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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. PMID:20022170

  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. PMID:21963174

  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. VITRIFICATION OF MUNICIPAL SOLID WASTE COMBUSTION AIR POLLUTION CONTROL RESIDUES USING CORNING, INC. PROCESS

    EPA Science Inventory

    A demonstration was conducted to vitrify municipal solid waste (MSW) combustor air pollution control residue (APC) under the USEPA Municipal Waste Innovative Technology Evaluation Program. uplicate demonstration was conducted using a process developed by Corning Inc. in a cold cr...

  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. On-site treatment and landfilling of MSWI air pollution control residues.

    PubMed

    Lundtorp, K; Jensen, D L; Sørensen, M A; Mosbaek, H; Christensen, T H

    2003-02-28

    Air pollution control (APC) residues from municipal solid waste incineration (MSWI) are difficult to landfill due to substantial leaching of trace metals. An on-site pretreatment prior to landfilling of APC-residues was investigated in terms of bench-scale experiments with a semidry APC-residue and a fly ash. The treatment involved mixing of the residues with a ferrous sulphate solution and subsequent oxidation of the suspension. Afterwards, the suspension was spread on a dedicated landfill section and allowed to drain by gravity through the drainage system of the landfill. The wastewater from the process, collected through the drainage system, contained large concentrations of salts (Cl: 14-30 g/l, Na: 4-9 g/l, K: 5-11 g/l, Ca: 2-12 g/l) but low concentrations of trace metals (e.g. Pb: 14-100 microg/l, Cd: <2-7 microg/l). The treated residues left in the landfills were later subject to leaching by simulated rainfall. The leachate contained low concentrations of trace metals (Pb: <120 microg/l, Cd: <2 microg/l, Cr: <485 microg/l). The leachate concentrations from the treated APC-residues were substantially reduced compared to concentrations in leachate from untreated APC-residues. Particularly in the early stages of the leaching, concentrations of trace metals were reduced by up to four orders of magnitude. PMID:12573829

  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. 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. PMID:19773123

  9. 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. PMID:20599249

  10. Controls on metal leaching from secondary Pb smelter air-pollution-control residues.

    PubMed

    Ettler, Vojtech; Sebek, Ondrej; Grygar, Tomás; Klementová, Mariana; Bezdicka, Petr; Slavíková, Halka

    2008-11-01

    Air-pollution-control (APC) residues are among the most toxic waste materials from secondary Pb metallurgy. Two distinct APC residues collected from bag-type filters of one Czech secondary Pb smelter were subjected to leaching experiments to determine the mineralogical and geochemical controls on leaching of metallic contaminants (Cd, Cu, Pb, Zn). A kinetic 720-h leaching test in deionized water at a liquid-to-solid (L/S) ratio of 10 L kg(-1) and a 48-h leaching test at various L/S ratios (0.5, 1, 5, 10, 50, 100, 500, and 1000 L kg(-1)) were performed and coupled with the mineralogical investigation of solid residues (TEM/EDS, XRD) and PHREEQC-2 speciation-solubility modeling. The rapid release of contaminants into the solution at all the L/S ratios showed the rapid dissolution of primary phases. The leaching at high L/S ratios, representing long-term predictions of leaching behavior, showed that primary alkaline sulfates and chlorides (Na3Pb2(S04)3Cl and KCl.2PbCl2) were dissolved and anglesite (PbSO4) was formed as their final and stable alteration product. Primary amorphous PbSO3 partly crystallized during leaching and oxidized to anglesite. These results are consistent with the mineralogical investigation of soils exposed for decades to Pb smelter emissions, where only anglesite was detected. The leaching experiments showed thatwashing residues at L/S >50 accompanied by spontaneous anglesite precipitation can be an alternative for improved technological treatment of these residues. Although this process would require further treatment of contaminated effluent, the newly precipitated anglesite is more favorable than the primary APC residue phases for an efficient metallurgical recovery of Pb. PMID:19031875

  11. 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. PMID:17728059

  12. Antimony and arsenic leaching from secondary lead smelter air-pollution-control residues.

    PubMed

    Ettler, Vojtech; Mihaljevic, Martin; Sebek, Ondrej

    2010-07-01

    Environments in the vicinity of the lead (Pb) smelters are contaminated by emissions containing high concentrations of antimony (Sb) and arsenic (As). Air-pollution-control (APC) residues from bag-type filters from a secondary Pb smelter were subjected to leaching experiments to elucidate the controlling mechanisms of Sb and As release. Kinetic batch leaching tests at a liquid-to-solid (L/S) ratio of 10 L kg(- 1) within the time frame of 720 hours and batch leaching at various L/S ratios (ranging from 1 to 1000 L kg(-1)) were performed. In contrast to other inorganic contaminants (Pb, Cd, Zn), less than 1% of the total Sb and As content was leached from the residues. At a L/S ratio of 10, the As and Sb concentrations in the leachates exceeded the EU limit values for non-hazardous waste (0.2 and 0.07 mg L(-1) ). According to PHREEQC-2 calculations, the concentrations of As and Sb are controlled by the precipitation of complex arsenates and antimonates mainly at low L/S ratios. The washing and related chemical/mineralogical transformation of APC residues was suggested as a technological pre-treatment process before their re-smelting in a blast furnace. The Ferrox-like processing of the resulting contaminated process water/leachate was simulated using the PHREEQC-2 code. Significant reduction was obtained in the concentration of some key contaminants (As, Cu, Pb, Zn) related to sorption on newly formed hydrous ferric oxides, whereas Sb and Cd exhibited only limited attenuation. PMID:19723825

  13. 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

  14. 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

  15. 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...

  16. 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

  17. Assessment of long-term leaching from waste incineration air-pollution-control residues.

    PubMed

    Astrup, T; Mosbaek, H; Christensen, T H

    2006-01-01

    Assessment of long-term leaching from MSWI air-pollution-control (APC) residues is discussed with respect to use in environmental impact assessment, such as life-cycle assessment (LCA). A method was proposed for estimating leaching as a function of the liquid-to-solid (L/S) ratio in a long-term perspective (L/S 5000l/kg). Data for changes in residue pH as a function of L/S was used in combination with pH dependent leaching data to predict leachate concentrations of Al, Ca, Cd, Ba, Mg, Ni, Pb, S, Pb, V and Zn as a function of L/S. Mass balance calculations were used to determine the element fractions leached with respect to L/S. The estimated long-term leaching from a semi-dry residue and a fly ash was compared with short-term leaching determined by batch tests at L/S 10l/kg, both carbonated and non-carbonated versions of the residues were investigated. Generally, very high L/S ratios above 2000l/kg were required to leach 20-30% of the solid contents. However, Ca and S were depleted at L/S 200-900l/kg. The long-term leachate concentrations were found to either remain at the same level as the initial leaching determined by the L/S 10 batch test, or to significantly decrease compared with the initial leaching. Only Al and Zn were found to show higher leachate concentrations at L/S ratios above 3000-5000l/kg. Carbonation generally prolonged the time needed for depletion from the solid residues; however, Ca and S were depleted faster than in the case of non-carbonated residues. This study shows that uncritical use of batch leaching data for assessing the potential leaching is highly problematic, and evaluations of residue disposal should include scenario specific quantification of the long-term leaching. PMID:16488595

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

    SciTech Connect

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

    2008-11-15

    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.

  19. 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

  20. 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

  1. 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. PMID:24045173

  2. 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. PMID:24616344

  3. 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. PMID:26233740

  4. 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...

  5. 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...

  6. 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. PMID:23181908

  7. 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.

  8. Belgian MSWI fly ashes and APC residues: a characterisation study.

    PubMed

    De Boom, Aurore; Degrez, Marc

    2012-06-01

    Municipal Solid Waste Incineration (MSWI) produces different sorts of residues, bottom ash, fly ashes and Air Pollution Control (APC) residues. Generally, fly ashes and APC residues are mixed at the MSWI plant and manage as a sole residue. In this study, fly ashes and APC residues have been sampled separately at different Belgian MSWI plant and analysed by X-ray fluorescence in order to highlight the composition differences that may appear between the solids. Ca and Cl are found to be the major elements in most of the samples. Lithophilic elements, such as Al and Si, are richer in furnace and boiler ashes, as can be expected. Leaching tests also show differences between the residues; leachates from furnace and boiler ashes are alkaline while those from bag filter residues present a pH value of 6, which impacts the leaching of heavy metals (Pb and Zn). The results suggest that it could be advantageous to manage fly ashes and APC residues separately by adjusting the treatment to their specificities. PMID:22244614

  9. Leaching behavior and possible resource recovery from air pollution control residues of fluidized bed combustion of municipal solid waste

    SciTech Connect

    Abbas, Z.; Andersson, B.A.; Steenari, B.M.

    1999-07-01

    Ash residues are generated at several points during combustion of municipal solid waste (MSW), i.e., in cyclones, electrostatic precipitators and fabric filters. Such residues are of a complex physical and chemical nature and are often enriched in soluble salts and heavy metals such as Pb, Cd and Zn. Fluidized bed combustion (FBC) of MSW is a relatively new technique and very little information is available about the leaching behavior of its residues. In this study, the total elemental composition, mineralogy and leaching behavior of cyclone and bag-house filter ashes from a bubbling fluidized bed (BFB) boiler fired with municipal solid waste have been investigated. In addition, the possibilities of recovery heavy metals from these ashes were studied. The long-term leaching behavior of the ash constituents was evaluated using a two-step batch leaching test known as the CEN-test, whereas short and medium term leaching behavior was evaluated using a Column test. The extraction of elements from cyclone and filter ashes with various acidic solutions was also investigated. The leaching behavior of acid washed ashes was evaluated using the CEN test. The cyclone ash was mainly composed of aluminosilicate minerals, whereas the filter ash consisted of chlorides and hydroxides of alkali and alkaline earth metals. The concentration of heavy metals such as Zn, Cu, Cd and Pb was higher in the filter ash than in the cyclone ash. The leached amounts of sulfates and Pb from the cyclone ash decreased with leaching test contact time, indicating the formation of secondary mineral phases. Large amounts of chlorides, sulfates, Ca, Cu and Pb were leached from the filter ash. Acid extraction removed large amounts ({gt}50%) of Zn, Pb and Cu from the filter ash and approximately 56% of the total amount of Zn present in the cyclone ash. An efficient removal of heavy metal species from these types of ashes can probably be achieved by application of a recycling or multi-step process.

  10. 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…

  11. ACRYLONITRILE PLANT AIR POLLUTION CONTROL

    EPA Science Inventory

    Based on available literature, the report identifies and ranks (in terms of efficiency, cost, and energy requirements) air pollution control technologies for each of four major air pollutant emission sources in acrylonitrile plants. The sources are: (1) absorber vent gas streams,...

  12. 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,…

  13. Application of accelerated carbonation on MSW combustion APC residues for metal immobilization and CO2 sequestration.

    PubMed

    Cappai, G; Cara, S; Muntoni, A; Piredda, M

    2012-03-15

    The present study focuses on the application of an aqueous phase accelerated carbonation treatment on air pollution control (APC) residues from municipal solid waste combustion, aimed at assessing its influence on the environmental behaviour of the residue under concern, as well as the potential of the process in terms of sequestration of the CO2. APC residues are considered hazardous waste and must be treated before final disposal in order to achieve the immobilization/mobilization of critical contaminants such as heavy metals as well as mobilization of soluble salts. The treatment applied proved to be effective in reducing the mobility of Pb, Zn, Cr, Cu and Mo, the optimum final pH for the carbonated APC residues being in a range of 10-10.5, whilst a mobilization effect was noticed for Sb and no effect was assessed for chlorides. The effect of carbonation treatment on the contaminant release was further evaluated by means of a sequential extraction procedure, indicating that the distribution of contaminants on water soluble, exchangeable and carbonate fraction was modified after treatment. The CO2 sequestration potential assessed for the APC residues showed that the carbonation technology could be a technically viable option in order to reduce emissions from WtE plants. PMID:21601357

  14. 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…

  15. 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)

  16. 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…

  17. 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...

  18. 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...

  19. 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)...

  20. 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...

  1. 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)...

  2. 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...

  3. 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)...

  4. 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)...

  5. 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)...

  6. 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...

  7. 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…

  8. 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. PMID:24291664

  9. 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. PMID:15885416

  10. Air pollution control system testing at the DOE offgas components test facility

    SciTech Connect

    Burns, D.B.; Speed, D.; VanPelt, W.; Burns, H.H.

    1997-06-01

    In 1997, the Department of Energy (DOE) Savannah River Site (SRS) plans to begin operation of the Consolidated Incineration Facility (CIF) to treat solid and liquid RCRA hazardous and mixed wastes. The Savannah River Technology Center (SRTC) leads an extensive technical support program designed to obtain incinerator and air pollution control equipment performance data to support facility start-up and operation. A key component of this technical support program includes the Offgas Components Test Facility (OCTF), a pilot-scale offgas system test bed. The primary goal for this test facility is to demonstrate and evaluate the performance of the planned CIF Air Pollution Control System (APCS). To accomplish this task, the OCTF has been equipped with a 1/10 scale CIF offgas system equipment components and instrumentation. In addition, the OCTF design maximizes the flexibility of APCS operation and facility instrumentation and sampling capabilities permit accurate characterization of all process streams throughout the facility. This allows APCS equipment performance to be evaluated in an integrated system under a wide range of possible operating conditions. This paper summarizes the use of this DOE test facility to successfully demonstrate APCS operability and maintainability, evaluate and optimize equipment and instrument performance, and provide direct CIF start-up support. These types of facilities are needed to permit resolution of technical issues associated with design and operation of systems that treat and dispose combustible hazardous, mixed, and low-level radioactive waste throughout and DOE complex.

  11. 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

  12. 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. PMID:25022549

  13. 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.

  14. 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...

  15. AIR POLLUTION CONTROL ALTERNATIVES FOR SHALE OIL PRODUCTION OPERATIONS

    EPA Science Inventory

    The report consolidates, evaluates, and presents available air pollution emission data and air pollution control technology relevant to oil shale production, for use by project developers in preparing environmental impact statements and permit applications under Clean Air Act and...

  16. 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.

  17. 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

  18. 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

  19. 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...

  20. 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...

  1. APPCD - INTEGRATED AIR POLLUTION CONTROL SYSTEM (IAPCS)COST MODEL

    EPA Science Inventory

    The Integrated Air Pollution Control System (IAPCS)Cost Model is a compiled model written in FORTRAN and C language which is designed to be used on an IBM or compatible PC with 640K or lower RAM and at least 1.5 Mb of hard drive space. It was developed over the past several years...

  2. 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.

  3. EVALUATION OF SOLIDIFICATION/STABILIZATION TREATMENT PROCESSES FOR MUNICIPAL WASTE COMBUSTION RESIDUES

    EPA Science Inventory

    Investigations were carried out to compare and evaluate solidification/stabilization (S/S) processes to treat residues from combustion (MWC). ull factorial experimental design was used to processes to treat bottom ash, air pollution control (APC) residue, The 5 S/S processes incl...

  4. 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

  5. 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.

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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. PMID:26268600

  12. Air pollution control in an age of prevention

    SciTech Connect

    Smith, J.C.

    1996-01-01

    In the case of air pollution control technology, the case for pollution prevention is frequently cast as a case against pollution control technology. The errors in this argument are that pollution control technology is always the more expensive compliance option and that pollution prevention techniques exist to solve all or most of US air quality problems. A true market-based clean air policy would not contain these assumptions, would set a goal and appoint the market as the arbiter of final compliance decisions. This article discusses the market-based option and the balance needed between pollution prevention and pollution control technologies.

  13. 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...

  14. 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...

  15. 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.

  16. Air pollution control and heat recovery system for industrial ovens

    SciTech Connect

    Jamaluddin, A.A.

    1980-12-30

    A system of air pollution control and heat recovery is provided for an arrangement of industrial ovens, especially for drum manufacture. A plurality of paint bake ovens of various capacities, lengths and heat input are provided for multi-stage processing in the manufacture of drums and lids therefor. A supply of high temperature water is provided for multi-stage cleaning and rinsing in the manufacturing operation. The combined exhaust from the oven is preheated in a heat exchanger and then all of the combustible components are burnt off by passing through the flames of an incinerator grid burner. The effluent from the burner first passes through the heat exchanger to preheat said oven exhaust gases and then through hot water coils to provide all of the necessary hot water for the system. High pressure hot water (275/sup 0/) is provided in this heat exchange operation. The hot gasses from the last heat exchanger, completely free of combustible contaminates, are mixed with fresh air to supply hot air for the dryers used in the process. There is a substantially complete recovery of heat and the gasses discharged to atmosphere meet air quality standards.

  17. 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

    ...EPA is proposing to approve revisions to the Placer County Air Pollution Control District (PCAPCD), Sacramento Metropolitan Air Quality Management District (SMAQMD), San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD), and South Coast Air Quality Management District (SCAQMD) portions of the California State Implementation Plan (SIP). These revisions concern volatile organic......

  18. 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...

  19. 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... On June 16, 2009 (74 FR 28467), EPA proposed to approve the following rules into the California SIP... topcoats; and that Ventura County Air Pollution Control District's (VCAPCD) rule has more stringent...

  20. 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... May 11, 2010 (75 FR 26102), we finalized a limited approval and limited disapproval of San Joaquin Valley Unified Air Pollution Control District (``SJVUAPCD'' or ``District'') Rules 2020 (Exemptions)...

  1. 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....

  2. 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...

  3. 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…

  4. Drying oven with heat reclamation and air pollution control system

    SciTech Connect

    Jamaluddin, A.A.

    1980-12-23

    A system of drying ovens is disclosed with associated means for heat reclamation and air pollution control. The ovens are primarily for drying or baking paint or other coatings on pipes or the like where the emissions are primarily hydrocarbons. In this system of ovens, hydrocarbon fumes are concentrated at the ends of the oven. Solvent laden fumes are, therefore, collected where the concentration is the highest. The exhaust from the oven is located at the central portion and leads to a combustion/incineration chamber where it is exhausted to atmosphere after incineration and a major part of the heat is recovered and recirculated to the oven. In a sequence of ovens, the exhaust from one oven is circulated to the next at a high linear velocity, but low volume (At 25% lel) and heated to a high temperature (1400/sup 0/F.) by in-line incineration of the fumes. The low volume, high velocity, high temperature gasses are mixed with a high volume, low velocity, low temperature exhaust collected from the end of that oven. This incineration and mixing and recirculation of gasses is repeated in each succeeding oven and no gasses are exhausted to atmosphere until the last oven. In the last oven, in sequence, a burner is provided to incinerate fumes recirculated at one end of the oven and the exhaust goes to atmosphere through an incinerator/heat exchanger where the reclaimed heat is supplied to outside air being fed to support combustion in the incinerator at one end of the last oven.

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. The effects of accelerated carbonation on CO(2) uptake and metal release from incineration APC residues.

    PubMed

    Baciocchi, Renato; Costa, Giulia; Di Bartolomeo, Elisabetta; Polettini, Alessandra; Pomi, Raffaella

    2009-12-01

    This work presents the results of a study on accelerated carbonation of incinerator air pollution control residues, with a particular focus on the modifications in the leaching behaviour of the ash. Aqueous carbonation experiments were carried out using 100% CO(2) at different temperatures, pressures and liquid-to-solid ratios, in order to assess their influence on process kinetics, CO(2) uptake and the leaching behaviour of major and trace elements. The ash showed a particularly high reactivity towards CO(2), owing to the abundance of calcium hydroxides phases, with a maximum CO(2) uptake of approximately 250g/kg. The main effects of carbonation on trace metal leaching involved a significant decrease in mobility for Pb, Zn and Cu at high pH values, a slight change or mobilization for Cr and Sb, and no major effects on the release of As and soluble salts. Geochemical modelling of leachates indicated solubility control by different minerals after carbonation. In particular, in the stability pH range of carbonates, solubility control by a number of metal carbonates was clearly suggested by modelling results. These findings indicate that accelerated carbonation of incinerator ashes has the potential to convert trace contaminants into sparingly soluble carbonate forms, with an overall positive effect on their leaching behaviour. PMID:19700299

  4. Effect of improving flue gas cleaning on characteristics and immobilisation of APC residues from MSW incineration.

    PubMed

    Geysen, D; Vandecasteele, C; Jaspers, M; Brouwers, E; Wauters, G

    2006-01-16

    The flue gas cleaning system of a MSW incinerator with a capacity of 350 kt/year was changed to improve the HCl elimination efficiency. Instead of the semi-wet operating spray reactor and subsequent baghouse, a two-step wet flue gas cleaning was added behind the baghouse. Elemental composition, X-ray powder diffraction patterns and TGA measurements showed that the resulting APC residue was totally different from the former residue. As a consequence, leaching characteristics of both residues also differed and another treatment was required prior to disposal. For the former residue, mainly leaching of Pb (>100 mg/l), necessitated treatment prior to landfilling. The lower alkalinity of the new residue resulted in a leachate pH of 9.7 and a Pb concentration of 0.8 mg/l. The leachate pH of the former residue was 12.4. The leaching of Pb and Zn increased above 100 mg/l when immobilising the new residue with cement. Better results were obtained when immobilising with micro silica. The high CaCl2 x 2H2O content of the new residue brought along clogging of the bag filter system. Adding 1.4% of CaO (or 1.9% of Ca(OH)2) to the residue already improved these inconveniences but again significantly changed the leaching behaviour of the residue. PMID:16386367

  5. 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

    ... AGENCY 40 CFR Part 52 Revisions to the California State Implementation Plan, Placer County Air Pollution... County Air Pollution Control District (PCAPCD) and Sacramento Metropolitan Air Quality Management... following local rules: PCAPCD Rule 236 (Wood Products and Coating Operations), PCAPCD Rule 238...

