentration of the activating solution significantly affects the properties. The broad particle size distribution of the APC residue glass used in these experiments results in a microstructure that contains unreacted glass particles included within a geopolymer binder phase. The high calcium content of APC residues may cause the formation of some amorphous calcium silicate hydrate (C-S-H) gel. A mix prepared with S/L=3.4, Si/Al=2.6 and [NaOH]=6M in the activating solution, produced high strength geopolymers with compressive strengths of approximately 130 MPa. This material had high density (2070 kg/m(3)) and low porosity. The research demonstrates for the first time that glass derived from DC plasma treatment of APC residues can be used to form high strength geopolymer-glass composites that have potential for use in a range of applications.

  2. Geopolymers prepared from DC plasma treated air pollution control (APC) residues glass: properties and characterisation of the binder phase.

    PubMed

    Kourti, Ioanna; Devaraj, Amutha Rani; Bustos, Ana Guerrero; Deegan, David; Boccaccini, Aldo R; Cheeseman, Christopher R

    2011-11-30

    Air pollution control (APC) residues have been blended with glass-forming additives and treated using DC plasma technology to produce a high calcium aluminosilicate glass (APC glass). This has been used to form geopolymer-glass composites that exhibit high strength and density, low porosity, low water absorption, low leaching and high acid resistance. The composites have a microstructure consisting of un-reacted residual APC glass particles imbedded in a complex geopolymer and C-S-H gel binder phase, and behave as particle reinforced composites. The work demonstrates that materials prepared from DC plasma treated APC residues have potential to be used to form high quality pre-cast products.

  3. Metals accumulations during thermal processing of sewage sludge - characterization of bottom ash and air pollution control (APC) residues

    NASA Astrophysics Data System (ADS)

    Kasina, Monika; Kowalski, Piotr R.; Michalik, Marek

    2016-04-01

    Due to increasing mass of sewage sludge, problems in its management have appeared. Over years sewage sludge was landfilled, however due to EU directives concerning environmental issues this option is no longer possible. This type of material is considered hazardous due to highly concentrated metals and harmful elements, toxic organic substances and biological components (e.g. parasites, microbes). Currently in Europe, incineration is considered to be the most reasonable method for sewage sludge treatment. As a result of sludge incineration significant amount of energy is recovered due to high calorific value of sewage sludge but bottom ash and APC residues are being produced. In this study we show the preliminary results of chemical and mineral analyses of both bottom ash and APC residues produced in fluidized bed boiler in sewage sludge incineration plant in Poland, with a special emphasis on metals which, as a part of incombustible fraction can accumulate in the residual materials after thermal processing. The bottom ash was a SiO2-P2O5-Fe2O3-CaO-Al2O3 dominated material. Main mineral phases identified in X-ray diffraction patterns were: quartz, feldspar, hematite, and phosphates (apatite and scholzite). The bottom ash was characterized by high content of Zn - 4472 mg kg‑1, Cu - 665.5 mg kg‑1, Pb - 138 mg kg‑1, Ni - 119.5 mg kg‑1, and interestingly high content of Au - 0.858 mg kg‑1 The APC residues composition was dominated by soluble phases which represent more than 90% of the material. The XRD patterns indicated thenardite, halite, anhydrite, calcite and apatite as main mineral phases. The removal of soluble phases by dissolution in deionised water caused a significant mass reduction (ca. 3% of material remained on the filters). Calcite, apatite and quartz were main identified phases. The content of metals in insoluble material is relatively high: Zn - 6326 mg kg‑1, Pb - 514.3 mg kg‑1, Cu - 476.6 mg kg‑1, Ni - 43.3 mg kg‑1. The content of Cd

  4. Metals accumulations during thermal processing of sewage sludge - characterization of bottom ash and air pollution control (APC) residues

    NASA Astrophysics Data System (ADS)

    Kasina, Monika; Kowalski, Piotr R.; Michalik, Marek

    2016-04-01

    Due to increasing mass of sewage sludge, problems in its management have appeared. Over years sewage sludge was landfilled, however due to EU directives concerning environmental issues this option is no longer possible. This type of material is considered hazardous due to highly concentrated metals and harmful elements, toxic organic substances and biological components (e.g. parasites, microbes). Currently in Europe, incineration is considered to be the most reasonable method for sewage sludge treatment. As a result of sludge incineration significant amount of energy is recovered due to high calorific value of sewage sludge but bottom ash and APC residues are being produced. In this study we show the preliminary results of chemical and mineral analyses of both bottom ash and APC residues produced in fluidized bed boiler in sewage sludge incineration plant in Poland, with a special emphasis on metals which, as a part of incombustible fraction can accumulate in the residual materials after thermal processing. The bottom ash was a SiO2-P2O5-Fe2O3-CaO-Al2O3 dominated material. Main mineral phases identified in X-ray diffraction patterns were: quartz, feldspar, hematite, and phosphates (apatite and scholzite). The bottom ash was characterized by high content of Zn - 4472 mg kg-1, Cu - 665.5 mg kg-1, Pb - 138 mg kg-1, Ni - 119.5 mg kg-1, and interestingly high content of Au - 0.858 mg kg-1 The APC residues composition was dominated by soluble phases which represent more than 90% of the material. The XRD patterns indicated thenardite, halite, anhydrite, calcite and apatite as main mineral phases. The removal of soluble phases by dissolution in deionised water caused a significant mass reduction (ca. 3% of material remained on the filters). Calcite, apatite and quartz were main identified phases. The content of metals in insoluble material is relatively high: Zn - 6326 mg kg-1, Pb - 514.3 mg kg-1, Cu - 476.6 mg kg-1, Ni - 43.3 mg kg-1. The content of Cd, As, Se and Hg was

  5. Solidification/stabilisation of air pollution control residues using Portland cement: Physical properties and chloride leaching.

    PubMed

    Lampris, C; Stegemann, J A; Cheeseman, C R

    2009-03-01

    Portland cement (CEMI) was used to solidify air pollution control (APC) residues from an energy-from-waste plant burning municipal solid waste. APC residue/CEMI mixes were prepared with CEMI additions ranging from 0 to 50 weight% (wt%) of total dry mass and water/solids ratios between 0.40 and 0.80. Isothermal conduction calorimetry was used to assess the effect of APC residues on the hydration of CEMI. Although up to 30wt% additions of APC residues accelerated CEMI hydration, the total heat of hydration during the initial 98h was significantly reduced. Higher levels of APC residues severely inhibited CEMI hydration. The consistence, setting time, compressive strength, porosity and chloride leaching characteristics of the solidified products were determined. As might be expected, increasing the CEMI addition and reducing the water content resulted in increased compressive strengths. All mixes achieved compressive strengths greater than 1MPa at 7 and 28days but only 50wt% samples did not show significant strength reduction when tested after immersion in water. Monolithic leaching tests indicated low physical immobilisation of chloride in the CEMI solidified APC residues, with chloride leaching in excess of relevant UK landfill waste acceptance criteria (WAC). The results of this study show that greater than 50% CEMI additions would be required to effectively treat APC residues to meet current WAC limits. PMID:18849156

  6. Recycling of air pollution control residues from municipal solid waste incineration into lightweight aggregates.

    PubMed

    Quina, Margarida J; Bordado, João M; Quinta-Ferreira, Rosa M

    2014-02-01

    This work focuses on the assessment of technological properties and on the leaching behavior of lightweight aggregates (LWA) produced by incorporating different quantities of air pollution control (APC) residues from municipal solid waste (MSW) incineration. Currently this hazardous waste has been mostly landfilled after stabilization/solidification. The LWA were produced by pelletizing natural clay, APC residues as-received from incineration plant, or after a washing treatment, a small amount of oil and water. The pellets were fired in a laboratory chamber furnace over calcium carbonate. The main technological properties of the LWA were evaluated, mainly concerning morphology, bulk and particle densities, compressive strength, bloating index, water adsorption and porosity. Given that APC residues do not own expansive (bloating) properties, the incorporation into LWA is only possible in moderate quantities, such as 3% as received or 5% after pre-washing treatment. The leaching behavior of heavy metals from sintered LWA using water or acid solutions was investigated, and despite the low acid neutralization capacity of the synthetic aggregates, the released quantities were low over a wide pH range. In conclusion, after a washing pre-treatment and if the percentage of incorporation is low, these residues may be incorporated into LWA. However, the recycling of APC residues from MSW incineration into LWA does not revealed any technical advantage.

  7. Recycling of air pollution control residues from municipal solid waste incineration into lightweight aggregates.

    PubMed

    Quina, Margarida J; Bordado, João M; Quinta-Ferreira, Rosa M

    2014-02-01

    This work focuses on the assessment of technological properties and on the leaching behavior of lightweight aggregates (LWA) produced by incorporating different quantities of air pollution control (APC) residues from municipal solid waste (MSW) incineration. Currently this hazardous waste has been mostly landfilled after stabilization/solidification. The LWA were produced by pelletizing natural clay, APC residues as-received from incineration plant, or after a washing treatment, a small amount of oil and water. The pellets were fired in a laboratory chamber furnace over calcium carbonate. The main technological properties of the LWA were evaluated, mainly concerning morphology, bulk and particle densities, compressive strength, bloating index, water adsorption and porosity. Given that APC residues do not own expansive (bloating) properties, the incorporation into LWA is only possible in moderate quantities, such as 3% as received or 5% after pre-washing treatment. The leaching behavior of heavy metals from sintered LWA using water or acid solutions was investigated, and despite the low acid neutralization capacity of the synthetic aggregates, the released quantities were low over a wide pH range. In conclusion, after a washing pre-treatment and if the percentage of incorporation is low, these residues may be incorporated into LWA. However, the recycling of APC residues from MSW incineration into LWA does not revealed any technical advantage. PMID:24238798

  8. Characterization of a mineral waste resulting from the melting treatment of air pollution control residues.

    PubMed

    Trujillo-vazquez, A; Metiver-pignon, H; Tiruta-barna, L; Piantone, P

    2009-02-01

    Air pollution control (APC) residues which are generated by municipal solid waste (MSW) incineration show a high-level of pollution potential. In order to stabilize such APC residues, the French power supply company (EDF) is developing a thermal treatment process which leads to the production of a vitrified material. A structural characterization of the vitrified product was carried out by applying complementary investigation methods: XRD, SEM, Raman spectroscopy, EPMA, and data interpretation methods such as mineralogical analysis and principal component analysis (PCA). The major phase of the material was a solid solution of melilite type composed of five end-members: gehlenite (44%), åkermanite (25%), ferri-gehlenite (5%), sodamelilite (14%) and hardystonite (11%). The minor phases identified were spinels and pyroxenes. An ANC leaching test was performed in order to observe the treatment effect on pollutant release. The natural pH was close to 10, and the major element release was less than in the case of untreated APC. This was a consequence of melilite formation. The effect of pH was fundamental for heavy metals release: lower solubilization occurs at pH 10 than at APC's natural pH (11-12).

  9. Leaching of carbonated air pollution control residues using compliance leaching tests.

    PubMed

    He, Pin-Jing; Zhang, Hua; Shao, Li-Ming; Lee, Duu-Jong

    2006-01-01

    The leaching characteristics of air pollution control (APC) residues collected in Shanghai, China, were compared by performing three compliance leaching tests. These were the standard Chinese method for determining the leaching toxicity of solid waste (GB 5086.1-1997), the USEPA's Toxicity Characteristic Leaching Procedure (TCLP), and the new European shake test (EN 12457-3). In particular, behaviors of raw samples and samples that had been subjected to natural aging were compared. Both the leaching tests and natural aging substantially affected the leaching results concerning the APC residue samples. Most importantly, EN and GB tests classified the raw APC residues as hazardous, but the residues passed the TCLP test as nonhazardous. After it had been naturally aged for 720 h, however, the aged sample was classified as hazardous by the TCLP and EN tests, but as nonhazardous by the GB test. Metals that are thought to have been immobilized by carbonation were released at pH 6.3. Model calculations based on the geochemical thermodynamic equilibrium model MINTEQA2 revealed that the formation of metal carbonates did not correspond to the noted change in the leaching behaviors in the three leaching tests. Rather, the partial neutralization of alkaline ash by dissolved CO2 changing the final pH of the leachate dominated the leaching characteristics. The leaching results showed a change in leachate pH.

  10. Properties of sintered glass-ceramics prepared from plasma vitrified air pollution control residues.

    PubMed

    Roether, J A; Daniel, D J; Rani, D Amutha; Deegan, D E; Cheeseman, C R; Boccaccini, A R

    2010-01-15

    Air pollution control (APC) residues, obtained from a major UK energy from waste (EfW) plant, processing municipal solid waste, have been blended with silica and alumina and melted using DC plasma arc technology. The glass produced was crushed, milled, uni-axially pressed and sintered at temperatures between 750 and 1150 degrees C, and the glass-ceramics formed were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Mechanical properties assessed included Vickers's hardness, flexural strength, Young's modulus and thermal shock resistance. The optimum sintering temperature was found to be 950 degrees C. This produced a glass-ceramic with high density (approximately 2.58 g/cm(3)), minimum water absorption (approximately 2%) and relatively high mechanical strength (approximately 81+/-4 MPa). Thermal shock testing showed that 950 degrees C sintered samples could withstand a 700 degrees C quench in water without micro-cracking. The research demonstrates that glass-ceramics can be readily formed from DC plasma treated APC residues and that these have comparable properties to marble and porcelain. This novel approach represents a technically and commercially viable treatment option for APC residues that allow the beneficial reuse of this problematic waste.

  11. Life-cycle assessment of selected management options for air pollution control residues from waste incineration.

    PubMed

    Fruergaard, Thilde; Hyks, Jiri; Astrup, Thomas

    2010-09-15

    Based on available technology and emission data seven selected management options for air-pollution-control (APC) residues from waste incineration were evaluated by life-cycle assessment (LCA) using the EASEWASTE model. Scenarios were evaluated with respect to both non-toxicity impact categories (e.g. global warming) and toxicity related impact categories (e.g. ecotoxicity and human toxicity). The assessment addressed treatment and final placement of 1 tonne of APC residue in seven scenarios: 1) direct landfilling without treatment (baseline), 2) backfilling in salt mines, 3) neutralization of waste acid, 4) filler material in asphalt, 5) Ferrox stabilization, 6) vitrification, and 7) melting with automobile shredder residues (ASR). The management scenarios were selected as examples of the wide range of different technologies available worldwide while at the same time using realistic technology data. Results from the LCA were discussed with respect to importance of: energy consumption/substitution, material substitution, leaching, air emissions, time horizon aspects for the assessment, and transportation distances. The LCA modeling showed that thermal processes were associated with the highest loads in the non-toxicity categories (energy consumption), while differences between the remaining alternatives were small and generally considered insignificant. In the toxicity categories, all treatment/utilization options were significantly better than direct landfilling without treatment (lower leaching), although the thermal processes had somewhat higher impacts than the others options (air emissions). Transportation distances did not affect the overall ranking of the management alternatives.

  12. Mineralogy of air-pollution-control residues from a secondary lead smelter: environmental implications.

    PubMed

    Ettler, Vojtech; Johan, Zdenek; Baronnet, Alain; Jankovsky, Filip; Gilles, Christian; Mihaljevic, Martin; Sebek, Ondrej; Strnad, Ladislav; Bezdicka, Petr

    2005-12-01

    The mineralogy and solubility of air-pollution-control (APC) residues from a secondary lead (Pb) smelter have been studied on samples from the Príbram smelter, Czech Republic, recycling car batteries, with the emphasis on their potential environmental effect. The presence of dominant anglesite (PbSO4) and laurionite (Pb(OH)Cl) was observed in a sintered residue from after-burning chambers (800-1000 degrees C). In contrast, low-temperature Pb-bearing phases, such as KCl x 2PbCl2 and caracolite (Na3Pb2(SO4)3Cl), were detected in the major APC residue from bag-type fabric filters. Metallic elements, zinc (Zn), cadmium (Cd), and tin (Sn) were found homogeneously distributed within this residue. The formation of anglesite, cotunnite (PbCl2), (Zn,Cd)2SnO4, and (Sb,As)2O3 was observed during the sintering of this APC residue at 500 degrees C in a rotary furnace. The 168 h leaching test on filter residue, representing the fraction that may escape the flue gas treatment system, indicated rapid release of Pb and other contaminants. Caracolite and KCl x 2PbCl2 are significantly dissolved, and anglesite and cotunnite form the alteration products, as was confirmed by mineralogical analysis and PHREEQC-2 modeling. The observed Pb-bearing chlorides have significantly higher solubility than anglesite and, following emission from the smelter stack, can readily dissolve, transferring Pb into the environmental milieu (soils, water, inhabited areas).

  13. Characterization of air pollution control residues produced in a municipal solid waste incinerator in Portugal.

    PubMed

    Quina, Margarida J; Santos, Regina C; Bordado, João C; Quinta-Ferreira, Rosa M

    2008-04-01

    This study is mainly related with the physical and chemical characterization of a solid waste, produced in a municipal solid waste (MSW) incineration process, which is usually referred as air pollution control (APC) residue. The moisture content, loss on ignition (LOI), particle size distribution, density, porosity, specific surface area and morphology were the physical properties addressed here. At the chemical level, total elemental content (TC), total availability (TA) and the leaching behaviour with compliance tests were determined, as well as the acid neutralization capacity (ANC). The main mineralogical crystalline phases were identified, and the thermal behaviour of the APC residues is also shown. The experimental work involves several techniques such as laser diffraction spectrometry, mercury porosimetry, helium pycnometry, gas adsorption, flame atomic absorption spectrometry (FAAS), ion chromatography, scanning electron microscopy (SEM), X-ray fluorescence (XRF), X-ray diffraction (XRD) and simultaneous thermal analysis (STA). The results point out that the APC residues do not comply with regulations in force at the developed countries, and therefore the waste should be considered hazardous. Among the considered heavy metals, lead, zinc and chromium were identified as the most problematic ones, and their total elemental quantities are similar for several samples collected in an industrial plant at different times. Moreover, the high amount of soluble salts (NaCl, KCl, calcium compounds) may constitute a major problem and should be taken into account for all management strategies. The solubility in water is very high (more than 24% for a solid/liquid ratio of 10) and thus the possible utilizations of this residue are very limited, creating difficulties also in the ordinary treatments, such as in solidification/stabilization with binders.

  14. Influences of ammonia contamination on leaching from air-pollution-control residues.

    PubMed

    Guan, Zhenzhen; Chen, Dezhen; Astrup, Thomas Fruergaard

    2014-12-01

    Application of selective non-catalytic reduction systems at municipal solid waste incinerators (MSWIs) often involves over-stoichiometric injection of ammonia into flue gases. Un-reacted ammonia may be deposited on fly ash particles and can ultimately influence the leaching behaviour of air-pollution-control (APC) residues. Batch tests were conducted to investigate the impacts of ammonia levels on leaching of a range of metals (sodium, potassium, calcium, aluminium, chromium, iron, lead, cadmium, copper, nickel and zinc), as well as chloride and dissolved organic carbon (DOC). Specific conductivity was also identified to reflect the soluble components. The results showed that with ammonia concentrations rising from a background level of 4 to 26,400 mg l(-1), the specific conductivity increased by 2-7 times as pH varied from alkaline to acidic values. DOC release was also significantly enhanced with high ammonia levels of 1400 mg l(-1) or higher at pH > 9; however at these high ammonia concentrations, the role of DOC in cadmium, copper, nickel and zinc leaching was negligible. Based on the experimental data, chloride, sodium and potassium were leached at high concentrations regardless of pH and ammonia concentrations. For aluminium, chromium, iron and lead, ammonia had little impact on their leaching behaviour. With respect to cadmium, copper, nickel and zinc, high ammonia concentrations significantly increased leaching in the pH range of 8-12 due to the formation of metal-ammonia complexes, which was also proved in the speciation calculations. However, the overall results suggest that typical levels of ammonia injection in MSWIs are not likely to affect metal leaching from APC residues. PMID:25147306

  15. Influences of ammonia contamination on leaching from air-pollution-control residues.

    PubMed

    Guan, Zhenzhen; Chen, Dezhen; Astrup, Thomas Fruergaard

    2014-12-01

    Application of selective non-catalytic reduction systems at municipal solid waste incinerators (MSWIs) often involves over-stoichiometric injection of ammonia into flue gases. Un-reacted ammonia may be deposited on fly ash particles and can ultimately influence the leaching behaviour of air-pollution-control (APC) residues. Batch tests were conducted to investigate the impacts of ammonia levels on leaching of a range of metals (sodium, potassium, calcium, aluminium, chromium, iron, lead, cadmium, copper, nickel and zinc), as well as chloride and dissolved organic carbon (DOC). Specific conductivity was also identified to reflect the soluble components. The results showed that with ammonia concentrations rising from a background level of 4 to 26,400 mg l(-1), the specific conductivity increased by 2-7 times as pH varied from alkaline to acidic values. DOC release was also significantly enhanced with high ammonia levels of 1400 mg l(-1) or higher at pH > 9; however at these high ammonia concentrations, the role of DOC in cadmium, copper, nickel and zinc leaching was negligible. Based on the experimental data, chloride, sodium and potassium were leached at high concentrations regardless of pH and ammonia concentrations. For aluminium, chromium, iron and lead, ammonia had little impact on their leaching behaviour. With respect to cadmium, copper, nickel and zinc, high ammonia concentrations significantly increased leaching in the pH range of 8-12 due to the formation of metal-ammonia complexes, which was also proved in the speciation calculations. However, the overall results suggest that typical levels of ammonia injection in MSWIs are not likely to affect metal leaching from APC residues.

  16. Treatment of air pollution control residues with iron rich waste sulfuric acid: does it work for antimony (Sb)?

    PubMed

    Okkenhaug, Gudny; Breedveld, Gijs D; Kirkeng, Terje; Lægreid, Marit; Mæhlum, Trond; Mulder, Jan

    2013-03-15

    Antimony (Sb) in air pollution control (APC) residues from municipal solid waste incineration has gained increased focus due to strict Sb leaching limits set by the EU landfill directive. Here we study the chemical speciation and solubility of Sb at the APC treatment facility NOAH Langøya (Norway), where iron (Fe)-rich sulfuric acid (∼3.6M, 2.3% Fe(II)), a waste product from the industrial extraction of ilmenite, is used for neutralization. Antimony in water extracts of untreated APC residues occurred exclusively as pentavalent antimonate, even at low pH and Eh values. The Sb solubility increased substantially at pH<10, possibly due to the dissolution of ettringite (at alkaline pH) or calcium (Ca)-antimonate. Treated APC residues, stored anoxically in the laboratory, simulating the conditions at the NOAH Langøya landfill, gave rise to decreasing concentrations of Sb in porewater, occurring exclusively as Sb(V). Concentrations of Sb decreased from 87-918μgL(-1) (day 3) to 18-69μgL(-1) (day 600). We hypothesize that an initial sorption of Sb to Fe(II)-Fe(III) hydroxides (green rust) and eventually precipitation of Ca- and Fe-antimonates (tripuhyite; FeSbO4) occurred. We conclude that Fe-rich, sulfuric acid waste is efficient to immobilize Sb in APC residues from waste incineration. PMID:23465722

  17. Evaluating the fate of metals in air pollution control residues from coal-fired power plants

    EPA Science Inventory

    Changes in air pollution control at coal-fired power plants are shifting mercury (Hg) and other metals from the flue gas at electric utilities to the coal ash. This paper presents data from the characterization of73 coal combustion residues (CCRs) evaluating the composition and c...

  18. The influence of electrodialytic remediation on dioxin (PCDD/PCDF) levels in fly ash and air pollution control residues.

    PubMed

    Dias-Ferreira, Celia; Kirkelund, Gunvor M; Jensen, Pernille E

    2016-04-01

    Fly ash and Air Pollution Control (APC) residues collected from three municipal solid waste incinerators in Denmark and Greenland were treated by electrodialytic remediation at pilot scale for 8-10 h. This work presents for the first time the effect of electrodialytic treatment on polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF), and how these levels impact on the valorization options for fly ash and APC residue. PCDD/PCDF levels in the original residues ranged between 4.85 and 197 ng g(-1), being higher for the electrostatic precipitator fly ash. The toxic equivalent (TEQ) varied ten fold, ranging 0.18-2.0 ng g(-1) I-TEQ, with penta and hexa-homologs being most significant for toxicity. After the electrodialytic treatment PCDD/PCDF levels increased in the residues (between 1.4 and 2.0 times). This does not mean PCDD/PCDF were synthesized, but else that soluble materials dissolve, leaving behind the non-water soluble compounds, such as PCDD/PCDF. According to the Basel Convention, PCDD/PCDF levels in these materials is low (<15 μg WHO-TEQ kg(-1)) and the fly ash and APC residue could eventually be valorized, for instance as construction material, provided end-of-waste criteria are set and that a risk assessment of individual options is carried out, including the end-of-life stage when the materials become waste again.

  19. The influence of electrodialytic remediation on dioxin (PCDD/PCDF) levels in fly ash and air pollution control residues.

    PubMed

    Dias-Ferreira, Celia; Kirkelund, Gunvor M; Jensen, Pernille E

    2016-04-01

    Fly ash and Air Pollution Control (APC) residues collected from three municipal solid waste incinerators in Denmark and Greenland were treated by electrodialytic remediation at pilot scale for 8-10 h. This work presents for the first time the effect of electrodialytic treatment on polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF), and how these levels impact on the valorization options for fly ash and APC residue. PCDD/PCDF levels in the original residues ranged between 4.85 and 197 ng g(-1), being higher for the electrostatic precipitator fly ash. The toxic equivalent (TEQ) varied ten fold, ranging 0.18-2.0 ng g(-1) I-TEQ, with penta and hexa-homologs being most significant for toxicity. After the electrodialytic treatment PCDD/PCDF levels increased in the residues (between 1.4 and 2.0 times). This does not mean PCDD/PCDF were synthesized, but else that soluble materials dissolve, leaving behind the non-water soluble compounds, such as PCDD/PCDF. According to the Basel Convention, PCDD/PCDF levels in these materials is low (<15 μg WHO-TEQ kg(-1)) and the fly ash and APC residue could eventually be valorized, for instance as construction material, provided end-of-waste criteria are set and that a risk assessment of individual options is carried out, including the end-of-life stage when the materials become waste again. PMID:26826780

  20. [Modeling research on impact of pH on metals leaching behavior of air pollution control residues from MSW incinerator].

    PubMed

    Zhang, Hua; He, Pin-Jing; Li, Xin-Jie; Shao, Li-Ming

    2008-01-01

    Metals leaching behavior of air pollution control residues (APC residues) from municipal solid waste incinerator (MSWI) is greatly dependent on the leachate pH. pH-varying leaching tests and Visual MINTEQ modeling were conducted to investigate the mechanism of pH effect on the metals leaching characteristics from MSWI APC residues. Results show that, under acidic environment (for Cd, Zn, and Ni, pH < 8; for Pb, Cu, and Cr, pH < 6; for Al, pH < 4), leaching concentrations of metals increase greatly with the decrease of pH. Release of amphoteric metals, Pb and Zn, can be induced in strong alkaline leachate, reaching to 42 and 2.4 mg x L(-1) at pH 12.5 respectively. The equilibrium modeling results are well in agreement with the analyzed leaching concentrations. Variation of leachate pH changes the metals speciation in the leaching system, thus influencing their leaching concentrations. Speciation and leaching behavior of Pb, Zn, Cu, Ca, and Al mainly depend on their dissolution/precipitation reactions under different leachate pH. Leachability of Cd, Cr, and Ni can be lowered under acidic and neutral leachate pH due to HFO adsorption, while under alkaline conditions, the effect of adsorption is not significant and dissolution/precipitation becomes the major reactions controlling the leaching toxicity of these heavy metals.

  1. Air pollution control residues from waste incineration: current UK situation and assessment of alternative technologies.

    PubMed

    Rani, D Amutha; Boccaccini, A R; Deegan, D; Cheeseman, C R

    2008-11-01

    Current disposal options for APC residues in the UK and alternative treatment technologies developed world-wide have been reviewed. APC residues are currently landfilled in the UK where they undergo in situ solidification, although the future acceptability of this option is uncertain because the EU waste acceptance criteria (WAC) introduce strict limits on leaching that are difficult to achieve. Other APC residue treatment processes have been developed which are reported to reduce leaching to below relevant regulatory limits. The Ferrox process, the VKI process, the WES-PHix process, stabilisation/solidification using cementitious binders and a range of thermal treatment processes are reviewed. Thermal treatment technologies convert APC residues combined with other wastes into inert glass or glass-ceramics that encapsulate heavy metals. The waste management industry will inevitably use the cheapest available option for treating APC residues and strict interpretation and enforcement of waste legislation is required if new, potentially more sustainable technologies are to become commercially viable.

  2. Element composition and mineralogical characterisation of air pollution control residue from UK energy-from-waste facilities.

    PubMed

    Bogush, Anna; Stegemann, Julia A; Wood, Ian; Roy, Amitava

    2015-02-01

    Air pollution control (APC) residues from energy-from-waste (EfW) are alkaline (corrosive) and contain high concentrations of metals, such as zinc and lead, and soluble salts, such as chlorides and sulphates. The EPA 3050B-extractable concentrations of 66 elements, including critical elements of strategic importance for advanced electronics and energy technologies, were determined in eight APC residues from six UK EfW facilities. The concentrations of Ag (6-15 mg/kg) and In (1-13 mg/kg), as well as potential pollutants, especially Zn (0.26-0.73 wt.%), Pb (0.05-0.2 wt.%), As, Cd, Cu, Mo, Sb, Sn and Se were found to be enriched in all APC residues compared to average crustal abundances. Results from a combination of scanning electron microscopy with energy dispersive X-ray spectroscopy and also powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy give an exceptionally full understanding of the mineralogy of these residues, which is discussed in the context of other results in the literature. The present work has shown that the bulk of the crystalline phases present in the investigated APC residues include Ca-based phases, such as CaCl(x)OH(2-x), CaCO3, Ca(OH)2, CaSO4, and CaO, as well as soluble salts, such as NaCl and KCl. Poorly-crystalline aragonite was identified by FTIR. Sulphur appears to have complex redox speciation, presenting as both anhydrite and hannebachite in some UK EfW APC residues. Hazardous elements (Zn and Pb) were widely associated with soluble Ca- and Cl-bearing phases (e.g. CaCl(x)OH(2-x) and sylvite), as well as unburnt organic matter and aluminosilicates. Specific metal-bearing minerals were also detected in some samples: e.g., Pb present as cerussite; Zn in gahnite, zincowoodwardite and copper nickel zinc oxide; Cu in tenorite, copper nickel zinc oxide and fedotovite. Aluminium foil pieces were present and abundantly covered by fine phases, particularly in any cracks, probably in the form of Friedel's salt

  3. Element composition and mineralogical characterisation of air pollution control residue from UK energy-from-waste facilities.

    PubMed

    Bogush, Anna; Stegemann, Julia A; Wood, Ian; Roy, Amitava

    2015-02-01

    Air pollution control (APC) residues from energy-from-waste (EfW) are alkaline (corrosive) and contain high concentrations of metals, such as zinc and lead, and soluble salts, such as chlorides and sulphates. The EPA 3050B-extractable concentrations of 66 elements, including critical elements of strategic importance for advanced electronics and energy technologies, were determined in eight APC residues from six UK EfW facilities. The concentrations of Ag (6-15 mg/kg) and In (1-13 mg/kg), as well as potential pollutants, especially Zn (0.26-0.73 wt.%), Pb (0.05-0.2 wt.%), As, Cd, Cu, Mo, Sb, Sn and Se were found to be enriched in all APC residues compared to average crustal abundances. Results from a combination of scanning electron microscopy with energy dispersive X-ray spectroscopy and also powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy give an exceptionally full understanding of the mineralogy of these residues, which is discussed in the context of other results in the literature. The present work has shown that the bulk of the crystalline phases present in the investigated APC residues include Ca-based phases, such as CaCl(x)OH(2-x), CaCO3, Ca(OH)2, CaSO4, and CaO, as well as soluble salts, such as NaCl and KCl. Poorly-crystalline aragonite was identified by FTIR. Sulphur appears to have complex redox speciation, presenting as both anhydrite and hannebachite in some UK EfW APC residues. Hazardous elements (Zn and Pb) were widely associated with soluble Ca- and Cl-bearing phases (e.g. CaCl(x)OH(2-x) and sylvite), as well as unburnt organic matter and aluminosilicates. Specific metal-bearing minerals were also detected in some samples: e.g., Pb present as cerussite; Zn in gahnite, zincowoodwardite and copper nickel zinc oxide; Cu in tenorite, copper nickel zinc oxide and fedotovite. Aluminium foil pieces were present and abundantly covered by fine phases, particularly in any cracks, probably in the form of Friedel's salt.

  4. Performance of a biogas upgrading process based on alkali absorption with regeneration using air pollution control residues.

    PubMed

    Baciocchi, Renato; Carnevale, Ennio; Costa, Giulia; Gavasci, Renato; Lombardi, Lidia; Olivieri, Tommaso; Zanchi, Laura; Zingaretti, Daniela

    2013-12-01

    This work analyzes the performance of an innovative biogas upgrading method, Alkali absorption with Regeneration (AwR) that employs industrial residues and allows to permanently store the separated CO2. This process consists in a first stage in which CO2 is removed from the biogas by means of chemical absorption with KOH or NaOH solutions followed by a second stage in which the spent absorption solution is contacted with waste incineration Air Pollution Control (APC) residues. The latter reaction leads to the regeneration of the alkali reagent in the solution and to the precipitation of calcium carbonate and hence allows to reuse the regenerated solution in the absorption process and to permanently store the separated CO2 in solid form. In addition, the final solid product is characterized by an improved environmental behavior compared to the untreated residues. In this paper the results obtained by AwR tests carried out in purposely designed demonstrative units installed in a landfill site are presented and discussed with the aim of verifying the feasibility of this process at pilot-scale and of identifying the conditions that allow to achieve all of the goals targeted by the proposed treatment. Specifically, the CO2 removal efficiency achieved in the absorption stage, the yield of alkali regeneration and CO2 uptake resulting for the regeneration stage, as well as the leaching behavior of the solid product are analyzed as a function of the type and concentration of the alkali reagent employed for the absorption reaction.

  5. Element composition and mineralogical characterisation of air pollution control residue from UK energy-from-waste facilities

    SciTech Connect

    Bogush, Anna; Stegemann, Julia A.; Wood, Ian; Roy, Amitava

    2015-02-15

    Highlights: • 66 elements, including “critical strategic elements” were determined in UK EfW APC residues. • Metal pollutants (Zn, Pb, As, Cd, Cu, Mo, Sb, Sn, Se, Ag and In) are enriched in APC residues. • Metal pollutants were widely associated with fine deposits of highly soluble CaCl{sub x}OH{sub 2−x}. • Specific metal (Zn, Pb, Cu)-bearing minerals were also detected in APC residues. - Abstract: Air pollution control (APC) residues from energy-from-waste (EfW) are alkaline (corrosive) and contain high concentrations of metals, such as zinc and lead, and soluble salts, such as chlorides and sulphates. The EPA 3050B-extractable concentrations of 66 elements, including critical elements of strategic importance for advanced electronics and energy technologies, were determined in eight APC residues from six UK EfW facilities. The concentrations of Ag (6–15 mg/kg) and In (1–13 mg/kg), as well as potential pollutants, especially Zn (0.26–0.73 wt.%), Pb (0.05–0.2 wt.%), As, Cd, Cu, Mo, Sb, Sn and Se were found to be enriched in all APC residues compared to average crustal abundances. Results from a combination of scanning electron microscopy with energy dispersive X-ray spectroscopy and also powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy give an exceptionally full understanding of the mineralogy of these residues, which is discussed in the context of other results in the literature. The present work has shown that the bulk of the crystalline phases present in the investigated APC residues include Ca-based phases, such as CaCl{sub x}OH{sub 2−x}, CaCO{sub 3}, Ca(OH){sub 2}, CaSO{sub 4}, and CaO, as well as soluble salts, such as NaCl and KCl. Poorly-crystalline aragonite was identified by FTIR. Sulphur appears to have complex redox speciation, presenting as both anhydrite and hannebachite in some UK EfW APC residues. Hazardous elements (Zn and Pb) were widely associated with soluble Ca- and Cl-bearing phases

  6. Hydrological and geochemical factors controlling the leaching of cemented MSWI air pollution control residues: A lysimeter field study

    NASA Astrophysics Data System (ADS)

    Ludwig, Christian; Johnson, C. Annette; Käppeli, Michael; Ulrich, Andrea; Riediker, Sonja

    2000-03-01

    A pilot landfill (area, 16 m 2; depth 1.5 m) containing cement-stabilized air pollution control (APC) residues from municipal solid waste incinerators (MSWI) was investigated in order to determine the hydrological and geochemical factors that control the leaching process. Between May and August 1996, 3 rain events were investigated. Rainfall and discharge were monitored and leachate samples taken for the analysis of major components. It was found that water from the rain events took 2-3 days to pass through the lysimeter. Leachate dilution at the beginning of rain events indicated that rainwater passed through the lysimeter as preferential flow. The change in the concentration of leachate components with time was found to be almost identical for most components. Conductivity, dominated by Na + and OH -, also positively correlated with the concentrations of Al, Cs, K, Si, sulfate, chloride, carbonate and organic substances in the drainage discharge. The Ca concentrations were not influenced by the rain events, indicating that this component was leached by rainwater from the lysimeter cover layer. This was also found to apply to observed changes in Sr concentrations. Both conductivity and Sr were used as tracers for rainwater in the leachate and results agreed well. The solubility of the main constituents, Ca, Si, and Al could be explained by thermodynamic equilibrium with the solids calcium silicate hydrate, ettringite and possibly K-feldspar. The results indicate that the leaching process (within the first 5 years) is dominated by pore waters between the cement blocks that are in equilibrium with the cement-stabilized APC residues (thus explaining the constant composition of the leachate) and is flushed out by rain events.

  7. Effects of injected activated carbon and solidification treatment on the leachability of polychlorinated dibenzo-p-dioxins and dibenzofurans from air pollution control residues of municipal waste incineration.

    PubMed

    Hsi, Hsing-Cheng; Wang, Lin-Chi; Yu, Tsung-Hsien

    2007-04-01

    To assess the effectiveness of the injected activated carbon, cement, and sulfur-containing chelating agent in controlling polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) release from the surface of air pollution control (APC) residues, this study examined the leachability of PCDD/Fs from APC residues generated by municipal solid waste incinerators. Results showed that PCDD/Fs were stably retained in the APC residues when the samples were leached with acetic acid solution. Highly chlorinated PCDD/F homologues (i.e., hepta- and octa-CDDs and CDFs) were relatively easy to leach. The leaching percentages of PCDD/Fs from raw APC residue samples containing activated carbon were smaller than those from samples without activated carbon, especially when n-hexane was used as the leachant. These results indicate that the flue gas injected activated carbon not only controls PCDD/F emissions, but also suppresses the leachability of PCDD/Fs from the APC residues. Solidification/stabilization (S/S) processes with 30wt% cement and 5wt% sulfur-containing agent can additionally decrease the leachability of PCDD/Fs with humic acid. Using n-hexane as the leachant, S/S processes increased the leachability of PCDD/Fs. Various low chlorinated PCDD/F congeners were moreover leached out of the APC residue samples, markedly increasing the leachate toxicity. The enhancement of leachability and toxicity owing to S/S processes may negatively impact the environment when APC residues are exposed to nonpolar organic solvents.

  8. Utilization of air pollution control residues for the stabilization/solidification of trace element contaminated soil.

    PubMed

    Travar, I; Kihl, A; Kumpiene, J

    2015-12-01

    The aim of this study was to evaluate the stabilization/solidification (S/S) of trace element-contaminated soil using air pollution control residues (APCRs) prior to disposal in landfill sites. Two soil samples (with low and moderate concentrations of organic matter) were stabilized using three APCRs that originated from the incineration of municipal solid waste, bio-fuels and a mixture of coal and crushed olive kernels. Two APCR/soil mixtures were tested: 30% APCR/70% soil and 50% APCR/50% soil. A batch leaching test was used to study immobilization of As and co-occurring metals Cr, Cu, Pb and Zn. Solidification was evaluated by measuring the unconfined compression strength (UCS). Leaching of As was reduced by 39-93% in APCR/soil mixtures and decreased with increased amounts of added APCR. Immobilization of As positively correlated with the amount of Ca in the APCR and negatively with the amount of soil organic matter. According to geochemical modelling, the precipitation of calcium arsenate (Ca3(AsO4)2/4H2O) and incorporation of As in ettringite (Ca6Al2(SO4)3(OH)12 · 26H2O) in soil/APCR mixtures might explain the reduced leaching of As. A negative effect of the treatment was an increased leaching of Cu, Cr and dissolved organic carbon. Solidification of APCR/soil was considerably weakened by soil organic matter.

  9. Recycling potential of air pollution control residue from sewage sludge thermal treatment as artificial lightweight aggregates.

    PubMed

    Bialowiec, Andrzej; Janczukowicz, Wojciech; Gusiatin, Zygmunt M; Thornton, Arthur; Rodziewicz, Joanna; Zielinska, Magdalena

    2014-03-01

    Thermal treatment of sewage sludge produces fly ash, also known as the air pollution control residue (APCR), which may be recycled as a component of artificial lightweight aggregates (ALWA). Properties of APCR are typical: high content of Ca, Mg, P2O5, as well as potential to induce alkaline reactions. These properties indicate that ALWA prepared with a high content of APCR may remove heavy metals, phosphorus, and ammonium nitrogen from wastewater with high efficiency. The aim of this preliminary study was to determine the optimal composition of ALWA for potential use as a filter media in wastewater treatment systems. Five kinds of ALWA were produced, with different proportions of ash (shown as percentages in subscripts) in mixture with bentonite: ALWA0 (reference), ALWA12.5, ALWA25, ALWA50, and ALWA100. The following parameters of ALWA were determined: density, bulk density, compressive strength, hydraulic conductivity, and removal efficiency of ions Zn(2+), NH4 (+), and PO4 (3-). Tests showed that ALWA had good mechanical and hydraulic properties, and might be used in wastewater filtering systems. Phosphates and zinc ions were removed with high efficiency (80-96%) by ALWA25-100 in static (batch) conditions. The efficiency of ammonium nitrogen removal was low, <18%. Artificial wastewater treatment performance in dynamic conditions (through-flow), showed increasing removal efficiency of Zn(2+), PO4 (3-) with a decrease in flow rate.

  10. Evaluation of the leachability of polychlorinated dibenzo-p-dioxins and dibenzofurans in raw and solidified air pollution control residues from municipal waste incinerators.

    PubMed

    Hsi, Hsing-Cheng; Yu, Tsung-Hsien

    2007-04-01

    Leachability of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from raw and solidified air pollution control (APC) residues with selected solvents, including acetic acid, simulated acid rain, humic acid, linear alkylbenzene sulfonate (LAS) and n-hexane was investigated. High-chlorinated PCDD/F congeners were observed in all leachates of raw APC residue samples, with the largest total leaching concentration (61.60 ngm(-3); 0.30 ngI-TEQm(-3)) from treatment with humic acid. Low-chlorinated congeners were mainly leached with LAS and n-hexane. Solidification and stabilization (S/S) processes with cement and sulfur-containing chelating agent decreased the leachability of PCDD/Fs by up to 98% with humic acid and LAS as solvents. However, S/S processes enhanced the leachability of both high- and low-chlorinated PCDD/F congeners with n-hexane as the solvent, which largely increased the toxic equivalent quantity of leachates. These results suggest that conventional S/S processes may effectively restrain the release of PCDD/Fs when APC residues are leached with rain water or natural organic compounds (e.g., humic acid), but may have a deteriorated effect when APC residues are leached with nonpolar organic solvents (e.g., n-hexane) coexisting in the landfill sites.

  11. The fate of mercury collected from air pollution control devices

    EPA Science Inventory

    The mercury that enters a coal-fired power plant, originates from the coal that is burned, and leaves through the output streams that include stack emissions and air pollution control (APC) residues (either in solid or liquid form). This article describes recent fmdings on the fa...

  12. Thermal treatment of stabilized air pollution control residues in a waste incinerator pilot plant. Part 1: Fate of elements and dioxins.

    PubMed

    Bergfeldt, Brita; Jay, Klaus; Seifert, Helmuth; Vehlow, Jürgen; Christensen, Thomas H; Baun, Dorthe L; Mogensen, Erhardt P B

    2004-02-01

    Air pollution control (APC) residues from municipal solid waste incinerator plants that are treated by means of the Ferrox process can be more safely disposed of due to reduction of soluble salts and stabilization of heavy metals in an iron oxide matrix. Further stabilization can be obtained by thermal treatment inside a combustion chamber of a municipal solid waste incinerator. The influence of the Ferrox products on the combustion process, the quality of the residues, and the partitioning of heavy metals between the various solids and the gas have been investigated in the Karlsruhe TAM-ARA pilot plant for waste incineration. During the experiments only few parameters were influenced. An increase in the SO2 concentration in the raw gas and slightly lower temperatures in the fuel bed could be observed compared with reference tests. Higher contents of Fe and volatile heavy metals such as Zn, Cd, Pb and partly Hg in the Ferrox products lead to increased concentration of these elements in the solid residues of the co-feeding tests. Neither the burnout nor the PCDD/F formation was altered by the addition of the Ferrox products. Co-feeding of treated APC residues seems to be a feasible approach for obtaining a single solid residue from waste incineration.

  13. Incubation of air-pollution-control residues from secondary Pb smelter in deciduous and coniferous organic soil horizons: leachability of lead, cadmium and zinc.

    PubMed

    Chrastný, Vladislav; Vaněk, Aleš; Komárek, Michael; Farkaš, Juraj; Drábek, Ondřej; Vokurková, Petra; Němcová, Jana

    2012-03-30

    The leachability of air-pollution-control (APC) residues from a secondary lead smelter in organic soil horizons (F and H) from a deciduous and a coniferous forest during incubation periods of 0, 3 and 6 months were compared in this work. While the concentration of Pb, Zn and Cd associated with the exchangeable/acid extractable fraction in the horizon F from the coniferous forest was higher compared to the deciduous, significantly lower concentrations in the humified horizon H was found. It is suggested that lower pH and a higher share of fulvic acids fraction (FAs) of solid phase soil organic matter (SOM) in the humified soil horizon H from the coniferous compared to the deciduous forest is responsible for a higher metal association with solid phase SOM and therefore a lower metal leaching in a soil system. From this point of view, the humified soil horizon H from the deciduous forest represents a soil system more vulnerable to Pb, Zn and Cd leaching from APC residues.

  14. Thermal treatment of stabilized air pollution control residues in a waste incinerator pilot plant. Part 2: Leaching characteristics of bottom ashes.

    PubMed

    Baun, Dorthe L; Christensen, Thomas H; Bergfeldt, Brita; Vehlow, Jürgen; Mogensen, Erhardt P B

    2004-02-01

    With the perspective of generating only one solid residue from waste incineration, co-feeding of municipal solid waste and air pollution control residues stabilized by the Ferrox process was investigated in the TAMARA pilot plant incinerator as described in Bergfeldt et al. (Waste Management Research, 22, 49-57, 2004). This paper reports on leaching from the combined bottom ashes. Batch leaching test, pH-static leaching tests, availability tests and column leaching tests were used to characterize the leaching properties. The leaching properties are key information in the context of reuse in construction or in landfilling of the combined residue. In general, the combined bottom ashes had leaching characteristics similar to the reference bottom ash, which contained no APC residue. However, As and Pb showed slightly elevated leaching from the combined bottom ashes, while Cr showed less leaching. The investigated combined bottom ashes had contents of metals comparable to what is expected at steady state after continuous co-feeding of APC residues. Only Cd and Pb were partly volatilized (30-40%) during the incineration process and thus the combined bottom ashes had lower contents of Cd and Pb than expected at steady state. Furthermore, a major loss of Hg was, not surprisingly, seen and co-feeding of Ferrox-products together with municipal solid waste will require dedicated removal of Hg in the flue gas to prevent a build up of Hg in the system. In spite of this, a combined single solid residue from waste incineration seems to be a significant environmental improvement to current technology.

  15. Treatment and use of air pollution control residues from MSW incineration: an overview.

    PubMed

    Quina, Margarida J; Bordado, João C; Quinta-Ferreira, Rosa M

    2008-11-01

    This work reviews strategies for the management of municipal solid waste incineration (MSWI) residues, particularly solid particles collected from flue gases. These tiny particles may be retained by different equipment, with or without additives (lime, activated carbon, etc.), and depending on the different possible combinations, their properties may vary. In industrial plants, the most commonly used equipment for heat recovery and the cleaning of gas emissions are: heat recovery devices (boiler, superheater and economiser); dry, semidry or wet scrubbers; electrostatic precipitators; bag filters; fabric filters, and cyclones. In accordance with the stringent regulations in force in developed countries, these residues are considered hazardous, and therefore must be treated before being disposed of in landfills. Nowadays, research is being conducted into specific applications for these residues in order to prevent landfill practices. There are basically two possible ways of handling these residues: landfill after adequate treatment or recycling as a secondary material. The different types of treatment may be grouped into three categories: separation processes, solidification/stabilization, and thermal methods. These residues generally have limited applications, mainly due to the fact that they tend to contain large quantities of soluble salts (NaCl, KCl, calcium compounds), significant amounts of toxic heavy metals (Pb, Zn, Cr, Cu, Ni, Cd) in forms that may easily leach out, and trace quantities of very toxic organic compounds (dioxin, furans). The most promising materials for recycling this residue are ceramics and glass-ceramic materials. The main purpose of the present paper is to review the published literature in this field. A range of studies have been summarized in a series of tables focusing upon management strategies used in various countries, waste composition, treatment processes and possible applications.

  16. AIR POLLUTION CONTROL TECHNOLOGIES

    EPA Science Inventory

    This is a chapter for John Wiley & Son's Mechanical Engineers' Handbook, and covers issues involving air pollution control. Various technologies for controlling sulfur oxides is considered including fuel desulfurization. It also considers control of nitrogen oxides including post...

  17. Sequestration of flue gas CO₂ by direct gas-solid carbonation of air pollution control system residues.

    PubMed

    Tian, Sicong; Jiang, Jianguo

    2012-12-18

    Direct gas-solid carbonation reactions of residues from an air pollution control system (APCr) were conducted using different combinations of simulated flue gas to study the impact on CO₂ sequestration. X-ray diffraction analysis of APCr determined the existence of CaClOH, whose maximum theoretical CO₂ sequestration potential of 58.13 g CO₂/kg APCr was calculated by the reference intensity ratio method. The reaction mechanism obeyed a model of a fast kinetics-controlled process followed by a slow product layer diffusion-controlled process. Temperature is the key factor in direct gas-solid carbonation and had a notable influence on both the carbonation conversion and the CO₂ sequestration rate. The optimal CO₂ sequestrating temperature of 395 °C was easily obtained for APCr using a continuous heating experiment. CO₂ content in the flue gas had a definite influence on the CO₂ sequestration rate of the kinetics-controlled process, but almost no influence on the final carbonation conversion. Typical concentrations of SO₂ in the flue gas could not only accelerate the carbonation reaction rate of the product layer diffusion-controlled process, but also could improve the final carbonation conversion. Maximum carbonation conversions of between 68.6% and 77.1% were achieved in a typical flue gas. Features of rapid CO₂ sequestration rate, strong impurities resistance, and high capture conversion for direct gas-solid carbonation were proved in this study, which presents a theoretical foundation for the applied use of this encouraging technology on carbon capture and storage.

  18. Fate of mercury collected from air pollution control devices

    SciTech Connect

    Constance L. Senior; Susan Thorneloe; Bernine Khan; David Goss

    2009-07-15

    Mercury that enters a coal-fired power plant originates from the coal that is burned and leaves through the output streams, which include stack emissions and air pollution control (APC) residues (either in solid or liquid form). This article describes recent findings on the fate and environmental stability of mercury in coal combustion residues (CCRs) such as fly ash and solid products from flue gas desulfurization (FGD) scrubbers when either disposed or reused in agricultural, commercial, or engineering applications. 19 refs., 4 figs., 5 tabs.

  19. Air Pollution Control, Part I.

    ERIC Educational Resources Information Center

    Strauss, Werner, Ed.

    Authoritative reviews in seven areas of current importance in air pollution control are supplied in this volume, the first of a two-part set. Titles contained in this book are: "Dispersion of Pollutants Emitted into the Atmosphere,""The Formation and Control of Oxides of Nitrogen in Air Pollution,""The Control of Sulfur Emissions from Combustion…

  20. Air Pollution Control, Part II.

    ERIC Educational Resources Information Center

    Strauss, Werner, Ed.

    This book contains five major articles in areas of current importance in air pollution control. They are written by authors who are actively participating in the areas on which they report. It is the aim of each article to completely cover theory, experimentation, and practice in the field discussed. The contents are as follows: Emissions,…

  1. 76 FR 298 - Revisions to the California State Implementation Plan, San Joaquin Valley Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... Valley Unified Air Pollution Control District (SJVUAPCD) portion of the California State Implementation......... 12/17/92 08/24/07 On September 17, 2007, the submittal for San Joaquin Valley Unified Air Pollution... require that fixed covers be equipped with a 95% efficient Air Pollution Control (APC) device. c....

  2. Effect of drying on leaching testing of treated municipal solid waste incineration APC-residues.

    PubMed

    Hu, Yuyan; Hyks, Jiri; Astrup, Thomas; Christensen, Thomas H

    2008-08-01

    Air-pollution-control (APC) residues from waste incinerators are hazardous waste according to European legislation and must be treated prior to landfilling. Batch and column leaching data determine which type of landfill can receive the treated APC-residues. CEN standards are prescribed for the batch and column leaching test; however, these standards do not specify whether or not the residue samples should be dried prior to the leaching testing. Laboratory tests were performed in parallel (dried/non-dried) on treated APC-residue samples and evaluated with respect to Cr, Cd, Cu, Pb and Zn leaching. The effect of drying of the wet APC-residue samples was particularly dramatic regarding the leaching of Cr. Drying resulted in 10-100 times more Cr leaching in both batch and columns test. Drying also affected the leaching of Cd, Cu and Pb. Initial Cd leaching was up to 100 times higher in column tests with dried APC-residue than in tests with wet residues. The effect of drying appeared to be a combination of decreasing the reduction capacity of the sample (Cr), decreasing pH (Cd, Cu) and in column tests also a wash-out of salts (probably affecting Cd and Pb). If the leaching tests are intended to mimic landfill conditions, the results of this paper suggest that the tests should be done on wet, non-dried residue samples, although this may be less practical than testing dried samples.

  3. A process for treatment of APC residues from municipal solid waste incinerators: Preliminary results

    SciTech Connect

    Hjelmar, O.; Birch, H.

    1997-12-01

    The problem of environmentally safe management of the residues from air pollution control (APC) systems at municipal solid waste (MSW) incinerators, particularly the residues from the semidry/dry acid gas cleaning processes (dry scrubber residues), has not yet been solved in a satisfactory and sustainable manner. These residues are in many cases simply stored indefinitely in big bags or they are landfilled under conditions that in the long term may not be able to prevent potentially harmful constituents from leaching and leaking into the environment. The APC residues, including fly ash, are in many countries classified as hazardous or special waste due to their high contents of soluble salts (particularly calcium chloride) and trace elements/heavy metals. The semidry/dry APC residues are strongly alkaline due to a content of excess lime, and the high pH favours the leaching of several contaminants, particularly lead. This paper presents preliminary results of a study of a process for treatment of semidry/dry APC residues and fly ash from MSW incinerators. In the process the contaminants are partly removed, partly immobilized thus improving the above mentioned situation and allowing for subsequent safe management (i.e. utilization or landfilling) of the treated residues.

  4. Career Guide for Air Pollution Control

    ERIC Educational Resources Information Center

    Baldwin, Lionel V.

    1975-01-01

    This guide to career opportunities in air pollution control includes resource information in this area and provides a listing of colleges and universities offering environmental science programs. The guide was prepared by the S-11 Education and Training Committee of the Air Pollution Control Association. (Author/BT)

  5. Product Guide/1972 [Air Pollution Control Association].

    ERIC Educational Resources Information Center

    Journal of the Air Pollution Control Association, 1971

    1971-01-01

    Reprinted in this pamphlet is the fifth annual directory of air pollution control products as compiled in the "Journal of the Air Pollution Control Association" for December, 1971. The 16-page guide lists manufacturers of emission control equipment and air pollution instrumentation under product classifications as derived from McGraw-Hill's "Air…

  6. Variance Design and Air Pollution Control

    ERIC Educational Resources Information Center

    Ferrar, Terry A.; Brownstein, Alan B.

    1975-01-01

    Air pollution control authorities were forced to relax air quality standards during the winter of 1972 by granting variances. This paper examines the institutional characteristics of these variance policies from an economic incentive standpoint, sets up desirable structural criteria for institutional design and arrives at policy guidelines for…

  7. Topics in Air Pollution Control (SI: 428).

    ERIC Educational Resources Information Center

    Rampacek, Anne; Chaput, Linda

    This course provides information about air pollution control efforts since the passage of the Clean Air Act and places in perspective various issues that have arisen since passage of the act--significant deterioration, maintenance of standards, indirect source review, and transportation controls. Court decisions affecting these issues are cited…

  8. 30 CFR 780.15 - Air pollution control plan.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Air pollution control plan. 780.15 Section 780....15 Air pollution control plan. (a) For all surface mining activities with projected production rates... application shall contain an air pollution control plan which includes the following: (1) An air...

  9. 30 CFR 784.26 - Air pollution control plan.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Air pollution control plan. 784.26 Section 784... § 784.26 Air pollution control plan. For all surface operations associated with underground mining activities, the application shall contain an air pollution control plan which includes the following: (a)...

  10. 30 CFR 784.26 - Air pollution control plan.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Air pollution control plan. 784.26 Section 784... § 784.26 Air pollution control plan. For all surface operations associated with underground mining activities, the application shall contain an air pollution control plan which includes the following: (a)...

  11. 30 CFR 784.26 - Air pollution control plan.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Air pollution control plan. 784.26 Section 784... § 784.26 Air pollution control plan. For all surface operations associated with underground mining activities, the application shall contain an air pollution control plan which includes the following: (a)...

  12. 30 CFR 780.15 - Air pollution control plan.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Air pollution control plan. 780.15 Section 780....15 Air pollution control plan. (a) For all surface mining activities with projected production rates... application shall contain an air pollution control plan which includes the following: (1) An air...

  13. 30 CFR 780.15 - Air pollution control plan.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Air pollution control plan. 780.15 Section 780....15 Air pollution control plan. (a) For all surface mining activities with projected production rates... application shall contain an air pollution control plan which includes the following: (1) An air...

  14. 30 CFR 784.26 - Air pollution control plan.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Air pollution control plan. 784.26 Section 784... § 784.26 Air pollution control plan. For all surface operations associated with underground mining activities, the application shall contain an air pollution control plan which includes the following: (a)...

  15. 30 CFR 784.26 - Air pollution control plan.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Air pollution control plan. 784.26 Section 784... § 784.26 Air pollution control plan. For all surface operations associated with underground mining activities, the application shall contain an air pollution control plan which includes the following: (a)...

  16. 30 CFR 780.15 - Air pollution control plan.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Air pollution control plan. 780.15 Section 780....15 Air pollution control plan. (a) For all surface mining activities with projected production rates... application shall contain an air pollution control plan which includes the following: (1) An air...

  17. 30 CFR 780.15 - Air pollution control plan.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Air pollution control plan. 780.15 Section 780....15 Air pollution control plan. (a) For all surface mining activities with projected production rates... application shall contain an air pollution control plan which includes the following: (1) An air...

  18. Occupational Structures and Profiles in Italy in the Field of Environmental Protection in the Public Service Sector with Reference to Air Pollution Control. CEDEFOP Panorama. National Report.

    ERIC Educational Resources Information Center

    Mannocci, Virgilio; And Others

    A study examined the knowledge and job skills required of persons employed in air pollution control (APC)-related occupations in Italy's public service sector. First, Italian legislation on APC and the functions/powers of Italy's public agencies responsible for APC were reviewed. The organization/operation of the public structures involved in…

  19. Environmental impact of APC residues from municipal solid waste incineration: reuse assessment based on soil and surface water protection criteria.

    PubMed

    Quina, Margarida J; Bordado, João C M; Quinta-Ferreira, Rosa M

    2011-01-01

    Waste management and environmental protection are mandatory requirements of modern society. In our study, air pollution control (APC) residues from municipal solid waste incinerators (MSWI) were considered as a mixture of fly ash and fine particulate solids collected in scrubbers and fabric filters. These are hazardous wastes and require treatment before landfill. Although there are a number of treatment options, it is highly recommended to find practical applications rather than just dump them in landfill sites. In general, for using a construction material, beyond technical specifications also soil and surface water criteria may be used to ensure environmental protection. The Dutch Building Materials Decree (BMD) is a valuable tool in this respect and it was used to investigate which properties do not meet the threshold criteria so that APC residues can be further used as secondary building material. To this end, some scenarios were evaluated by considering release of inorganic species from unmoulded and moulded applications. The main conclusion is that the high amount of soluble salts makes the APC residues a building material prohibited in any of the conditions tested. In case of moulding materials, the limits of heavy metals are complied, and their use in Category 1 would be allowed. However, also in this case, the soluble salts lead to the classification of "building material not allowed". The treatments with phosphates or silicates are able to solve the problem of heavy metals, but difficulties with the soluble salts are still observed. This analysis suggests that for APC residues to comply with soil and surface water protection criteria to be further used as building material at least a pre-treating for removing soluble salts is absolutely required.

  20. Stabilisation/solidification of APC residues from MSW incineration with hydraulic binders and chemical additives.

    PubMed

    Quina, Margarida J; Bordado, João C M; Quinta-Ferreira, Rosa M

    2014-01-15

    This study focuses on the stabilisation/solidification (S/S) treatment of air pollution control (APC) residues from municipal solid waste (MSW) incineration. Six formulations (T1-T6) were tested based on different cements as binders, for the immobilisation of pollutants and to prevent their entering into the environment at unacceptable rates. Soluble phosphates and silicates were considered in some cases to fix heavy metals. The performance of T1-T6 products was measured in terms of initial and final setting times, mechanical strength, total availability and leaching from S/S products. Two monolithic leaching tests were used to estimate emissions of pollutants over 48h and 64 days. The results showed that the setting time was reduced when soluble phosphates were used. Moreover, although all the treatments have met the threshold of 1MPa for unconfined compressive strength, this parameter was significantly reduced due to matrix dissolution during immersion. After three cycles of leaching, the limit of 10% for solubilisation was exceeded for all treatments with the exception of T5 (with phosphates). This study demonstrated that the S/S treatment used at the industrial level can be improved with respect to toxic heavy metals, by using soluble silicates or phosphates, but not regarding soluble salts.

  1. Leaching of APC residues from secondary Pb metallurgy using single extraction tests: the mineralogical and the geochemical approach.