  6. A NEW VAPOR RECOVERY NOZZLE FOR AIR POLLUTION CONTROL - PHASE II

    EPA Science Inventory

    The vapor recovery nozzle is an air pollution control device which relates to Stage II emission control equipment designed to capture gasoline vapors during automobile refueling at service stations. The existing vapor recovery nozzles are difficult to handle, the bellows pr...

  7. 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…

  8. 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

    ...EPA is proposing a limited approval and limited disapproval of revisions to the Imperial County Air Pollution Control District (ICAPCD) portion of the California State Implementation Plan (SIP). These revisions concern coarse particulate matter (PM10) emissions from sources of fugitive dust such as construction sites, unpaved roads, and disturbed soils in open and agricultural......

  9. 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…

  10. 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…

  11. 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

    ... to Implement the 8-Hour Ozone National Ambient Air Quality Standard--Phase 2,'' 70 FR 71612 (November.... SUMMARY: EPA is proposing to approve revisions to the San Joaquin Valley Air Pollution Control District... an earlier version of Rule 4103 into the SIP on November 10, 2009 (74 FR 57907). The SJVUAPCD...

  12. 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... December 13, 1994 (59 FR 64132), EPA approved into the SIP a previous version of Rule 4402, SJVUAPCD...

  13. 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... IV. Statutory and Executive Order Reviews I. Proposed Action On April 27, 2012 (77 FR 25109), EPA... and Budget under Executive Order 12866 (58 FR 51735, October 4, 1993); does not impose an...

  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... March 27, 1997 (62 FR 14639). The SDAPCD adopted revisions to the SIP- approved version on December...

  15. 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... III. EPA Action IV. Statutory and Executive Order Reviews I. Proposed Action On January 7, 2013 (78 FR... not acting on Rule 802 at this time. \\2\\ See, e.g., 75 FR 8010 (February 23, 2010). Comment...

  16. 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... Action On November 9, 2012 (77 FR 67322), EPA proposed to approve the following rule into the...

  17. 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...

  18. 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...

  19. 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

    ...: EPA is proposing to approve revisions to the Imperial County Air Pollution Control District (ICAPCD... 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...

  20. 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... earlier version of Rule 102 into the SIP on June 29, 1999 (64 FR 34558). PCAPCD adopted revisions to...

  1. 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...

  2. 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...

  3. 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... July 8, 2010 (75 FR 39366), we published a limited approval and limited disapproval of the...

  4. 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

    ... Implementation of Title I of the Clean Air Act Amendments of 1990,'' 59 FR 41998 (August 16, 1994). 5. ``PM-10...: EPA is proposing to approve revisions to the Imperial County Air Pollution Control District (ICAPCD...-2008 monitoring period (74 FR 63309). This determination suspended some of the planning...

  5. 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... earlier version of PCAPCD Rule 218 into the SIP on July 18, 1996 (61 FR 37390). The PCAPCD...

  6. 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...

  7. 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... Order Reviews I. Proposed Action On December 18, 2009 (74 FR 67154), EPA proposed to approve the... and Budget under Executive Order 12866 (58 FR 51735, October 4, 1993); Does not impose an...

  8. 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.... Proposed Action On November 19, 2008 (73 FR 69593), EPA proposed to approve the following rules into...

  9. 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:...

  10. 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...

  11. 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... February 9, 2011 (76 FR 7142), EPA proposed to approve the following rules into the California SIP....

  12. 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... FR 54993), EPA proposed a limited approval and limited disapproval of the following rule that...

  13. 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

    ... FR 2643). III. Statutory and Executive Order Reviews Under the Clean Air Act, the Administrator is... 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...

  14. 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

    ... 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 (August...: EPA is proposing to approve revisions to the Imperial County Air Pollution Control District...

  15. 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... earlier version of Rule 2 into the SIP on February 3, 2000 (65 FR 5262). C. What is the purpose of the... Federalism (64 FR 43255, August 10, 1999) revokes and replaces Executive Orders 12612 (Federalism) and...

  16. 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…

  17. 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

    .... Background On January 13, 2010 (75 FR 1716), EPA published a final limited approval and limited disapproval of revisions to the San Joaquin Valley Unified Air Pollution Control District (SJVUAPCD) portion of... 12866 (58 FR 51735, October 4, 1993), this action is not a ``significant regulatory action''...

  18. 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... previous version of Rule 420 (see 68 FR 8839). CARB has made no subsequent submittals of the rule. C. What..., Imperial County was reclassified as a serious PM nonattainment area (see 69 FR 48792 and 40 CFR part...

  19. 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...

  20. 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

    ... and Executive Order Reviews I. Proposed Action On July 14, 2009 (74 FR 33948), EPA proposed a limited... facilities. Also, please see our response to CPF comment 3. B. San Joaquin Valley Air Pollution Control.... Executive Order 13132, Federalism Federalism (64 FR 43255, August 10, 1999) revokes and replaces...

  1. INTEGRATED AIR POLLUTION CONTROL SYSTEM, VERSION 4.0 - VOLUME 3: PROGRAMMER'S MAINTENANCE 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 ...

  2. 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…

  3. 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 ...

  4. 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...

  5. 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 ...

  6. 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 ...

  7. 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...

  8. 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...

  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

    ... Control District AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: EPA is proposing to approve revisions to the Placer County Air Pollution Control District (PCAPCD) and Sacramento... commercial boilers, stationary internal combustion engines and water heaters. We are proposing to...

  10. INTEGRATED AIR POLLUTION CONTROL FOR COAL-FIRED UTILITY BOILERS: A COMPUTER MODEL APPROACH FOR DESIGN AND COST-ESTIMATING

    EPA Science Inventory

    The paper describes the Integrated Air Pollution Control System (IAPCS), a computerized program that can be used to estimate the cost and performance of pre-combustion, in situ, and post-combustion air pollution control configurations in pulverized-coal-fired utility boilers of 1...

  11. 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

    ... AGENCY Air Pollution Control: Proposed Actions on Clean Air Act Section 105 Grant to the Lane Regional... air pollution control programs will be less than its expenditures were for such programs during the... programs were cut by 31% each while land quality program funds were cut by 44%. ODEQ then reduced...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  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, 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...

  4. 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...

  5. Biocatalytic coatings for air pollution control: a proof of concept study on VOC biodegradation.

    PubMed

    Estrada, José M; Bernal, Oscar I; Flickinger, Michael C; Muñoz, Raúl; Deshusses, Marc A

    2015-02-01

    Although biofilm-based biotechnologies exhibit a large potential as solutions for off-gas treatment, the high water content of biofilms often causes pollutant mass transfer limitations, which ultimately limit their widespread application. The present study reports on the proof of concept of the applicability of bioactive latex coatings for air pollution control. Toluene vapors served as a model volatile organic compound (VOC). The results showed that Pseudomonas putida F1 cells could be successfully entrapped in nanoporous latex coatings while preserving their toluene degradation activity. Bioactive latex coatings exhibited toluene specific biodegradation rates 10 times higher than agarose-based biofilms, because the thin coatings were less subject to diffusional mass transfer limitations. Drying and pollutant starvation were identified as key factors inducing a gradual deterioration of the biodegradation capacity in these innovative coatings. This study constitutes the first application of bioactive latex coatings for VOC abatement. These coatings could become promising means for air pollution control. PMID:25115963

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. Air pollution control and decreasing new particle formation lead to strong climate warming

    NASA Astrophysics Data System (ADS)

    Makkonen, R.; Asmi, A.; Kerminen, V.-M.; Boy, M.; Arneth, A.; Hari, P.; Kulmala, M.

    2011-09-01

    The number of cloud droplets determines several climatically relevant cloud properties. A major cause for the high uncertainty in the indirect aerosol forcing is the availability of cloud condensation nuclei (CCN), which in turn is highly sensitive to atmospheric new particle formation. Here we present the effect of new particle formation on anthropogenic aerosol forcing in present-day (year 2000) and future (year 2100) conditions. The total aerosol forcing (-1.61 W m-2 in year 2000) is simulated to be greatly reduced in the future, to -0.23 W m-2, mainly due to decrease in SO2 emissions and resulting decrease in new particle formation. With the total aerosol forcing decreasing in response to air pollution control measures taking effect, warming from increased greenhouse gas concentrations can potentially increase at a very rapid rate.

  18. Waste minimization versus air pollution controls for a leather finishing facility

    SciTech Connect

    Galligan, J.P.; Korn, D.L.; Serfass, R.W.

    1994-12-31

    This article presents a case study of a leather finishing company faced with meeting the requirements of Best Available Control Technology (BACT) for volatile organic compounds (VOCs) under the Federal Clean Air Act. A Comprehensive Plan Approval Permit Application, including a BACT demonstration addressing each of the facility`s VOC emitting leather coating lines was performed and submitted to the State environmental regulatory agency. The BACT demonstration was a top-down analysis of the environmental, economic, and energy impacts of available, technically feasible air pollution control alternatives. It concluded that a waste minimization plan consisting of coating reformation and process equipment modification represented BACT for the facility on the basis that it was the second most stringent alternative in terms of total VOC control, required the least energy use, generated no liquid VOC waste, and was the most cost effective alternative identified.

  19. Benefit-cost analysis with uncertain information: an application in air pollution control

    SciTech Connect

    Ruby, M.G.

    1981-01-01

    This dissertation develops and demonstrates a form of the net present value decision rule for evaluating the economic advisability of air pollution control policies and projects. It follows a line of argument advanced by earlier authors to derive a formulation of the net present value rule that discounts future benefits and costs at the social rate of time preference but accounts for the lost opportunity costs of the higher returns available to private investments. Using this form, it explores the uncertainties in the resulting calculations, due to inadequate data, for an air pollution control project at a model stationary source of sulfur dioxide air emissions. It examines each of the variables in the rule for both a meso-scale and a long-range transport cast at three levels of background pollutant concentrations. Estimates are given for both the dominance of the variables at specific nominal values and the uncertainty in the individual terms. Detailed reviews are presented of the various financial, effects, and value variables required by the benefit-cost calculation for the model project. The value of an improvement in visibility from a reduction in sulfate particulate matter is calculated for both cases and each background concentration. The economic value of the reduction of ''regional haze'' was found to be greater than the value associated with reducing ''plume blight'' in even the low background case. The calculations of the relative importance and the relative contributions to uncertainty of the different variables gave similar results. Among the more important terms were the pollution estimates from the dispersion model, the value of (the change in risk of) morbidity, the dose-response functions and the thresholds for morbidity, and the financial terms, such as rates of interest. (JMT)

  20. METHODS DEVELOPMENT FOR ASSESSING AIR POLLUTION CONTROL BENEFITS. VOLUME II. EXPERIMENTS IN VALUING NON-MARKET GOODS: A CASE STUDY OF ALTERNATIVE BENEFIT MEASURES OF AIR POLLUTION CONTROL IN THE SOUTH COAST AIR BASIN OF SOUTHERN CALIFORNIA

    EPA Science Inventory

    This volume includes the empirical results obtained from two experiments to measure the health and aesthetic benefits of air pollution control. Each experiment involved the same six neighborhood pairs, where the pairings were made on the basis of similarities in housing character...

  1. EVALUATION OF PILOT-SCALE AIR POLLUTION CONTROL DEVICES ON A REFUSE AND COAL-FIRED BOILER

    EPA Science Inventory

    The project report describes the operation of pilot-scale air pollution control devices to gather data on air pollution efficiency versus several different operating parameters on various waste-as-fuel combustio processes. It also includes a test of a full scale fabric filter use...

  2. CONTROL OF AIR EMISSIONS FROM HAZARDOUS WASTE COMBUSTION SOURCES: FIELD EVALUATIONS OF PILOT-SCALE AIR POLLUTION CONTROL DEVICES

    EPA Science Inventory

    Pilot scale air pollution control devices supplied by Hydro-Sonic Systems, ETS, Inc., and Vulcan Engineering Company were installed at the ENSCO, Inc. Incinerator in El Dorado, Arkansas, in the spring of 1984. Each of these units treated an uncontrolled slipstream of the incinera...

  3. METHODS DEVELOPMENT FOR ASSESSING AIR POLLUTION CONTROL BENEFITS. VOLUME IV. STUDIES ON PARTIAL EQUILIBRIUM APPROACHES TO VALUATION OF ENVIRONMENTAL AMENITIES

    EPA Science Inventory

    The research presented in this volume of a five volume study of the economic benefits of air pollution control explores various facets of the two central project objectives that have not been given adequate attention in the previous volumes. The valuations developed in these prev...

  4. 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

    ... 40 Protection of Environment 9 2013-07-01 2013-07-01 false When must I inspect my HMIWI equipment and air pollution control devices? 62.14441 Section 62.14441 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal...

  5. 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

    ... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Applicability; description of the covered calcium carbide furnaces with wet air pollution control devices subcategory. 424.40 Section 424.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS FERROALLOY MANUFACTURING POINT...

  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

    ... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Applicability; description of the open electric furnaces with wet air pollution control devices subcategory. 424.10 Section 424.10 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS FERROALLOY MANUFACTURING POINT SOURCE CATEGORY...

  7. 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…

  8. INTEGRATED AIR POLLUTION CONTROL SYSTEM (IAPCS) COST MODEL (AIR POLLUTION TECHNOLOGY BRANCH, AIR POLLUTION PREVENTION AND CONTROL DIVISION, NRMRL)

    EPA Science Inventory

    The Air Pollution Technology Branch's (APPCD, NRMRL) Integrated Air Pollution Control System Cost Model is a compiled model written in FORTRAN and C language that is designed to be used on an IBM or compatible PC with 640K or lower RAM and at least 1.5 Mb of hard drive space. It ...

  9. Air pollution control and decreasing new particle formation lead to strong climate warming

    NASA Astrophysics Data System (ADS)

    Makkonen, R.; Asmi, A.; Kerminen, V.-M.; Boy, M.; Arneth, A.; Hari, P.; Kulmala, M.

    2012-02-01

    The number concentration of cloud droplets determines several climatically relevant cloud properties. A major cause for the high uncertainty in the indirect aerosol forcing is the availability of cloud condensation nuclei (CCN), which in turn is highly sensitive to atmospheric new particle formation. Here we present the effect of new particle formation on anthropogenic aerosol forcing in present-day (year 2000) and future (year 2100) conditions. The present-day total aerosol forcing is increased from -1.0 W m-2 to -1.6 W m-2 when nucleation is introduced into the model. Nucleation doubles the change in aerosol forcing between years 2000 and 2100, from +0.6 W m-2 to +1.4 W m-2. Two climate feedbacks are studied, resulting in additional negative forcings of -0.1 W m-2 (+10% DMS emissions in year 2100) and -0.5 W m-2 (+50% BVOC emissions in year 2100). With the total aerosol forcing diminishing in response to air pollution control measures taking effect, warming from increased greenhouse gas concentrations can potentially increase at a very rapid rate.

  10. 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. PMID:20713298

  11. 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

  12. Risk-Based Prioritization among Air Pollution Control Strategies in the Yangtze River Delta, China

    PubMed Central

    Zhou, Ying; Fu, Joshua S.; Zhuang, Guoshun; Levy, Jonathan I.

    2010-01-01

    Background The Yangtze River Delta (YRD) in China is a densely populated region with recent dramatic increases in energy consumption and atmospheric emissions. Objectives We studied how different emission sectors influence population exposures and the corresponding health risks, to inform air pollution control strategy design. Methods We applied the Community Multiscale Air Quality (CMAQ) Modeling System to model the marginal contribution to baseline concentrations from different sectors. We focused on nitrogen oxide (NOx) control while considering other pollutants that affect fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] and ozone concentrations. We developed concentration–response (C-R) functions for PM2.5 and ozone mortality for China to evaluate the anticipated health benefits. Results In the YRD, health benefits per ton of emission reductions varied significantly across pollutants, with reductions of primary PM2.5 from the industry sector and mobile sources showing the greatest benefits of 0.1 fewer deaths per year per ton of emission reduction. Combining estimates of health benefits per ton with potential emission reductions, the greatest mortality reduction of 12,000 fewer deaths per year [95% confidence interval (CI), 1,200–24,000] was associated with controlling primary PM2.5 emissions from the industry sector and reducing sulfur dioxide (SO2) from the power sector, respectively. Benefits were lower for reducing NOx emissions given lower consequent reductions in the formation of secondary PM2.5 (compared with SO2) and increases in ozone concentrations that would result in the YRD. Conclusions Although uncertainties related to C-R functions are significant, the estimated health benefits of emission reductions in the YRD are substantial, especially for sectors and pollutants with both higher health benefits per unit emission reductions and large potential for emission reductions. PMID:20478762

  13. 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.

  14. Nuclear APC.

    PubMed

    Neufeld, Kristi L

    2009-01-01

    Mutational inactivation of the tumor suppressor gene APC (Adenomatous polyposis coli) is thought to be an initiating step in the progression of the vast majority ofcolorectal cancers. Attempts to understand APC function have revealed more than a dozen binding partners as well as several subcellular localizations including at cell-cell junctions, associated with microtubules at the leading edge of migrating cells, at the apical membrane, in the cytoplasm and in the nucleus. The present chapter focuses on APC localization and functions in the nucleus. APC contains two classical nuclear localization signals, with a third domain that can enhance nuclear import. Along with two sets of nuclear export signals, the nuclear localization signals enable the large APC protein to shuttle between the nucleus and cytoplasm. Nuclear APC can oppose beta-catenin-mediated transcription. This down-regulation of nuclear beta-catenin activity by APC most likely involves nuclear sequestration of beta-catenin from the transcription complex as well as interaction of APC with transcription corepressor CtBP. Additional nuclear binding partners for APC include transcription factor activator protein AP-2alpha, nuclear export factor Crm1, protein tyrosine phosphatase PTP-BL and perhaps DNA itself. Interaction of APC with polymerase beta and PCNA, suggests a role for APC in DNA repair. The observation that increases in the cytoplasmic distribution of APC correlate with colon cancer progression suggests that disruption of these nuclear functions of APC plays an important role in cancer progression. APC prevalence in the cytoplasm of quiescent cells points to a potential function for nuclear APC in control of cell proliferation. Clear definition of APC's nuclear function(s) will expand the possibilities for early colorectal cancer diagnostics and therapeutics targeted to APC. PMID:19928349

  15. Impact of air pollution control regulations on thermal enhanced oil recovery production in the United States. Final report

    SciTech Connect

    Norton, J.F.; Rouge, J.D.; Beekley, P.K.; Husband, S.N.; Arnold, C.W.; Menzies, W.R.; Balentine, H.W.

    1982-03-01

    This study assesses the impact of air pollution control regulations on the costs of present and future thermal enhanced oil recovery (TEOR) production. The conclusions of this study indicate that lengthy permitting processes, limited control sytem availability, and costly control system requirements complicate regulatory compliance and constrain TEOR production expansion. Seven heavy oil production areas with potential for increased TEOR production were selected for detailed analyses. Five of these areas are in California: central Kern County, western Kern County, Coalinga, San Ardo, and Los Angeles Basin. The other two areas are the Slocum field in Texas and the Smackover field in Arkansas. Air pollution control rule and regulation requirements were determined for each production area. State-of-the-art air pollution control technology was assessed and costs were estimated for the control systems needed to comply with previous new source review (NSR) and retrofit rules in each area. For each California production area, the maximum potential increase in TEOR production was estimated, based on available emission offsets. Potential increases in the Texas and Arkansas fields were not projected because production is expected to decrease in these areas. Costs were calculated for the control systems required to allow the maximum increase in TEOR production. An air quality impact analysis was performed for the four largest production areas in California. The results of this analysis allowed estimation of the air quality changes associated with the maximum TEOR production increase and compliance with retrofit and NSR rules.

  16. 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.

  17. 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

  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. PMID:25463568

  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. 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

  1. 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.

  2. Fine filtration fabric options designed to help meet the increased demand for more efficient air pollution control equipment

    SciTech Connect

    Winston, A.

    1999-07-01

    The ability to successfully design, purchase, install, and operate air pollution control equipment while still maintaining clean air requirements has become a real challenge to the production sector. Fabric selection for fabric filter dust collectors is part of the air pollution control equipment decision that must be made on a site-specific basis and cannot be generalized from dust collector to dust collector. Filter bags/elements represent a major investment as well as a highly technical decision, which warrants extensive evaluation. After choosing the correct filter bags/elements, it is equally important to protect them in order to keep production at maximum capacity while keeping emissions as low as possible. This paper will discuss the fact that each dust collector has its own set of characteristics and system parameters that are important to evaluate in order to choose a fabric that is best suited for the system. Some of the variables include: Temperature; Moisture Level; Particulate Size; Gas Stream Chemistry; Air-To-Cloth Ratio; Particulate Abrasiveness; and mechanical factors, such as cleaning style, installation, etc. All of these variables will be discussed as they relate to fabric selection and dust collector operation. The specific characteristics of traditional filtration fabrics will also be reviewed to give the audience a proper understanding of what products are available in the marketplace. The main focus of the paper will then be devoted to the developments in filtration technology that have improved the efficiency and operation of dust collection systems in all industries and applications. These developments have been mostly in the areas of expanded polytetrafluoroethylene (PTFE) membrane for fine particulate collection and pleated filter elements utilizing spun bonded media to increase cloth area and efficiency.

  3. Quasi-dynamic leaching characteristics of polychlorinated dibenzo-p-dioxins and dibenzofurans from raw and solidified waste incineration residues.

    PubMed

    Hsi, Hsing-Cheng; Wang, Lin-Chi; Yu, Tsung-Hsien; Chang-Chien, Guo-Ping

    2008-03-01

    Quasi-dynamic leaching characteristics of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from raw and solidified air pollution control (APC) residues were examined via a nine-time multiple leaching test. The effect of injected activated carbon in the APC residues on the PCDD/F leachability was also evaluated. When humic acid solution was used as a leachant, the leaching concentrations of PCDD/Fs fluctuated between the first and the fifth leaching, followed by a gradual increase and then suddenly reached maximum values at the leaching sequences around seventh and eighth. This significant enhancement in PCDD/F leachability was mainly due to an increase in the release of highly chlorinated PCDD/Fs. Leaching of PCDD/Fs with n-hexane was, in contrast, primarily caused by the partitioning of hydrophobic PCDD/Fs between the APC residue surface and the liquid phase of n-hexane. Consequently, the largest leaching concentrations for n-hexane tests achieved at the first leaching, followed by a decrease and reached plateaus. Solidification/stabilization (S/S) decreased the PCDD/F leachability up to the fifth leaching by the use of humic acid solution. However, S/S increased the PCDD/F leaching concentrations and rates with n-hexane. The activated carbon in APC residues significantly inhibited the release of PCDD/F with n-hexane. The inhibiting effect provided by activated carbon was, however, less significant by the use of humic acid solution. PMID:18028984

  4. COMMUNICATING RISK INFORMATION TO STATE AND LOCAL AIR POLLUTION CONTROL AGENCIES VIA U.S. EPA'S AIR RISK INFORMATION SUPPORT CENTER (AIR RISC)

    EPA Science Inventory

    The Air Risk Information Support Center (Air RISC) has been organized by U.S. EPA's offices of Air Quality Planning and Standards and Health and Environmental Assessment. The center has been developed in cooperation with the State and Territorial air Pollution Control Program Adm...

  5. 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

  6. A cost benefit approach to reactor sizing and nutrient supply for biotrickling filters for air pollution control

    SciTech Connect

    Deshusses, M.A.; Cox, H.H.J.

    1999-07-01

    In the present paper, a general model was developed that allows the selection of the most cost-effective operation of biotrickling filters for air pollution control. The model was demonstrated for a typical case of industrial pollution: 10,000 m{sup 3} h{sup {minus}1} airstream contaminated with 1.5 g m{sup {minus}3} toluene. The reactor design and operation were optimized with respect to the nutrient (nitrate) loading, which influenced the pollutant elimination capacity and the rate of reactor clogging by biomass. Integration of all pertinent costs and experimental data into the model demonstrated that biotrickling filtration was very competitive compared to conventional treatment technologies. For the case studied, a treatment cost optimum was obtained at a nutrient loading of 8 g N-nitrate per cubic meter bed volume per day. The range of cost effective treatment was 4 to 30 g N-nitrate m{sup {minus}3} d{sup {minus}1}. Overall, the general approach presented herein is widely applicable for the determination of the best reactor design and the optimum reactor operating conditions.

  7. 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.

  8. 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.

  9. 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.

  10. 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. PMID:25592372

  11. 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. PMID:24467277

  12. 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.

  13. 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

  14. Mechanism of APC/CCDC20 activation by mitotic phosphorylation.

    PubMed

    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

    2016-05-10

    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/C(CDC20) 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/C(CDC20) 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/C(CDC20) 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

  15. 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…

  16. Industrial strength lithography APC

    NASA Astrophysics Data System (ADS)

    Ausschnitt, Christopher P.; Barker, Brian; Muth, William A.; Postiglione, Marc; Walentosky, Thomas

    2003-06-01

    Fully automated semiconductor manufacturing, becoming a reality with the ramping of 300mm fabricators throughout the world, demands the integration of advanced process control (APC). APC is particularly critical for the lithography sector, whose performance correlates to yield and whose productivity often gates the line. We describe the implementation of a comprehensive lithography APC system at the IBM Center for Nanoelectronics, a 300mm manufacturing and development facility. The base lithography APC function encompasses closed-loop run-to-run control of exposure tool inputs to sustain the overlay and critical dimension outputs consistent with product specifications. Automation demands that no decision regarding the appropriate exposure tool run-time settings be left to human judgment. For each lot, the APC system provides optimum settings based on existing data derived from pertinent process streams. In the case where insufficient prior data exists, the APC system either invokes the appropriate combination of send ahead processing and/or pre-determined defaults. We give specific examples of the application of APC to stitched field and dose control, and quantify its technical benefits. Field matching < 0.1 ppm and critical dimension control < 2.5% is achieved among multiple exposure tools and masks.

  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. PMID:24290536

  20. 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

  1. 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...

  2. 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...

  3. Reduced expression of APC-1B but not APC-1A by the deletion of promoter 1B is responsible for familial adenomatous polyposis.

    PubMed

    Yamaguchi, Kiyoshi; Nagayama, Satoshi; Shimizu, Eigo; Komura, Mitsuhiro; Yamaguchi, Rui; Shibuya, Tetsuo; Arai, Masami; Hatakeyama, Seira; Ikenoue, Tsuneo; Ueno, Masashi; Miyano, Satoru; Imoto, Seiya; Furukawa, Yoichi

    2016-01-01

    Germline mutations in the tumor suppressor gene APC are associated with familial adenomatous polyposis (FAP). Here we applied whole-genome sequencing (WGS) to the DNA of a sporadic FAP patient in which we did not find any pathological APC mutations by direct sequencing. WGS identified a promoter deletion of approximately 10 kb encompassing promoter 1B and exon1B of APC. Additional allele-specific expression analysis by deep cDNA sequencing revealed that the deletion reduced the expression of the mutated APC allele to as low as 11.2% in the total APC transcripts, suggesting that the residual mutant transcripts were driven by other promoter(s). Furthermore, cap analysis of gene expression (CAGE) demonstrated that the deleted promoter 1B region is responsible for the great majority of APC transcription in many tissues except the brain. The deletion decreased the transcripts of APC-1B to 39-45% in the patient compared to the healthy controls, but it did not decrease those of APC-1A. Different deletions including promoter 1B have been reported in FAP patients. Taken together, our results strengthen the evidence that analysis of structural variations in promoter 1B should be considered for the FAP patients whose pathological mutations are not identified by conventional direct sequencing. PMID:27217144

  4. Reduced expression of APC-1B but not APC-1A by the deletion of promoter 1B is responsible for familial adenomatous polyposis

    PubMed Central

    Yamaguchi, Kiyoshi; Nagayama, Satoshi; Shimizu, Eigo; Komura, Mitsuhiro; Yamaguchi, Rui; Shibuya, Tetsuo; Arai, Masami; Hatakeyama, Seira; Ikenoue, Tsuneo; Ueno, Masashi; Miyano, Satoru; Imoto, Seiya; Furukawa, Yoichi

    2016-01-01

    Germline mutations in the tumor suppressor gene APC are associated with familial adenomatous polyposis (FAP). Here we applied whole-genome sequencing (WGS) to the DNA of a sporadic FAP patient in which we did not find any pathological APC mutations by direct sequencing. WGS identified a promoter deletion of approximately 10 kb encompassing promoter 1B and exon1B of APC. Additional allele-specific expression analysis by deep cDNA sequencing revealed that the deletion reduced the expression of the mutated APC allele to as low as 11.2% in the total APC transcripts, suggesting that the residual mutant transcripts were driven by other promoter(s). Furthermore, cap analysis of gene expression (CAGE) demonstrated that the deleted promoter 1B region is responsible for the great majority of APC transcription in many tissues except the brain. The deletion decreased the transcripts of APC-1B to 39–45% in the patient compared to the healthy controls, but it did not decrease those of APC-1A. Different deletions including promoter 1B have been reported in FAP patients. Taken together, our results strengthen the evidence that analysis of structural variations in promoter 1B should be considered for the FAP patients whose pathological mutations are not identified by conventional direct sequencing. PMID:27217144

  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. 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 ...

  7. 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…

  8. Air pollution control at a DOE facility

    SciTech Connect

    Curn, B.L.

    1995-11-01

    The Department of Energy (DOE) plutonium production program Produced some of the greatest scientific and engineering accomplishments of all time. It is remarkable to consider the accomplishments of the Manhattan Project. The Reactor on the Hanford Site, the first production reactor in the world, began operation only 13 months after the start of construction. The DOE nuclear production program was also instrumental in pioneering other fields such as health physics an radiation monitoring. The safety record of these installations is remarkable considering that virtually every significant accomplishment was on the technological threshold of the time. One other area that the DOE Facilities pioneered was the control of radioactive particles and gases emitted to the atmosphere. The high efficiency particulate air filter (HEPA) was a development that provided high collection efficiencies of particulates to protect workers and the public. The halogen and noble gases also were of particular concern. Radioactive iodine is captured by adsorption on activated carbon or synthetic zeolites. Besides controlling radioncuclide air pollution, DOE facilities are concerned with other criteria pollutants and hazardous air pollutant emissions. The Hanford Site encompasses all those air pollution challenges.

  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. LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C.

    PubMed

    Masuda, Kenta; Chiyoda, Tatsuyuki; Sugiyama, Naoyuki; Segura-Cabrera, Aldo; Kabe, Yasuaki; Ueki, Arisa; Banno, Kouji; Banno, Koji; Suematsu, Makoto; Aoki, Daisuke; Ishihama, Yasushi; Saya, Hideyuki; Kuninaka, Shinji

    2015-01-01

    In budding yeast, the Mitotic Exit Network (MEN) regulates anaphase promoting complex/cyclosome (APC/C) via the Dbf2-Cdc14 signaling cascade. Dbf2 kinase phosphorylates and activates Cdc14 phosphatase, which removes the inhibitory phosphorylation of the APC/C cofactor Cdh1. Although each component of the MEN was highly conserved during evolution, there is presently no evidence supporting direct phosphorylation of CDC14 by large tumor suppressor kinase 1 (LATS1), the human counterpart of Dbf2; hence, it is unclear how LATS1 regulates APC/C. Here, we demonstrate that LATS1 phosphorylates the Thr7 (T7) residue of the APC/C component CDC26 directly. Nocodazole-induced phosphorylation of T7 was reduced by knockdown of LATS1 and LATS2 in HeLa cells, indicating that both of these kinases contribute to the phosphorylation of CDC26 in vivo. The T7 residue of CDC26 is critical for its interaction with APC6, a tetratricopeptide repeat-containing subunit of APC/C, and mutation of this residue to Asp (T7D) reduced the interaction of CDC26 with APC6. Replacement of endogenous CDC26 in HeLa cells with exogenous phosphor-mimic T7D-mutated CDC26 increased the elution size of APC/C subunits in a gel filtration assay, implying a change in the APC/C assembly upon phosphorylation of CDC26. Furthermore, T7D-mutated CDC26 promoted the ubiquitination of polo-like kinase 1, a well-known substrate of APC/C. Overall, these results suggest that LATS1/2 are novel kinases involved in APC/C phosphorylation and indicate a direct regulatory link between LATS1/2 and APC/C. PMID:25723520

  11. LATS1 and LATS2 Phosphorylate CDC26 to Modulate Assembly of the Tetratricopeptide Repeat Subcomplex of APC/C

    PubMed Central

    Masuda, Kenta; Chiyoda, Tatsuyuki; Sugiyama, Naoyuki; Segura-Cabrera, Aldo; Kabe, Yasuaki; Ueki, Arisa; Banno, Koji; Suematsu, Makoto; Aoki, Daisuke; Ishihama, Yasushi; Saya, Hideyuki; Kuninaka, Shinji

    2015-01-01

    In budding yeast, the Mitotic Exit Network (MEN) regulates anaphase promoting complex/cyclosome (APC/C) via the Dbf2-Cdc14 signaling cascade. Dbf2 kinase phosphorylates and activates Cdc14 phosphatase, which removes the inhibitory phosphorylation of the APC/C cofactor Cdh1. Although each component of the MEN was highly conserved during evolution, there is presently no evidence supporting direct phosphorylation of CDC14 by large tumor suppressor kinase 1 (LATS1), the human counterpart of Dbf2; hence, it is unclear how LATS1 regulates APC/C. Here, we demonstrate that LATS1 phosphorylates the Thr7 (T7) residue of the APC/C component CDC26 directly. Nocodazole-induced phosphorylation of T7 was reduced by knockdown of LATS1 and LATS2 in HeLa cells, indicating that both of these kinases contribute to the phosphorylation of CDC26 in vivo. The T7 residue of CDC26 is critical for its interaction with APC6, a tetratricopeptide repeat-containing subunit of APC/C, and mutation of this residue to Asp (T7D) reduced the interaction of CDC26 with APC6. Replacement of endogenous CDC26 in HeLa cells with exogenous phosphor-mimic T7D-mutated CDC26 increased the elution size of APC/C subunits in a gel filtration assay, implying a change in the APC/C assembly upon phosphorylation of CDC26. Furthermore, T7D-mutated CDC26 promoted the ubiquitination of polo-like kinase 1, a well-known substrate of APC/C. Overall, these results suggest that LATS1/2 are novel kinases involved in APC/C phosphorylation and indicate a direct regulatory link between LATS1/2 and APC/C. PMID:25723520

  12. 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

  13. Regulation of the phosphorylation and nuclear import and export of β-catenin by APC and its cancer-related truncated form.

    PubMed

    Wang, Lili; Liu, Xiaoyong; Gusev, Ekaterina; Wang, Chuanxin; Fagotto, François

    2014-04-15

    We report the first direct analysis of the endogenous β-catenin phosphorylation activity in colon cancer SW480 cells. By comparing parental SW480 cells that harbor a typical truncated adenomatous polyposis coli (APC) form, cells expressing full-length APC and APC-depleted cells, we provide the formal demonstration that APC is necessary for β-catenin phosphorylation, both for priming of the protein at residue serine 45 and for the subsequent phosphorylation of residues 33, 37 and 41. Truncated APC still sustains a surprisingly high phosphorylation activity, which requires the protein to bind to β-catenin through the APC 20-amino-acid (20AA) repeats, thus providing a biochemical explanation for the precise truncations found in cancer cells. We also show that most of the β-catenin phosphorylation activity is associated with a dense insoluble fraction. We finally examine the impact of full-length and truncated APC on β-catenin nuclear transport. We observe that β-catenin is transported much faster than previously thought. Although this fast translocation is largely insensitive to the presence of wild-type or truncated APC, the two forms appear to limit the pool of β-catenin that is available for transport, which could have an impact on β-catenin nuclear activities in normal and cancer cells. PMID:24496450

  14. APC functions at the centrosome to stimulate microtubule growth.

    PubMed

    Lui, Christina; Ashton, Cahora; Sharma, Manisha; Brocardo, Mariana G; Henderson, Beric R

    2016-01-01

    The adenomatous polyposis coli (APC) tumor suppressor is multi-functional. APC is known to localize at the centrosome, and in mitotic cells contributes to formation of the mitotic spindle. To test whether APC contributes to nascent microtubule (MT) growth at interphase centrosomes, we employed MT regrowth assays in U2OS cells to measure MT assembly before and after nocodazole treatment and release. We showed that siRNA knockdown of full-length APC delayed both initial MT aster formation and MT elongation/regrowth. In contrast, APC-mutant SW480 cancer cells displayed a defect in MT regrowth that was unaffected by APC knockdown, but which was rescued by reconstitution of full-length APC. Our findings identify APC as a positive regulator of centrosome MT initial assembly and suggest that this process is disrupted by cancer mutations. We confirmed that full-length APC associates with the MT-nucleation factor γ-tubulin, and found that the APC cancer-truncated form (1-1309) also bound to γ-tubulin through APC amino acids 1-453. While binding to γ-tubulin may help target APC to the site of MT nucleation complexes, additional C-terminal sequences of APC are required to stimulate and stabilize MT growth. PMID:26556314

  15. 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

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

    PubMed

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

    2016-02-01

    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 PP2A(B56) allows Ube2S to bind the APC/C and catalyze ubiquitin chain elongation. PP2A(B56) 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

  17. Attenuated APC alleles produce functional protein from internal translation initiation

    PubMed Central

    Heppner Goss, Kathleen; Trzepacz, Chris; Tuohy, Thérèse M. F.; Groden, Joanna

    2002-01-01

    Some truncating mutations of the APC tumor suppressor gene are associated with an attenuated phenotype of familial adenomatous polyposis coli (AAPC). This work demonstrates that APC alleles with 5′ mutations produce APC protein that down-regulates β-catenin, inhibits β-catenin/T cell factor-mediated transactivation, and induces cell-cycle arrest. Transfection studies demonstrate that cap-independent translation is initiated internally at an AUG at codon 184 of APC. Furthermore, APC coding sequence between AAPC mutations and AUG 184 permits internal ribosome entry in a bicistronic vector. These data suggest that AAPC alleles in vivo may produce functional APC by internal initiation and establish a functional correlation between 5′ APC mutations and their associated clinical phenotype. PMID:12034871

  18. 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.

  19. 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

    2016-05-12

    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

  20. 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

  1. 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

  2. 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.

  3. HAZARDOUS/TOXIC AIR POLLUTANT CONTROL TECHNOLOGY: A LITERATURE REVIEW

    EPA Science Inventory

    The report summarizes literature on hazardous/toxic air pollutant (HAP) sources and control techniques employed in their reduction and/or destruction. The information was abstracted from an extensive computerized and manual literature search and data base development study. The p...

  4. 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.

  5. AIR CLEANERS FOR INDOOR AIR POLLUTION CONTROL (CHAPTER 10)

    EPA Science Inventory

    The chapter describes an experimental study to evaluate performance characteristics of currently available controls for indoor air pollutants, including both particles and gases. he study evaluated the particle-size-dependent collection efficiency of seven commercially available ...

  6. Hot metal runner system with air pollution controls

    SciTech Connect

    La Bate, M.D.

    1982-10-26

    A runner for hot metal as from a blast furnace is formed of a series of interconnected modular units which are prefabricated, preferably from refractory based materials. A plurality of flat slab-like covers are positioned continuously on the runners formed of the interconnected modular units so as to confine fumes , gas, smoke and other air pollutants. Live steam is introduced at selected locations along the runners to collect, absorb and mix with the fumes, gases and air pollutants. Vacuum devices in communication with the covered runners remove the air, steam and pollutants and direct them through scrubbers and/or precipitron equipment to remove the air pollutants before the air entrained in the system is released to the atmosphere.

  7. 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,…

  8. Interaction between APC and Fen1 during breast carcinogenesis.

    PubMed

    Narayan, Satya; Jaiswal, Aruna S; Law, Brian K; Kamal, Mohammad A; Sharma, Arun K; Hromas, Robert A

    2016-05-01

    Aberrant DNA base excision repair (BER) contributes to malignant transformation. However, inter-individual variations in DNA repair capacity plays a key role in modifying breast cancer risk. We review here emerging evidence that two proteins involved in BER - adenomatous polyposis coli (APC) and flap endonuclease 1 (Fen1) - promote the development of breast cancer through novel mechanisms. APC and Fen1 expression and interaction is increased in breast tumors versus normal cells, APC interacts with and blocks Fen1 activity in Pol-β-directed LP-BER, and abrogation of LP-BER is linked with cigarette smoke condensate-induced transformation of normal breast epithelial cells. Carcinogens increase expression of APC and Fen1 in spontaneously immortalized human breast epithelial cells, human colon cancer cells, and mouse embryonic fibroblasts. Since APC and Fen1 are tumor suppressors, an increase in their levels could protect against carcinogenesis; however, this does not seem to be the case. Elevated Fen1 levels in breast and lung cancer cells may reflect the enhanced proliferation of cancer cells or increased DNA damage in cancer cells compared to normal cells. Inactivation of the tumor suppressor functions of APC and Fen1 is due to their interaction, which may act as a susceptibility factor for breast cancer. The increased interaction of APC and Fen1 may occur due to polypmorphic and/or mutational variation in these genes. Screening of APC and Fen1 polymorphic and/or mutational variations and APC/Fen1 interaction may permit assessment of individual DNA repair capability and the risk for breast cancer development. Such individuals might lower their breast cancer risk by reducing exposure to carcinogens. Stratifying individuals according to susceptibility would greatly assist epidemiologic studies of the impact of suspected environmental carcinogens. Additionally, a mechanistic understanding of the interaction of APC and Fen1 may provide the basis for developing new and

  9. APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome

    PubMed Central

    Kops, Geert J. P. L.; van der Voet, Monique; Manak, Michael S.; van Osch, Maria H. J.; Naini, Said M.; Brear, Andrea; McLeod, Ian X.; Hentschel, Dirk M.; Yates, John R.; van den Heuvel, Sander; Shah, Jagesh V.