    PubMed

    Ettler, Vojtech; Mihaljevic, Martin; Sebek, Ondrej; Strnad, Ladislav

    2005-05-20

    Two air-pollution-control (APC) residues--one from flue gas cooling with alkaline water and one from deionized water cooling--from secondary lead metallurgy were submitted to two different standardized short-term leaching protocols: US EPA toxicity characteristic leaching procedure (TCLP) and static leaching according to Czech/European norm EN 12457-2. The experimental procedure was coupled with detailed mineralogical investigation of the solid material (SEM, XRPD) and speciation-solubility calculations using the PHREEQC-2 geochemical code. Both types of residues were considered as hazardous materials exhibiting substantial leaching of Pb (up to 7130 mg/l) and other inorganic contaminants. However, the APC residue produced by flue gas cooling with alkaline water (sample B) exhibits more favourable leaching and environmental characteristics than that produced by simple deionised water cooling (sample A). At pH < 5, primary caracolite (Na3Pb2(SO4)3Cl) and potassium lead chloride (KCl.2PbCl2) are completely or partially dissolved and transformed to residual anglesite (PbSO4), cotunnite (PbCl2) and laurionite (Pb(OH)Cl). At pH 5-6, anglesite is still the principal residual product, whereas at pH > 6, phosgenite (PbCl2.PbCO3) became the dominant secondary phase. The results are consistent with the mineralogical and geochemical studies focused on acidic forest soils highly polluted by smelter emissions, where anglesite, as a unique Pb-bearing phase, has been detected. From the technological point of view, the mixing of APC residue with alkaline water, followed by an increase in the suspension pH and equilibration with atmospheric CO2, may be used to ensure the precipitation of less soluble Pb carbonates, which are more easily recycled in the Pb recovery process in the metallurgical plant.

  2. Air pollution control systems in WtE units: an overview.

    PubMed

    Vehlow, J

    2015-03-01

    All WtE (waste-to-energy) plants, based on combustion or other thermal processes, need an efficient gas cleaning for compliance with legislative air emission standards. The development of gas cleaning technologies started along with environment protection regulations in the late 1960s. Modern APC (air pollution control) systems comprise multiple stages for the removal of fly ashes, inorganic and organic gases, heavy metals, and dioxins from the flue gas. The main technologies and devices used for abatement of the various pollutants are described and their basic principles, their peculiarities, and their application are discussed. Few systems for cleaning of synthesis gas from waste gasification plants are included. Examples of APC designs in full scale plants are shown and cautious prospects for the future development of APC systems are made.

  3. VERIFICATION TESTING OF AIR POLLUTION CONTROL TECHNOLOGY QUALITY MANAGEMENT PLAN

    EPA Science Inventory

    This document is the basis for quality assurance for the Air Pollution Control Technology Verification Center (APCT Center) operated under the U.S. Environmental Protection Agency (EPA). It describes the policies, organizational structure, responsibilities, procedures, and qualit...

  4. Environmental impact of APC residues from municipal solid waste incineration: Reuse assessment based on soil and surface water protection criteria

    SciTech Connect

    Quina, Margarida J.; Bordado, Joao C.M.; Quinta-Ferreira, Rosa M.

    2011-09-15

    Highlights: > The Dutch Building Material Decree (BMD) was used to APC residues from MSWI. > BMD is a straightforward tool to calculate expectable loads to the environment of common pollutants. > Chloride load to the environment lead to classification of building material not allowed. > At least a pre-treatment (e.g. washing) is required in order to remove soluble salts. > The stabilization with phosphates or silicates eliminate the problem of heavy metals. - Abstract: Waste management and environmental protection are mandatory requirements of modern society. In our study, air pollution control (APC) residues from municipal solid waste incinerators (MSWI) were considered as a mixture of fly ash and fine particulate solids collected in scrubbers and fabric filters. These are hazardous wastes and require treatment before landfill. Although there are a number of treatment options, it is highly recommended to find practical applications rather than just dump them in landfill sites. In general, for using a construction material, beyond technical specifications also soil and surface water criteria may be used to ensure environmental protection. The Dutch Building Materials Decree (BMD) is a valuable tool in this respect and it was used to investigate which properties do not meet the threshold criteria so that APC residues can be further used as secondary building material. To this end, some scenarios were evaluated by considering release of inorganic species from unmoulded and moulded applications. The main conclusion is that the high amount of soluble salts makes the APC residues a building material prohibited in any of the conditions tested. In case of moulding materials, the limits of heavy metals are complied, and their use in Category 1 would be allowed. However, also in this case, the soluble salts lead to the classification of 'building material not allowed'. The treatments with phosphates or silicates are able to solve the problem of heavy metals, but

  5. Operation of a 1/10 scale mixed water incinerator air pollution control system

    SciTech Connect

    Burns, D.B.; Wong, A.; Walker, W.

    1996-08-01

    The Consolidated Incineration Facility (CIF) at the Savannah River Site is designed to treat solid and liquid RCRA hazardous and mixed wastes generated by site operations and clean-up activities. The technologies selected for use in the CIF air pollution control system (APCS) were based on reviews of existing commercial and DOE incinerators, on-site air pollution control experience, and recommendations from contracted consultants. In order to study the CIF APCS prior to operation, a 1/10 scale pilot facility, known as the Offgas Components Test Facility (OCTF) was constructed and has been in operation since late 1994. Its current mission is to demonstrate the design integrity of the CIF APCS and optimize equipment/instrument performance of the full scale production facility. Due to the nature of the wastes to be incinerated at the CIF, High Efficiency Particulate Air (HEPA) filters are used to remove hazardous and radioactive particulates from the exhaust gas stream before being released into the atmosphere. The HEPA filter change-out frequency has been a potential issue and was the first technical issue to be studied at the OCTF. Tests were conducted to evaluate the performance of HEPA filters under different operating conditions. These tests included evaluating the impact on HEPA life of scrubber operating parameters and the type of HEPA prefilter used. This pilot-scale testing demonstrated satisfactory HEPA filter life when using cleanable metal prefilters and high flows of steam and water in the offgas scrubber.

  6. 75 FR 56889 - Revisions to the California State Implementation Plan, San Diego County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-17

    ...: EPA is taking direct final action to approve revisions to the San Diego County Air Pollution Control... Environmental protection, Air pollution control, Incorporation by reference, Intergovernmental relations.... * * * * * (c) * * * (379) * * * (i) * * * (B) San Diego County Air Pollution Control District. (1) Rule...

  7. Air pollution control system research: An iterative approach to developing affordable systems

    SciTech Connect

    Watt, L.C.; Cannon, F.S.; Heinsohn, R.J.; Spaeder, T.A.; Darvin, C.H.

    1993-12-31

    The research will be accomplished on lab scale, pilot scale, and production air pollution control systems (APCS). The production system, to be installed at Marine Corps Logistics Base (MCLB) Barstow, CA, will treat the exhaust from three paint booths which will be modified to recirculate a large percentage of their exhaust. These recirculation systems are, themselves, a critical element in the overall R and D effort. The goal of the program is to conduct an R and D effort which will improve and demonstrate a combination of technologies intended to make VOC treatment both effective and affordable. The US Marine Corps, the other services and industry will each benefit.

  8. The release of As, Cr and Cu from contaminated soil stabilized with APC residues under landfill conditions.

    PubMed

    Travar, I; Kihl, A; Kumpiene, J

    2015-03-15

    The aim of this study was to investigate the stability of As, Cr and Cu in contaminated soil treated with air pollution control residues under landfill conditions. The influence of landfill gas and temperature on the release of trace elements from stabilized soil was simulated using a diffusion test. The air pollution control residues immobilized As through the precipitation of Ca-As minerals (calcium arsenate (Ca5H2(AsO4)3 × 5H2O), weilite (CaAsO4) and johnbaumite (Ca5(AsO4)3(OH)), incorporation of As into ettringite (Ca6Al2(SO4)3(OH)12 × 26H2O) and adsorption by calcite (CaCO3). The air pollution control residues generally showed a high resistance to pH reduction, indicating high buffer capacity and stability of immobilized As in a landfill over time. Generation of heat in a landfill might increase the release of trace elements. The release of As from stabilized soil was diffusion-controlled at 60 °C, while surface wash-off, dissolution, and depletion prevailed at 20 °C. The air pollution control residues from the incineration of municipal solid waste immobilized Cr, indicating its stability in a landfill. The treatment of soil with air pollution control residues was not effective in immobilization of Cu. Contaminated soils treated with air pollution control residues will probably have a low impact on overall leachate quality from a landfill. PMID:25528268

  9. 76 FR 39357 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-06

    ... Pollution Control District, Kern County Air Pollution Control District, and Ventura County Air Pollution... proposing to approve revisions to the Imperial County Air Pollution Control District (ICAPCD), Kern County Air Pollution Control District (KCAPCD), and Ventura County Air Pollution Control District...

  10. 75 FR 3996 - Revisions to the California State Implementation Plan, San Joaquin Valley Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-26

    ... Planning, San Joaquin Valley Air Pollution Control District; letter dated and received August 17, 2009... Sadredin, Executive Director/Air Pollution Control Officer of San Joaquin Valley Air Pollution Control...: EPA's Analysis of San Joaquin Valley Unified Air Pollution Control District's Rule 4684,...

  11. The influence of pH on the leaching behaviour of inorganic components from municipal solid waste APC residues

    SciTech Connect

    Quina, Margarida J. Bordado, Joao C.M.; Quinta-Ferreira, Rosa M.

    2009-09-15

    The influence of pH on the leaching behaviour of air pollution control (APC) residues produced in municipal solid waste incineration (MSWI) is addressed in this study. The residue is considered hazardous waste, and in accordance with their chemical properties, the leaching of contaminants into the environment is the main concern. Several leaching tests can be used for research studies or regulatory purposes, where a wide variety of conditions may be tested. Our work deals mainly with the leaching behaviour of toxic heavy metals (Pb, Cd, Zn, Cr, Ni, Cu) and inorganics associated with soluble salts (Na, K, Ca, Cl). The main goal is to obtain an overview of the leachability of APC residues produced in a Portuguese MSWI process. Among the different variables that may have influence on the leaching behaviour, pH of the leachant solution is the most important one, and was evaluated through pH static tests. The acid neutralization capacity (ANC) of the residue was also determined, which is in the range of 6.2-6.8 meq g{sup -1} (for pH = 7) and 10.1-11.6 meq g{sup -1} (for pH = 4). The analysis of the leaching behaviour is particularly important when the leaching is solubility controlled. The amphoteric behaviour of some elements was observed, namely for Pb and Zn, which is characterized through high solubilization at low and high pH and moderate or low solubility at neutral or moderate high pH. The solubility curves for Pb, Cd, Zn, Cr, Ni and Cu as a function of pH were obtained, which are very useful for predicting the leaching behaviour in different scenarios. The solubility of K and Na reveals to be nearly independent of the solution pH and the released amount is mainly availability-controlled. Moreover, the pH static test showed that Cl{sup -} is the most pH-independent species. The APC residue turns out to be a hazardous waste because of the high leaching of lead and chloride. On the other hand, leaching of elements like cadmium, nickel and copper is limited by the

  12. The influence of pH on the leaching behaviour of inorganic components from municipal solid waste APC residues.

    PubMed

    Quina, Margarida J; Bordado, João C M; Quinta-Ferreira, Rosa M

    2009-09-01

    The influence of pH on the leaching behaviour of air pollution control (APC) residues produced in municipal solid waste incineration (MSWI) is addressed in this study. The residue is considered hazardous waste, and in accordance with their chemical properties, the leaching of contaminants into the environment is the main concern. Several leaching tests can be used for research studies or regulatory purposes, where a wide variety of conditions may be tested. Our work deals mainly with the leaching behaviour of toxic heavy metals (Pb, Cd, Zn, Cr, Ni, Cu) and inorganics associated with soluble salts (Na, K, Ca, Cl). The main goal is to obtain an overview of the leachability of APC residues produced in a Portuguese MSWI process. Among the different variables that may have influence on the leaching behaviour, pH of the leachant solution is the most important one, and was evaluated through pH static tests. The acid neutralization capacity (ANC) of the residue was also determined, which is in the range of 6.2-6.8 meq g(-1) (for pH=7) and 10.1-11.6 meq g(-1) (for pH=4). The analysis of the leaching behaviour is particularly important when the leaching is solubility controlled. The amphoteric behaviour of some elements was observed, namely for Pb and Zn, which is characterized through high solubilization at low and high pH and moderate or low solubility at neutral or moderate high pH. The solubility curves for Pb, Cd, Zn, Cr, Ni and Cu as a function of pH were obtained, which are very useful for predicting the leaching behaviour in different scenarios. The solubility of K and Na reveals to be nearly independent of the solution pH and the released amount is mainly availability-controlled. Moreover, the pH static test showed that Cl(-) is the most pH-independent species. The APC residue turns out to be a hazardous waste because of the high leaching of lead and chloride. On the other hand, leaching of elements like cadmium, nickel and copper is limited by the high pH of the

  13. ENVIRONMENTAL TECHNOLOGY VERIFICATION FOR AIR POLLUTION CONTROL TECHNOLOGIES

    EPA Science Inventory

    The report describes the activities and progress of the pilot Air Pollution Control Technologies (APCT) portion of the Environmental Technology Verification (ETV) Program during the period from 09/15/97 to 09/15/02. The objective of the ETV Program is to verify the performance of...

  14. Testing cleanable/reuseable HEPA prefilters for mixed waste incinerator air pollution control systems

    SciTech Connect

    Burns, D.B.; Wong, A.; Walker, B.W.; Paul, J.D.

    1997-08-01

    The Consolidated Incineration Facility (CIF) at the US DOE Savannah River Site is undergoing preoperational testing. The CIF is designed to treat solid and liquid RCRA hazardous and mixed wastes from site operations and clean-up activities. The technologies selected for use in the air pollution control system (APCS) were based on reviews of existing incinerators, air pollution control experience, and recommendations from consultants. This approach resulted in a facility design using experience from other operating hazardous/radioactive incinerators. In order to study the CIF APCS prior to operation, a 1/10 scale pilot facility, the Offgas Components Test Facility (OCTF), was constructed and has been in operation since late 1994. Its mission is to demonstrate the design integrity of the CIF APCS and optimize equipment/instrument performance of the full scale production facility. Operation of the pilot facility has provided long-term performance data of integrated systems and critical facility components. This has reduced facility startup problems and helped ensure compliance with facility performance requirements. Technical support programs assist in assuring all stakeholders the CIF can properly treat combustible hazardous, mixed, and low-level radioactive wastes. High Efficiency Particulate Air (HEPA) filters are used to remove hazardous and radioactive particulates from the exhaust gas strewn before being released into the atmosphere. The HEPA filter change-out frequency has been a potential issue and was the first technical issue to be studied at the OCTF. Tests were conducted to evaluate the performance of HEPA filters under different operating conditions. These tests included evaluating the impact on HEPA life of scrubber operating parameters and the type of HEPA prefilter used. This pilot-scale testing demonstrated satisfactory HEPA filter life when using cleanable metal prefilters and high flows of steam and water in the offgas scrubber. 8 figs., 2 tabs.

  15. 21. Interior view of citric acid air pollution control room ...

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

    21. Interior view of citric acid air pollution control room (also known as scrubber room) in Components Test Laboratory (T-27), looking southeast. Photograph shows upgraded instrumentation, piping, tanks, and technological modifications installed in 1997-99 to accommodate component testing requirements for the Atlas V missile. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  16. 76 FR 31242 - Revisions to the California State Implementation Plan, Santa Barbara County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... Environmental protection, Air pollution control, Incorporation by reference, Intergovernmental relations... Identification of plan. * * * * * (c) * * * (359) * * * (i) * * * (E) Santa Barbara County Air Pollution Control... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Santa Barbara County...

  17. Air pollution control systems in WtE units: An overview

    SciTech Connect

    Vehlow, J.

    2015-03-15

    Highlights: • The paper describes in brief terms the development of gas cleaning in waste incineration. • The main technologies for pollutant removal are described including their basic mechanisms. • Their respective efficiencies and their application are discussed. • A cautious outlook regarding future developments is made. - Abstract: All WtE (waste-to-energy) plants, based on combustion or other thermal processes, need an efficient gas cleaning for compliance with legislative air emission standards. The development of gas cleaning technologies started along with environment protection regulations in the late 1960s. Modern APC (air pollution control) systems comprise multiple stages for the removal of fly ashes, inorganic and organic gases, heavy metals, and dioxins from the flue gas. The main technologies and devices used for abatement of the various pollutants are described and their basic principles, their peculiarities, and their application are discussed. Few systems for cleaning of synthesis gas from waste gasification plants are included. Examples of APC designs in full scale plants are shown and cautious prospects for the future development of APC systems are made.

  18. Air classification: Potential treatment method for optimized recycling or utilization of fine-grained air pollution control residues obtained from dry off-gas cleaning high-temperature processing systems.

    PubMed

    Lanzerstorfer, Christof

    2015-11-01

    In the dust collected from the off-gas of high-temperature processes, usually components that are volatile at the process temperature are enriched. In the recycling of the dust, the concentration of these volatile components is frequently limited to avoid operation problems. Also, for external utilization the concentration of such volatile components, especially heavy metals, is often restricted. The concentration of the volatile components is usually higher in the fine fractions of the collected dust. Therefore, air classification is a potential treatment method to deplete the coarse material from these volatile components by splitting off a fines fraction with an increased concentration of those volatile components. In this work, the procedure of a sequential classification using a laboratory air classifier and the calculations required for the evaluation of air classification for a certain application were demonstrated by taking the example of a fly ash sample from a biomass combustion plant. In the investigated example, the Pb content in the coarse fraction could be reduced to 60% by separation of 20% fines. For the non-volatile Mg the content was almost constant. It can be concluded that air classification is an appropriate method for the treatment of off-gas cleaning residues.

  19. 76 FR 5319 - Revisions to the California State Implementation Plan, Santa Barbara Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-31

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Santa Barbara Air Pollution Control District, Placer County Air Pollution Control District, Antelope Valley Air Quality Management District, and Ventura County Air Pollution Control District AGENCY: Environmental Protection Agency...

  20. 76 FR 30080 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-24

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution Control District and Ventura County Air Pollution Control District AGENCY: Environmental Protection Agency... Pollution Control District (PCAPCD) and Ventura County Air Pollution Control District (VCAPCD) portion...

  1. 76 FR 40660 - Revisions to the California State Implementation Plan, San Joaquin Valley Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    .... SUMMARY: EPA is proposing to approve revisions to the San Joaquin Valley Air Pollution Control District....0 for the following terms: Air Pollution Control Officer, Board, Environmental Protection Agency.... New Section 6.3 requires the SJVUAPCD Air Pollution Control Officer (APCO) to prepare and present...

  2. 76 FR 30025 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-24

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution Control District and Ventura County Air Pollution Control District AGENCY: Environmental Protection Agency... the Placer County Air Pollution Control District (PCAPCD) and Ventura County Air Pollution...

  3. 75 FR 10690 - Revisions to the California State Implementation Plan, San Joaquin Valley Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... is finalizing approval of revisions to the San Joaquin Valley Air Pollution Control District (SJVAPCD...)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control... Joaquin Valley Unified Air Pollution Control District. (1) Rule 4104, ``Reduction of Animal Matter,''...

  4. 76 FR 39303 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-06

    ... Pollution Control District, Kern County Air Pollution Control District, and Ventura County Air Pollution... taking direct final action to approve revisions to the Imperial County Air Pollution Control District (ICAPCD), Kern County Air Pollution Control District (KCAPCD), and Ventura County Air Pollution...

  5. 76 FR 5277 - Revisions to the California State Implementation Plan, Santa Barbara Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-31

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Santa Barbara Air Pollution Control District, Antelope Valley Air Quality Management District, Ventura County Air Pollution Control District and Placer County Air Pollution Control District AGENCY: Environmental Protection Agency...

  6. Development of foamed emulsion bioreactor for air pollution control.

    PubMed

    Kan, Eunsung; Deshusses, Marc A

    2003-10-20

    A new type of bioreactor for air pollution control has been developed. The new process relies on an organic-phase emulsion and actively growing pollutant-degrading microorganisms, made into a foam with the air being treated. This new reactor is referred to as a foamed emulsion bioreactor (FEBR). As there is no packing in the reactor, the FEBR is not subject to clogging. Mathematical modeling of the process and proof of concept using a laboratory prototype revealed that the foamed emulsion bioreactor greatly surpasses the performance of existing gas-phase bioreactors. Experimental results showed a toluene elimination capacity as high as 285 g(toluene) m(-3) (reactor) h(-1) with a removal efficiency of 95% at a gas residence time of 15 s and a toluene inlet concentration of 1-1.3 g x m(-3). Oxygen limited the reactor performance at toluene concentration above about 0.7-1.0 g x m(-3); consequently, performance was significantly improved when pure oxygen was added to the contaminated air. The elimination capacity increased from 204 to 408 g x m(-3) h(-1) with >77% toluene removal at toluene inlet concentrations of 2-2.2 g x m(-3). Overall, the results show that the performance of the FEBR far exceeds that of currently used bioreactors for air pollution control.

  7. 40 CFR 60.2141 - By what date must I conduct the initial air pollution control device inspection?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... air pollution control device inspection? 60.2141 Section 60.2141 Protection of Environment... initial air pollution control device inspection? (a) The initial air pollution control device inspection... startup. (b) Within 10 operating days following an air pollution control device inspection, all...

  8. 40 CFR 60.2141 - By what date must I conduct the initial air pollution control device inspection?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... air pollution control device inspection? 60.2141 Section 60.2141 Protection of Environment... initial air pollution control device inspection? (a) The initial air pollution control device inspection... startup. (b) Within 10 operating days following an air pollution control device inspection, all...

  9. Leachability of organic and inorganic contaminants in ashes from lime-based air pollution control devices on a municipal waste incinerator

    SciTech Connect

    Sawell, S.E.; Bridle, T.R.; Constable, T.W. )

    1987-01-01

    Concern for public health, coupled with the implementation of more stringent guidelines for exhaust gas emissions from municipal solid waste (MSW) incineration units, has resulted in the development of more efficient flue gas cleaning systems. While these systems help reduce emissions of airborne contaminants, they also increase the quantities of ash which require proper disposal. Although recent studies have identified MSW incinerator bottom ash as a relatively benign waste, they have also indicated that MSW incinerator flue gas ashes may not be environmentally acceptable for landfilling. In 1984, the Wastewater Technology Centre began conducting a series of studies on the leachability of MSW incinerator ash, under Environment Canada's National Incinerator Testing and Evaluation Program (NITEP). The studies were undertaken to obtain additional information on the chemical and physical characteristics of these ashes and to assist in the development of solid waste management criteria for their ultimate disposal. This paper focuses on the results from the second study in the series, which was conducted on residues collected from an air pollution control (APC) pilot plant built by FLAKT Canada.

  10. Field Operations and Enforcement Manual for Air Pollution Control. Volume I: Organization and Basic Procedures.

    ERIC Educational Resources Information Center

    Weisburd, Melvin I.

    The Field Operations and Enforcement Manual for Air Pollution Control, Volume I, explains in detail the following: sources and classification of pollutants; meteorological influence on air quality; the air pollution control agency; the field enforcement officer; the enforcement process; prosecuting violation; and inspection techniques including…

  11. 77 FR 73392 - Revisions to the California State Implementation Plan, Monterey Bay Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-10

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Monterey Bay Unified Air Pollution Control District AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: EPA is proposing to approve revisions to the Monterey Bay Unified Air Pollution Control...

  12. 75 FR 56942 - Revisions to the California State Implementation Plan, San Diego County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-17

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, San Diego County Air Pollution Control District AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: EPA is proposing to approve revisions to the San Diego Air Pollution Control District...

  13. 78 FR 6736 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... taking direct final action to approve revisions to the Placer County Air Pollution Control District..., however, provide for Air Pollution Control Officer (APCO) discretion to allow burning on a No-Burn...

  14. 78 FR 37130 - Revisions to the California State Implementation Plan, San Diego Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, San Diego Air Pollution... taking direct final action to approve a revision to the San Diego Air Pollution Control District (SDAPCD... Part 52 Environmental protection, Air pollution control, Incorporation by reference,...

  15. 78 FR 896 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-07

    ... is finalizing approval of revisions to the Imperial County Air Pollution Control District (ICAPCD...)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Imperial County...

  16. 75 FR 27975 - Revisions to the California State Implementation Plan; Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-19

    ...: EPA is proposing to approve revisions to the Imperial County Air Pollution Control District (ICAPCD... of Subjects in 40 CFR Part 52 Environmental protection, Air pollution control, Intergovernmental... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan; Imperial County...

  17. 76 FR 76046 - Interim Final Determination To Defer Sanctions, San Joaquin Valley Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... approval of revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD or... Valley Unified Air Pollution Control District (``SJVUAPCD'' or ``District'') Rules 2020 (Exemptions) and... AGENCY 40 CFR Part 52 Interim Final Determination To Defer Sanctions, San Joaquin Valley Unified...

  18. 76 FR 26615 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-09

    .... SUMMARY: EPA is finalizing approval of revisions to the Imperial County Air Pollution Control District... various air pollution sources. We are approving local rules that regulate these emission sources under the... CFR Part 52 Environmental protection, Air pollution control, Incorporation by...

  19. 76 FR 17347 - Revision to the California State Implementation Plan, Great Basin Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-29

    ...) * * * (D) Great Basin Unified Air Pollution Control District (1) Rule 201, ``Exemptions,'' adopted on... AGENCY 40 CFR Part 52 Revision to the California State Implementation Plan, Great Basin Unified Air Pollution Control District CFR Correction In Title 40 of the Code of Federal Regulations, Part 52 (Sec....

  20. 77 FR 2643 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-19

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... finalizing a limited approval and limited disapproval of revisions to the Placer County Air Pollution Control...) * * * (i) * * * (D) Placer County Air Pollution Control District (1) Rule 233, ``Biomass Boilers,''...

  1. 75 FR 45082 - Revisions to the California State Implementation Plan, Santa Barbara County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-02

    ... Air Pollution Control District (SBCAPCD) portion of the California State Implementation Plan (SIP... Preamble for the Implementation of Title I of the Clean Air Act Amendments of 1990'', 57 FR 13498, April 16... Environmental protection, Air pollution control, Intergovernmental relations, Nitrogen dioxide, Ozone,...

  2. 75 FR 2796 - Revisions to the California State Implementation Plan, San Joaquin Valley Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-19

    ... is finalizing approval of revisions to the San Joaquin Valley Air Pollution Control District portion... topcoats; and that Ventura County Air Pollution Control District's (VCAPCD) rule has more stringent VOC...)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution...

  3. 77 FR 25109 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ...: EPA is proposing to approve revisions to the Imperial County Air Pollution Control District (ICAPCD... Implementation of Title I of the Clean Air Act Amendments of 1990,'' 59 FR 41998 (August 16, 1994). 5. ``PM-10... of Subjects in 40 CFR Part 52 Air pollution control, Environmental protection,...

  4. 76 FR 75795 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... taking direct final action to approve revisions to the Placer County Air Pollution Control District... CFR Part 52 Environmental protection, Air pollution control, Incorporation by reference, Reporting...

  5. 76 FR 45199 - Interim Final Determination To Defer Sanctions, San Joaquin Valley Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-28

    ... of revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... Subjects in 40 CFR Part 52 Environmental protection, Air pollution control, Incorporation by reference... AGENCY 40 CFR Part 52 Interim Final Determination To Defer Sanctions, San Joaquin Valley Unified...

  6. 75 FR 2079 - Revisions to the California State Implementation Plan, San Joaquin Valley Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-14

    ... facilities. Also, please see our response to CPF comment 3. B. San Joaquin Valley Air Pollution Control...) San Joaquin Valley Unified Air Pollution Control District. (1) Rule 4570, ``Confined Animal Facilities... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, San Joaquin Valley...

  7. 78 FR 53249 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-29

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... finalizing approval of revisions to the Placer County Air Pollution Control District (PCAPCD) portion of the... 40 CFR Part 52 Environmental protection, Air pollution control, Incorporation by...

  8. 78 FR 23677 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-22

    ... is finalizing approval of revisions to the Imperial County Air Pollution Control District (ICAPCD... Air Pollution Control District (SJVAPCD). Response #4--The comment does not identify and we are not... submittal and review process such as contained in SJVAPCD Rule 4550 and Great Basin Unified Air...

  9. 75 FR 24406 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution Control District, Sacramento Metropolitan Air Quality Management District, San Joaquin Valley Unified Air Pollution Control District, and South Coast Air Quality Management District AGENCY: Environmental...

  10. 75 FR 24544 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution Control District, Sacramento Metropolitan Air Quality Management District, San Joaquin Valley Unified Air Pollution Control District, and South Coast Air Quality Management District AGENCY: Environmental...

  11. 40 CFR 424.10 - Applicability; description of the open electric furnaces with wet air pollution control devices...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... electric furnaces with wet air pollution control devices subcategory. 424.10 Section 424.10 Protection of... MANUFACTURING POINT SOURCE CATEGORY Open Electric Furnaces With Wet Air Pollution Control Devices Subcategory § 424.10 Applicability; description of the open electric furnaces with wet air pollution control...

  12. 40 CFR 60.5215 - By what date must I conduct annual air pollution control device inspections and make any...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... air pollution control device inspections and make any necessary repairs? (a) You must conduct an annual inspection of each air pollution control device used to comply with the emission limits, according to § 60.5220(c), no later than 12 months following the previous annual air pollution control...

  13. 40 CFR 60.2706 - By what date must I conduct the initial air pollution control device inspection?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... air pollution control device inspection? 60.2706 Section 60.2706 Protection of Environment... Requirements § 60.2706 By what date must I conduct the initial air pollution control device inspection? (a) The initial air pollution control device inspection must be conducted within 60 days after installation of...

  14. 40 CFR 424.10 - Applicability; description of the open electric furnaces with wet air pollution control devices...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... electric furnaces with wet air pollution control devices subcategory. 424.10 Section 424.10 Protection of... MANUFACTURING POINT SOURCE CATEGORY Open Electric Furnaces With Wet Air Pollution Control Devices Subcategory § 424.10 Applicability; description of the open electric furnaces with wet air pollution control...

  15. 40 CFR 60.5215 - By what date must I conduct annual air pollution control device inspections and make any...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... air pollution control device inspections and make any necessary repairs? (a) You must conduct an annual inspection of each air pollution control device used to comply with the emission limits, according to § 60.5220(c), no later than 12 months following the previous annual air pollution control...

  16. 40 CFR 60.2716 - By what date must I conduct the annual air pollution control device inspection?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... air pollution control device inspection? 60.2716 Section 60.2716 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... annual air pollution control device inspection), you must complete the air pollution control...

  17. 40 CFR 60.2141 - By what date must I conduct the initial air pollution control device inspection?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... air pollution control device inspection? 60.2141 Section 60.2141 Protection of Environment... Compliance Requirements § 60.2141 By what date must I conduct the initial air pollution control device inspection? (a) The initial air pollution control device inspection must be conducted within 60 days...

  18. 40 CFR 60.2151 - By what date must I conduct the annual air pollution control device inspection?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... air pollution control device inspection? 60.2151 Section 60.2151 Protection of Environment... annual air pollution control device inspection? On an annual basis (no more than 12 months following the previous annual air pollution control device inspection), you must complete the air pollution...

  19. 40 CFR 424.10 - Applicability; description of the open electric furnaces with wet air pollution control devices...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... electric furnaces with wet air pollution control devices subcategory. 424.10 Section 424.10 Protection of... MANUFACTURING POINT SOURCE CATEGORY Open Electric Furnaces With Wet Air Pollution Control Devices Subcategory § 424.10 Applicability; description of the open electric furnaces with wet air pollution control...

  20. 40 CFR 60.2716 - By what date must I conduct the annual air pollution control device inspection?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... air pollution control device inspection? 60.2716 Section 60.2716 Protection of Environment... Requirements § 60.2716 By what date must I conduct the annual air pollution control device inspection? On an annual basis (no more than 12 months following the previous annual air pollution control...

  1. 40 CFR 62.14441 - When must I inspect my HMIWI equipment and air pollution control devices?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and air pollution control devices? 62.14441 Section 62.14441 Protection of Environment ENVIRONMENTAL... my HMIWI equipment and air pollution control devices? (a) You must inspect your large, medium, small... inspect the air pollution control devices on your large, medium, small or small rural HMIWI by May...

  2. 40 CFR 60.2716 - By what date must I conduct the annual air pollution control device inspection?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... air pollution control device inspection? 60.2716 Section 60.2716 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... annual air pollution control device inspection), you must complete the air pollution control...

  3. 40 CFR 60.2716 - By what date must I conduct the annual air pollution control device inspection?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... air pollution control device inspection? 60.2716 Section 60.2716 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... annual air pollution control device inspection), you must complete the air pollution control...

  4. 40 CFR 60.5215 - By what date must I conduct annual air pollution control device inspections and make any...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... air pollution control device inspections and make any necessary repairs? (a) You must conduct an annual inspection of each air pollution control device used to comply with the emission limits, according to § 60.5220(c), no later than 12 months following the previous annual air pollution control...

  5. 40 CFR 424.10 - Applicability; description of the open electric furnaces with wet air pollution control devices...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... electric furnaces with wet air pollution control devices subcategory. 424.10 Section 424.10 Protection of... MANUFACTURING POINT SOURCE CATEGORY Open Electric Furnaces With Wet Air Pollution Control Devices Subcategory § 424.10 Applicability; description of the open electric furnaces with wet air pollution control...

  6. 40 CFR 424.10 - Applicability; description of the open electric furnaces with wet air pollution control devices...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... electric furnaces with wet air pollution control devices subcategory. 424.10 Section 424.10 Protection of... MANUFACTURING POINT SOURCE CATEGORY Open Electric Furnaces With Wet Air Pollution Control Devices Subcategory § 424.10 Applicability; description of the open electric furnaces with wet air pollution control...

  7. 40 CFR 60.5215 - By what date must I conduct annual air pollution control device inspections and make any...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... air pollution control device inspections and make any necessary repairs? (a) You must conduct an annual inspection of each air pollution control device used to comply with the emission limits, according to § 60.5220(c), no later than 12 months following the previous annual air pollution control...

  8. 40 CFR 60.2141 - By what date must I conduct the initial air pollution control device inspection?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... air pollution control device inspection? 60.2141 Section 60.2141 Protection of Environment... Compliance Requirements § 60.2141 By what date must I conduct the initial air pollution control device inspection? (a) The initial air pollution control device inspection must be conducted within 60 days...

  9. 40 CFR 60.2151 - By what date must I conduct the annual air pollution control device inspection?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... air pollution control device inspection? 60.2151 Section 60.2151 Protection of Environment... annual air pollution control device inspection? On an annual basis (no more than 12 months following the previous annual air pollution control device inspection), you must complete the air pollution...

  10. 40 CFR 62.14441 - When must I inspect my HMIWI equipment and air pollution control devices?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and air pollution control devices? 62.14441 Section 62.14441 Protection of Environment ENVIRONMENTAL... my HMIWI equipment and air pollution control devices? (a) You must inspect your large, medium, small... inspect the air pollution control devices on your large, medium, small or small rural HMIWI by May...

  11. INTEGRATED AIR POLLUTION CONTROL SYSTEM, VERSION 4.0 - VOLUME 2: TECHNICAL DOCUMENTATION MANUAL

    EPA Science Inventory

    The Integrated Air Pollution Control System (IAPCS) was developed for the U.S. EPA's Air and Energy Engineering Research Laboratory to estimate costs and performance for emission control systems applied to coal-fired utility boilers. The model can project a material balance, and ...

  12. INTEGRATED AIR POLLUTION CONTROL SYSTEM, VERSION 4.0 - VOLUME 3: PROGRAMMER'S MAINTENACE MANUAL

    EPA Science Inventory

    The Integrated Air Pollution Control System (IAPCS) was developed for the U.S. EPA's Air and Energy Engineering Research Laboratory to estimate costs and performance for emission control systems applied to coal-fired utility boilers. The model can project a material balance, and ...

  13. INTEGRATED AIR POLLUTION CONTROL SYSTEM, VERSION 4.0 - VOLUME 1: USER'S GUIDE

    EPA Science Inventory

    The Integrated Air Pollution Control System (IAPCS) was developed for the U.S. EPA's Air and Energy Engineering Research Laboratory to estimate costs and performance for emission control systems applied to coal-fired utility boilers. The model can project a material balance, and ...

  14. BUILDING AN ENVIRONMENTAL TRAINING MODEL, MAPCORE - A TRAINING EXERCISE FOR AIR POLLUTION CONTROL.

    ERIC Educational Resources Information Center

    SIEGEL, GILBERT B.; SULLIVAN, DONALD M.

    NEW AIR POLLUTION CONTROL PROGRAMS HAVE RESULTED FROM THE "CLEAN AIR ACT" PASSED BY CONGRESS IN DECEMBER 1963. THE UNIVERSITY OF SOUTHERN CALIFORNIA DEVELOPED A TRAINING MODEL, CALLED "MAPCORE," WHICH PROVIDES A SEMISTRUCTURED ENVIRONMENT, IS PRACTICAL AND REALISTIC IN APPROACH, PROVIDES OPPORTUNITY FOR HIGH CREATIVITY, PROVIDES AN…

  15. METRO-APEX Volume 7.1: Air Pollution Control Officer's Manual. Revised.

    ERIC Educational Resources Information Center

    University of Southern California, Los Angeles. COMEX Research Project.

    The Air Pollution Control Officer's Manual is one of a set of twenty-one manuals used in METRO-APEX 1974, a computerized college and professional level, computer-supported, role-play, simulation exercise of a community with "normal" problems. Stress is placed on environmental quality considerations. APEX 1974 is an expansion of APEX--Air Pollution…

  16. APEX (Air Pollution Exercise) Volume 3: Air Pollution Control Officer's Manual.

    ERIC Educational Resources Information Center

    Environmental Protection Agency, Research Triangle Park, NC. Office of Manpower Development.

    The Air Pollution Control Officer's (APCO) Manual is part of a set of 21 manuals (AA 001 009-001 029) used in APEX (Air Pollution Exercise) a computerized college and professional level "real world" game simulation of a community with urban and rural problems, industrial activities, and air pollution difficulties, The first two sections, which are…

  17. 40 CFR 63.13 - Addresses of State air pollution control agencies and EPA Regional Offices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Addresses of State air pollution... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES General Provisions § 63.13 Addresses of State air pollution control...

  18. 40 CFR 63.13 - Addresses of State air pollution control agencies and EPA Regional Offices.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 10 2014-07-01 2014-07-01 false Addresses of State air pollution... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES General Provisions § 63.13 Addresses of State air pollution control...

  19. APEX (Air Pollution Exercise) Volume 21: Legal References: Air Pollution Control Regulations.

    ERIC Educational Resources Information Center

    Environmental Protection Agency, Research Triangle Park, NC. Office of Manpower Development.

    The Legal References: Air Pollution Control Regulations Manual is the last in a set of 21 manuals (AA 001 009-001 029) used in APEX (Air Pollution Exercise), a computerized college and professional level "real world" game simulation of a community with urban and rural problems, industrial activities, and air pollution difficulties. The manual…

  20. 75 FR 1284 - Revisions to the California State Implementation Plan, Ventura County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Ventura County Air Pollution... finalizing approval of revisions to the Ventura County Air Pollution Control District (VCAPCD) portion of the...)(2)). List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution...

  1. 76 FR 75857 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... proposing to approve revisions to the Placer County Air Pollution Control District (PCAPCD) portion of the... local rules to regulate these emission sources under the Clean Air Act as amended in 1990 (CAA or...

  2. 40 CFR 63.13 - Addresses of State air pollution control agencies and EPA Regional Offices.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 10 2013-07-01 2013-07-01 false Addresses of State air pollution... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES General Provisions § 63.13 Addresses of State air pollution control...

  3. 40 CFR 63.13 - Addresses of State air pollution control agencies and EPA Regional Offices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Addresses of State air pollution... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES General Provisions § 63.13 Addresses of State air pollution control...

  4. 77 FR 73322 - Revisions to the California State Implementation Plan, Monterey Bay Unified Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-10

    ...: EPA is taking direct final action to approve revisions to the Monterey Bay Unified Air Pollution... Part 52 Environmental protection, Air pollution control, Incorporation by reference, Intergovernmental... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Monterey Bay Unified...

  5. 78 FR 37176 - Revisions to the California State Implementation Plan, San Diego Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, San Diego Air Pollution... proposing to approve a revision to the San Diego Air Pollution Control District (SDAPCD) portion of the... sources under the Clean Air Act (CAA or the Act). DATES: Any comments on this proposal must arrive by...

  6. 78 FR 922 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-07

    ...: EPA is proposing to approve revisions to the Imperial County Air Pollution Control District (ICAPCD... for the Implementation of Title I of the Clean Air Act Amendments of 1990,'' 57 FR 13498 (April 16... Preamble for the Implementation of Title I of the Clean Air Act Amendments of 1990,'' 59 FR 41998...

  7. 40 CFR 63.13 - Addresses of State air pollution control agencies and EPA Regional Offices.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 10 2012-07-01 2012-07-01 false Addresses of State air pollution... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES General Provisions § 63.13 Addresses of State air pollution control...

  8. 78 FR 894 - Interim Final Determination To Stay Sanctions, Imperial County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-07

    ... AGENCY 40 CFR Part 52 Interim Final Determination To Stay Sanctions, Imperial County Air Pollution... of revisions to the Imperial County Air Pollution Control District (ICAPCD) portion of the California...- line instructions. 2. Email: steckel.andrew@epa.gov . 3. Mail or deliver: Andrew Steckel (Air-4),...

  9. 76 FR 67396 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-01

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... proposing to approve revisions to the Placer County Air Pollution Control District (PCAPCD) and Sacramento Metro Air Quality Management District (SMAQMD) portions of the California State Implementation Plan...

  10. 78 FR 6784 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... proposing to approve revisions to the Placer County Air Pollution Control District (PCAPCD) portion of the... approve local rules to regulate this emission source under the Clean Air Act (CAA or the Act). DATES:...

  11. 77 FR 67322 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... proposing to approve revisions to the Placer County Air Pollution Control District (PCAPCD) portion of the... FR 2643). III. Statutory and Executive Order Reviews Under the Clean Air Act, the Administrator...

  12. INTEGRATED AIR POLLUTION CONTROL SYSTEM VERSION 5.0 - VOLUME 1: USER'S GUIDE

    EPA Science Inventory

    The three volume report and two diskettes document the Integrated Air Pollution Control System (IAPCS), developed for the U.S. EPA to estimate costs and performance for emission control systems applied to coal-fired utility boilers. The model can project a material balance, an eq...

  13. INTEGRATED AIR POLLUTION CONTROL SYSTEM VERSION 5.0 - VOLUME 2: TECHNICAL DOCUMENTATION

    EPA Science Inventory

    The three volume report and two diskettes document the Integrated Air Pollution Control System (IAPCS), developed for the U.S. EPA to estimate costs and performance for emission control systems applied to coal-fired utility boilers. The model can project a material balance, an eq...

  14. INTEGRATED AIR POLLUTION CONTROL SYSTEM VERSION 5.0 - VOLUME 3: PROGRAMMER'S MAINTENANCE MANUAL

    EPA Science Inventory

    The three volume report and two diskettes document the Integrated Air Pollution Control System (IAPCS), developed for the U.S. EPA to estimate costs and performance for emission control systems applied to coal-fired utility boilers. The model can project a material balance, an eq...

  15. 78 FR 58460 - Revision of Air Quality Implementation Plan; California; Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ... Pollution Control District and Feather River Air Quality Management District; Stationary Source Permits... California as a revision to the Placer County Air Pollution Control District (PCAPCD) and Feather River Air Quality Management District (FRAQMD) portion of the California State Implementation Plan (SIP)....

  16. 78 FR 12243 - Interim Final Determination To Stay and Defer Sanctions, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ... Pollution Control District and Feather River Air Quality Management District AGENCY: Environmental... proposed approval of a revision to the Placer County Air Pollution Control District (PCAPCD) and Feather River Air Quality Management District (FRAQMD) portion of the California State Implementation Plan...

  17. 76 FR 71886 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-21

    ... Control District and Sacramento Metropolitan Air Quality Management District AGENCY: Environmental... Office of Management and Budget under Executive Order 12866 (58 FR 51735, October 4, 1993); Does not... revisions to the Placer County Air Pollution Control District (PCAPCD) and Sacramento Metropolitan...

  18. Field Operations and Enforcement Manual for Air Pollution Control. Volume III: Inspection Procedures for Specific Industries.

    ERIC Educational Resources Information Center

    Weisburd, Melvin I.

    The Field Operations and Enforcement Manual for Air Pollution Control, Volume III, explains in detail the following: inspection procedures for specific sources, kraft pulp mills, animal rendering, steel mill furnaces, coking operations, petroleum refineries, chemical plants, non-ferrous smelting and refining, foundries, cement plants, aluminum…

  19. 40 CFR 60.2151 - By what date must I conduct the annual air pollution control device inspection?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... air pollution control device inspection? 60.2151 Section 60.2151 Protection of Environment... Compliance Requirements § 60.2151 By what date must I conduct the annual air pollution control device inspection? On an annual basis (no more than 12 months following the previous annual air pollution...

  20. 40 CFR 424.40 - Applicability; description of the covered calcium carbide furnaces with wet air pollution control...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... covered calcium carbide furnaces with wet air pollution control devices subcategory. 424.40 Section 424.40... FERROALLOY MANUFACTURING POINT SOURCE CATEGORY Covered Calcium Carbide Furnaces With Wet Air Pollution... with wet air pollution control devices subcategory. The provisions of this subpart are applicable...

  1. 40 CFR 60.2151 - By what date must I conduct the annual air pollution control device inspection?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... air pollution control device inspection? 60.2151 Section 60.2151 Protection of Environment... Compliance Requirements § 60.2151 By what date must I conduct the annual air pollution control device inspection? On an annual basis (no more than 12 months following the previous annual air pollution...

  2. 40 CFR 424.40 - Applicability; description of the covered calcium carbide furnaces with wet air pollution control...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... covered calcium carbide furnaces with wet air pollution control devices subcategory. 424.40 Section 424.40... FERROALLOY MANUFACTURING POINT SOURCE CATEGORY Covered Calcium Carbide Furnaces With Wet Air Pollution... with wet air pollution control devices subcategory. The provisions of this subpart are applicable...

  3. 40 CFR 60.4895 - By what date must I conduct annual air pollution control device inspections and make any...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Compliance Requirements § 60.4895 By what date must I conduct annual air pollution control device inspections and make any necessary repairs? (a) You must conduct an annual inspection of each air pollution... following the previous annual air pollution control device inspection. (b) Within 10 operating...

  4. 40 CFR 60.4895 - By what date must I conduct annual air pollution control device inspections and make any...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Compliance Requirements § 60.4895 By what date must I conduct annual air pollution control device inspections and make any necessary repairs? (a) You must conduct an annual inspection of each air pollution... following the previous annual air pollution control device inspection. (b) Within 10 operating...

  5. 40 CFR 60.2706 - By what date must I conduct the initial air pollution control device inspection?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... air pollution control device inspection? 60.2706 Section 60.2706 Protection of Environment... pollution control device inspection? (a) The initial air pollution control device inspection must be... meeting the amended emission limitations. (b) Within 10 operating days following an air pollution...

  6. 40 CFR 60.4895 - By what date must I conduct annual air pollution control device inspections and make any...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Compliance Requirements § 60.4895 By what date must I conduct annual air pollution control device inspections and make any necessary repairs? (a) You must conduct an annual inspection of each air pollution... following the previous annual air pollution control device inspection. (b) Within 10 operating...

  7. 40 CFR 424.40 - Applicability; description of the covered calcium carbide furnaces with wet air pollution control...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... covered calcium carbide furnaces with wet air pollution control devices subcategory. 424.40 Section 424.40... FERROALLOY MANUFACTURING POINT SOURCE CATEGORY Covered Calcium Carbide Furnaces With Wet Air Pollution... with wet air pollution control devices subcategory. The provisions of this subpart are applicable...

  8. 40 CFR 424.40 - Applicability; description of the covered calcium carbide furnaces with wet air pollution control...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... covered calcium carbide furnaces with wet air pollution control devices subcategory. 424.40 Section 424.40... FERROALLOY MANUFACTURING POINT SOURCE CATEGORY Covered Calcium Carbide Furnaces With Wet Air Pollution... with wet air pollution control devices subcategory. The provisions of this subpart are applicable...

  9. 40 CFR 60.2706 - By what date must I conduct the initial air pollution control device inspection?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... air pollution control device inspection? 60.2706 Section 60.2706 Protection of Environment... pollution control device inspection? (a) The initial air pollution control device inspection must be... meeting the amended emission limitations. (b) Within 10 operating days following an air pollution...

  10. 40 CFR 60.2706 - By what date must I conduct the initial air pollution control device inspection?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... air pollution control device inspection? 60.2706 Section 60.2706 Protection of Environment... pollution control device inspection? (a) The initial air pollution control device inspection must be... meeting the amended emission limitations. (b) Within 10 operating days following an air pollution...

  11. 40 CFR 60.4895 - By what date must I conduct annual air pollution control device inspections and make any...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Compliance Requirements § 60.4895 By what date must I conduct annual air pollution control device inspections and make any necessary repairs? (a) You must conduct an annual inspection of each air pollution... following the previous annual air pollution control device inspection. (b) Within 10 operating...

  12. 40 CFR 424.40 - Applicability; description of the covered calcium carbide furnaces with wet air pollution control...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... covered calcium carbide furnaces with wet air pollution control devices subcategory. 424.40 Section 424.40... FERROALLOY MANUFACTURING POINT SOURCE CATEGORY Covered Calcium Carbide Furnaces With Wet Air Pollution... with wet air pollution control devices subcategory. The provisions of this subpart are applicable...

  13. 40 CFR 60.5195 - By what date must I conduct the initial air pollution control device inspection and make any...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... air pollution control device inspection and make any necessary repairs? 60.5195 Section 60.5195... air pollution control device inspection and make any necessary repairs? (a) You must conduct an air... approved state plan, Federal plan, or delegation, as applicable. For air pollution control...

  14. 40 CFR 60.4875 - By what date must I conduct the initial air pollution control device inspection and make any...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... air pollution control device inspection and make any necessary repairs? 60.4875 Section 60.4875... Initial Compliance Requirements § 60.4875 By what date must I conduct the initial air pollution control device inspection and make any necessary repairs? (a) You must conduct an air pollution control...

  15. 40 CFR 60.5195 - By what date must I conduct the initial air pollution control device inspection and make any...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... air pollution control device inspection and make any necessary repairs? 60.5195 Section 60.5195... air pollution control device inspection and make any necessary repairs? (a) You must conduct an air... approved state plan, Federal plan, or delegation, as applicable. For air pollution control...

  16. 40 CFR 60.4875 - By what date must I conduct the initial air pollution control device inspection and make any...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... air pollution control device inspection and make any necessary repairs? 60.4875 Section 60.4875... Initial Compliance Requirements § 60.4875 By what date must I conduct the initial air pollution control device inspection and make any necessary repairs? (a) You must conduct an air pollution control...

  17. 40 CFR 60.5195 - By what date must I conduct the initial air pollution control device inspection and make any...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... air pollution control device inspection and make any necessary repairs? 60.5195 Section 60.5195... air pollution control device inspection and make any necessary repairs? (a) You must conduct an air... approved state plan, Federal plan, or delegation, as applicable. For air pollution control...

  18. 40 CFR 60.4875 - By what date must I conduct the initial air pollution control device inspection and make any...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... air pollution control device inspection and make any necessary repairs? 60.4875 Section 60.4875... Initial Compliance Requirements § 60.4875 By what date must I conduct the initial air pollution control device inspection and make any necessary repairs? (a) You must conduct an air pollution control...

  19. 40 CFR 60.4875 - By what date must I conduct the initial air pollution control device inspection and make any...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... air pollution control device inspection and make any necessary repairs? 60.4875 Section 60.4875... Initial Compliance Requirements § 60.4875 By what date must I conduct the initial air pollution control device inspection and make any necessary repairs? (a) You must conduct an air pollution control...

  20. 40 CFR 60.5195 - By what date must I conduct the initial air pollution control device inspection and make any...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... air pollution control device inspection and make any necessary repairs? 60.5195 Section 60.5195... air pollution control device inspection and make any necessary repairs? (a) You must conduct an air... approved state plan, Federal plan, or delegation, as applicable. For air pollution control...

  1. Air pollution control system research: An iterative approach to developing affordable systems

    NASA Technical Reports Server (NTRS)

    Watt, Lewis C.; Cannon, Fred S.; Heinsohn, Robert J.; Spaeder, Timothy A.

    1995-01-01

    This paper describes a Strategic Environmental Research and Development Program (SERDP) funded project led jointly by the Marine Corps Multi-Commodity Maintenance Centers, and the Air and Energy Engineering Research Laboratory (AEERL) of the USEPA. The research focuses on paint booth exhaust minimization using recirculation, and on volatile organic compound (VOC) oxidation by the modules of a hybrid air pollution control system. The research team is applying bench, pilot and full scale systems to accomplish the goals of reduced cost and improved effectiveness of air treatment systems for paint booth exhaust.

  2. Ambient concentrations of aldehydes in relation to Beijing Olympic air pollution control measures

    NASA Astrophysics Data System (ADS)

    Gong, J. C.; Zhu, T.; Hu, M.; Zhang, L. W.; Cheng, H.; Zhang, L.; Tong, J.; Zhang, J.

    2010-08-01

    Aldehydes are ubiquitous constituents of the atmosphere. Their concentrations are elevated in polluted urban atmospheres. The present study was carried out to characterize three aldehydes of most health concern (formaldehyde, acetaldehyde, and acrolein) in a central Beijing site in the summer and early fall of 2008 (from June to October). Measurements were made before, during, and after the Beijing Olympics to examine whether the air pollution control measures implemented to improve Beijing's air quality during the Olympics had any impact on concentrations of the three aldehydes. Average concentrations of formaldehyde, acetaldehyde and acrolein were 29.34 ± 15.12 μg/m3, 27.09 ± 15.74 μg/m3 and 2.32 ± 0.95 μg/m3, respectively, for the entire period of measurements, all being the highest among the levels measured in cities around the world in photochemical smog seasons. Among the three measured aldehydes, only acetaldehyde had a substantially reduced mean concentration during the Olympic air pollution control period compared to the pre-Olympic period. Formaldehyde and acrolein followed the changing pattern of temperature and were each significantly correlated with ozone (a secondary product of photochemical reactions). In contrast, acetaldehyde was significantly correlated with several pollutants emitted mainly from local emission sources (e.g., NO2, CO, and PM2.5). These findings suggest that local direct emissions had a larger impact on acetaldehyde than formaldehyde and acrolein.

  3. Portable air pollution control equipment for the control of toxic particulate emissions

    SciTech Connect

    Chaurushia, A.; Odabashian, S.; Busch, E.

    1997-12-31

    Chromium VI (Cr VI) has been identified by the environmental regulatory agencies as a potent carcinogen among eleven heavy metals. A threshold level of 0.0001 lb/year for Cr VI emissions has been established by the California Air Resources Board for reporting under Assembly Bill 2588. A need for an innovative control technology to reduce fugitive emissions of Cr VI was identified during the Air Toxic Emissions Reduction Program at Northrop Grumman Military Aircraft Systems Division (NGMASD). NGMASD operates an aircraft assembly facility in El Segundo, CA. Nearly all of the aircraft components are coated with a protective coating (primer) prior to assembly. The primer has Cr VI as a component for its excellent corrosion resistance property. The complex assembly process requires fasteners which also need primer coating. Therefore, NGMASD utilizes High Volume Low Pressure (HVLP) guns for the touch-up spray coating operations. During the touch-up spray coating operations, Cr VI particles are atomized and transferred to the aircraft surface. The South Coast Air Quality Management District (SCAQMD) has determined that the HVLP gun transfers 65% of the paint particles onto the substrate and the remaining 35% are emitted as an overspray if air pollution controls are not applied. NGMASD has developed the Portable Air Pollution Control Equipment (PAPCE) to capture and control the overspray in order to reduce fugitive Cr VI emissions from the touch-up spray coating operations. A source test was performed per SCAQMD guidelines and the final report has been approved by the SCAQMD.

  4. Removal efficiencies of PCDDs/PCDFs by air pollution control devices in municipal solid waste incinerators.

    PubMed

    Kim, S C; Jeon, S H; Jung, I R; Kim, K H; Kwon, M H; Kim, J H; Yi, J H; Kim, S J; You, J C; Jung, D H

    2001-01-01

    Removal efficiencies of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDDs/PCDFs) by air pollution control devices (APCDs) in the commercial-scale municipal solid waste (MSW) incinerators with a capacity of above 200 ton/day were evaluated. The removal efficiencies of PCDDs/PCDFs were up to 95% when the activated carbon (AC) was injected in front of electrostatic precipitator (EP). Spray dryer absorber/bag filter (SDA/BF) had high removal efficiency (99%)) of PCDDs/PCDFs when a mixture of lime and AC was sprayed into the SDA. When the AC was not added in scrubbing solution, the whole congeners of PCDDs/PCDFs were enriched in the wet scrubber (WS) with negative removal efficiencies of -25% to -5731%. Discharge of PCDDs/PCDFs was decreased with increasing the proportions of AC added in scrubbing solution. Selective catalytic reduction (SCR) system had the removal efficiencies of up to 93% during the test operation.

  5. Remote sensing techniques from helicopter for water quality and air pollution control

    SciTech Connect

    Geraci, A.L.; Landolina, F.F.

    1996-11-01

    Aircraft remote sensing provides a number of benefits, allowing to vary the detection parameters, giving better resolution, and being little affected by weather conditions and no replaceable under emergency situations. Also as a part of projects funded by the Commission of the European Communities, through the Regional Government of Sicily, applications of remote sensing techniques were carried out from helicopter over selected study areas in Sicily, for water quality and air pollution control. In particular, remotely-sensed data were acquired, using LASER techniques and thermal infrared imagery, for the monitoring of water quality and the assessment of oil pollution. Furthermore, air quality was investigated, using LASER techniques and correlation spectroscopy. In a perspective of integration, the investigations carried out proved effective and useful, confirming the important role of the helicopter as monitoring platform for environmental remote sensing applications. 6 refs., 11 figs.

  6. Quantification of local and global benefits from air pollution control in Mexico City.

    PubMed

    Mckinley, Galen; Zuk, Miriam; Höjer, Morten; Avalos, Montserrat; González, Isabel; Iniestra, Rodolfo; Laguna, Israel; Martínez, Miguel A; Osnaya, Patricia; Reynales, Luz M; Valdés, Raydel; Martínez, Julia

    2005-04-01

    Complex sociopolitical, economic, and geographical realities cause the 20 million residents of Mexico City to suffer from some of the worst air pollution conditions in the world. Greenhouse gas emissions from the city are also substantial, and opportunities for joint local-global air pollution control are being sought. Although a plethora of measures to improve local air quality and reduce greenhouse gas emissions have been proposed for Mexico City, resources are not available for implementation of all proposed controls and thus prioritization must occur. Yet policy makers often do not conduct comprehensive quantitative analyses to inform these decisions. We reanalyze a subset of currently proposed control measures, and derive cost and health benefit estimates that are directly comparable. This study illustrates that improved quantitative analysis can change implementation prioritization for air pollution and greenhouse gas control measures in Mexico City.

  7. Effectiveness of national air pollution control policies on the air quality in metropolitan areas of China.

    PubMed

    Wang, Shuxiao; Xing, Jia; Zhao, Bin; Jang, Carey; Hao, Jiming

    2014-01-01

    Understanding the effectiveness of national air pollution controls is important for control policy design to improve the future air quality in China. This study evaluated the effectiveness of major national control policies implemented recently in China through a modeling analysis. The sulfur dioxide (SO2) control policy during the 11th Five Year Plan period (2006-2010) had succeeded in reducing the national SO2 emission in 2010 by 14% from its 2005 level, which correspondingly reduced ambient SO2 and sulfate (SO4(2-)) concentrations by 13%-15% and 8%-10% respectively over east China. The nitrogen oxides (NO(x)) control policy during the 12th Five Year Plan period (2011-2015) targets the reduction of the national NO(x) emission in 2015 by 10% on the basis of 2010. The simulation results suggest that such a reduction in NO(x) emission will reduce the ambient nitrogen dioxide (NO2), nitrate (NO3(-)), 1-hr maxima ozone (O3) concentrations and total nitrogen deposition by 8%, 3%-14%, 2% and 2%-4%, respectively over east China. The application of new emission standards for power plants will further reduce the NO2, NO3(-), 1-hr maxima O(3 concentrations and total nitrogen deposition by 2%-4%, 1%-6%, 0-2% and 1%-2%, respectively. Sensitivity analysis was conducted to evaluate the inter-provincial impacts of emission reduction in Beijing-Tianjin-Hebei and the Yangtze River Delta, which indicated the need to implement joint regional air pollution control.

  8. Effectiveness of national air pollution control policies on the air quality in metropolitan areas of China.

    PubMed

    Wang, Shuxiao; Xing, Jia; Zhao, Bin; Jang, Carey; Hao, Jiming

    2014-01-01

    Understanding the effectiveness of national air pollution controls is important for control policy design to improve the future air quality in China. This study evaluated the effectiveness of major national control policies implemented recently in China through a modeling analysis. The sulfur dioxide (SO2) control policy during the 11th Five Year Plan period (2006-2010) had succeeded in reducing the national SO2 emission in 2010 by 14% from its 2005 level, which correspondingly reduced ambient SO2 and sulfate (SO4(2-)) concentrations by 13%-15% and 8%-10% respectively over east China. The nitrogen oxides (NO(x)) control policy during the 12th Five Year Plan period (2011-2015) targets the reduction of the national NO(x) emission in 2015 by 10% on the basis of 2010. The simulation results suggest that such a reduction in NO(x) emission will reduce the ambient nitrogen dioxide (NO2), nitrate (NO3(-)), 1-hr maxima ozone (O3) concentrations and total nitrogen deposition by 8%, 3%-14%, 2% and 2%-4%, respectively over east China. The application of new emission standards for power plants will further reduce the NO2, NO3(-), 1-hr maxima O(3 concentrations and total nitrogen deposition by 2%-4%, 1%-6%, 0-2% and 1%-2%, respectively. Sensitivity analysis was conducted to evaluate the inter-provincial impacts of emission reduction in Beijing-Tianjin-Hebei and the Yangtze River Delta, which indicated the need to implement joint regional air pollution control. PMID:24649687

  9. Aggregate material formulated with MSWI bottom ash and APC fly ash for use as secondary building material

    SciTech Connect

    Valle-Zermeño, R. del; Formosa, J.; Chimenos, J.M.; Martínez, M.; Fernández, A.I.

    2013-03-15

    Highlights: ► A concrete formulation was optimized using Bottom Ash and APC ash. ► 10% of APC ash achieves good compromise between economic and performance aspects. ► The crushed concrete was evaluated as secondary building granular material. ► The environmental behavior allows its use as secondary material. ► The abrasion resistance is not good enough for its use as a road sub-base material. - Abstract: The main goal of this paper is to obtain a granular material formulated with Municipal Solid Waste Incineration (MSWI) bottom ash (BA) and air pollution control (APC) fly ash to be used as secondary building material. Previously, an optimum concrete mixture using both MSWI residues as aggregates was formulated. A compromise between the environmental behavior whilst maximizing the reuse of APC fly ash was considered and assessed. Unconfined compressive strength and abrasion resistance values were measured in order to evaluate the mechanical properties. From these results, the granular mixture was not suited for certain applications owing to the high BA/APC fly ash content and low cement percentages used to reduce the costs of the final product. Nevertheless, the leaching test performed showed that the concentrations of all heavy metals were below the limits established by the current Catalan legislation for their reutilization. Therefore, the material studied might be mainly used in embankments, where high mechanical properties are not needed and environmental safety is assured.

  10. Field Operations and Enforcement Manual for Air Pollution Control. Volume II: Control Technology and General Source Inspection.

    ERIC Educational Resources Information Center

    Weisburd, Melvin I.