    2010-01-01

    Error-free chromosome segregation depends on timely activation of the multi-subunit E3 ubiquitin ligase APC/C. Activation of the APC/C initiates chromosome segregation and mitotic exit by targeting critical cell-cycle regulators for destruction. The APC/C is the principle target of the mitotic checkpoint, which prevents segregation while chromosomes are unattached to spindle microtubules. We now report the identification and characterization of APC16, a conserved subunit of the APC/C. APC16 was found in association with tandem-affinity-purified mitotic checkpoint complex protein complexes. APC16 is a bona fide subunit of human APC/C: it is present in APC/C complexes throughout the cell cycle, the phenotype of APC16-depleted cells copies depletion of other APC/C subunits, and APC16 is important for APC/C activity towards mitotic substrates. APC16 sequence homologues can be identified in metazoans, but not fungi, by four conserved primary sequence stretches. We provide evidence that the C. elegans gene K10D2.4 and the D. rerio gene zgc:110659 are functional equivalents of human APC16. Our findings show that APC/C is composed of previously undescribed subunits, and raise the question of why metazoan APC/C is molecularly different from unicellular APC/C. PMID:20392738

  10. HectD1 E3 ligase modifies adenomatous polyposis coli (APC) with polyubiquitin to promote the APC-axin interaction.

    PubMed

    Tran, Hoanh; Bustos, Daisy; Yeh, Ronald; Rubinfeld, Bonnee; Lam, Cynthia; Shriver, Stephanie; Zilberleyb, Inna; Lee, Michelle W; Phu, Lilian; Sarkar, Anjali A; Zohn, Irene E; Wertz, Ingrid E; Kirkpatrick, Donald S; Polakis, Paul

    2013-02-01

    The adenomatous polyposis coli (APC) protein functions as a negative regulator of the Wnt signaling pathway. In this capacity, APC forms a "destruction complex" with Axin, CK1α, and GSK3β to foster phosphorylation of the Wnt effector β-catenin earmarking it for Lys-48-linked polyubiquitylation and proteasomal degradation. APC is conjugated with Lys-63-linked ubiquitin chains when it is bound to Axin, but it is unclear whether this modification promotes the APC-Axin interaction or confers upon APC an alternative function in the destruction complex. Here we identify HectD1 as a candidate E3 ubiquitin ligase that modifies APC with Lys-63 polyubiquitin. Knockdown of HectD1 diminished APC ubiquitylation, disrupted the APC-Axin interaction, and augmented Wnt3a-induced β-catenin stabilization and signaling. These results indicate that HectD1 promotes the APC-Axin interaction to negatively regulate Wnt signaling. PMID:23277359

  11. Functional Comparison of Human Adenomatous Polyposis Coli (APC) and APC-Like in Targeting Beta-Catenin for Degradation

    PubMed Central

    Schneikert, Jean; Vijaya Chandra, Shree Harsha; Ruppert, Jan Gustav; Ray, Suparna; Wenzel, Eva Maria; Behrens, Jürgen

    2013-01-01

    Truncating mutations affect the adenomatous polyposis coli (APC) gene in most cases of colon cancer, resulting in the stabilization of β-catenin and uncontrolled cell proliferation. We show here that colon cancer cell lines express also the paralog APC-like (APCL or APC2). RNA interference revealed that it controls the level and/or the activity of β-catenin, but it is less efficient and binds less well to β-catenin than APC, thereby providing one explanation as to why the gene is not mutated in colon cancer. A further comparison indicates that APCL down-regulates the β-catenin level despite the lack of the 15R region known to be important in APC. To understand this discrepancy, we performed immunoprecipitation experiments that revealed that phosphorylated β-catenin displays a preference for binding to the 15 amino acid repeats (15R) rather than the first 20 amino acid repeat of APC. This suggests that the 15R region constitutes a gate connecting the steps of β-catenin phosphorylation and subsequent ubiquitination/degradation. Using RNA interference and domain swapping experiments, we show that APCL benefits from the 15R of truncated APC to target β-catenin for degradation, in a process likely involving heterodimerization of the two partners. Our data suggest that the functional complementation of APCL by APC constitutes a substantial facet of tumour development, because the truncating mutations of APC in colorectal tumours from familial adenomatous polyposis (FAP) patients are almost always selected for the retention of at least one 15R. PMID:23840886

  12. 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

  13. Intestinal flora of FAP patients containing APC-like sequences.

    PubMed

    Hainova, K; Adamcikova, Z; Ciernikova, S; Stevurkova, V; Tyciakova, S; Zajac, V

    2014-01-01

    Colorectal cancer mortality is one of the most common cause of cancer-related mortality. A multiple risk factors are associated with colorectal cancer, including hereditary, enviromental and inflammatory syndromes affecting the gastrointestinal tract. Familial adenomatous polyposis (FAP) is characterized by the emergence of hundreds to thousands of colorectal adenomatous polyps and FAP syndrome is caused by mutations within the adenomatous polyposis coli (APC) tumor suppressor gene. We analyzed 21 rectal bacterial subclones isolated from FAP patient 41-1 with confirmed 5bp ACAAA deletion within codons 1060-1063 for the presence of APC-like sequences in longest exon 15. The studied section was defined by primers 15Efor-15Erev, what correlates with mutation cluster region (MCR) in which the 75% of all APC germline mutations were detected. More than 90% homology was showed by sequencing and subsequent software comparison. The expression of APC-like sequences was demostrated by Western blot analysis using monoclonal and polyclonal antibodies against APC protein. To study missing link between the DNA analysis (PCR, DNA sequencing) and protein expresion experiments (Western blotting) we analyzed bacterial transcripts containing the 15Efor-15Erev sequence of APC gene by reverse transcription-PCR, what indicated that an APC gene derived fragment may be produced. We observed 97-100 % homology after computer comparison of cDNA PCR products. Our results suggest that presence of APC-like sequences in intestinal/rectal bacteria is enrichment of bacterial genetic information in which horizontal gene transfer between humans and microflora play an important role. PMID:24824929

  14. 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

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

    PubMed

    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

  16. EM Structure of human APC/CCDH1-EMI1 reveals multimodal mechanism of E3 ligase shutdown

    PubMed Central

    Frye, Jeremiah J.; Brown, Nicholas G.; Petzold, Georg; Watson, Edmond R.; Grace, Christy R. R.; Nourse, Amanda; Jarvis, Marc A.; Kriwacki, Richard W.; Peters, Jan-Michael; Stark, Holger; Schulman, Brenda A.

    2013-01-01

    The Anaphase Promoting Complex/Cyclosome (APC/C) is a ~1.5 MDa multiprotein E3 ligase enzyme that regulates cell division by promoting timely ubiquitin-mediated proteolysis of key cell cycle regulatory proteins. Inhibition of human APC/CCDH1 during interphase by Early Mitotic Inhibitor 1 (EMI1) is essential for accurate coordination of DNA synthesis and mitosis. Here, we report a hybrid structural approach involving NMR, electron microscopy, and enzymology, which reveal that EMI1’s 143-residue C-terminal domain inhibits multiple APC/CCDH1 functions. The intrinsically disordered D-box, Linker, and Tail elements, together with a structured zinc-binding domain, bind distinct regions of APC/CCDH1 to synergistically both block the substrate-binding site and inhibit ubiquitin chain elongation. The functional importance of intrinsic structural disorder is explained by enabling a small inhibitory domain to bind multiple sites to shut down multiple functions of a “molecular machine” nearly 100 times its size. PMID:23708605

  17. APC germline mutations in families with familial adenomatous polyposis.

    PubMed

    De Queiroz Rossanese, Lillian Barbosa; De Lima Marson, Fernando Augusto; Ribeiro, José Dirceu; Coy, Claudio Saddy Rodrigues; Bertuzzo, Carmen Silvia

    2013-11-01

    Adenomatous polyposis coli (APC) germline mutations are responsible for the occurrence of familial adenomatous polyposis (FAP). Somatic mutations lead to malignant transformation of adenomas. In this context, considering the significance of APC germline mutations in FAP, we aimed to identify APC germline mutations. In the present study, 20 FAP patients were enrolled. The determination of APC germline mutations was performed using sequencing, and the mutations were compared with clinical markers (gender, age at diagnosis, smoking habits, TNM stage, Astler‑Coller stage, degree of differentiation of adenocarcinoma). The data were compared using the SPSS program, with the Fisher's exact test and χ2 test, considering α=0.05. According to the main results in our sample, 16 alleles with deleterious mutations (80% of the patients) were identified while 7 (35%) patients had no deleterious mutations. There was a predominance of nonsense (45% of the patients) and frameshift (20% of the patients) mutations. There was no statistical significance between the APC germline mutations identified and the clinical variables considered in our study. Only TNM stage was associated with the presence of deleterious mutations. Patients with deleterious mutations had an OR, 0.086 (IC=0.001-0.984); TNM stage I+II in comparison with III+IV, when compared with the patients with no deleterious mutations identified. In this context, as a conclusion, we demonstrated the molecular heterogeneity of APC germline mutations in FAP and the difficulty to perform molecular diagnostics in a Brazilian population, considering the admixed population analyzed. PMID:23970361

  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. Cell-Type Specific Expression of Apc in Lung Development, Injury and Repair

    PubMed Central

    Li, Aimin; Xing, Yiming; Chan, Belinda; Heisterkamp, Nora; Groffen, John; Borok, Zea; Minoo, Parviz; Li, Changgong

    2010-01-01

    Adenomatous polyposis coli (Apc) is critical for Wnt signaling and cell migration. The current study examined Apc expression during lung development, injury and repair. Apc was first detectable in smooth muscle layers in early lung morphogenesis, and was highly expressed in ciliated and neuroendocrine cells in the advanced stages. No Apc immunoreactivity was detected in Clara or basal cells, which function as stem/progenitor cell in adult lung. In ciliated cells, Apc is associated mainly with apical cytoplasmic domain. In response to naphthalene induced injury, Apcpositive cells underwent squamous metaplasia, accompanied by changes in Apc subcellular distribution. In conclusion, both spatial and temporal expression of Apc is dynamically regulated during lung development and injury repair. Differential expression of Apc in progenitor vs. non-progenitor cells suggests a functional role in cell type specification. Subcellular localization changes of Apc in response to naphthalene injury suggest a role in cell shape and cell migration. PMID:20658693

  20. 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

  1. 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.

  2. APC mutations in colorectal tumors with mismatch repair deficiency.

    PubMed Central

    Huang, J; Papadopoulos, N; McKinley, A J; Farrington, S M; Curtis, L J; Wyllie, A H; Zheng, S; Willson, J K; Markowitz, S D; Morin, P; Kinzler, K W; Vogelstein, B; Dunlop, M G

    1996-01-01

    We have investigated the influence of genetic instability [replication error (RER) phenotype] on APC (adenomatous polyposis coli), a gene thought to initiate colorectal tumorigenesis. The prevalence of APC mutations was similar in RER and non-RER tumors, indicating that both tumor types share this step in neoplastic transformation. However, in a total of 101 sequenced mutations, we noted a substantial excess of APC frameshift mutations in the RER cases (70% in RER tumors versus 47% in non-RER tumors, P < 0.04). These frameshifts were characteristic of mutations arising in cells deficient in DNA mismatch repair, with a predilection for mononucleotide repeats in the RER tumors (P < 0.0002), particularly (A)n tracts (P < 0.00007). These findings suggest that the genetic instability that is reflected by the RER phenotype precedes, and is responsible for, APC mutation in RER large bowel tumors and have important implications for understanding the very earliest stages of neoplasia in patients with tumors deficient in mismatch repair. Images Fig. 2 PMID:8799152

  3. 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

  4. Redefining the subcellular location and transport of APC: new insights using a panel of antibodies

    PubMed Central

    Brocardo, Mariana; Näthke, Inke S; Henderson, Beric R

    2005-01-01

    Adenomatous polyposis coli (APC) is a tumour suppressor involved in colon cancer progression. We and others previously described nuclear–cytoplasmic shuttling of APC. However, there are conflicting reports concerning the localization of endogenous wild-type and tumour-associated, truncated APC. To resolve this issue, we compared APC localization using immunofluorescence (IF) microscopy and cell fractionation with nine different APC antibodies. We found that three commonly used APC antibodies showed nonspecific nuclear staining by IF and validated this conclusion in cells where APC was inactivated using small interfering RNA or Cre/Flox. Fractionation showed that wild-type and truncated APC from colon cancer cells were primarily cytoplasmic, but increased in the nucleus after leptomycin B treatment, consistent with CRM1-dependent nuclear export. In contrast to recent reports, our biochemical data indicate that APC nuclear localization is not regulated by changes in cell density, and that APC nuclear export is not prevented by truncating mutations in cancer. These results verify that the bulk of APC resides in the cytoplasm and indicate the need for caution when evaluating the nuclear accumulation of APC. PMID:15678162

  5. 42 CFR 419.31 - Ambulatory payment classification (APC) system and payment weights.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Ambulatory payment classification (APC) system and... Outpatient Services § 419.31 Ambulatory payment classification (APC) system and payment weights. (a) APC... OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM PROSPECTIVE PAYMENT SYSTEM FOR...

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

    PubMed

    Di Fiore, Barbara; Davey, Norman E; Hagting, Anja; Izawa, Daisuke; Mansfeld, Jörg; Gibson, Toby J; Pines, Jonathon

    2015-02-01

    The anaphase-promoting complex or cyclosome (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 recognizes 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 we show that it binds to the APC/C coactivator 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

  7. 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

  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. 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

  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. The APC tumor suppressor is required for epithelial cell polarization and three-dimensional morphogenesis.

    PubMed

    Lesko, Alyssa C; Goss, Kathleen H; Yang, Frank F; Schwertner, Adam; Hulur, Imge; Onel, Kenan; Prosperi, Jenifer R

    2015-03-01

    The Adenomatous Polyposis Coli (APC) tumor suppressor has been previously implicated in the control of apical-basal polarity; yet, the consequence of APC loss-of-function in epithelial polarization and morphogenesis has not been characterized. To test the hypothesis that APC is required for the establishment of normal epithelial polarity and morphogenesis programs, we generated APC-knockdown epithelial cell lines. APC depletion resulted in loss of polarity and multi-layering on permeable supports, and enlarged, filled spheroids with disrupted polarity in 3D culture. Importantly, these effects of APC knockdown were independent of Wnt/β-catenin signaling, but were rescued with either full-length or a carboxy (c)-terminal segment of APC. Moreover, we identified a gene expression signature associated with APC knockdown that points to several candidates known to regulate cell-cell and cell-matrix communication. Analysis of epithelial tissues from mice and humans carrying heterozygous APC mutations further supports the importance of APC as a regulator of epithelial behavior and tissue architecture. These data also suggest that the initiation of epithelial-derived tumors as a result of APC mutation or gene silencing may be driven by loss of polarity and dysmorphogenesis. PMID:25578398

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

    PubMed

    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

  14. Cellular Factors Targeting APCs to Modulate Adaptive T Cell Immunity

    PubMed Central

    Do, Jeongsu; Min, Booki

    2014-01-01

    The fate of adaptive T cell immunity is determined by multiple cellular and molecular factors, among which the cytokine milieu plays the most important role in this process. Depending on the cytokines present during the initial T cell activation, T cells become effector cells that produce different effector molecules and execute adaptive immune functions. Studies thus far have primarily focused on defining how these factors control T cell differentiation by targeting T cells themselves. However, other non-T cells, particularly APCs, also express receptors for the factors and are capable of responding to them. In this review, we will discuss how APCs, by responding to those cytokines, influence T cell differentiation and adaptive immunity. PMID:25126585

  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. APC/C is an essential regulator of centrosome clustering.

    PubMed

    Drosopoulos, Konstantinos; Tang, Chan; Chao, William C H; Linardopoulos, Spiros

    2014-01-01

    Centrosome amplification has been extensively associated with cancer. Cancer cells with extra centrosomes have the ability to cluster the extra centrosomes and divide in a bipolar fashion. Although a number of proteins have been shown to be involved in centrosome clustering, a mechanistic understanding of how this process is coordinated is not yet well defined. Here, to reveal regulators of centrosome clustering, we perform small interfering RNA (siRNA) screens with multiple assay readouts in a human isogenic cellular model. We find that APC/C activity is essential for centrosome clustering. We show that the motor kinesin Eg5 is a substrate of APC/C-CDH1, and that inhibition of APC/C results in stabilization of Eg5. Increased Eg5 protein levels disturb the balance of forces on the spindle and prevent centrosome clustering. This process is completely reversed after a short treatment with the Eg5 inhibitor, monastrol. These data advance our understanding of the regulation of centrosome clustering. PMID:24751481

  17. Multiloop photolithography control using hierarchical context information for APC models

    NASA Astrophysics Data System (ADS)

    Stuber, John D.

    2003-06-01

    Automated process control loops running in semiconductor manufacturing facilities must be able to compensate for machine variations as well as identify differences between products. With a number of exposure tools, pattern levels, and active devices manufactured in a typical ASIC fab, for photo APC system must maintain thousands of control loops. Control loop context information in TI's Semiconductor Manufacturing System (SMS) is defined in a hierarchal fashion which allows default values in a manufacturing specification to be overridden for particular products or lots. ProcessWORKS APC software automatically adds new control loops for new devices and pattern levels to a defined model structure. This system scales well and supports hundreds of thousands of control loops from a single database server in TI fabs. Application of product specific control systems for alignment and exposure control has provided increased exposure capacity due to decreased reworks and setup time, a substantial reduction in engineering maintenance and improved process capability. The APC system has evolved into a requirement for leading edge photolithography processes in Texas Instruments.

  18. Intestinal Peyer's patches prevent tumorigenesis in Apc (Min/+) mice.

    PubMed

    Fujimoto, Kyoko; Fujii, Gen; Sakurai, Hitomi; Yoshitome, Hiroko; Mutoh, Michihiro; Wada, Morimasa

    2015-01-01

    Peyer's patches are nodules that play a central role in intestinal immunity. Few studies demonstrate the relationship between the number of Peyer's patches and intestinal polyps. Here we identify a statistically significant inverse correlation between the quantity of Peyer's patches and of the development of intestinal polyps in Apc (Min/+) mice, which are a useful model to clarify the role of Peyer's patches in intestinal tumorigenesis. Using this model, we increased the number of Peyer's patches using 0.1% and 1% corn husk arabinoxylan through feed. Intestinal polyp formation significantly decreased, concomitant with an increase in Peyer's patches development (n = 12/group). In Aly (-/-) Apc (Min/+) mice (negative control; no Peyer's patches) there was no change in the amount of intestinal polyps (n = 10/group). Immune reaction following corn husk arabinoxylan treatment was measured by cytokine array. Increasing the number of Peyer's patches decreased interleukin-17 production, which showed a dose dependent correlation with transcription factor/lymphoid enhancer-binding factor. This study identified a relationship between levels of Peyer's patches and intestinal polyp formation, partly explained by the involvement of interleukin-17 production and β-catenin signaling in Apc (Min/+) mice. PMID:25678750

  19. The tissue effect of argon-plasma coagulation with prior submucosal injection (Hybrid-APC) versus standard APC: A randomized ex-vivo study

    PubMed Central

    Neugebauer, Alexander; Scharpf, Marcus; Braun, Kirsten; May, Andrea; Ell, Christian; Fend, Falko; Enderle, Markus D

    2014-01-01

    Background Thermal ablation for Barrett’s oesophagus has widely been established in gastrointestinal endoscopy during the last decade. The mainly used methods of radiofrequency ablation (RFA) and argon-plasma coagulation (APC) carry a relevant risk of stricture formation of up to 5–15%. Newer ablation techniques that are able to overcome this disadvantage would therefore be desirable. The aim of the present study was to compare the depth of tissue injury of the new method of Hybrid-APC versus standard APC within a randomized study in a porcine oesophagus model. Methods Using a total of eight explanted pig oesophagi, 48 oesophageal areas were ablated either by standard or Hybrid-APC (APC with prior submucosal fluid injection) using power settings of 50 and 70 W. The depth of tissue injury to the oesophageal wall was analysed macroscopically and histopathologically. Results Using 50 W, mean coagulation depth was 937 ± 469 µm during standard APC, and 477 ± 271 µm during Hybrid-APC (p = 0.064). Using 70 W, coagulation depth was 1096 ± 320 µm (standard APC) and 468 ± 136 µm (Hybrid-APC; p = 0.003). During all settings, damage to the muscularis mucosae was observed. Using standard APC, damage to the submucosal layer was observed in 4/6 (50 W) and 6/6 cases (70 W). During Hybrid-APC, coagulation of the submucosal layer occurred in 2/6 (50 W) and 1/6 cases (70 W). The proper muscle layer was only damaged during conventional APC (50 W: 1/6; 70 W: 3/6). Limitations Ex-vivo animal study with limited number of cases. Conclusions Hybrid-APC reduces coagulation depth by half in comparison with standard APC, with no thermal injury to the proper muscle layer. It may therefore lead to a lower rate of stricture formation during clinical application. PMID:25360316

  20. Nuclear-cytoplasmic shuttling of APC regulates beta-catenin subcellular localization and turnover.

    PubMed

    Henderson, B R

    2000-09-01

    Mutational inactivation of the APC gene is a key early event in the development of familial adenomatous polyposis and colon cancer. APC suppresses tumour progression by promoting degradation of the oncogenic transcriptional activator beta-catenin. APC gene mutations can lead to abnormally high levels of beta-catenin in the nucleus, and the consequent activation of transforming genes. Here, we show that APC is a nuclear-cytoplasmic shuttling protein, and that it can function as a beta-catenin chaperone. APC contains two active nuclear export sequences (NES) at the amino terminus, and mutagenesis of these conserved motifs blocks nuclear export dependent on the CRM1 export receptor. Treatment of cells with the CRM1-specific export inhibitor leptomycin B shifts APC from cytoplasm to nucleus. beta-catenin localization is also regulated by CRM1, but in an APC-dependent manner. Transient expression of wild-type APC in SW480 (APCmut/mut) colon cancer cells enhances nuclear export and degradation of beta-catenin, and these effects can be blocked by mutagenesis of the APC NES. These findings suggest that wild-type APC controls the nuclear accumulation of beta-catenin by a combination of nuclear export and cytoplasmic degradation. PMID:10980707

  1. The ins and outs of APC and β-catenin nuclear transport

    PubMed Central

    Henderson, Beric R.; Fagotto, Francois

    2002-01-01

    Adenomatous polyposis coli (APC) and β-catenin, two key interacting proteins implicated in development and cancer, were recently found to traffic into and out of the nucleus in response to internal and external signals. The two proteins can enter and exit the nucleus independently, a discovery that has prompted debate about the previously proposed role of APC as a β-catenin chaperone. Here, we review the regulation of APC and β-catenin subcellular localization, in particular in cancer cells. We speculate that, in non-stimulated cells, APC actively exports β-catenin from the nucleus to the cytoplasm where its levels are regulated by degradation; and, conversely, that, in cancer cells or those stimulated by Wnt signaling, β-catenin degradation is inhibited and the accruing protein is capable of moving between the nucleus and cytoplasm independently of APC. Models that link APC and β-catenin transport to function are discussed. PMID:12223464

  2. The ins and outs of APC and beta-catenin nuclear transport.

    PubMed

    Henderson, Beric R; Fagotto, Francois

    2002-09-01

    Adenomatous polyposis coli (APC) and beta-catenin, two key interacting proteins implicated in development and cancer, were recently found to traffic into and out of the nucleus in response to internal and external signals. The two proteins can enter and exit the nucleus independently, a discovery that has prompted debate about the previously proposed role of APC as a beta-catenin chaperone. Here, we review the regulation of APC and beta-catenin subcellular localization, in particular in cancer cells. We speculate that, in non-stimulated cells, APC actively exports beta-catenin from the nucleus to the cytoplasm where its levels are regulated by degradation; and, conversely, that, in cancer cells or those stimulated by Wnt signaling, beta-catenin degradation is inhibited and the accruing protein is capable of moving between the nucleus and cytoplasm independently of APC. Models that link APC and beta-catenin transport to function are discussed. PMID:12223464

  3. 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

  4. Extensive metabolic disorders are present in APC(min) tumorigenesis mice.

    PubMed

    Liu, Zhenzhen; Xiao, Yi; Zhou, Zhengxiang; Mao, Xiaoxiao; Cai, Jinxing; Xiong, Lu; Liao, Chaonan; Huang, Fulian; Liu, Zehao; Ali Sheikh, Md Sayed; Plutzky, Jorge; Huang, He; Yang, Tianlun; Duan, Qiong

    2016-05-15

    Wnt signaling plays essential role in mesenchymal stem cell (MSC) differentiation. Activation of Wnt signaling suppresses adipogenesis, but promotes osteogenesis in MSC. Adenomatous polyposis coli (APC) is a negative regulator of β-catenin and Wnt signaling activity. The mutation of APC gene leads to the activation of Wnt signaling and is responsible for tumorigenesis in APC(min) mouse; however, very few studies focused on its metabolic abnormalities. The present study reports a widespread metabolic disorder phenotype in APC(min) mice. The old APC(min) mice have decreased body weight and impaired adipogenesis, but severe hyperlipidemia, which mimic the phenotypes of Familial Adenomatous Polyposis (FAP), an inherited disease also caused by APC gene mutation in human. We found that the expression of lipid metabolism and free fat acids (FA) use genes in the white adipose tissue (WAT) of the APC(min) mice is much lower than those of control. The changed gene expression pattern may lead to the disability of circulatory lipid transportation and storage at WAT. Moreover, the APC(min) mice could not maintain the core body temperature in cold condition. PET-CT determination revealed that the BAT of APC(min) mice has significantly impaired ability to take up (18)FDG from the blood. Morphological studies identified that the brown adipocytes of APC(min) mice were filled with lipid droplets but fewer mitochondria. These results matched with the findings of impaired BAT function in APC(min) mice. Collectively, our study explores a new mechanism that explains abnormal metabolism in APC(min) mice and provides insights into studying the metabolic disorders of FAP patients. PMID:26948948

  5. 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.

  6. 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.

  7. 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.

  8. APC mutation and the crypt cycle in murine and human intestine.

    PubMed Central

    Bjerknes, M.; Cheng, H.; Hay, K.; Gallinger, S.

    1997-01-01

    Dysplastic colon adenomas are thought to arise from growth of clones of APC -/- colonic epithelial cells. Isolated clusters of dysplastic crypts are often observed in patients with familial adenomatous polyposis. These patients have genotype APC +/-, and the clusters of dysplastic crypts (called microadenoma or aberrant crypt foci) are thought to represent an early stage in the expansion of a mutant clone of APC -/- cells. It is thought that the growth of these clusters of mutant crypts results from crypt replication through a process similar to what occurs in the normal crypt cycle. We measured the relative replication rate of mutant crypts by analyzing the size of clusters of mutant crypts in APC +/- individuals and found that mutant APC -/- crypts replicate more rapidly than do normal APC +/- (i.e., nonneoplastic) crypts. In contrast, the replication rate of mutant crypts in Apc +/- mice is not significantly different from that of normal crypts, thus supporting previous findings that aberrant crypt foci do not contribute significantly to the colon adenoma population in adult Apc +/- mice. Intriguingly, we found an effect of Apc heterozygosity on the frequency of branching crypts in young mice. PMID:9060821

  9. 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.

  10. A trellis-searched APC (adaptive predictive coding) speech coder

    SciTech Connect

    Malone, K.T. ); Fischer, T.R. . Dept. of Electrical and Computer Engineering)

    1990-01-01

    In this paper we formulate a speech coding system that incorporates trellis coded vector quantization (TCVQ) and adaptive predictive coding (APC). A method for optimizing'' the TCVQ codebooks is presented and experimental results concerning survivor path mergings are reported. Simulation results are given for encoding rates of 16 and 9.6 kbps for a variety of coder parameters. The quality of the encoded speech is deemed excellent at an encoding rate of 16 kbps and very good at 9.6 kbps. 13 refs., 2 figs., 4 tabs.

  11. Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon.

    PubMed

    2006-01-01

    Sipuleucel-T [APC 8015, Provenge] is an autologous, dendritic cell-based vaccine under development with Dendreon Corporation for the treatment of androgen-independent and androgen-dependent prostate cancer. It was generated using the company's active immunotherapy platform to stimulate a patient's own immune system to specifically target and destroy cancer cells, while leaving healthy cells unharmed. This approach could provide patients with a meaningful survival benefit and an improved tolerability profile over existing anticancer therapies. Sipuleucel-T selectively targets the prostate-specific antigen (PSA) known as prostatic acid phosphatase (PAP) that is expressed in approximately 95% of prostate cancers. It is produced by ex vivo exposure of dendritic cell precursors to PA 2024, a recombinant fusion protein composed of the PAP target fused to granulocyte-macrophage colony-stimulating factor (GM-CSF) and incorporated into Dendreon's proprietary Antigen Delivery Cassette. Patients are typically administered three intravenous (IV)-infusions of the vaccine over a 1-month period as a complete course of therapy. It is undergoing late-stage clinical evaluation among patients with early and advanced prostate cancer. In November 2003, Kirin Brewery returned to Dendreon the full rights to Sipuleucel-T for Asia. In exchange, Dendreon licensed patent rights relating to the use of certain HLA-DR antibodies to Kirin for $US20 million. This amended agreement enables Dendreon to complete ongoing discussions for a worldwide marketing and sales partnership for Sipuleucel-T. Similarly, Kirin is able to develop its HLA-DR monoclonal antibodies free of potential infringement claims arising from Dendreon's patent rights to HLA-DR. The licensing agreement relates to patent rights owned by Dendreon relating to monoclonal antibodies against the HLA-DR antigen. In addition, Dendreon retains rights to develop and commercialise its two existing HLA-DR monoclonal antibodies, DN 1921 and

  12. Tumorigenic fragments of APC cause dominant defects in directional cell migration in multiple model systems.

    PubMed

    Nelson, Scott A; Li, Zhouyu; Newton, Ian P; Fraser, David; Milne, Rachel E; Martin, David M A; Schiffmann, David; Yang, Xuesong; Dormann, Dirk; Weijer, Cornelis J; Appleton, Paul L; Näthke, Inke S

    2012-11-01

    Nonsense mutations that result in the expression of truncated, N-terminal, fragments of the adenomatous polyposis coli (APC) tumour suppressor protein are found in most sporadic and some hereditary colorectal cancers. These mutations can cause tumorigenesis by eliminating β-catenin-binding sites from APC, which leads to upregulation of β-catenin and thereby results in the induction of oncogenes such as MYC. Here we show that, in three distinct experimental model systems, expression of an N-terminal fragment of APC (N-APC) results in loss of directionality, but not speed, of cell motility independently of changes in β-catenin regulation. We developed a system to culture and fluorescently label live pieces of gut tissue to record high-resolution three-dimensional time-lapse movies of cells in situ. This revealed an unexpected complexity of normal gut cell migration, a key process in gut epithelial maintenance, with cells moving with spatial and temporal discontinuity. Quantitative comparison of gut tissue from wild-type mice and APC heterozygotes (APC(Min/+); multiple intestinal neoplasia model) demonstrated that cells in precancerous epithelia lack directional preference when moving along the crypt-villus axis. This effect was reproduced in diverse experimental systems: in developing chicken embryos, mesoderm cells expressing N-APC failed to migrate normally; in amoeboid Dictyostelium, which lack endogenous APC, expressing an N-APC fragment maintained cell motility, but the cells failed to perform directional chemotaxis; and multicellular Dictyostelium slug aggregates similarly failed to perform phototaxis. We propose that N-terminal fragments of APC represent a gain-of-function mutation that causes cells within tissue to fail to migrate directionally in response to relevant guidance cues. Consistent with this idea, crypts in histologically normal tissues of APC(Min/+) intestines are overpopulated with cells, suggesting that a lack of migration might cause cell

  13. 42 CFR 419.31 - Ambulatory payment classification (APC) system and payment weights.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Ambulatory payment classification (APC) system and payment weights. 419.31 Section 419.31 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT... Outpatient Services § 419.31 Ambulatory payment classification (APC) system and payment weights. (a)...

  14. 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...

  15. 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

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

    DOE PAGESBeta

    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

  17. Modeling the effect of APC truncation on destruction complex function in colorectal cancer cells.

    PubMed

    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 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. 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. Specific inhibition of CK1ε is predicted to limit binding of

  18. Critical Current Properties in Longitudinal Magnetic Field of YBCO Superconductor with APC

    NASA Astrophysics Data System (ADS)

    Kido, R.; Kiuchi, M.; Otabe, E. S.; Matsushita, T.; Jha, A. K.; Matsumoto, K.

    The critical current density (Jc) properties of the Artificial Pinning Center (APC) introduced YBa2Cu3O7 (YBCO) films in the longitudinal magnetic field were measured. Y2O3 or Y2BaCuO5 (Y211) was introduced as APCs to YBCO, and YBCO films with APC were fabricated on SrTiO3 single crystal substrate. The sizes of Y2O3 and Y211 were 5-10 nm and 10-20 nm, respectively. As a result, Jc enhancement in the longitudinal magnetic field was observed in Y2O3 introduced YBCO films. However, it was not observed in Y211 introduced YBCO films. Therefore, it was considered that Jc properties in the longitudinal magnetic field were affected by introducing of small size APC, and it was necessary that APC does not disturb the current pathway in the superconductor.

  19. A knock-in mouse model reveals roles for nuclear Apc in cell proliferation, Wnt signal inhibition and tumor suppression.

    PubMed

    Zeineldin, M; Cunningham, J; McGuinness, W; Alltizer, P; Cowley, B; Blanchat, B; Xu, W; Pinson, D; Neufeld, K L

    2012-05-10

    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 the 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 cofactor for genes required for cell proliferation such as cyclin-D1 and c-Myc. In cultured cells, APC shuttles between the nucleus and the cytoplasm, with nuclear APC implicated in the inhibition of Wnt target gene expression. Adopting 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 (NLSs) of Apc (Apc(mNLS)). Apc(mNLS/mNLS) mice are viable and fractionation of mouse embryonic fibroblasts (MEFs) isolated from these mice revealed a significant reduction in nuclear Apc as compared with Apc(+/+) MEFs. The levels of Apc and β-catenin protein were not significantly altered in small intestinal epithelia from Apc(mNLS/mNLS) mice. Compared with Apc(+/+) mice, Apc(mNLS/mNLS) mice showed increased proliferation in epithelial cells from the jejunum, ileum and colon. These same tissues from Apc(mNLS/mNLS) mice showed more mRNA from three genes upregulated in response to canonical Wnt signal, c-Myc, axin-2 and cyclin-D1, and less mRNA from Hath-1, which is downregulated in response to Wnt. These observations suggest a role for nuclear Apc in the inhibition of canonical Wnt signaling and the control of epithelial proliferation in intestinal tissue. Furthermore, we found Apc(Min/+) mice, which harbor a mutation that truncates Apc, to have an increased polyp size and multiplicity if they also carry the Apc(mNLS) allele. Taken together, this analysis of the novel Apc(mNLS) mouse model supports a role for nuclear Apc in the control of Wnt target genes

  20. Loss of Rassf1a co-operates with ApcMin to accelerate intestinal tumourigenesis

    PubMed Central

    van der Weyden, L.; Arends, M.J.; Dovey, O.M.; Harrison, H. L.; Lefebvre, G.; Conte, N.; Gergely, F.V.; Bradley, A.; Adams, D.J.

    2013-01-01

    Promoter methylation of the RAS-association domain family 1, isoform A gene (RASSF1A) is one of the most frequent events found in human tumours. In this study we set out to test the hypothesis that loss of Rassf1a can co-operate with inactivation of the adenomatous polyposis coli (Apc) gene to accelerate intestinal tumourigenesis using the Apc-Min (ApcMin/+) mouse model, as mutational or deletional inactivation of APC is a frequent early event in the genesis of intestinal cancer. Further, loss of RASSF1A has also been reported to occur in premalignant adenomas of the bowel. RASSF1A has been implicated in an array of pivotal cellular processes, including regulation of the cell cycle, apoptosis, microtubule stability and most recently in the β-catenin signalling pathway. By interbreeding isoform specific Rassf1a knockout mice with Apc+/Min mice we showed that loss of Rassf1a results in a significant increase in adenomas of the small intestine and accelerated intestinal tumourigenesis leading to the earlier death of adenocarcinoma-bearing mice and decreased overall survival. Comparative genomic hybridization of adenomas from Rassf1a−/−; Apc+/Min mice revealed no evidence of aneuploidy or gross chromosomal instability (no difference to adenomas from Rassf1a+/+; Apc+/Min mice). Immunohistochemical analysis of adenomas revealed increased nuclear β-catenin accumulation in adenomas from Rassf1a−/−; Apc+/Min mice, compared to those from Rassf1a+/+; Apc+/Min mice, but no differences in proliferation marker (Ki67) staining patterns. Collectively these data demonstrate co-operation between inactivation of Rassf1a and Apc resulting in accelerated intestinal tumourigenesis, with adenomas showing increased nuclear accumulation of β-catenin, supporting a mechanistic link via loss of the known interaction of Rassf1 with β-TrCP that usually mediates degradation of β-catenin. PMID:18391979

  1. Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells.

    PubMed

    Wong, N C; Novakovic, B; Weinrich, B; Dewi, C; Andronikos, R; Sibson, M; Macrae, F; Morley, R; Pertile, M D; Craig, J M; Saffery, R

    2008-09-01

    Methylation of the human APC gene promoter is associated with several different types of cancers and has also been documented in some pre-cancerous tissues. We have examined the methylation of APC gene promoters in human placenta and choriocarcinoma cells. This revealed a general hypomethylation of the APC-1b promoter and a pattern with monoallelic methylation of the APC-1a promoter in full term placental tissue. However, there was no evidence of a parent-of-origin effect, suggesting random post zygotic origin of methylation. Increased methylation of this promoter was observed in all choriocarcinoma-derived trophoblast cell lines, suggesting a trophoblastic origin of placental APC methylation and implicating APC hypermethylation in the development of this group of gestational tumours. Our demonstration of placental methylation of the APC-1a promoter represents the first observation of monoallelic methylation of this gene in early development, and provides further support for a role of canonical Wnt signalling in placental trophoblast invasiveness. This also implicates tumour suppressor gene silencing as an integral part of normal human placental development. PMID:18485586

  2. APC2 and Axin promote mitotic fidelity by facilitating centrosome separation and cytoskeletal regulation.

    PubMed

    Poulton, John S; Mu, Frank W; Roberts, David M; Peifer, Mark

    2013-10-01

    To ensure the accurate transmission of genetic material, chromosome segregation must occur with extremely high fidelity. Segregation errors lead to chromosomal instability (CIN), with deleterious consequences. Mutations in the tumor suppressor adenomatous polyposis coli (APC) initiate most colon cancers and have also been suggested to promote disease progression through increased CIN, but the mechanistic role of APC in preventing CIN remains controversial. Using fly embryos as a model, we investigated the role of APC proteins in CIN. Our findings suggest that APC2 loss leads to increased rates of chromosome segregation error. This occurs through a cascade of events beginning with incomplete centrosome separation leading to failure to inhibit formation of ectopic cleavage furrows, which result in mitotic defects and DNA damage. We test several hypotheses related to the mechanism of action of APC2, revealing that APC2 functions at the embryonic cortex with several protein partners, including Axin, to promote mitotic fidelity. Our in vivo data demonstrate that APC2 protects genome stability by modulating mitotic fidelity through regulation of the cytoskeleton. PMID:24026117

  3. Parafibromin and APC as screening markers for malignant potential in atypical parathyroid adenomas.

    PubMed

    Juhlin, C Christofer; Nilsson, Inga-Lena; Johansson, Kenth; Haglund, Felix; Villablanca, Andrea; Höög, Anders; Larsson, Catharina

    2010-09-01

    The identification of parathyroid carcinomas is based upon histopathological criteria in which an invasive growth pattern or distant metastasis is demonstrated. A dilemma arises when tumours present with atypical histopathological features but lack direct evidence of malignancy. Recently, reduced expression or loss of the tumour suppressor proteins parafibromin and adenomatous polyposis coli (APC) has been associated with parathyroid malignancy. We report results from APC and parafibromin expression analyses by immunohistochemistry and Western blot in five cases of atypical adenoma, a single case of carcinoma and 54 adenomas without atypical features. Complete loss of APC immunoreactivity and reduced expression of parafibromin was evident in two of the atypical adenomas and in the parathyroid carcinoma. By contrast, all adenomas displayed APC expression, including two cases with hyperparathyroidism 2 gene (HRPT2) mutations and loss of parafibromin expression. We conclude that loss of APC is a frequent molecular event in atypical adenomas and carcinomas, but not in adenomas. Following verification in an independent material, APC could become a valuable tool when assessing parathyroid tumours in the clinical setting. Furthermore, the molecular resemblance of atypical adenomas with carcinoma concerning parafibromin and APC expression indicates that atypical adenomas should be subjects to watchful follow-up. PMID:20473645

  4. 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

  5. Prostate Cancer Induced by Loss of Apc Is Restrained by TGFβ Signaling

    PubMed Central

    Bjerke, Glen A.; Pietrzak, Karolina; Melhuish, Tiffany A.; Frierson Jr., Henry F.; Paschal, Bryce M.; Wotton, David

    2014-01-01

    Recent work with mouse models of prostate cancer (CaP) has shown that inactivation of TGFβ signaling in prostate epithelium can cooperate with deletion of the Pten tumor suppressor to drive locally aggressive cancer and metastatic disease. Here, we show that inactivating the TGFβ pathway by deleting the gene encoding the TGFβ type II receptor (Tgfbr2) in combination with a deletion of the Apc tumor suppressor gene specifically in mouse prostate epithelium, results in the rapid onset of invasive CaP. Micro-metastases were observed in the lymph nodes and lungs of a proportion of the double mutant mice, whereas no metastases were observed in Apc single mutant mice. Prostate-specific Apc;Tgfbr2 mutants had a lower frequency of metastasis and survived significantly longer than Pten;Tgfbr2 double mutants. However, all Apc;Tgfbr2 mutants developed invasive cancer by 30 weeks of age, whereas invasive cancer was rarely observed in Apc single mutant animals, even by one year of age. Further comparison of the Pten and Apc models of CaP revealed additional differences, including adenosquamous carcinoma in the Apc;Tgfbr2 mutants that was not seen in the Pten model, and a lack of robust induction of the TGFβ pathway in Apc null prostate. In addition to causing high-grade prostate intra-epithelial neoplasia (HGPIN), deletion of either Pten or Apc induced senescence in affected prostate ducts, and this restraint was overcome by loss of Tgfbr2. In summary, this work demonstrates that TGFβ signaling restrains the progression of CaP induced by different tumor suppressor mutations, suggesting that TGFβ signaling exerts a general tumor suppressive effect in prostate. PMID:24651496

  6. Tumorigenic fragments of APC cause dominant defects in directional cell migration in multiple model systems

    PubMed Central

    Nelson, Scott A.; Li, Zhouyu; Newton, Ian P.; Fraser, David; Milne, Rachel E.; Martin, David M. A.; Schiffmann, David; Yang, Xuesong; Dormann, Dirk; Weijer, Cornelis J.; Appleton, Paul L.; Näthke, Inke S.