    The Field Operations and Enforcement Manual for Air Pollution Control, Volume II, explains in detail the following: technology of source control, modification of operations, particulate control equipment, sulfur dioxide removal systems for power plants, and control equipment for gases and vapors; inspection procedures for general sources, fuel…

  11. Healy Clean Coal Project, Healy FCM testing at Niro Air Pollution Control Pilot Facility. Final report

    SciTech Connect

    Not Available

    1992-10-01

    In September, 1991, pilot testing was performed at the Niro Air Pollution Control Pilot Plant in Copenhagen, Denmark in support of the Healy Clean Coal Project (HCCP), which is part of the United States Department of Energy (DOE) Clean Coal Technology Ill Program. The HCCP is a proposed new coal fired power plant, located in Healy, Alaska. It consists of a TRW entrained combustion system, coupled with a limestone calciner, which operates in synergism with a Joy/Niro Spray Dryer Absorber (SDA) system equipped with a lime activation system that is designed to increase the utilization of the calcined product for sulfur capture in the SDA. The pilot tests, which were funded by the United States Department of Energy (DOE) and the Alaska Industrial Development and Export Authority (AIDEA), were conducted to investigate the characteristics of the TRW combustor/limestone calciner product, referred to as Flash Calcined Material (FCM) with respect to its ability to remove S0{sub 2 } in the Joy/Niro Activated Recycle SDA system. This report describes the pilot facility, the test objectives and methods, and the results of the tests.

  12. Healy Clean Coal Project, Healy FCM testing at Niro Air Pollution Control Pilot Facility

    SciTech Connect

    Not Available

    1992-10-01

    In September, 1991, pilot testing was performed at the Niro Air Pollution Control Pilot Plant in Copenhagen, Denmark in support of the Healy Clean Coal Project (HCCP), which is part of the United States Department of Energy (DOE) Clean Coal Technology Ill Program. The HCCP is a proposed new coal fired power plant, located in Healy, Alaska. It consists of a TRW entrained combustion system, coupled with a limestone calciner, which operates in synergism with a Joy/Niro Spray Dryer Absorber (SDA) system equipped with a lime activation system that is designed to increase the utilization of the calcined product for sulfur capture in the SDA. The pilot tests, which were funded by the United States Department of Energy (DOE) and the Alaska Industrial Development and Export Authority (AIDEA), were conducted to investigate the characteristics of the TRW combustor/limestone calciner product, referred to as Flash Calcined Material (FCM) with respect to its ability to remove S0[sub 2 ] in the Joy/Niro Activated Recycle SDA system. This report describes the pilot facility, the test objectives and methods, and the results of the tests.

  13. Statistical estimate of mercury removal efficiencies for air pollution control devices of municipal solid waste incinerators.

    PubMed

    Takahashi, Fumitake; Kida, Akiko; Shimaoka, Takayuki

    2010-10-15

    Although representative removal efficiencies of gaseous mercury for air pollution control devices (APCDs) are important to prepare more reliable atmospheric emission inventories of mercury, they have been still uncertain because they depend sensitively on many factors like the type of APCDs, gas temperature, and mercury speciation. In this study, representative removal efficiencies of gaseous mercury for several types of APCDs of municipal solid waste incineration (MSWI) were offered using a statistical method. 534 data of mercury removal efficiencies for APCDs used in MSWI were collected. APCDs were categorized as fixed-bed absorber (FA), wet scrubber (WS), electrostatic precipitator (ESP), and fabric filter (FF), and their hybrid systems. Data series of all APCD types had Gaussian log-normality. The average removal efficiency with a 95% confidence interval for each APCD was estimated. The FA, WS, and FF with carbon and/or dry sorbent injection systems had 75% to 82% average removal efficiencies. On the other hand, the ESP with/without dry sorbent injection had lower removal efficiencies of up to 22%. The type of dry sorbent injection in the FF system, dry or semi-dry, did not make more than 1% difference to the removal efficiency. The injection of activated carbon and carbon-containing fly ash in the FF system made less than 3% difference. Estimation errors of removal efficiency were especially high for the ESP. The national average of removal efficiency of APCDs in Japanese MSWI plants was estimated on the basis of incineration capacity. Owing to the replacement of old APCDs for dioxin control, the national average removal efficiency increased from 34.5% in 1991 to 92.5% in 2003. This resulted in an additional reduction of about 0.86Mg emission in 2003. Further study using the methodology in this study to other important emission sources like coal-fired power plants will contribute to better emission inventories.

  14. Evaluation of mercury speciation and removal through air pollution control devices of a 190 MW boiler.

    PubMed

    Wu, Chengli; Cao, Yan; Dong, Zhongbing; Cheng, Chinmin; Li, Hanxu; Pan, Weiping

    2010-01-01

    Air pollution control devices (APCDs) are installed at coal-fired power plants for air pollutant regulation. Selective catalytic reduction (SCR) and wet flue gas desulfurization (FGD) systems have the co-benefits of air pollutant and mercury removal. Configuration and operational conditions of APCDs and mercury speciation affect mercury removal efficiently at coal-fired utilities. The Ontario Hydro Method (OHM) recommended by the U.S. Environmental Protection Agency (EPA) was used to determine mercury speciation simultaneously at five sampling locations through SCR-ESP-FGD at a 190 MW unit. Chlorine in coal had been suggested as a factor affecting the mercury speciation in flue gas; and low-chlorine coal was purported to produce less oxidized mercury (Hg2+) and more elemental mercury (Hg0) at the SCR inlet compared to higher chlorine coal. SCR could oxidize elemental mercury into oxidized mercury when SCR was in service, and oxidation efficiency reached 71.0%. Therefore, oxidized mercury removal efficiency was enhanced through a wet FGD system. In the non-ozone season, about 89.5%-96.8% of oxidized mercury was controlled, but only 54.9%-68.8% of the total mercury was captured through wet FGD. Oxidized mercury removal efficiency was 95.9%-98.0%, and there was a big difference in the total mercury removal efficiencies from 78.0% to 90.2% in the ozone season. Mercury mass balance was evaluated to validate reliability of OHM testing data, and the ratio of mercury input in the coal to mercury output at the stack was from 0.84 to 1.08.

  15. Evaluation of mercury speciation and removal through air pollution control devices of a 190 MW boiler.

    PubMed

    Wu, Chengli; Cao, Yan; Dong, Zhongbing; Cheng, Chinmin; Li, Hanxu; Pan, Weiping

    2010-01-01

    Air pollution control devices (APCDs) are installed at coal-fired power plants for air pollutant regulation. Selective catalytic reduction (SCR) and wet flue gas desulfurization (FGD) systems have the co-benefits of air pollutant and mercury removal. Configuration and operational conditions of APCDs and mercury speciation affect mercury removal efficiently at coal-fired utilities. The Ontario Hydro Method (OHM) recommended by the U.S. Environmental Protection Agency (EPA) was used to determine mercury speciation simultaneously at five sampling locations through SCR-ESP-FGD at a 190 MW unit. Chlorine in coal had been suggested as a factor affecting the mercury speciation in flue gas; and low-chlorine coal was purported to produce less oxidized mercury (Hg2+) and more elemental mercury (Hg0) at the SCR inlet compared to higher chlorine coal. SCR could oxidize elemental mercury into oxidized mercury when SCR was in service, and oxidation efficiency reached 71.0%. Therefore, oxidized mercury removal efficiency was enhanced through a wet FGD system. In the non-ozone season, about 89.5%-96.8% of oxidized mercury was controlled, but only 54.9%-68.8% of the total mercury was captured through wet FGD. Oxidized mercury removal efficiency was 95.9%-98.0%, and there was a big difference in the total mercury removal efficiencies from 78.0% to 90.2% in the ozone season. Mercury mass balance was evaluated to validate reliability of OHM testing data, and the ratio of mercury input in the coal to mercury output at the stack was from 0.84 to 1.08. PMID:20397418

  16. Interdisciplinary study of atmospheric processes and constituents of the mid-Atlantic coastal region.. [air pollution control studies in Virginia

    NASA Technical Reports Server (NTRS)

    Kindle, E. C.; Bandy, E. C.; Copeland, G.; Blais, R.; Levy, G.; Sonenshine, D.

    1975-01-01

    Past research projects for the year 1974-1975 are listed along with future research programs in the area of air pollution control, remote sensor analysis of smoke plumes, the biosphere component, and field experiments. A detailed budget analysis is presented. Attachments are included on the following topics: mapping forest vegetation with ERTS-1 MSS data and automatic data processing techniques, and use of LARS system for the quantitative determination of smoke plume lateral diffusion coefficients from ERTS images of Virginia.

  17. Mobility of organic carbon from incineration residues

    SciTech Connect

    Ecke, Holger Svensson, Malin

    2008-07-01

    Dissolved organic carbon (DOC) may affect the transport of pollutants from incineration residues when landfilled or used in geotechnical construction. The leaching of dissolved organic carbon (DOC) from municipal solid waste incineration (MSWI) bottom ash and air pollution control residue (APC) from the incineration of waste wood was investigated. Factors affecting the mobility of DOC were studied in a reduced 2{sup 6-1} experimental design. Controlled factors were treatment with ultrasonic radiation, full carbonation (addition of CO{sub 2} until the pH was stable for 2.5 h), liquid-to-solid (L/S) ratio, pH, leaching temperature and time. Full carbonation, pH and the L/S ratio were the main factors controlling the mobility of DOC in the bottom ash. Approximately 60 weight-% of the total organic carbon (TOC) in the bottom ash was available for leaching in aqueous solutions. The L/S ratio and pH mainly controlled the mobilization of DOC from the APC residue. About 93 weight-% of TOC in the APC residue was, however, not mobilized at all, which might be due to a high content of elemental carbon. Using the European standard EN 13 137 for determination of total organic carbon (TOC) in MSWI residues is inappropriate. The results might be biased due to elemental carbon. It is recommended to develop a TOC method distinguishing between organic and elemental carbon.

  18. Will joint regional air pollution control be more cost-effective? An empirical study of China's Beijing-Tianjin-Hebei region.

    PubMed

    Wu, Dan; Xu, Yuan; Zhang, Shiqiu

    2015-02-01

    By following an empirical approach, this study proves that joint regional air pollution control (JRAPC) in the Beijing-Tianjin-Hebei region will save the expense on air pollution control compared with a locally-based pollution control strategy. The evidences below were found. (A) Local pollutant concentration in some of the cities is significantly affected by emissions from their surrounding areas. (B) There is heterogeneity in the marginal pollutant concentration reduction cost among various districts as a result of the cities' varying contribution of unit emission reduction to the pollutant concentration reduction, and their diverse unit cost of emission reduction brought about by their different industry composition. The results imply that the cost-efficiency of air pollution control will be improved in China if the conventional locally based regime of air pollution control can shift to a regionally based one.

  19. Life-cycle-assessment of the historical development of air pollution control and energy recovery in waste incineration.

    PubMed

    Damgaard, Anders; Riber, Christian; Fruergaard, Thilde; Hulgaard, Tore; Christensen, Thomas H

    2010-07-01

    Incineration of municipal solid waste is a debated waste management technology. In some countries it is the main waste management option whereas in other countries it has been disregarded. The main discussion point on waste incineration is the release of air emissions from the combustion of the waste, but also the energy recovery efficiency has a large importance. The historical development of air pollution control in waste incineration was studied through life-cycle-assessment modelling of eight different air pollution control technologies. The results showed a drastic reduction in the release of air emissions and consequently a significant reduction in the potential environmental impacts of waste incineration. Improvements of a factor 0.85-174 were obtained in the different impact potentials as technology developed from no emission control at all, to the best available emission control technologies of today (2010). The importance of efficient energy recovery was studied through seven different combinations of heat and electricity recovery, which were modelled to substitute energy produced from either coal or natural gas. The best air pollution control technology was used at the incinerator. It was found that when substituting coal based energy production total net savings were obtained in both the standard and toxic impact categories. However, if the substituted energy production was based on natural gas, only the most efficient recovery options yielded net savings with respect to the standard impacts. With regards to the toxic impact categories, emissions from the waste incineration process were always larger than those from the avoided energy production based on natural gas. The results shows that the potential environmental impacts from air emissions have decreased drastically during the last 35 years and that these impacts can be partly or fully offset by recovering energy which otherwise should have been produced from fossil fuels like coal or natural gas.

  20. Life-cycle-assessment of the historical development of air pollution control and energy recovery in waste incineration

    SciTech Connect

    Damgaard, Anders; Riber, Christian; Fruergaard, Thilde; Hulgaard, Tore; Christensen, Thomas H.

    2010-07-15

    Incineration of municipal solid waste is a debated waste management technology. In some countries it is the main waste management option whereas in other countries it has been disregarded. The main discussion point on waste incineration is the release of air emissions from the combustion of the waste, but also the energy recovery efficiency has a large importance. The historical development of air pollution control in waste incineration was studied through life-cycle-assessment modelling of eight different air pollution control technologies. The results showed a drastic reduction in the release of air emissions and consequently a significant reduction in the potential environmental impacts of waste incineration. Improvements of a factor 0.85-174 were obtained in the different impact potentials as technology developed from no emission control at all, to the best available emission control technologies of today (2010). The importance of efficient energy recovery was studied through seven different combinations of heat and electricity recovery, which were modelled to substitute energy produced from either coal or natural gas. The best air pollution control technology was used at the incinerator. It was found that when substituting coal based energy production total net savings were obtained in both the standard and toxic impact categories. However, if the substituted energy production was based on natural gas, only the most efficient recovery options yielded net savings with respect to the standard impacts. With regards to the toxic impact categories, emissions from the waste incineration process were always larger than those from the avoided energy production based on natural gas. The results shows that the potential environmental impacts from air emissions have decreased drastically during the last 35 years and that these impacts can be partly or fully offset by recovering energy which otherwise should have been produced from fossil fuels like coal or natural gas.

  1. Aggregate material formulated with MSWI bottom ash and APC fly ash for use as secondary building material.

    PubMed

    del Valle-Zermeño, R; Formosa, J; Chimenos, J M; Martínez, M; Fernández, A I

    2013-03-01

    The main goal of this paper is to obtain a granular material formulated with Municipal Solid Waste Incineration (MSWI) bottom ash (BA) and air pollution control (APC) fly ash to be used as secondary building material. Previously, an optimum concrete mixture using both MSWI residues as aggregates was formulated. A compromise between the environmental behavior whilst maximizing the reuse of APC fly ash was considered and assessed. Unconfined compressive strength and abrasion resistance values were measured in order to evaluate the mechanical properties. From these results, the granular mixture was not suited for certain applications owing to the high BA/APC fly ash content and low cement percentages used to reduce the costs of the final product. Nevertheless, the leaching test performed showed that the concentrations of all heavy metals were below the limits established by the current Catalan legislation for their reutilization. Therefore, the material studied might be mainly used in embankments, where high mechanical properties are not needed and environmental safety is assured. PMID:23102641

  2. Structure of an APC3-APC16 complex: Insights into assembly of the Anaphase Promoting Complex/Cyclosome

    PubMed Central

    Yamaguchi, Masaya; Yu, Shanshan; Qiao, Renping; Weissmann, Florian; Miller, Darcie J.; VanderLinden, Ryan; Brown, Nicholas G.; Frye, Jeremiah J.; Peters, Jan-Michael; Schulman, Brenda A.

    2015-01-01

    The Anaphase Promoting Complex/Cyclosome (APC/C) is a massive E3 ligase that controls mitosis by catalyzing ubiquitination of key cell cycle regulatory proteins. The APC/C assembly contains two subcomplexes: the “Platform” centers around a cullin-RING-like E3 ligase catalytic core; the “Arc Lamp” is a hub that mediates transient association with regulators and ubiquitination substrates. The Arc Lamp contains the small subunits APC16, CDC26, and APC13, and tetratricopeptide repeat (TPR) proteins (APC7, APC3, APC6, and APC8) that homodimerize and stack with quasi-twofold symmetry. Within the APC/C complex, APC3 serves as center for regulation. APC3’s TPR motifs recruit substrate-binding coactivators, CDC20 and CDH1, via their C-terminal conserved Ile-Arg (IR) tail sequences. Human APC3 also binds APC16 and APC7, and contains a >200-residue loop that is heavily phosphorylated during mitosis, although the basis for APC3 interactions and whether loop phosphorylation is required for ubiquitination are unclear. Here, we map the basis for human APC3 assembly with APC16 and APC7, report crystal structures of APC3Δloop alone and in complex with the C-terminal domain of APC16, and test roles of APC3’s loop and IR-tail binding surfaces in APC/C-catalyzed ubiquitination. The structures show how one APC16 binds asymmetrically to the symmetric APC3 dimer, and together with biochemistry and prior data explain how APC16 recruits APC7 to APC3, show how APC3’s C-terminal domain is rearranged in the full APC/C assembly, and visualize residues in the IR-tail binding cleft important for coactivator-dependent ubiquitination. Overall, the results provide insights into assembly, regulation, and interactions of TPR proteins and the APC/C. PMID:25490258

  3. Influence of proxy attributes on multiattribute decision analysis: An empirical investigation in the context of air pollution control

    SciTech Connect

    Damodaran, N.

    1988-01-01

    Three separate studies in decision analysis were conducted in the context of air pollution control wherein the preferences of informed subjects were individually assessed. The first study was designed to develop a decision model for the control of sulfur dioxide emissions by incorporating multi-media effects of pollution control using both fundamental and proxy attributes. The second study specifically compared fundamental and proxy attributes and tested the hypothesis that proxy attributes lead to biased decisions. The third study validated the results of the previous one and was extended to examine the hypothesis that proxy bias could be reduced by appropriate elicitation techniques. The findings of this study indicated that subjects behaved according to the norms of expected utility theory when the unidimensional utility function for the proxy attribute was assessed. However, subjects exhibited a near universal bias to overweight the proxy attribute, relative to prescriptions of expected utility theory, in a multi-attribute scenario.

  4. Air pollution control in the Mexico City Metropolitan area. Results for the short-term program. Consolidated final report (revised). Export trade information

    SciTech Connect

    Not Available

    1991-06-01

    The report represents the efforts of teams of experts from Mexico, Germany, France, and the United States in the area of air pollution control for the Mexico City metropolitan area. Specific tasks performed were: emissions data analysis; air quality monitoring program; control measure evaluation; and air quality modelling and analysis.

  5. How well have China's recent five-year plans been implemented for energy conservation and air pollution control?

    PubMed

    Mao, XianQiang; Zhou, Ji; Corsetti, Gabriel

    2014-09-01

    This study evaluates how well China's 11th and 12th Five-Year Plans have been implemented in terms of energy conservation and air pollution control and deconstructs the effects of the economic, energy, and environmental policies included in the Plans. A "counterfactual" comparative-scenario method is deployed, which assumes a business as usual scenario in which the changes in economic, energy, and environmental parameters are "frozen", and then reactivates them one by one, with the help of LEAP modeling. It is found that during the 11th Five-Year Plan period, the binding targets were basically achieved. Economic growth put a great strain upon the energy demand and the environment, but energy policy made a decisive contribution by promoting energy efficiency and structure. Environmental policy promoted the deployment of end-of-pipe treatment which led to the control of certain air pollutants but at the expense of an increase in energy use and in the emission of other pollutants. During the ongoing 12th Five-Year Plan period, energy policy's potential for efficiency improvement is shrinking, but economic policy is restraining economic growth thus making a positive contribution. Environmental policy attempts to enforce multipollutant reduction, but there is still insufficient focus on the cocontrol of different pollutants and CO2.

  6. Effect of municipal solid waste incinerator types on characteristics of ashes from different air pollution control devices.

    PubMed

    Lu, Chien-Hsing; Chuang, Kui-Hao

    2016-01-01

    The purpose of this paper is to investigate the characteristics of fly and bottom ashes sampled from both fluidized bed (FB) and mass-burning (MB) municipal solid waste incinerators (MSWIs), respectively. Fly ashes from different locations at FB and MB MSWIs equipped with a cyclone, a semi-dry scrubber, and a bag filter as air pollution control devices were examined to provide the baseline information between physicochemical properties and leaching ability. Experimental results of leachability indicated that the bag filter fly ash (FB-FA(B)) from the FB incinerator meets Taiwan regulatory standards set through the toxicity characteristic leaching procedure. X-ray diffraction results revealed the presence of Cr5O12 and Pb2O3 in the cyclone fly ash (MB-FA(C)) and bag filter fly ash (MB-FA(B)), respectively, from the MB incinerator. To observe lead incorporation mechanism, mixture of simulate lead-laden waste with bed material were fired between 600 °C and 900 °C in a laboratory scale FB reactor. The results clearly demonstrate a substantial decrease in lead leaching ratio for products with an appropriate temperature. The concentration of Pb in the MB-FA(B) was 250 times that in the FB-FA(B), suggesting that incineration of MSW in FB is a good strategy for stabilizing hazardous metals.

  7. Effect of municipal solid waste incinerator types on characteristics of ashes from different air pollution control devices.

    PubMed

    Lu, Chien-Hsing; Chuang, Kui-Hao

    2016-01-01

    The purpose of this paper is to investigate the characteristics of fly and bottom ashes sampled from both fluidized bed (FB) and mass-burning (MB) municipal solid waste incinerators (MSWIs), respectively. Fly ashes from different locations at FB and MB MSWIs equipped with a cyclone, a semi-dry scrubber, and a bag filter as air pollution control devices were examined to provide the baseline information between physicochemical properties and leaching ability. Experimental results of leachability indicated that the bag filter fly ash (FB-FA(B)) from the FB incinerator meets Taiwan regulatory standards set through the toxicity characteristic leaching procedure. X-ray diffraction results revealed the presence of Cr5O12 and Pb2O3 in the cyclone fly ash (MB-FA(C)) and bag filter fly ash (MB-FA(B)), respectively, from the MB incinerator. To observe lead incorporation mechanism, mixture of simulate lead-laden waste with bed material were fired between 600 °C and 900 °C in a laboratory scale FB reactor. The results clearly demonstrate a substantial decrease in lead leaching ratio for products with an appropriate temperature. The concentration of Pb in the MB-FA(B) was 250 times that in the FB-FA(B), suggesting that incineration of MSW in FB is a good strategy for stabilizing hazardous metals. PMID:26226945

  8. Integrated Air Pollution Control System (IAPS), executable model and source model (version 5.a) (on diskette). Model-Simulation

    SciTech Connect

    1997-09-01

    The Integrated Air Pollution Control System (IAPCS) Cost Model was developed to estimate costs and performance for emission control systems applied to coal-fired utility boilers. The model can project a material balance, an equipment list, and capital investment and revenue requirements based on user-specified input data. The model includes conventional and emerging technologies for controlling nitrogen oxides (NOX), sulfur dioxide, and particulate matter emissions. A variety of technology modules built into the model can be incorporated and combined. Cost and performance estimates can be analyzed in terms of integrated technologies. Conventional and emerging technologies included are low NOX combustion (overfire air/low NOX burners), natural gas reburning, advanced gas reburning, selective catalytic reduction, selective noncatalytic reduction, limestone injection multistage burners, the advanced silicate process, wet limestone flue gas desulfurization, dry sorbent injection, physical coal cleaning, coal switching, lime spray drying, spray humidification, electrostatic precipitators, fabric filters, atmospheric fluidized bed combustion, pressurized fluidized bed combustion, the integrated gasfication combined cycle process, and pulverized coal burning boilers. The following revisions have been made to version 5.a: - Addition of Gas Substitution (GS) to the Natural Gas Reburning (NGR) and Advanced Gas Reburning (AGR) Module. Gas Substitution (GS) was added to allow the user to estimate the cost of substituting natural gas for coal in a utility boiler. - Flue Gas Flow Rate Revision. The user can now choose to use coal analyses to compute the mass and volumetric flue gas flow rate. Previously, an F-Factor was used, which calculated flue gas flow rate as a function of heat input to the boiler (dscf/MMBtu). ADVACATE Revision. The maximum size of a tower mill is 60 MW. The previous ADVACATE cost equations were based on a tower mill size of 100 MW.

  9. Characteristics of ashes from different locations at the MSW incinerator equipped with various air pollution control devices

    SciTech Connect

    Song, Geum-Ju; Kim, Ki-Heon; Seo, Yong-Chil; Kim, Sam-Cwan

    2004-07-01

    The characteristics of ashes from different locations at a municipal solid waste incinerator (MSWI) equipped with a water spray tower (WST) as a cooling system, and a spray dryer adsorber (SDA), a bag filter (BF) and a selective catalytic reactor (SCR) as air pollution control devices (APCD) was investigated to provide the basic data for further treatment of ashes. A commercial MSWI with a capacity of 100 tons per day was selected. Ash was sampled from different locations during the normal operation of the MSWI and was analyzed to obtain chemical composition, basicity, metal contents and leaching behavior of heavy metals. Basicity and pH of ash showed a broad range between 0.08-9.07 and 3.5-12.3, respectively. Some major inorganics in ash were identified and could affect the basicity. This could be one of the factors to determine further treatment means. Partitioning of hazardous heavy metals such as Pb, Cu, Cr, Hg and Cd was investigated. Large portions of Hg and Cd were emitted from the furnace while over 90% of Pb, Cu and Cr remained in bottom ash. However 54% of Hg was captured by WST and 41% by SDA/BF and 3.6% was emitted through the stack, while 81.5% of Cd was captured by SDA/BF. From the analysis data of various metal contents in ash and leach analysis, such capturing of metal was confirmed and some heavy metals found to be easily released from ash. Based on the overall characteristics of ash in different locations at the MSWI during the investigation, some considerations and suggestions for determining the appropriate treatment methods of ash were made as conclusions.

  10. Structure of an APC3–APC16 Complex: Insights into Assembly of the Anaphase-Promoting Complex/Cyclosome

    SciTech Connect

    Yamaguchi, Masaya; Yu, Shanshan; Qiao, Renping; Weissmann, Florian; Miller, Darcie J.; VanderLinden, Ryan; Brown, Nicholas G.; Frye, Jeremiah J.; Peters, Jan-Michael; Schulman, Brenda A.

    2015-08-21

    The anaphase-promoting complex/cyclosome (APC/C) is a massive E3 ligase that controls mitosis by catalyzing ubiquitination of key cell cycle regulatory proteins. The APC/C assembly contains two subcomplexes: the “Platform” centers around a cullin-RING-like E3 ligase catalytic core; the “Arc Lamp” is a hub that mediates transient association with regulators and ubiquitination substrates. The Arc Lamp contains the small subunits APC16, CDC26, and APC13, and tetratricopeptide repeat (TPR) proteins (APC7, APC3, APC6, and APC8) that homodimerize and stack with quasi-2-fold symmetry. Within the APC/C complex, APC3 serves as center for regulation. APC3's TPR motifs recruit substrate-binding coactivators, CDC20 and CDH1, via their C-terminal conserved Ile-Arg (IR) tail sequences. Human APC3 also binds APC16 and APC7 and contains a > 200-residue loop that is heavily phosphorylated during mitosis, although the basis for APC3 interactions and whether loop phosphorylation is required for ubiquitination are unclear. Here, we map the basis for human APC3 assembly with APC16 and APC7, report crystal structures of APC3Δloop alone and in complex with the C-terminal domain of APC16, and test roles of APC3's loop and IR tail binding surfaces in APC/C-catalyzed ubiquitination. The structures show how one APC16 binds asymmetrically to the symmetric APC3 dimer and, together with biochemistry and prior data, explain how APC16 recruits APC7 to APC3, show how APC3's C-terminal domain is rearranged in the full APC/C assembly, and visualize residues in the IR tail binding cleft important for coactivator-dependent ubiquitination. Overall, the results provide insights into assembly, regulation, and interactions of TPR proteins and the APC/C.

  11. Thermal treatment of solid residues from WtE units: A review

    SciTech Connect

    Lindberg, Daniel Molin, Camilla Hupa, Mikko

    2015-03-15

    Highlights: • We review the thermal treatment methods for ashes and residues from WtE plants. • We review the results from extensive laboratory work on vitrification, melting and vaporization of ash. • We analyze the results from the extensive patent literature on thermal treatment. • We review industrial concepts for thermal treatment of ash. - Abstract: Thermal treatment methods of bottom ash, fly ash and various types of APC (air pollution control) residues from waste-to-energy plants can be used to obtain environmentally stable material. The thermal treatment processes are meant to reduce the leachability of harmful residue constituents, destroy toxic organic compounds, reduce residue volume, and produce material suitable for utilization. Fly ash and APC residues often have high levels of soluble salts, particularly chlorides, metals such as cadmium, lead, copper and zinc, and trace levels of organic pollutants such as dioxins and furans. Different thermal treatment methods can be used to either decompose or stabilize harmful elements and compounds in the ash, or separate them from the ash to get a material that can be safely stored or used as products or raw materials. In the present paper, thermal treatment methods, such as sintering, vitrification, and melting have been reviewed. In addition to a review of the scientific literature, a survey has been made of the extensive patent literature in the field.

  12. Impact of air pollution control costs on the cost and spatial arrangement of cellulosic biofuel production in the U.S.

    PubMed

    Murphy, Colin W; Parker, Nathan C

    2014-02-18

    Air pollution emissions regulation can affect the location, size, and technology choice of potential biofuel production facilities. Difficulty in obtaining air pollutant emission permits and the cost of air pollution control devices have been cited by some fuel producers as barriers to development. This paper expands on the Geospatial Bioenergy Systems Model (GBSM) to evaluate the effect of air pollution control costs on the availability, cost, and distribution of U.S. biofuel production by subjecting potential facility locations within U.S. Clean Air Act nonattainment areas, which exceed thresholds for healthy air quality, to additional costs. This paper compares three scenarios: one with air quality costs included, one without air quality costs, and one in which conversion facilities were prohibited in Clean Air Act nonattainment areas. While air quality regulation may substantially affect local decisions regarding siting or technology choices, their effect on the system as a whole is small. Most biofuel facilities are expected to be sited near to feedstock supplies, which are seldom in nonattainment areas. The average cost per unit of produced energy is less than 1% higher in the scenarios with air quality compliance costs than in scenarios without such costs. When facility construction is prohibited in nonattainment areas, the costs increase by slightly over 1%, due to increases in the distance feedstock is transported to facilities in attainment areas.

  13. Thermal treatment of solid residues from WtE units: a review.

    PubMed

    Lindberg, Daniel; Molin, Camilla; Hupa, Mikko

    2015-03-01

    Thermal treatment methods of bottom ash, fly ash and various types of APC (air pollution control) residues from waste-to-energy plants can be used to obtain environmentally stable material. The thermal treatment processes are meant to reduce the leachability of harmful residue constituents, destroy toxic organic compounds, reduce residue volume, and produce material suitable for utilization. Fly ash and APC residues often have high levels of soluble salts, particularly chlorides, metals such as cadmium, lead, copper and zinc, and trace levels of organic pollutants such as dioxins and furans. Different thermal treatment methods can be used to either decompose or stabilize harmful elements and compounds in the ash, or separate them from the ash to get a material that can be safely stored or used as products or raw materials. In the present paper, thermal treatment methods, such as sintering, vitrification, and melting have been reviewed. In addition to a review of the scientific literature, a survey has been made of the extensive patent literature in the field.

  14. High performance APCS conceptual design and evaluation scoping study

    SciTech Connect

    Soelberg, N.; Liekhus, K.; Chambers, A.; Anderson, G.

    1998-02-01

    This Air Pollution Control System (APCS) Conceptual Design and Evaluation study was conducted to evaluate a high-performance (APC) system for minimizing air emissions from mixed waste thermal treatment systems. Seven variations of high-performance APCS designs were conceptualized using several design objectives. One of the system designs was selected for detailed process simulation using ASPEN PLUS to determine material and energy balances and evaluate performance. Installed system capital costs were also estimated. Sensitivity studies were conducted to evaluate the incremental cost and benefit of added carbon adsorber beds for mercury control, specific catalytic reduction for NO{sub x} control, and offgas retention tanks for holding the offgas until sample analysis is conducted to verify that the offgas meets emission limits. Results show that the high-performance dry-wet APCS can easily meet all expected emission limits except for possibly mercury. The capability to achieve high levels of mercury control (potentially necessary for thermally treating some DOE mixed streams) could not be validated using current performance data for mercury control technologies. The engineering approach and ASPEN PLUS modeling tool developed and used in this study identified APC equipment and system performance, size, cost, and other issues that are not yet resolved. These issues need to be addressed in feasibility studies and conceptual designs for new facilities or for determining how to modify existing facilities to meet expected emission limits. The ASPEN PLUS process simulation with current and refined input assumptions and calculations can be used to provide system performance information for decision-making, identifying best options, estimating costs, reducing the potential for emission violations, providing information needed for waste flow analysis, incorporating new APCS technologies in existing designs, or performing facility design and permitting activities.

  15. Mechanism of APC/CCDC20 activation by mitotic phosphorylation

    PubMed Central

    Qiao, Renping; Weissmann, Florian; Yamaguchi, Masaya; Brown, Nicholas G.; VanderLinden, Ryan; Imre, Richard; Jarvis, Marc A.; Brunner, Michael R.; Davidson, Iain F.; Litos, Gabriele; Haselbach, David; Mechtler, Karl; Stark, Holger; Schulman, Brenda A.; Peters, Jan-Michael

    2016-01-01

    Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/CCDC20 activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a mitotic checkpoint complex until all chromosomes are bioriented on the spindle. APC/C contains 14 different types of subunits, most of which are phosphorylated in mitosis on multiple sites. However, it is unknown which of these phospho-sites enable APC/CCDC20 activation and by which mechanism. Here we have identified 68 evolutionarily conserved mitotic phospho-sites on human APC/C bound to CDC20 and have used the biGBac technique to generate 47 APC/C mutants in which either all 68 sites or subsets of them were replaced by nonphosphorylatable or phospho-mimicking residues. The characterization of these complexes in substrate ubiquitination and degradation assays indicates that phosphorylation of an N-terminal loop region in APC1 is sufficient for binding and activation of APC/C by CDC20. Deletion of the N-terminal APC1 loop enables APC/CCDC20 activation in the absence of mitotic phosphorylation or phospho-mimicking mutations. These results indicate that binding of CDC20 to APC/C is normally prevented by an autoinhibitory loop in APC1 and that its mitotic phosphorylation relieves this inhibition. The predicted location of the N-terminal APC1 loop implies that this loop controls interactions between the N-terminal domain of CDC20 and APC1 and APC8. These results reveal how APC/C phosphorylation enables CDC20 to bind and activate the APC/C in mitosis. PMID:27114510

  16. Occupational Structures and Profiles in the Federal Republic of Germany in the Field of Environmental Protection in the Public Service Sector with Reference to Air Pollution Control. CEDEFOP Panorama. National Report.

    ERIC Educational Resources Information Center

    Nitschke, Christoph; Funderich, Kirk

    A study examined the knowledge and job skills required of persons employed in air pollution control-related occupations in Germany's public service sector. In all, 18 persons from 11 offices in 10 public institutions were interviewed. In seven cases, two people from the same institution (one performing managerial duties and the other directly…

  17. To what extent can China’s near-term air pollution control policy protect air quality and human health? A case study of the Pearl River Delta region

    NASA Astrophysics Data System (ADS)

    Jiang, Xujia; Hong, Chaopeng; Zheng, Yixuan; Zheng, Bo; Guan, Dabo; Gouldson, Andy; Zhang, Qiang; He, Kebin

    2015-10-01

    Following a series of extreme air pollution events, the Chinese government released the Air Pollution Prevention and Control Action Plan in 2013 (China’s State Council 2013). The Action Plan sets clear goals for key regions (i.e. cities above the prefecture level, Beijing-Tianjin-Hebei Province, the Yangtze River Delta and the Pearl River Delta) and establishes near-term control efforts for the next five years. However, the extent to which the Action Plan can direct local governments’ activities on air pollution control remains unknown. Here we seek to evaluate the air quality improvement and associated health benefits achievable under the Action Plan in the Pearl River Delta (PRD) area from 2012 to 2017. Measure-by-measure quantification results show that the Action Plan would promise effective emissions reductions of 34% of SO2, 28% of NOx, 26% of PM2.5 (particulate matter less than 2.5 μm in diameter), and 10% of VOCs (volatile organic compounds). These emissions abatements would lower the PM2.5 concentration by 17%, surpassing the 15% target established in the Action Plan, thereby avoiding more than 2900 deaths and 4300 hospital admissions annually. We expect the implementation of the Action Plan in the PRD would be productive; the anticipated impacts, however, fall short of the goal of protecting the health of local residents, as there are still more than 33 million people living in places where the annual mean ambient PM2.5 concentrations are greater than 35 μg m-3, the interim target-3 of the World Health Organization (WHO). We therefore propose the next steps for air pollution control that are important not only for the PRD but also for all other regions of China as they develop and implement effective air pollution control policies.

  18. Removal of residual particulate matter from filter media

    SciTech Connect

    Almlie, Jay C; Miller, Stanley J

    2014-11-11

    A method for removing residual filter cakes that remain adhered to a filter after typical particulate removal methodologies have been employed, such as pulse-jet filter element cleaning, for all cleanable filters used for air pollution control, dust control, or powder control.

  19. On the ASR and ASR thermal residues characterization of full scale treatment plant.

    PubMed

    Mancini, G; Viotti, P; Luciano, A; Fino, D

    2014-02-01

    In order to obtain 85% recycling, several procedures on Automotive Shredder Residue (ASR) could be implemented, such as advanced metal and polymer recovery, mechanical recycling, pyrolysis, the direct use of ASR in the cement industry, and/or the direct use of ASR as a secondary raw material. However, many of these recovery options appear to be limited, due to the possible low acceptability of ASR based products on the market. The recovery of bottom ash and slag after an ASR thermal treatment is an option that is not usually considered in most countries (e.g. Italy) due to the excessive amount of contaminants, especially metals. The purpose of this paper is to provide information on the characteristics of ASR and its full-scale incineration residues. Experiments have been carried out, in two different experimental campaigns, in a full-scale tyre incineration plant specifically modified to treat ASR waste. Detailed analysis of ASR samples and combustion residues were carried out and compared with literature data. On the basis of the analytical results, the slag and bottom ash from the combustion process have been classified as non-hazardous wastes, according to the EU waste acceptance criteria (WAC), and therefore after further tests could be used in future in the construction industry. It has also been concluded that ASR bottom ash (EWC - European Waste Catalogue - code 19 01 12) could be landfilled in SNRHW (stabilized non-reactive hazardous waste) cells or used as raw material for road construction, with or without further treatment for the removal of heavy metals. In the case of fly ash from boiler or Air Pollution Control (APC) residues, it has been found that the Cd, Pb and Zn concentrations exceeded regulatory leaching test limits therefore their removal, or a stabilization process, would be essential prior to landfilling the use of these residues as construction material.

  20. On the ASR and ASR thermal residues characterization of full scale treatment plant.

    PubMed

    Mancini, G; Viotti, P; Luciano, A; Fino, D

    2014-02-01

    In order to obtain 85% recycling, several procedures on Automotive Shredder Residue (ASR) could be implemented, such as advanced metal and polymer recovery, mechanical recycling, pyrolysis, the direct use of ASR in the cement industry, and/or the direct use of ASR as a secondary raw material. However, many of these recovery options appear to be limited, due to the possible low acceptability of ASR based products on the market. The recovery of bottom ash and slag after an ASR thermal treatment is an option that is not usually considered in most countries (e.g. Italy) due to the excessive amount of contaminants, especially metals. The purpose of this paper is to provide information on the characteristics of ASR and its full-scale incineration residues. Experiments have been carried out, in two different experimental campaigns, in a full-scale tyre incineration plant specifically modified to treat ASR waste. Detailed analysis of ASR samples and combustion residues were carried out and compared with literature data. On the basis of the analytical results, the slag and bottom ash from the combustion process have been classified as non-hazardous wastes, according to the EU waste acceptance criteria (WAC), and therefore after further tests could be used in future in the construction industry. It has also been concluded that ASR bottom ash (EWC - European Waste Catalogue - code 19 01 12) could be landfilled in SNRHW (stabilized non-reactive hazardous waste) cells or used as raw material for road construction, with or without further treatment for the removal of heavy metals. In the case of fly ash from boiler or Air Pollution Control (APC) residues, it has been found that the Cd, Pb and Zn concentrations exceeded regulatory leaching test limits therefore their removal, or a stabilization process, would be essential prior to landfilling the use of these residues as construction material. PMID:24290536

  1. Percolation and batch leaching tests to assess release of inorganic pollutants from municipal solid waste incinerator residues.

    PubMed

    Quina, Margarida J; Bordado, João C M; Quinta-Ferreira, Rosa M

    2011-02-01

    In this study, percolation and batch leaching tests were considered in order to characterize the behaviour of air pollution control (APC) residues produced in a municipal solid waste incinerator (MSWI) as a function of the liquid to solid ratio (L/S). This waste is hazardous, and taking into account their physical and chemical properties, leaching of contaminants into the environment is the main concern. In our work the leaching behaviour of toxic heavy metals (Pb, Zn, Cr, Ni and Cu) and inorganics associated with soluble salts (Na, K, Ca and Cl) was addressed. Although pH of the leaching solution is the most important variable, L/S may also play an important role in leaching processes. In our work, results from column and batch tests were compared in terms of concentration (mg/L) and releasing (mg/kg). The APC residues revealed to be hazardous according to both tests, and both Pb and Cl(-) far exceeded the regulatory thresholds. The material exhibits high solubility, and when the liquid to solid ratio was high, more than 50% can be solubilised. The patterns of release may be in some cases availability or solubility controlled, and the former was easier to identify. When the results from column and batch experiments were compared by representing the cumulative released amounts (in mg/kg) as a function of L/S, both curves match for Zn, Ni, Cu, K, Na, Cl and Ca, but for Cr and Pb a significant difference was observed. In fact, the column experiments revealed that under percolation conditions it should be expected slow releasing of Pb along time. From this study, it can be concluded that the released amounts obtained in batch experiments for a certain L/S should be considered as the worst case for medium term. Some simple models proposed on the literature and based on local equilibrium assumption showed good fitting to experimental data for soluble species (non-reactive solutes).

  2. Metallic elements fractionation in municipal solid waste incineration residues

    NASA Astrophysics Data System (ADS)

    Kowalski, Piotr R.; Kasina, Monika; Michalik, Marek

    2016-04-01

    Municipal solid waste incineration (MSWI) residues are represented by three main materials: bottom ash, fly ash and air pollution control (APC) residues. Among them ˜80 wt% is bottom ash. All of that materials are products of high temperature (>1000° C) treatment of waste. Incineration process allows to obtain significant reduction of waste mass (up to 70%) and volume (up to 90%) what is commonly used in waste management to reduce the amount need to be landfilled or managed in other way. Incineration promote accumulation non-combustible fraction of waste, which part are metallic elements. That type of concentration is object of concerns about the incineration residues impact on the environment and also gives the possibility of attempts to recover them. Metallic elements are not equally distributed among the materials. Several factors influence the process: melting points, volatility and place and forms of metallic occurrence in the incinerated waste. To investigate metallic elements distribution in MSWI residues samples from one of the biggest MSW incineration plant in Poland were collected in 2015. Chemical analysis with emphasis on the metallic elements content were performed using inductively coupled plasma optical emission (ICP-OES) and mass spectrometry (ICP-MS). The bottom ash was a SiO2-CaO-Al2O3-Fe2O3-Na2O rich material, whereas fly ash and APC residues were mostly composed of CaO and SiO2. All of the materials were rich in amorphous phase occurring together with various, mostly silicate crystalline phases. In a mass of bottom ash 11 wt% were metallic elements but also in ashes 8.5 wt% (fly ash) and ˜4.5 wt% (APC residues) of them were present. Among the metallic elements equal distribution between bottom and fly ash was observed for Al (˜3.85 wt%), Mn (770 ppm) and Ni (˜65 ppm). In bottom ash Fe (5.5 wt%), Cr (590 ppm) and Cu (1250 ppm) were concentrated. These values in comparison to fly ash were 5-fold higher for Fe, 3-fold for Cu and 1.5-fold for

  3. Characterization of Coal Combustion Residues from Electric Utilities Using Wet Scrubbers for Multi-Pollutant Control

    EPA Science Inventory

    This report evaluates changes that may occur to coal combustion residues (CCRs) in response to changes in air pollution control technology at coal-fired power plants, which will reduce emissions from the flue gas stack by transferring pollutants to fly ash and other air pollution...

  4. Characterization of Coal Combustion Residues from Electric Utilities--Leaching and Characterization Data

    EPA Science Inventory

    This report evaluates changes in composition and constituent release by leaching that may occur to fly ash and other coal combustion residues (CCRs) in response to changes in air pollution control technology at coal-fired power plants. The addition of flue-gas desulfurization (FG...

  5. Combustion engine. [for air pollution control

    NASA Technical Reports Server (NTRS)

    Houseman, J. (Inventor)

    1977-01-01

    An arrangement for an internal combustion engine is provided in which one or more of the cylinders of the engine are used for generating hydrogen rich gases from hydrocarbon fuels, which gases are then mixed with air and injected into the remaining cylinders to be used as fuel. When heavy load conditions are encountered, hydrocarbon fuel may be mixed with the hydrogen rich gases and air and the mixture is then injected into the remaining cylinders as fuel.

  6. Effective Stack Design in Air Pollution Control.

    ERIC Educational Resources Information Center

    Clarke, John H.

    1968-01-01

    Stack design problems fall into two general caterories--(1) those of building re-entry, and (2) those of general area pollution. Extensive research has developed adequate information, available in the literature, to permit effective stack design. A major roadblock to effective design has been the strong belief by architects and engineers that high…

  7. Power plant air pollutant control 'Mega' symposium

    SciTech Connect

    2008-07-01

    Topics covered carbon management technologies, mercury (FGD-based controls, sorbents, TOXECON, additives and SO{sub 3} countermeasures 0, NOx (combined controls, SCR), SO{sub 2}, SO{sub 3}, multi-pollutant controls, particulates, and coal combustion products. The poster papers are also included.

  8. AIR POLLUTION CONTROL TECHNOLOGIES (CHAPTER 65)

    EPA Science Inventory

    The chapter discusses the use of technologies for reducing air pollution emissions from stationary sources, with emphasis on the control of combustion gen-erated air pollution. Major stationary sources include utility power boilers, industrial boilers and heaters, metal smelting ...

  9. Atomic-Resolution Structures of the APC/C Subunits Apc4 and the Apc5 N-Terminal Domain

    PubMed Central

    Cronin, Nora B.; Yang, Jing; Zhang, Ziguo; Kulkarni, Kiran; Chang, Leifu; Yamano, Hiroyuki; Barford, David

    2015-01-01

    Many essential biological processes are mediated by complex molecular machines comprising multiple subunits. Knowledge on the architecture of individual subunits and their positions within the overall multimeric complex is key to understanding the molecular mechanisms of macromolecular assemblies. The anaphase-promoting complex/cyclosome (APC/C) is a large multisubunit complex that regulates cell cycle progression by ubiquitinating cell cycle proteins for proteolysis by the proteasome. The holo-complex is composed of 15 different proteins that assemble to generate a complex of 20 subunits. Here, we describe the crystal structures of Apc4 and the N-terminal domain of Apc5 (Apc5N). Apc4 comprises a WD40 domain split by a long α-helical domain, whereas Apc5N has an α-helical fold. In a separate study, we had fitted these atomic models to a 3.6-Å-resolution cryo-electron microscopy map of the APC/C. We describe how, in the context of the APC/C, regions of Apc4 disordered in the crystal assume order through contacts to Apc5, whereas Apc5N shows small conformational changes relative to its crystal structure. We discuss the complementary approaches of high-resolution electron microscopy and protein crystallography to the structure determination of subunits of multimeric complexes. PMID:26343760

  10. ApcD, ApcF and ApcE are not required for the Orange Carotenoid Protein related phycobilisome fluorescence quenching in the cyanobacterium Synechocystis PCC 6803.

    PubMed

    Jallet, Denis; Gwizdala, Michal; Kirilovsky, Diana

    2012-08-01

    In cyanobacteria, strong blue-green light induces a photoprotective mechanism involving an increase of energy thermal dissipation at the level of phycobilisome (PB), the cyanobacterial antenna. This leads to a decrease of the energy arriving to the reaction centers. The photoactive Orange Carotenoid Protein (OCP) has an essential role in this mechanism. The binding of the red photoactivated OCP to the core of the PB triggers energy and PB fluorescence quenching. The core of PBs is constituted of allophycocyanin trimers emitting at 660 or 680nm. ApcD, ApcF and ApcE are the responsible of the 680nm emission. In this work, the role of these terminal emitters in the photoprotective mechanism was studied. Single and double Synechocystis PCC 6803 mutants, in which the apcD or/and apcF genes were absent, were constructed. The Cys190 of ApcE which binds the phycocyanobilin was replaced by a Ser. The mutated ApcE attached an unusual chromophore emitting at 710nm. The activated OCP was able to induce the photoprotective mechanism in all the mutants. Moreover, in vitro reconstitution experiments showed similar amplitude and rates of fluorescence quenching. Our results demonstrated that ApcD, ApcF and ApcE are not required for the OCP-related fluorescence quenching and they strongly suggested that the site of quenching is one of the APC trimers emitting at 660nm. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial. PMID:22172739

  11. APC15 mediates CDC20 auto-ubiquitylation by APC/CMCC and MCC disassembly

    PubMed Central

    Uzunova, Kristina; Dye, Billy T.; Schutz, Hannelore; Ladurner, Rene; Petzold, Georg; Toyoda, Yusuke; Jarvis, Marc A.; Brown, Nicholas G.; Poser, Ina; Novatchkova, Maria; Mechtler, Karl; Hyman, Anthony A.; Stark, Holger; Schulman, Brenda A.; Peters, Jan-Michael

    2012-01-01

    The anaphase-promoting complex/cyclosome bound to CDC20 (APC/CCDC20) initiates anaphase by ubiquitylating B-type cyclins and securin. During chromosome bi-orientation, CDC20 assembles with MAD2, BUBR1 and BUB3 into a mitotic checkpoint complex (MCC) which inhibits substrate recruitment to the APC/C. APC/C activation depends on MCC disassembly, which has been proposed to require CDC20 auto-ubiquitylation. Here we characterized APC15, a human APC/C subunit related to yeast Mnd2. APC15 is located near APC/C’s MCC binding site, is required for APC/CMCC-dependent CDC20 auto-ubiquitylation and degradation, and for timely anaphase initiation, but is dispensable for substrate ubiquitylation by APC/CCDC20 and APC/CCDH1. Our results support the view that MCC is continuously assembled and disassembled to enable rapid activation of APC/CCDC20 and that CDC20 auto-ubiquitylation promotes MCC disassembly. We propose that APC15 and Mnd2 negatively regulate APC/C coactivators, and report the first generation of recombinant human APC/C. PMID:23007861

  12. Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substrates

    PubMed Central

    Min, Mingwei; Mayor, Ugo; Lindon, Catherine

    2013-01-01

    Ordered progression of mitosis requires precise control in abundance of mitotic regulators. The anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase plays a key role by directing ubiquitin-mediated destruction of targets in a temporally and spatially defined manner. Specificity in APC/C targeting is conferred through recognition of substrate D-box and KEN degrons, while the specificity of ubiquitination sites, as another possible regulated dimension, has not yet been explored. Here, we present the first analysis of ubiquitination sites in the APC/C substrate ubiquitome. We show that KEN is a preferred ubiquitin acceptor in APC/C substrates and that acceptor sites are enriched in predicted disordered regions and flanked by serine residues. Our experimental data confirm a role for the KEN lysine as an ubiquitin acceptor contributing to substrate destruction during mitotic progression. Using Aurora A and Nek2 kinases as examples, we show that phosphorylation on the flanking serine residue could directly regulate ubiquitination and subsequent degradation of substrates. We propose a novel layer of regulation in substrate ubiquitination, via phosphorylation adjacent to the KEN motif, in APC/C-mediated targeting. PMID:24004664

  13. Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation

    PubMed Central

    Craney, Allison; Kelly, Aileen; Jia, Luying; Fedrigo, Indro; Yu, Hongtao; Rape, Michael

    2016-01-01

    Most metazoan E3 ligases contain a signature RING domain that promotes the transfer of ubiquitin from the active site of E2 conjugating enzymes to lysine residues in substrates. Although these RING-E3s depend on E2 enzymes for catalysis, how they turn on their E2s at the right time and place remains poorly understood. Here we report a phosphorylation-dependent mechanism that ensures timely activation of the E2 Ube2S by its RING-E3, the anaphase-promoting complex (APC/C); while phosphorylation of a specific serine residue in the APC/C coactivator Cdc20 prevents delivery of Ube2S to the APC/C, removal of this mark by PP2AB56 allows Ube2S to bind the APC/C and catalyze ubiquitin chain elongation. PP2AB56 also stabilizes kinetochore–microtubule attachments to shut off the spindle checkpoint, suggesting that cells regulate the E2–E3 interplay to coordinate ubiquitination with critical events during cell division. PMID:26811472

  14. Increased biomass production and glycogen accumulation in apcE gene deleted Synechocystis sp. PCC 6803

    PubMed Central

    2014-01-01

    The effect of phycobilisome antenna-truncation in the cyanobacterium Synechocystis sp. PCC 6803 on biomass production and glycogen accumulation have not yet been fully clarified. To investigate these effects here, the apcE gene, which encodes the anchor protein linking the phycobilisome to the thylakoid membrane, was deleted in a glucose tolerant strain of Synechocystis sp. PCC 6803. Biomass production of the apcE-deleted strain under photoautotrophic and atmospheric air conditions was 1.6 times higher than that of strain PCC 6803 (1.32 ± 0.01 versus 0.84 ± 0.07 g cell-dry weight L−1, respectively) after 15 days of cultivation. In addition, the glycogen content of the apcE-deleted strain (24.2 ± 0.7%) was also higher than that of strain PCC 6803 (11.1 ± 0.3%). Together, these results demonstrate that antenna truncation by deleting the apcE gene was effective for increasing biomass production and glycogen accumulation under photoautotrophic and atmospheric air conditions in Synechocystis sp. PCC 6803. PMID:24949254

  15. Integrated metrology: an enabler for advanced process control (APC)

    NASA Astrophysics Data System (ADS)

    Schneider, Claus; Pfitzner, Lothar; Ryssel, Heiner

    2001-04-01

    Advanced process control (APC) techniques become more and more important as short innovation cycles in microelectronics and a highly competitive market requires cost-effective solutions in semiconductor manufacturing. APC marks a paradigm shift from statistically based techniques (SPC) using monitor wafers for sampling measurement data towards product wafer control. The APC functionalities including run-to-run control, fault detection, and fault analysis allow to detect process drifts and excursions at an early stage and to minimize the number of misprocessed wafers. APC is being established as part of factory control systems through the definition of an APC framework. A precondition for APC is the availability of sensors and measurement methods providing the necessary wafer data. This paper discusses integrated metrology as an enabler for APC and demonstrates practical implementations in semiconductor manufacturing.

  16. The Efficacy of Air Pollution Control Efforts: Evidence from AURA

    NASA Technical Reports Server (NTRS)

    Dickerson, Russell R.; Canty, Tim; Duncan, Bryan N.; Hao, He; Krotkov, Nickolay A.; Salawitch, Ross J.; Stehr, Jeffrey W.; Vinnikov, Konstatin

    2014-01-01

    Observations of NO2, SO2, and H2CO from OMI on AURA provide an excellent record of pollutant concentrations for the past decade. Abatement strategies to control criteria pollutants including ozone and fine particulate matter (PM2.5) have met with varying degrees of success. Sulfur controls had a profound impact on local SO2 concentrations and a measurable impact on PM2.5. Although substantial effort has gone into VOC control, ozone in the eastern US has responded dramatically to NOx emissions controls.

  17. Integrated Assessment of Air Pollution Control Measures for Megacities

    NASA Astrophysics Data System (ADS)

    Friedrich, R.; Theloke, J.; Denier-van-der-Gon, H.; Kugler, U.; Kampffmeyer, T.; Roos, J.; Torras, S.

    2012-04-01

    Air pollution in large cities is still a matter of concern. Especially the concentration of fine particles (PM10 and PM2.5) is largest in large cities leading to severe health impacts. Furthermore the PM10 thresholds of the EU Air Quality Directive are frequently exceeded. Thus the question arises, whether the initiated policies and measures for mitigating air pollution are sufficient to meet the air quality targets and - if not - which efficient further pollution mitigation measures exist. These questions have been addressed in the EU research project MEGAPOLI for the four European megacities respectively agglomerations London, Paris, Rhine-Ruhr area and Po valley. Firstly, a reference scenario of future activities and emissions has been compiled for the megacities for the years 2020, 2030 and 2050 for all relevant air pollutants (CO, NH3, NMVOC, NOx, PM10, PM2.5 and SO2) and greenhouse gases (CO2, CH4 and N2O). The reference scenario takes into account as well population changes as technical progress and economic growth. As pollution flowing in from outside the city is about as important as pollution caused by emissions in the city, the analysis covers the whole of Europe and not only the city area. Emissions are then transformed into concentrations using atmospheric models. The higher concentrations in cities were estimated with a newly developed 'urban increment' model. Results show, that in the megacities the limits of the Air Quality Directive (2008/50/EC) will be exceeded. Thus additional efforts are necessary to reduce emissions further. Thus, a number of further measures (not implemented in current legislation) were selected and assessed. These included mitigation options for road transport, other mobile sources, large combustion plants, small and medium combustion plants and industry. For each measure and in addition for various bundles of measures a cost-benefit analysis has been carried out. Benefits (avoided health risks and climate change risks) have been calculated for each measure using the impact pathway or full chain approach. First the changes of emissions - compared with the reference scenario - are estimated, that occur, if the different options are implemented. Then, for each policy scenario the concentrations of pollutants are estimated. Using concentration-response-relationships, impacts, especially risks to human health, are calculated. These impact are then converted into DALYs (disability adjusted life years) and further into monetary values using contingent valuation methods (willingness to pay approach). The most efficient measures are the use of solar energy for heating,insulation of buildings combined with a mechanical ventilation system, wind energy for electricity production, use of more efficient combustion techniques and low and later zero emission zones for vehicles in cities. However, even if all available options are implemented, the air quality requirements for PM10 will not be met under all meteorological conditions.

  18. Asbestos: The Need for and Feasibility of Air Pollution Controls.

    ERIC Educational Resources Information Center

    National Academy of Sciences - National Research Council, Washington, DC. Div. of Medical Sciences.

    The monograph presents a brief summary of the problems associated with airborne asbestos. It discusses the evidence regarding the pathogenicity of asbestos in man and animals, considers the evidence of human non-occupational exposure to asbestos, evaluates the evidence regarding health risks associated with various degrees and types of exposure,…

  19. Air pollution control and waste management in a new world

    SciTech Connect

    McIlvaine, R.W. )

    1993-03-01

    The McIlvaine Co. has been preparing forecasts for the March issue of the [open quotes]Journal of Air and Waste Management Association[close quotes] for many years. Reviewing past forecasts reveals a consistent pattern; the forecasts have generally been accurate when governmental and industrial environmental policies have been rational, but some major errors in forecasting have resulted from unanticipated irrational governmental policies. The author begins this article by confessing some of his company's past forecasting errors, attributing them to the false assumption of a rational government policy. He then proceeds to base the new forecast on a rational proactive government policy. The forecast offers a program of renewal and hope. The author discusses the program in relation to utility waste handling, particulate emissions, global warming, spending on pollution control equipment, and US investment in air toxics reduction for 1993. The administration at this point gives every indication that this forecast is justified. This view is strengthened by the observation the US Vice President Gore understands the importance of the role that information will play in future environmental actions. 7 figs.

  20. Studies on the Contribution of Human Cytomegalovirus UL21a and UL97 to Viral Growth and Inactivation of the Anaphase-Promoting Complex/Cyclosome (APC/C) E3 Ubiquitin Ligase Reveal a Unique Cellular Mechanism for Downmodulation of the APC/C Subunits APC1, APC4, and APC5

    PubMed Central

    Clark, Elizabeth

    2015-01-01

    ABSTRACT Human cytomegalovirus (HCMV) deregulates the cell cycle by several means, including inactivation of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. Viral proteins UL97 and UL21a, respectively, affect the APC/C by phosphorylation of APC/C coactivator Cdh1 and by inducing the degradation of subunits APC4 and APC5, which along with APC1 form the APC/C platform subcomplex. The aim of this study was to further characterize the mechanism of APC/C inactivation and define the relative contributions of UL21a and UL97 to APC/C substrate accumulation and to viral growth. We show that in uninfected cells, UL21a but not UL97 can disrupt APC/C function, leading to the accumulation of substrates. We find that UL21a is necessary and sufficient to induce the degradation of APC1, in addition to the previously reported APC4 and APC5. We also demonstrate that there is a previously unreported cellular mechanism for a specific decrease in the levels of all three platform subunits, APC1, APC4, and APC5, upon the depletion of any one of these subunits or of subunit APC8. Finally, we show that at a low multiplicity of infection, either UL97 or UL21a can partially complement a growth-defective mutant virus lacking both UL21a and UL97, with significantly greater benefit afforded by the expression of both proteins. This double mutant also can be partially rescued by inactivation of the APC/C using small interfering RNAs against specific subunits. These results further our understanding of HCMV's interaction with the cell cycle machinery and reveal a new cellular pattern of APC/C subunit downmodulation. IMPORTANCE HCMV lytic infection subverts the host cell cycle machinery in multiple ways. A major effect is inactivation of the APC/C, which plays a central role in the control of cell cycle progression. This study provides further insight into the mechanism of inactivation. We discovered that the APC1 subunit, which along with APC4 and APC5 form the platform

  1. Molecular mechanism of APC/C activation by mitotic phosphorylation.

    PubMed

    Zhang, Suyang; Chang, Leifu; Alfieri, Claudio; Zhang, Ziguo; Yang, Jing; Maslen, Sarah; Skehel, Mark; Barford, David

    2016-04-27

    In eukaryotes, the anaphase-promoting complex (APC/C, also known as the cyclosome) regulates the ubiquitin-dependent proteolysis of specific cell-cycle proteins to coordinate chromosome segregation in mitosis and entry into the G1 phase. The catalytic activity of the APC/C and its ability to specify the destruction of particular proteins at different phases of the cell cycle are controlled by its interaction with two structurally related coactivator subunits, Cdc20 and Cdh1. Coactivators recognize substrate degrons, and enhance the affinity of the APC/C for its cognate E2 (refs 4-6). During mitosis, cyclin-dependent kinase (Cdk) and polo-like kinase (Plk) control Cdc20- and Cdh1-mediated activation of the APC/C. Hyperphosphorylation of APC/C subunits, notably Apc1 and Apc3, is required for Cdc20 to activate the APC/C, whereas phosphorylation of Cdh1 prevents its association with the APC/C. Since both coactivators associate with the APC/C through their common C-box and Ile-Arg tail motifs, the mechanism underlying this differential regulation is unclear, as is the role of specific APC/C phosphorylation sites. Here, using cryo-electron microscopy and biochemical analysis, we define the molecular basis of how phosphorylation of human APC/C allows for its control by Cdc20. An auto-inhibitory segment of Apc1 acts as a molecular switch that in apo unphosphorylated APC/C interacts with the C-box binding site and obstructs engagement of Cdc20. Phosphorylation of the auto-inhibitory segment displaces it from the C-box-binding site. Efficient phosphorylation of the auto-inhibitory segment, and thus relief of auto-inhibition, requires the recruitment of Cdk-cyclin in complex with a Cdk regulatory subunit (Cks) to a hyperphosphorylated loop of Apc3. We also find that the small-molecule inhibitor, tosyl-l-arginine methyl ester, preferentially suppresses APC/C(Cdc20) rather than APC/C(Cdh1), and interacts with the binding sites of both the C-box and Ile-Arg tail motifs. Our

  2. Identification of Mom12 and Mom13, two novel modifier loci of Apc (Min) -mediated intestinal tumorigenesis.

    PubMed

    Crist, Richard C; Roth, Jacquelyn J; Lisanti, Michael P; Siracusa, Linda D; Buchberg, Arthur M

    2011-04-01

    Colorectal cancer is a heterogeneous disease resulting from a combination of genetic and environmental factors. The C57BL/6J (B6) Apc (Min/+) mouse develops polyps throughout the gastrointestinal tract and has been a valuable model for understanding the genetic basis of intestinal tumorigenesis. Apc (Min/+) mice have been used to study known oncogenes and tumor suppressor genes on a controlled genetic background. These studies often utilize congenic knockout alleles, which can carry an unknown amount of residual donor DNA. The Apc (Min) model has also been used to identify modifer loci, known as Modifier of Min (Mom) loci, which alter Apc (Min) -mediated intestinal tumorigenesis. B6 mice carrying a knockout allele generated in WW6 embryonic stem cells were crossed to B6 Apc (Min/+) mice to determine the effect on polyp multiplicity. The newly generated colony developed significantly more intestinal polyps than Apc (Min/+) controls. Polyp multiplicity did not correlate with inheritance of the knockout allele, suggesting the presence of one or more modifier loci segregating in the colony. Genotyping of simple sequence length polymorphism (SSLP) markers revealed residual 129X1/SvJ genomic DNA within the congenic region of the parental knockout line. An analysis of polyp multiplicity data and SSLP genotyping indicated the presence of two Mom loci in the colony: 1) Mom12, a dominant modifier linked to the congenic region on chromosome 6, and 2) Mom13, which is unlinked to the congenic region and whose effect is masked by Mom12. The identification of Mom12 and Mom13 demonstrates the potential problems resulting from residual heterozygosity present in congenic lines. PMID:21386660

  3. Regulation of APC Activity by Phosphorylation and Regulatory Factors

    PubMed Central

    Kotani, Shuji; Tanaka, Hirofumi; Yasuda, Hideyo; Todokoro, Kazuo

    1999-01-01

    Ubiquitin-dependent proteolysis of Cut2/Pds1 and Cyclin B is required for sister chromatid separation and exit from mitosis, respectively. Anaphase-promoting complex/cyclosome (APC) specifically ubiquitinates Cut2/Pds1 at metaphase–anaphase transition, and ubiquitinates Cyclin B in late mitosis and G1 phase. However, the exact regulatory mechanism of substrate-specific activation of mammalian APC with the right timing remains to be elucidated. We found that not only the binding of the activators Cdc20 and Cdh1 and the inhibitor Mad2 to APC, but also the phosphorylation of Cdc20 and Cdh1 by Cdc2-Cyclin B and that of APC by Polo-like kinase and cAMP-dependent protein kinase, regulate APC activity. The cooperation of the phosphorylation/dephosphorylation and the regulatory factors in regulation of APC activity may thus control the precise progression of mitosis. PMID:10459014

  4. Specific immunotherapy by genetically engineered APCs: the "guided missile" strategy.

    PubMed

    Wu, B; Wu, J M; Miagkov, A; Adams, R N; Levitsky, H I; Drachman, D B

    2001-04-01

    We tested the hypothesis that APCs genetically engineered to present an Ag and to express Fas ligand (FasL) simultaneously can target and eliminate Ag-specific T cells. Transgenic T cells specific for influenza hemagglutinin (HA) were used as targets. We prepared recombinant vaccinia virus vectors (VVV) to transfer the gene constructs individually or simultaneously into APCs. We prevented unwanted viral replication by attenuating the VVVs with psoralen-UV light treatment. For presentation of the HA Ag, APCs were transduced with cDNA for HA flanked by sequences of the lysosome-associated membrane protein that direct efficient processing and presentation of the Ag by APCs. As a "warhead" for the APCs, we transduced them with the gene for FasL, which induces apoptosis of Fas-expressing activated T cells. To protect the transduced APCs from self-destruction by FasL, we transferred cDNA for a truncated form of Fas-associated death domain, which inhibits Fas-mediated cell death. Our results show that the engineered APCs effectively expressed the genes of interest. APCs transduced with VVV carrying all three gene constructs specifically killed HA-transgenic T cells in culture. Coculture with T cells specific for an unrelated Ag (OVA) had no significant effect. Our in vitro findings show that APCs can be genetically engineered to target and kill Ag-specific T cells and represent a promising novel strategy for the specific treatment of autoimmune diseases. PMID:11254740

  5. Analysis of APC mutation in human ameloblastoma and clinical significance.

    PubMed

    Li, Ning; Liu, Bing; Sui, Chengguang; Jiang, Youhong

    2016-01-01

    As a highly conserved signaling pathway, Wnt/β-catenin signal transduction pathway plays an important role in many processes. Either in the occurrence or development of tumor, activation of this pathway takes an important place. APC inhibits Wnt/β-catenin pathway to regulate cell proliferation and differentiation. This study aimed to investigate the function of cancer suppressor gene. PCR amplification and sequencing method was used to analyze APC mutations of human clinical specimens. The pathological specimens were collected for PCR and clear electrophoretic bands were obtained after electrophoresis. The gene sequence obtained after purification and sequencing analysis was compared with the known APC gene sequence (NM_000038.5). Base mutations at APC 1543 (T → C), APC-4564 (G → A), APC-5353 (T → G), APC-5550 (T → A) and APC-5969 (G → A) locus existed in 22 (27.5 %), 12 (15 %), 5 (6.25 %), 13 (16.25 %) and 12 patients (15 %), respectively. Gene mutations existed in ameloblastoma, and the mutation loci were 1543 locus (T → C), 4564 locus (G → A), 5353 locus (T → G), 5550 locus (T → A) and 5969 locus (G → A) 15 %, respectively. APC mutation plays a certain role in monitoring the tumor malignant degree as it may indicate the transition process of ameloblastoma malignant phenotype. PMID:27065015

  6. Investigations of the mechanical behavior of graphite/PEEK (APC-2) composites

    SciTech Connect

    Lee, K.

    1991-01-01

    The purpose was to investigate the effects of two phenomena specific to thermoplastic resin composites. These phenomena are: (a) significant nonlinear creep, that occurs especially at high temperatures, which affects the residual thermal stresses in a geometrically constrained structure; and (b) spatially nonuniform transverse crystallinity that develops in some fiber-reinforced thermoplastic composites, which introduces spatial variability and nonlinearity in the stiffness of the composite. The first part is related to (a). It presents a computational scheme for the optimal temperature path for APC-2 composite laminate, modeled as nonlinear, thermorheologically complex, viscoelastic material. The laminate is assumed to be sufficiently thin to obviate accounting for temperature nonuniformities across the thickness. The second part concerns (b) and presents analytical/computational results for the in-plane stresses in a moderately thick, cross-ply, graphite/PEEK (APC-2) laminate accounting for effects of nonuniform PEEK crystallinity across the plate's thickness.

  7. WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity.

    PubMed

    Li, Qiuhong; Chang, Leifu; Aibara, Shintaro; Yang, Jing; Zhang, Ziguo; Barford, David

    2016-09-20

    The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1(WD40)). To understand how Apc1(WD40) contributes to APC/C activity, a mutant form of the APC/C with Apc1(WD40) deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1(WD40) abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C-Cdh1 complex with Apc1(WD40) deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1(WD40) is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C.

  8. WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity.

    PubMed

    Li, Qiuhong; Chang, Leifu; Aibara, Shintaro; Yang, Jing; Zhang, Ziguo; Barford, David

    2016-09-20

    The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1(WD40)). To understand how Apc1(WD40) contributes to APC/C activity, a mutant form of the APC/C with Apc1(WD40) deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1(WD40) abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C-Cdh1 complex with Apc1(WD40) deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1(WD40) is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C. PMID:27601667

  9. Measuring APC/C-Dependent Ubiquitylation In Vitro.

    PubMed

    Jarvis, Marc A; Brown, Nicholas G; Watson, Edmond R; VanderLinden, Ryan; Schulman, Brenda A; Peters, Jan-Michael

    2016-01-01

    The anaphase-promoting complex/cyclosome (APC/C) is a 1.2 MDa ubiquitin ligase complex with important functions in both proliferating and post-mitotic differentiated cells. In proliferating cells, APC/C controls cell cycle progression by targeting inhibitors of chromosome segregation and mitotic exit for degradation by the 26S proteasome. To understand how APC/C recruits and ubiquitylates its substrate proteins and how these processes are controlled, it is essential to analyze APC/C activity in vitro. In the past, such experiments have been limited by the fact that large quantities of purified APC/C were difficult to obtain and that mutated versions of the APC/C could not be easily generated. In this chapter we review recent advances in generating and purifying recombinant forms of the human APC/C and its co-activators, using methods that are scalable and compatible with mutagenesis. We also describe a method that allows the quantitative analysis of APC/C activity using fluorescently labeled substrate proteins.

  10. Panta rhei: The APC/C at steady state

    PubMed Central

    2013-01-01

    The anaphase-promoting complex or cyclosome (APC/C) is a conserved, multisubunit E3 ubiquitin (Ub) ligase that is active both in dividing and in postmitotic cells. Its contributions to life are especially well studied in the domain of cell division, in which the APC/C lies at the epicenter of a regulatory network that controls the directionality and timing of cell cycle events. Biochemical and structural work is shedding light on the overall organization of APC/C subunits and on the mechanism of substrate recognition and Ub chain initiation and extension as well as on the molecular mechanisms of a checkpoint that seizes control of APC/C activity during mitosis. Here, we review how these recent advancements are modifying our understanding of the APC/C. PMID:23589490

  11. Zomepirac sodium vs APC with codeine for oral surgery pain.

    PubMed

    Mehlisch, D R; Joy, E D

    1981-06-01

    In this double-blind, repeat-dose study, 323 outpatients with moderate to severe pain after oral surgery assessed zomepirac sodium, a new oral, single-entity, nonnarcotic analgesic, and APC with codeine, 30 mg, a reference standard. Pain relief obtained with 100 mg of zomepirac sodium was significantly superior to that of APC with codeine, 30 mg; 50 mg of zomepirac sodium was as effective as the reference drug. The analgesic acceptability was highest for 100 mg of zomepirac sodium. Both doses of this new drug produced significantly fewer adverse reactions than APC with codeine, 30 mg.

  12. Evaluation of resource recovery from waste incineration residues--the case of zinc.

    PubMed

    Fellner, J; Lederer, J; Purgar, A; Winterstetter, A; Rechberger, H; Winter, F; Laner, D

    2015-03-01

    Solid residues generated at European Waste to Energy plants contain altogether about 69,000 t/a of Zn, of which more than 50% accumulates in air pollution control residues, mainly boiler and filter ashes. Intensive research activities aiming at Zn recovery from such residues recently resulted in a technical scale Zn recovery plant at a Swiss waste incinerator. By acidic leaching and subsequent electrolysis this technology (FLUREC) allows generating metallic Zn of purity>99.9%. In the present paper the economic viability of the FLUREC technology with respect to Zn recovery from different solid residues of waste incineration has been investigated and subsequently been categorised according to the mineral resource classification scheme of McKelvey. The results of the analysis demonstrate that recovery costs for Zn are highly dependent on the costs for current fly ash disposal (e.g. cost for subsurface landfilling). Assuming current disposal practice costs of 220€/ton fly ash, resulting recovery costs for Zn are generally higher than its current market price of 1.6€/kg Zn. With respect to the resource classification this outcome indicates that none of the identified Zn resources present in incineration residues can be economically extracted and thus cannot be classified as a reserve. Only for about 4800 t/a of Zn an extraction would be marginally economic, meaning that recovery costs are only slightly (less than 20%) higher than the current market price for Zn. For the remaining Zn resources production costs are between 1.5 and 4 times (7900 t/a Zn) and 10-80 times (55,300 t/a Zn) higher than the current market value. The economic potential for Zn recovery from waste incineration residues is highest for filter ashes generated at grate incinerators equipped with wet air pollution control. PMID:25458759

  13. Evaluation of resource recovery from waste incineration residues--the case of zinc.

    PubMed

    Fellner, J; Lederer, J; Purgar, A; Winterstetter, A; Rechberger, H; Winter, F; Laner, D

    2015-03-01

    Solid residues generated at European Waste to Energy plants contain altogether about 69,000 t/a of Zn, of which more than 50% accumulates in air pollution control residues, mainly boiler and filter ashes. Intensive research activities aiming at Zn recovery from such residues recently resulted in a technical scale Zn recovery plant at a Swiss waste incinerator. By acidic leaching and subsequent electrolysis this technology (FLUREC) allows generating metallic Zn of purity>99.9%. In the present paper the economic viability of the FLUREC technology with respect to Zn recovery from different solid residues of waste incineration has been investigated and subsequently been categorised according to the mineral resource classification scheme of McKelvey. The results of the analysis demonstrate that recovery costs for Zn are highly dependent on the costs for current fly ash disposal (e.g. cost for subsurface landfilling). Assuming current disposal practice costs of 220€/ton fly ash, resulting recovery costs for Zn are generally higher than its current market price of 1.6€/kg Zn. With respect to the resource classification this outcome indicates that none of the identified Zn resources present in incineration residues can be economically extracted and thus cannot be classified as a reserve. Only for about 4800 t/a of Zn an extraction would be marginally economic, meaning that recovery costs are only slightly (less than 20%) higher than the current market price for Zn. For the remaining Zn resources production costs are between 1.5 and 4 times (7900 t/a Zn) and 10-80 times (55,300 t/a Zn) higher than the current market value. The economic potential for Zn recovery from waste incineration residues is highest for filter ashes generated at grate incinerators equipped with wet air pollution control.

  14. Antigen targeting to APC: from mice to veterinary species.

    PubMed

    Alvarez, B; Poderoso, T; Alonso, F; Ezquerra, A; Domínguez, J; Revilla, C

    2013-10-01

    Antigen delivery to receptors expressed on antigen presenting cells (APC) has shown to improve immunogenicity of vaccines in mice. An enhancement of cytotoxic T lymphocyte (CTL), helper T cell or humoral responses was obtained depending on the type of APC and the surface molecule targeted. Although this strategy is being also evaluated in livestock animals with promising results, some discrepancies have been found between species and pathogens. The genetic diversity of livestock animals, the different pattern of expression of some receptors among species, the use of different markers to characterize APC in large animals and sometimes the lack of reagents make difficult to compare results obtained in different species. In this review, we summarize the data available regarding antigen targeting to APC receptors in cattle, sheep and pig and discuss the results found in these animals in the context of what has been obtained in mice. PMID:23648645

  15. Antigen targeting to APC: from mice to veterinary species.

    PubMed

    Alvarez, B; Poderoso, T; Alonso, F; Ezquerra, A; Domínguez, J; Revilla, C

    2013-10-01

    Antigen delivery to receptors expressed on antigen presenting cells (APC) has shown to improve immunogenicity of vaccines in mice. An enhancement of cytotoxic T lymphocyte (CTL), helper T cell or humoral responses was obtained depending on the type of APC and the surface molecule targeted. Although this strategy is being also evaluated in livestock animals with promising results, some discrepancies have been found between species and pathogens. The genetic diversity of livestock animals, the different pattern of expression of some receptors among species, the use of different markers to characterize APC in large animals and sometimes the lack of reagents make difficult to compare results obtained in different species. In this review, we summarize the data available regarding antigen targeting to APC receptors in cattle, sheep and pig and discuss the results found in these animals in the context of what has been obtained in mice.

  16. Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

    PubMed Central

    Ruane, Peter T.; Gumy, Laura F.; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J.; Hoogenraad, Casper C.; Allan, Victoria J.

    2016-01-01

    Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C-terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons. PMID:27272132

  17. Insights into anaphase promoting complex TPR subdomain assembly from a CDC26-APC6 structure

    SciTech Connect

    Wang, Jing; Dye, Billy T; Rajashankar, Kanagalaghatta R; Kurinov, Igor; Schulman, Brenda A

    2009-12-01

    The multisubunit anaphase promoting complex (APC) is an essential cell-cycle regulator. Although CDC26 is known to have a role in APC assembly, its molecular function has remained unclear. Biophysical, structural and genetic studies presented here reveal that CDC26 stabilizes the structure of APC6, a core TPR protein required for APC integrity. Notably, CDC26-APC6 association involves an intermolecular TPR mimic composed of one helix from each protein.

  18. The ABBA motif binds APC/C activators and is shared by APC/C substrates and regulators

    PubMed Central

    Hagting, Anja; Izawa, Daisuke; Mansfeld, Jörg; Gibson, Toby J.; Pines, Jonathon

    2016-01-01

    The APC/C is the ubiquitin ligase that regulates mitosis by targeting specific proteins for degradation at specific times under the control of the Spindle Assembly Checkpoint (SAC). How the APC/C recognises its different substrates is a key problem in the control of cell division. Here, we have identified the ABBA motif in Cyclin A, BUBR1, BUB1 and Acm1, and show that it binds to the APC/C co-activator CDC20. The ABBA motif in Cyclin A is required for its proper degradation in prometaphase through competing with BUBR1 for the same site on CDC20. Moreover, the ABBA motifs in BUBR1 and BUB1 are necessary for the SAC to work at full strength and to recruit CDC20 to kinetochores. Thus, we have identified a conserved motif integral to the proper control of mitosis that connects APC/C substrate recognition with the SAC. PMID:25669885

  19. Differential RNA-seq analysis comparing APC-defective and APC-restored SW480 colorectal cancer cells

    PubMed Central

    King, Lauren E.; Love, Christopher G.; Sieber, Oliver M.; Faux, Maree C.; Burgess, Antony W.

    2016-01-01

    The adenomatous polyposis coli (APC) tumour suppressor gene is mutated in about 80% of colorectal cancers (CRC) Brannon et al. (2014) [1]. APC is a large multifunctional protein that regulates many biological functions including Wnt signalling (through the regulation of beta-catenin stability) Reya and Clevers (2005) [2], cell migration Kroboth et al. (2007), Sansom et al. (2004) [3], [4], mitosis Kaplan et al. (2001) [5], cell adhesion Faux et al. (2004), Carothers et al. (2001) [6], [7] and differentiation Sansom et al. (2004) [4]. Although the role of APC in CRC is often described as the deregulation of Wnt signalling, its other biological functions suggest that there are other factors at play that contribute to the onset of adenomas and the progression of CRC upon the truncation of APC. To identify genes and pathways that are dysregulated as a consequence of loss of function of APC, we compared the gene expression profiles of the APC mutated human CRC cell line SW480 following reintroduction of wild-type APC (SW480 + APC) or empty control vector (SW480 + vector control) Faux et al. (2004) . Here we describe the RNA-seq data derived for three biological replicates of parental SW480, SW480 + vector control and SW480 + APC cells, and present the bioinformatics pipeline used to test for differential gene expression and pathway enrichment analysis. A total of 1735 genes showed significant differential expression when APC was restored and were enriched for genes associated with cell polarity, Wnt signalling and the epithelial to mesenchymal transition. There was additional enrichment for genes involved in cell–cell adhesion, cell–matrix junctions, angiogenesis, axon morphogenesis and cell movement. The raw and analysed RNA-seq data have been deposited in the Gene Expression Omnibus (GEO) database under accession number GSE76307. This dataset is useful for further investigations of the impact of APC mutation on the properties of colorectal cancer cells

  20. Some fine-structural findings on the thyroid gland in Apc1638T/1638T mice that express a C-terminus lacking truncated Apc.

    PubMed

    Yokoyama, Atsushi; Nomura, Ryuji; Kurosumi, Masafumi; Shimomura, Atsushi; Onouchi, Takanori; Iizuka-Kogo, Akiko; Smits, Ron; Fodde, Riccardo; Itoh, Mditsuyasu; Senda, Takao

    2012-06-01

    Adenomatous polyposis coli (Apc) is a multifunctional protein as well as a tumor suppressor. To determine the functions of the C-terminal domain of Apc, we examined Apc(1638T/1638T) mice that express a truncated Apc lacking the C-terminal domain. The Apc(1638T/1638T) mice were tumor free and exhibited growth retardation. We recently reported abnormalities in thyroid morphology and functions of Apc(1638T/1638T) mice, although the mechanisms underlying these abnormalities are not known. In the present study, we further compared thyroid gland morphology in Apc(1638T/1638T) and Apc(+/+) mice. The diameters of thyroid follicles in the left and right lobes of the same thyroid gland of Apc(1638T/1638T) mice were significantly different whereas the Apc(+/+) mice showed no significant differences in thyroid follicle diameter between these lobes. To assess the secretory activities of thyroid follicular cells, we performed double-immunostaining of thyroglobulin, a major secretory protein of these cells, and the rough endoplasmic reticulum (rER) marker calreticulin. In the Apc(1638T/1638T) follicular epithelial cells, thyroglobulin was mostly colocalized with calreticulin whereas in the Apc(+/+) follicular epithelial cells, a significant amount of the cytoplasmic thyroglobulin did not colocalize with calreticulin. In addition, in thyroid-stimulating hormone (TSH)-treated Apc(1638T/1638T) mice, electron microscopic analysis indicated less frequent pseudopod formation at the apical surface of the thyroid follicular cells than in Apc(+/+) mice, indicating that reuptake of colloid droplets containing iodized thyroglobulin is less active. These results imply defects in intracellular thyroglobulin transport and in pseudopod formation in the follicular epithelial cells of Apc(1638T/1638T) mice and suggest suppressed secretory activities of these cells.

  1. Phosphorylation and dephosphorylation regulate APC/CCdh1 substrate degradation

    PubMed Central

    Simpson-Lavy, Kobi J; Zenvirth, Drora; Brandeis, Michael

    2015-01-01

    The Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase activated by its G1 specific adaptor protein Cdh1 is a major regulator of the cell cycle. The APC/CCdh1 mediates degradation of dozens of proteins, however, the kinetics and requirements for their degradation are largely unknown. We demonstrate that overexpression of the constitutive active CDH1m11 mutant that is not inhibited by phosphorylation results in mitotic exit in the absence of the FEAR and MEN pathways, and DNA re-replication in the absence of Cdc7 activity. This mode of mitotic exit also reveals additional requirements for APC/CCdh1 substrate degradation, which for some substrates such as Pds1 or Clb5 is dephosphorylation, but for others such as Cdc5 is phosphorylation. PMID:26252546

  2. Characterization of Colorectal Cancer Development in Apc (min/+) Mice.

    PubMed

    Nalbantoglu, ILKe; Blanc, Valerie; Davidson, Nicholas O

    2016-01-01

    The Apc (min/+) mouse provides an excellent experimental model for studying genetic, environmental, and therapeutic aspects of intestinal neoplasia in humans. In this chapter, we will describe techniques for studying colon cancer development in Apc (min/+) mice on C57BL/6J (B6) background, focusing on the roles of environmental modifiers, including Dextran Sulfate Sodium (DSS), high fat diet, and bile acid supplementation in the context of experimental colorectal cancer. This chapter also includes protocols describing extraction and purification of DSS-contaminated RNA, as well as sampling, harvesting, and tissue processing. The common pathologic lesions encountered in these animals are described in detail. PMID:27246043

  3. ApcMin, A Mutation in the Murine Apc Gene, Predisposes to Mammary Carcinomas and Focal Alveolar Hyperplasias

    NASA Astrophysics Data System (ADS)

    Moser, Amy Rapaich; Mattes, Ellen M.; Dove, William F.; Lindstrom, Mary J.; Haag, Jill D.; Gould, Michael N.

    1993-10-01

    ApcMin (Min, multiple intestinal neoplasia) is a point mutation in the murine homolog of the APC gene. Min/+ mice develop multiple intestinal adenomas, as do humans carrying germ-line mutations in APC. Female mice carrying Min are also prone to develop mammary tumors. Min/+ mammary glands are more sensitive to chemical carcinogenesis than are +/+ mammary glands. Transplantation of mammary cells from Min/+ or +/+ donors into +/+ hosts demonstrates that the propensity to develop mammary tumors is intrinsic to the Min/+ mammary cells. Long-term grafts of Min/+ mammary glands also gave rise to focal alveolar hyperplasias, indicating that the presence of the Min mutation also has a role in the development of these lesions.

  4. Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human activated protein C (APC). Sodium ion in the APC crystal structure is coordinated to four carbonyl groups from two separate loops.

    PubMed

    Schmidt, Amy E; Padmanabhan, Kaillathe; Underwood, Matthew C; Bode, Wolfram; Mather, Timothy; Bajaj, S Paul

    2002-08-01

    The serine protease domain of activated protein C (APC) contains a Na+ and a Ca2+ site. However, the number and identity of the APC residues that coordinate to Na+ is not precisely known. Further, the functional link between the Na+ and the Ca2+ site is insufficiently defined, and their linkage to the substrate S1 site has not been studied. Here, we systematically investigate the functional significance of these two cation sites and their thermodynamic links to the S1 site. Kinetic data reveal that Na+ binds to the substrate-occupied APC with K(d) values of approximately 24 mm in the absence and approximately 6 mm in the presence of Ca2+. Sodium-occupied APC has approximately 100-fold increased catalytic efficiency ( approximately 4-fold decrease in K(m) and approximately 25-fold increase in k(cat)) in hydrolyzing S-2288 (H-d-Ile-Pro-Arg-p-nitroanilide) and Ca2+ further increases this k(cat) slightly ( approximately 1.2-fold). Ca2+ binds to the protease domain of APC with K(d) values of approximately 438 microm in the absence and approximately 105 microm in the presence of Na+. Ca2+ binding to the protease domain of APC does not affect K(m) but increases the k(cat) approximately 10-fold, and Na+ further increases this k(cat) approximately 3-fold and decreases the K(m) value approximately 3.7-fold. In agreement with the K(m) data, sodium-occupied APC has approximately 4-fold increased affinity in binding to p-aminobenzamidine (S1 probe). Crystallographically, the Ca2+ site in APC is similar to that in trypsin, and the Na+ site is similar to that in factor Xa but not thrombin. Collectively, the Na+ site is thermodynamically linked to the S1 site as well as to the protease domain Ca2+ site, whereas the Ca2+ site is only linked to the Na+ site. The significance of these findings is that under physiologic conditions, most of the APC will exist in Na2+-APC-Ca2+ form, which has 110-fold increased proteolytic activity. PMID:12029084

  5. Timing of APC/C substrate degradation is determined by fzy/fzr specificity of destruction boxes

    PubMed Central

    Zur, Amit; Brandeis, Michael

    2002-01-01

    The anaphase promoting complex/cyclosome (APC/C), activated by fzy and fzr, degrades cell cycle proteins that carry RXXL or KEN destruction boxes (d-boxes). APC/C substrates regulate sequential events and must be degraded in the correct order during mitosis and G1. We studied how d-boxes determine APC/Cfzy/APC/Cfzr specificity and degradation timing. Cyclin B1 has an RXXL box and is degraded by both APC/Cfzy and APC/Cfzr; fzy has a KEN box and is degraded by APC/Cfzr only. We characterized the degradation of substrates with swapped d-boxes. Cyclin B1 with KEN was degraded by APC/Cfzr only. Fzy with RXXL could be degraded by APC/Cfzy and APC/Cfzr. Interestingly, APC/Cfzy- but not APC/Cfzr-specific degradation is highly dependent on the location of RXXL. We studied degradation of tagged substrates in real time and observed that APC/Cfzr is activated in early G1. These observations demonstrate how d-box specificities of APC/Cfzy and APC/Cfzr, and the successive activation of APC/C by fzy and fzr, establish the temporal degradation pattern. Our observations can explain further why some endogenous RXXL substrates are degraded by APC/Cfzy, while others are restricted to APC/Cfzr. PMID:12198152

  6. Metabolomics of Apc Min/+ mice genetically susceptible to intestinal cancer

    PubMed Central

    2014-01-01

    Background To determine how diets high in saturated fat could increase polyp formation in the mouse model of intestinal neoplasia, Apc Min/+ , we conducted large-scale metabolome analysis and association study of colon and small intestine polyp formation from plasma and liver samples of Apc Min/+ vs. wild-type littermates, kept on low vs. high-fat diet. Label-free mass spectrometry was used to quantify untargeted plasma and acyl-CoA liver compounds, respectively. Differences in contrasts of interest were analyzed statistically by unsupervised and supervised modeling approaches, namely Principal Component Analysis and Linear Model of analysis of variance. Correlation between plasma metabolite concentrations and polyp numbers was analyzed with a zero-inflated Generalized Linear Model. Results Plasma metabolome in parallel to promotion of tumor development comprises a clearly distinct profile in Apc Min/+ mice vs. wild type littermates, which is further altered by high-fat diet. Further, functional metabolomics pathway and network analyses in Apc Min/+ mice on high-fat diet revealed associations between polyp formation and plasma metabolic compounds including those involved in amino-acids metabolism as well as nicotinamide and hippuric acid metabolic pathways. Finally, we also show changes in liver acyl-CoA profiles, which may result from a combination of Apc Min/+ -mediated tumor progression and high fat diet. The biological significance of these findings is discussed in the context of intestinal cancer progression. Conclusions These studies show that high-throughput metabolomics combined with appropriate statistical modeling and large scale functional approaches can be used to monitor and infer changes and interactions in the metabolome and genome of the host under controlled experimental conditions. Further these studies demonstrate the impact of diet on metabolic pathways and its relation to intestinal cancer progression. Based on our results, metabolic signatures

  7. The Anaphase-Promoting Complex (APC) ubiquitin ligase affects chemosensory behavior in C. elegans.

    PubMed

    Wang, Julia; Jennings, Alexandra K; Kowalski, Jennifer R

    2016-01-01

    The regulation of fundamental aspects of neurobiological function has been linked to the ubiquitin signaling system (USS), which regulates the degradation and activity of proteins and is catalyzed by E1, E2, and E3 enzymes. The Anaphase-Promoting Complex (APC) is a multi-subunit E3 ubiquitin ligase that controls diverse developmental and signaling processes in post-mitotic neurons; however, potential roles for the APC in sensory function have yet to be explored. In this study, we examined the effect of the APC ubiquitin ligase on chemosensation in Caenorhabditis elegans by testing chemotaxis to the volatile odorants, diacetyl, pyrazine, and isoamyl alcohol, to which wild-type worms are attracted. Animals with loss of function mutations in either of two alleles (g48 and ye143) of the gene encoding the APC subunit EMB-27 APC6 showed increased chemotaxis towards diacetyl and pyrazine, odorants sensed by AWA neurons, but exhibited normal chemotaxis to isoamyl alcohol, which is sensed by AWC neurons. The statistically significant increase in chemotaxis in the emb-27 APC6 mutants suggests that the APC inhibits AWA-mediated chemosensation in C. elegans. Increased chemotaxis to pyrazine was also seen with mutants lacking another essential APC subunit, MAT-2 APC1; however, mat-2 APC1 mutants exhibited wild type responses to diacetyl. The difference in responsiveness of these two APC subunit mutants may be due to differential strength of these hypomorphic alleles or may indicate the presence of functional sub-complexes of the APC at work in this process. These findings are the first evidence for APC-mediated regulation of chemosensation and lay the groundwork for further studies aimed at identifying the expression levels, function, and targets of the APC in specific sensory neurons. Because of the similarity between human and C. elegans nervous systems, the role of the APC in sensory neurons may also advance our understanding of human sensory function and disease. PMID

  8. The Anaphase-Promoting Complex (APC) ubiquitin ligase affects chemosensory behavior in C. elegans

    PubMed Central

    Wang, Julia; Jennings, Alexandra K.

    2016-01-01

    The regulation of fundamental aspects of neurobiological function has been linked to the ubiquitin signaling system (USS), which regulates the degradation and activity of proteins and is catalyzed by E1, E2, and E3 enzymes. The Anaphase-Promoting Complex (APC) is a multi-subunit E3 ubiquitin ligase that controls diverse developmental and signaling processes in post-mitotic neurons; however, potential roles for the APC in sensory function have yet to be explored. In this study, we examined the effect of the APC ubiquitin ligase on chemosensation in Caenorhabditis elegans by testing chemotaxis to the volatile odorants, diacetyl, pyrazine, and isoamyl alcohol, to which wild-type worms are attracted. Animals with loss of function mutations in either of two alleles (g48 and ye143) of the gene encoding the APC subunit EMB-27 APC6 showed increased chemotaxis towards diacetyl and pyrazine, odorants sensed by AWA neurons, but exhibited normal chemotaxis to isoamyl alcohol, which is sensed by AWC neurons. The statistically significant increase in chemotaxis in the emb-27 APC6 mutants suggests that the APC inhibits AWA-mediated chemosensation in C. elegans. Increased chemotaxis to pyrazine was also seen with mutants lacking another essential APC subunit, MAT-2 APC1; however, mat-2 APC1 mutants exhibited wild type responses to diacetyl. The difference in responsiveness of these two APC subunit mutants may be due to differential strength of these hypomorphic alleles or may indicate the presence of functional sub-complexes of the APC at work in this process. These findings are the first evidence for APC-mediated regulation of chemosensation and lay the groundwork for further studies aimed at identifying the expression levels, function, and targets of the APC in specific sensory neurons. Because of the similarity between human and C. elegans nervous systems, the role of the APC in sensory neurons may also advance our understanding of human sensory function and disease. PMID

  9. Single-molecule spectroscopy and femtosecond transient absorption studies on the excitation energy transfer process in ApcE(1-240) dimers.

    PubMed

    Long, Saran; Zhou, Meng; Tang, Kun; Zeng, Xiao-Li; Niu, Yingli; Guo, Qianjin; Zhao, Kai-Hong; Xia, Andong

    2015-05-28

    ApcE(1-240) dimers with one intrinsic phycocyanobilin (PCB) chromophore in each monomer that is truncated from the core-membrane linker (ApcE) of phycobilisomes (PBS) in Nostoc sp. PCC 7120 show a sharp and significantly red-shifted absorption. Two explanations either conformation-dependent Förster resonance energy transfer (FRET) or the strong exciton coupling limit have been proposed for red-shifted absorption. This is a classic example of the special pair in the photosynthetic light harvesting proteins, but the mechanism of this interaction is still a matter of intense debate. We report the studies using single-molecule and transient absorption spectra on the interaction in the special pair of ApcE dimers. Our results demonstrate the presence of conformation-dependent FRET between the two PCB chromophores in ApcE dimers. The broad distributions of fluorescence intensities, lifetimes and polarization difference from single-molecule measurements reveal the heterogeneity of local protein-pigment environments in ApcE dimers, where the same molecular structures but different protein environments are the main reason for the two PCB chromophores with different spectral properties. The excitation energy transfer rate between the donor and the acceptor about (110 ps)(-1) is determined from transient absorption measurements. The red-shifted absorption in ApcE dimers could result from more extending conformation, which shows another type of absorption redshift that does not depend on strong exciton coupling. The results here stress the importance of conformation-controlled spectral properties of the chemically identical chromophores, which could be a general feature to control energy/electron transfer, widely existing in the light harvesting complexes. PMID:25925197

  10. A l-Lysine Transporter of High Stereoselectivity of the Amino Acid-Polyamine-Organocation (APC) Superfamily

    PubMed Central

    Kaur, Jagdeep; Olkhova, Elena; Malviya, Viveka Nand; Grell, Ernst; Michel, Hartmut

    2014-01-01

    Membrane proteins of the amino acid-polyamine-organocation (APC) superfamily transport amino acids and amines across membranes and play an important role in the regulation of cellular processes. We report the heterologous production of the LysP-related transporter STM2200 from Salmonella typhimurium in Escherichia coli, its purification, and functional characterization. STM2200 is assumed to be a proton-dependent APC transporter of l-lysine. The functional interaction between basic amino acids and STM2200 was investigated by thermoanalytical methods, i.e. differential scanning and isothermal titration calorimetry. Binding of l-lysine to STM2200 in its solubilized monomer form is entropy-driven. It is characterized by a dissociation constant of 40 μm at pH 5.9 and is highly selective; no evidence was found for the binding of l-arginine, l-ornithine, l-2,4-diaminobutyric acid, and l-alanine. d-Lysine is bound 45 times more weakly than its l-chiral form. We thus postulate that STM2200 functions as a specific transport protein. Based on the crystal structure of ApcT (Shaffer, P. L., Goehring, A., Shankaranarayanan, A., and Gouaux, E. (2009) Science 325, 1010–1014), a proton-dependent amino acid transporter of the APC superfamily, a homology model of STM2200 was created. Docking studies allowed identification of possible ligand binding sites. The resulting predictions indicated that Glu-222 and Arg-395 of STM2200 are markedly involved in ligand binding, whereas Lys-163 is suggested to be of structural and functional relevance. Selected variants of STM2200 where these three amino acid residues were substituted using single site-directed mutagenesis showed no evidence for l-lysine binding by isothermal titration calorimetry, which confirmed the predictions. Molecular aspects of the observed ligand specificity are discussed. PMID:24257746

  11. Colorectal Tumors from APC*I1307K Carriers Principally Harbor Somatic APC Mutations outside the A8 Tract

    PubMed Central

    Zauber, Peter; Bishop, Timothy; Taylor, Claire; Sabbath-Solitare, Marlene; Marotta, Stephen; Tomlinson, Ian

    2014-01-01

    Purpose APC*I1307K (c.3920T>A) is an inherited variant associated with colorectal tumour risk found almost exclusively in those of Ashkenazi Jewish ancestry. A single nucleotide substitution creates an oligo-adenine tract (A8) that appears to be inherently prone to further mis-pairing and slippage. The reported multiple tumor phenotype of carriers is not easily reconciled with molecular and population genetics data. We postulated that some c.3920T>A carriers with multiple adenomas have other unidentified APC germ line or somatic mutations. Methods DNA from 82 colonic tumours and accompanying normal tissue collected from 29 carriers with multiple colorectal tumors was directly sequenced between codons 716 and 1604. We also assessed APC gene loss of heterozygosity. Results One patient (3.4%) was found to have an additional APC germ line mutation. Twenty-five of the tumours showed no significant somatic molecular change, 36 showed one change, 20 showed two, and one tumour showed more than 2 changes. Our data suggest a correlation between advancing histology and fewer beta-catenin binding sites remaining in the mutant proteins. Conclusions There were no other common germ line variants identified within the region of the APC gene examined, suggesting that any effect from this region on tumour production is attributable to the c.3920T>A allele. Our findings further suggest the only somatic genetic change clearly attributable to the c.3920T>A mutation is the c.3924_3925insA. PMID:24416237

  12. A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC

    PubMed Central

    Schell, Michael J.; Yang, Mingli; Teer, Jamie K.; Lo, Fang Yin; Madan, Anup; Coppola, Domenico; Monteiro, Alvaro N. A.; Nebozhyn, Michael V.; Yue, Binglin; Loboda, Andrey; Bien-Willner, Gabriel A.; Greenawalt, Danielle M.; Yeatman, Timothy J.

    2016-01-01

    Colorectal cancer (CRC) is a highly heterogeneous disease, for which prognosis has been relegated to clinicopathologic staging for decades. There is a need to stratify subpopulations of CRC on a molecular basis to better predict outcome and assign therapies. Here we report targeted exome-sequencing of 1,321 cancer-related genes on 468 tumour specimens, which identified a subset of 17 genes that best classify CRC, with APC playing a central role in predicting overall survival. APC may assume 0, 1 or 2 truncating mutations, each with a striking differential impact on survival. Tumours lacking any APC mutation carry a worse prognosis than single APC mutation tumours; however, two APC mutation tumours with mutant KRAS and TP53 confer the poorest survival among all the subgroups examined. Our study demonstrates a prognostic role for APC and suggests that sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC. PMID:27302369

  13. Enhancement of accelerated carbonation of alkaline waste residues by ultrasound.

    PubMed

    Araizi, Paris K; Hills, Colin D; Maries, Alan; Gunning, Peter J; Wray, David S

    2016-04-01

    The continuous growth of anthropogenic CO2 emissions into the atmosphere and the disposal of hazardous wastes into landfills present serious economic and environmental issues. Reaction of CO2 with alkaline residues or cementitius materials, known as accelerated carbonation, occurs rapidly under ambient temperature and pressure and is a proven and effective process of sequestering the gas. Moreover, further improvement of the reaction efficiency would increase the amount of CO2 that could be permanently sequestered into solid products. This paper examines the potential of enhancing the accelerated carbonation of air pollution control residues, cement bypass dust and ladle slag by applying ultrasound at various water-to-solid (w/s) ratios. Experimental results showed that application of ultrasound increased the CO2 uptake by up to four times at high w/s ratios, whereas the reactivity at low water content showed little change compared with controls. Upon sonication, the particle size of the waste residues decreased and the amount of calcite precipitates increased. Finally, the sonicated particles exhibited a rounded morphology when observed by scanning electron microscopy.

  14. Enhancement of accelerated carbonation of alkaline waste residues by ultrasound.

    PubMed

    Araizi, Paris K; Hills, Colin D; Maries, Alan; Gunning, Peter J; Wray, David S

    2016-04-01

    The continuous growth of anthropogenic CO2 emissions into the atmosphere and the disposal of hazardous wastes into landfills present serious economic and environmental issues. Reaction of CO2 with alkaline residues or cementitius materials, known as accelerated carbonation, occurs rapidly under ambient temperature and pressure and is a proven and effective process of sequestering the gas. Moreover, further improvement of the reaction efficiency would increase the amount of CO2 that could be permanently sequestered into solid products. This paper examines the potential of enhancing the accelerated carbonation of air pollution control residues, cement bypass dust and ladle slag by applying ultrasound at various water-to-solid (w/s) ratios. Experimental results showed that application of ultrasound increased the CO2 uptake by up to four times at high w/s ratios, whereas the reactivity at low water content showed little change compared with controls. Upon sonication, the particle size of the waste residues decreased and the amount of calcite precipitates increased. Finally, the sonicated particles exhibited a rounded morphology when observed by scanning electron microscopy. PMID:26905698

  15. 75 FR 78246 - Medicare Program; Re-Chartering of the Advisory Panel on Ambulatory Payment Classification (APC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-15

    ... Charter effective through November 21, 2012. FOR FURTHER INFORMATION CONTACT: Shirl Ackerman-Ross, (410... new technology APCs to clinical APCs). Evaluating APC group weights. Reviewing packaging the cost of... methodology for packaging and the impact of packaging on APC group structure and payment. Removing...

  16. Structural insights into the EB1–APC interaction

    PubMed Central

    Honnappa, Srinivas; John, Corinne M; Kostrewa, Dirk; Winkler, Fritz K; Steinmetz, Michel O

    2005-01-01

    EB1 proteins bind to microtubule ends where they act in concert with other components, including the adenomatous polyposis coli (APC) tumor suppressor, to regulate the microtubule filament system. We find that EB1 is a stable dimer with a parallel coiled coil and show that dimerization is essential for the formation of its C-terminal domain (EB1-C). The crystal structure of EB1-C reveals a highly conserved surface patch with a deep hydrophobic cavity at its center. EB1-C binds two copies of an APC-derived C-terminal peptide (C-APCp1) with equal 5 μM affinity. The conserved APC Ile2805–Pro2806 sequence motif serves as an anchor for the interaction of C-APCp1 with the hydrophobic cavity of EB1-C. Phosphorylation of the conserved Cdc2 site Ser2789–Lys2792 in C-APCp1 reduces binding four-fold, indicating that the interaction APC–EB1 is post-translationally regulated in cells. Our findings provide a basis for understanding the dynamic crosstalk of EB1 proteins with their molecular targets in eukaryotic organisms. PMID:15616574

  17. APC is required for muscle stem cell proliferation and skeletal muscle tissue repair

    PubMed Central

    Parisi, Alice; Lacour, Floriane; Giordani, Lorenzo; Colnot, Sabine; Maire, Pascal

    2015-01-01

    The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues. PMID:26304725

  18. APC is required for muscle stem cell proliferation and skeletal muscle tissue repair.

    PubMed

    Parisi, Alice; Lacour, Floriane; Giordani, Lorenzo; Colnot, Sabine; Maire, Pascal; Le Grand, Fabien

    2015-08-31

    The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues. PMID:26304725

  19. The Unique N-terminus of the UbcH10 E2 Enzyme Controls the Threshold for APC Activation and Enhances Checkpoint Regulation of the APC

    PubMed Central

    Summers, Matthew K.; Pan, Borlan; Mukhyala, Kiran; Jackson, Peter K.

    2008-01-01

    Summary In vitro, the Anaphase Promoting Complex (APC) E3 ligase functions with E2 ubiquitin conjugating enzymes of the E2–C and Ubc4/5 families to ubiquitinate substrates. However, only the use of the E2–C family, notably UbcH10, is genetically well validated. Here, we biochemically demonstrate preferential use of UbcH10 by the APC, specified by the E2 core domain. Importantly, an additional E2–E3 interaction mediated by the N-terminal extension of UbcH10 regulates APC activity. Mutating the highly conserved N-terminus increases substrate ubiquitination, the number of substrate lysines targeted, allows ubiquitination of APC substrates lacking their destruction-boxes, increases resistance to the APC inhibitors Emi1 and BubR1 in vitro, and bypasses the spindle checkpoint in vivo. Fusion of the UbcH10 N-terminus to UbcH5 restricts ubiquitination activity, but does not direct specific interactions with the APC. Thus, UbcH10 combines a specific E2–E3 interface and regulation via its N-terminal extension to limit APC activity for substrate selection and checkpoint control. PMID:18722180

  20. Synergistic inhibition of the APC/C by the removal of APC15 in HCT116 cells lacking UBE2C

    PubMed Central

    Garvanska, Dimitriya H.; Larsen, Marie Sofie Yoo

    2016-01-01

    ABSTRACT The spindle assembly checkpoint (SAC) inhibits the anaphase-promoting complex/cyclosome (APC/C) in response to unattached kinetochores by generating a diffusible inhibitor termed the mitotic checkpoint complex (MCC). At metaphase, rapid activation of the APC/C requires removal of the MCC, a process that has been shown to depend on the APC/C E2 enzymes, UBE2C and UBE2S. Here we investigate the in vivo role of the APC/C E2 enzymes in SAC silencing using CRISPR/Cas9 genetically engineered HCT116 UBE2C or UBE2S null cell lines. Using live cell assays, we show that UBE2C and UBE2S make a minor contribution to SAC silencing in HCT116 cells. Strikingly, in cells specifically lacking UBE2C, we observe a strong synergistic inhibition of mitotic progression when we stabilize the MCC on the APC/C by depleting APC15, potentially reflecting increased competition between the MCC and the remaining initiating E2 enzyme UBE2D. In conclusion, we provide in vivo insight into the APC/C E2 module and its interplay with SAC silencing components. PMID:27591192

  1. Apc bridges Wnt/{beta}-catenin and BMP signaling during osteoblast differentiation of KS483 cells

    SciTech Connect

    Miclea, Razvan L.; Horst, Geertje van der; Robanus-Maandag, Els C.; Loewik, Clemens W.G.M.; Oostdijk, Wilma; Wit, Jan M.; Karperien, Marcel

    2011-06-10

    The canonical Wnt signaling pathway influences the differentiation of mesenchymal cell lineages in a quantitative and qualitative fashion depending on the dose of {beta}-catenin signaling. Adenomatous polyposis coli (Apc) is the critical intracellular regulator of {beta}-catenin turnover. To better understand the molecular mechanisms underlying the role of Apc in regulating the differentiation capacity of skeletal progenitor cells, we have knocked down Apc in the murine mesenchymal stem cell-like KS483 cells by stable expression of Apc-specific small interfering RNA. In routine culture, KSFrt-Apc{sub si} cells displayed a mesenchymal-like spindle shape morphology, exhibited markedly decreased proliferation and increased apoptosis. Apc knockdown resulted in upregulation of the Wnt/{beta}-catenin and the BMP/Smad signaling pathways, but osteogenic differentiation was completely inhibited. This effect could be rescued by adding high concentrations of BMP-7 to the differentiation medium. Furthermore, KSFrt-Apc{sub si} cells showed no potential to differentiate into chondrocytes or adipocytes. These results demonstrate that Apc is essential for the proliferation, survival and differentiation of KS483 cells. Apc knockdown blocks the osteogenic differentiation of skeletal progenitor cells, a process that can be overruled by high BMP signaling.

  2. Identification of APC mutations and evaluation of their expression level using a functional screening assay

    SciTech Connect

    Varesco, L.; Gismondi, V.; Bafico, A.

    1994-09-01

    A functional screen for chain-terminating mutations in the APC gene recently has been developed. It is based on the PCR and cloning of a segment of the gene in-frame with a colorimetric marker gene (lacz) followed by screening for the level of activity of the marker polypeptide (beta-galactosidase). This method scores colony number with different blue colors that are produced by bacteria containing normal and mutant APC segments. In the present work this method was used to screen the entire APC coding region by using eight primer pairs. DNA segments with known APC mutations at different positions in the gene were used as controls and were clearly identifiable with this assay. In addition, the entire APC coding region has been examined in 21 APC patients in whom PCR-SSCP did not identify an APC mutation. Novel mutations (n=14) were identified by the blue/white assay and were all confirmed by sequence analysis. This method also was used to quantitate the expression of paternal and maternal APC alleles taking advantage of an RsaI site polymorphism at position 1458 in a small number of informative individuals. Differential expression of some known mutant APC mRNAs was observed.

  3. Analytic Patch Configuration (APC) gateway version 1.0 user's guide

    NASA Technical Reports Server (NTRS)

    Bingel, Bradford D.

    1990-01-01

    The Analytic Patch Configuration (APC) is an interactive software tool which translates aircraft configuration geometry files from one format into another. This initial release of the APC Gateway accommodates six formats: the four accepted APC formats (89f, 89fd, 89u, and 89ud), the PATRAN 2.x phase 1 neutral file format, and the Integrated Aerodynamic Analysis System (IAAS) General Geometry (GG) format. Written in ANSI FORTRAN 77 and completely self-contained, the APC Gateway is very portable and was already installed on CDC/NOS, VAX/VMS, SUN, SGI/IRIS, CONVEX, and GRAY hosts.

  4. Controlling the response to DNA damage by the APC/C-Cdh1.

    PubMed

    de Boer, H Rudolf; Guerrero Llobet, S; van Vugt, Marcel A T M

    2016-03-01

    Proper cell cycle progression is safeguarded by the oscillating activities of cyclin/cyclin-dependent kinase complexes. An important player in the regulation of mitotic cyclins is the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase. Prior to entry into mitosis, the APC/C remains inactive, which allows the accumulation of mitotic regulators. APC/C activation requires binding to either the Cdc20 or Cdh1 adaptor protein, which sequentially bind the APC/C and facilitate targeting of multiple mitotic regulators for proteasomal destruction, including Securin and Cyclin B, to ensure proper chromosome segregation and mitotic exit. Emerging data have indicated that the APC/C, particularly in association with Cdh1, also functions prior to mitotic entry. Specifically, the APC/C-Cdh1 is activated in response to DNA damage in G2 phase cells. These observations are in line with in vitro and in vivo genetic studies, in which cells lacking Cdh1 expression display various defects, including impaired DNA repair and aberrant cell cycle checkpoints. In this review, we summarize the current literature on APC/C regulation in response to DNA damage, the functions of APC/C-Cdh1 activation upon DNA damage, and speculate how APC/C-Cdh1 can control cell fate in the context of persistent DNA damage.

  5. APC: A New Code for Atmospheric Polarization Computations

    NASA Technical Reports Server (NTRS)

    Korkin, Sergey V.; Lyapustin, Alexei I.; Rozanov, Vladimir V.

    2014-01-01

    A new polarized radiative transfer code Atmospheric Polarization Computations (APC) is described. The code is based on separation of the diffuse light field into anisotropic and smooth (regular) parts. The anisotropic part is computed analytically. The smooth regular part is computed numerically using the discrete ordinates method. Vertical stratification of the atmosphere, common types of bidirectional surface reflection and scattering by spherical particles or spheroids are included. A particular consideration is given to computation of the bidirectional polarization distribution function (BPDF) of the waved ocean surface.

  6. Sequestration of CDH1 by MAD2L2 prevents premature APC/C activation prior to anaphase onset

    PubMed Central

    Listovsky, Tamar

    2013-01-01

    The switch from activation of the anaphase-promoting complex/cyclosome (APC/C) by CDC20 to CDH1 during anaphase is crucial for accurate mitosis. APC/CCDC20 ubiquitinates a limited set of substrates for subsequent degradation, including Cyclin B1 and Securin, whereas APC/CCDH1 has a broader specificity. This switch depends on dephosphorylation of CDH1 and the APC/C, and on the degradation of CDC20. Here we show, in human cells, that the APC/C inhibitor MAD2L2 also contributes to ensuring the sequential activation of the APC/C by CDC20 and CDH1. In prometaphase, MAD2L2 sequestered free CDH1 away from the APC/C. At the onset of anaphase, MAD2L2 was rapidly degraded by APC/CCDC20, releasing CDH1 to activate the dephosphorylated APC/C. Loss of MAD2L2 led to premature association of CDH1 with the APC/C, early destruction of APC/CCDH1 substrates, and accelerated mitosis with frequent mitotic aberrations. Thus, MAD2L2 helps to ensure a robustly bistable switch between APC/CCDC20 and APC/CCDH1 during the metaphase-to-anaphase transition, thereby contributing to mitotic fidelity. PMID:24100295

  7. An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating ubiquitination

    PubMed Central

    Zeng, Xing; King, Randall W.

    2012-01-01

    The Anaphase-Promoting Complex/Cyclosome (APC) is a ubiquitin ligase required for exit from mitosis. We previously showed that Tosyl Arginine Methyl Ester (TAME) inhibits APC-dependent proteolysis by competing with the C-terminal IR-tail of the APC activator Cdc20 for APC binding. Here we show that in the absence of APC substrates, TAME ejects Cdc20 from the APC by promoting Cdc20 auto-ubiquitination in its N-terminal region. Cyclin B1 antagonizes TAME's effect by promoting binding of free Cdc20 to the APC and suppressing Cdc20 auto-ubiquitination. Nevertheless, TAME stabilizes cyclin B1 in Xenopus extract by two mechanisms. First, it reduces the kcat of the APCCdc20/cyclin B1 complex without affecting the Km, slowing the initial ubiquitination of unmodified cyclin B1. Second, as cyclin B1 becomes ubiquitinated, it loses its ability to promote Cdc20 binding to the APC in the presence of TAME. As a result, cyclin B1 ubiquitination terminates before reaching the threshold necessary for proteolysis. PMID:22366722

  8. REMOVAL OF ARSENIC IN DRINKING WATER: ARS CFU-50 APC ELECTROFLOCCULATION AND FILTRATION WATER TREATMENT SYSTEM

    EPA Science Inventory

    ETV testing of the ARS CFU-50 APC Electroflocculation and Filtration Water Treatment System (ARS CFU-50 APC) for arsenic removal was conducted at the Town of Bernalillo Well #3 site from April 18 through May 2, 2006. The source water was chlorinated groundwater from two supply w...

  9. Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells

    PubMed Central

    Barua, Dipak; Hlavacek, William S.

    2013-01-01

    In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of β—catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, β—catenin, serine/threonine kinases, and other proteins. The kinases and , which are recruited by Axin, mediate phosphorylation of β—catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of β—catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of a rule-based computational model, we investigated the regulation of β—catenin phosphorylation and degradation by APC and the effect of APC truncation on function of the destruction complex. The model integrates available mechanistic knowledge about site-specific interactions and phosphorylation of destruction complex components and is consistent with an array of published data. We find that the phosphorylated truncated form of APC can outcompete Axin for binding to β—catenin, provided that Axin is limiting, and thereby sequester β—catenin away from Axin and the Axin-recruited kinases and . Full-length APC also competes with Axin for binding to β—catenin; however, full-length APC is able, through its SAMP repeats, which bind Axin and which are missing in truncated oncogenic forms of APC, to bring β—catenin into indirect association with Axin and Axin-recruited kinases. Because our model indicates that the positive effects of truncated APC on β—catenin levels depend on phosphorylation of APC, at the first 20-amino acid repeat, and because phosphorylation of this site is mediated by , we suggest that is a potential target for therapeutic intervention in colorectal cancer. Specific inhibition of is predicted to limit binding of β—catenin to truncated

  10. Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells

    SciTech Connect

    Barua, Dipak; Hlavacek, William S.

    2013-09-26

    In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of β—catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, β—catenin, serine/threonine kinases, and other proteins. The kinases CK1α and GSK–3β, which are recruited by Axin, mediate phosphorylation of β—catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of β—catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of a rule-based computational model, we investigated the regulation of β—catenin phosphorylation and degradation by APC and the effect of APC truncation on function of the destruction complex. The model integrates available mechanistic knowledge about site-specific interactions and phosphorylation of destruction complex components and is consistent with an array of published data. In this paper, we find that the phosphorylated truncated form of APC can outcompete Axin for binding to β—catenin, provided that Axin is limiting, and thereby sequester β—catenin away from Axin and the Axin-recruited kinases CK1α and GSK–3β. Full-length APC also competes with Axin for binding to β—catenin; however, full-length APC is able, through its SAMP repeats, which bind Axin and which are missing in truncated oncogenic forms of APC, to bring β—catenin into indirect association with Axin and Axin-recruited kinases. Because our model indicates that the positive effects of truncated APC on β—catenin levels depend on phosphorylation of APC, at the first 20-amino acid repeat, and because phosphorylation of this site is mediated by CK1ϵ, we suggest that CK1ϵ is a potential target for therapeutic intervention in colorectal cancer. Finally, specific inhibition

  11. Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells

    DOE PAGES

    Barua, Dipak; Hlavacek, William S.

    2013-09-26

    In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of β—catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, β—catenin, serine/threonine kinases, and other proteins. The kinases CK1α and GSK–3β, which are recruited by Axin, mediate phosphorylation of β—catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of β—catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of amore » rule-based computational model, we investigated the regulation of β—catenin phosphorylation and degradation by APC and the effect of APC truncation on function of the destruction complex. The model integrates available mechanistic knowledge about site-specific interactions and phosphorylation of destruction complex components and is consistent with an array of published data. In this paper, we find that the phosphorylated truncated form of APC can outcompete Axin for binding to β—catenin, provided that Axin is limiting, and thereby sequester β—catenin away from Axin and the Axin-recruited kinases CK1α and GSK–3β. Full-length APC also competes with Axin for binding to β—catenin; however, full-length APC is able, through its SAMP repeats, which bind Axin and which are missing in truncated oncogenic forms of APC, to bring β—catenin into indirect association with Axin and Axin-recruited kinases. Because our model indicates that the positive effects of truncated APC on β—catenin levels depend on phosphorylation of APC, at the first 20-amino acid repeat, and because phosphorylation of this site is mediated by CK1ϵ, we suggest that CK1ϵ is a potential target for therapeutic intervention in colorectal cancer. Finally, specific

  12. APC binds intermediate filaments and is required for their reorganization during cell migration.

    PubMed

    Sakamoto, Yasuhisa; Boëda, Batiste; Etienne-Manneville, Sandrine

    2013-02-01

    Intermediate filaments (IFs) are components of the cytoskeleton involved in most cellular functions, including cell migration. Primary astrocytes mainly express glial fibrillary acidic protein, vimentin, and nestin, which are essential for migration. In a wound-induced migration assay, IFs reorganized to form a polarized network that was coextensive with microtubules in cell protrusions. We found that the tumor suppressor adenomatous polyposis coli (APC) was required for microtubule interaction with IFs and for microtubule-dependent rearrangements of IFs during astrocyte migration. We also show that loss or truncation of APC correlated with the disorganization of the IF network in glioma and carcinoma cells. In migrating astrocytes, vimentin-associated APC colocalized with microtubules. APC directly bound polymerized vimentin via its armadillo repeats. This binding domain promoted vimentin polymerization in vitro and contributed to the elongation of IFs along microtubules. These results point to APC as a crucial regulator of IF organization and confirm its fundamental role in the coordinated regulation of cytoskeletons.

  13. Evaluation and analysis of SEASAT-A Scanning Multichannel Microwave Radiometer (SMMR) Antenna Pattern Correction (APC) algorithm

    NASA Technical Reports Server (NTRS)

    Kitzis, J. L.; Kitzis, S. N.

    1979-01-01

    An evaluation of the versions of the SEASAT-A SMMR antenna pattern correction (APC) algorithm is presented. Two efforts are focused upon in the APC evaluation: the intercomparison of the interim, box, cross, and nominal APC modes; and the development of software to facilitate the creation of matched spacecraft and surface truth data sets which are located together in time and space. The problems discovered in earlier versions of the APC, now corrected, are discussed.

  14. Evaluating the organizational effectiveness of APC implementation efforts.

    PubMed

    Patel, Rajan

    2002-06-01

    To optimize revenue under the Medicare outpatient prospective payment system's new coding-based ambulatory payment classifications (APCs), healthcare providers need to ensure several key steps are taken at the organizational level. Individuals who manage coding need to identify areas of overlap and adjust billing systems to reflect changes under the system. Billing managers should develop practices and protocols that provide detailed reviews of claims, implement a formal denial management program, track reasons for denials, and communicate denial information with their staffs. Proper evaluation of financial practices also is important. Financial managers need to develop formal ways to monitor financial performance consistently and on an ongoing basis and ensure the hospital is generating sufficient volume and keeping service costs in line with payments.

  15. Stable MCC binding to the APC/C is required for a functional spindle assembly checkpoint

    PubMed Central

    Hein, Jamin B; Nilsson, Jakob

    2014-01-01

    The spindle assembly checkpoint (SAC) delays progression into anaphase until all chromosomes have aligned on the metaphase plate by inhibiting Cdc20, the mitotic co-activator of the APC/C. Mad2 and BubR1 bind and inhibit Cdc20, thereby forming the mitotic checkpoint complex (MCC), which can bind stably to the APC/C. Whether MCC formation per se is sufficient for a functional SAC or MCC association with the APC/C is required remains unclear. Here, we analyze the role of two conserved motifs in Cdc20, IR and C-Box, in binding of the MCC to the APC/C. Mutants in both motifs assemble the MCC normally, but IR motif integrity is particularly important for stable binding to the APC/C. Cells expressing Cdc20 with a mutated IR motif have a compromised SAC, as uninhibited Cdc20 can compete with the MCC for APC/C binding and activate it. We thus show that stable MCC association with the APC/C is critical for a functional SAC. PMID:24464857

  16. Oscillation of APC/C activity during cell cycle arrest promotes centrosome amplification

    PubMed Central

    Prosser, Suzanna L.; Samant, Mugdha D.; Baxter, Joanne E.; Morrison, Ciaran G.; Fry, Andrew M.

    2014-01-01

    Centrosome duplication is licensed by the disengagement, or ‘uncoupling’, of centrioles during late mitosis. However, arrest of cells in G2 can trigger premature centriole disengagement. Here, we show that premature disengagement results from untimely activation of the APC/C leading to securin degradation and release of active separase. APC/C activation during G2 arrest is dependent on Plk1-mediated degradation of the APC/C inhibitor, Emi1, but Plk1 also has a second APC/C-independent role in promoting disengagement. Importantly, APC/C and Plk1 activity also stimulate centriole disengagement in response to hydroxyurea or DNA damage-induced cell cycle arrest and this leads to centrosome amplification. However, the re-duplication of disengaged centrioles is dependent on Cdk2 activity and Cdk2 activation coincides with a subsequent inactivation of the APC/C and re-accumulation of cyclin A. Release from these arrests leads to mitotic entry but, due to the presence of disengaged and/or amplified centrosomes, formation of abnormal mitotic spindles that lead to chromosome missegregation. Thus, oscillation of APC/C activity during cell cycle arrest promotes both centrosome amplification and genome instability. PMID:22956538

  17. Flow analysis of heavy metals in a pilot-scale incinerator for residues from waste electrical and electronic equipment dismantling.