    2012-01-01

    SUMMARY Nonsense mutations that result in the expression of truncated, N-terminal, fragments of the adenomatous polyposis coli (APC) tumour suppressor protein are found in most sporadic and some hereditary colorectal cancers. These mutations can cause tumorigenesis by eliminating β-catenin-binding sites from APC, which leads to upregulation of β-catenin and thereby results in the induction of oncogenes such as MYC. Here we show that, in three distinct experimental model systems, expression of an N-terminal fragment of APC (N-APC) results in loss of directionality, but not speed, of cell motility independently of changes in β-catenin regulation. We developed a system to culture and fluorescently label live pieces of gut tissue to record high-resolution three-dimensional time-lapse movies of cells in situ. This revealed an unexpected complexity of normal gut cell migration, a key process in gut epithelial maintenance, with cells moving with spatial and temporal discontinuity. Quantitative comparison of gut tissue from wild-type mice and APC heterozygotes (APCMin/+; multiple intestinal neoplasia model) demonstrated that cells in precancerous epithelia lack directional preference when moving along the crypt-villus axis. This effect was reproduced in diverse experimental systems: in developing chicken embryos, mesoderm cells expressing N-APC failed to migrate normally; in amoeboid Dictyostelium, which lack endogenous APC, expressing an N-APC fragment maintained cell motility, but the cells failed to perform directional chemotaxis; and multicellular Dictyostelium slug aggregates similarly failed to perform phototaxis. We propose that N-terminal fragments of APC represent a gain-of-function mutation that causes cells within tissue to fail to migrate directionally in response to relevant guidance cues. Consistent with this idea, crypts in histologically normal tissues of APCMin/+ intestines are overpopulated with cells, suggesting that a lack of migration might cause

  7. Adenomatous polyposis coli (APC) regulates multiple signaling pathways by enhancing glycogen synthase kinase-3 (GSK-3) activity.

    PubMed

    Valvezan, Alexander J; Zhang, Fang; Diehl, J Alan; Klein, Peter S

    2012-02-01

    Glycogen synthase kinase-3 (GSK-3) is essential for many signaling pathways and cellular processes. As Adenomatous Polyposis Coli (APC) functions in many of the same processes, we investigated a role for APC in the regulation of GSK-3-dependent signaling. We find that APC directly enhances GSK-3 activity. Furthermore, knockdown of APC mimics inhibition of GSK-3 by reducing phosphorylation of glycogen synthase and by activating mTOR, revealing novel roles for APC in the regulation of these enzymes. Wnt signaling inhibits GSK-3 through an unknown mechanism, and this results in both stabilization of β-catenin and activation of mTOR. We therefore hypothesized that Wnts may regulate GSK-3 by disrupting the interaction between APC and the Axin-GSK-3 complex. We find that Wnts rapidly induce APC dissociation from Axin, correlating with β-catenin stabilization. Furthermore, Axin interaction with the Wnt co-receptor LRP6 causes APC dissociation from Axin. We propose that APC regulates multiple signaling pathways by enhancing GSK-3 activity, and that Wnts induce APC dissociation from Axin to reduce GSK-3 activity and activate downstream signaling. APC regulation of GSK-3 also provides a novel mechanism for Wnt regulation of multiple downstream effectors, including β-catenin and mTOR. PMID:22184111

  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. Impact of Atomic Gap Size on Sensitivity and Backaction of APC Displacement Detectors

    NASA Astrophysics Data System (ADS)

    Flowers-Jacobs, N. E.; Lehnert, K. W.

    2008-03-01

    Recently our group created a mesoscopic displacement detector formed by coupling an atomic point contact (APC) to a nanomechanical beam and demonstrated a displacement imprecision limited by the fundamental shot-noise in the number of electrons that tunnel across the APC [1]. We continue this work by using a cryogenic apparatus that flexes the device substrate to mechanically adjust the size of the APC atomic gap in situ. The resulting changes in the APC displacement detector's intrinsic noise properties are measured by observing the 1 K random thermal motion of the nanomechanical beam at resonance frequencies up to 200 MHz. The goal of this work is to explore the effect of atomic gap size and shape on displacement sensitivity, understand the origin of the observed measurement backaction, and measure the recoil force of tunneling electrons. [1] N. E. Flowers-Jacobs, D. R. Schmidt, and K. W. Lehnert, Phys. Rev. Lett. 98, 096804 (2007)

  10. Quercetin Supplementation Attenuates the Progression of Cancer Cachexia in ApcMin/+ Mice123

    PubMed Central

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

    2014-01-01

    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 ApcMin/+ 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 ApcMin/+ mice gavaged with V (ApcMin/+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 ApcMin/+ mice gavaged with quercetin (ApcMin/+Q; −9% ± 1.3). At 18 wk of age, the loss of grip strength and muscle mass shown in ApcMin/+V mice was significantly attenuated (P < 0.05) in ApcMin/+Q mice. Furthermore, ApcMin/+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 ApcMin/+Q mice, despite having a similar tumor burden. Quercetin treatment did not improve treadmill run-time-to-fatigue, hyperglycemia, or hyperlipidemia in cachectic ApcMin/+ mice. Overall, quercetin supplementation positively affected several aspects of

  11. 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.

  12. 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

  13. 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

  14. The APC/C Ubiquitin Ligase: From Cell Biology to Tumorigenesis

    PubMed Central

    Penas, Clara; Ramachandran, Vimal; Ayad, Nagi George

    2011-01-01

    The ubiquitin proteasome system (UPS) is required for normal cell proliferation, vertebrate development, and cancer cell transformation. The UPS consists of multiple proteins that work in concert to target a protein for degradation via the 26S proteasome. Chains of an 8.5-kDa protein called ubiquitin are attached to substrates, thus allowing recognition by the 26S proteasome. Enzymes called ubiquitin ligases or E3s mediate specific attachment to substrates. Although there are over 600 different ubiquitin ligases, the Skp1–Cullin–F-box (SCF) complexes and the anaphase promoting complex/cyclosome (APC/C) are the most studied. SCF involvement in cancer has been known for some time while APC/C’s cancer role has recently emerged. In this review we will discuss the importance of APC/C to normal cell proliferation and development, underscoring its possible contribution to transformation. We will also examine the hypothesis that modulating a specific interaction of the APC/C may be therapeutically attractive in specific cancer subtypes. Finally, given that the APC/C pathway is relatively new as a cancer target, therapeutic interventions affecting APC/C activity may be beneficial in cancers that are resistant to classical chemotherapy. PMID:22655255

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

    PubMed

    Chang, Leifu; Zhang, Ziguo; Yang, Jing; McLaughlin, Stephen H; Barford, David

    2015-06-25

    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 early mitotic inhibitor 1 (Emi1) ensures the correct order and timing of distinct cell-cycle transitions. Here we use 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 future experiments to investigate APC/C functions in vivo. PMID:26083744

  16. Adenomatous Polyposis Coli (APC) Is Required for Normal Development of Skin and Thymus

    PubMed Central

    Kuraguchi, Mari; Wang, Xiu-Ping; Bronson, Roderick T; Rothenberg, Rebecca; Ohene-Baah, Nana Yaw; Lund, Jennifer J; Kucherlapati, Melanie; Maas, Richard L; Kucherlapati, Raju

    2006-01-01

    The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt signaling pathway that is involved in development and tumorigenesis. Heterozygous knockout mice for Apc have a tumor predisposition phenotype and homozygosity leads to embryonic lethality. To understand the role of Apc in development we generated a floxed allele. These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. Mice homozygous for the floxed allele that also carry the K14-cre transgene were viable but had stunted growth and died before weaning. Histological and immunochemical examinations revealed that K14-cre–mediated Apc loss resulted in aberrant growth in many ectodermally derived squamous epithelia, including hair follicles, teeth, and oral and corneal epithelia. In addition, squamous metaplasia was observed in various epithelial-derived tissues, including the thymus. The aberrant growth of hair follicles and other appendages as well as the thymic abnormalities in K14-cre; ApcCKO/CKO mice suggest the Apc gene is crucial in embryonic cells to specify epithelial cell fates in organs that require epithelial–mesenchymal interactions for their development. PMID:17002498

  17. Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts.

    PubMed

    Lorca, T; Castro, A; Martinez, A M; Vigneron, S; Morin, N; Sigrist, S; Lehner, C; Dorée, M; Labbé, J C

    1998-07-01

    The Xenopus homologue of Drosophila Fizzy and budding yeast CDC20 has been characterized. The encoded protein (X-FZY) is a component of a high molecular weight complex distinct from the APC/cyclosome. Antibodies directed against FZY were produced and shown to prevent calmodulin-dependent protein kinase II (CaMKII) from inducing the metaphase to anaphase transition of spindles assembled in vitro in Xenopus egg extracts, and this was associated with suppression of the degradation of mitotic cyclins. The same antibodies suppressed M phase-promoting factor (MPF)-dependent activation of the APC/cyclosome in interphase egg extracts, although they did not appear to alter the pattern or extent of MPF-dependent phosphorylation of APC/cyclosome subunits. As these phosphorylations are thought to be essential for APC/cyclosome activation in eggs and early embryos, we conclude that at least two events are required for MPF to activate the APC/cyclosome, allowing both chromatid segregation and full degradation of mitotic cyclins. The first one, which does not require FZY function, is the phosphorylation of APC/cyclosome subunits. The second one, that requires FZY function (even in the absence of MAD2 protein and when the spindle assembly checkpoint is not activated) is not yet understood at its molecular level. PMID:9649427

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

    PubMed

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

    2016-02-01

    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. 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

  20. 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

  1. 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

    ... SIP on April 2, 1998 (64 FR 15922). We approved an earlier version of SMAQMD Rule 466 into the SIP on May 5, 2010 (75 FR 24406). We approved an earlier version of SCAQMD Rule 1171 into the SIP on July 1, 2005 (70 FR 38023). There are no previous versions of SCAMQD Rule 1148.1 in the SIP. C. What is...

  2. 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

    ... SIP on April 30, 1996 (61 FR 18962), February 12, 1996 (61 FR 5288), and January 24, 1985 (50 FR 3338... Office of Management and Budget under Executive Order 12866 (58 FR 51735, October 4, 1993); Does not... Executive Order 13132 (64 FR 43255, August 10, 1999); Is not an economically significant regulatory...

  3. A COMPUTER SIMULATION MODEL--FOR ANALYZING MOBILE SOURCE AIR POLLUTION CONTROL STRATEGIES

    EPA Science Inventory

    This report describes MATHAIR, a computer model that simulates the impacts of strategies for controlling mobile source air pollutants. Vehicle miles traveled (VMT) for different modes of ground transportation are predicted by a transportation module. Given VMT predictions, an inv...

  4. 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…

  5. 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

    ... and Executive Order Reviews I. Proposed Action On May 19, 2011 (76 FR 28944), EPA proposed a limited... Federalism (64 FR 43255, August 10, 1999) revokes and replaces Executive Orders 12612 (Federalism) and 12875..., entitled ``Consultation and Coordination with Indian Tribal Governments'' (65 FR 67249, November 9,...

  6. 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

    ... EPA. I. Background On July 27, 2011 (76 FR 44809), we published a limited approval and limited... Federal sanctions and imposes no additional requirements. Under Executive Order 12866 (58 FR 51735..., ``Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use'' (66...

  7. 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

    ... EPA rulemaking (76 FR 44809, July 27, 2011). EPA is also making a technical amendment to the Code of... February 22, 2013 (78 FR 12267), EPA proposed a limited approval and limited disapproval of the following.... See 78 FR 12267, 12269 second column (``If EPA finalizes the limited approval and limited...

  8. 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

    ... June 23, 1982 (47 FR 27065) and May 18, 1981 (46 FR 27115), respectively. The PCAPCD originally adopted...'s May 5, 2010 (75 FR 24409) reclassification as a severe ozone nonattainment area, the rules... EPA. (67 FR 80186) \\1\\ While the District uses the term BACT as the level of control required,...

  9. Preparation of Nanofibrous Metal-Organic Framework Filters for Efficient Air Pollution Control.

    PubMed

    Zhang, Yuanyuan; Yuan, Shuai; Feng, Xiao; Li, Haiwei; Zhou, Junwen; Wang, Bo

    2016-05-11

    Environmental challenges especially air pollution (particulate matter (PM) and toxic gases) pose serious threats to public health globally. Metal-organic frameworks (MOFs) are crystalline materials with high porosity, tunable pore size, and rich functionalities, holding the promise for poisonous pollutants capture. Here, nanocrystals of four unique MOF structures are processed into nanofibrous filters (noted as MOFilter) with high MOF loadings (up to 60 wt %). The MOFilters show high PM removal efficiencies up to 88.33 ± 1.52% and 89.67 ± 1.33% for PM2.5 and PM10, respectively, in the hazy environment, and the performance remains largely unchanged over 48 h of continuous filtration. For the first time, the interactions between such porous crystalline material and particulate pollutants were explored. These thin MOFilters can further selectively capture and retain SO2 when exposed to a stream of SO2/N2 mixture, and their hierarchical nanostructures can easily permeate fresh air at high gas flow rate with the pressure drop <20 Pa. PMID:27090776

  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

    ... compound (VOC) emissions from steam-enhanced crude oil production well vents, aerospace coating operations.... Statutory and Executive Order Reviews I. Proposed Action On July 17, 2009 (74 FR 34704), EPA proposed a... 4684 but not addressed by the 2008 CTG. See 74 FR 34705. SJVAPCD Aug. 17 Comment #2: The...

  11. 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...

  12. 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,...

  13. Removal of polynuclear aromatic hydrocarbons from primary aluminum air pollution control scrubber wastewater

    SciTech Connect

    Dempsey, C.R.; Dostal, K.A.; Osantowski, R.A.

    1984-05-01

    A pilot-scale study was conducted at a primary aluminum plant to evaluate the removal of benzo(a)pyrene and other polynuclear aromatic hydrocarbons (PAH's) from potline scrubber wastewater. Specific objectives included determining the need for granular activated carbon to remove the PAH's to 10 micrograms/l and evaluating the use of benzo(a)pyrene as an indicator for the removal of all PAH's.

  14. 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

    ... compound (VOC) emissions from solvent cleaning machines and solvent cleaning operations and oil and gas... local rules: SBAPCD Rule 321, ``Solvent Cleaning Machines and Solvent Cleaning'', SMAQMD Rule...

  15. 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)

  16. 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).

  17. 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....

  18. Pollution-control equipment (Chile). Air-pollution-control equipment, September 1991. Export trade information

    SciTech Connect

    Not Available

    1991-09-01

    Chile relies upon imports to satisfy its needs for equipment for environmental control. Despite the lack of specific statistics that could provide precise information, environmental specialists evaluate the U.S. position as quite promising in terms of sales prospects. As far as current market share in domestic market it is estimated that U.S. products have 40% of the Chilean market. U.S. imports should grow at least 30%, at the same growth rate of the total market.

  19. 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. PMID:12188464

  20. 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

    ... the Clean Air Act Amendments of 1990''; 57 FR ] 13498 (April 16, 1992); 57 FR 18070 (April 28, 1992... 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...

  1. 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.

  2. 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.

  3. 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... Rule 400 into the SIP on August 11, 2005 (70 FR 46770). The MBUAPCD adopted revisions to the SIP.../15/04 version of the rule on June 30, 2010 (75 FR 37727) C. What is the purpose of the submitted...

  4. New Application of Seawater and Electrolyzed Seawater in Air Pollution Control of Marine Diesel Engine

    NASA Astrophysics Data System (ADS)

    An, Sukheon; Nishida, Osami

    It is the purpose of this paper to introduce the usage of seawater and its electrolysis for the exhaust emission control in marine diesel engines. First, with using only seawater that is naturally alkaline (pH typically around 8.1), the SO2 and SO3 are absorbed by relatively high solubility compared to other components of exhaust pollutants, and PMs (Particulate Matter) are removed through direct contact with the sprayed seawater droplets. Besides, the electrolyzed alkaline seawater by electrolysis, which contains mainly NaOH together with alkali metal ions (i. e. Na+, Mg2+, Ca2+), is used as the absorption medium of NOx and CO2. Conditionally, before the NOx absorption treatment with using the alkaline seawater, nitric oxide (NO) must be adequately oxidized to nitrogen dioxide (NO2) by the acidic seawater in order to increase NOx absorption rate into the alkaline seawater. Because NOx absorption is the most suited to conditions when both volume fractions (NO: NO2 ratio) are of equal portions. Finally, this research would also plan to treat the effluent by applying electro-dialysis and electro-flotation techniques in the future. The way to reduce emissions from the marine diesel engines is to make it attractive from an operating perspective, as well as an environmental perspective.

  5. 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

    ... minimis level. Id. at 42011. \\19\\ 75 FR 8008, 8010, and proposal TSD, pp. 5-7. Open areas: --Windblown... Order Reviews I. Summary of Proposed Action On February 23, 2010 (75 FR 8008), EPA proposed a limited... section E.6 for recreational use of public lands in Imperial County. \\6\\ 75 FR 8008, 8010-8011 and...

  6. 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)....

  7. RETROFIT AIR POLLUTION CONTROL FILTER FOR RESTAURANT UNDERFIRED CHARBROILERS - PHASE I

    EPA Science Inventory

    Each day about 700,000 U.S. food service operations/restaurants emit more than 285 tons of particulate matter (PM) and more than 41 tons of volatile organic compounds (VOCs), a significant source of environmental air pollution that can adversely impact health. An estimated 32...

  8. 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

    ... SIP on April 30, 1996 (61 FR 18962), July 27, 2002 (67 FR 47701), and August 25, ] 1994 (59 FR 43751... Budget under Executive Order 12866 (58 FR 51735, October 4, 1993); Does not impose an information...); Does not have Federalism implications as specified in Executive Order 13132 (64 FR 43255, August...

  9. APPLICATION OF GAME THEORY IN THE DESIGN OF OPTIMAL AIR POLLUTION CONTROL MEASURES

    EPA Science Inventory

    Methods of game theory are used to develop a technique for finding optimal solutions to air quality problems that involve multiple objectives. The technique is demonstrated using a hypothetical problem in which sites for two new power plants are sought that optimally satisfy five...

  10. 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,…

  11. 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. PMID:18173380

  12. 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. PMID:26595398

  13. 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.

  14. INSPECTION AND OPERATING AND MAINTENANCE GUIDELINES FOR SECONDARY LEAD SMELTER AIR POLLUTION CONTROL

    EPA Science Inventory

    The prevention of emissions from secondary lead smelters depends upon the procedures implemented to achieve initial compliance and remain in a state of continuing compliance with applicable emission limitations. The ability to remain in continuing compliance depends largely on op...

  15. 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

    ... Pollution Control District AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: EPA... 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...

  16. 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.