    PubMed

    Long, Yu-Yang; Feng, Yi-Jian; Cai, Si-Shi; Ding, Wei-Xu; Shen, Dong-Sheng

    2013-10-15

    The large amount of residues generated from dismantling waste electrical and electronic equipment (WEEE) results in a considerable environmental burden. We used material flow analysis to investigate heavy metal behavior in an incineration plant in China used exclusively to incinerate residues from WEEE dismantling. The heavy metals tested were enriched in the bottom and fly ashes after incineration. However, the contents of heavy metals in the bottom ash, fly ash and exhaust gas do not have a significant correlation with that of the input waste. The evaporation and recondensation behavior of heavy metals caused their contents to differ with air pollution control equipment because of the temperature difference during gas venting. Among the heavy metals tested, Cd had the strongest tendency to transfer during incineration (TCd=69.5%) because it had the lowest melting point, followed by Cu, Ni, Pb and Zn. The exchangeable and residual fractions of heavy metals increased substantially in the incineration products compared with that of the input residues. Although the mass of residues from WEEE dismantling can be reduced by 70% by incineration, the safe disposal of the metal-enriched bottom and fly ashes is still required. PMID:23973476

  18. Understanding household demand for indoor air pollution control in developing countries.

    PubMed

    Larson, Bruce A; Rosen, Sydney

    2002-08-01

    More than 2 billion people rely on solid fuels and traditional stoves or open fires for cooking, lighting, and/or heating. Exposure to emissions caused by burning these fuels is believed to be responsible for a significant share of the global burden of disease. To achieve widespread health improvements, interventions that reduce exposures to indoor air pollution will need to be adopted and consistently used by large numbers of households in the developing world. Given that such interventions remain to be adopted by large numbers of these households, much remains to be learned about household demand for interventions designed (in part at least) to reduce indoor air pollution. A general household framework is developed that identifies in detail the determinants of household demand for indoor air pollution interventions, where demand for an intervention is expressed in terms of willingness to pay. Household demand is shown to be a combination of three terms: (1) the direct consumption effect; (2) the child health effect; and (3) the adult health effect. While micro-level data are not available to estimate directly this model, existing data and information are used to estimate just the health effects component of household demand. Based on such existing information, it might be concluded that household demand should seemingly be strong given that willingness to pay, based on existing information, is seemingly large compared to costs for common interventions like improved stoves. Given that household demand is not strong for existing interventions, this analysis shows that more clearly focused research on household demand for interventions is needed if such interventions are going to be demanded (i.e. adopted and used) by large numbers of households throughout the developing world. Four priority areas for future research are: (1) improving information on dose-response relationships between indoor air pollution and various health effects (e.g. increased mortality and morbidity risks); (2) improving information on impacts from interventions in terms of air pollution reductions and also cooking times, fuel use, and heat intensities; (3) improving information on household shadow values for improved health, with separate information for adult and child health; and (4) considering more directly household information, and its adequacy, for their ability to evaluate the relationships between fuel use and health.

  19. Improving air pollution control policy in China--A perspective based on cost-benefit analysis.

    PubMed

    Gao, Jinglei; Yuan, Zengwei; Liu, Xuewei; Xia, Xiaoming; Huang, Xianjin; Dong, Zhanfeng

    2016-02-01

    To mitigate serious air pollution, the State Council of China promulgated the Air Pollution Prevention and Control Action Plan in 2013. To verify the feasibility and validity of industrial energy-saving and emission-reduction policies in the action plan, we conducted a cost-benefit analysis of implementing these policies in 31 provinces for the period of 2013 to 2017. We also completed a scenario analysis in this study to assess the cost-effectiveness of different measures within the energy-saving and the emission-reduction policies individually. The data were derived from field surveys, statistical yearbooks, government documents, and published literatures. The results show that total cost and total benefit are 118.39 and 748.15 billion Yuan, respectively, and the estimated benefit-cost ratio is 6.32 in the S3 scenario. For all the scenarios, these policies are cost-effective and the eastern region has higher satisfactory values. Furthermore, the end-of-pipe scenario has greater emission reduction potential than energy-saving scenario. We also found that gross domestic product and population are significantly correlated with the benefit-cost ratio value through the regression analysis of selected possible influencing factors. The sensitivity analysis demonstrates that benefit-cost ratio value is more sensitive to unit emission-reduction cost, unit subsidy, growth rate of gross domestic product, and discount rate among all the parameters. Compared with other provinces, the benefit-cost ratios of Beijing and Tianjin are more sensitive to changes of unit subsidy than unit emission-reduction cost. These findings may have significant implications for improving China's air pollution prevention policy.

  20. Effect of inlet temperature on the performance of a catalytic reactor. [air pollution control

    NASA Technical Reports Server (NTRS)

    Anderson, D. N.

    1978-01-01

    A 12 cm diameter by 15 cm long catalytic reactor was tested with No. 2 diesel fuel in a combustion test rig at inlet temperatures of 700, 800, 900, and 1000 K. Other test conditions included pressures of 3 and 6 x 10 to the 5th power Pa, reference velocities of 10, 15, and 20 m/s, and adiabatic combustion temperatures in the range 1100 to 1400 K. The combustion efficiency was calculated from measurements of carbon monoxide and unburned hydrocarbon emissions. Nitrogen oxide emissions and reactor pressure drop were also measured. At a reference velocity of 10 m/s, the CO and unburned hydrocarbons emissions, and, therefore, the combustion efficiency, were independent of inlet temperature. At an inlet temperature of 1000 K, they were independent of reference velocity. Nitrogen oxides emissions resulted from conversion of the small amount (135 ppm) of fuel-bound nitrogen in the fuel. Up to 90 percent conversion was observed with no apparent effect of any of the test variables. For typical gas turbine operating conditions, all three pollutants were below levels which would permit the most stringent proposed automotive emissions standards to be met.

  1. [Application of analytical pyrolysis in air pollution control for green sand casting industry].

    PubMed

    Wang, Yu-jue; Zhao, Qi; Chen, Ying; Wang, Cheng-wen

    2010-02-01

    Analytic pyrolysis was conducted to simulate the heating conditions that the raw materials of green sand would experience during metal casting process. The volatile organic compound (VOC) and hazardous air pollutant (HAP) emissions from analytical pyrolysis were analyzed by gas chromatograph-flame ionization detector/mass spectrometry (GC-FID/MS). The emissions from analytical pyrolysis exhibited some similarity in the compositions and distributions with those from actual casting processes. The major compositions of the emissions included benzene, toluene and phenol. The relative changes of emission levels that were observed in analytical pyrolysis of the various raw materials also showed similar trends with those observed in actual metal casting processes. The emission testing results of both analytic pyrolysis and pre-production foundry have shown that compared to the conventional phenolic urethane binder, the new non-naphthalene phenolic urethane binder diminished more than 50% of polycyclic aromatic hydrocarbon emissions, and the protein-based binder diminished more than 90% of HAP emissions. The similar trends in the two sets of tests offered promise that analytical pyrolysis techniques could be a fast and accurate way to establish the emission inventories, and to evaluate the relative emission levels of various raw materials of casting industry. The results of analytical pyrolysis could provide useful guides for the foundries to select and develop proper clean raw materials for the casting production. PMID:20391731

  2. Energy-efficient air pollution controls for fossil-fueled plants: Technology assessment

    SciTech Connect

    Sayer, J.H.

    1995-06-01

    The 1990 Clean Air Act Amendments require most fossil-fuel fired power plants to reduce sulfur dioxide, nitrogen oxides, and particulate emissions. While emission-control equipment is available to help most of New York State`s 91 utility units in 31 power plants comply with the new regulations, technologies currently available consume energy, increase carbon dioxide emissions, reduce operating efficiency, and may produce large amounts of solid and/or semisolid byproducts that use additional energy for processing and disposal. This report discribes several pollution-control technologies that are more energy efficient compared to traditional technologies for controlling sulfur dioxide, nitrogen oxide, and particulates, that may have application in New York State. These technologies are either in commercial use, under development, or in the demonstration phase; This report also presents operating characteristics for these technologies and discusses solutions to dispose of pollution-control system byproducts. Estimated energy consumption for emission-control systems relative to a plant`s gross generating capacity is 3 to 5 for reducing up to 90% sulfur dioxide emissions from coal-fired plants. 0.5 to 2.5% for reducing nitrogen oxide emissions by up to 80% from all fossil-fuel fired plants; and 0.5 to 1.5 % for controlling particulate emissions from oil- and coal-fired plants. While fuel switching and/or cofiring with natural gas are options to reduce emissions, these techniques are not considered in this report; the discussion is limited to fossil-fueled steam-generating plants.

  3. Applications for activated carbons from waste tires: Natural gas storage and air pollution control

    USGS Publications Warehouse

    Brady, T.A.; Rostam-Abadi, M.; Rood, M.J.

    1996-01-01

    Natural gas storage for natural gas vehicles and the separation and removal of gaseous contaminants from gas streams represent two emerging applications for carbon adsorbents. A possible precursor for such adsorbents is waste tires. In this study, activated carbon has been developed from waste tires and tested for its methane storage capacity and SO2 removal from a simulated flue-gas. Tire-derived carbons exhibit methane adsorption capacities (g/g) within 10% of a relatively expensive commercial activated carbon; however, their methane storage capacities (Vm/Vs) are almost 60% lower. The unactivated tire char exhibits SO2 adsorption kinetics similar to a commercial carbon used for flue-gas clean-up. Copyright ?? 1996 Elsevier Science Ltd.

  4. Effect of air pollution control on mortality and hospital admissions in Ireland.

    PubMed

    Dockery, Douglas W; Rich, David Q; Goodman, Patrick G; Clancy, Luke; Ohman-Strickland, Pamela; George, Prethibha; Kotlov, Tania

    2013-07-01

    During the 1980s the Republic of Ireland experienced repeated severe pollution episodes. Domestic coal burning was a major source of this pollution. In 1990 the Irish government introduced a ban on the marketing, sale, and distribution of coal in Dublin. The ban was extended to Cork in 1995 and to 10 other communities in 1998 and 2000. We previously reported decreases in particulate black smoke (BS*) and sulfur dioxide (SO2) concentrations, measured as total gaseous acidity, in Dublin after the 1990 coal ban (Clancy et al. 2002). In the current study we explored and compared the effectiveness of the sequential 1990, 1995, and 1998 bans in reducing community air pollution and in improving public health. We compiled records of daily BS, total gaseous acidity (SO2), and counts of cause-specific deaths from 1981 to 2004 for Dublin County Borough (1990 ban), county Cork (1995 ban), and counties Limerick, Louth, Wexford, and Wicklow (1998 ban). We also compiled daily counts of hospital admissions for cardiovascular, respiratory, and digestive diagnoses for Cork County Borough (1991 to 2004) and counties Limerick, Louth, Wexford, and Wicklow (1993 to 2004). We compared pre-ban and post-ban BS and SO2 concentrations for each city. Using interrupted time-series methods, we estimated the change in cause-specific, directly standardized mortality rates in each city or county after the corresponding local coal ban. We regressed weekly age- and sex-standardized mortality rates against an indicator of the post- versus pre-ban period, adjusting for influenza epidemics, weekly mean temperature, and a season smooth of the standardized mortality rates in Coastal counties presumably not affected by the bans. We compared these results with similar analyses in Midlands counties also presumably unaffected by the bans. We also estimated the change in cause-specific, directly standardized, weekly hospital admissions rates normalized for underreporting in each city or county after the 1995 and 1998 bans, adjusting for influenza epidemics, weekly mean temperature, and local admissions for digestive diagnoses. Mean BS concentrations fell in all affected population centers post-ban compared with the pre-ban period, with decreases ranging from 4 to 35 microg/m3 (corresponding to reductions of 45% to 70%, respectively), but we observed no clear pattern in SO2 measured as total gaseous acidity associated with the bans. In comparisons with the pre-ban periods, no significant reduction was found in total death rates associated with the 1990 (1% reduction), 1995 (4% reduction), or 1998 (0% reduction) bans, nor for cardiovascular mortality (0%, 4%, and 1% reductions for the 1990, 1995, and 1998 bans, respectively). Respiratory mortality was reduced in association with the bans (17%, 9%, and 3%, respectively). We found a 4% decrease in hospital admissions for cardiovascular disease associated with the 1995 ban and a 3% decrease with the 1998 ban. Admissions for respiratory disease were not consistently lower after the bans; admissions for pneumonia, chronic obstructive pulmonary disease (COPD), and asthma were reduced. However, underreporting of hospital admissions data and lack of control and comparison series tempered our confidence in these results. The successive coal bans resulted in immediate and sustained decreases in particulate concentrations in each city or town; with the largest decreases in winter and during the heating season. The bans were associated with reductions in respiratory mortality but no detectable improvement in cardiovascular mortality. The changes in hospital admissions for respiratory and cardiovascular disease were supportive of these findings but cannot be considered confirming. Detecting changes in public health indicators associated even with clear improvements in air quality, as in this case, remains difficult when there are simultaneous secular improvements in the same health indicators.

  5. 76 FR 54993 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-06

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... proposing a limited approval and limited disapproval of ] revisions to the Placer County Air Pollution... the Clean Air Act Amendments of 1990''; 57 FR ] 13498 (April 16, 1992); 57 FR 18070 (April 28,...

  6. 78 FR 21542 - Revisions to the California State Implementation Plan, Santa Barbara County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... into the SIP on December 20, 2000 (65 FR 79752). We approved an earlier version of SCAQMD Rule 461 into the SIP on April 11, 2006 (71 FR 18216). The SCAQMD adopted revisions to the SIP-approved version on... review by the Office of Management and Budget under Executive Order 12866 (58 FR 51735, October 4,...

  7. Air cleaners for indoor-air-pollution control (Chapter 10). Book chapter, Feb 89-Jul 90

    SciTech Connect

    Viner, A.S.; Ramanathan, K.; Hanley, J.T.; Smith, D.D.; Ensor, D.S.

    1991-01-01

    The chapter describes an experimental study to evaluate performance characteristics of currently available controls for indoor air pollutants, including both particles and gases. The study evaluated the particle-size-dependent collection efficiency of seven commercially available devices for particulate control: a common furnace filter, four industrial filters, and two electronic air cleaners (EACs). The furnance filter had negligible effect on particles with diameters between 0.1 and 1 micrometer. The industrial filters, with ASHRAE ratings of 95, 85, 65, and 40% showed minimum efficiency at about 0.1 micrometer, which was substantially less than the ASHRAE efficiency. One EAC, essentially a furnance filter with a high-voltage electrode, reached a maximum efficiency of 30% at low flowrates (7 cu m/min); however, it had a negligible effect at higher flowrates. The other EAC, similar to an industrial ESP, showed efficiencies of 80-90% over the entire size range at low to moderate flowrates. At the highest flowrate, a minimum efficiency was detected at 0.35 micrometer. The study also evaluated the suitability of commerically available carbon-based sorbents (wood, coal, and coconut) for removing low concentrations of volatile organic compounds (benzene, acetaldehyde, and 1,1,1-trichloroethane).

  8. A Critical Review of the Effect of Air Pollution Control Regulations on Land Use Planning

    ERIC Educational Resources Information Center

    Roberts, John J.; And Others

    1975-01-01

    Although a number of recent federal initiatives explicitly require greater coordination of land use and air quality management, viable working relationships among the planning and regulatory agencies have not been developed. The concept of emission density zoning is endorsed. (Author/BT)

  9. Mortality reduction following the air pollution control measures during the 2010 Asian Games

    NASA Astrophysics Data System (ADS)

    Lin, Hualiang; Zhang, Yonghui; Liu, Tao; Xiao, Jianpeng; Xu, Yanjun; Xu, Xiaojun; Qian, Zhenmin; Tong, Shilu; Luo, Yuan; Zeng, Weilin; Ma, Wenjun

    2014-07-01

    Though increased particulate air pollution has been consistently associated with elevated mortality, evidence regarding whether diminished particulate air pollution would lead to mortality reduction is limited. Citywide air pollution mitigation program during the 2010 Asian Games in Guangzhou, China, provided such an opportunity. Daily mortality from non-accidental, cardiovascular and respiratory diseases was compared for 51 intervention days (November 1-December 21) in 2010 with the same calendar date of baseline years (2006-2009 and 2011). Relative risk (RR) and 95% confidence interval (95% CI) were estimated using a time series Poisson model, adjusting for day of week, public holidays, daily mean temperature and relative humidity. Daily PM10 (particle with aerodynamic diameter less than 10 μm) decreased from 88.64 μg/m3 during the baseline period to 80.61 μg/m3 during the Asian Games period. Other measured air pollutants and weather variables did not differ substantially. Daily mortality from non-accidental, cardiovascular and respiratory diseases decreased from 32, 11 and 6 during the baseline period to 25, 8 and 5 during the Games period, the corresponding RR for the Games period compared with the baseline period was 0.79 (95% CI: 0.73-0.86), 0.77 (95% CI: 0.66-0.89) and 0.68 (95% CI: 0.57-0.80), respectively. No significant decreases were observed in other months of 2010 in Guangzhou and intervention period in two control cities. This finding supports the efforts to reduce air pollution and improve public health through transportation restriction and industrial emission control.

  10. Operation of Oil Burning Equipment and Incinerators. An Air Pollution Control Workbook, Preliminary Edition.

    ERIC Educational Resources Information Center

    New Jersey State Dept. of Environmental Protection, Trenton. Bureau of Air Pollution Control.

    This workbook has been prepared for use by persons charged with the burning of fuels and waste products in the State of New Jersey. It is written for building superintendents, custodians, porters, handymen and operating engineers of public, apartment, commercial and office buildings. The manual emphasizes operating procedures that will help meet…

  11. Field demonstration and commercialization of silent discharge plasma hazardous air pollutant control technology

    SciTech Connect

    Rosocha, L.A.; Coogan, J.J.; Korzekwa, R.A.; Secker, D.A.; Reimers, R.F.; Herrmann, P.G.; Chase, P.J.; Gross, M.P. |; Jones, M.R.

    1996-07-01

    Silent electrical discharge plasma (dielectric barrier) reactors can decompose gas-phase pollutants by free-radical attack or electron-induced fragmentation. The radicals or electrons are produced by the large average volume nonthermal plasmas generated in the reactor. In the past decade, the barrier configuration has attracted attention for destroying toxic chemical agents for the military, removing harmful greenhouse gases, and treating other environmentally- hazardous chemical compounds. At the Los Alamos National Laboratory, we have been studying the silent discharge plasma (SDP) for processing gaseous-based hazardous chemicals for approximately five years. The key objective is to convert hazardous or toxic chemicals into non-hazardous compounds or into materials which are more easily managed. The main applications have been for treating off-gases from thermal treatment units, and for abating hazardous air-pollutant emissions (e.g., industrial air emissions, vapors extracted from contaminated soil or groundwater). In this paper, we will summarize the basic principles of SDP processing, discuss illustrative applications of the technology, and present results from small-scale field tests that are relevant to our commercialization effort.

  12. Toxic Acid Gas Absorber Design Considerations for Air Pollution Control in Process Industries

    ERIC Educational Resources Information Center

    Manyele, S. V.

    2008-01-01

    This paper analyses the design parameters for an absorber used for removal of toxic acid gas (in particular sulfur dioxide) from a process gas stream for environmental health protection purposes. Starting from the equilibrium data, Henry's law constant was determined from the slope of the y-x diagram. Based on mass balances across the absorber,…

  13. 76 FR 71922 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-21

    ... volatile organic compound (VOC) emissions from coatings and strippers used on wood products, wood paneling... following local rules: PCAPCD Rule 236 (Wood Products and Coating Operations), PCAPCD Rule 238 (Factory Coating of Flat Wood Paneling), and SMAQMD Rule 451 (Surface Coating of Miscellaneous Metal Parts...

  14. 75 FR 39365 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-08

    ... Order Reviews I. Summary of Proposed Action On February 23, 2010 (75 FR 8008), EPA proposed a limited... are significant and consequently require BACM pursuant to EPA guidance. This determination was based... section E.6 for recreational use of public lands in Imperial County. \\6\\ 75 FR 8008, 8010-8011 and...

  15. 76 FR 7142 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-09

    ... versions of these rules? We approved an earlier version of Rule 201 into the SIP on January 3, 2007 (72 FR... permit exemptions. Rule 103 was approved into the SIP on May 31, 1972 (37 FR 10842). The ICAPCD... 12866 (58 FR 51735, October 4, 1993); Does not impose an information collection burden under...

  16. 75 FR 8008 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-23

    ... for the Implementation of Title I of the Clean Air Act Amendments of 1990,'' 57 FR 13498 (April 16, 1992); 57 FR 18070 (April 28, 1992). 4. ``State Implementation Plans for Serious PM-10 Nonattainment... Preamble for the Implementation of Title I of the Clean Air Act Amendments of 1990,'' 59 FR 41998...

  17. 76 FR 67366 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-01

    ..., stationary internal combustion engines and water heaters. We are approving local rules that regulate these... Heaters. PCAPCD 242 Stationary Internal 04/10/03 12/07/10 Combustion Engines. PCAPCD 246 Natural Gas-Fired... Emissions from Stationary Reciprocating Internal Combustion Engines'', US EPA 453/R-93-032 (July 1993)....

  18. 75 FR 69002 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-10

    ... and Executive Order Reviews I. Proposed Action On May 19, 2010 (75 FR 27975), EPA proposed to approve.... Response #1: Our proposed action (75 FR 27976) and the associated TSD (pages 2-3) both refer to two ICAPCD... provided by the District relate to the 5 g/m\\3\\ standard set forth in 59 FR 41998 (August 16,...

  19. 78 FR 12267 - Revision of Air Quality Implementation Plan; California; Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ... in a previous EPA rulemaking (76 FR 44809, July 27, 2011). DATES: Any comments must arrive by March... previous version of Rules 502 and 10.1, into the SIP on July 27, 2011 (76 FR 44809).\\1\\ \\1\\ In our previous... deficiencies identified by EPA on July 27, 2011 (76 FR 44809). II. EPA's Evaluation and Proposed Action A....

  20. 78 FR 21581 - Revisions to the California State Implementation Plan, Santa Barbara County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... compound (VOC) and oxides of nitrogen (NO X ) emissions from gas-fired fan-type central furnaces, small... Fan-Type Central Furnaces and Small Water Heaters and SCAQMD Rule 461 Gasoline Transfer and...

  1. Gas-phase photocatalytic oxidation: Cost comparison with other air pollution control technologies

    SciTech Connect

    Turchi, C S; Wolfrum, E J; Miller, R A

    1994-11-01

    Gas-phase photocatalytic oxidation (PCO) appears to be particularly well suited for waste streams with low pollutant concentrations (1000 ppm or less) and low to moderate flow rates (< 20,000 cubic feet per minute, cfm). The PCO technology is modular in nature and thus is well suited to treat dispersed or low flow rate streams. This same attribute minimizes the advantages of scale for PCO and makes the technology comparatively less attractive for high volume waste streams. Key advantages for PCO lie in its low operating cost and ability to completely destroy pollutants at ambient temperature and pressure.

  2. Air pollution control by economic incentives in the U.S.: Policy, problems, and progress

    NASA Astrophysics Data System (ADS)

    Lakhani, Hyder

    1982-01-01

    This paper deals with cost-effectiveness of the economic incentive policies of the bubble concept and offset credits relative to the policy of direct regulations of air emissions. The second section discusses single- and multi-plant bubbles, their adoption across regions and industries, the methods used to control emissions and the extent of savings in costs. We conclude that despite the delay resulting from duplication of review of state implementation plans by both the state and the Environmental Protection Agency, the required technological commands, the requirement to model air quality and the restrictions to permit bubbling only in the attainment areas, the policy is progressing successfully and should be encouraged by eliminating the restrictions. The third section analyzes the policy of emission offset credit, trading, and banking which can permit economic growth in nonattainment areas. It reviews the available literature, which deals only with aggregation of offsets across cities instead of individual offset trades. Progress by individual offset trades is analyzed in terms of the number of offsets, their acceptance across regions, the extent of reductions in emissions, and the classification of the offsets into internal and external trades. Comparison of estimated capital costs and prices of individual offsets with direct regulation costs reveals that the former are economical. We conclude that despite the problems of high tradeoff ratios, the short and uncertain life of the emission offset credits and the technological commands, the policy is progressing successfully and should be encouraged further by relaxing restrictions.

  3. 76 FR 28944 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... Control District and Feather River Air Quality Management District AGENCY: Environmental Protection Agency... EPA. (67 FR 80186) \\1\\ While the District uses the term BACT as the level of control required, a... Office of Management and Budget under Executive Order 12866 (58 FR 51735, October 4, 1993); Does...

  4. 76 FR 44809 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-27

    ... Control District and Feather River Air Quality Management District ACTION: Final rule. SUMMARY: EPA is... Pollution Control District (PCAPCD) and Feather River Air Quality Management District (FRAQMD) portions of... and Executive Order Reviews I. Proposed Action On May 19, 2011 (76 FR 28944), EPA proposed a...

  5. Ancillary benefits for climate change mitigation and air pollution control in the world's motor vehicle fleets.

    PubMed

    Walsh, Michael P

    2008-01-01

    The global motor vehicle population has grown very rapidly in the past half century and is expected to continue to grow rapidly for the next several decades, especially in developing countries. As a result, vehicles are a major source of urban air pollution in many cities and are the fastest-growing source of greenhouse emissions. Strategies exist to reduce both problems, but many countries emphasize one over the other rather than pursuing strategies that reduce both concerns. Using diesel as an example, this article illustrates that it is now possible not only to reduce carbon dioxide with the increased use of diesel vehicles but also to improve urban air pollution. Doing so requires both stringent emissions regulations and clean fuels. Several principles contained in the Bellagio Memorandum are highlighted as guides for policy makers.

  6. 76 FR 60376 - Revisions to the California State Implementation Plan, Santa Barbara Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... operations and oil and gas production wells. We are approving local rules that regulate these emission... 2/1/08 4/5/11 Operations. SCAQMD 1148.1 Oil and Gas Production Adopted 3/5/04 1/10/10 Wells. On... solvent cleaning machines, the application of solvents, and from oil and gas production wells....

  7. 76 FR 60405 - Revisions to the California State Implementation Plan, Santa Barbara Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... production wells. We are proposing to approve local rules to regulate these emission sources under the Clean... Gas Production Wells.'' In the Rules and Regulations section of this Federal Register, we...

  8. β-Catenin destruction complex-independent regulation of Hippo–YAP signaling by APC in intestinal tumorigenesis

    PubMed Central

    Cai, Jing; Maitra, Anirban; Anders, Robert A.; Taketo, Makoto M.; Pan, Duojia

    2015-01-01

    Mutations in Adenomatous polyposis coli (APC) underlie familial adenomatous polyposis (FAP), an inherited cancer syndrome characterized by the widespread development of colorectal polyps. APC is best known as a scaffold protein in the β-catenin destruction complex, whose activity is antagonized by canonical Wnt signaling. Whether other effector pathways mediate APC's tumor suppressor function is less clear. Here we report that activation of YAP, the downstream effector of the Hippo signaling pathway, is a general hallmark of tubular adenomas from FAP patients. We show that APC functions as a scaffold protein that facilitates the Hippo kinase cascade by interacting with Sav1 and Lats1. Consistent with the molecular link between APC and the Hippo signaling pathway, genetic analysis reveals that YAP is absolutely required for the development of APC-deficient adenomas. These findings establish Hippo–YAP signaling as a critical effector pathway downstream from APC, independent from its involvement in the β-catenin destruction complex. PMID:26193883

  9. The zinc-binding region (ZBR) fragment of Emi2 can inhibit APC/C by targeting its association with the coactivator Cdc20 and UBE2C-mediated ubiquitylation

    PubMed Central

    Shoji, Shisako; Muto, Yutaka; Ikeda, Mariko; He, Fahu; Tsuda, Kengo; Ohsawa, Noboru; Akasaka, Ryogo; Terada, Takaho; Wakiyama, Motoaki; Shirouzu, Mikako; Yokoyama, Shigeyuki

    2014-01-01

    Anaphase-promoting complex or cyclosome (APC/C) is a multisubunit ubiquitin ligase E3 that targets cell-cycle regulators. Cdc20 is required for full activation of APC/C in M phase, and mediates substrate recognition. In vertebrates, Emi2/Erp1/FBXO43 inhibits APC/C-Cdc20, and functions as a cytostatic factor that causes long-term M phase arrest of mature oocytes. In this study, we found that a fragment corresponding to the zinc-binding region (ZBR) domain of Emi2 inhibits cell-cycle progression, and impairs the association of Cdc20 with the APC/C core complex in HEK293T cells. Furthermore, we revealed that the ZBR fragment of Emi2 inhibits in vitro ubiquitin chain elongation catalyzed by the APC/C cullin-RING ligase module, the ANAPC2–ANAPC11 subcomplex, in combination with the ubiquitin chain-initiating E2, E2C/UBE2C/UbcH10. Structural analyses revealed that the Emi2 ZBR domain uses different faces for the two mechanisms. Thus, the double-faced ZBR domain of Emi2 antagonizes the APC/C function by inhibiting both the binding with the coactivator Cdc20 and ubiquitylation mediated by the cullin-RING ligase module and E2C. In addition, the tail region between the ZBR domain and the C-terminal RL residues [the post-ZBR (PZ) region] interacts with the cullin subunit, ANAPC2. In the case of the ZBR fragment of the somatic paralogue of Emi2, Emi1/FBXO5, these inhibitory activities against cell division and ubiquitylation were not observed. Finally, we identified two sets of key residues in the Emi2 ZBR domain that selectively exert each of the dual Emi2-specific modes of APC/C inhibition, by their mutation in the Emi2 ZBR domain and their transplantation into the Emi1 ZBR domain. PMID:25161877

  10. A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells.

    PubMed

    Mao, Diane D; Gujar, Amit D; Mahlokozera, Tatenda; Chen, Ishita; Pan, Yanchun; Luo, Jingqin; Brost, Taylor; Thompson, Elizabeth A; Turski, Alice; Leuthardt, Eric C; Dunn, Gavin P; Chicoine, Michael R; Rich, Keith M; Dowling, Joshua L; Zipfel, Gregory J; Dacey, Ralph G; Achilefu, Samuel; Tran, David D; Yano, Hiroko; Kim, Albert H

    2015-06-23

    Glioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma.

  11. Quercetin supplementation attenuates the progression of cancer cachexia in ApcMin/+ mice.

    PubMed

    Velázquez, Kandy T; Enos, Reilly T; Narsale, Aditi A; Puppa, Melissa J; Davis, J Mark; Murphy, E Angela; Carson, James A

    2014-06-01

    Although there are currently no approved treatments for cancer cachexia, there is an intensified interest in developing therapies because of the high mortality index associated with muscle wasting diseases. Successful treatment of the cachectic patient focuses on improving or maintaining body weight and musculoskeletal function. Nutraceutical compounds, including the natural phytochemical quercetin, are being examined as potential treatments because of their anti-inflammatory, antioxidant, and anticarcinogenic properties. The purpose of this study was to determine the effect of quercetin supplementation on the progression of cachexia in the adenomatous polyposis coli (Apc)(Min/+) mouse model of colorectal cancer. At 15 wk of age, C57BL/6 and male Apc(Min/+) mice were supplemented with 25 mg/kg of quercetin or vehicle solution mix of Tang juice and water (V) daily for 3 wk. Body weight, strength, neuromuscular performance, and fatigue were assessed before and after quercetin or V interventions. Indicators of metabolic dysfunction and inflammatory signaling were also assessed. During the treatment period, the relative decrease in body weight in the Apc(Min/+) mice gavaged with V (Apc(Min/+)V; -14% ± 2.3) was higher than in control mice gavaged with V (+0.6% ± 1.0), control mice gavaged with quercetin (-2% ± 1.0), and Apc(Min/+) mice gavaged with quercetin (Apc(Min/+)Q; -9% ± 1.3). At 18 wk of age, the loss of grip strength and muscle mass shown in Apc(Min/+)V mice was significantly attenuated (P < 0.05) in Apc(Min/+)Q mice. Furthermore, Apc(Min/+)V mice had an induction of plasma interleukin-6 and muscle signal transducer and activator of transcription 3 phosphorylation, which were significantly (P < 0.05) mitigated in Apc(Min/+)Q mice, despite having a similar tumor burden. Quercetin treatment did not improve treadmill run-time-to-fatigue, hyperglycemia, or hyperlipidemia in cachectic Apc(Min/+) mice. Overall, quercetin supplementation positively affected

  12. A Minimal Anaphase Promoting Complex/Cyclosome (APC/C) in Trypanosoma brucei

    PubMed Central

    Bessat, Mohamed; Knudsen, Giselle; Burlingame, Alma L.; Wang, Ching C.

    2013-01-01

    The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that initiates chromosome segregation and mitotic exit by targeting critical cell-cycle regulators for proteolytic destruction. Previously, seven APC/C subunit homologues were identified in the genome of Trypanosoma brucei. In the present study, we tested five of them in yeast complementation studies and found none of them capable of complementing the yeast mutants lacking the corresponding subunits, suggesting significant discrepancies between the two APC/C’s. Subunit homologues of mitotic checkpoint complex (MCC) have not yet been identified in T. brucei, raising the possibility that a MCC-APC/C complex equivalent may not exist in T. brucei. We performed tandem affinity purification of the protein complex containing a APC1 fusion protein expressed in the cells enriched in different phases of the cell cycle of procyclic form T. brucei, and compared their protein profiles using LC-MS/MS analyses. The seven putative APC/C subunits were identified in the protein complex throughout the cell cycle together with three additional proteins designated the associated proteins (AP) AP1, AP2 and AP3. Abundance of the 10 proteins remained relatively unchanged throughout the cell cycle, suggesting that they are the core subunits of APC/C. AP1 turned out to be a homologue of APC4. An RNAi knockdown of APC4 and AP3 showed no detectable cellular phenotype, whereas an AP2 knockdown enriched the cells in G2/M phase. The AP2-depleted cells showed stabilized mitotic cyclin B. An accumulation of poly-ubiquitinated cyclin B was indicated in the cells treated with the proteasome inhibitor MG132, demonstrating the involvement of proteasome in degrading poly-ubiquitinated cyclin B. In all, a 10-subunit APC/C machinery with a conserved function is identified in T. brucei without linking to a MCC-like complex, thus indicating a unique T. brucei APC/C. PMID:23533609

  13. Black raspberries suppress colonic adenoma development in ApcMin/+ mice: relation to metabolite profiles.

    PubMed

    Pan, Pan; Skaer, Chad W; Wang, Hsin-Tzu; Stirdivant, Steven M; Young, Matthew R; Oshima, Kiyoko; Stoner, Gary D; Lechner, John F; Huang, Yi-Wen; Wang, Li-Shu

    2015-10-01

    Freeze-dried black raspberries (BRBs) have demonstrated chemopreventive effects in a dietary intervention trial with human colorectal cancer patients. The aim of this study was to investigate BRB-caused metabolite changes using the Apc(Min/+) mouse as a model of human colorectal cancer. Wild-type (WT) mice were fed control diet, and Apc(Min/+) mice were fed either control diet or control diet supplemented with 5% BRBs for 8 weeks. Colonic and intestinal polyp size and number were measured. A non-targeted metabolomic analysis was conducted on colonic mucosa, liver and fecal specimens. Eight weeks of BRB treatment significantly decreased intestinal and colonic polyp number and size in Apc(Min/+) mice. The apc gene mutation significantly changed 52 metabolites in colonic mucosa associated with increased amino acid and decreased lipid metabolites, as well as 39 liver and 8 fecal metabolites. BRBs significantly reversed 23 apc-regulated metabolites, including 13 colonic mucosa, 8 liver and 2 fecal metabolites that were involved in amino acid, glutathione, lipid and nucleotide metabolism. Of these, changes in eight metabolites were linearly correlated with decreased colonic polyp number and size in BRB-treated Apc(Min/+) mice. Elevated levels of putrescine and linolenate in Apc(Min/+) mice were significantly decreased by BRBs. Ornithine decarboxylase expression, the key enzyme in putrescine generation, was fully suppressed by BRBs. These results suggest that BRBs produced beneficial effects against colonic adenoma development in Apc(Min/+) mice and modulated multiple metabolic pathways. The metabolite changes produced by BRBs might potentially reflect the BRB-mediated chemopreventive effects in colorectal cancer patients.

  14. Synergistic Blockade of Mitotic Exit by Two Chemical Inhibitors of the APC/C

    PubMed Central

    Sackton, Katharine L.; Dimova, Nevena; Zeng, Xing; Tian, Wei; Zhang, Mengmeng; Sackton, Timothy B.; Meaders, Johnathan; Pfaff, Kathleen L.; Sigoillot, Frederic; Yu, Hongtao; Luo, Xuelian; King, Randall W.

    2014-01-01

    Summary Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the Anaphase-Promoting Complex/Cyclosome (APC/C), a thirteen-subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome1,2. Because blocking mitotic exit is an effective approach for inducing tumor cell death3,4, the APC/C represents a potential novel target for cancer therapy. APC/C activation in mitosis requires binding of Cdc205, which forms a co-receptor with the APC/C to recognize substrates containing a Destruction box (D-box)6-14. Here we demonstrate that we can synergistically inhibit APC/C-dependent proteolysis and mitotic exit by simultaneously disrupting two protein-protein interactions within the APC/C-Cdc20-substrate ternary complex. We identified a small molecule, called apcin (APC inhibitor), which binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin-Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of apcin to block mitotic exit is synergistically amplified by co-addition of tosyl-L-arginine methyl ester (TAME), a small molecule that blocks the APC/C-Cdc20 interaction15,16. This work suggests that simultaneous disruption of multiple, weak protein-protein interactions is an effective approach for inactivating a protein machine. PMID:25156254

  15. Evaluation and Analysis of Seasat a Scanning Multichannel Microwave Radiometer (SMMR) Antenna Pattern Correction (APC) Algorithm

    NASA Technical Reports Server (NTRS)

    Kitzis, S. N.; Kitzis, J. L.

    1979-01-01

    The accuracy of the SEASAT-A SMMR antenna pattern correction (APC) algorithm was assessed. Interim APC brightness temperature measurements for the SMMR 6.6 GHz channels are compared with surface truth derived sea surface temperatures. Plots and associated statistics are presented for SEASAT-A SMMR data acquired for the Gulf of Alaska experiment. The cross-track gradients observed in the 6.6 GHz brightness temperature data are discussed.

  16. Atomic structure of the APC/C and its mechanism of protein ubiquitination

    PubMed Central

    Yang, Jing; McLaughlin, Stephen H.; Barford, David

    2015-01-01

    The anaphase-promoting complex (APC/C) is a multimeric RING E3 ubiquitin ligase that controls chromosome segregation and mitotic exit. Its regulation by coactivator subunits, phosphorylation, the mitotic checkpoint complex, and interphase inhibitor Emi1 ensures the correct order and timing of distinct cell cycle transitions. Here, we used cryo-electron microscopy to determine atomic structures of APC/C-coactivator complexes with either Emi1 or a UbcH10-ubiquitin conjugate. These structures define the architecture of all APC/C subunits, the position of the catalytic module, and explain how Emi1 mediates inhibition of the two E2s UbcH10 and Ube2S. Definition of Cdh1 interactions with the APC/C indicates how they are antagonized by Cdh1 phosphorylation. The structure of the APC/C with UbcH10-ubiquitin reveals insights into the initiating ubiquitination reaction. Our results provide a quantitative framework for the design of experiments to further investigate APC/C functions in vivo. PMID:26083744

  17. Spontaneous Intestinal Tumorigenesis in Apc/Min+ Mice Requires Altered T Cell Development with IL-17A

    PubMed Central

    Chae, Wook-Jin; Bothwell, Alfred L. M.

    2015-01-01

    The control of inflammatory diseases requires functional regulatory T cells (Tregs) with significant Gata-3 expression. Here we address the inhibitory role of Tregs on intestinal tumorigenesis in the Apc/Min+ mouse model that resembles human familial adenomatous polyposis (FAP). Apc/Min+ mice had a markedly increased frequency of Foxp3+ Tregs and yet decreased Gata-3 expression in the lamina propria. To address the role of heterozygous Apc gene mutation in Tregs, we generated Foxp3-Cre, Apcflox/+ mice. Tregs from these mice effectively inhibited tumorigenesis comparable to wild type Tregs after adoptive transfer into Apc/Min+ mice, demonstrating that the heterozygous Apc gene mutation in Tregs does not induce the loss of control over tumor microenvironment. Adoptive transfer of in vitro generated Apc/Min+ iTregs (inducible Tregs) failed to inhibit intestinal tumorigenesis, suggesting that naïve CD4 T cells generated from Apc/Min+ mice thymus were impaired. We also showed that adoptively transferred IL-17A-deficient Apc/Min+ Tregs inhibited tumor growth, suggesting that IL-17A was critical to impair the tumor regression function of Apc/Min+ Tregs. Taken together, our results suggest that both T cell development in a functional thymus and IL-17A control the ability of Treg to inhibit intestinal tumorigenesis in Apc/Min+ mice. PMID:26146642

  18. APC binds the Miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane

    PubMed Central

    Mills, Kate M.; Brocardo, Mariana G.; Henderson, Beric R.

    2016-01-01

    Mutations in adenomatous polyposis coli (APC) disrupt regulation of Wnt signaling, mitosis, and the cytoskeleton. We describe a new role for APC in the transport of mitochondria. Silencing of wild-type APC by small interfering RNA caused mitochondria to redistribute from the cell periphery to the perinuclear region. We identified novel APC interactions with the mitochondrial kinesin-motor complex Miro/Milton that were mediated by the APC C-terminus. Truncating mutations in APC abolished its ability to bind Miro/Milton and reduced formation of the Miro/Milton complex, correlating with disrupted mitochondrial distribution in colorectal cancer cells that could be recovered by reconstitution of wild-type APC. Using proximity ligation assays, we identified endogenous APC-Miro/Milton complexes at mitochondria, and live-cell imaging showed that loss of APC slowed the frequency of anterograde mitochondrial transport to the membrane. We propose that APC helps drive mitochondria to the membrane to supply energy for cellular processes such as directed cell migration, a process disrupted by cancer mutations. PMID:26658612

  19. Activated protein C cofactor function of protein S: a novel role for a γ-carboxyglutamic acid residue.

    PubMed

    Ahnström, Josefin; Andersson, Helena M; Canis, Kevin; Norstrøm, Eva; Yu, Yao; Dahlbäck, Björn; Panico, Maria; Morris, Howard R; Crawley, James T B; Lane, David A

    2011-06-16

    Protein S has an important anticoagulant function by acting as a cofactor for activated protein C (APC). We recently reported that the EGF1 domain residue Asp95 is critical for APC cofactor function. In the present study, we examined whether additional interaction sites within the Gla domain of protein S might contribute to its APC cofactor function. We examined 4 residues, composing the previously reported "Face1" (N33S/P35T/E36A/Y39V) variant, as single point substitutions. Of these protein S variants, protein S E36A was found to be almost completely inactive using calibrated automated thrombography. In factor Va inactivation assays, protein S E36A had 89% reduced cofactor activity compared with wild-type protein S and was almost completely inactive in factor VIIIa inactivation; phospholipid binding was, however, normal. Glu36 lies outside the ω-loop that mediates Ca(2+)-dependent phospholipid binding. Using mass spectrometry, it was nevertheless confirmed that Glu36 is γ-carboxylated. Our finding that Gla36 is important for APC cofactor function, but not for phospholipid binding, defines a novel function (other than Ca(2+) coordination/phospholipid binding) for a Gla residue in vitamin K-dependent proteins. It also suggests that residues within the Gla and EGF1 domains of protein S act cooperatively for its APC cofactor function.

  20. Detection and Analysis of Cell Cycle-Associated APC/C-Mediated Cellular Ubiquitylation In Vitro and In Vivo.

    PubMed

    Cedeño, Cesyen; La Monaca, Esther; Esposito, Mara; Gutierrez, Gustavo J

    2016-01-01

    The anaphase-promoting complex or cyclosome (APC/C) is one of the major orchestrators of the cell division cycle in mammalian cells. The APC/C acts as a ubiquitin ligase that triggers sequential ubiquitylation of a significant number of substrates which will be eventually degraded by proteasomes during major transitions of the cell cycle. In this chapter, we present accessible methodologies to assess both in in vitro conditions and in cellular systems ubiquitylation reactions mediated by the APC/C. In addition, we also describe techniques to evidence the changes in protein stability provoked by modulation of the activity of the APC/C. Finally, specific methods to analyze interactors or posttranslational modifications of particular APC/C subunits are also discussed. Given the crucial role played by the APC/C in the regulation of the cell cycle, this review only focuses on its action and effects in actively proliferating cells. PMID:27613041

  1. APC promoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors

    PubMed Central

    Ginesta, Mireia M.; Diaz-Riascos, Zamira Vanessa; Busquets, Juli; Pelaez, Núria; Serrano, Teresa; Peinado, Miquel Àngel; Jorba, Rosa; García-Borobia, Francisco Javier; Capella, Gabriel; Fabregat, Joan

    2016-01-01

    Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-1 (EN-1) promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of the APC, HRH2, CDH13, SPARC and EN-1 promoters was analyzed using methylation specific-melting curve analysis (MS-MCA). Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed, APC (71%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation had a high sensitivity (71–80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms.

  2. APC promoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors

    PubMed Central

    Ginesta, Mireia M.; Diaz-Riascos, Zamira Vanessa; Busquets, Juli; Pelaez, Núria; Serrano, Teresa; Peinado, Miquel Àngel; Jorba, Rosa; García-Borobia, Francisco Javier; Capella, Gabriel; Fabregat, Joan

    2016-01-01

    Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-1 (EN-1) promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of the APC, HRH2, CDH13, SPARC and EN-1 promoters was analyzed using methylation specific-melting curve analysis (MS-MCA). Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed, APC (71%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation had a high sensitivity (71–80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms. PMID:27602165

  3. The Spindle Assembly Checkpoint Is Not Essential for Viability of Human Cells with Genetically Lowered APC/C Activity

    PubMed Central

    Wild, Thomas; Larsen, Marie Sofie Yoo; Narita, Takeo; Schou, Julie; Nilsson, Jakob; Choudhary, Chunaram

    2016-01-01

    Summary The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin-conjugating enzymes—UBE2C and UBE2S. We show that APC/C activity in human cells is tuned by the combinatorial use of three E2s, namely UBE2C, UBE2S, and UBE2D. Genetic deletion of UBE2C and UBE2S, individually or in combination, leads to discriminative reduction in APC/C function and sensitizes cells to UBE2D depletion. Reduction of APC/C activity results in loss of switch-like metaphase-to-anaphase transition and, strikingly, renders cells insensitive to chemical inhibition of MPS1 and genetic ablation of MAD2, both of which are essential for the SAC. These results provide insights into the regulation of APC/C activity and demonstrate that the essentiality of the SAC is imposed by the strength of the APC/C. PMID:26904940

  4. High order overlay modeling and APC simulation with Zernike-Legendre polynomials

    NASA Astrophysics Data System (ADS)

    Ju, JawWuk; Kim, MinGyu; Lee, JuHan; Sherwin, Stuart; Hoo, George; Choi, DongSub; Lee, Dohwa; Jeon, Sanghuck; Lee, Kangsan; Tien, David; Pierson, Bill; Robinson, John C.; Levy, Ady; Smith, Mark D.

    2015-03-01

    Feedback control of overlay errors to the scanner is a well-established technique in semiconductor manufacturing [1]. Typically, overlay errors are measured, and then modeled by least-squares fitting to an overlay model. Overlay models are typically Cartesian polynomial functions of position within the wafer (Xw, Yw), and of position within the field (Xf, Yf). The coefficients from the data fit can then be fed back to the scanner to reduce overlay errors in future wafer exposures, usually via a historically weighted moving average. In this study, rather than using the standard Cartesian formulation, we examine overlay models using Zernike polynomials to represent the wafer-level terms, and Legendre polynomials to represent the field-level terms. Zernike and Legendre polynomials can be selected to have the same fitting capability as standard polynomials (e.g., second order in X and Y, or third order in X and Y). However, Zernike polynomials have the additional property of being orthogonal over the unit disk, which makes them appropriate for the wafer-level model, and Legendre polynomials are orthogonal over the unit square, which makes them appropriate for the field-level model. We show several benefits of Zernike/Legendre-based models in this investigation in an Advanced Process Control (APC) simulation using highly-sampled fab data. First, the orthogonality property leads to less interaction between the terms, which makes the lot-to-lot variation in the fitted coefficients smaller than when standard polynomials are used. Second, the fitting process itself is less coupled - fitting to a lower-order model, and then fitting the residuals to a higher order model gives very similar results as fitting all of the terms at once. This property makes fitting techniques such as dual pass or cascading [2] unnecessary, and greatly simplifies the options available for the model recipe. The Zernike/Legendre basis gives overlay performance (mean plus 3 sigma of the residuals

  5. Polarizing T and B Cell Responses by APC-Targeted Subunit Vaccines

    PubMed Central

    Grødeland, Gunnveig; Fossum, Even; Bogen, Bjarne

    2015-01-01

    Current influenza vaccines mostly aim at the induction of specific neutralizing antibodies. While antibodies are important for protection against a particular virus strain, T cells can recognize epitopes that will offer broader protection against influenza. We have previously developed a DNA vaccine format by which protein antigens can be targeted specifically to receptors on antigen presenting cells (APCs). The DNA-encoded vaccine proteins are homodimers, each chain consisting of a targeting unit, a dimerization unit, and an antigen. The strategy of targeting antigen to APCs greatly enhances immune responses as compared to non-targeted controls. Furthermore, targeting of antigen to different receptors on APCs can polarize the immune response to different arms of immunity. Here, we discuss how targeting of hemagglutinin to MHC class II molecules increases Th2 and IgG1 antibody responses, whereas targeting to chemokine receptors XCR1 or CCR1/3/5 increases Th1 and IgG2a responses, in addition to CD8+ T cell responses. We also discuss these results in relation to work published by others on APC-targeting. Differential targeting of APC surface molecules may allow the induction of tailor-made phenotypes of adaptive immune responses that are optimal for protection against various infectious agents, including influenza virus. PMID:26257735

  6. APC-PC Combined Scheme in Gilbert Two State Model: Proposal and Study

    NASA Astrophysics Data System (ADS)

    Bulo, Yaka; Saring, Yang; Bhunia, Chandan Tilak

    2016-08-01

    In an automatic repeat request (ARQ) scheme, a packet is retransmitted if it gets corrupted due to transmission errors caused by the channel. However, an erroneous packet may contain both erroneous bits and correct bits and hence it may still contain useful information. The receiver may be able to combine this information from multiple erroneous copies to recover the correct packet. Packet combining (PC) is a simple and elegant scheme of error correction in transmitted packet, in which two received copies are XORed to obtain the bit location of erroneous bits. Thereafter, the packet is corrected by bit inversion of bit located as erroneous. Aggressive packet combining (APC) is a logic extension of PC primarily designed for wireless communication with objective of correcting error with low latency. PC offers higher throughput than APC, but PC does not correct double bit errors if occur in same bit location of erroneous copies of the packet. A hybrid technique is proposed to utilize the advantages of both APC and PC while attempting to remove the limitation of both. In the proposed technique, applications of APC-PC on Gilbert two state model has been studied. The simulation results show that the proposed technique offers better throughput than the conventional APC and lesser packet error rate than PC scheme.

  7. Defective sister chromatid cohesion is synthetically lethal with impaired APC/C function.

    PubMed

    de Lange, Job; Faramarz, Atiq; Oostra, Anneke B; de Menezes, Renee X; van der Meulen, Ida H; Rooimans, Martin A; Rockx, Davy A; Brakenhoff, Ruud H; van Beusechem, Victor W; King, Randall W; de Winter, Johan P; Wolthuis, Rob M F

    2015-01-01

    Warsaw breakage syndrome (WABS) is caused by defective DDX11, a DNA helicase that is essential for chromatid cohesion. Here, a paired genome-wide siRNA screen in patient-derived cell lines reveals that WABS cells do not tolerate partial depletion of individual APC/C subunits or the spindle checkpoint inhibitor p31(comet). A combination of reduced cohesion and impaired APC/C function also leads to fatal mitotic arrest in diploid RPE1 cells. Moreover, WABS cell lines, and several cancer cell lines with cohesion defects, display a highly increased response to a new cell-permeable APC/C inhibitor, apcin, but not to the spindle poison paclitaxel. Synthetic lethality of APC/C inhibition and cohesion defects strictly depends on a functional mitotic spindle checkpoint as well as on intact microtubule pulling forces. This indicates that the underlying mechanism involves cohesion fatigue in response to mitotic delay, leading to spindle checkpoint re-activation and lethal mitotic arrest. Our results point to APC/C inhibitors as promising therapeutic agents targeting cohesion-defective cancers. PMID:26423134

  8. Defective sister chromatid cohesion is synthetically lethal with impaired APC/C function

    PubMed Central

    de Lange, Job; Faramarz, Atiq; Oostra, Anneke B.; de Menezes, Renee X.; van der Meulen, Ida H.; Rooimans, Martin A.; Rockx, Davy A.; Brakenhoff, Ruud H.; van Beusechem, Victor W.; King, Randall W.; de Winter, Johan P.; Wolthuis, Rob M. F.

    2015-01-01

    Warsaw breakage syndrome (WABS) is caused by defective DDX11, a DNA helicase that is essential for chromatid cohesion. Here, a paired genome-wide siRNA screen in patient-derived cell lines reveals that WABS cells do not tolerate partial depletion of individual APC/C subunits or the spindle checkpoint inhibitor p31comet. A combination of reduced cohesion and impaired APC/C function also leads to fatal mitotic arrest in diploid RPE1 cells. Moreover, WABS cell lines, and several cancer cell lines with cohesion defects, display a highly increased response to a new cell-permeable APC/C inhibitor, apcin, but not to the spindle poison paclitaxel. Synthetic lethality of APC/C inhibition and cohesion defects strictly depends on a functional mitotic spindle checkpoint as well as on intact microtubule pulling forces. This indicates that the underlying mechanism involves cohesion fatigue in response to mitotic delay, leading to spindle checkpoint re-activation and lethal mitotic arrest. Our results point to APC/C inhibitors as promising therapeutic agents targeting cohesion-defective cancers. PMID:26423134

  9. Co-regulation proteomics reveals substrates and mechanisms of APC/C-dependent degradation.

    PubMed

    Singh, Sasha A; Winter, Dominic; Kirchner, Marc; Chauhan, Ruchi; Ahmed, Saima; Ozlu, Nurhan; Tzur, Amit; Steen, Judith A; Steen, Hanno

    2014-02-18

    Using multiplexed quantitative proteomics, we analyzed cell cycle-dependent changes of the human proteome. We identified >4,400 proteins, each with a six-point abundance profile across the cell cycle. Hypothesizing that proteins with similar abundance profiles are co-regulated, we clustered the proteins with abundance profiles most similar to known Anaphase-Promoting Complex/Cyclosome (APC/C) substrates to identify additional putative APC/C substrates. This protein profile similarity screening (PPSS) analysis resulted in a shortlist enriched in kinases and kinesins. Biochemical studies on the kinesins confirmed KIFC1, KIF18A, KIF2C, and KIF4A as APC/C substrates. Furthermore, we showed that the APC/C(CDH1)-dependent degradation of KIFC1 regulates the bipolar spindle formation and proper cell division. A targeted quantitative proteomics experiment showed that KIFC1 degradation is modulated by a stabilizing CDK1-dependent phosphorylation site within the degradation motif of KIFC1. The regulation of KIFC1 (de-)phosphorylation and degradation provides insights into the fidelity and proper ordering of substrate degradation by the APC/C during mitosis. PMID:24510915

  10. Apc restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer

    PubMed Central

    Simon, Janelle; Tschaharganeh, Darjus F; van Es, Johan H; Clevers, Hans; Lowe, Scott W

    2015-01-01

    The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated in the vast majority of human colorectal cancers (CRC) and leads to deregulated Wnt signaling. To determine whether Apc disruption is required for tumor maintenance, we developed a mouse model of CRC whereby Apc can be conditionally suppressed using a doxycycline-regulated shRNA. Apc suppression produces adenomas in both the small intestine and colon that, in the presence of Kras and p53 mutations, can progress to invasive carcinoma. In established tumors, Apc restoration drives rapid and widespread tumor-cell differentiation and sustained regression without relapse. Tumor regression is accompanied by the re-establishment of normal crypt-villus homeostasis, such that once aberrantly proliferating cells reacquire self-renewal and multi-lineage differentiation capability. Our study reveals that CRC cells can revert to functioning normal cells given appropriate signals, and provide compelling in vivo validation of the Wnt pathway as a therapeutic target for treatment of CRC. PMID:26091037

  11. AGILE integration into APC for high mix logic fab

    NASA Astrophysics Data System (ADS)

    Gatefait, M.; Lam, A.; Le Gratiet, B.; Mikolajczak, M.; Morin, V.; Chojnowski, N.; Kocsis, Z.; Smith, I.; Decaunes, J.; Ostrovsky, A.; Monget, C.

    2015-09-01

    mix logic Fab) in term of product and technology portfolio AGILE corrects for up to 120nm of product topography error on process layer with less than 50nm depth of focus Based on tool functionalities delivered by ASML and on high volume manufacturing requirement, AGILE integration is a real challenge. Regarding ST requirements "Automatic AGILE" functionality developed by ASML was not a turnkey solution and a dedicated functionality was needed. A "ST homemade AGILE integration" has been fully developed and implemented within ASML and ST constraints. This paper describes this integration in our Advanced Process Control platform (APC).

  12. A knock-in mouse model reveals roles for nuclear Apc in cell proliferation, Wnt signal inhibition and tumor suppression

    PubMed Central

    Zeineldin, Maged; Cunningham, Jamie; McGuinness, William; Alltizer, Preston; Cowley, Brett; Blanchat, Bryan; Xu, Wenhao; Pinson, David; Neufeld, Kristi L.

    2011-01-01

    Mutation of the tumor suppressor adenomatous polyposis coli (APC) is considered an initiating step in the genesis of the vast majority of colorectal cancers. APC inhibits the Wnt signaling pathway by targeting proto-oncogene β-catenin for destruction by cytoplasmic proteasomes. In the presence of a Wnt signal, or in the absence of functional APC, β-catenin can serve as a transcription co-factor for genes required for cell proliferation such as cyclin D1 and c-Myc. In cultured cells, APC shuttles between the nucleus and cytoplasm, with nuclear APC implicated in inhibition of Wnt target gene expression. Taking a genetic approach to evaluate the functions of nuclear APC in the context of a whole organism, we generated a mouse model with mutations that inactivate the nuclear localization signals of Apc (ApcmNLS). ApcmNLS/mNLS mice are viable and fractionation of embryonic fibroblasts (MEFs) isolated from these mice revealed a significant reduction in nuclear Apc compared to Apc+/+ MEFs. The levels of Apc and β-catenin protein were not significantly altered in small intestinal epithelia from ApcmNLS/mNLS mice. Compared to Apc+/+ mice, ApcmNLS/mNLS mice displayed increased proliferation in epithelial cells from the jejunum, ileum, and colon. These same tissues from ApcmNLS/mNLS mice displayed more mRNA from three genes up-regulated in response to canonical Wnt signal, c-Myc, Axin2, and Cyclin D1, and less mRNA from Hath 1 which is down-regulated in response to Wnt. These observations suggest a role for nuclear Apc in inhibition of canonical Wnt signaling and control of epithelial proliferation in intestinal tissue. Furthermore, we found ApcMin/+ mice, which harbor a mutation that truncates Apc, have increased polyp size and multiplicity if they also carry the ApcmNLS allele. Taken together, this analysis of the novel ApcmNLS mouse model supports a role for nuclear Apc in control of Wnt target genes, intestinal epithelial cell proliferation and polyp formation. PMID

  13. Characterization of the male ApcMin/+ mouse as a hypogonadism model related to cancer cachexia

    PubMed Central

    White, James P.; Puppa, Melissa J.; Narsale, Aditi; Carson, James A.

    2013-01-01

    Summary Cancer cachexia, the unintentional loss of lean body mass, is associated with decreased quality of life and poor patient survival. Hypogonadism, involving a reduction in circulating testosterone, is associated with the cachectic condition. At this time there is a very limited understanding of the role of hypogonadism in cancer cachexia progression. This gap in our knowledge is related to a lack of functional hypogonadal models associated with cancer cachexia. The ApcMin/+ mouse is an established colorectal cancer model that develops an IL-6 dependent cachexia which is physiologically related to human disease due to the gradual progression of tumor development and cachexia. The purpose of this study was to assess the utility of the ApcMin/+ mouse for the examination of hypogonadism during cancer cachexia and to investigate if IL-6 has a role in this process. We report that ApcMin/+ mice that are weight stable have comparable testosterone levels and gonad size compared to wild type mice. Cachectic ApcMin/+ mice exhibit a reduction in circulating testosterone and gonad size, which has a significant association with the degree of muscle mass and functional strength loss. Circulating testosterone levels were also significantly associated with the suppression of myofibrillar protein synthesis. Skeletal muscle and testes androgen receptor expression were decreased with severe cachexia. Although testes STAT3 phosphorylation increased with severe cachexia, systemic IL-6 over-expression for 2 weeks was not sufficient to reduce either testes weight or circulating testosterone. Inhibition of systemic IL-6 signaling by an IL-6 receptor antibody to ApcMin/+ mice that had already initiated weight loss was sufficient to attenuate a reduction in testes size and circulating testosterone. In summary, the ApcMin/+ mouse becomes hypogonadal with the progression of cachexia severity and elevated circulating IL-6 levels may have a role in the development of hypogonadism during

  14. Characterization of elastic-plastic properties of AS4/APC-2 thermoplastic composite

    NASA Technical Reports Server (NTRS)

    Sun, C. T.; Yoon, K. J.

    1988-01-01

    Elastic and inelastic properties of AS4/APC-2 composites were characterized with respect to temperature variation by using a one-parameter orthotropic plasticity model and a one parameter failure criterion. Simple uniaxial off-axis tension tests were performed on coupon specimens of unidirectional AS4/APC-2 thermoplastic composite at various temperatures. To avoid the complication caused by the extension-shear coupling effect in off-axis testing, new tabs were designed and used on the test specimens. The experimental results showed that the nonlinear behavior of constitutive relations and the failure strengths can be characterized quite well using the one parameter plasticity model and the failure criterion, respectively.

  15. The CDC20-APC/SOX2 signaling axis: An achilles' heel for glioblastoma

    PubMed Central

    Gujar, Amit D.; Yano, Hiroko; Kim, Albert H.

    2016-01-01

    ABSTRACT Glioblastoma stem-like cells (GSCs) play a critical role in glioblastoma progression and recurrence. We discuss recent results on the role of the mitotic ubiquitin ligase cell division cycle 20–anaphase-promoting complex (CDC20-APC) in the governance of cardinal GSC functions through a mechanism involving the transcription factor sex-determining region Y-box 2 (SOX2). These findings expand the non-mitotic roles of CDC20-APC with implications for stem cell biology. PMID:27314081

  16. How holistic process control translates into high mix logic fab APC?

    NASA Astrophysics Data System (ADS)

    Le-Gratiet, B.; Gatefait, M.; Ducotè, J.; Decaunes, J.; Lam, A.; Beraud, B.; Mikolajczak, M.; Pelletier, A.; Orlando, B.; Sundermann, F.; Ostrovsky, A.; Lapeyre, C.