  17. 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

    .... SBCAPCD 333 Control of Emissions from 06/19/08 10/20/08 Reciprocating Internal Combustion Engines. On... proposed a limited approval and a limited disapproval (60 FR 6049) but did not finalize the action. The... FR 55620, November 25, 1992. 2. ``Issues Relating to VOC Regulation Cutpoints, Deficiencies,...

  18. 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

    ... IV. Statutory and Executive Order Reviews I. Proposed Action On August 2, 2010 (75 FR 45082), EPA..., result from this action. E. Executive Order 13132, Federalism Federalism (64 FR 43255, August 10, 1999... Tribal Governments'' (65 FR 67249, November 9, 2000), requires EPA to develop an accountable process...

  19. Human Immunodeficiencies Related to Defective APC/T Cell Interaction

    PubMed Central

    Kallikourdis, Marinos; Viola, Antonella; Benvenuti, Federica

    2015-01-01

    The primary event for initiating adaptive immune responses is the encounter between T lymphocytes and antigen presenting cells (APCs) in the T cell area of secondary lymphoid organs and the formation of highly organized intercellular junctions referred to as immune synapses (IS). In vivo live-cell imaging of APC–T cell interactions combined to functional studies unveiled that T cell fate is dictated, in large part, by the stability of the initial contact. Immune cell interaction is equally important during delivery of T cell help to B cells and for the killing of target cells by cytotoxic T cells and NK cells. The critical role of contact dynamics and synapse stability on the immune response is well illustrated by human immune deficiencies in which disease pathogenesis is linked to altered adhesion or defective cross-talk between the synaptic partners. The Wiskott–Aldrich syndrome (WAS) is a severe primary immunodeficiency caused by mutations in the Wiskott–Aldrich syndrome protein (WASp), a scaffold that promotes actin polymerization and links TCR stimulation to T cell activation. Absence or mutations in WASp affects intercellular APC–T cell communications by interfering with multiple mechanisms on both sides of the IS. The warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is caused by mutations in CXCR4, a chemokine receptor that in mutant form leads to impairment of APC–T cell interactions. Present evidences suggest that other recently characterized primary immune deficiencies caused by mutation in genes linked to actin cytoskeletal reorganization, such as WIP and DOCK8, may also depend on altered synapse stability. Here, we will discuss in details the mechanisms of disturbed APC–T cell interactions in WAS and WHIM. Moreover, we will summarize the evidence pointing to a compromised conjugate formation in WIP, DOCK8, and X-linked lymphoproliferative syndrome. PMID:26379669

  20. 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

  1. 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

  2. The Apc(min) mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS.

    PubMed

    Lane, Steven W; Sykes, Stephen M; Al-Shahrour, Fatima; Shterental, Sebastian; Paktinat, Mahnaz; Lo Celso, Cristina; Jesneck, Jonathan L; Ebert, Benjamin L; Williams, David A; Gilliland, D Gary

    2010-04-29

    Apc, a negative regulator of the canonical Wnt signaling pathway, is a bona-fide tumor suppressor whose loss of function results in intestinal polyposis. APC is located in a commonly deleted region on human chromosome 5q, associated with myelodysplastic syndrome (MDS), suggesting that haploinsufficiency of APC contributes to the MDS phenotype. Analysis of the hematopoietic system of mice with the Apc(min) allele that results in a premature stop codon and loss of function showed no abnormality in steady state hematopoiesis. Bone marrow derived from Apc(min) mice showed enhanced repopulation potential, indicating a cell intrinsic gain of function in the long-term hematopoietic stem cell (HSC) population. However, Apc(min) bone marrow was unable to repopulate secondary recipients because of loss of the quiescent HSC population. Apc(min) mice developed a MDS/myeloproliferative phenotype. Our data indicate that Wnt activation through haploinsufficiency of Apc causes insidious loss of HSC function that is only evident in serial transplantation strategies. These data provide a cautionary note for HSC-expansion strategies through Wnt pathway activation, provide evidence that cell extrinsic factors can contribute to the development of myeloid disease, and indicate that loss of function of APC may contribute to the phenotype observed in patients with MDS and del(5q). PMID:20197553

  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. Deconstructing the ßcatenin destruction complex: mechanistic roles for the tumor suppressor APC in regulating Wnt signaling.

    PubMed

    Roberts, David M; Pronobis, Mira I; Poulton, John S; Waldmann, Jon D; Stephenson, Elise M; Hanna, Shahnaz; Peifer, Mark

    2011-06-01

    Negatively regulating signaling by targeting key effectors for ubiquitination/destruction is essential for development and oncogenesis. The tumor suppressor adenomatous polyposis coli (APC), an essential negative regulator of Wnt signaling, provides a paradigm. APC mutations occur in most colon cancers. Acting in the "destruction complex" with Axin, glycogen synthase kinase 3, and casein kinase, APC targets ßcatenin (ßcat) for phosphorylation and recognition by an E3 ubiquitin-ligase. Despite 20 years of work, the internal workings of the destruction complex and APC's role remain largely mysterious. We use both Drosophila and colon cancer cells to test hypotheses for APC's mechanism of action. Our data are inconsistent with current models suggesting that high-affinity ßcat-binding sites on APC play key roles. Instead, they suggest that multiple ßcat-binding sites act additively to fine-tune signaling via cytoplasmic retention. We identify essential roles for two putative binding sites for new partners--20-amino-acid repeat 2 and conserved sequence B--in destruction complex action. Finally, we demonstrate that APC interacts with Axin by two different modes and provide evidence that conserved sequence B helps ensure release of APC from Axin, with disassembly critical in regulating ßcat levels. Using these data, we suggest a new model for destruction complex action in development, which also provides new insights into functions of truncated APC proteins in cancer. PMID:21471006

  5. Xenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activity

    PubMed Central

    Schmidt, Andreas; Duncan, Peter I.; Rauh, Nadine R.; Sauer, Guido; Fry, Andrew M.; Nigg, Erich A.; Mayer, Thomas U.

    2005-01-01

    Metaphase-to-anaphase transition is a fundamental step in cell cycle progression where duplicated sister-chromatids segregate to the future daughter cells. The anaphase-promoting complex/cyclosome (APC/C) is a highly regulated ubiquitin-ligase that triggers anaphase onset and mitotic exit by targeting securin and mitotic cyclins for destruction. It was previously shown that the Xenopus polo-like kinase Plx1 is essential to activate APC/C upon release from cytostatic factor (CSF) arrest in Xenopus egg extract. Although the mechanism by which Plx1 regulates APC/C activation remained unclear, the existence of a putative APC/C inhibitor was postulated whose activity would be neutralized by Plx1 upon CSF release. Here we identify XErp1, a novel Plx1-regulated inhibitor of APC/C activity, and we demonstrate that XErp1 is required to prevent anaphase onset in CSF-arrested Xenopus egg extract. Inactivation of XErp1 leads to premature APC/C activation. Conversely, addition of excess XErp1 to Xenopus egg extract prevents APC/C activation. Plx1 phosphorylates XErp1 in vitro at a site that targets XErp1 for degradation upon CSF release. Thus, our data lead to a model of APC/C activation in Xenopus egg extract in which Plx1 targets the APC/C inhibitor XErp1 for degradation. PMID:15713843

  6. 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).

  7. 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

  8. Polyethylene glycol inhibits intestinal neoplasia and induces epithelial apoptosis in Apc(min) mice.

    PubMed

    Roy, Hemant K; Gulizia, James; DiBaise, John K; Karolski, William J; Ansari, Sajid; Madugula, Madhavi; Hart, John; Bissonnette, Marc; Wali, Ramesh K

    2004-11-01

    Efficacy of a safe and clinically utilized polyethylene glycol formulation (PEG-3350) to suppress intestinal tumors was investigated in the Apc(min) mouse-model of experimental carcinogenesis. Furthermore, based on our previous finding on the induction of apoptosis in HT-29 cells by PEG, we evaluated its ability to stimulate epithelial cell apoptosis in both Apc(min) mouse as well as AOM-treated rat as a potential molecular mechanism of chemoprevention. Twenty-two Apc(min) mice were randomized equally to PEG or vehicle (control) supplementation. Tumors were scored and uninvolved intestinal mucosal apoptosis was assayed using a modified terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) assay and by immunohistochemical detection of cleaved caspase-3. Supplementation of Apc(min) mice with 10% PEG 3350 (in drinking water) resulted in a 48% (P<0.05) reduction in intestinal tumor burden and induced 2-3 fold increase in mucosal apoptosis. Dietary supplementation of polyethylene glycol (5%) also stimulated colonic mucosal apoptosis 4-5 fold in AOM-treated rats, the regimen that we previously reported to reduce tumor burden by 76% (P<0.05). In summary, we demonstrate, for the first time, that PEG does protect against Apc(min) mouse tumorigenesis. The correlation between pro-apoptotic actions and chemopreventive efficacy of PEG in these models strongly implicates induction of apoptosis as one of the impending mechanisms of chemoprevention. PMID:15374630

  9. Co-regulation proteomics reveals substrates and mechanisms of APC/C-dependent degradation

    PubMed Central

    Singh, Sasha A; Winter, Dominic; Kirchner, Marc; Chauhan, Ruchi; Ahmed, Saima; Ozlu, Nurhan; Tzur, Amit; Steen, Judith A; Steen, Hanno

    2014-01-01

    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/CCDH1-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. Modulation of APC Function and Anti-Tumor Immunity by Anti-Cancer Drugs

    PubMed Central

    Martin, Kea; Schreiner, Jens; Zippelius, Alfred

    2015-01-01

    Professional antigen-presenting cells (APCs), such as dendritic cells (DCs), are central to the initiation and regulation of anti-cancer immunity. However, in the immunosuppressive environment within a tumor APCs may antagonize anti-tumor immunity by inducing regulatory T cells (Tregs) or anergy of effector T cells due to lack of efficient costimulation. Hence, in an optimal setting, anti-cancer drugs have the power to reduce tumor size and thereby may induce the release of tumor antigens and, at the same time, modulate APC function toward efficient priming of antigen-specific effector T cells. Selected cytotoxic agents may revert APC dysfunction either by directly maturing DCs or through induction of immunogenic tumor cell death. Furthermore, specific cytotoxic agents may support adaptive immunity by selectively depleting regulatory subsets, such as Tregs or myeloid-derived suppressor cells. Perspectively, this will allow developing effective combination strategies with novel immunotherapies to exert complementary pressure on tumors via direct toxicity as well as immune activation. We, here, review our current knowledge on the capacity of anti-cancer drugs to modulate APC functions to promote durable anti-cancer immune responses. PMID:26483791

  11. Adenomatous polyposis coli (APC) membrane recruitment 3, a member of the APC membrane recruitment family of APC-binding proteins, is a positive regulator of Wnt-β-catenin signalling.

    PubMed

    Brauburger, Katharina; Akyildiz, Senem; Ruppert, Jan G; Graeb, Michael; Bernkopf, Dominic B; Hadjihannas, Michel V; Behrens, Jürgen

    2014-02-01

    The adenomatous polyposis coli (APC) membrane recruitment (Amer) family proteins Amer1/Wilms tumour gene on the X chromosome and Amer2 are binding partners of the APC tumour suppressor protein, and act as negative regulators in the Wnt signalling cascade. So far, nothing has been known about the third member of the family, Amer3. Here we show that Amer3 binds to the armadillo repeat domain of APC, similarly to Amer1 and Amer2. Amer3 also binds to the Wnt pathway regulator conductin/axin2. Furthermore, we identified Amer1 as binding partner of Amer3. Whereas Amer1 and Amer2 are linked to the plasma membrane by an N-terminal membrane localization domain, Amer3 lacks this domain. Amer3 localizes to the cytoplasm and nucleus of epithelial cells, and this is dependent on specific nuclear import and export sequences. Functionally, exogenous Amer3 enhances the expression of a β-catenin/T-cell factor-dependent reporter gene, and knockdown of endogenous Amer3 reduces Wnt target gene expression in colorectal cancer cells. Thus, Amer3 acts as an activator of Wnt signalling, in contrast to Amer1 and Amer2, which are inhibitors, suggesting a nonredundant role of Amer proteins in the regulation of this pathway. Our data, together with those of previous studies, provide a comprehensive picture of similarities and differences within the Amer protein family. PMID:24251807

  12. The CDK-APC/C Oscillator Predominantly Entrains Periodic Cell-Cycle Transcription.

    PubMed

    Rahi, Sahand Jamal; Pecani, Kresti; Ondracka, Andrej; Oikonomou, Catherine; Cross, Frederick R

    2016-04-01

    Throughout cell-cycle progression, the expression of multiple transcripts oscillate, and whether these are under the centralized control of the CDK-APC/C proteins or can be driven by a de-centralized transcription factor (TF) cascade is a fundamental question for understanding cell-cycle regulation. In budding yeast, we find that the transcription of nearly all genes, as assessed by RNA-seq or fluorescence microscopy in single cells, is dictated by CDK-APC/C. Three exceptional genes are transcribed in a pulsatile pattern in a variety of CDK-APC/C arrests. Pursuing one of these transcripts, the SIC1 inhibitor of B-type cyclins, we use a combination of mathematical modeling and experimentation to provide evidence that, counter-intuitively, Sic1 provides a failsafe mechanism promoting nuclear division when levels of mitotic cyclins are low. PMID:27058667

  13. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients.

    PubMed Central

    Miyoshi, Y; Ando, H; Nagase, H; Nishisho, I; Horii, A; Miki, Y; Mori, T; Utsunomiya, J; Baba, S; Petersen, G

    1992-01-01

    We searched for germ-line mutations of the APC gene in 79 unrelated patients with familial adenomatous polyposis using a ribonuclease protection analysis coupled with polymerase chain reaction amplifications of genomic DNA. Mutations were found in 53 patients (67%); 28 of the mutations were small deletions and 2 were 1- to 2-base-pair insertions; 19 were point mutations resulting in stop codons and only 4 were missense point mutations. Thus, 92% of the mutations were predicted to result in truncations of the APC protein. More than two-thirds (68%) of the mutations were clustered in the 5' half of the last exon, and nearly two-fifths of the total mutations occurred at one of five positions. This information has significant implications for understanding the role of APC mutation in inherited forms of colorectal neoplasia and for designing effective methods for genetic counseling and presymptomatic diagnosis. Images PMID:1316610

  14. Attenuated familial adenomatous polyposis with desmoids caused by an APC mutation.

    PubMed

    Ikenoue, Tsuneo; Yamaguchi, Kiyoshi; Komura, Mitsuhiro; Imoto, Seiya; Yamaguchi, Rui; Shimizu, Eigo; Kasuya, Shinichi; Shibuya, Tetsuo; Hatakeyama, Seira; Miyano, Satoru; Furukawa, Yoichi

    2015-01-01

    We present here a case of attenuated familial adenomatous polyposis (AFAP) with a family history of desmoids and thyroid tumors. This patient had no colonic polyps but did have multiple desmoids. Genetic analysis identified a 4-bp deletion in codon 2644 (c.7932_7935delTTAT: p.Tyr2645LysfsX14) of the adenomatous polyposis coli (APC) gene. In cases with limited numbers of colonic polyps and desmoids, AFAP may be caused by a mutation in the 3' region of APC. PMID:27081525

  15. Attenuated familial adenomatous polyposis with desmoids caused by an APC mutation

    PubMed Central

    Ikenoue, Tsuneo; Yamaguchi, Kiyoshi; Komura, Mitsuhiro; Imoto, Seiya; Yamaguchi, Rui; Shimizu, Eigo; Kasuya, Shinichi; Shibuya, Tetsuo; Hatakeyama, Seira; Miyano, Satoru; Furukawa, Yoichi

    2015-01-01

    We present here a case of attenuated familial adenomatous polyposis (AFAP) with a family history of desmoids and thyroid tumors. This patient had no colonic polyps but did have multiple desmoids. Genetic analysis identified a 4-bp deletion in codon 2644 (c.7932_7935delTTAT: p.Tyr2645LysfsX14) of the adenomatous polyposis coli (APC) gene. In cases with limited numbers of colonic polyps and desmoids, AFAP may be caused by a mutation in the 3′ region of APC. PMID:27081525

  16. 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.

  17. Orthotropic elasto-plastic behavior of AS4/APC-2 thermoplastic composite in compression

    NASA Technical Reports Server (NTRS)

    Sun, C. T.; Rui, Y.

    1989-01-01

    Uniaxial compression tests were performed on off-axis coupon specimens of unidirectional AS4/APC-2 thermoplastic composite at various temperatures. The elasto-plastic and strength properties of AS4/APC-2 composite were characterized with respect to temperature variation by using a one-parameter orthotropic plasticity model and a one-parameter failure criterion. Experimental results show that the orthotropic plastic behavior can be characterized quite well using the plasticity model, and the matrix-dominant compressive strengths can be predicted very accurately by the one-parameter failure criterion.

  18. 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

  19. 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. PMID:27226481

  20. An AT-rich region in the APC gene may cause misinterpretation of familial adenomatous polyposis molecular screening.

    PubMed

    Palmirotta, Raffaele; De Marchis, Maria Laura; Ludovici, Giorgia; Leone, Barbara; Valente, Maria Giovanna; Alessandroni, Jhessica; Spila, Antonella; Della-Morte, David; Guadagni, Fiorella

    2012-05-01

    Familial adenomatous polyposis (FAP) is an autosomal-dominant condition mainly due to a mutation of the adenomatous polyposis coli (APC) gene. The present study reports evidence of a technical issue occurring during the mutational analysis of APC exon 4. Genetic conventional direct sequence analysis of a repetitive AT-rich region in the splice acceptor site of APC intron 3 could be misinterpreted as a pathogenetic frameshift result. However, this potential bias may be bypassed adopting a method for random mutagenesis of DNA based on the use of a triphosphate nucleoside analogues mixture. Using this method as a second-level analysis, we also demonstrated the nonpathogenic nature of the variant in the poly A trait in APC exon 4 region (c.423-4delA) that do not result in aberrant splicing of APC exons 3-4; conversely, we did not find a previously reported T deletion/insertion polymorphism. PMID:22447671

  1. 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.

  2. The future of APCs: a look at Medicare's 2005 changes and industry trends.

    PubMed

    Leary, Renee S; Farley, Dean

    2005-03-01

    As the healthcare industry continues to struggle with an ever-evolving APC-based hospital outpatient PPS, it's important to be aware of some of the latest changes affecting providers and to recognize areas that may present particular challenges for private payers. PMID:17233243

  3. Detection of APC mosaicism by next-generation sequencing in an FAP patient.

    PubMed

    Yamaguchi, Kiyoshi; Komura, Mitsuhiro; Yamaguchi, Rui; Imoto, Seiya; Shimizu, Eigo; Kasuya, Shinichi; Shibuya, Tetsuo; Hatakeyama, Seira; Takahashi, Norihiko; Ikenoue, Tsuneo; Hata, Keisuke; Tsurita, Giichiro; Shinozaki, Masaru; Suzuki, Yutaka; Sugano, Sumio; Miyano, Satoru; Furukawa, Yoichi

    2015-05-01

    Familial adenomatous polyposis (FAP) of the colon is characterized by multiple polyps in the intestine and extra-colonic manifestations. Most FAP cases are caused by a germline mutation in the tumor-suppressor gene APC, but some cases of adenomatous polyposis result from germline mutations in MUTYH, POLD1 or POLE. Although sequence analysis of APC by the Sanger method is routinely performed for genetic testing, there remain cases whose mutations are not detected by the analysis. Next-generation sequencing has enabled us to analyze the comprehensive human genome, improving the chance of identifying disease causative variants. In this study, we conducted whole-genome sequencing of a sporadic FAP patient in which we did not find any pathogenic APC mutations by the conventional Sanger sequencing. Whole-genome sequencing and subsequent deep sequencing identified a mosaic mutation of c.3175G>T, p.E1059X in ~12% of his peripheral leukocytes. Additional deep sequencing of his buccal mucosa, hair follicles, non-cancerous mucosa of the stomach and colon disclosed that these tissues harbored the APC mutation at different frequencies. Our data implied that genetic analysis by next-generation sequencing is an effective strategy to identify genetic mosaicism in hereditary diseases. PMID:25716913

  4. PIK3CA and APC Mutations are Synergistic in the Development of Intestinal Cancers

    PubMed Central

    Deming, Dustin A.; Leystra, Alyssa A.; Nettekoven, Laura; Sievers, Chelsea; Miller, Devon; Middlebrooks, Malisa; Clipson, Linda; Albrecht, Dawn; Bacher, Jeff; Washington, Mary Kay; Weichert, Jamey; Halberg, Richard B.