    2014-10-01

    Advanced CMOS nodes require more and more information to get the wafer process well setup. Process tool intrinsic capabilities are not sufficient to secure specifications. APC systems (Advanced Process Control) are being developed in waferfab to manage process context information to automatically adjust and tune wafer processing. The APC manages today Run to Run component from and between various process steps plus a sub-recipes/profiles corrections management. This paper will outline the architecture of an integrated/holistic process control system for a high mix advanced logic waferfoundry.

  17. An APC/C-Cdh1 Biosensor Reveals the Dynamics of Cdh1 Inactivation at the G1/S Transition

    PubMed Central

    Ondracka, Andrej; Robbins, Jonathan A.; Cross, Frederick R.

    2016-01-01

    B-type cyclin-dependent kinase activity must be turned off for mitotic exit and G1 stabilization. B-type cyclin degradation is mediated by the anaphase-promoting complex/cyclosome (APC/C); during and after mitotic exit, APC/C is dependent on Cdh1. Cdh1 is in turn phosphorylated and inactivated by cyclin-CDK at the Start transition of the new cell cycle. We developed a biosensor to assess the cell cycle dynamics of APC/C-Cdh1. Nuclear exit of the G1 transcriptional repressor Whi5 is a known marker of Start; APC/C-Cdh1 is inactivated 12 min after Whi5 nuclear exit with little measurable cell-to-cell timing variability. Multiple phosphorylation sites on Cdh1 act in a redundant manner to repress its activity. Reducing the number of phosphorylation sites on Cdh1 can to some extent be tolerated for cell viability, but it increases variability in timing of APC/C-Cdh1 inactivation. Mutants with minimal subsets of phosphorylation sites required for viability exhibit striking stochasticity in multiple responses including budding, nuclear division, and APC/C-Cdh1 activity itself. Multiple cyclin-CDK complexes, as well as the stoichiometric inhibitor Acm1, contribute to APC/C-Cdh1 inactivation; this redundant control is likely to promote rapid and reliable APC/C-Cdh1 inactivation immediately following the Start transition. PMID:27410035

  18. Dual control by Cdk1 phosphorylation of the budding yeast APC/C ubiquitin ligase activator Cdh1

    PubMed Central

    Höckner, Sebastian; Neumann-Arnold, Lea; Seufert, Wolfgang

    2016-01-01

    The antagonism between cyclin-dependent kinases (Cdks) and the ubiquitin ligase APC/C-Cdh1 is central to eukaryotic cell cycle control. APC/C-Cdh1 targets cyclin B and other regulatory proteins for degradation, whereas Cdks disable APC/C-Cdh1 through phosphorylation of the Cdh1 activator protein at multiple sites. Budding yeast Cdh1 carries nine Cdk phosphorylation sites in its N-terminal regulatory domain, most or all of which contribute to inhibition. However, the precise role of individual sites has remained unclear. Here, we report that the Cdk phosphorylation sites of yeast Cdh1 are organized into autonomous subgroups and act through separate mechanisms. Cdk sites 1–3 had no direct effect on the APC/C binding of Cdh1 but inactivated a bipartite nuclear localization sequence (NLS) and thereby controlled the partitioning of Cdh1 between cytoplasm and nucleus. In contrast, Cdk sites 4–9 did not influence the cell cycle–regulated localization of Cdh1 but prevented its binding to the APC/C. Cdk sites 4–9 reside near two recently identified APC/C interaction motifs in a pattern conserved with the human Cdh1 orthologue. Thus a Cdk-inhibited NLS goes along with Cdk-inhibited APC/C binding sites in yeast Cdh1 to relay the negative control by Cdk1 phosphorylation of the ubiquitin ligase APC/C-Cdh1. PMID:27226481

  19. An APC/C-Cdh1 Biosensor Reveals the Dynamics of Cdh1 Inactivation at the G1/S Transition.

    PubMed

    Ondracka, Andrej; Robbins, Jonathan A; Cross, Frederick R

    2016-01-01

    B-type cyclin-dependent kinase activity must be turned off for mitotic exit and G1 stabilization. B-type cyclin degradation is mediated by the anaphase-promoting complex/cyclosome (APC/C); during and after mitotic exit, APC/C is dependent on Cdh1. Cdh1 is in turn phosphorylated and inactivated by cyclin-CDK at the Start transition of the new cell cycle. We developed a biosensor to assess the cell cycle dynamics of APC/C-Cdh1. Nuclear exit of the G1 transcriptional repressor Whi5 is a known marker of Start; APC/C-Cdh1 is inactivated 12 min after Whi5 nuclear exit with little measurable cell-to-cell timing variability. Multiple phosphorylation sites on Cdh1 act in a redundant manner to repress its activity. Reducing the number of phosphorylation sites on Cdh1 can to some extent be tolerated for cell viability, but it increases variability in timing of APC/C-Cdh1 inactivation. Mutants with minimal subsets of phosphorylation sites required for viability exhibit striking stochasticity in multiple responses including budding, nuclear division, and APC/C-Cdh1 activity itself. Multiple cyclin-CDK complexes, as well as the stoichiometric inhibitor Acm1, contribute to APC/C-Cdh1 inactivation; this redundant control is likely to promote rapid and reliable APC/C-Cdh1 inactivation immediately following the Start transition.

  20. Dual control by Cdk1 phosphorylation of the budding yeast APC/C ubiquitin ligase activator Cdh1.

    PubMed

    Höckner, Sebastian; Neumann-Arnold, Lea; Seufert, Wolfgang

    2016-07-15

    The antagonism between cyclin-dependent kinases (Cdks) and the ubiquitin ligase APC/C-Cdh1 is central to eukaryotic cell cycle control. APC/C-Cdh1 targets cyclin B and other regulatory proteins for degradation, whereas Cdks disable APC/C-Cdh1 through phosphorylation of the Cdh1 activator protein at multiple sites. Budding yeast Cdh1 carries nine Cdk phosphorylation sites in its N-terminal regulatory domain, most or all of which contribute to inhibition. However, the precise role of individual sites has remained unclear. Here, we report that the Cdk phosphorylation sites of yeast Cdh1 are organized into autonomous subgroups and act through separate mechanisms. Cdk sites 1-3 had no direct effect on the APC/C binding of Cdh1 but inactivated a bipartite nuclear localization sequence (NLS) and thereby controlled the partitioning of Cdh1 between cytoplasm and nucleus. In contrast, Cdk sites 4-9 did not influence the cell cycle-regulated localization of Cdh1 but prevented its binding to the APC/C. Cdk sites 4-9 reside near two recently identified APC/C interaction motifs in a pattern conserved with the human Cdh1 orthologue. Thus a Cdk-inhibited NLS goes along with Cdk-inhibited APC/C binding sites in yeast Cdh1 to relay the negative control by Cdk1 phosphorylation of the ubiquitin ligase APC/C-Cdh1.

  1. Inactivation and Disassembly of the Anaphase-Promoting Complex during Human Cytomegalovirus Infection Is Associated with Degradation of the APC5 and APC4 Subunits and Does Not Require UL97-Mediated Phosphorylation of Cdh1 ▿

    PubMed Central

    Tran, Karen; Kamil, Jeremy P.; Coen, Donald M.; Spector, Deborah H.

    2010-01-01

    Infection of quiescent cells by human cytomegalovirus (HCMV) elicits severe cell cycle deregulation, resulting in a G1/S arrest, which can be partly attributed to the inactivation of the anaphase-promoting complex (APC). As we previously reported, the premature phosphorylation of its coactivator Cdh1 and/or the dissociation of the core complex can account for the inactivation. We have expanded on these results and further delineated the key components required for disabling the APC during HCMV infection. The viral protein kinase UL97 was hypothesized to phosphorylate Cdh1, and consistent with this, phosphatase assays utilizing a virus with a UL97 deletion mutation (ΔUL97 virus) indicated that Cdh1 is hypophosphorylated at early times in the infection. Mass spectrometry analysis demonstrated that UL97 can phosphorylate Cdh1 in vitro, and the majority of the sites identified correlated with previously characterized cyclin-dependent kinase (Cdk) consensus sites. Analysis of the APC core complex during ΔUL97 virus infection showed APC dissociation occurring at the same time as during infection with wild-type virus, suggesting that the UL97-mediated phosphorylation of Cdh1 is not required for this to occur. Further investigation of the APC subunits showed a proteasome-dependent loss of the APC5 and APC4 subunits that was temporally associated with the disassembly of the APC. Immediate early viral gene expression was not sufficient for the degradation of APC4 and APC5, indicating that a viral early gene product(s), possibly in association with a de novo-synthesized cellular protein(s), is involved. PMID:20686030

  2. Co-activator independent differences in how the metaphase and anaphase APC/C recognise the same substrate

    PubMed Central

    Matsusaka, Takahiro; Enquist-Newman, Maria; Morgan, David O.; Pines, Jonathon

    2014-01-01

    ABSTRACT The Anaphase Promoting Complex or Cyclosome (APC/C) is critical to the control of mitosis. The APC/C is an ubiquitin ligase that targets specific mitotic regulators for proteolysis at distinct times in mitosis, but how this is achieved is not well understood. We have addressed this question by determining whether the same substrate, cyclin B1, is recognised in the same way by the APC/C at different times in mitosis. Unexpectedly, we find that distinct but overlapping motifs in cyclin B1 are recognised by the APC/C in metaphase compared with anaphase, and this does not depend on the exchange of Cdc20 for Cdh1. Thus, changes in APC/C substrate specificity in mitosis can potentially be conferred by altering interaction sites in addition to exchanging Cdc20 for Cdh1. PMID:25217616

  3. Leaching characteristics of calcium-based compounds in MSWI Residues: From the viewpoint of clogging risk.

    PubMed

    Xia, Yi; Zhang, Hua; Phoungthong, Khamphe; Shi, Dong-Xiao; Shen, Wen-Hui; Shao, Li-Ming; He, Pin-Jing

    2015-08-01

    Leachate collection system (LCS) clogging caused by calcium precipitation would be disadvantageous to landfill stability and operation. Meanwhile, calcium-based compounds are the main constituents in both municipal solid waste incineration bottom ash (MSWIBA) and stabilized air pollution control residues (SAPCR), which would increase the risk of LCS clogging once these calcium-rich residues were disposed in landfills. The leaching behaviors of calcium from the four compounds and municipal solid waste incineration (MSWI) residues were studied, and the influencing factors on leaching were discussed. The results showed that pH was the crucial factor in the calcium leaching process. CaCO3 and CaSiO3 began leaching when the leachate pH decreased to less than 7 and 10, respectively, while Ca3(PO4)2 leached at pH<12. CaSO4 could hardly dissolve in the experimental conditions. Moreover, the sequence of the leaching rate for the different calcium-based compounds is as follows: CaSiO3>Ca3(PO4)2>CaCO3. The calcium leaching from the MSWIBA and SAPCR separately started from pH<7 and pH<12, resulting from CaCO3 and Ca3(PO4)2 leaching respectively, which was proven by the X-ray diffraction results. Based on the leaching characteristics of the different calcium compounds and the mineral phase of calcium in the incineration residues, simulated computation of their clogging potential was conducted, providing the theoretical basis for the risk assessment pertaining to LCS clogging in landfills. PMID:25934218

  4. APC/C-Cdh1 coordinates neurogenesis and cortical size during development

    NASA Astrophysics Data System (ADS)

    Delgado-Esteban, Maria; García-Higuera, Irene; Maestre, Carolina; Moreno, Sergio; Almeida, Angeles

    2013-12-01

    The morphology of the adult brain is the result of a delicate balance between neural progenitor proliferation and the initiation of neurogenesis in the embryonic period. Here we assessed whether the anaphase-promoting complex/cyclosome (APC/C) cofactor, Cdh1—which regulates mitosis exit and G1-phase length in dividing cells—regulates neurogenesis in vivo. We use an embryo-restricted Cdh1 knockout mouse model and show that functional APC/C-Cdh1 ubiquitin ligase activity is required for both terminal differentiation of cortical neurons in vitro and neurogenesis in vivo. Further, genetic ablation of Cdh1 impairs the ability of APC/C to promote neurogenesis by delaying the exit of the progenitor cells from the cell cycle. This causes replicative stress and p53-mediated apoptotic death resulting in decreased number of cortical neurons and cortex size. These results demonstrate that APC/C-Cdh1 coordinates cortical neurogenesis and size, thus posing Cdh1 in the molecular pathogenesis of congenital neurodevelopmental disorders, such as microcephaly.

  5. Cdh1/Hct1-APC is essential for the survival of postmitotic neurons.

    PubMed

    Almeida, Angeles; Bolaños, Juan P; Moreno, Sergio

    2005-09-01

    Cell division at the end of mitosis and G1 is controlled by Cdh1/Hct1, an activator of the E3-ubiquitin ligase anaphase-promoting complex (APC) that promotes the ubiquitylation and degradation of mitotic cyclins and other substrates. Cdh1-APC is active in postmitotic neurons, where it regulates axonal growth and patterning in the developing brain. However, it remains unknown whether Cdh1-APC is involved in preventing cell-cycle progression in terminally differentiated neurons. To address this issue, we used the small hairpin RNA strategy to deplete Cdh1 in postmitotic neurons. We observed that Cdh1 silencing rapidly triggered apoptotic neuronal death. To investigate the underlying mechanism, we focused on cyclin B1, a major Cdh1-APC substrate. Our results demonstrate that Cdh1 is required to prevent the accumulation of cyclin B1 in terminally differentiated neurons. Moreover, by keeping cyclin B1 low, Cdh1 prevented these neurons from entering an aberrant S phase that led to apoptotic cell death. These results provide an explanation for the mechanism of cyclin B1 reactivation that occurs in the brain of patients suffering from neurodegenerative diseases, such as Alzheimer's disease.

  6. Multiple mechanisms determine the order of APC/C substrate degradation in mitosis

    PubMed Central

    Lu, Dan; Hsiao, Jennifer Y.; Davey, Norman E.; Van Voorhis, Vanessa A.; Foster, Scott A.

    2014-01-01

    The ubiquitin protein ligase anaphase-promoting complex or cyclosome (APC/C) controls mitosis by promoting ordered degradation of securin, cyclins, and other proteins. The mechanisms underlying the timing of APC/C substrate degradation are poorly understood. We explored these mechanisms using quantitative fluorescence microscopy of GFP-tagged APC/CCdc20 substrates in living budding yeast cells. Degradation of the S cyclin, Clb5, begins early in mitosis, followed 6 min later by the degradation of securin and Dbf4. Anaphase begins when less than half of securin is degraded. The spindle assembly checkpoint delays the onset of Clb5 degradation but does not influence securin degradation. Early Clb5 degradation depends on its interaction with the Cdk1–Cks1 complex and the presence of a Cdc20-binding “ABBA motif” in its N-terminal region. The degradation of securin and Dbf4 is delayed by Cdk1-dependent phosphorylation near their Cdc20-binding sites. Thus, a remarkably diverse array of mechanisms generates robust ordering of APC/CCdc20 substrate destruction. PMID:25287299

  7. 42 CFR 419.31 - Ambulatory payment classification (APC) system and payment weights.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... services within a group are not comparable with respect to the use of resources if the highest median cost for an item or service within the group is more than 2 times greater than the lowest median cost for... the Federal Food, Drug and Cosmetic Act. (3) The payment rate determined for an APC group...

  8. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors).

    PubMed

    Alman, B A; Li, C; Pajerski, M E; Diaz-Cano, S; Wolfe, H J

    1997-08-01

    Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues

  9. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors).

    PubMed Central

    Alman, B. A.; Li, C.; Pajerski, M. E.; Diaz-Cano, S.; Wolfe, H. J.

    1997-01-01

    Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues

  10. Curcumin suppresses intestinal polyps in APC Min mice fed a high fat diet.

    PubMed

    Pettan-Brewer, Christina; Morton, John; Mangalindan, Ruby; Ladiges, Warren

    2011-01-01

    Colorectal cancer (CRC) is a leading cause of cancer deaths in the United States. Various risk factors have been associated with CRC including increasing age and diet. Epidemiological and experimental studies have implicated a diet high in fat as an important risk factor for colon cancer. High fat diets can promote obesity resulting in insulin resistance and inflammation and the development of oxidative stress, increased cell proliferation, and suppression of apoptosis. Because of the high consumption of dietary fats, especially saturated fats, by Western countries, it is of interest to see if non-nutrient food factors might be effective in preventing or delaying CRC in the presence of high saturated fat intake. Curcumin (Curcuma longa), the main yellow pigment in turmeric, was selected to test because of its reported anti-tumor activity. APC Min mice, which develop intestinal polyps and have many molecular features of CRC, were fed a diet containing 35% pork fat, 33% sucrose, and a protein and vitamin mineral mixture (HFD) with or without 0.5% curcumin. These cohorts were compared to APC Min mice receiving standard rodent chow (RC) with 8% fat. APC Min mice fed the HFD for 3 months had a 23% increase in total number of polyps compared to APC Min mice on RC. Curcumin was able to significantly reverse the accelerated polyp development associated with the HFD suggesting it may be effective clinically in helping prevent colon cancer even when ingesting high amounts of fatty foods. The anti-tumor effect of curcumin was shown to be associated with enhanced apoptosis and increased efficiency of DNA repair. Since curcumin prevented the gain in body weight seen in APC Min mice ingesting the HFD, modulation of energy metabolism may also be a factor.

  11. Targeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit

    PubMed Central

    Meghini, Francesco; Martins, Torcato; Tait, Xavier; Fujimitsu, Kazuyuki; Yamano, Hiroyuki; Glover, David M.; Kimata, Yuu

    2016-01-01

    A multi-subunit ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), regulates critical cellular processes including the cell cycle. To accomplish its diverse functions, APC/C activity must be precisely regulated in time and space. The interphase APC/C activator Fizzy-related (Fzr or Cdh1) is localized at centrosomes in animal cells. However, neither the mechanism of its localization nor its importance is clear. Here we identify the centrosome component Spd2 as a major partner of Fzr in Drosophila. The localization of Fzr to the centriole during interphase depends on direct interaction with Spd2. By generating Spd2 mutants unable to bind Fzr, we show that centrosomal localization of Fzr is essential for optimal APC/C activation towards its centrosomal substrate Aurora A. Finally, we show that Spd2 is also a novel APC/CFzr substrate. Our study is the first to demonstrate the critical importance of distinct subcellular pools of APC/C activators in the spatiotemporal control of APC/C activity. PMID:27558644

  12. Targeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit.

    PubMed

    Meghini, Francesco; Martins, Torcato; Tait, Xavier; Fujimitsu, Kazuyuki; Yamano, Hiroyuki; Glover, David M; Kimata, Yuu

    2016-08-25

    A multi-subunit ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), regulates critical cellular processes including the cell cycle. To accomplish its diverse functions, APC/C activity must be precisely regulated in time and space. The interphase APC/C activator Fizzy-related (Fzr or Cdh1) is localized at centrosomes in animal cells. However, neither the mechanism of its localization nor its importance is clear. Here we identify the centrosome component Spd2 as a major partner of Fzr in Drosophila. The localization of Fzr to the centriole during interphase depends on direct interaction with Spd2. By generating Spd2 mutants unable to bind Fzr, we show that centrosomal localization of Fzr is essential for optimal APC/C activation towards its centrosomal substrate Aurora A. Finally, we show that Spd2 is also a novel APC/C(Fzr) substrate. Our study is the first to demonstrate the critical importance of distinct subcellular pools of APC/C activators in the spatiotemporal control of APC/C activity.

  13. Dietary fat overcomes the protective activity of thrombospondin-1 signaling in the Apc(Min/+) model of colon cancer.

    PubMed

    Soto-Pantoja, D R; Sipes, J M; Martin-Manso, G; Westwood, B; Morris, N L; Ghosh, A; Emenaker, N J; Roberts, D D

    2016-01-01

    Thrombospondin 1 is a glycoprotein that regulates cellular phenotype through interactions with its cellular receptors and extracellular matrix-binding partners. Thrombospondin 1 locally regulates angiogenesis and inflammatory responses that contribute to colorectal carcinogenesis in Apc(Min/+) mice. The ability of thrombospondin 1 to regulate responses of cells and tissues to a variety of stresses suggested that loss of thrombospondin 1 may also have broader systemic effects on metabolism to modulate carcinogenesis. Apc(Min/+):Thbs1(-/-) mice exhibited decreased survival and higher tumor multiplicities in the small and large intestine relative to Apc(Min/+) mice when fed a low (5%) fat western diet. However, the protective effect of endogenous thrombospondin 1 was lost when the mice were fed a western diet containing 21% fat. Biochemical profiles of liver tissue identified systemic metabolic changes accompanying the effects of thrombospondin 1 and dietary lipid intake on tumorigenesis. A high-fat western diet differentially regulated elements of amino acid, energy and lipid metabolism in Apc(Min/+):Thbs1(-/-) mice relative to Apc(Min/+):Thbs1(+/+)mice. Metabolic changes in ketone body and tricarboxylic acid cycle intermediates indicate functional interactions between Apc and thrombospondin 1 signaling that control mitochondrial function. The cumulative diet-dependent differential changes observed in Apc(Min/+):Thbs1(-/-) versus Apc(Min/+) mice include altered amino acid and lipid metabolism, mitochondrial dysfunction, eicosanoids and ketone body formation. This metabolic profile suggests that the protective role of thrombospondin 1 to decrease adenoma formation in Apc(Min/+) mice results in part from improved mitochondrial function. PMID:27239962

  14. Rapid detection of translation-terminating mutations at the adenomatous polyposis coli (APC) gene by direct protein truncation test

    SciTech Connect

    Van Der Luut, R.; Khan, P.M.; Van Leeuwen, C.; Tops, C.; Roest, P.; Den Dunnen, J. )

    1994-03-01

    Familial adenomatous polyposis (FAP) is usually associated with protein truncating mutations in the adenomatous polyposis coli (APC) gene. The APC mutations are known to play a major role in colorectal carcinogensis. For the identification of protein truncating mutations of the APC gene, the authors developed a rapid, sensitive, and direct screening procedure. The technique is based on the in vitro transcription and translation of the genomic PCR products and is called the protein truncation test. Samples of DNA from individual FAP patients, members of a FAP family, colorectal tumors, and colorectal tumor-derived cell lines were used to show the effectiveness of this method. 9 refs., 2 figs.

  15. Synergism between K-rasVal12 and mutant Apc accelerates murine large intestinal tumourigenesis.

    PubMed

    Luo, Feijun; Poulogiannis, George; Ye, Hongtao; Hamoudi, Rifat; Arends, Mark J

    2011-07-01

    K-ras (KRAS) is mutated in 40-50% of human colorectal adenomas and carcinomas and plays key roles in cell proliferation, apoptosis, motility and differentiation, but its functional contribution to intestinal tumourigenesis in vivo remains incompletely understood. We have previously crossed K-rasVal12 transgenic mice with Ah-Cre mice to produce K-rasVal12/Cre offspring that inducibly express K-rasVal12 4A and 4B in the intestines, but this alone showed no significant effect on intestinal adenoma formation. Here, we crossed these mice with Min mice to evaluate the effect of K-rasVal12 and Apc mutation on intestinal tumourigenesis in vivo. The double mutant K-rasVal12/Cre/ApcMin/+ mice showed a moderate (1.86-fold) increase in adenomas in the small intestines, but a striking acceleration (6-fold increase) of large intestinal adenoma formation (P<0.01) and significantly reduced survival (by ~5 weeks) compared with control ApcMin/+ mice (P<0.01). There was recombination of the mutant K-rasVal12 transgene in 80% of large intestinal adenomas with expression of both K-rasVal12 4A and 4B isoform transcripts and expression of K-RasVal12 protein. The large intestinal adenomas showed immunohistochemical evidence of activation of MapK, Akt and Wnt signaling pathways and this was confirmed by quantitative RT-PCR analysis of relative transcript expression levels of target genes using a panel of 23 selected genes evaluated in both adenomas and non-tumour-bearing intestines. Several genes including Tiam1, Gastrin, CD44, uPA, Igfbp4, VEGF and Cox-2 that are known to be transcriptionally regulated by activation of the Wnt signaling pathway were found to be expressed at higher levels in the large intestinal adenomas from K-rasVal12/Cre/ApcMin/+ mice compared with those from controls, although other Wnt signaling pathway target genes remained unchanged. These data show that intestinal expression of K-rasVal12 accelerates Apc-initiated intestinal adenomagenesis in vivo with

  16. Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/CCdh1

    PubMed Central

    Lai, Fenju; Hu, Kaishun; Wu, Yuanzhong; Tang, Jianjun; Sang, Yi; Cao, Jingying; Kang, Tiebang

    2012-01-01

    A recently identified protein, FAN1 (FANCD2-associated nuclease 1, previously known as KIAA1018), is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking (ICL) agents. The mechanisms of FAN1 regulation have not yet been explored. Here, we provide evidence that FAN1 is degraded during mitotic exit, suggesting that FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex (APC/C). Indeed, Cdh1, but not Cdc20, was capable of regulating the protein level of FAN1 through the KEN box and the D-box. Moreover, the up- and down-regulation of FAN1 affected the progression to mitotic exit. Collectively, these data suggest that FAN1 may be a new mitotic substrate of APC/CCdh1 that plays a key role during mitotic exit. PMID:22854063

  17. Cubism and the cell cycle: the many faces of the APC/C.

    PubMed

    Pines, Jonathon

    2011-07-01

    One does not often look to analytic cubism for insights into the control of the cell cycle, but Pablo Picasso beautifully encapsulated the fundamentals when he said that "every act of creation is, first of all, an act of destruction". The rapid destruction of specific cell cycle regulators at just the right moment in the cell cycle ensures that daughter cells receive an equal and identical set of chromosomes from their mother and that DNA replication always follows mitosis. Remarkably, one protein complex is responsible for this surgical precision, the APC/C (anaphase-promoting complex, also known as the cyclosome). The APC/C is tightly regulated by its co-activators and by the spindle assembly checkpoint. PMID:21633387

  18. Wasp recruitment to the T cell:APC contact site occurs independently of Cdc42 activation.

    PubMed

    Cannon, J L; Labno, C M; Bosco, G; Seth, A; McGavin, M H; Siminovitch, K A; Rosen, M K; Burkhardt, J K

    2001-08-01

    Cdc42 and WASP are critical regulators of actin polymerization whose function during T cell signaling is poorly understood. Using a novel reagent that specifically detects Cdc42-GTP in fixed cells, we found that activated Cdc42 localizes to the T cell:APC contact site in an antigen-dependent manner. TCR signaling alone was sufficient to induce localization of Cdc42-GTP, and functional Lck and Zap-70 kinases were required. WASP also localized to the T cell:APC contact site in an antigen-dependent manner. Surprisingly, WASP localization was independent of the Cdc42 binding domain but required the proline-rich domain. Our results indicate that localized WASP activation requires the integration of multiple signals: WASP is recruited via interaction with SH3 domain-containing proteins and is activated by Cdc42-GTP concentrated at the same site. PMID:11520460

  19. Cubism and the cell cycle: the many faces of the APC/C.

    PubMed

    Pines, Jonathon

    2011-06-02

    One does not often look to analytic cubism for insights into the control of the cell cycle, but Pablo Picasso beautifully encapsulated the fundamentals when he said that "every act of creation is, first of all, an act of destruction". The rapid destruction of specific cell cycle regulators at just the right moment in the cell cycle ensures that daughter cells receive an equal and identical set of chromosomes from their mother and that DNA replication always follows mitosis. Remarkably, one protein complex is responsible for this surgical precision, the APC/C (anaphase-promoting complex, also known as the cyclosome). The APC/C is tightly regulated by its co-activators and by the spindle assembly checkpoint.

  20. APC/C-Mediated Degradation of dsRNA-Binding Protein 4 (DRB4) Involved in RNA Silencing

    PubMed Central

    Marrocco, Katia; Criqui, Marie-Claire; Zervudacki, Jérôme; Schott, Gregory; Eisler, Herfried; Parnet, Aude; Dunoyer, Patrice; Genschik, Pascal

    2012-01-01

    Background Selective protein degradation via the ubiquitin-26S proteasome is a major mechanism underlying DNA replication and cell division in all Eukaryotes. In particular, the APC/C (Anaphase Promoting Complex or Cyclosome) is a master ubiquitin protein ligase (E3) that targets regulatory proteins for degradation allowing sister chromatid separation and exit from mitosis. Interestingly, recent work also indicates that the APC/C remains active in differentiated animal and plant cells. However, its role in post-mitotic cells remains elusive and only a few substrates have been characterized. Methodology/Principal Findings In order to identify novel APC/C substrates, we performed a yeast two-hybrid screen using as the bait Arabidopsis APC10/DOC1, one core subunit of the APC/C, which is required for substrate recruitment. This screen identified DRB4, a double-stranded RNA binding protein involved in the biogenesis of different classes of small RNA (sRNA). This protein interaction was further confirmed in vitro and in plant cells. Moreover, APC10 interacts with DRB4 through the second dsRNA binding motif (dsRBD2) of DRB4, which is also required for its homodimerization and binding to its Dicer partner DCL4. We further showed that DRB4 protein accumulates when the proteasome is inactivated and, most importantly, we found that DRB4 stability depends on APC/C activity. Hence, depletion of Arabidopsis APC/C activity by RNAi leads to a strong accumulation of endogenous DRB4, far beyond its normal level of accumulation. However, we could not detect any defects in sRNA production in lines where DRB4 was overexpressed. Conclusions/Significance Our work identified a first plant substrate of the APC/C, which is not a regulator of the cell cycle. Though we cannot exclude that APC/C-dependent degradation of DRB4 has some regulatory roles under specific growth conditions, our work rather points to a housekeeping function of APC/C in maintaining precise cellular

  1. Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice.

    PubMed

    Sasada, Tatsunari; Hinoi, Takao; Saito, Yasufumi; Adachi, Tomohiro; Takakura, Yuji; Kawaguchi, Yasuo; Sotomaru, Yusuke; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru; Ohdan, Hideki

    2015-01-01

    The gastrointestinal tract is continuously exposed to a variety of chemicals and commensal bacteria. Recent studies have shown that changes in gut microbial populations caused by chlorine or other chemicals in the drinking water influence the development of human colorectal cancer, although the mechanism of tumorigenesis in the gut epithelium is obfuscated by the diversity of microflora and complexity of the tumor microenvironment. In this regard, mouse models that recapitulate human colorectal cancer are an invaluable tool. In this study, we used two conditional adenomatous polyposis coli (Apc) knockout mouse models to investigate the effect of chlorinated water on tumorigenesis in the digestive tract. Mice with colon-specific carcinoma--caused by either chromosomal (CDX2P 9.5-NLS Cre;Apc(+/flox), abbreviated to CPC;Apc) or microsatellite (CDX2P9.5-G19Cre;Apc(flox/flox) and CDX2P9.5-G22Cre;Apc(flox/flox)) instability, respectively--were administered chlorinated (10.0 mg/L chlorine) or tap (0.7 mg/L chlorine) water and evaluated for colon polyp formation. In CPC;Apc mice given chlorinated drinking water, tumors tended to develop in the colon, whereas in those that drank tap water, tumors were mostly observed in the small intestine. There was no difference in the rate of tumor formation of CDX2P9.5-G19Cre;Apc(flox/flox) and CDX2P9.5-G22Cre;Apc(flox/flox) mice consuming chlorinated as compared to tap water, suggesting that microsatellite instability in the Apc gene does not significantly affect tumorigenesis. Chlorinated water altered the enteric environment by reducing the fecal populations of the obligatory anaerobes Clostridium perfringens and C. difficile, as well as species belonging to the Atopobium cluster, including Enterobacteriaceae and Staphylococcus sp., which was associated with colon tumorigenesis in CPC;Apc mice. These results suggest that differences in tumorigenesis among CPC;Apc mice consuming chlorinated versus tap water may be due to differences

  2. Severe Gardner syndrome in families with mutations restricted to a specific region of the APC gene

    SciTech Connect

    Davies, D.R.; Armstrong, J.G.; Thakker, N.

    1995-11-01

    Familial adenomatous polyposis (FAP) is associated with a number of extraintestinal manifestations, which include osteomas, epidermoid cysts, and desmoid tumors, often referred to as {open_quotes}Gardner syndrome.{close_quotes} Recent studies have suggested that some of the phenotypic features of FAP are dependent on the position of the mutation within the APC gene. In particular, the correlation between congenital hypertrophy of the retinal pigment epithelium (CHRPE) and APC genotype indicates that affected families may be divided into distinct groups. We have investigated the association between the dento-osseous features of GS on dental panoramic radiographs (DPRs) and APC genotype in a regional cohort of FAP families. DPRs were performed on 84 affected individuals from 36 families, and the dento-osseous features of FAP were quantified by a weighted scoring system. Significant DPR abnormalities were present in 69% of affected individuals. The APC gene mutation was identified in 27 of these families, and for statistical analysis these were subdivided into three groups. Group 1 comprised 18 affected individuals from seven families with mutations 5{prime} of exon 9; these families (except one) did not express CHRPE. Groups 2 comprised 38 individuals from 16 families with mutations between exon 9 and codon 1444, all of whom expressed CHRPE. Group 3 comprised 11 individuals from four families with mutations 3{prime} of codon 1444, none of whom expressed CHRPE. Families with mutations 3{prime} of codon 1444 had significantly more lesions on DPRs (P < .001) and appeared to have a higher incidence of desmoid tumors. These results suggest that severity of some of the features of Gardner syndrome may correlate with genotype in FAP. 32 refs., 2 figs., 2 tabs.

  3. Specific immunotherapy of experimental myasthenia by genetically engineered APCs: the "guided missile" strategy.

    PubMed

    Drachman, D B; Wu, J-M; Miagkov, A; Williams, M A; Adams, R N; Wu, B

    2003-09-01

    Although treatment of MG with general immunosuppressive agents is often effective, it has important drawbacks, including suppression of the immune system as a whole, with the risks of infection and neoplasia, and numerous other adverse side effects. Ideally, treatment of MG should eliminate the specific pathogenic autoimmune response to AChR, without otherwise suppressing the immune system or producing other adverse side effects. Although antibodies to AChR are directly responsible for the loss of AChRs at neuromuscular junctions in MG, the AChR antibody response is T cell-dependent, and immunotherapy directed at T cells can abrogate the autoantibody response, with resulting benefit. As in other autoimmune diseases, the T cell response in MG is highly heterogeneous. The design of specific immunotherapy must take this heterogeneity into account and target the entire repertoire of AChR-specific T cells. We describe our investigation of a novel strategy for specific immunotherapy of MG, involving gene transfer to convert antigen-presenting cells (APCs) to "guided missiles" that target AChR-specific T cells, and that induce apoptosis and elimination of those T cells. This strategy uses the ability of APCs from a given individual to present the entire spectrum of AChR epitopes unique for that individual, and thereby to target the entire repertoire of antigen-specific T cells of the same individual. Using viral vectors, we have genetically engineered the APCs to process and present the most important domain of the AChR molecule, and to express a "warhead" of Fas ligand (FasL) to eliminate the activated AChR-specific T cells with which they interact. Our results show that the APCs express the appropriate gene products, and effectively and specifically eliminate AChR-specific T cells by the Fas/FasL pathway, while sparing T cells of other specificities. PMID:14592923

  4. Olfactomedin 4 deletion induces colon adenocarcinoma in ApcMin/+ mice

    PubMed Central

    Liu, W; Li, H; Hong, S-H; Piszczek, G P; Chen, W; Rodgers, G P

    2016-01-01

    Colon carcinogenesis is a multiple-step process involving the accumulation of a series of genetic and epigenetic alterations. The most commonly initiating event of intestinal carcinogenesis is mutation of the adenomatous polyposis coli (APC) gene, which leads to activation of the Wnt/β-catenin pathway. Olfactomedin 4 (OLFM4) has emerged as an intestinal stem-cell marker, but its biological function in the intestine remains to be determined. Here we show that Olfm4 deletion induced colon adenocarcinoma in the distal colon of ApcMin/+ mice. Mechanistically, we found that OLFM4 is a target gene of the Wnt/β-catenin pathway and can downregulate β-catenin signaling by competing with Wnt ligands for binding to Frizzled receptors, as well as by inhibition of the Akt-GSK-3β (Akt-glycogen synthase kinase-3β) pathway. We have shown that both Wnt and nuclear factor-κB (NF-κB) signaling were boosted in tumor tissues of Apc Olfm4 double-mutant mice. These data establish OLFM4 as a critical negative regulator of the Wnt/β-catenin and NF-κB pathways that inhibits colon-cancer development initiated by APC mutation. In addition, Olfm4 deletion significantly enhanced intestinal-crypt proliferation and inflammation induced by azoxymethane/dextran sodium sulfate. Thus, OLFM4 has an important role in the regulation of intestinal inflammation and tumorigenesis, and could be a potential therapeutic target for intestinal malignant tumors. Unlike the human colonic epithelium, the mouse colonic epithelium does not express OLFM4, but nevertheless, systemic OLFM4 deletion promotes colon tumorigenesis and that loss from mucosal neutrophils may have a role to play. PMID:26973250

  5. Feedback regulation between atypical E2Fs and APC/CCdh1 coordinates cell cycle progression.

    PubMed

    Boekhout, Michiel; Yuan, Ruixue; Wondergem, Annelotte P; Segeren, Hendrika A; van Liere, Elsbeth A; Awol, Nesibu; Jansen, Imke; Wolthuis, Rob M F; de Bruin, Alain; Westendorp, Bart

    2016-03-01

    E2F transcription factors control the oscillating expression pattern of multiple target genes during the cell cycle. Activator E2Fs, E2F1-3, induce an upswing of E2F targets, which is essential for the G1-to-S phase transition, whereas atypical E2Fs, E2F7 and E2F8, mediate a downswing of the same targets during late S, G2, and M phases. Expression of atypical E2Fs is induced by E2F1-3, but it is unknown how atypical E2Fs are inactivated in a timely manner. Here, we demonstrate that E2F7 and E2F8 are substrates of the anaphase-promoting complex/cyclosome (APC/C). Removal of CDH1, or mutating the CDH1-interacting KEN boxes, stabilized E2F7/8 from anaphase onwards and during G1. Expressing KEN mutant E2F7 during G1 impairs S phase entry and eventually results in cell death. Furthermore, we show that E2F8, but not E2F7, interacts also with APC/C(C) (dc20). Importantly, atypical E2Fs can activate APC/C(C) (dh1) by repressing its inhibitors cyclin A, cyclin E, and Emi1. In conclusion, we discovered a feedback loop between atypical E2Fs and APC/C(C) (dh1), which ensures balanced expression of cell cycle genes and normal cell cycle progression.

  6. Quality and generation rate of solid residues in the boiler of a waste-to-energy plant.

    PubMed

    Allegrini, E; Boldrin, A; Jansson, S; Lundtorp, K; Fruergaard Astrup, T

    2014-04-15

    The Danish waste management system relies significantly on waste-to-energy (WtE) plants. The ash produced at the energy recovery section (boiler ash) is classified as hazardous waste, and is commonly mixed with fly ash and air pollution control residues before disposal. In this study, a detailed characterization of boiler ash from a Danish grate-based mass burn type WtE was performed, to evaluate the potential for improving ash management. Samples were collected at 10 different points along the boiler's convective part, and analysed for grain size distribution, content of inorganic elements, polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD and PCDF), and leaching of metals. For all samples, PCDD and PCDF levels were below regulatory limits, while high pH values and leaching of e.g. Cl were critical. No significant differences were found between boiler ash from individual sections of the boiler, in terms of total content and leaching, indicating that separate management of individual ash fractions may not provide significant benefits.

  7. Quality and generation rate of solid residues in the boiler of a waste-to-energy plant.

    PubMed

    Allegrini, E; Boldrin, A; Jansson, S; Lundtorp, K; Fruergaard Astrup, T

    2014-04-15

    The Danish waste management system relies significantly on waste-to-energy (WtE) plants. The ash produced at the energy recovery section (boiler ash) is classified as hazardous waste, and is commonly mixed with fly ash and air pollution control residues before disposal. In this study, a detailed characterization of boiler ash from a Danish grate-based mass burn type WtE was performed, to evaluate the potential for improving ash management. Samples were collected at 10 different points along the boiler's convective part, and analysed for grain size distribution, content of inorganic elements, polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD and PCDF), and leaching of metals. For all samples, PCDD and PCDF levels were below regulatory limits, while high pH values and leaching of e.g. Cl were critical. No significant differences were found between boiler ash from individual sections of the boiler, in terms of total content and leaching, indicating that separate management of individual ash fractions may not provide significant benefits. PMID:24565930

  8. Increased IκBα expression is essential for the tolerogenic property of TGF-β-exposed APCs

    PubMed Central

    Ghafoori, Paiman; Yoshimura, Takeru; Turpie, Bruce; Masli, Sharmila

    2009-01-01

    IκBα is an inhibitor of the transcriptional factor NF-κB, and it is an essential component of the signaling pathways that lead to expression of inflammatory molecules. These include cytokines and costimulatory molecules associated with antigen presentation in an inflammatory immune response. In this study, we report that antigen-presenting cells exposed to TGF-β induce peripheral tolerance by increasing IκBα expression. Exposure of antigen presenting cells (APCs) to TGF-β is known to impair their ability to secrete IL-12, and such impairment correlated with reduced NF-κB activity as indicated by significantly reduced nuclear levels of p50, an essential subunit of NF-κB for IL-12 transcription. Blockade of increased nuclear IκBα in APCs by expression of small interfering RNA molecules (siRNAs) targeting IκBα transcripts prevented IL-12 impairment and the decline in nuclear p50 levels. Furthermore, such IκBα blockade also interfered with the tolerogenic property of TGF-β- exposed APCs. However, increased expression of IκBα in APCs, independent of TGF-β exposure, reduced nuclear p50 levels and permitted tolerance induction by APCs. Thus, our findings attribute a direct and significant role to IκBα in the tolerogenic potential of APCs. Increased IκBα expression in APCs may therefore offer a therapeutic approach to achieve antigen-specific immunomodulation.—Ghafoori, P., Yoshimura, T., Turpie, B., Masli, S. Increased IκBα expression is essential for the tolerogenic property of TGF-β-exposed APCs. PMID:19237504

  9. Cohesion Fatigue Explains Why Pharmacological Inhibition of the APC/C Induces a Spindle Checkpoint-Dependent Mitotic Arrest

    PubMed Central

    Lara-Gonzalez, Pablo; Taylor, Stephen S.

    2012-01-01

    The Spindle Assembly Checkpoint (SAC) delays the onset of anaphase in response to unattached kinetochores by inhibiting the activity of the Anaphase-Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase. Once all the chromosomes have bioriented, SAC signalling is somehow silenced, which allows progression through mitosis. Recent studies suggest that the APC/C itself participates in SAC silencing by targeting an unknown factor for proteolytic degradation. Key evidence in favour of this model comes from the use of proTAME, a small molecule inhibitor of the APC/C. In cells, proTAME causes a mitotic arrest that is SAC-dependent. Even though this observation comes at odds with the current view that the APC/C acts downstream of the SAC, it was nonetheless argued that these results revealed a role for APC/C activity in SAC silencing. However, we show here that the mitotic arrest induced by proTAME is due to the induction of cohesion fatigue, a phenotype that is caused by the loss of sister chromatid cohesion following a prolonged metaphase. Under these conditions, the SAC is re-activated and APC/C inhibition is maintained independently of proTAME. Therefore, these results provide a simpler explanation for why the proTAME-induced mitotic arrest is also dependent on the SAC. While these observations question the notion that the APC/C is required for SAC silencing, we nevertheless show that APC/C activity does partially contribute to its own release from inhibitory complexes, and importantly, this does not depend on proteasome-mediated degradation. PMID:23145059

  10. Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C.

    PubMed

    Brown, Nicholas G; VanderLinden, Ryan; Watson, Edmond R; Weissmann, Florian; Ordureau, Alban; Wu, Kuen-Phon; Zhang, Wei; Yu, Shanshan; Mercredi, Peter Y; Harrison, Joseph S; Davidson, Iain F; Qiao, Renping; Lu, Ying; Dube, Prakash; Brunner, Michael R; Grace, Christy R R; Miller, Darcie J; Haselbach, David; Jarvis, Marc A; Yamaguchi, Masaya; Yanishevski, David; Petzold, Georg; Sidhu, Sachdev S; Kuhlman, Brian; Kirschner, Marc W; Harper, J Wade; Peters, Jan-Michael; Stark, Holger; Schulman, Brenda A

    2016-06-01

    Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination.

  11. Cdh1-APC/C, cyclin B-Cdc2, and Alzheimer's disease pathology

    SciTech Connect

    Aulia, Selina; Tang, Bor Luen . E-mail: bchtbl@nus.edu.sg

    2006-01-06

    The anaphase-promoting complex/cyclosome (APC/C) is a key E3 ubiquitin ligase complex that functions in regulating cell cycle transitions in proliferating cells and has, as revealed recently, novel roles in postmitotic neurons. Regulated by its activator Cdh1 (or Hct1), whose level is high in postmitotic neurons, APC/C seems to have multiple functions at different cellular locations, modulating diverse processes such as synaptic development and axonal growth. These processes do not, however, appear to be directly connected to cell cycle regulation. It is now shown that Cdh1-APC/C activity may also have a basic role in suppressing cyclin B levels, thus preventing terminally differentiated neurons from aberrantly re-entering the cell cycle. The result of an aberrant cyclin B-induced S-phase entry, at least for some of these neurons, would be death via apoptosis. Cdh1 thus play an active role in maintaining the terminally differentiated, non-cycling state of postmitotic neurons-a function that could become impaired in Alzheimer's and other neurodegenerative diseases.

  12. The Specificity of Targeted Vaccines for APC Surface Molecules Influences the Immune Response Phenotype

    PubMed Central

    Grødeland, Gunnveig; Mjaaland, Siri; Tunheim, Gro; Fredriksen, Agnete B.; Bogen, Bjarne

    2013-01-01

    Different diseases require different immune responses for efficient protection. Thus, prophylactic vaccines should prime the immune system for the particular type of response needed for protection against a given infectious agent. We have here tested fusion DNA vaccines which encode proteins that bivalently target influenza hemagglutinins (HA) to different surface molecules on antigen presenting cells (APC). We demonstrate that targeting to MHC class II molecules predominantly induced an antibody/Th2 response, whereas targeting to CCR1/3/5 predominantly induced a CD8+/Th1 T cell response. With respect to antibodies, the polarizing effect was even more pronounced upon intramuscular (i.m) delivery as compared to intradermal (i.d.) vaccination. Despite these differences in induced immune responses, both vaccines protected against a viral challenge with influenza H1N1. Substitution of HA with ovalbumin (OVA) demonstrated that polarization of immune responses, as a consequence of APC targeting specificity, could be extended to other antigens. Taken together, the results demonstrate that vaccination can be tailor-made to induce a particular phenotype of adaptive immune responses by specifically targeting different surface molecules on APCs. PMID:24244595

  13. The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF.

    PubMed

    Hamada, Fumihiko; Bienz, Mariann

    2004-11-01

    Adenomatous polyposis coli (APC) is an important tumor suppressor in the colon. APC antagonizes the transcriptional activity of the Wnt effector beta-catenin by promoting its nuclear export and its proteasomal destruction in the cytoplasm. Here, we show that a third function of APC in antagonizing beta-catenin involves C-terminal binding protein (CtBP). APC is associated with CtBP in vivo and binds to CtBP in vitro through its conserved 15 amino acid repeats. Failure of this association results in elevated levels of beta-catenin/TCF complexes and of TCF-mediated transcription. Notably, CtBP is neither associated with TCF in vivo nor does mutation of the CtBP binding motifs in TCF-4 alter its transcriptional activity. This questions the idea that CtBP is a direct corepressor of TCF. Our evidence indicates that APC is an adaptor between beta-catenin and CtBP and that CtBP lowers the availability of free nuclear beta-catenin for binding to TCF by sequestering APC/beta-catenin complexes. PMID:15525529

  14. Association between aberrant APC promoter methylation and breast cancer pathogenesis: a meta-analysis of 35 observational studies

    PubMed Central

    Zhou, Dan; Tang, Weiwei; Wang, Wenyi; Pan, Xiaoyan

    2016-01-01

    Background. Adenomatous polyposis coli (APC) is widely known as an antagonist of the Wnt signaling pathway via the inactivation of β-catenin. An increasing number of studies have reported that APC methylation contributes to the predisposition to breast cancer (BC). However, recent studies have yielded conflicting results. Methods. Herein, we systematically carried out a meta-analysis to assess the correlation between APC methylation and BC risk. Based on searches of the Cochrane Library, PubMed, Web of Science and Embase databases, the odds ratio (OR) with 95% confidence interval (CI) values were pooled and summarized. Results. A total of 31 articles involving 35 observational studies with 2,483 cases and 1,218 controls met the inclusion criteria. The results demonstrated that the frequency of APC methylation was significantly higher in BC cases than controls under a random effect model (OR = 8.92, 95% CI [5.12–15.52]). Subgroup analysis further confirmed the reliable results, regardless of the sample types detected, methylation detection methods applied and different regions included. Interestingly, our results also showed that the frequency of APC methylation was significantly lower in early-stage BC patients than late-stage ones (OR = 0.62, 95% CI [0.42–0.93]). Conclusion. APC methylation might play an indispensable role in the pathogenesis of BC and could be regarded as a potential biomarker for the diagnosis of BC. PMID:27478702

  15. Targeting the anaphase-promoting complex/cyclosome (APC/C)- bromodomain containing 7 (BRD7) pathway for human osteosarcoma

    PubMed Central

    Han, An-Jia; Shi, Hui-Juan; Wang, Fen; Wang, Xin; Zhong, Li; Duan, Tingmei; Wu, Yuanzhong; Cao, Jingying; Tang, Jianjun; Sang, Yi; Wang, Li; Lv, Xiaobin; Xu, Shuangbing; Zhang, Ru-Hua; Deng, Wu-Guo; Li, Sheng-Ping; Zeng, Yi-Xin; Kang, Tiebang

    2014-01-01

    Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence and has a propensity for local invasion and early lung metastasis. However, the current therapies often result in chemoresistance, and a therapeutic target is not available in the clinic for osteosarcoma. Here, we report that BRD7 forms a complex with the anaphase-promoting complex/cyclosome (APC/C) and is degraded by APC/Ccdh1 and APC/Ccdc20 during the cell cycle. Moreover, BRD7 is a tumor suppressor in osteosarcoma, and the BRD7 mutant resistant to degradation by APC/C is more efficient than the wild-type protein at suppressing proliferation, colony formation, and tumor growth of osteosarcoma in vitro and in vivo. The combination of proTAME, an inhibitor of APC/C, with chemotherapeutic drugs efficiently targets osteosarcoma in vitro. Furthermore, there is a strong inverse correlation of protein levels between BRD7 and Cdh1 or Cdc20, and lower BRD7 expression is an indicator for poor prognosis in patients with osteosarcoma. Collectively, our results indicate that targeting the APC/C-BRD7 pathway may be a novel strategy for treating osteosarcoma. PMID:24840027

  16. A novel approach to assess the spontaneous gastrointestinal bleeding risk of antithrombotic agents using Apc(min/+) mice.

    PubMed

    Wei, Huijun; Shang, Jin; Keohane, CarolAnn; Wang, Min; Li, Qiu; Ni, Weihua; O'Neill, Kim; Chintala, Madhu

    2014-06-01

    Assessment of the bleeding risk of antithrombotic agents is usually performed in healthy animals with some form of vascular injury to peripheral organs to induce bleeding. However, bleeding observed in patients with currently marketed antithrombotic drugs is typically spontaneous in nature such as intracranial haemorrhage (ICH) and gastrointestinal (GI) bleeding, which happens most frequently on top of preexisting pathologies such as GI ulcerations and polyps. Apc(min/+) mice are reported to develop multiple adenomas through the entire intestinal tract and display progressive anaemia.In this study, we evaluated the potential utility of Apc(min/+) mice as a model for assessing spontaneous GI bleeding with antithrombotic agents. Apc(min/+) mice exhibited progressive blood loss starting at the age of nine weeks. Despite the increase in bleeding, Apc(min/+) mice were in a hypercoagulable state and displayed an age-dependent increase in thrombin generation and circulating fibrinogen as well as a significant decrease in clotting times. We evaluated the effect of warfarin, dabigatran etexilate, apixaban and clopidogrel in this model by administering them in diet or in the drinking water to mice for 1-4 weeks. All of these marketed drugs significantly increased GI bleeding in Apc(min/+) mice, but not in wild-type mice. Although different exposure profiles of these antithrombotic agents make it challenging to compare the bleeding risk of compounds, our results indicate that the Apc(min/+) mouse may be a sensitive preclinical model for assessing the spontaneous GI bleeding risk of novel antithrombotic agents.

  17. Molecular genetic analysis of exons 1 to 6 of the APC gene in non-polyposis familial colorectal cancer.

    PubMed

    Joyce, J A; Froggatt, N J; Davies, R; Evans, D G; Trembath, R; Barton, D E; Maher, E R

    1995-12-01

    Familial adenomatous polyposis coli is caused by constitutional mutations in the APC gene. The hallmark of familial adenomatous polyposis coli is the presence of numerous (> 100) colorectal polyps, but mutations in the 5' end of the APC gene have been associated with familial colorectal cancer without florid polyposis. Although familial adenomatous polyposis coli accounts for only a minority of familial colorectal cancer cases, we hypothesised that APC mutations which were not associated with florid polyposis might make a significant contribution to nonpolyposis familial colorectal cancer. To investigate this possibility, we analysed 40 unrelated patients with familial colorectal cancer without classical familial adenomatous polyposis coli for mutations in exons 1 to 6 (codons 1 to 243) of the APC gene. No mutations were detected, but a C-->T polymorphism at nucleotide 333 (Arg-->Trp at codon 99) was identified. No 5' APC mutations were detected in two patients with desmoid tumours and a family history of colorectal cancer and polyps. We conclude that mutations in exons 1 to 6 of the APC gene are infrequent in patients with familial colorectal cancer who do not have many colorectal polyps. PMID:8835324

  18. Association between aberrant APC promoter methylation and breast cancer pathogenesis: a meta-analysis of 35 observational studies.

    PubMed

    Zhou, Dan; Tang, Weiwei; Wang, Wenyi; Pan, Xiaoyan; An, Han-Xiang; Zhang, Yun

    2016-01-01

    Background. Adenomatous polyposis coli (APC) is widely known as an antagonist of the Wnt signaling pathway via the inactivation of β-catenin. An increasing number of studies have reported that APC methylation contributes to the predisposition to breast cancer (BC). However, recent studies have yielded conflicting results. Methods. Herein, we systematically carried out a meta-analysis to assess the correlation between APC methylation and BC risk. Based on searches of the Cochrane Library, PubMed, Web of Science and Embase databases, the odds ratio (OR) with 95% confidence interval (CI) values were pooled and summarized. Results. A total of 31 articles involving 35 observational studies with 2,483 cases and 1,218 controls met the inclusion criteria. The results demonstrated that the frequency of APC methylation was significantly higher in BC cases than controls under a random effect model (OR = 8.92, 95% CI [5.12-15.52]). Subgroup analysis further confirmed the reliable results, regardless of the sample types detected, methylation detection methods applied and different regions included. Interestingly, our results also showed that the frequency of APC methylation was significantly lower in early-stage BC patients than late-stage ones (OR = 0.62, 95% CI [0.42-0.93]). Conclusion. APC methylation might play an indispensable role in the pathogenesis of BC and could be regarded as a potential biomarker for the diagnosis of BC. PMID:27478702

  19. Interphase APC/C–Cdc20 inhibition by cyclin A2–Cdk2 ensures efficient mitotic entry

    PubMed Central

    Hein, Jamin B.; Nilsson, Jakob

    2016-01-01

    Proper cell-cycle progression requires tight temporal control of the Anaphase Promoting Complex/Cyclosome (APC/C), a large ubiquitin ligase that is activated by one of two co-activators, Cdh1 or Cdc20. APC/C and Cdc20 are already present during interphase but APC/C–Cdc20 regulation during this window of the cell cycle, if any, is unknown. Here we show that cyclin A2–Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C–Cdc20 activity. Preventing Cdc20 phosphorylation results in pre-mature activation of the APC/C–Cdc20 and several substrates, including cyclin B1 and A2, are destabilized which lengthens G2 and slows mitotic entry. Expressing non-degradable cyclin A2 but not cyclin B1 restores mitotic entry in these cells. We have thus uncovered a novel positive feedback loop centred on cyclin A2–Cdk2 inhibition of interphase APC/C–Cdc20 to allow further cyclin A2 accumulation and mitotic entry. PMID:26960431

  20. A relay mechanism between EB1 and APC facilitate STIM1 puncta assembly at endoplasmic reticulum-plasma membrane junctions.

    PubMed

    Asanov, Alexander; Sherry, Ryan; Sampieri, Alicia; Vaca, Luis

    2013-09-01

    The assembly of STIM1 protein puncta near endoplasmic reticulum-plasma membrane (ER-PM) junctions is required for optimal activation of store-operated channels (SOC). The mechanisms controlling the translocation of STIM1 puncta to ER-PM junctions remain largely unknown. In the present study, we have explored the role of the microtubule binding protein adenomatous polyposis coli (APC), on STIM1 puncta and store-operated calcium entry (SOCE). APC-depleted cells showed reduced STIM1 puncta near ER-PM junctions, instead puncta is found at the ER surrounding the cell nucleus. Reduced STIM1 puncta near ER-PM junctions in APC-depleted cells correlates with a strong inhibition of SOCE and diminished Orai whole-cell currents. Immunoprecipitation and confocal microscopy co-localization studies indicate that, upon depletion of the ER, STIM1 dissociates from EB1 and associates to APC. Deletion analysis identified an APC-binding domain in the carboxyl terminus of STIM1 (STIM1 650-685). These results together position APC as an important element in facilitating the translocation of STIM1 puncta near ER-PM junctions, which in turn is required for efficient SOCE and Orai activation upon depletion of the ER.

  1. Improving residue-residue contact prediction via low-rank and sparse decomposition of residue correlation matrix.

    PubMed

    Zhang, Haicang; Gao, Yujuan; Deng, Minghua; Wang, Chao; Zhu, Jianwei; Li, Shuai Cheng; Zheng, Wei-Mou; Bu, Dongbo

    2016-03-25

    Strategies for correlation analysis in protein contact prediction often encounter two challenges, namely, the indirect coupling among residues, and the background correlations mainly caused by phylogenetic biases. While various studies have been conducted on how to disentangle indirect coupling, the removal of background correlations still remains unresolved. Here, we present an approach for removing background correlations via low-rank and sparse decomposition (LRS) of a residue correlation matrix. The correlation matrix can be constructed using either local inference strategies (e.g., mutual information, or MI) or global inference strategies (e.g., direct coupling analysis, or DCA). In our approach, a correlation matrix was decomposed into two components, i.e., a low-rank component representing background correlations, and a sparse component representing true correlations. Finally the residue contacts were inferred from the sparse component of correlation matrix. We trained our LRS-based method on the PSICOV dataset, and tested it on both GREMLIN and CASP11 datasets. Our experimental results suggested that LRS significantly improves the contact prediction precision. For example, when equipped with the LRS technique, the prediction precision of MI and mfDCA increased from 0.25 to 0.67 and from 0.58 to 0.70, respectively (Top L/10 predicted contacts, sequence separation: 5 AA, dataset: GREMLIN). In addition, our LRS technique also consistently outperforms the popular denoising technique APC (average product correction), on both local (MI_LRS: 0.67 vs MI_APC: 0.34) and global measures (mfDCA_LRS: 0.70 vs mfDCA_APC: 0.67). Interestingly, we found out that when equipped with our LRS technique, local inference strategies performed in a comparable manner to that of global inference strategies, implying that the application of LRS technique narrowed down the performance gap between local and global inference strategies. Overall, our LRS technique greatly facilitates

  2. Drosophila Homologues of Adenomatous Polyposis Coli (APC) and the Formin Diaphanous Collaborate by a Conserved Mechanism to Stimulate Actin Filament Assembly*

    PubMed Central

    Jaiswal, Richa; Stepanik, Vince; Rankova, Aneliya; Molinar, Olivia; Goode, Bruce L.; McCartney, Brooke M.

    2013-01-01

    Adenomatous polyposis coli (APC) is a large multidomain protein that regulates the cytoskeleton. Recently, it was shown that vertebrate APC through its Basic domain directly collaborates with the formin mDia1 to stimulate actin filament assembly in the presence of nucleation barriers. However, it has been unclear whether these activities extend to homologues of APC and Dia in other organisms. Drosophila APC and Dia are each required to promote actin furrow formation in the syncytial embryo, suggesting a potential collaboration in actin assembly, but low sequence homology between the Basic domains of Drosophila and vertebrate APC has left their functional and mechanistic parallels uncertain. To address this question, we purified Drosophila APC1 and Dia and determined their individual and combined effects on actin assembly using both bulk fluorescence assays and total internal reflection fluorescence microscopy. Our data show that APC1, similar to its vertebrate homologue, bound to actin monomers and nucleated and bundled filaments. Further, Drosophila Dia nucleated actin assembly and protected growing filament barbed ends from capping protein. Drosophila APC1 and Dia directly interacted and collaborated to promote actin assembly in the combined presence of profilin and capping protein. Thus, despite limited sequence homology, Drosophila and vertebrate APCs exhibit highly related activities and mechanisms and directly collaborate with formins. These results suggest that APC-Dia interactions in actin assembly are conserved and may underlie important in vivo functions in a broad range of animal phyla. PMID:23558679

  3. The APC I1307K allele conveys a significant increased risk for cancer.

    PubMed

    Leshno, Ari; Shapira, Shiran; Liberman, Eliezer; Kraus, Sarah; Sror, Miri; Harlap-Gat, Amira; Avivi, Doran; Galazan, Lior; David, Maayan; Maharshak, Nitsan; Moanis, Serhan; Arber, Nadir; Moshkowitz, Menachem

    2016-03-15

    This study is the first attempt to evaluate the association between the APC I1307K variant and overall cancer risk. It is unique in both its large sample size and in the reliability of data in the control group. The findings described in this article have major implications in terms of identifying asymptomatic individuals who are at increased risk to harbor cancer and therefore targeted to be enrolled in specific early detection and prevention programs. The prevalence of the APC I1307K missense mutation among Ashkenazi Jews is ∼ 6%. Carriers are at an increased risk for colorectal neoplasia. In this study, we examined the association of this variant with non-colorectal cancers. Consecutive 13,013 healthy subjects who underwent screening at the Integrated Cancer Prevention Center between 2006 and 2014 were enrolled. This population was supplemented with 1,611 cancer patients from the same institution. Demographics, medical history, and pathological data were recorded. Mortality data were obtained from the Ministry of Health's registry. The prevalence of APC I1307K in cancer patients and healthy subjects was compared. The APC I1307K variant was detected in 189 (11.8%) cancer patients compared to 614 (4.7%) healthy subjects, reflecting an adjusted age and sex odds ratio (OR) of 2.53 (p < 0.0001). History of two or more cancer types was associated with a positive carrier prevalence (OR = 4.38 p < 0.0001). Males had significantly increased carrier prevalence in lung, urologic, pancreatic, and skin cancers. The carrier prevalence among females was significantly higher only in breast and skin cancers. Female carriers developed cancer at a significantly older age compared to non-carriers (average 62.7 years vs. 57.8, respectively, p = 0.027), had better survival rates (HR = 0.58, p = 0.022) and overall increased longevity (average age of death 78.8 vs. 70.4 years, respectively, p = 0.003). In conclusion, the APC I1307K variant is a reliable marker for overall cancer risk

  4. A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine

    PubMed Central

    Reed, Karen R; Meniel, Valerie S; Marsh, Victoria; Cole, Alicia; Sansom, Owen J; Clarke, Alan R

    2008-01-01

    Background p53 is an important tumour suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated. Methods We have conditionally deleted the Adenomatous Polyposis coli gene (Apc) from the adult murine intestine in wild type and p53 deficient environments and subsequently compared the phenotype and transcriptome profiles in both genotypes. Results Expression of p53 was shown to be elevated following the conditional deletion of Apc in the adult small intestine. Furthermore, p53 status was shown to impact on the transcription profile observed following Apc loss. A number of key Wnt pathway components and targets were altered in the p53 deficient environment. However, the aberrant phenotype observed following loss of Apc (rapid nuclear localisation of β-catenin, increased levels of DNA damage, nuclear atypia, perturbed cell death, proliferation, differentiation and migration) was not significantly altered by the absence of p53. Conclusion p53 related feedback mechanisms regulating Wnt signalling activity are present in the intestine, and become activated following loss of Apc. However, the physiological Wnt pathway regulation by p53 appears to be overwhelmed by Apc loss and consequently the activity of these regulatory mechanisms is not sufficient to modulate the immediate phenotypes seen following Apc loss. Thus we are able to provide an explanation to the apparent contradiction that, despite having a Wnt regulatory capacity, p53 loss is not associated with early lesion development. PMID:18533991

  5. Correlation between the expression of DNMT1, and GSTP1 and APC, and the methylation status of GSTP1 and APC in association with their clinical significance in prostate cancer

    PubMed Central

    ZHANG, WEIJIE; JIAO, HONGLIANG; ZHANG, XUDONG; ZHAO, RUIHUA; WANG, FENG; HE, WEI; ZONG, HONG; FAN, QINGXIA; WANG, LIUXING

    2015-01-01

    The aim of the present study was to investigate the correlation between the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1), glutathione S-transferase-P1 (GSTP1) and adenomatous polyposis coli (APC), and the methylation status of GSTP1 and APC in prostate cancer (PCa) and benign prostatic hyperplasia (BPH), and to examine its clinical significance. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of DNMT1, GSTP1 and APC in 56 samples of PCa tissue and 10 samples of BPH tissue. Methylation-specific-PCR was used to detect the methylation status of the CpG island promoters of GSTP1 and APC. The positive rate of expression of DNMT1 in poorly-differentiated PCa, moderately-differentiated PCa, well-differentiated PCa and BPH was 86.7%, 70.6%, 55.6% and 30.0%, respectively (P<0.05); for GSTP1, the positive rate was 13.3%, 29.4%, 44.4% and 90.0%, respectively (P<0.05); and for APC, the positive rate was 23.3%, 47.6%, 55.6% and 70.0%, respectively (P<0.05). The correlation coefficient for the association between the expression of DNMT1 and GSTP1 was −0.891 (P<0.05). Between the expression of DNMT1 and APC, the correlation coefficient was −0.721 (P<0.05). GSTP1 and APC were hypermethylated in the majority of PCa tissue samples. The positive rate of methylation of these genes in poorly-differentiated PCa was 83.3% and 73.3%, respectively. By contrast, hypomethylation (or demethylation) was observed in BPH samples, in which the positive rate of methylation was 10.0% and 20.0%, respectively (P<0.05). The increased expression of DNMT1, and the reduced expression of GSTP1 and APC have an important role in the development of PCa. Due to the high expression of DNMT1 mRNA, it is likely that the hypermethylation of CpG islands contributed to the silencing of GSTP1 and APC in PCa tissues. PMID:25738352

  6. The four canonical tpr subunits of human APC/C form related homo-dimeric structures and stack in parallel to form a TPR suprahelix.

    PubMed

    Zhang, Ziguo; Chang, Leifu; Yang, Jing; Conin, Nora; Kulkarni, Kiran; Barford, David

    2013-11-15

    The anaphase-promoting complex or cyclosome (APC/C) is a large E3 RING-cullin ubiquitin ligase composed of between 14 and 15 individual proteins. A striking feature of the APC/C is that only four proteins are involved in directly recognizing target proteins and catalyzing the assembly of a polyubiquitin chain. All other subunits, which account for >80% of the mass of the APC/C, provide scaffolding functions. A major proportion of these scaffolding subunits are structurally related. In metazoans, there are four canonical tetratricopeptide repeat (TPR) proteins that form homo-dimers (Apc3/Cdc27, Apc6/Cdc16, Apc7 and Apc8/Cdc23). Here, we describe the crystal structure of the N-terminal homo-dimerization domain of Schizosaccharomyces pombe Cdc23 (Cdc23(Nterm)). Cdc23(Nterm) is composed of seven contiguous TPR motifs that self-associate through a related mechanism to those of Cdc16 and Cdc27. Using the Cdc23(Nterm) structure, we generated a model of full-length Cdc23. The resultant "V"-shaped molecule docks into the Cdc23-assigned density of the human APC/C structure determined using negative stain electron microscopy (EM). Based on sequence conservation, we propose that Apc7 forms a homo-dimeric structure equivalent to those of Cdc16, Cdc23 and Cdc27. The model is consistent with the Apc7-assigned density of the human APC/C EM structure. The four canonical homo-dimeric TPR proteins of human APC/C stack in parallel on one side of the complex. Remarkably, the uniform relative packing of neighboring TPR proteins generates a novel left-handed suprahelical TPR assembly. This finding has implications for understanding the assembly of other TPR-containing multimeric complexes.

  7. The Four Canonical TPR Subunits of Human APC/C Form Related Homo-Dimeric Structures and Stack in Parallel to Form a TPR Suprahelix☆

    PubMed Central

    Zhang, Ziguo; Chang, Leifu; Yang, Jing; Conin, Nora; Kulkarni, Kiran; Barford, David

    2013-01-01

    The anaphase-promoting complex or cyclosome (APC/C) is a large E3 RING-cullin ubiquitin ligase composed of between 14 and 15 individual proteins. A striking feature of the APC/C is that only four proteins are involved in directly recognizing target proteins and catalyzing the assembly of a polyubiquitin chain. All other subunits, which account for > 80% of the mass of the APC/C, provide scaffolding functions. A major proportion of these scaffolding subunits are structurally related. In metazoans, there are four canonical tetratricopeptide repeat (TPR) proteins that form homo-dimers (Apc3/Cdc27, Apc6/Cdc16, Apc7 and Apc8/Cdc23). Here, we describe the crystal structure of the N-terminal homo-dimerization domain of Schizosaccharomyces pombe Cdc23 (Cdc23Nterm). Cdc23Nterm is composed of seven contiguous TPR motifs that self-associate through a related mechanism to those of Cdc16 and Cdc27. Using the Cdc23Nterm structure, we generated a model of full-length Cdc23. The resultant “V”-shaped molecule docks into the Cdc23-assigned density of the human APC/C structure determined using negative stain electron microscopy (EM). Based on sequence conservation, we propose that Apc7 forms a homo-dimeric structure equivalent to those of Cdc16, Cdc23 and Cdc27. The model is consistent with the Apc7-assigned density of the human APC/C EM structure. The four canonical homo-dimeric TPR proteins of human APC/C stack in parallel on one side of the complex. Remarkably, the uniform relative packing of neighboring TPR proteins generates a novel left-handed suprahelical TPR assembly. This finding has implications for understanding the assembly of other TPR-containing multimeric complexes. PMID:23583778

  8. Impact of air pollution control measures and weather conditions on asthma during the 2008 Summer Olympic Games in Beijing.

    PubMed

    Li, Yi; Wang, Wen; Wang, Jizhi; Zhang, Xiaoling; Lin, Weili; Yang, Yuanqin

    2011-07-01

    The alternative transportation strategy implemented during the 2008 Summer Olympic Games in Beijing provided an opportunity to study the impact of the control measures and weather conditions on air quality and asthma morbidity. An ecological study compared the 41 days of the Olympic Games (8 August-17 September 2008) to a baseline period (1-30 June). Also, in order to emphasize the impact of weather conditions on air quality, a pollution linking meteorological index (Plam) was introduced to represent the air pollution meteorological condition. Our study showed that the average number of outpatient visits for asthma was 12.5 per day at baseline and 7.3 per day during the Olympics-a 41.6% overall decrease. Compared with the baseline, the Games were associated with a significant reduction in asthma visits (RR 0.58, 95%CI: 0.52-0.65). At 16.5 visits per day, asthma visits were also significantly higher, during the pre-Olympic period (RR 1.32, 95% CI: 1.15-1.52). The study also showed that the RR of asthma events on a given day, as well as the average daily peak ozone concentration during the preceding 48-72 h, increased at cumulative ozone concentrations of 70 to 100 ppb and 100 ppb or more compared with ozone concentrations of less than 70 ppb (P < 0.05). We concluded that along with "good" weather conditions, efforts to reduce traffic congestion in Beijing during the Olympic Games were associated with a prolonged reduction in air pollution and significantly lower rates of adult asthma events. These data provide support for efforts to reduce air pollution and improve health via reductions in motor vehicle traffic. PMID:21076997

  9. Bimetallic Pt-Au Nanocatalysts on ZnO/Al2O3/Monolith for Air Pollution Control.

    PubMed

    Kim, Ki-Joong; Ahn, Ho-Geun

    2015-08-01

    The catalytic activity of a monolithic catalyst with nanosized Pt and Au particles on ZnO/Al2O3 (Pt-Au/ZnO/Al2O3/M) prepared by a wash-coat method was examined, specifically for toluene oxidation. Scanning electron microscopy image showed clearly the formation of a ZnO/Al2O3 layer on the monolith. Nanosized Pt-Au particles on ZnO/Al2O3/M with different sizes could be found in the Pt-Au/ZnO/Al2O3/M catalyst. The conversion of toluene decreased with increasing toluene concentration and was also largely affected by the feed flow rate. The Pt-Au/ZnO/Al2O3/M catalysts prepared in this work have almost the same activity (molecules of toluene per second) compared with a powder Pt-Au/ZnO/Al2O3 catalyst with the same loadings of Pt and Au components; thus this catalyst could be used in controlling air pollution with very low concentrations and high flow rate. PMID:26369207

  10. Impact of air pollution control measures and weather conditions on asthma during the 2008 Summer Olympic Games in Beijing.

    PubMed

    Li, Yi; Wang, Wen; Wang, Jizhi; Zhang, Xiaoling; Lin, Weili; Yang, Yuanqin

    2011-07-01

    The alternative transportation strategy implemented during the 2008 Summer Olympic Games in Beijing provided an opportunity to study the impact of the control measures and weather conditions on air quality and asthma morbidity. An ecological study compared the 41 days of the Olympic Games (8 August-17 September 2008) to a baseline period (1-30 June). Also, in order to emphasize the impact of weather conditions on air quality, a pollution linking meteorological index (Plam) was introduced to represent the air pollution meteorological condition. Our study showed that the average number of outpatient visits for asthma was 12.5 per day at baseline and 7.3 per day during the Olympics-a 41.6% overall decrease. Compared with the baseline, the Games were associated with a significant reduction in asthma visits (RR 0.58, 95%CI: 0.52-0.65). At 16.5 visits per day, asthma visits were also significantly higher, during the pre-Olympic period (RR 1.32, 95% CI: 1.15-1.52). The study also showed that the RR of asthma events on a given day, as well as the average daily peak ozone concentration during the preceding 48-72 h, increased at cumulative ozone concentrations of 70 to 100 ppb and 100 ppb or more compared with ozone concentrations of less than 70 ppb (P < 0.05). We concluded that along with "good" weather conditions, efforts to reduce traffic congestion in Beijing during the Olympic Games were associated with a prolonged reduction in air pollution and significantly lower rates of adult asthma events. These data provide support for efforts to reduce air pollution and improve health via reductions in motor vehicle traffic.

  11. A paradox for air pollution controlling in China revealed by “APEC Blue” and “Parade Blue”

    NASA Astrophysics Data System (ADS)

    Liu, Haoran; Liu, Cheng; Xie, Zhouqing; Li, Ying; Huang, Xin; Wang, Shanshan; Xu, Jin; Xie, Pinhua

    2016-09-01

    A series of strict emission control measures were implemented in Beijing and surrounding regions to ensure good air quality during the 2014 Asia-Pacific Economic Cooperation (APEC) summit and 2015 Grand Military Parade (Parade), which led to blue sky days during these two events commonly referred to as “APEC Blue” and “Parade Blue”. Here we calculated Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) and Ozone Monitoring Instrument (OMI) NO2 and HCHO results based on well known DOAS trace gas fitting algorithm and WRF-Chem model (with measured climatology parameter and newest emission inventor) simulated trace gases profiles. We found the NO2 columns abruptly decreased both Parade (43%) and APEC (21%) compared with the periods before these two events. The back-trajectory cluster analysis and the potential source contribution function (PSCF) proved regional transport from southern peripheral cities plays a key role in pollutants observed at Beijing. The diminishing transport contribution from southern air mass during Parade manifests the real effect of emission control measures on NO2 pollution. Based on the ratios of HCHO over NO2 we found there were not only limited the NO2 pollutant but also suppress the O3 contaminant during Parade, while O3 increased during the APEC.

  12. Air pollution control technology for municipal solid waste-to-energy conversion facilities: capabilities and research needs

    SciTech Connect

    Lynch, J F; Young, J C

    1980-09-01

    Three major categories of waste-to-energy conversion processes in full-scale operation or advanced demonstration stages in the US are co-combustion, mass incineration, and pyrolysis. These methods are described and some information on US conversion facilities is tabulated. Conclusions and recommendations dealing with the operation, performance, and research needs for these facilities are given. Section II identifies research needs concerning air pollution aspects of the waste-to-energy processes and reviews significant operating and research findings for the co-combustion, mass incinceration, and pyrolysis waste-to-energy systems.

  13. 78 FR 51184 - Air Pollution Control: Proposed Actions on Clean Air Act Section 105 Grant to the Lane Regional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    ... Lane Regional Air Protection Agency (LRAPA) in Eugene, Oregon is a result of agency wide non-selective... the non-selective reductions made to address reductions in revenue due to adverse economic conditions... public hearing, determines that a reduction in expenditures is attributable to a non-selective...

  14. EFFECT OF AIR-POLLUTION CONTROL ON DEATH RATES IN DUBLIN, IRELAND: AN INTERVENTION STUDY. (R827353C006)

    EPA Science Inventory

    Background Particulate air pollution episodes have been associated with increased daily death. However, there is little direct evidence that diminished particulate air pollution concentrations would lead to reductions in death rates. We assessed the effect of ...

  15. 77 FR 20625 - Air Pollution Control: Proposed Action on Clean Air Act Grants to the Idaho Department of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-05

    ... state budget cycle runs from July 1 of the current through June 30 of the following year. For the 2010... Water Program (Recurring Appropriation)......... 7,847,700 6,012,700 -1,835000 -23.38 Water Program (One... administration, water and waste. Only the smaller Coeur D'Alene Basin Commission showed any increase. Based...

  16. EFFECT OF STARVATION ON THE PERFORMANCE AND RE-ACCLIMATION OF BIOTRICKLING FILTERS FOR AIR POLLUTION CONTROL. (R825392)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  17. A paradox for air pollution controlling in China revealed by “APEC Blue” and “Parade Blue”

    PubMed Central

    Liu, Haoran; Liu, Cheng; Xie, Zhouqing; Li, Ying; Huang, Xin; Wang, Shanshan; Xu, Jin; Xie, Pinhua

    2016-01-01

    A series of strict emission control measures were implemented in Beijing and surrounding regions to ensure good air quality during the 2014 Asia-Pacific Economic Cooperation (APEC) summit and 2015 Grand Military Parade (Parade), which led to blue sky days during these two events commonly referred to as “APEC Blue” and “Parade Blue”. Here we calculated Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) and Ozone Monitoring Instrument (OMI) NO2 and HCHO results based on well known DOAS trace gas fitting algorithm and WRF-Chem model (with measured climatology parameter and newest emission inventor) simulated trace gases profiles. We found the NO2 columns abruptly decreased both Parade (43%) and APEC (21%) compared with the periods before these two events. The back-trajectory cluster analysis and the potential source contribution function (PSCF) proved regional transport from southern peripheral cities plays a key role in pollutants observed at Beijing. The diminishing transport contribution from southern air mass during Parade manifests the real effect of emission control measures on NO2 pollution. Based on the ratios of HCHO over NO2 we found there were not only limited the NO2 pollutant but also suppress the O3 contaminant during Parade, while O3 increased during the APEC. PMID:27680499

  18. Impact of air pollution control measures and weather conditions on asthma during the 2008 Summer Olympic Games in Beijing

    NASA Astrophysics Data System (ADS)

    Li, Yi; Wang, Wen; Wang, Jizhi; Zhang, Xiaoling; Lin, Weili; Yang, Yuanqin

    2011-07-01

    The alternative transportation strategy implemented during the 2008 Summer Olympic Games in Beijing provided an opportunity to study the impact of the control measures and weather conditions on air quality and asthma morbidity. An ecological study compared the 41 days of the Olympic Games (8 August-17 September 2008) to a baseline period (1-30 June). Also, in order to emphasize the impact of weather conditions on air quality, a pollution linking meteorological index (Plam) was introduced to represent the air pollution meteorological condition. Our study showed that the average number of outpatient visits for asthma was 12.5 per day at baseline and 7.3 per day during the Olympics—a 41.6% overall decrease. Compared with the baseline, the Games were associated with a significant reduction in asthma visits (RR 0.58, 95%CI: 0.52-0.65). At 16.5 visits per day, asthma visits were also significantly higher, during the pre-Olympic period (RR 1.32, 95% CI: 1.15-1.52). The study also showed that the RR of asthma events on a given day, as well as the average daily peak ozone concentration during the preceding 48-72 h, increased at cumulative ozone concentrations of 70 to 100 ppb and 100 ppb or more compared with ozone concentrations of less than 70 ppb ( P < 0.05). We concluded that along with "good" weather conditions, efforts to reduce traffic congestion in Beijing during the Olympic Games were associated with a prolonged reduction in air pollution and significantly lower rates of adult asthma events. These data provide support for efforts to reduce air pollution and improve health via reductions in motor vehicle traffic.

  19. Quantifying the efficiency and equity implications of power plant air pollution control strategies in the United States

    SciTech Connect

    Levy, J.I.; Wilson, A.M.; Zwack, L.M.

    2007-05-15

    We modeled the public health benefits and the change in the spatial inequality of health risk for a number of hypothetical control scenarios for power plants in the United States to determine optimal control strategies. We simulated various ways by which emission reductions of sulfur dioxide (SO{sub 2}), nitrogen oxides, and fine particulate matter (PM2.5) could be distributed to reach national emissions caps. We applied a source-receptor matrix to determine the PM2.5 concentration changes associated with each control scenario and estimated the mortality reductions. We estimated changes in the spatial inequality of health risk using the Atkinson index and other indicators, following previously derived axioms for measuring health risk inequality. In our baseline model, benefits ranged from 17,000-21,000 fewer premature deaths per year across control scenarios. Scenarios with greater health benefits also tended to have greater reductions in the spatial inequality of health risk, as many sources with high health benefits per unit emissions of SO{sub 2} were in areas with high background PM2.5 concentrations. Sensitivity analyses indicated that conclusions were generally robust to the choice of indicator and other model specifications. Our analysis demonstrates an approach for formally quantifying both the magnitude and spatial distribution of health benefits of pollution control strategies, allowing for joint consideration of efficiency and equity.

  20. Evaluation of pilot-scale air pollution control devices on a municipal waterfall incinerator. Project report, June 1978-June 1980

    SciTech Connect

    Hall, F.D.; Bruck, J.M.; Albrinck, D.N.

    1985-10-01

    The project report describes the results of a program for the testing of two pilot-scale pollution control devices, a fabric filter, and a venturi scrubber at the Braintree, Massachusetts Municipal Solid Waste Incinerator. It includes operation, sampling, and analytical efforts and outlines the plant operating conditions at the time of testing of the two pilot control devices. The Braintree Municipal Incinerator is a mass-burn, water-wall type consisting of two furnaces, each designed to burn 4.7 Mg (5 tons) per hour of unprocessed refuse.

  1. Leaching characteristics of calcium-based compounds in MSWI Residues: From the viewpoint of clogging risk

    SciTech Connect

    Xia, Yi; Zhang, Hua; Phoungthong, Khamphe; Shi, Dong-Xiao; Shen, Wen-Hui; Shao, Li-Ming; He, Pin-Jing

    2015-08-15

    Highlights: • The leaching behavior of Ca-based compounds commonly in MSWI residues was studied. • pH is the crucial factor for calcium leaching process. • CaCO{sub 3} was the most sensitive to leaching temperature and Ca{sub 3}(PO{sub 4}){sub 2} was the least. • Ca leaching of MSWIBA and SAPCR attributed to CaCO{sub 3} and Ca{sub 3}(PO{sub 4}){sub 2} respectively. • Potential clogging ability of MSWI residues leachate in open air was calculated. - Abstract: Leachate collection system (LCS) clogging caused by calcium precipitation would be disadvantageous to landfill stability and operation. Meanwhile, calcium-based compounds are the main constituents in both municipal solid waste incineration bottom ash (MSWIBA) and stabilized air pollution control residues (SAPCR), which would increase the risk of LCS clogging once these calcium-rich residues were disposed in landfills. The leaching behaviors of calcium from the four compounds and municipal solid waste incineration (MSWI) residues were studied, and the influencing factors on leaching were discussed. The results showed that pH was the crucial factor in the calcium leaching process. CaCO{sub 3} and CaSiO{sub 3} began leaching when the leachate pH decreased to less than 7 and 10, respectively, while Ca{sub 3}(PO{sub 4}){sub 2} leached at pH < 12. CaSO{sub 4} could hardly dissolve in the experimental conditions. Moreover, the sequence of the leaching rate for the different calcium-based compounds is as follows: CaSiO{sub 3} > Ca{sub 3}(PO{sub 4}){sub 2} > CaCO{sub 3}. The calcium leaching from the MSWIBA and SAPCR separately started from pH < 7 and pH < 12, resulting from CaCO{sub 3} and Ca{sub 3}(PO{sub 4}){sub 2} leaching respectively, which was proven by the X-ray diffraction results. Based on the leaching characteristics of the different calcium compounds and the mineral phase of calcium in the incineration residues, simulated computation of their clogging potential was conducted, providing the

  2. Controlling dioxins from municipal waste combustion

    SciTech Connect

    Hasselriis, F.

    1995-07-01

    Improved combustion practices and air pollution control research within the past decade have made MWCs a minor- and diminishing -source of dioxins in the environment. This article describes air pollution controls which have reduced the amount of dioxin releases. Topics include: dioxin and furan formation; controlling dioxin emissions; effective control in units with scrubber/baghouses; reducing APC system temperatures; effectiveness of activated carbon injection; reductions at existing facilities with ESPs; will reducing the feed chlorine work?. 35 refs., 5 figs.

  3. Dietary acrylamide intake and the risk of colorectal cancer with specific mutations in KRAS and APC.

    PubMed

    Hogervorst, Janneke G F; de Bruijn-Geraets, Daisy; Schouten, Leo J; van Engeland, Manon; de Kok, Theo M C M; Goldbohm, R Alexandra; van den Brandt, Piet A; Weijenberg, Matty P

    2014-05-01

    Acrylamide, a probable human carcinogen, is present in heat-treated carbohydrate-rich foods. Epidemiological studies have not shown a clear association between acrylamide intake and colorectal cancer (CRC) risk. This may be due to the molecular heterogeneity in colorectal tumors, which was not taken into consideration before. Since the acrylamide metabolite glycidamide induces specific DNA mutations in rodents, we investigated whether acrylamide is associated with CRC risk characterized by mutations in Kirsten-ras (KRAS) and adenomatous polyposis coli (APC); key genes in colorectal carcinogenesis. This case-cohort analysis, within the Netherlands Cohort Study on diet and cancer, was based on 7.3 years of follow-up. Acrylamide intake was assessed with a food frequency questionnaire. Mutation analysis of codons 1286-1520 in exon 15 in APC and codons 12 and 13 in exon 1 in KRAS was performed on tumor tissue of 733 cases. Hazard ratios (HR) were calculated using Cox proportional hazards analysis. Among men, acrylamide intake was statistically significantly associated with an increased risk of particularly tumors with an activating KRAS mutation {HR fourth versus first quartile: 2.12 [95% confidence interval (CI): 1.16-3.87], P trend: 0.01}. Among women, acrylamide intake was statistically significantly associated with a decreased risk of particularly tumors with a truncating APC mutation (fourth versus first quartile: 0.47 (95% CI: 0.23-0.94), P trend: 0.02), but only in the highest quartile of intake. This is the first study to show that acrylamide might be associated with CRC with specific somatic mutations, differentially in men and women. More research is needed to corroborate or refute these findings.

  4. New origin firing is inhibited by APC/CCdh1 activation in S-phase after severe replication stress.

    PubMed

    Ercilla, Amaia; Llopis, Alba; Feu, Sonia; Aranda, Sergi; Ernfors, Patrik; Freire, Raimundo; Agell, Neus

    2016-06-01

    Defects in DNA replication and repair are known to promote genomic instability, a hallmark of cancer cells. Thus, eukaryotic cells have developed complex mechanisms to ensure accurate duplication of their genomes. While DNA damage response has been extensively studied in tumour cells, the pathways implicated in the response to replication stress are less well understood especially in non-transformed cells. Here we show that in non-transformed cells, APC/C(Cdh1) is activated upon severe replication stress. Activation of APC/C(Cdh1) prevents new origin firing and induces permanent arrest in S-phase. Moreover, Rad51-mediated homologous recombination is also impaired under these conditions. APC/C(Cdh1) activation in S-phase occurs after replication forks have been processed into double strand breaks. Remarkably, this activation, which correlates with decreased Emi1 levels, is not prevented by ATR/ATM inhibition, but it is abrogated in cells depleted of p53 or p21. Importantly, we found that the lack of APC/C(Cdh1) activity correlated with an increase in genomic instability. Taken together, our results define a new APC/C(Cdh1) function that prevents cell cycle resumption after prolonged replication stress by inhibiting origin firing, which may act as an additional mechanism in safeguarding genome integrity. PMID:26939887

  5. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner.

    PubMed

    Song, Min Sup; Carracedo, Arkaitz; Salmena, Leonardo; Song, Su Jung; Egia, Ainara; Malumbres, Marcos; Pandolfi, Pier Paolo

    2011-01-21

    PTEN is a frequently mutated tumor suppressor gene that opposes the PI3K/AKT pathway through dephosphorylation of phosphoinositide-3,4,5-triphosphate. Recently, nuclear compartmentalization of PTEN was found as a key component of its tumor-suppressive activity; however its nuclear function remains poorly defined. Here we show that nuclear PTEN interacts with APC/C, promotes APC/C association with CDH1, and thereby enhances the tumor-suppressive activity of the APC-CDH1 complex. We find that nuclear exclusion but not phosphatase inactivation of PTEN impairs APC-CDH1. This nuclear function of PTEN provides a straightforward mechanistic explanation for the fail-safe cellular senescence response elicited by acute PTEN loss and the tumor-suppressive activity of catalytically inactive PTEN. Importantly, we demonstrate that PTEN mutant and PTEN null states are not synonymous as they are differentially sensitive to pharmacological inhibition of APC-CDH1 targets such as PLK1 and Aurora kinases. This finding identifies a strategy for cancer patient stratification and, thus, optimization of targeted therapies. PAPERCLIP:

  6. Nuclear PTEN regulates the APC-CDH1 tumor suppressive complex in a phosphatase-independent manner

    PubMed Central

    Song, Min Sup; Carracedo, Arkaitz; Salmena, Leonardo; Song, Su Jung; Egia, Ainara; Malumbres, Marcos; Pandolfi, Pier Paolo

    2011-01-01

    SUMMARY PTEN is a frequently mutated tumor suppressor gene that opposes the PI3K-AKT pathway through dephosphorylation of phosphoinositide-3,4,5-triphosphate. Recently, nuclear compartmentalization of PTEN was found as a key component of its tumor suppressive activity, however its nuclear function remains poorly defined. Here we show that nuclear PTEN interacts with APC/C, promotes APC/C association with CDH1, and thereby enhances the tumor suppressive activity of the APC-CDH1 complex. We find that nuclear exclusion but not phosphatase inactivation of PTEN impairs APC-CDH1. This nuclear function of PTEN provides a straightforward mechanistic explanation for the fail-safe cellular senescence response elicited by acute PTEN loss and the tumor suppressive activity of catalytically-inactive PTEN. Importantly, we demonstrate that PTEN-mutant and PTEN-null states are not synonymous since they are differentially sensitive to pharmacological inhibition of APC-CDH1 targets such as PLK1 and Aurora Kinases. This finding identifies a strategy for cancer patient stratification and thus, optimization of targeted therapies. PMID:21241890

  7. Insights into Degron Recognition by APC/C Coactivators from the Structure of an Acm1-Cdh1 Complex

    PubMed Central

    He, Jun; Chao, William C.H.; Zhang, Ziguo; Yang, Jing; Cronin, Nora; Barford, David

    2013-01-01

    Summary The anaphase-promoting complex/cyclosome (APC/C) regulates sister chromatid segregation and the exit from mitosis. Selection of most APC/C substrates is controlled by coactivator subunits (either Cdc20 or Cdh1) that interact with substrate destruction motifs—predominantly the destruction (D) box and KEN box degrons. How coactivators recognize D box degrons and how this is inhibited by APC/C regulatory proteins is not defined at the atomic level. Here, from the crystal structure of S. cerevisiae Cdh1 in complex with its specific inhibitor Acm1, which incorporates D and KEN box pseudosubstrate motifs, we describe the molecular basis for D box recognition. Additional interactions between Acm1 and Cdh1 identify a third protein-binding site on Cdh1 that is likely to confer coactivator-specific protein functions including substrate association. We provide a structural rationalization for D box and KEN box recognition by coactivators and demonstrate that many noncanonical APC/C degrons bind APC/C coactivators at the D box coreceptor. PMID:23707760

  8. APC/C and retinoblastoma interaction: cross-talk of retinoblastoma protein with the ubiquitin proteasome pathway.

    PubMed

    Ramanujan, Ajeena; Tiwari, Swati

    2016-10-01

    The ubiquitin (Ub) ligase anaphase promoting complex/cyclosome (APC/C) and the tumour suppressor retinoblastoma protein (pRB) play key roles in cell cycle regulation. APC/C is a critical regulator of mitosis and G1-phase of the cell cycle whereas pRB keeps a check on proliferation by inhibiting transition to the S-phase. APC/C and pRB interact with each other via the co-activator of APC/C, FZR1, providing an alternative pathway of regulation of G1 to S transition by pRB using a post-translational mechanism. Both pRB and FZR1 have complex roles and are implicated not only in regulation of cell proliferation but also in differentiation, quiescence, apoptosis, maintenance of chromosomal integrity and metabolism. Both are also targeted by transforming viruses. We discuss recent advances in our understanding of the involvement of APC/C and pRB in cell cycle based decisions and how these insights will be useful for development of anti-cancer and anti-viral drugs.

  9. Intestinal APCs of the endogenous nanomineral pathway fail to express PD-L1 in Crohn’s disease

    PubMed Central

    Robertson, Jack; Haas, Carolin T.; Pele, Laetitia C.; Monie, Tom P.; Charalambos, Charles; Parkes, Miles; Hewitt, Rachel E.; Powell, Jonathan J.

    2016-01-01

    Crohn’s disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn’s disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn’s disease show selective failure in PD-L1 expression. Therefore, in Crohn’s disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease. PMID:27226337

  10. Irreversible APC(Cdh1) Inactivation Underlies the Point of No Return for Cell-Cycle Entry.

    PubMed

    Cappell, Steven D; Chung, Mingyu; Jaimovich, Ariel; Spencer, Sabrina L; Meyer, Tobias

    2016-06-30

    Proliferating cells must cross a point of no return before they replicate their DNA and divide. This commitment decision plays a fundamental role in cancer and degenerative diseases and has been proposed to be mediated by phosphorylation of retinoblastoma (Rb) protein. Here, we show that inactivation of the anaphase-promoting complex/cyclosome (APC(Cdh1)) has the necessary characteristics to be the point of no return for cell-cycle entry. Our study shows that APC(Cdh1) inactivation is a rapid, bistable switch initiated shortly before the start of DNA replication by cyclin E/Cdk2 and made irreversible by Emi1. Exposure to stress between Rb phosphorylation and APC(Cdh1) inactivation, but not after APC(Cdh1) inactivation, reverted cells to a mitogen-sensitive quiescent state, from which they can later re-enter the cell cycle. Thus, APC(Cdh1) inactivation is the commitment point when cells lose the ability to return to quiescence and decide to progress through the cell cycle. PMID:27368103

  11. The Cdk1-APC/C cell cycle oscillator circuit functions as a time-delayed, ultrasensitive switch

    PubMed Central

    Yang, Qiong; Ferrell, James E.

    2013-01-01

    Despite the complexity and variety of biological oscillators, their core design invariably includes an essential negative feedback loop. In the Xenopus laevis embryonic cell cycle oscillator, this loop consists of the kinase cyclin B-Cdk1 and the ubiquitin ligase APC/CCdc20; active Cdk1 activates APC/CCdc20, which then brings about cyclin B degradation and inactivates Cdk1. Here we ask how this negative feedback loop functions quantitatively, with the aim of understanding what mechanisms keep the Cdk1-APC/CCdc20 system from settling into a stable steady state with intermediate levels of Cdk1 and APC/CCdc20 activity. We found that the system operates as a time-delayed, digital switch, with a time lag of ~15 min between Cdk1 and APC/CCdc20 activation and a tremendously high degree of ultrasensitivity (nH ≈ 17). Computational modeling shows how these attributes contribute to the generation of robust, clock-like oscillations. Principles uncovered here may also apply to other activator-repressor oscillators and help in designing robust synthetic clocks. PMID:23624406

  12. APC/C and retinoblastoma interaction: cross-talk of retinoblastoma protein with the ubiquitin proteasome pathway

    PubMed Central

    Ramanujan, Ajeena; Tiwari, Swati

    2016-01-01

    The ubiquitin (Ub) ligase anaphase promoting complex/cyclosome (APC/C) and the tumour suppressor retinoblastoma protein (pRB) play key roles in cell cycle regulation. APC/C is a critical regulator of mitosis and G1-phase of the cell cycle whereas pRB keeps a check on proliferation by inhibiting transition to the S-phase. APC/C and pRB interact with each other via the co-activator of APC/C, FZR1, providing an alternative pathway of regulation of G1 to S transition by pRB using a post-translational mechanism. Both pRB and FZR1 have complex roles and are implicated not only in regulation of cell proliferation but also in differentiation, quiescence, apoptosis, maintenance of chromosomal integrity and metabolism. Both are also targeted by transforming viruses. We discuss recent advances in our understanding of the involvement of APC/C and pRB in cell cycle based decisions and how these insights will be useful for development of anti-cancer and anti-viral drugs. PMID:27402801

  13. Intestinal APCs of the endogenous nanomineral pathway fail to express PD-L1 in Crohn's disease.

    PubMed

    Robertson, Jack; Haas, Carolin T; Pele, Laetitia C; Monie, Tom P; Charalambos, Charles; Parkes, Miles; Hewitt, Rachel E; Powell, Jonathan J

    2016-05-26

    Crohn's disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn's disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn's disease show selective failure in PD-L1 expression. Therefore, in Crohn's disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease.

  14. APC/C and SCF(cyclin F) Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry.

    PubMed

    Choudhury, Rajarshi; Bonacci, Thomas; Arceci, Anthony; Lahiri, Debojyoti; Mills, Christine A; Kernan, Jennifer L; Branigan, Timothy B; DeCaprio, James A; Burke, Daniel J; Emanuele, Michael J

    2016-09-20

    The anaphase promoting complex/cyclosome (APC/C) is an ubiquitin ligase and core component of the cell-cycle oscillator. During G1 phase, APC/C binds to its substrate receptor Cdh1 and APC/C(Cdh1) plays an important role in restricting S-phase entry and maintaining genome integrity. We describe a reciprocal feedback circuit between APC/C and a second ubiquitin ligase, the SCF (Skp1-Cul1-F box). We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1. These data indicate that the coordinated, temporal ordering of cyclin F and Cdh1 degradation, organized in a double-negative feedback loop, represents a fundamental aspect of cell-cycle control. This mutual antagonism could be a feature of other oscillating systems.

  15. Irreversible APC(Cdh1) Inactivation Underlies the Point of No Return for Cell-Cycle Entry.

    PubMed

    Cappell, Steven D; Chung, Mingyu; Jaimovich, Ariel; Spencer, Sabrina L; Meyer, Tobias

    2016-06-30

    Proliferating cells must cross a point of no return before they replicate their DNA and divide. This commitment decision plays a fundamental role in cancer and degenerative diseases and has been proposed to be mediated by phosphorylation of retinoblastoma (Rb) protein. Here, we show that inactivation of the anaphase-promoting complex/cyclosome (APC(Cdh1)) has the necessary characteristics to be the point of no return for cell-cycle entry. Our study shows that APC(Cdh1) inactivation is a rapid, bistable switch initiated shortly before the start of DNA replication by cyclin E/Cdk2 and made irreversible by Emi1. Exposure to stress between Rb phosphorylation and APC(Cdh1) inactivation, but not after APC(Cdh1) inactivation, reverted cells to a mitogen-sensitive quiescent state, from which they can later re-enter the cell cycle. Thus, APC(Cdh1) inactivation is the commitment point when cells lose the ability to return to quiescence and decide to progress through the cell cycle.

  16. New origin firing is inhibited by APC/CCdh1 activation in S-phase after severe replication stress.

    PubMed

    Ercilla, Amaia; Llopis, Alba; Feu, Sonia; Aranda, Sergi; Ernfors, Patrik; Freire, Raimundo; Agell, Neus

    2016-06-01

    Defects in DNA replication and repair are known to promote genomic instability, a hallmark of cancer cells. Thus, eukaryotic cells have developed complex mechanisms to ensure accurate duplication of their genomes. While DNA damage response has been extensively studied in tumour cells, the pathways implicated in the response to replication stress are less well understood especially in non-transformed cells. Here we show that in non-transformed cells, APC/C(Cdh1) is activated upon severe replication stress. Activation of APC/C(Cdh1) prevents new origin firing and induces permanent arrest in S-phase. Moreover, Rad51-mediated homologous recombination is also impaired under these conditions. APC/C(Cdh1) activation in S-phase occurs after replication forks have been processed into double strand breaks. Remarkably, this activation, which correlates with decreased Emi1 levels, is not prevented by ATR/ATM inhibition, but it is abrogated in cells depleted of p53 or p21. Importantly, we found that the lack of APC/C(Cdh1) activity correlated with an increase in genomic instability. Taken together, our results define a new APC/C(Cdh1) function that prevents cell cycle resumption after prolonged replication stress by inhibiting origin firing, which may act as an additional mechanism in safeguarding genome integrity.

  17. Substrate Recognition by the Cdh1 Destruction Box Receptor Is a General Requirement for APC/CCdh1-mediated Proteolysis.

    PubMed

    Qin, Liang; Guimarães, Dimitrius Santiago P S F; Melesse, Michael; Hall, Mark C

    2016-07-22

    The anaphase-promoting complex, or cyclosome (APC/C), is a ubiquitin ligase that selectively targets proteins for degradation in mitosis and the G1 phase and is an important component of the eukaryotic cell cycle control system. How the APC/C specifically recognizes its substrates is not fully understood. Although well characterized degron motifs such as the destruction box (D-box) and KEN-box are commonly found in APC/C substrates, many substrates apparently lack these motifs. A variety of alternative APC/C degrons have been reported, suggesting either that multiple modes of substrate recognition are possible or that our definitions of degron structure are incomplete. We used an in vivo yeast assay to compare the G1 degradation rate of 15 known substrates of the APC/C co-activator Cdh1 under normal conditions and conditions that impair binding of D-box, KEN-box, and the recently identified ABBA motif degrons to Cdh1. The D-box receptor was required for efficient proteolysis of all Cdh1 substrates, despite the absence of canonical D-boxes in many. In contrast, the KEN-box receptor was only required for normal proteolysis of a subset of substrates and the ABBA motif receptor for a single substrate in our system. Our results suggest that binding to the D-box receptor may be a shared requirement for recognition and processing of all Cdh1 substrates.

  18. APC/C and SCF(cyclin F) Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry.

    PubMed

    Choudhury, Rajarshi; Bonacci, Thomas; Arceci, Anthony; Lahiri, Debojyoti; Mills, Christine A; Kernan, Jennifer L; Branigan, Timothy B; DeCaprio, James A; Burke, Daniel J; Emanuele, Michael J

    2016-09-20

    The anaphase promoting complex/cyclosome (APC/C) is an ubiquitin ligase and core component of the cell-cycle oscillator. During G1 phase, APC/C binds to its substrate receptor Cdh1 and APC/C(Cdh1) plays an important role in restricting S-phase entry and maintaining genome integrity. We describe a reciprocal feedback circuit between APC/C and a second ubiquitin ligase, the SCF (Skp1-Cul1-F box). We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1. These data indicate that the coordinated, temporal ordering of cyclin F and Cdh1 degradation, organized in a double-negative feedback loop, represents a fundamental aspect of cell-cycle control. This mutual antagonism could be a feature of other oscillating systems. PMID:27653696

  19. Liver inflammation and metabolic signaling in ApcMin/+ mice: the role of cachexia progression.

    PubMed

    Narsale, Aditi A; Enos, Reilly T; Puppa, Melissa J; Chatterjee, Saurabh; Murphy, E Angela; Fayad, Raja; Pena, Majorette O'; Durstine, J Larry; Carson, James A

    2015-01-01

    The ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER)-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia) was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein), IRE-1α (endoplasmic reticulum to nucleus signaling 1), and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3). While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase) and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase) activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3). Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin), despite a suppression of Akt (thymoma viral proto-oncogene 1) and S6 (ribosomal protein S6) phosphorylation. Thus, cancer

  20. The ubiquitin ligase APC/CCdh1 puts the brakes on DNA-end resection

    PubMed Central

    Lafranchi, Lorenzo; Sartori, Alessandro A

    2015-01-01

    DNA double-strand breaks (DSBs) are highly deleterious lesions and their misrepair can promote genomic instability, a hallmark of cancer. DNA-end resection is a cell cycle-regulated mechanism that is required for the faithful repair of DSBs. We recently discovered that the anaphase-promoting complex/cyclosome-Cdh1 (APC/CCdh1) ubiquitin ligase is responsible for the timely degradation of CtBP-interacting protein (CtIP), a key DNA-end resection factor, providing a new layer of regulation of DSB repair in human cells. PMID:27308488

  1. Ink-jetting AJL8/APC for D-fiber electric field sensors.

    PubMed

    Kvavle, Joshua; Schultz, Stephen; Selfridge, Richard

    2009-10-01

    Spin casting electro-optic polymers for in-fiber device fabrication is problematic due to the flexibility and high-contrast topography of optical fibers. An ink-jetting method is developed for the deposition of AJL8/APC using a commercially available printer. The method results in more consistent control of film thickness and uses 1000 times less material than the spin-coating method. A D-fiber electric field sensor is fabricated using this deposition method and exhibits a sensitivity of 157 V/(m square root(Hz)) at a modulation frequency of 6 GHz.

  2. 1H, 13C, and 15N backbone, side-chain, and heme chemical shift assignments for oxidized and reduced forms of the monoheme c-type cytochrome ApcA isolated from the acidophilic metal-reducing bacterium Acidiphilium cryptum.

    SciTech Connect

    Cort, John R.; Swenson, Michael; Magnuson, Timothy S.

    2011-03-04

    We report the 1H, 13C, and 15N chemical shift assignments of both oxidized and reduced forms of an abundant periplasmic c-type cytochrome, designated ApcA, from the acidophilic gram-negative facultatively anaerobic metal-reducing alpha-proteobacterium Acidiphilium cryptum. These resonance assignments prove that ApcA is a monoheme cytochrome c2 and the product of the Acry_2099 gene. An absence of resonance peaks in the NMR spectra for the 21 N-terminal residues suggests that a predicted N-terminal signal sequence is cleaved. We also describe the preparation and purification of the protein in labeled form from laboratory cultures of A. cryptum growing on 13C- and 15N- labeled substrates.

  3. The Poly(ADP-ribose) Polymerase Enzyme Tankyrase Antagonizes Activity of the β-Catenin Destruction Complex through ADP-ribosylation of Axin and APC2.

    PubMed

    Croy, Heather E; Fuller, Caitlyn N; Giannotti, Jemma; Robinson, Paige; Foley, Andrew V A; Yamulla, Robert J; Cosgriff, Sean; Greaves, Bradford D; von Kleeck, Ryan A; An, Hyun Hyung; Powers, Catherine M; Tran, Julie K; Tocker, Aaron M; Jacob, Kimberly D; Davis, Beckley K; Roberts, David M

    2016-06-10

    Most colon cancer cases are initiated by truncating mutations in the tumor suppressor, adenomatous polyposis coli (APC). APC is a critical negative regulator of the Wnt signaling pathway that participates in a multi-protein "destruction complex" to target the key effector protein β-catenin for ubiquitin-mediated proteolysis. Prior work has established that the poly(ADP-ribose) polymerase (PARP) enzyme Tankyrase (TNKS) antagonizes destruction complex activity by promoting degradation of the scaffold protein Axin, and recent work suggests that TNKS inhibition is a promising cancer therapy. We performed a yeast two-hybrid (Y2H) screen and uncovered TNKS as a putative binding partner of Drosophila APC2, suggesting that TNKS may play multiple roles in destruction complex regulation. We find that TNKS binds a C-terminal RPQPSG motif in Drosophila APC2, and that this motif is conserved in human APC2, but not human APC1. In addition, we find that APC2 can recruit TNKS into the β-catenin destruction complex, placing the APC2/TNKS interaction at the correct intracellular location to regulate β-catenin proteolysis. We further show that TNKS directly PARylates both Drosophila Axin and APC2, but that PARylation does not globally regulate APC2 protein levels as it does for Axin. Moreover, TNKS inhibition in colon cancer cells decreases β-catenin signaling, which we find cannot be explained solely through Axin stabilization. Instead, our findings suggest that TNKS regulates destruction complex activity at the level of both Axin and APC2, providing further mechanistic insight into TNKS inhibition as a potential Wnt pathway cancer therapy. PMID:27068743

  4. A functional network of the tumor suppressors APC, hDlg, and PTEN, that relies on recognition of specific PDZ-domains.

    PubMed

    Sotelo, Natalia S; Valiente, Miguel; Gil, Anabel; Pulido, Rafael

    2012-08-01

    APC and PTEN are tumor suppressor proteins that bind through their C-termini to the PDZ domain containing-hDlg scaffolding protein. We have found that co-expression of PTEN and hDlg enhanced the negative regulation of the PI3K/Akt pathway by PTEN, indicating the physiologic importance of these interactions. APC and PTEN share other PDZ domain containing-interacting partners, including the MAGI scaffolding proteins and the MAST family of protein kinases. Mutational analysis revealed that the C-terminal PDZ-binding motifs from APC and PTEN were differentially recognized by distinct PDZ domains. APC bound to the three PDZ domains from hDlg, whereas PTEN mainly bound to PDZ-2/hDlg. This indicates the existence of overlapping, but distinct PDZ-domain recognition patterns by APC and PTEN. Furthermore, a ternary complex formed by APC, PTEN, and hDlg was detected, suggesting that hDlg may serve as a platform to bring in proximity APC and PTEN tumor suppressor activities. In line with this, tumor-related mutations targeting the PDZ-2/hDlg domain diminished its interaction with APC and PTEN. Our results expand the PDZ-domain counterparts for the tumor suppressor APC, show that APC and PTEN share PDZ-domain partners but have individual molecular determinants for specific recognition of PDZ domains, and suggest the participation of the tumor suppressors APC, PTEN, and hDlg in PDZ-domain interaction networks which may be relevant in oncogenesis.

  5. Testing Models of the APC Tumor Suppressor/β-Catenin Interaction Reshapes Our View of the Destruction Complex in Wnt Signaling

    PubMed Central

    Yamulla, Robert J.; Kane, Eric G.; Moody, Alexandra E.; Politi, Kristin A.; Lock, Nicole E.; Foley, Andrew V. A.; Roberts, David M.

    2014-01-01

    The Wnt pathway is a conserved signal transduction pathway that contributes to normal development and adult homeostasis, but is also misregulated in human diseases such as cancer. The tumor suppressor adenomatous polyposis coli (APC) is an essential negative regulator of Wnt signaling inactivated in >80% of colorectal cancers. APC participates in a multiprotein “destruction complex” that targets the proto-oncogene β-catenin for ubiquitin-mediated proteolysis; however, the mechanistic role of APC in the destruction complex remains unknown. Several models of APC function have recently been proposed, many of which have emphasized the importance of phosphorylation of high-affinity β-catenin-binding sites [20-amino-acid repeats (20Rs)] on APC. Here we test these models by generating a Drosophila APC2 mutant lacking all β-catenin-binding 20Rs and performing functional studies in human colon cancer cell lines and Drosophila embryos. Our results are inconsistent with current models, as we find that β-catenin binding to the 20Rs of APC is not required for destruction complex activity. In addition, we generate an APC2 mutant lacking all β-catenin-binding sites (including the 15Rs) and find that a direct β-catenin/APC interaction is also not essential for β-catenin destruction, although it increases destruction complex efficiency in certain developmental contexts. Overall, our findings support a model whereby β-catenin-binding sites on APC do not provide a critical mechanistic function per se, but rather dock β-catenin in the destruction complex to increase the efficiency of β-catenin destruction. Furthermore, in Drosophila embryos expressing some APC2 mutant transgenes we observe a separation of β-catenin destruction and Wg/Wnt signaling outputs and suggest that cytoplasmic retention of β-catenin likely accounts for this difference. PMID:24931405

  6. Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

    PubMed Central

    Fatehullah, A.; Sharma, S.; Newton, I. P.; Langlands, A. J.; Lay, H.; Nelson, S. A.; McMahon, R. K.; McIlvenny, N.; Appleton, P. L.; Cochran, S.; Näthke, I. S.

    2016-01-01

    Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic. PMID:27406832

  7. Dietary Methyl Donor Depletion Protects Against Intestinal Tumorigenesis in ApcMin/+ Mice

    PubMed Central

    Kadaveru, Krishna; Protiva, Petr; Greenspan, Emily J; Kim, Young-In; Rosenberg, Daniel W

    2012-01-01

    Despite recent population data, the influence of dietary folate supplementation on colon cancer risk remains controversial. This study examines the effects of folate deficiency, in combination with choline, methionine and vitamin B12 depletion, on intestinal tumorigenesis in ApcMin/+ mice. Methyl donor sufficient (MDS) and deficient (MDD) diets were started at 5 or 10 weeks of age and tumors evaluated at 16 weeks. MDD suppressed intestinal tumor formation in ApcMin/+ mice (~80%) when started at 5 weeks of age. The protective effect was lost when MDD was initiated at 10 weeks of age, indicating an important time-dependency on cancer suppression. Concomitant with cancer protection, MDD restricted body weight gain. Therefore, a second study was conducted in which MDS was given ad libitum or pair-fed with MDD. While small intestinal tumors were reduced 54% in pair-fed MDS mice, MDD caused a further reduction (96%). In colon, although MDD did not affect tumor numbers, tumor size was reduced. Gene expression profiling of normal-appearing colonic mucosa after 11 weeks on MDD identified a total of 493 significantly down-regulated genes relative to the MDS group. Pathway analysis placed many of these genes within general categories of inflammatory signaling and cell cycle regulation, consistent with recently published human data obtained during folate depletion (1). Further studies are warranted to investigate the complex interplay of methyl donor status and cancer protection in high-risk populations. PMID:22677908

  8. APC/C-CCS52A complexes control meristem maintenance in the Arabidopsis root.

    PubMed

    Vanstraelen, Marleen; Baloban, Mikhail; Da Ines, Olivier; Cultrone, Antonietta; Lammens, Tim; Boudolf, Véronique; Brown, Spencer C; De Veylder, Lieven; Mergaert, Peter; Kondorosi, Eva

    2009-07-14

    Plant organs originate from meristems where stem cells are maintained to produce continuously daughter cells that are the source of different cell types. The cell cycle switch gene CCS52A, a substrate specific activator of the anaphase promoting complex/cyclosome (APC/C), controls the mitotic arrest and the transition of mitotic cycles to endoreduplication (ER) cycles as part of cell differentiation. Arabidopsis, unlike other organisms, contains 2 CCS52A isoforms. Here, we show that both of them are active and regulate meristem maintenance in the root tip, although through different mechanisms. The CCS52A1 activity in the elongation zone of the root stimulates ER and mitotic exit, and contributes to the border delineation between dividing and expanding cells. In contrast, CCS52A2 acts directly in the distal region of the root meristem to control identity of the quiescent center (QC) cells and stem cell maintenance. Cell proliferation assays in roots suggest that this control involves CCS52A2 mediated repression of mitotic activity in the QC cells. The data indicate that the CCS52A genes favor a low mitotic state in different cell types of the root tip that is required for meristem maintenance, and reveal a previously undescribed mechanism for APC/C mediated control in plant development.

  9. Polo-Like Kinase-1 Controls Aurora A Destruction by Activating APC/C-Cdh1

    PubMed Central

    van Leuken, Renske; Lim, Dan; Yao, XueBiao; Wolthuis, Rob M. F.; Yaffe, Michael B.; Medema, René H.; van Vugt, Marcel A. T. M.

    2009-01-01

    Polo-like kinase-1 (Plk1) is activated before mitosis by Aurora A and its cofactor Bora. In mitosis, Bora is degraded in a manner dependent on Plk1 kinase activity and the E3 ubiquitin ligase SCF-βTrCP. Here, we show that Plk1 is also required for the timely destruction of its activator Aurora A in late anaphase. It has been shown that Aurora A destruction is controlled by the auxiliary subunit Cdh1 of the Anaphase-Promoting Complex/Cyclosome (APC/C). Remarkably, we found that Plk1-depletion prevented the efficient dephosphorylation of Cdh1 during mitotic exit. Plk1 mediated its effect on Cdh1, at least in part, through direct phosphorylation of the human phosphatase Cdc14A, controlling the phosphorylation state of Cdh1. We conclude that Plk1 facilitates efficient Aurora A degradation through APC/C-Cdh1 activation after mitosis, with a potential role for hCdc14A. PMID:19390576

  10. Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene.

    PubMed Central

    Eccles, D. M.; van der Luijt, R.; Breukel, C.; Bullman, H.; Bunyan, D.; Fisher, A.; Barber, J.; du Boulay, C.; Primrose, J.; Burn, J.; Fodde, R.

    1996-01-01

    Desmoid tumors are slowly growing fibrous tumors highly resistant to therapy and often fatal. Here, we report hereditary desmoid disease (HDD), a novel autosomal dominant trait with 100% penetrance affecting a three-generation kindred. Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early development of premalignant adenomatous polyps in the colorectum due to chain-terminating mutations of the APC gene. In general, one or more members in approximately 10% of the FAP families manifest desmoid tumors. Affected individuals from the HDD kindred are characterized by multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Osteomas, epidermal cysts, and other congenital features were also observed. We show that HDD segregates with an unusual germ-line chain-terminating mutation at the 3' end of the APC gene (codon 1924) with somatic loss of the wild-type allele leading to tumor development. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:8940264

  11. Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

    NASA Astrophysics Data System (ADS)

    Fatehullah, A.; Sharma, S.; Newton, I. P.; Langlands, A. J.; Lay, H.; Nelson, S. A.; McMahon, R. K.; McIlvenny, N.; Appleton, P. L.; Cochran, S.; Näthke, I. S.

    2016-07-01

    Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

  12. Lovastatin, but not orlistat, reduces intestinal polyp volume in an ApcMin/+ mouse model.

    PubMed

    Notarnicola, Maria; Barone, Michele; Francavilla, Antonio; Tutino, Valeria; Bianco, Giusy; Tafaro, Angela; Minoia, Mario; Polimeno, Lorenzo; Napoli, Anna; Scavo, Maria Principia; Caruso, Maria Gabriella

    2016-08-01

    The statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and orlistat, an inhibitor of fatty acid synthase (FAS), inhibit tumor cell growth by restricting cholesterol and fatty acid synthesis, respectively. We previously demonstrated that an omega (ω)-3 polyunsaturated fatty acid (PUFA)- or olive oil-enriched diet reduced the polyp number and volume in ApcMin/+ mice. This phenomenon was associated with a significant inhibition of FAS and HMGCoAR, as well as an increase in the estrogen receptor (ER)β/α ratio. Herein, we evaluated the effect of lovastatin and orlistat on polyp development and ER expression in ApcMin/+ mice, in order to confirm previous data obtained with ω‑3-PUFAs and olive oil. As expected, the use of lovastatin and orlistat significantly reduced HMGCoAR and FAS enzymatic activities and gene expression in colonic tissues, but did not affect the number of intestinal polyps, while there was a statistically significant reduction in polyp volume only in the mouse group treated with lovastatin. In the mice receiving orlistat, we observed a significant increase in cell proliferation in the polyp tissue, as well as enhanced expression of ERα. Moreover, the overexpression of ERα was associated with a statistically significant increase in PES1, Shh and Gli1 protein levels, considered ERα-related molecular targets. PMID:27277576

  13. Cdh1 regulates craniofacial development via APC-dependent ubiquitination and activation of Goosecoid.

    PubMed

    Shao, Rui; Liu, Jia; Yan, Guang; Zhang, Jinfang; Han, Yujiao; Guo, Jianfeng; Xu, Zhan; Yuan, Zhu; Liu, Jiankang; Malumbres, Marcos; Wan, Lixin; Wei, Wenyi; Zou, Weiguo

    2016-06-01

    Craniofacial anomalies (CFAs) characterized by birth defects of skull and facial bones are the most frequent congenital disease. Genomic analysis has identified multiple genes responsible for CFAs; however, the underlying genetic mechanisms for the majority of CFAs remain largely unclear. Our previous study revealed that the Wwp2 E3 ubiquitin ligase facilitates craniofacial development in part through inducing monoubiquitination and activation of the paired-like homeobox transcription factor, Goosecoid (Gsc). Here we report that Gsc is also ubiquitinated and activated by the APC(Cdh1) E3 ubiquitin ligase, leading to transcriptional activation of various Gsc target genes crucial for craniofacial development. Consistenly, neural crest-specific Cdh1-knockout mice display similar bone malformation as Wwp2-deficient mice in the craniofacial region, characterized by a domed skull, a short snout and a twisted nasal bone. Mechanistically, like Wwp2-deficient mice, mice with Cdh1 deficiency in neural crest cells exhibit reduced Gsc/Sox6 transcriptional activities. Simultaneous deletion of Cdh1 and Wwp2 results in a more severe craniofacial defect compared with single gene deletion, suggesting a synergistic augmentation of Gsc activity by these two E3 ubiquitin ligases. Hence, our study reveals a novel role for Cdh1 in craniofacial development through promoting APC-dependent non-proteolytic ubiquitination and activation of Gsc.

  14. Berberine Inhibits Intestinal Polyps Growth in Apc (min/+) Mice via Regulation of Macrophage Polarization

    PubMed Central

    Piao, Meiyu; Cao, Hailong; He, NaNa; Yang, Boli; Dong, Wenxiao; Xu, Mengque; Yan, Fang; Zhou, Bing

    2016-01-01

    Antitumor effect of berberine has been reported in a wide spectrum of cancer, however, the mechanisms of which are not fully understood. The aim of this study was to investigate the hypothesis that berberine suppresses tumorigenesis in the familial adenomatous polyposis (FAP) by regulating the macrophage polarization in Apc (min/+) mouse model. Berberine was given to Apc (min/+) mice for 12 weeks. Primary macrophages were isolated; after berberine treatment, the change in signaling cascade was determined. The total number and size of polyps were reduced remarkably in berberine group, compared with control group. A significant decrease in protein levels of F4/80, mannose receptor (MR), and COX-2 in stroma of intestinal polyps and an increase in the level of iNOS were observed after berberine treatment. The mRNA level of MR and Arg-1 in berberine group was significantly lower than those in IL-10 or IL-4 group, while no significant difference in mRNA levels of iNOS and CXCL10 was observed. The migration and invasiveness assays in vitro showed that berberine could reduce the capability of migration and invasiveness. These findings suggest that berberine attenuates intestinal tumorigenesis by inhibiting the migration and invasion of colorectal tumor cells via regulation of macrophage polarization. PMID:27493671

  15. Berberine Inhibits Intestinal Polyps Growth in Apc (min/+) Mice via Regulation of Macrophage Polarization.

    PubMed

    Piao, Meiyu; Cao, Hailong; He, NaNa; Yang, Boli; Dong, Wenxiao; Xu, Mengque; Yan, Fang; Zhou, Bing; Wang, Bangmao

    2016-01-01

    Antitumor effect of berberine has been reported in a wide spectrum of cancer, however, the mechanisms of which are not fully understood. The aim of this study was to investigate the hypothesis that berberine suppresses tumorigenesis in the familial adenomatous polyposis (FAP) by regulating the macrophage polarization in Apc (min/+) mouse model. Berberine was given to Apc (min/+) mice for 12 weeks. Primary macrophages were isolated; after berberine treatment, the change in signaling cascade was determined. The total number and size of polyps were reduced remarkably in berberine group, compared with control group. A significant decrease in protein levels of F4/80, mannose receptor (MR), and COX-2 in stroma of intestinal polyps and an increase in the level of iNOS were observed after berberine treatment. The mRNA level of MR and Arg-1 in berberine group was significantly lower than those in IL-10 or IL-4 group, while no significant difference in mRNA levels of iNOS and CXCL10 was observed. The migration and invasiveness assays in vitro showed that berberine could reduce the capability of migration and invasiveness. These findings suggest that berberine attenuates intestinal tumorigenesis by inhibiting the migration and invasion of colorectal tumor cells via regulation of macrophage polarization. PMID:27493671

  16. A novel approach to assess the spontaneous gastrointestinal bleeding risk of antithrombotic agents using Apc(min/+) mice.

    PubMed

    Wei, Huijun; Shang, Jin; Keohane, CarolAnn; Wang, Min; Li, Qiu; Ni, Weihua; O'Neill, Kim; Chintala, Madhu

    2014-06-01

    Assessment of the bleeding risk of antithrombotic agents is usually performed in healthy animals with some form of vascular injury to peripheral organs to induce bleeding. However, bleeding observed in patients with currently marketed antithrombotic drugs is typically spontaneous in nature such as intracranial haemorrhage (ICH) and gastrointestinal (GI) bleeding, which happens most frequently on top of preexisting pathologies such as GI ulcerations and polyps. Apc(min/+) mice are reported to develop multiple adenomas through the entire intestinal tract and display progressive anaemia.In this study, we evaluated the potential utility of Apc(min/+) mice as a model for assessing spontaneous GI bleeding with antithrombotic agents. Apc(min/+) mice exhibited progressive blood loss starting at the age of nine weeks. Despite the increase in bleeding, Apc(min/+) mice were in a hypercoagulable state and displayed an age-dependent increase in thrombin generation and circulating fibrinogen as well as a significant decrease in clotting times. We evaluated the effect of warfarin, dabigatran etexilate, apixaban and clopidogrel in this model by administering them in diet or in the drinking water to mice for 1-4 weeks. All of these marketed drugs significantly increased GI bleeding in Apc(min/+) mice, but not in wild-type mice. Although different exposure profiles of these antithrombotic agents make it challenging to compare the bleeding risk of compounds, our results indicate that the Apc(min/+) mouse may be a sensitive preclinical model for assessing the spontaneous GI bleeding risk of novel antithrombotic agents. PMID:24430131

  17. Proteomics Suggests a Role for APC-Survivin in Response to Somatostatin Analog Treatment of Neuroendocrine Tumors

    PubMed Central

    Kjellin, Hanna; Hashemi, Jamileh; Barriuso, Jorge; Juhlin, C. Christofer; Lu, Ming; Höög, Anders; Pastrián, Laura G.; Lamarca, Angela; Soto, Victoria Heredia; Zedenius, Jan; Mendiola, Marta; Lehtiö, Janne; Kjellman, Magnus

    2016-01-01

    Context: Somatostatin analogs are established in the treatment of neuroendocrine tumors (NETs) including small intestinal NET; however, the molecular mechanisms are not well known. Here, we examined the direct effects of lanreotide in NET cell line models. Setting and Design: The cell lines HC45 and H727 were treated with 10nM lanreotide for different time periods and alterations of the proteome were analyzed by in-depth high-resolution isoelectric focusing tandem liquid chromatography-mass spectrometry. We next investigated whether the observed suppression of survivin was mediated by adenomatous polyposis coli (APC) and possible effects on tumor proliferation in vitro. Expression of survivin was assessed by immunohistochemistry in 112 NET cases and compared with patient outcome. Results: We quantified 6451 and 7801 proteins in HC45 and H727, respectively. After short time lanreotide treatment APC was increased and survivin reduced. Overexpression of APC in H727 cells decreased, and APC knock-down elevated the survivin level. The lanreotide regulation of APC-survivin could be suppressed by small interfering RNA against somatostatin receptor 2. Although lanreotide only gave slight inhibition of proliferation, targeting of survivin with the small molecule YM155 dramatically reduced proliferation. Moderate or high as compared with low or absent total survivin expression was associated with shorter progression-free survival, independent of tumor stage, grade, and localization. Conclusions: We report a proteome-wide analysis of changes in response to lanreotide in NET cell lines. This analysis suggests a connection between somatostatin analog, APC, and survivin levels. Survivin is a possible prognostic factor and a new potential therapeutic target in NETs. PMID:27459532

  18. Association of APC, GSTP1 and SOCS1 promoter methylation with the risk of hepatocellular carcinoma: a meta-analysis.

    PubMed

    Liu, Meng; Cui, Lian-Hua; Li, Cheng-Cheng; Zhang, Li

    2015-11-01

    Studies of the relationships of adenomatous polyposis coli (APC), glutathione-S-transferase P1 (GSTP1) and suppressor of the cytokine signalling 1 (SOCS1) promoter region methylation with the risk of hepatocellular carcinoma (HCC) have yielded inconsistent results. We carried out the current meta-analysis to comprehensively assess the associations between APC, GSTP1 and SOCS1 promoter methylation frequency and the risk of HCC. All relevant reports were identified by searching the PubMed, Embase, Web of Science, CNKI and the Chinese BioMedical Literature databases before 1 March 2014, with restriction to articles published in the Chinese and English languages. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to investigate the rates of APC, GSTP1 and SOCS1 promoter methylation and the risk of HCC. Our meta-analysis identified relationships of APC (12 studies with 592 HCC tumour tissues), GSTP1 (14 studies including 646 HCC tumour tissues) and SOCS1 (11 studies with 512 HCC tumour tissues) promoter methylation with the risk of HCC. Compared with paracancerous tissues, the pooled ORs of APC, GSTP1 and SOCS1 promoter region methylation in HCC cancer tissues were 5.32 (95% CI=2.96-9.56), 5.65, (95% CI=3.41-9.35) and 2.73 (95% CI=1.37-5.44), respectively. Compared with normal liver tissues as controls, the pooled ORs of APC, GSTP1 and SOCS1 promoter region methylation in HCC cancer tissues were 20.43 (95% CI=5.56-75.08), 18.78 (95% CI=5.76-61.19) and 13.00 (95% CI=5.20-32.47), respectively. Subgroup analysis by ethnicity showed that APC, GSTP1 and SOCS1 promoter methylation was associated significantly with the risk of HCC in both Asian and White populations (all P<0.05). Our meta-analysis suggested strong associations between APC, GSTP1 and SOCS1 gene promoter methylation and the risk of HCC, suggesting these to be promising biomarkers for HCC. PMID:25853848

  19. A role for cyclin-dependent kinase(s) in the modulation of fast anterograde axonal transport: effects defined by olomoucine and the APC tumor suppressor protein

    NASA Technical Reports Server (NTRS)

    Ratner, N.; Bloom, G. S.; Brady, S. T.

    1998-01-01

    Proteins that interact with both cytoskeletal and membrane components are candidates to modulate membrane trafficking. The tumor suppressor proteins neurofibromin (NF1) and adenomatous polyposis coli (APC) both bind to microtubules and interact with membrane-associated proteins. The effects of recombinant NF1 and APC fragments on vesicle motility were evaluated by measuring fast axonal transport along microtubules in axoplasm from squid giant axons. APC4 (amino acids 1034-2844) reduced only anterograde movements, whereas APC2 (aa 1034-2130) or APC3 (aa 2130-2844) reduced both anterograde and retrograde transport. NF1 had no effect on organelle movement in either direction. Because APC contains multiple cyclin-dependent kinase (CDK) consensus phosphorylation motifs, the kinase inhibitor olomoucine was examined. At concentrations in which olomoucine is specific for cyclin-dependent kinases (5 microM), it reduced only anterograde transport, whereas anterograde and retrograde movement were both affected at concentrations at which other kinases are inhibited as well (50 microM). Both anterograde and retrograde transport also were inhibited by histone H1 and KSPXK peptides, substrates for proline-directed kinases, including CDKs. Our data suggest that CDK-like axonal kinases modulate fast anterograde transport and that other axonal kinases may be involved in modulating retrograde transport. The specific effect of APC4 on anterograde transport suggests a model in which the binding of APC to microtubules may limit the activity of axonal CDK kinase or kinases in restricted domains, thereby affecting organelle transport.

  20. The postsynaptic adenomatous polyposis coli (APC) multiprotein complex is required for localizing neuroligin and neurexin to neuronal nicotinic synapses in vivo.

    PubMed

    Rosenberg, Madelaine M; Yang, Fang; Mohn, Jesse L; Storer, Elizabeth K; Jacob, Michele H

    2010-08-18

    Synaptic efficacy requires that presynaptic and postsynaptic specializations align precisely and mature coordinately. The underlying mechanisms are poorly understood, however. We propose that adenomatous polyposis coli protein (APC) is a key coordinator of presynaptic and postsynaptic maturation. APC organizes a multiprotein complex that directs nicotinic acetylcholine receptor (nAChR) localization at postsynaptic sites in avian ciliary ganglion neurons in vivo. We hypothesize that the APC complex also provides retrograde signals that direct presynaptic active zones to develop in register with postsynaptic nAChR clusters. In our model, the APC complex provides retrograde signals via postsynaptic neuroligin that interacts extracellularly with presynaptic neurexin. S-SCAM (synaptic cell adhesion molecule) and PSD-93 (postsynaptic density-93) are scaffold proteins that bind to neuroligin. We identify S-SCAM as a novel component of neuronal nicotinic synapses. We show that S-SCAM, PSD-93, neuroligin and neurexin are enriched at alpha3*-nAChR synapses. PSD-93 and S-SCAM bind to APC and its binding partner beta-catenin, respectively. Blockade of selected APC and beta-catenin interactions, in vivo, leads to decreased postsynaptic accumulation of S-SCAM, but not PSD-93. Importantly, neuroligin synaptic clusters are also decreased. On the presynaptic side, there are decreases in neurexin and active zone proteins. Further, presynaptic terminals are less mature structurally and functionally. We define a novel neural role for APC by showing that the postsynaptic APC multiprotein complex is required for anchoring neuroligin and neurexin at neuronal synapses in vivo. APC human gene mutations correlate with autism spectrum disorders, providing strong support for the importance of the association, demonstrated here, between APC, neuroligin and neurexin.

  1. Artificial antigen presenting cell (aAPC) mediated activation and expansion of natural killer T cells.

    PubMed

    East, James E; Sun, Wenji; Webb, Tonya J

    2012-01-01

    Natural killer T (NKT) cells are a unique subset of T cells that display markers characteristic of both natural killer (NK) cells and T cells(1). Unlike classical T cells, NKT cells recognize lipid antigen in the context of CD1 molecules(2). NKT cells express an invariant TCRα chain rearrangement: Vα14Jα18 in mice and Vα24Jα18 in humans, which is associated with Vβ chains of limited diversity(3-6), and are referred to as canonical or invariant NKT (iNKT) cells. Similar to conventional T cells, NKT cells develop from CD4-CD8- thymic precursor T cells following the appropriate signaling by CD1d (7). The potential to utilize NKT cells for therapeutic purposes has significantly increased with the ability to stimulate and expand human NKT cells with α-Galactosylceramide (α-GalCer) and a variety of cytokines(8). Importantly, these cells retained their original phenotype, secreted cytokines, and displayed cytotoxic function against tumor cell lines. Thus, ex vivo expanded NKT cells remain functional and can be used for adoptive immunotherapy. However, NKT cell based-immunotherapy has been limited by the use of autologous antigen presenting cells and the quantity and quality of these stimulator cells can vary substantially. Monocyte-derived DC from cancer patients have been reported to express reduced levels of costimulatory molecules and produce less inflammatory cytokines(9,10). In fact, murine DC rather than autologous APC have been used to test the function of NKT cells from CML patients(11). However, this system can only be used for in vitro testing since NKT cells cannot be expanded by murine DC and then used for adoptive immunotherapy. Thus, a standardized system that relies on artificial Antigen Presenting Cells (aAPC) could produce the stimulating effects of DC without the pitfalls of allo- or xenogeneic cells(12, 13). Herein, we describe a method for generating CD1d-based aAPC. Since the engagement of the T cell receptor (TCR) by CD1d-antigen complexes is

  2. Improved leaching test methods for environmental assessment of coal ash and recycled materials used on construction

    EPA Science Inventory

    Changes in air pollution control at coal-fired power plants will result in lower emissions of mercury and other pollutants. Fly ash, flue gas desulfurization gypsum, and other air pollution control residues are used in agricultural, commercial, and engineering applications. Resea...

  3. The Schizosaccharomyces pombe dim1+ Gene Interacts with the Anaphase-Promoting Complex or Cyclosome (APC/C) Component lid1+ and Is Required for APC/C Function

    PubMed Central

    Berry, Lynne D.; Feoktistova, Anna; Wright, Melanie D.; Gould, Kathleen L.

    1999-01-01

    The Schizosaccharomyces pombe dim1+ gene is required for entry into mitosis and for chromosome segregation during mitosis. To further understand dim1p function, we undertook a synthetic lethal screen with the temperature-sensitive dim1-35 mutant and isolated lid (for lethal in dim1-35) mutants. Here, we describe the temperature-sensitive lid1-6 mutant. At the restrictive temperature of 36°C, lid1-6 mutant cells arrest with a “cut” phenotype similar to that of cut4 and cut9 mutants. An epitope-tagged version of lid1p is a component of a multiprotein ∼20S complex; the presence of lid1p in this complex depends upon functional cut9+. lid1p-myc coimmunoprecipitates with several other proteins, including cut9p and nuc2p, and the presence of cut9p in a 20S complex depends upon the activity of lid1+. Further, lid1+ function is required for the multiubiquitination of cut2p, an anaphase-promoting complex or cyclosome (APC/C) target. Thus, lid1p is a component of the S. pombe APC/C. In dim1 mutants, the abundances of lid1p and the APC/C complex decline significantly, and the ubiquitination of an APC/C target is abolished. These data suggest that at least one role of dim1p is to maintain or establish the steady-state level of the APC/C. PMID:10082519

  4. Application of the microbiological method DEFT/APC to detect minimally processed vegetables treated with gamma radiation

    NASA Astrophysics Data System (ADS)

    Araújo, M. M.; Duarte, R. C.; Silva, P. V.; Marchioni, E.; Villavicencio, A. L. C. H.

    2009-07-01

    Marketing of minimally processed vegetables (MPV) are gaining impetus due to its convenience, freshness and apparent health effect. However, minimal processing does not reduce pathogenic microorganisms to safe levels. Food irradiation is used to extend the shelf life and to inactivate food-borne pathogens. In combination with minimal processing it could improve safety and quality of MPV. A microbiological screening method based on the use of direct epifluorescent filter technique (DEFT) and aerobic plate count (APC) has been established for the detection of irradiated foodstuffs. The aim of this study was to evaluate the applicability of this technique in detecting MPV irradiation. Samples from retail markets were irradiated with 0.5 and 1.0 kGy using a 60Co facility. In general, with a dose increment, DEFT counts remained similar independent of the irradiation while APC counts decreased gradually. The difference of the two counts gradually increased with dose increment in all samples. It could be suggested that a DEFT/APC difference over 2.0 log would be a criteria to judge if a MPV was treated by irradiation. The DEFT/APC method could be used satisfactorily as a screening method for indicating irradiation processing.

  5. Creation of an engineered APC system to explore and optimize the presentation of immunodominant peptides of major allergens

    PubMed Central

    Rosskopf, Sandra; Jutz, Sabrina; Neunkirchner, Alina; Candia, Martín R.; Jahn-Schmid, Beatrice; Bohle, Barbara; Pickl, Winfried F.; Steinberger, Peter

    2016-01-01

    We have generated engineered APC to present immunodominant peptides derived from the major aero-allergens of birch and mugwort pollen, Bet v 1142–153 and Art v 125–36, respectively. Jurkat-based T cell reporter lines expressing the cognate allergen-specific T cell receptors were used to read out the presentation of allergenic peptides on the engineered APC. Different modalities of peptide loading and presentation on MHC class II molecules were compared. Upon exogenous loading with allergenic peptides, the engineered APC elicited a dose-dependent response in the reporter T cells and the presence of chemical loading enhancers strongly increased reporter activation. Invariant chain-based MHC class II targeting strategies of endogenously expressed peptides resulted in stronger activation of the reporters than exogenous loading. Moreover, we used Bet v 1 as model allergen to study the ability of K562 cells to present antigenic peptides derived from whole proteins either taken up or endogenously expressed as LAMP-1 fusion protein. In both cases the ability of these cells to process and present peptides derived from whole proteins critically depended on the expression of HLA-DM. We have identified strategies to achieve efficient presentation of allergenic peptides on engineered APC and demonstrate their use to stimulate T cells from allergic individuals. PMID:27539532

  6. 77 FR 34455 - In the Matter of Aegis Assessments, Inc., APC Group, Inc., Aurelio Resource Corp., BioAuthorize...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION In the Matter of Aegis Assessments, Inc., APC Group, Inc., Aurelio Resource Corp., BioAuthorize... securities of BioAuthorize Holdings, Inc. because it has not filed any periodic reports since the...

  7. SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs

    PubMed Central

    van der Lelij, Petra; Stocsits, Roman R; Ladurner, Rene; Petzold, Georg; Kreidl, Emanuel; Koch, Birgit; Schmitz, Julia; Neumann, Beate; Ellenberg, Jan; Peters, Jan-Michael

    2014-01-01

    Although splicing is essential for the expression of most eukaryotic genes, inactivation of splicing factors causes specific defects in mitosis. The molecular cause of this defect is unknown. Here, we show that the spliceosome subunits SNW1 and PRPF8 are essential for sister chromatid cohesion in human cells. A transcriptome-wide analysis revealed that SNW1 or PRPF8 depletion affects the splicing of specific introns in a subset of pre-mRNAs, including pre-mRNAs encoding the cohesion protein sororin and the APC/C subunit APC2. SNW1 depletion causes cohesion defects predominantly by reducing sororin levels, which causes destabilisation of cohesin on DNA. SNW1 depletion also reduces APC/C activity and contributes to cohesion defects indirectly by delaying mitosis and causing “cohesion fatigue”. Simultaneous expression of sororin and APC2 from intron-less cDNAs restores cohesion in SNW1-depleted cells. These results indicate that the spliceosome is required for mitosis because it enables expression of genes essential for cohesion. Our transcriptome-wide identification of retained introns in SNW1- and PRPF8-depleted cells may help to understand the aetiology of diseases associated with splicing defects, such as retinosa pigmentosum and cancer. PMID:25257309

  8. Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity

    PubMed Central

    Nabti, Ibtissem; Bormann, Jenny; Kudo, Nobuaki R.

    2014-01-01

    Female meiosis is driven by the activities of two major kinases, cyclin-dependent kinase 1 (Cdk1) and mitogen-activated protein kinase (MAPK). To date, the role of MAPK in control of meiosis is thought to be restricted to maintaining metaphase II arrest through stabilizing Cdk1 activity. In this paper, we find that MAPK and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates essential for meiosis I. Furthermore, inhibition of MAPK around the onset of APC/C activity at the transition from meiosis I to meiosis II led to accelerated completion of meiosis I and an increase in aneuploidy at metaphase II. These effects appear to be mediated via a Cdk1/MAPK-dependent stabilization of the spindle assembly checkpoint, which when inhibited leads to increased APC/C activity. These findings demonstrate new roles for MAPK in the regulation of meiosis in mammalian oocytes. PMID:24637322

  9. Efficient APC/C substrate degradation in cells undergoing mitotic exit depends on K11 ubiquitin linkages

    PubMed Central

    Min, Mingwei; Mevissen, Tycho E. T.; De Luca, Maria; Komander, David; Lindon, Catherine

    2015-01-01

    The ubiquitin proteasome system (UPS) directs programmed destruction of key cellular regulators via posttranslational modification of its targets with polyubiquitin chains. These commonly contain Lys-48 (K48)–directed ubiquitin linkages, but chains containing atypical Lys-11 (K11) linkages also target substrates to the proteasome—for example, to regulate cell cycle progression. The ubiquitin ligase called the anaphase-promoting complex/cyclosome (APC/C) controls mitotic exit. In higher eukaryotes, the APC/C works with the E2 enzyme UBE2S to assemble K11 linkages in cells released from mitotic arrest, and these are proposed to constitute an improved proteolytic signal during exit from mitosis. We tested this idea by correlating quantitative measures of in vivo K11-specific ubiquitination of individual substrates, including Aurora kinases, with their degradation kinetics tracked at the single-cell level. All anaphase substrates tested by this methodology are stabilized by depletion of K11 linkages via UBE2S knockdown, even if the same substrates are significantly modified with K48-linked polyubiquitin. Specific examination of substrates depending on the APC/C coactivator Cdh1 for their degradation revealed Cdh1-dependent enrichment of K11 chains on these substrates, whereas other ubiquitin linkages on the same substrates added during mitotic exit were Cdh1-independent. Therefore we show that K11 linkages provide the APC/C with a means to regulate the rate of substrate degradation in a coactivator-specified manner. PMID:26446837

  10. Casein Kinase 1δ Is an APC/CCdh1 Substrate that Regulates Cerebellar Granule Cell Neurogenesis

    PubMed Central

    Penas, Clara; Govek, Eve-Ellen; Fang, Yin; Ramachandran, Vimal; Daniel, Mark; Wang, Weiping; Maloof, Marie E.; Rahaim, Ronald J.; Bibian, Mathieu; Kawauchi, Daisuke; Finkelstein, David; Han, Jeng-Liang; Long, Jun; Li, Bin; Robbins, David J.; Malumbres, Marcos; Roussel, Martine F.; Roush, William R.; Hatten, Mary E.; Ayad, Nagi G.

    2015-01-01

    SUMMARY Although casein kinase 1δ (CK1δ) is at the center of multiple signaling pathways, its role in the expansion of central nervous system progenitor cells is unknown. Using mouse cerebellar granule cell progenitors (GCPs) as a model for brain neurogenesis, we demonstrate that the loss of CK1δ or treatment of GCPs with a highly selective small molecule inhibits GCP expansion. In contrast, CK1δ overexpression increases GCP proliferation. Thus, CK1δ appears to regulate GCP neurogenesis. CK1δ is targeted for proteolysis via the anaphase-promoting complex/cyclosome (APC/CCdh1) ubiquitin ligase, and conditional deletion of the APC/CCdh1 activator Cdh1 in cerebellar GCPs results in higher levels of CK1δ. APC/CCdh1 also downregulates CK1δ during cell cycle exit. Therefore, we conclude that APC/CCdh1 controls CK1δ levels to balance proliferation and cell cycle exit in the developing central nervous system. Similar studies in medulloblastoma cells showed that CK1δ holds promise as a new therapeutic target. PMID:25843713

  11. APC/CCdh1 controls CtIP stability during the cell cycle and in response to DNA damage

    PubMed Central

    Lafranchi, Lorenzo; de Boer, Harmen R; de Vries, Elisabeth GE; Ong, Shao-En; Sartori, Alessandro A; van Vugt, Marcel ATM

    2014-01-01

    Human cells have evolved elaborate mechanisms for responding to DNA damage to maintain genome stability and prevent carcinogenesis. For instance, the cell cycle can be arrested at different stages to allow time for DNA repair. The APC/CCdh1 ubiquitin ligase mainly regulates mitotic exit but is also implicated in the DNA damage-induced G2 arrest. However, it is currently unknown whether APC/CCdh1 also contributes to DNA repair. Here, we show that Cdh1 depletion causes increased levels of genomic instability and enhanced sensitivity to DNA-damaging agents. Using an integrated proteomics and bioinformatics approach, we identify CtIP, a DNA-end resection factor, as a novel APC/CCdh1 target. CtIP interacts with Cdh1 through a conserved KEN box, mutation of which impedes ubiquitylation and downregulation of CtIP both during G1 and after DNA damage in G2. Finally, we find that abrogating the CtIP–Cdh1 interaction results in delayed CtIP clearance from DNA damage foci, increased DNA-end resection, and reduced homologous recombination efficiency. Combined, our results highlight the impact of APC/CCdh1 on the maintenance of genome integrity and show that this is, at least partially, achieved by controlling CtIP stability in a cell cycle- and DNA damage-dependent manner. PMID:25349192

  12. Creation of an engineered APC system to explore and optimize the presentation of immunodominant peptides of major allergens.

    PubMed

    Rosskopf, Sandra; Jutz, Sabrina; Neunkirchner, Alina; Candia, Martín R; Jahn-Schmid, Beatrice; Bohle, Barbara; Pickl, Winfried F; Steinberger, Peter

    2016-01-01

    We have generated engineered APC to present immunodominant peptides derived from the major aero-allergens of birch and mugwort pollen, Bet v 1142-153 and Art v 125-36, respectively. Jurkat-based T cell reporter lines expressing the cognate allergen-specific T cell receptors were used to read out the presentation of allergenic peptides on the engineered APC. Different modalities of peptide loading and presentation on MHC class II molecules were compared. Upon exogenous loading with allergenic peptides, the engineered APC elicited a dose-dependent response in the reporter T cells and the presence of chemical loading enhancers strongly increased reporter activation. Invariant chain-based MHC class II targeting strategies of endogenously expressed peptides resulted in stronger activation of the reporters than exogenous loading. Moreover, we used Bet v 1 as model allergen to study the ability of K562 cells to present antigenic peptides derived from whole proteins either taken up or endogenously expressed as LAMP-1 fusion protein. In both cases the ability of these cells to process and present peptides derived from whole proteins critically depended on the expression of HLA-DM. We have identified strategies to achieve efficient presentation of allergenic peptides on engineered APC and demonstrate their use to stimulate T cells from allergic individuals. PMID:27539532

  13. Positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis in budding yeast.

    PubMed

    Hatano, Yuhki; Naoki, Koike; Suzuki, Asuka; Ushimaru, Takashi

    2016-10-01

    The mitotic inhibitor securin is degraded via the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdc20 after anaphase onset. This triggers activation of the mitotic protease separase and thereby sister chromatid separation. However, only a proportion of securin molecules are degraded at metaphase-anaphase transition and the remaining molecules are still present in anaphase. The roles of securin and separase in late mitosis remain elusive. Here, we show that securin still inhibits separase to repress mitotic exit in anaphase in budding yeast. APC/C-Cdh1-mediated securin degradation at telophase further liberated separase, which promotes Cdc14 release and mitotic exit. Separase executed these events via its proteolytic action and that in the Cdc14 early release (FEAR) network. Cdc14 release further activated APC/C-Cdh1 in the manner of a positive feedback loop. Thus, the positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis. This study shows the importance of the two-step degradation mode of securin and the role of separase in mitotic exit.

  14. Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity.

    PubMed

    Nabti, Ibtissem; Marangos, Petros; Bormann, Jenny; Kudo, Nobuaki R; Carroll, John

    2014-03-17

    Female meiosis is driven by the activities of two major kinases, cyclin-dependent kinase 1 (Cdk1) and mitogen-activated protein kinase (MAPK). To date, the role of MAPK in control of meiosis is thought to be restricted to maintaining metaphase II arrest through stabilizing Cdk1 activity. In this paper, we find that MAPK and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates essential for meiosis I. Furthermore, inhibition of MAPK around the onset of APC/C activity at the transition from meiosis I to meiosis II led to accelerated completion of meiosis I and an increase in aneuploidy at metaphase II. These effects appear to be mediated via a Cdk1/MAPK-dependent stabilization of the spindle assembly checkpoint, which when inhibited leads to increased APC/C activity. These findings demonstrate new roles for MAPK in the regulation of meiosis in mammalian oocytes. PMID:24637322

  15. Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice

    PubMed Central

    Sasada, Tatsunari; Hinoi, Takao; Saito, Yasufumi; Adachi, Tomohiro; Takakura, Yuji; Kawaguchi, Yasuo; Sotomaru, Yusuke; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru; Ohdan, Hideki

    2015-01-01

    The gastrointestinal tract is continuously exposed to a variety of chemicals and commensal bacteria. Recent studies have shown that changes in gut microbial populations caused by chlorine or other chemicals in the drinking water influence the development of human colorectal cancer, although the mechanism of tumorigenesis in the gut epithelium is obfuscated by the diversity of microflora and complexity of the tumor microenvironment. In this regard, mouse models that recapitulate human colorectal cancer are an invaluable tool. In this study, we used two conditional adenomatous polyposis coli (Apc) knockout mouse models to investigate the effect of chlorinated water on tumorigenesis in the digestive tract. Mice with colon-specific carcinoma—caused by either chromosomal (CDX2P 9.5-NLS Cre;Apc+/flox, abbreviated to CPC;Apc) or microsatellite (CDX2P9.5-G19Cre;Apcflox/flox and CDX2P9.5-G22Cre;Apcflox/flox) instability, respectively—were administered chlorinated (10.0 mg/L chlorine) or tap (0.7 mg/L chlorine) water and evaluated for colon polyp formation. In CPC;Apc mice given chlorinated drinking water, tumors tended to develop in the colon, whereas in those that drank tap water, tumors were mostly observed in the small intestine. There was no difference in the rate of tumor formation of CDX2P9.5-G19Cre;Apcflox/flox and CDX2P9.5-G22Cre;Apcflox/flox mice consuming chlorinated as compared to tap water, suggesting that microsatellite instability in the Apc gene does not significantly affect tumorigenesis. Chlorinated water altered the enteric environment by reducing the fecal populations of the obligatory anaerobes Clostridium perfringens and C. difficile, as well as species belonging to the Atopobium cluster, including Enterobacteriaceae and Staphylococcus sp., which was associated with colon tumorigenesis in CPC;Apc mice. These results suggest that differences in tumorigenesis among CPC;Apc mice consuming chlorinated versus tap water may be due to differences in

  16. Swelling behavior of O-alkylated APCS coals as examined by the EPR spin probe method

    SciTech Connect

    Ding, Ruisong; Tucker, D.; Kispert, L.D.

    1995-12-31

    Known O-alkylation procedures have been used to derivatize the carboxyl and hydroxyl groups in the APCS coals Lewiston-Stockton, Wyodak-Anderson, Beulah-Zap, Illinois {number_sign}6, Upper Freeport, and Pittsburgh {number_sign}8. In general the resulting decrease in hydrogen bonding reduced the cyclical variation in nitroxide spin probe retention observed for nonalkylated coals when small amounts (<1%) of pyridine are present in the toluene swelling solvent. An increase in spin probe retention by the O-alkylated coals relative to the underivatized coals indicates a more open arrangement in the coal due to a decrease in attractive forces, confirming that microporosity increases with increasing rank.

  17. The role of APC/C(Cdh1) in replication stress and origin of genomic instability.

    PubMed

    Greil, C; Krohs, J; Schnerch, D; Follo, M; Felthaus, J; Engelhardt, M; Wäsch, R

    2016-06-01

    It has been proposed that the APC/C(Cdh1) functions as a tumor suppressor by maintaining genomic stability. However, the exact nature of genomic instability following loss of Cdh1 is unclear. Using biochemistry and live cell imaging of single cells we found that Cdh1 knockdown (kd) leads to strong nuclear stabilization of the substrates cyclin A and B and deregulated kinetics of DNA replication. Restoration of the Cdh1-dependent G2 DNA damage checkpoint did not result in G2 arrest but blocked cells in prometaphase, suggesting that these cells enter mitosis despite incomplete replication. This results in DNA double-strand breaks, anaphase bridges, cytokinesis defects and tetraploidization. Tetraploid cells are the source of supernumerary centrosomes following Cdh1-kd, leading to multipolar mitosis or centrosome clustering, in turn resulting in merotelic attachment and lagging chromosomes. Whereas some of these events cause apoptosis during mitosis, surviving cells may accumulate chromosomal aberrations. PMID:26455319

  18. The role of APC/C(Cdh1) in replication stress and origin of genomic instability.

    PubMed

    Greil, C; Krohs, J; Schnerch, D; Follo, M; Felthaus, J; Engelhardt, M; Wäsch, R

    2016-06-01

    It has been proposed that the APC/C(Cdh1) functions as a tumor suppressor by maintaining genomic stability. However, the exact nature of genomic instability following loss of Cdh1 is unclear. Using biochemistry and live cell imaging of single cells we found that Cdh1 knockdown (kd) leads to strong nuclear stabilization of the substrates cyclin A and B and deregulated kinetics of DNA replication. Restoration of the Cdh1-dependent G2 DNA damage checkpoint did not result in G2 arrest but blocked cells in prometaphase, suggesting that these cells enter mitosis despite incomplete replication. This results in DNA double-strand breaks, anaphase bridges, cytokinesis defects and tetraploidization. Tetraploid cells are the source of supernumerary centrosomes following Cdh1-kd, leading to multipolar mitosis or centrosome clustering, in turn resulting in merotelic attachment and lagging chromosomes. Whereas some of these events cause apoptosis during mitosis, surviving cells may accumulate chromosomal aberrations.

  19. Homozygous patients with APC resistance may remain paucisymptomatic or asymptomatic during oral contraception.

    PubMed

    Girolami, A; Simioni, P; Girolami, B; Radossi, P

    1996-09-01

    The effect of oral contraceptive therapy was studied in five patients with homozygous activated protein C resistance. Patients with this congenital abnormality, in contrast to those with antithrombin, protein C or protein S deficiencies, showed only a mild thrombotic tendency. In fact, only two of six observations (one patient took the pill on two separate occasions many years apart) showed deep vein thrombosis. No patient had pulmonary embolism. Two additional patients had a superficial vein thrombosis of the legs. In two instances, a superficial vein thrombosis and a deep vein thrombosis, concomitant risk factors were present (immobilization and surgery for an ovarian cyst, respectively). However, compared with heterozygous for the same abnormality, the symptomatic homozygous patients with APC resistance appeared to develop thrombosis after a shorter period of oral contraception.

  20. Diverse HLA-I Peptide Repertoires of the APC Lines MUTZ3-Derived Immature and Mature Dendritic Cells and THP1-Derived Macrophages.

    PubMed

    Nyambura, Lydon Wainaina; Jarmalavicius, Saulius; Baleeiro, Renato Brito; Walden, Peter

    2016-09-15

    Dendritic cells (DCs) and macrophages are specialized APCs that process and present self-Ags for induction of tolerance and foreign Ags to initiate T cell-mediated immunity. Related to differentiation states they have specific phenotypes and functions. However, the impact of these differentiations on Ag processing and presentation remains poorly defined. To gain insight into this, we analyzed and compared the HLA-I peptidomes of MUTZ3-derived human immature and mature DC lines and THP1-derived macrophages by liquid chromatography tandem mass spectrometry. We found that the HLA-I peptidomes were heterogeneous and individualized and were dominated by nonapeptides with similar HLA-I binding affinities and anchor residues. MUTZ3-derived DCs and THP1-derived macrophages were able to sample peptides from source proteins of almost all subcellular locations and were involved in various cellular functions in similar proportion, with preference to proteins involved in cell communication, signal transduction, protein metabolism, and transcription factor/regulator activity. PMID:27543614

  1. Hematopoietic prostaglandin D synthase suppresses intestinal adenomas in ApcMin/+ mice.

    PubMed

    Park, Jae Man; Kanaoka, Yoshihide; Eguchi, Naomi; Aritake, Kosuke; Grujic, Sava; Materi, Alicia M; Buslon, Virgilio S; Tippin, Brigette L; Kwong, Alan M; Salido, Eduardo; French, Samuel W; Urade, Yoshihiro; Lin, Henry J

    2007-02-01

    Aspirin and other nonsteroidal anti-inflammatory drugs prevent some cases of colon cancer by inhibiting prostaglandin (PG) synthesis. PGE(2) promotes colon neoplasia, as shown by knockout mouse studies on enzymes and receptors in the PG cascade. A few experiments 20 to 30 years ago suggested that PGD(2) may suppress tumors, but a role for biosynthetic enzymes for PGD(2) in tumor development has not been studied. We report here that disruption of the gene for hematopoietic PGD synthase in Apc(Min/+) mice led to approximately 50% more intestinal adenomas compared with controls. Tumor size was not affected. By immunohistochemistry, we detected hematopoietic PGD synthase mainly in macrophages and monocytes of the gut mucosa. The mean number of tumors did not increase with knockout of the gene for the lipocalin type of the enzyme, which is not produced in the intestine. On the other hand, Apc(Min/+) mice with transgenic human hematopoietic PGD synthase tended to have 80% fewer intestinal adenomas. The transgene produced high mRNA levels (375-fold over endogenous). There was a suggestion of higher urinary excretion of 11beta-PGF(2alpha) and a lower excretion of a PGE(2) metabolite in transgenic mice, but differences (30-40%) were not statistically significant. The results support an interpretation that hematopoietic PGD synthase controls an inhibitory effect on intestinal tumors. Further studies will be needed to prove possible mechanisms, such as routing of PG production away from protumorigenic PGE(2) or inhibition of the nuclear factor-kappaB cascade by PGD(2) metabolites. PMID:17283118

  2. Validity of APCS score as a risk prediction score for advanced colorectal neoplasia in Chinese asymptomatic subjects

    PubMed Central

    Li, Wenbin; Zhang, Lili; Hao, Jianyu; Wu, Yongdong; Lu, Di; Zhao, Haiying; Wang, Zhenjie; Xu, Tianming; Yang, Hong; Qian, Jiaming; Li, Jingnan

    2016-01-01

    Abstract The Asia-Pacific Colorectal Screening (APCS) score is a risk-stratification tool that helps predict the risk for advanced colorectal neoplasia (ACN) in asymptomatic Asian populations, but has not yet been assessed for its validity of use in Mainland China. The aim of the study was to assess the validity of APCS score in asymptomatic Chinese population, and to identify other risk factors associated with ACN. Asymptomatic subjects (N = 1010) who underwent colonoscopy screening between 2012 and 2014 in Beijing were enrolled. APCS scores based on questionnaires were used to stratify subjects into high, moderate, and average-risk tiers. Cochran–Armitage test for trend was used to assess the association between ACN and risk tiers. Univariate and multivariate logistic regression was performed with ACN as the outcome, adjusting for APCS score, body mass index, alcohol consumption, self-reported diabetes, and use of nonsteroidal anti-inflammatory drugs as independent variables. The average age was 53.5 (standard deviation 8.4) years. The prevalence of ACN was 4.1% overall, and in the high, moderate, and average-risk tiers, the prevalence was 8.8%, 2.83%, and 1.55%, respectively (P < 0.001). High-risk tier had 3.3 and 6.1-fold increased risk of ACN as compared with those in the moderate and average-risk tiers, respectively. In univariate analysis, high-risk tier, obesity, diabetes, and alcohol consumption were associated with ACN. In multivariate analysis, only high-risk tier was an independent predictor of ACN. The APCS score can effectively identify a subset of asymptomatic Chinese population at high risk for ACN. Further studies are required to identify other risk factors, and the acceptability of the score to the general population will need to be further examined. PMID:27741134

  3. Chemoprevention of Familial Adenomatous Polyposis by Bromo-noscapine (EM011) in the ApcMin/+ Mouse Model

    PubMed Central

    Li, Shiwang; Ghaleb, Amr M.; He, Jing; Bughani, Usha; Bialkowska, Agnieszka B.; Yang, Vincent W.; Joshi, Harish C.

    2011-01-01

    Germline mutation of the tumor suppressor gene, adenomatous polyposis coli (APC), is responsible for familial adenomatous polyposis (FAP) with nearly 100% risk for colon cancer at an early age. Although FAP is involved in only 1% of all colon cancer cases, over 80% of sporadic cancers harbor somatic mutations of APC. We show here that bromo-onoscapine (EM011), a rationally-designed synthetic derivative of a natural non-toxic tubulin-binding alkaloid-noscapine, that reduces the dynamics of microtubules, causes a reversible G2/M arrest in wild type mouse embryonic fibroblasts (MEFs), but an aberrant exit from a brief mitotic block, followed by apoptosis in MEFs after APC deletion with siRNA. Furthermore, both β-catenin levels and activity fell to half the original levels with a concomitant reduction of cell proliferation-inducing cyclin D1, c-Myc, and induction of cytostatic protein p21 prior to caspase-3 activation. Additionally, we show a statistically significant reduction in the number of newly emerging intestinal polyps (to 35% compared with untreated mice) as well as the mean size of polyps (to 42% compared with untreated mice) in EM011-treated ApcMin/+ mice as compared to their sham-treated control littermates. The remaining polyps in the EM011 treated group of ApcMin/+ mice showed evidence of elevated apoptosis as revealed by immunohistochemistry. We failed to detect any evidence of histopathological and hematological toxicities following EM011 treatment. Taken together, our data are persuasive that a clinical trial of EM011 is possible for the prevention/amelioration of polyposis in FAP patients. PMID:22052467

  4. Nek2A destruction marks APC/C activation at the prophase-to-prometaphase transition by spindle-checkpoint-restricted Cdc20.

    PubMed

    Boekhout, Michiel; Wolthuis, Rob

    2015-04-15

    Nek2 isoform A (Nek2A) is a presumed substrate of the anaphase-promoting complex/cyclosome containing Cdc20 (APC/C(Cdc20)). Nek2A, like cyclin A, is degraded in mitosis while the spindle checkpoint is active. Cyclin A prevents spindle checkpoint proteins from binding to Cdc20 and is recruited to the APC/C in prometaphase. We found that Nek2A and cyclin A avoid being stabilized by the spindle checkpoint in different ways. First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A, whereas Nek2A disappeared at a normal rate. Second, depleting Cdc20 effectively stabilized cyclin A but not Nek2A. Nevertheless, Nek2A destruction crucially depended on Cdc20 binding to the APC/C. Third, in contrast to cyclin A, Nek2A was recruited to the APC/C before the start of mitosis. Interestingly, the spindle checkpoint very effectively stabilized an APC/C-binding mutant of Nek2A, which required the Nek2A KEN box. Apparently, in cells, the spindle checkpoint primarily prevents Cdc20 from binding destruction motifs. Nek2A disappearance marks the prophase-to-prometaphase transition, when Cdc20, regardless of the spindle checkpoint, activates the APC/C. However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/C(Cdc20) catalytic activity. PMID:25673878

  5. Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain Spindle Checkpoint Arrests

    PubMed Central

    Syred, Heather M.; van der Sar, Sjaak; Patel, Hitesh; Moresco, James J.; Sarkeshik, Ali; Yates, John R.; Rappsilber, Juri; Hardwick, Kevin G.

    2016-01-01

    The spindle checkpoint is a mitotic surveillance system which ensures equal segregation of sister chromatids. It delays anaphase onset by inhibiting the action of the E3 ubiquitin ligase known as the anaphase promoting complex or cyclosome (APC/C). Mad3/BubR1 is a key component of the mitotic checkpoint complex (MCC) which binds and inhibits the APC/C early in mitosis. Mps1Mph1 kinase is critical for checkpoint signalling and MCC-APC/C inhibition, yet few substrates have been identified. Here we identify Mad3 as a substrate of fission yeast Mps1Mph1 kinase. We map and mutate phosphorylation sites in Mad3, producing mutants that are targeted to kinetochores and assembled into MCC, yet display reduced APC/C binding and are unable to maintain checkpoint arrests. We show biochemically that Mad3 phospho-mimics are potent APC/C inhibitors in vitro, demonstrating that Mad3p modification can directly influence Cdc20Slp1-APC/C activity. This genetic dissection of APC/C inhibition demonstrates that Mps1Mph1 kinase-dependent modifications of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests. PMID:26882497

  6. Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C–Cdc20 complex

    PubMed Central

    Sedgwick, Garry G; Hayward, Daniel G; Di Fiore, Barbara; Pardo, Mercedes; Yu, Lu; Pines, Jonathon; Nilsson, Jakob

    2013-01-01

    The Anaphase Promoting Complex/Cyclosome (APC/C) in complex with its co-activator Cdc20 is responsible for targeting proteins for ubiquitin-mediated degradation during mitosis. The activity of APC/C–Cdc20 is inhibited during prometaphase by the Spindle Assembly Checkpoint (SAC) yet certain substrates escape this inhibition. Nek2A degradation during prometaphase depends on direct binding of Nek2A to the APC/C via a C-terminal MR dipeptide but whether this motif alone is sufficient is not clear. Here, we identify Kif18A as a novel APC/C–Cdc20 substrate and show that Kif18A degradation depends on a C-terminal LR motif. However in contrast to Nek2A, Kif18A is not degraded until anaphase showing that additional mechanisms contribute to Nek2A degradation. We find that dimerization via the leucine zipper, in combination with the MR motif, is required for stable Nek2A binding to and ubiquitination by the APC/C. Nek2A and the mitotic checkpoint complex (MCC) have an overlap in APC/C subunit requirements for binding and we propose that Nek2A binds with high affinity to apo-APC/C and is degraded by the pool of Cdc20 that avoids inhibition by the SAC. PMID:23288039

  7. Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex

    PubMed Central

    Kunttas-Tatli, Ezgi; Roberts, David M.; McCartney, Brooke M.

    2014-01-01

    The tumor suppressor adenomatous polyposis coli (APC) is an essential negative regulator of Wnt signaling through its activity in the destruction complex with Axin, GSK3β, and CK1 that targets β-catenin/Armadillo (β-cat/Arm) for proteosomal degradation. The destruction complex forms macromolecular particles we termed the destructosome. Whereas APC functions in the complex through its ability to bind both β-cat and Axin, we hypothesize that APC proteins play an additional role in destructosome assembly through self-association. Here we show that a novel N-terminal coil, the APC self-association domain (ASAD), found in vertebrate and invertebrate APCs, directly mediates self-association of Drosophila APC2 and plays an essential role in the assembly and stability of the destructosome that regulates β-cat degradation in Drosophila and human cells. Consistent with this, removal of the ASAD from the Drosophila embryo results in β-cat/Arm accumulation and aberrant Wnt pathway activation. These results suggest that APC proteins are required not only for the activity of the destructosome, but also for the assembly and stability of this macromolecular machine. PMID:25208568

  8. Clustering of T cell ligands on artificial APC membranes influences T cell activation and protein kinase C theta translocation to the T cell plasma membrane.

    PubMed

    Giannoni, Francesca; Barnett, Joellen; Bi, Kun; Samodal, Rodrigo; Lanza, Paola; Marchese, Patrizia; Billetta, Rosario; Vita, Randi; Klein, Mark R; Prakken, Berent; Kwok, William W; Sercarz, Eli; Altman, Amnon; Albani, Salvatore

    2005-03-15

    T cell activation is associated with active clustering of relevant molecules in membrane microdomains defined as the supramolecular activation cluster. The contact area between these regions on the surface of T cells and APC is defined as the immunological synapse. It has been recently shown that preclustering of MHC-peptide complexes in membrane microdomains on the APC surface affects the efficiency of immune synapse formation and the related T cell activation. Disruption of such clusters may reduce the efficiency of stimulation. We describe here an entirely artificial system for Ag-specific, ex vivo stimulation of human polyclonal T cells (artificial APC (aAPC)). aAPC are based on artificial membrane bilayers containing discrete membrane microdomains encompassing T cell ligands (i.e., appropriate MHC-peptide complexes in association with costimulatory molecules). We show here that preclustering of T cell ligands triggered a degree of T cell activation significantly higher than the one achieved when we used either soluble tetramers or aAPC in which MHC-peptide complexes were uniformly distributed within artificial bilayer membranes. This increased efficiency in stimulation was mirrored by increased translocation from the cytoplasm to the membrane of protein kinase theta, a T cell signaling molecule that colocalizes with the TCR within the supramolecular activation cluster, thus indicating efficient engagement of T cell activation pathways. Engineered aAPC may have immediate application for basic and clinical immunology studies pertaining to modulation of T cells ex vivo.

  9. Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure

    SciTech Connect

    Migliaccio, Christopher T. . E-mail: christopher.migliaccio@umontana.edu; Hamilton, Raymond F.; Holian, Andrij

    2005-06-01

    Silica inhalation results in chronic lung inflammation and fibrosis. While the role of the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology, the etiology is not completely understood. Evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. In order to study the effects of crystalline silica on the APC activity of pulmonary macrophages, mice were exposed intranasally and changes in pulmonary macrophage populations were assessed using flow cytometry. Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers (MHC class II, CD11c). In addition, an in vitro system using bone marrow-derived macrophages (BMDM) was generated to assess the effects of silica on the APC activity of macrophages in vitro. Data using BMDM in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO{sub 2}). Using a combination of in vivo and in vitro experiments, the current study describes a significant increase in an interstitial macrophage subset with an APC phenotype, as well as an increase in the APC activity of both AM and BMDM, as a direct result of exposure to crystalline silica. These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis.

  10. Methylation status of the APC and RASSF1A promoter in cell-free circulating DNA and its prognostic role in patients with colorectal cancer

    PubMed Central

    MATTHAIOS, DIMITRIOS; BALGKOURANIDOU, IOANNA; KARAYIANNAKIS, ANASTASIOS; BOLANAKI, HELEN; XENIDIS, NIKOLAOS; AMARANTIDIS, KYRIAKOS; CHELIS, LEONIDAS; ROMANIDIS, KONSTANTINOS; CHATZAKI, AIKATERINI; LIANIDOU, EVI; TRYPSIANIS, GRIGORIOS; KAKOLYRIS, STYLIANOS

    2016-01-01

    DNA methylation is the most frequent epigenetic alteration. Using methylation-specific polymerase chain reaction (MSP), the methylation status of the adenomatous polyposis coli (APC) and Ras association domain family 1 isoform A (RASSF1A) genes was examined in cell-free circulating DNA from 155 plasma samples obtained from patients with early and advanced colorectal cancer (CRC). APC and RASSF1A hypermethylation was frequently observed in both early and advanced disease, and was significantly associated with a poorer disease outcome. The methylation status of the APC and RASSF1A promoters was investigated in cell-free DNA of patients with CRC. Using MSP, the promoter methylation status of APC and RASSF1A was examined in 155 blood samples obtained from patients with CRC, 88 of whom had operable CRC (oCRC) and 67 had metastatic CRC (mCRC). The frequency of APC methylation in patients with oCRC was 33%. Methylated APC promoter was significantly associated with older age (P=0.012), higher stage (P=0.014) and methylated RASSF1A status (P=0.050). The frequency of APC methylation in patients with mCRC was 53.7%. In these patients, APC methylation was significantly associated with methylated RASSF1A status (P=0.016). The frequency of RASSF1A methylation in patients with oCRC was 25%. Methylated RASSF1A in oCRC was significantly associated with higher stage (P=0.021). The frequency of RASSF1A methylation in mCRC was 44.8%. Methylated RASSF1A in mCRC was associated with moderate differentiation (P=0.012), high levels of carcinoembryonic antigen (P=0.023) and methylated APC status (P=0.016). Patients with an unmethylated APC gene had better survival in both early (81±5 vs. 27±4 months, P<0.001) and advanced disease (37±7 vs. 15±3 months, P<0.001), compared with patients with methylated APC. Patients with an unmethylated RASSF1A gene had better survival in both early (71±6 vs. 46±8 months, P<0.001) and advanced disease (28±4 vs. 16±3 months, P<0.001) than patients with

  11. Spatiotemporal organization of Aurora-B by APC/CCdh1 after mitosis coordinates cell spreading through FHOD1

    PubMed Central

    Floyd, Suzanne; Whiffin, Nicola; Gavilan, Maria P.; Kutscheidt, Stefan; De Luca, Maria; Marcozzi, Chiara; Min, Mingwei; Watkins, Johnathan; Chung, Kathryn; Fackler, Oliver T.; Lindon, Catherine

    2013-01-01

    Summary Spatiotemporal regulation of mitotic kinase activity underlies the extensive rearrangement of cellular components required for cell division. One highly dynamic mitotic kinase is Aurora-B (AurB), which has multiple roles defined by the changing localisation of the chromosome passenger complex (CPC) as cells progress through mitosis, including regulation of cytokinesis and abscission. Like other mitotic kinases, AurB is a target of the anaphase-promoting complex (APC/C) ubiquitin ligase during mitotic exit, but it is not known if APC/C-mediated destruction plays any specific role in controlling AurB activity. We have examined the contribution of the Cdh1 coactivator-associated APC/CCdh1 to the organization of AurB activity as cells exit mitosis and re-enter interphase. We report that APC/CCdh1-dependent proteolysis restricts a cell-cortex-associated pool of active AurB in space and time. In early G1 phase this pool of AurB is found at protrusions associated with cell spreading. AurB retention at the cortex depends on a formin, FHOD1, critically required to organize the cytoskeleton after division. We identify AurB phosphorylation sites in FHOD1 and show that phosphomutant FHOD1 is impaired in post-mitotic assembly of oriented actin cables. We propose that Cdh1 contributes to spatiotemporal organization of AurB activity and that organization of FHOD1 activity by AurB contributes to daughter cell spreading after mitosis. PMID:23613471

  12. Prognostic role of APC and RASSF1A promoter methylation status in cell free circulating DNA of operable gastric cancer patients.

    PubMed

    Balgkouranidou, I; Matthaios, D; Karayiannakis, A; Bolanaki, H; Michailidis, P; Xenidis, N; Amarantidis, K; Chelis, L; Trypsianis, G; Chatzaki, E; Lianidou, E S; Kakolyris, S

    2015-08-01

    Gastric carcinogenesis is a multistep process including not only genetic mutations but also epigenetic alterations. The best known and more frequent epigenetic alteration is DNA methylation affecting tumor suppressor genes that may be involved in various carcinogenetic pathways. The aim of the present study was to investigate the methylation status of APC promoter 1A and RASSF1A promoter in cell free DNA of operable gastric cancer patients. Using methylation specific PCR, we examined the methylation status of APC promoter 1A and RASSF1A promoter in 73 blood samples obtained from patients with gastric cancer. APC and RASSF1A promoters were found to be methylated in 61 (83.6%) and 50 (68.5%) of the 73 gastric cancer samples examined, but in none of the healthy control samples (p < 0.001). A significant association between methylated RASSF1A promoter status and lymph node positivity was observed (p = 0.005). Additionally, a significant correlation between a methylated APC promoter and elevated CEA (p = 0.033) as well as CA-19.9 (p = 0.032) levels, was noticed. The Kaplan-Meier estimates of survival, significantly favored patients with a non-methylated APC promoter status (p = 0.008). No other significant correlations between APC and RASSF1A methylation status and different tumor variables examined was observed. Serum RASSF1A and APC promoter hypermethylation is a frequent epigenetic event in patients with early operable gastric cancer. The observed correlations between APC promoter methylation status and survival as well as between a hypermethylated RASSF1A promoter and nodal positivity may be indicative of a prognostic role for those genes in early operable gastric cancer. Additional studies, in a larger cohort of patients are required to further explore whether these findings could serve as potential molecular biomarkers of survival and/or response to specific treatments. PMID:26073472

  13. The E3 Ligase APC/C-Cdh1 Is Required for Associative Fear Memory and Long-Term Potentiation in the Amygdala of Adult Mice

    ERIC Educational Resources Information Center

    Pick, Joseph E.; Malumbres, Marcos; Klann, Eric

    2013-01-01

    The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating…

  14. Liver fatty acid-binding protein (L-Fabp) modifies intestinal fatty acid composition and adenoma formation in ApcMin/+ mice.

    PubMed

    Dharmarajan, Sekhar; Newberry, Elizabeth P; Montenegro, Grace; Nalbantoglu, Ilke; Davis, Victoria R; Clanahan, Michael J; Blanc, Valerie; Xie, Yan; Luo, Jianyang; Fleshman, James W; Kennedy, Susan; Davidson, Nicholas O

    2013-10-01

    Evidence suggests a relationship between dietary fat intake, obesity, and colorectal cancer, implying a role for fatty acid metabolism in intestinal tumorigenesis that is incompletely understood. Liver fatty acid-binding protein (L-Fabp), a dominant intestinal fatty acid-binding protein, regulates intestinal fatty acid trafficking and metabolism, and L-Fabp deletion attenuates diet-induced obesity. Here, we examined whether changes in intestinal fatty acid metabolism following L-Fabp deletion modify adenoma development in Apc(Min)(/+) mice. Compound L-Fabp(-/-)Apc(Min)(/+) mice were generated and fed a 10% fat diet balanced equally between saturated, monounsaturated, and polyunsaturated fat. L-Fabp(-/-)Apc(Min)(/+) mice displayed significant reductions in adenoma number and total polyp area compared with Apc(Min)(/+)controls, reflecting a significant shift in distribution toward smaller polyps. Adenomas from L-Fabp(-/-)Apc(Min)(/+) mice exhibited reductions in cellular proliferation, high-grade dysplasia, and nuclear β-catenin translocation. Intestinal fatty acid content was increased in L-Fabp(-/-)Apc(Min)(/+) mice, and lipidomic profiling of intestinal mucosa revealed significant shifts to polyunsaturated fatty acid species with reduced saturated fatty acid species. L-Fabp(-/-)Apc(Min)(/+) mice also showed corresponding changes in mRNA expression of enzymes involved in fatty acid elongation and desaturation. Furthermore, adenomas from L-Fabp(-/-)Apc(Min)(/+) mice displayed significant reductions in mRNA abundance of nuclear hormone receptors involved in cellular proliferation and in enzymes involved in lipogenesis. These findings collectively implicate L-Fabp as an important genetic modifier of intestinal tumorigenesis, and identify fatty acid trafficking and metabolic compartmentalization as an important pathway linking dietary fat intake, obesity, and intestinal tumor formation.

  15. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice.

    PubMed

    Myzak, Melinda C; Dashwood, W Mohaiza; Orner, Gayle A; Ho, Emily; Dashwood, Roderick H

    2006-03-01

    Sulforaphane (SFN) is an isothiocyanate from broccoli that induces phase 2 detoxification enzymes. We recently reported that SFN acts as a histone deacetylase (HDAC) inhibitor in human colon cancer cells in vitro, and the present study sought to extend these findings in vivo. In mice treated with a single oral dose of 10 mumol SFN, there was significant inhibition of HDAC activity in the colonic mucosa after 6 h, and immunoblots revealed a concomitant increase in acetylated histones H3 and H4, which returned to control levels by 48 h. Longer-term treatment with SFN in the diet resulted in levels of acetylated histones and p21(WAF1) in the ileum, colon, prostate, and peripheral blood mononuclear cells that were elevated compared with controls. Consistent with these findings, SFN suppressed tumor development in Apc(min) mice, and there was an increase in acetylated histones in the polyps, including acetylated histones specifically associated with the promoter region of the P21 and bax genes. These results provide the first evidence for HDAC inhibition by SFN in vivo and imply that such a mechanism might contribute to the cancer chemoprotective and therapeutic effects of SFN, alone or in combination with other HDAC inhibitors currently undergoing clinical trials.

  16. First military use of activated Factor VII in an APC-III pelvic fracture.

    PubMed

    Williams, D J; Thomas, G O R; Pambakian, S; Parker, P J

    2005-03-01

    A male soldier in shock with an APC-III pelvic fracture was flown to an Air Assault Surgical Group (AASG) of 16 Close Support Medical Regiment at Al Amarah in Iraq. A pelvic external fixator was applied and his condition stabilized. Ultrasound scanning (FAST) showed an absent bladder, and a spreading retroperitoneal haematoma combined with intra-abdominal, free blood. Unfortunately he continued to bleed and required transfusion with the unit's entire stock of type-specific blood. At emergency laparotomy, uncontrollable pelvic bleeding was encountered and the abdominal aorta required clamping above the iliac bifurcation. Branches of the right internal iliac artery were the source and this was ligated. Some bleeding continued post-operatively: administration of activated Factor VII was associated with a marked reduction in the oozing from his fixator pin-sites and an improvement in his pH from 7.1 to 7.3. In total, 25 units of blood were transfused, 8 of which were fresh whole blood donated by individual members of the AASG. The patient survived, returned to the UK, had his injuries reconstructed, and is currently undergoing rehabilitation. This case illustrates the benefits of forward resuscitation surgery in wartime and the need for a multidisciplinary approach to trauma care.

  17. Prdm5 suppresses Apc(Min)-driven intestinal adenomas and regulates monoacylglycerol lipase expression.

    PubMed

    Galli, G G; Multhaupt, H A; Carrara, M; de Lichtenberg, K H; Christensen, I B J; Linnemann, D; Santoni-Rugiu, E; Calogero, R A; Lund, A H

    2014-06-19

    PRDM proteins are tissue-specific transcription factors often deregulated in diseases, particularly in cancer where different members have been found to act as oncogenes or tumor suppressors. PRDM5 is a poorly characterized member of the PRDM family for which several studies have reported a high frequency of promoter hypermethylation in cancer types of gastrointestinal origin. We report here the characterization of Prdm5 knockout mice in the context of intestinal carcinogenesis. We demonstrate that loss of Prdm5 increases the number of adenomas throughout the murine small intestine on an Apc(Min) background. By using the genome-wide ChIP-seq (chromatin immunoprecipitation (ChIP) followed by DNA sequencing) and transcriptome analyses we identify loci encoding proteins involved in metabolic processes as prominent PRDM5 targets and characterize monoacylglycerol lipase (Mgll) as a direct PRDM5 target in human colon cancer cells and in Prdm5 mutant mouse intestines. Moreover, we report the downregulation of PRDM5 protein expression in human colon neoplastic lesions. In summary, our data provide the first causal link between Prdm5 loss and intestinal carcinogenesis, and uncover an extensive and novel PRDM5 target repertoire likely facilitating the tumor-suppressive functions of PRDM5.

  18. Task-based imaging of colon cancer in the ApcMin/+ mouse model

    NASA Astrophysics Data System (ADS)

    McNally, James B.; Kirkpatrick, Nathaniel D.; Hariri, Lida P.; Tumlinson, Alexandre R.; Besselsen, David G.; Gerner, Eugene W.; Utzinger, Urs; Barton, Jennifer K.

    2006-05-01

    Optical coherence tomography (OCT), laser-induced fluorescence (LIF), and laser-scanning confocal microscopy (LSCM) were used for the task of multimodal study of healthy and adenomatous mouse colon. The results from each modality were compared with histology, which served as the gold standard. The ApcMin/+ genetic mouse model of colon cancer was compared with wild-type mice. In addition, a special diet was used for the task of studying the origins of a 680 nm autofluorescent signal that was previously observed in colon. The study found close agreement among each of the modalities and with histology. All four modalities were capable of identifying diseased tissue accurately. The OCT and LSCM images provided complementary structural information about the tissue, while the autofluorescence signal measured by LIF and LSCM provided biochemical information. OCT and LIF were performed in vivo and nondestructively, while the LSCM and histology required extraction of the tissue. The magnitude of the 680 nm signal correlates with chlorophyll content in the mouse diet, suggesting that the autofluorescent compound is a dietary metabolite.

  19. Suppression of intestinal carcinogenesis in Apc-mutant mice by limonin

    PubMed Central

    Shimizu, Satomi; Miyamoto, Shingo; Fujii, Gen; Nakanishi, Ruri; Onuma, Wakana; Ozaki, Yoshihiko; Fujimoto, Kyoko; Yano, Tomohiro; Mutoh, Michihiro

    2015-01-01

    Limonoids in citrus fruits are known to possess multiple biological functions, such as anti-proliferative functions in human cancer cell lines. Therefore, we aimed to investigate the suppressive effect of limonin on intestinal polyp development in Apc-mutant Min mice. Five-week-old female Min mice were fed a basal diet or a diet containing 250 or 500 ppm limonin for 8 weeks. The total number of polyps in mice treated with 500 ppm limonin decreased to 74% of the untreated control value. Neoplastic cell proliferation in the polyp parts was assessed by counting PCNA positive cells, and a tendency of reduction was obtained by limonin treatment. Moreover, expression levels of c-Myc and MCP-1 mRNA in the polyp part were reduced by administration of limonin. We finally confirmed the effects of limonin on β-catenin signaling, and found limonin significantly inhibited T-cell factor/lymphocyte enhancer factor-dependent transcriptional activity in a dose-dependent manner in the Caco-2 human colon cancer cell line. Our results suggest that limonin might be a candidate chemopreventive agent against intestinal carcinogenesis. PMID:26236099

  20. Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability

    PubMed Central

    Horn, Sarah R.; Thomenius, Michael J.; Johnson, Erika Segear; Freel, Christopher D.; Wu, Judy Q.; Coloff, Jonathan L.; Yang, Chih-Sheng; Tang, Wanli; An, Jie; Ilkayeva, Olga R.; Rathmell, Jeffrey C.; Newgard, Christopher B.; Kornbluth, Sally

    2011-01-01

    Homeostatic maintenance of cellular mitochondria requires a dynamic balance between fission and fusion, and controlled changes in morphology are important for processes such as apoptosis and cellular division. Interphase mitochondria have been described as an interconnected network that fragments as cells enter mitosis, and this mitotic mitochondrial fragmentation is known to be regulated by the dynamin-related GTPase Drp1 (dynamin-related protein 1), a key component of the mitochondrial division machinery. Loss of Drp1 function and the subsequent failure of mitochondrial division during mitosis lead to incomplete cytokinesis and the unequal distribution of mitochondria into daughter cells. During mitotic exit and interphase, the mitochondrial network reforms. Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1, catalyzed by the APC/CCdh1 (anaphase-promoting complex/cyclosome and its coactivator Cdh1) E3 ubiquitin ligase complex. Importantly, inhibition of Cdh1-mediated Drp1 ubiquitylation and proteasomal degradation during interphase prevents the normal G1 phase regrowth of mitochondrial networks following cell division. PMID:21325626