    2013-01-01

    Human colorectal cancers are known to possess multiple mutations, though how these mutations interact in tumor development and progression has not been fully investigated. We have previously described the FCPIK3ca* murine colon cancer model which expresses a constitutively activated phosphoinositide-3 kinase (PI3K) in the intestinal epithelium. The expression of this dominantly active form of PI3K results in hyperplasia and invasive mucinous adenocarcinomas. These cancers form via a non-canonical mechanism of tumor initiation that is mediated through activation of PI3K and not through aberrations in WNT signaling. Since the Adenomatous Polyposis Coli (APC) gene is mutated in the vast majority of human colon cancers and often occurs simultaneously with PIK3CA mutations, we sought to better understand the interaction between APC and PIK3CA mutations in the mammalian intestine. In this study, we have generated mice in which the expression of a constitutively active PI3K and the loss of APC occur simultaneously in the distal small intestine and colon. Here we demonstrate that expression of a dominant active PI3K synergizes with loss of APC activity resulting in a dramatic changes in tumor multiplicity, size, morphology, and invasiveness. Activation of the PI3K pathway is not able to directly activate WNT signaling through the nuclear localization of CTNNB1 (β-catenin) in the absence of aberrant WNT signaling. Alterations at the transcriptional level, including increased CCND1, may be the etiology of synergy between these activated pathways. PMID:23708654

  5. Tumor promotion and inhibition by phenobarbital in livers of conditional Apc-deficient mice.

    PubMed

    Braeuning, Albert; Gavrilov, Alina; Geissler, Miriam; Wenz, Christine; Colnot, Sabine; Templin, Markus F; Metzger, Ute; Römer, Michael; Zell, Andreas; Schwarz, Michael

    2016-06-01

    Activation of Wnt/β-catenin signaling is important for human and rodent hepatocarcinogenesis. In mice, the tumor promoter phenobarbital (PB) selects for hepatocellular tumors with activating β-catenin mutations via constitutive androstane receptor activation. PB-dependent tumor promotion was studied in mice with genetic inactivation of Apc, a negative regulator of β-catenin, to circumvent the problem of randomly induced mutations by chemical initiators and to allow monitoring of PB- and Wnt/β-catenin-dependent tumorigenesis in the absence of unknown genomic alterations. Moreover, the study was designed to investigate PB-induced proliferation of liver cells with activated β-catenin. PB treatment provided Apc-deficient hepatocytes with only a minor proliferative advantage, and additional connexin 32 deficiency did not affect the proliferative response. PB significantly promoted the outgrowth of Apc-deficient hepatocellular adenoma (HCA), but simultaneously inhibited the formation of Apc-deficient hepatocellular carcinoma (HCC). The probability of tumor promotion by PB was calculated to be much lower for hepatocytes with loss of Apc, as compared to mutational β-catenin activation. Comprehensive transcriptomic and phosphoproteomic characterization of HCA and HCC revealed molecular details of the two tumor types. HCC were characterized by a loss of differentiated hepatocellular gene expression, enhanced proliferative signaling, and massive over-activation of Wnt/β-catenin signaling. In conclusion, PB exerts a dual role in liver tumor formation by promoting the growth of HCA but inhibiting the growth of HCC. Data demonstrate that one and the same compound can produce opposite effects on hepatocarcinogenesis, depending on context, highlighting the necessity to develop a more differentiated view on the tumorigenicity of this model compound. PMID:26838046

  6. A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth.

    PubMed

    Lau, Ted; Chan, Emily; Callow, Marinella; Waaler, Jo; Boggs, Jason; Blake, Robert A; Magnuson, Steven; Sambrone, Amy; Schutten, Melissa; Firestein, Ron; Machon, Ondrej; Korinek, Vladimir; Choo, Edna; Diaz, Dolores; Merchant, Mark; Polakis, Paul; Holsworth, Daniel D; Krauss, Stefan; Costa, Mike

    2013-05-15

    Most colorectal cancers (CRC) are initiated by mutations of APC, leading to increased β-catenin-mediated signaling. However, continued requirement of Wnt/β-catenin signaling for tumor progression in the context of acquired KRAS and other mutations is less well-established. To attenuate Wnt/β-catenin signaling in tumors, we have developed potent and specific small-molecule tankyrase inhibitors, G007-LK and G244-LM, that reduce Wnt/β-catenin signaling by preventing poly(ADP-ribosyl)ation-dependent AXIN degradation, thereby promoting β-catenin destabilization. We show that novel tankyrase inhibitors completely block ligand-driven Wnt/β-catenin signaling in cell culture and display approximately 50% inhibition of APC mutation-driven signaling in most CRC cell lines. It was previously unknown whether the level of AXIN protein stabilization by tankyrase inhibition is sufficient to impact tumor growth in the absence of normal APC activity. Compound G007-LK displays favorable pharmacokinetic properties and inhibits in vivo tumor growth in a subset of APC-mutant CRC xenograft models. In the xenograft model most sensitive to tankyrase inhibitor, COLO-320DM, G007-LK inhibits cell-cycle progression, reduces colony formation, and induces differentiation, suggesting that β-catenin-dependent maintenance of an undifferentiated state may be blocked by tankyrase inhibition. The full potential of the antitumor activity of G007-LK may be limited by intestinal toxicity associated with inhibition of Wnt/β-catenin signaling and cell proliferation in intestinal crypts. These results establish proof-of-concept antitumor efficacy for tankyrase inhibitors in APC-mutant CRC models and uncover potential diagnostic and safety concerns to be overcome as tankyrase inhibitors are advanced into the clinic. PMID:23539443

  7. Disruption of the APC gene by t(5;7) translocation in a Turcot family.

    PubMed

    Sahnane, Nora; Bernasconi, Barbara; Carnevali, Ileana; Furlan, Daniela; Viel, Alessandra; Sessa, Fausto; Tibiletti, Maria Grazia

    2016-03-01

    Turcot syndrome (TS) refers to the combination of colorectal polyps and primary tumours of the central nervous system. TS is a heterogeneous genetic condition due to APC and/or mismatch repair germline mutations. When APC is involved the vast majority of mutations are truncating, but in approximately 20%-30% of patients with familial polyposis no germline mutation can be found. A 30-year-old Caucasian woman with a positive pedigree for TS was referred to our Genetic Counselling Service. She was negative for APC and MUTYH but showed a reciprocal balanced translocation t(5;7)(q22;p15) at chromosome analysis. FISH analysis using specific BAC probes demonstrated that 5q22 breakpoint disrupted the APC gene. Transcript analysis by MLPA and digital PCR revealed that the cytogenetic rearrangement involving the 3' end of the APC gene caused a defective expression of a truncated transcript. This result allowed cytogenetic analysis to be offered to all the other family members and segregation analysis clearly demonstrated that all the carriers were affected, whereas non-carriers did not have the polyposis. A cytogenetic approach permitted the identification of the mutation-causing disease in this family, and the segregation analysis together with the transcript study supported the pathogenetic role of this mutation. Karyotype analysis was used as a predictive test in all members of this family. This family suggests that clinically positive TS and FAP cases, which test negative with standard molecular analysis, could be easily and cost-effectively resolved by a classical and molecular cytogenetic approach. PMID:26797314

  8. 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

  9. Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein.

    PubMed Central

    Munemitsu, S; Albert, I; Souza, B; Rubinfeld, B; Polakis, P

    1995-01-01

    The APC tumor-suppressor protein associates with beta-catenin, a cell adhesion protein that is upregulated by the WNT1 oncogene. We examined the effects of exogenous APC expression on the distribution and amount of beta-catenin in a colorectal cancer cell containing only mutant APC. Expression of wild-type APC caused a pronounced reduction in total beta-catenin levels by eliminating an excessive supply of cytoplasmic beta-catenin indigenous to the SW480 colorectal cancer cell line. This reduction was due to an enhanced rate of beta-catenin protein degradation. Truncated mutant APC proteins, characteristic of those associated with cancer, lacked this activity. Mutational analysis revealed that the central region of the APC protein, which is typically deleted or severely truncated in tumors, was responsible for the down-regulation of beta-catenin. These results suggest that the tumor-suppressor activity of mutant APC may be compromised due to a defect in its ability to regulate beta-catenin. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7708772

  10. Cryo-EM of Mitotic Checkpoint Complex-Bound APC/C Reveals Reciprocal and Conformational Regulation of Ubiquitin Ligation.

    PubMed

    Yamaguchi, Masaya; VanderLinden, Ryan; Weissmann, Florian; Qiao, Renping; Dube, Prakash; Brown, Nicholas G; Haselbach, David; Zhang, Wei; Sidhu, Sachdev S; Peters, Jan-Michael; Stark, Holger; Schulman, Brenda A

    2016-08-18

    The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). APC/C(CDC20) and two E2s, UBE2C and UBE2S, catalyze ubiquitination through distinct architectures for linking ubiquitin (UB) to substrates and elongating polyUB chains, respectively. MCC, which contains a second molecule of CDC20, blocks APC/C(CDC20)-UBE2C-dependent ubiquitination of Securin and Cyclins, while differentially determining or inhibiting CDC20 ubiquitination to regulate spindle surveillance, checkpoint activation, and checkpoint termination. Here electron microscopy reveals conformational variation of APC/C(CDC20)-MCC underlying this multifaceted regulation. MCC binds APC/C-bound CDC20 to inhibit substrate access. However, rotation about the CDC20-MCC assembly and conformational variability of APC/C modulate UBE2C-catalyzed ubiquitination of MCC's CDC20 molecule. Access of UBE2C is limiting for subsequent polyubiquitination by UBE2S. We propose that conformational dynamics of APC/C(CDC20)-MCC modulate E2 activation and determine distinctive ubiquitination activities as part of a response mechanism ensuring accurate sister chromatid segregation. PMID:27522463

  11. APC Activation Restores Functional CD4+CD25+ Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development

    PubMed Central

    Manirarora, Jean N.; Kosiewicz, Michele M.; Parnell, Sarah A.; Alard, Pascale

    2008-01-01

    Background Defects in APC and regulatory cells are associated with diabetes development in NOD mice. We have shown previously that NOD APC are not effective at stimulating CD4+CD25+ regulatory cell function in vitro. We hypothesize that failure of NOD APC to properly activate CD4+CD25+ regulatory cells in vivo could compromise their ability to control pathogenic cells, and activation of NOD APC could restore this defect, thereby preventing disease. Methodology/Principal Findings To test these hypotheses, we used the well-documented ability of complete Freund's adjuvant (CFA), an APC activator, to prevent disease in NOD mice. Phenotype and function of CD4+CD25+ regulatory cells from untreated and CFA-treated NOD mice were determined by FACS, and in vitro and in vivo assays. APC from these mice were also evaluated for their ability to activate regulatory cells in vitro. We have found that sick NOD CD4+CD25+ cells expressed Foxp3 at the same percentages, but decreased levels per cell, compared to young NOD or non-NOD controls. Treatment with CFA increased Foxp3 expression in NOD cells, and also increased the percentages of CD4+CD25+Foxp3+ cells infiltrating the pancreas compared to untreated NOD mice. Moreover, CD4+CD25+ cells from pancreatic LN of CFA-treated, but not untreated, NOD mice transferred protection from diabetes. Finally, APC isolated from CFA-treated mice increased Foxp3 and granzyme B expression as well as regulatory function by NOD CD4+CD25+ cells in vitro compared to APC from untreated NOD mice. Conclusions/Significance These data suggest that regulatory T cell function and ability to control pathogenic cells can be enhanced in NOD mice by activating NOD APC. PMID:19011680

  12. Sugar-carrying Polystyrenes Facilitate Harvesting of APCs from MLRs: Possible Application of Sugar-carrying Polystyrenes to Immunotherapy.

    PubMed

    Imaizumi, Akira; Onishi, Hideya; Yamasaki, Akio; Kawamoto, Makoto; Morisaki, Takashi; Goto, Mitsuaki; Iwama, Masamichi; Akaike, Toshihiro; Hasumi, Kenichiro

    2016-02-01

    Antigen-presenting cells (APCs) play a pivotal role in cancer immunotherapy. APCs in conventionally used flasks are harvested by enzymatic digestion or cell scraping for application to cancer immunotherapy. However, these methods may impair functional molecules expressed on the APC surface and reduce their effects in cancer immunotherapy. Recently, we found that APCs could be harvested by shaking at 4°C in flasks coated with poly[N-p-vinylbenzyl-O-2-acetoamide-2-deoxy-β-D-glucopyranosyl-(1→4)-2-acetoamide-2-deoxy-β-D-gluconamide] (PVGlcNAc) or a copolymer consisting of sulfonylurea (SU) linked to poly[N-p-vinyl-benzyl-4-O-β-D-galactopyranosyl-D-gluconamide] [P(VLA-co-SU)]. In the present study, we compared the functions of cytotoxic T-lymphocytes (CTLs) induced by APCs generated in PVGlcNAc- or P(VLA-co-SU)-coated flasks and conventional flasks. APCs from PVGlcNAc- or P(VLA-co-SU)-coated flasks showed higher expression of cluster of differentiation (CD)80/86, CD11c, and major histocompatibility complex class II alloantigen I-A(d), and higher cytotoxicity than APCs from conventional flasks. These results suggest that the use of PVGlcNAc- or P(VLA-co-SU)-coated flasks is optimal for harvesting APCs. The generated APCs also have a higher antigen-presenting ability compared to those generated in conventional flasks. Our results may contribute to the development of effective cancer immunotherapies. PMID:26851023

  13. APC/β-catenin-rich complexes at membrane protrusions regulate mammary tumor cell migration and mesenchymal morphology

    PubMed Central

    2013-01-01

    Background The APC tumor suppressor is mutated or downregulated in many tumor types, and is prominently localized to punctate clusters at protrusion tips in migratory cells, such as in astrocytes where it has been implicated in directed cell motility. Although APC loss is considered an initiating event in colorectal cancer, for example, it is less clear what role APC plays in tumor cell motility and whether loss of APC might be an important promoter of tumor progression in addition to initiation. Methods The localization of APC and β-catenin was analyzed in multiple cell lines, including non-transformed epithelial lines treated with a proteasome inhibitor or TGFβ to induce an epithelial-to-mesenchymal transition (EMT), as well as several breast cancer lines, by immunofluorescence. APC expression was knocked down in 4T07 mammary tumor cells using lentiviral-mediated delivery of APC-specific short-hairpin (sh) RNAs, and assessed using quantitative (q) reverse-transcriptase (RT)-PCR and western blotting. Tumor cell motility was analyzed by performing wound-filling assays, and morphology via immunofluorescence (IF) and phase-contrast microscopy. Additionally, proliferation was measured using BrdU incorporation, and TCF reporter assays were performed to determine β-catenin/TCF-mediated transcriptional activity. Results APC/β-catenin-rich complexes were observed at protrusion ends of migratory epithelial cells treated with a proteasome inhibitor or when EMT has been induced and in tumor cells with a mesenchymal, spindle-like morphology. 4T07 tumor cells with reduced APC levels were significantly less motile and had a more rounded morphology; yet, they did not differ significantly in proliferation or β-catenin/TCF transcriptional activity. Furthermore, we found that APC/β-catenin-rich complexes at protrusion ends were dependent upon an intact microtubule cytoskeleton. Conclusions These findings indicate that membrane protrusions with APC/β-catenin-containing puncta

  14. 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

  15. Targeting the DNA replication checkpoint by pharmacologic inhibition of Chk1 kinase: a strategy to sensitize APC mutant colon cancer cells to 5-fluorouracil chemotherapy

    PubMed Central

    Martino-Echarri, Estefania

    2014-01-01

    5-fluorouracil (5-FU) is the first line component used in colorectal cancer (CRC) therapy however even in combination with other chemotherapeutic drugs recurrence is common. Mutations of the adenomatous polyposis coli (APC) gene are considered as the initiating step of transformation in familial and sporadic CRCs. We have previously shown that APC regulates the cellular response to DNA replication stress and recently hypothesized that APC mutations might therefore influence 5-FU resistance. To test this, we compared CRC cell lines and show that those expressing truncated APC exhibit a limited response to 5-FU and arrest in G1/S-phase without undergoing lethal damage, unlike cells expressing wild-type APC. In SW480 APC-mutant CRC cells, 5-FU-dependent apoptosis was restored after transient expression of full length APC, indicating a direct link between APC and drug response. Furthermore, we could increase sensitivity of APC truncated cells to 5-FU by inactivating the Chk1 kinase using drug treatment or siRNA-mediated knockdown. Our findings identify mutant APC as a potential tumor biomarker of resistance to 5-FU, and importantly we show that APC-mutant CRC cells can be made more sensitive to 5-FU by use of Chk1 inhibitors. PMID:25301724

  16. APC alterations are frequently involved in the pathogenesis of acinar cell carcinoma of the pancreas, mainly through gene loss and promoter hypermethylation.

    PubMed

    Furlan, Daniela; Sahnane, Nora; Bernasconi, Barbara; Frattini, Milo; Tibiletti, Maria Grazia; Molinari, Francesca; Marando, Alessandro; Zhang, Lizhi; Vanoli, Alessandro; Casnedi, Selenia; Adsay, Volkan; Notohara, Kenji; Albarello, Luca; Asioli, Sofia; Sessa, Fausto; Capella, Carlo; La Rosa, Stefano

    2014-05-01

    Genetic and epigenetic alterations involved in the pathogenesis of pancreatic acinar cell carcinomas (ACCs) are poorly characterized, including the frequency and role of gene-specific hypermethylation, chromosome aberrations, and copy number alterations (CNAs). A subset of ACCs is known to show alterations in the APC/β-catenin pathway which includes mutations of APC gene. However, it is not known whether, in addition to mutation, loss of APC gene function can occur through alternative genetic and epigenetic mechanisms such as gene loss or promoter methylation. We investigated the global methylation profile of 34 tumor suppressor genes, CNAs of 52 chromosomal regions, and APC gene alterations (mutation, methylation, and loss) together with APC mRNA level in 45 ACCs and related peritumoral pancreatic tissues using methylation-specific multiplex ligation probe amplification (MS-MLPA), fluorescence in situ hybridization (FISH), mutation analysis, and reverse transcription-droplet digital PCR. ACCs did not show an extensive global gene hypermethylation profile. RASSF1 and APC were the only two genes frequently methylated. APC mutations were found in only 7 % of cases, while APC loss and methylation were more frequently observed (48 and 56 % of ACCs, respectively). APC mRNA low levels were found in 58 % of cases and correlated with CNAs. In conclusion, ACCs do not show extensive global gene hypermethylation. APC alterations are frequently involved in the pathogenesis of ACCs mainly through gene loss and promoter hypermethylation, along with reduction of APC mRNA levels. PMID:24590585

  17. Reversible modification of adenomatous polyposis coli (APC) with K63-linked polyubiquitin regulates the assembly and activity of the β-catenin destruction complex.

    PubMed

    Tran, Hoanh; Polakis, Paul

    2012-08-17

    The adenomatous polyposis coli (APC) tumor suppressor forms a complex with Axin and GSK3β to promote the phosphorylation and degradation of β-catenin, a key co-activator of Wnt-induced transcription. Here, we establish that APC is modified predominantly with K63-linked ubiquitin chains when it is bound to Axin in unstimulated HEK293 cells. Wnt3a stimulation induced a time-dependent loss of K63-polyubiquitin adducts from APC, an effect synchronous with the dissociation of Axin from APC and the stabilization of cytosolic β-catenin. RNAi-mediated depletion of Axin or β-catenin, which negated the association between APC and Axin, resulted in the absence of K63-adducts on APC. Overexpression of wild-type and phosphodegron-mutant β-catenin, combined with analysis of thirteen human cancer cell lines that harbor oncogenic mutations in APC, Axin, or β-catenin, support the hypothesis that a fully assembled APC-Axin-GSK3β-phospho-β-catenin complex is necessary for the K63-polyubiquitylation of APC. Intriguingly, the degree of this modification on APC appears to correlate inversely with the levels of β-catenin in cells. Together, our results indicate that K63-linked polyubiquitin adducts on APC regulate the assembly and/or efficiency of the β-catenin destruction complex. PMID:22761442

  18. 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

  19. 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

  20. 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. PMID:27259151

  1. 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

  2. The utility of Apc-mutant rats in modeling human colon cancer

    PubMed Central

    Irving, Amy A.; Yoshimi, Kazuto; Hart, Marcia L.; Parker, Taybor; Clipson, Linda; Ford, Madeline R.; Kuramoto, Takashi; Dove, William F.; Amos-Landgraf, James M.

    2014-01-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer. PMID:25288683

  3. 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.

  4. 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

  5. APC is an RNA-Binding Protein and its Interactome Provides a Link to Neural Development and Microtubule Assembly

    PubMed Central

    Preitner, Nicolas; Quan, Jie; Nowakowski, Dan W.; Hancock, Melissa L.; Shi, Jianhua; Tcherkezian, Joseph; Young-Pearse, Tracy L.; Flanagan, John G.

    2014-01-01

    SUMMARY Adenomatous polyposis coli (APC) is a microtubule plus-end scaffolding protein important in biology and disease. APC is implicated in RNA localization, although the mechanisms and functional significance remain unclear. We show that APC is an RNA-binding protein, and identify an RNA interactome by HITS-CLIP. Targets were highly enriched for APC-related functions, including microtubule organization, cell motility, cancer and neurologic disease. Among the targets is β2B-tubulin, known to be required in human neuron and axon migration. We show β2B-tubulin is synthesized in axons and localizes preferentially to dynamic microtubules in the growth cone periphery. APC binds the β2B-tubulin 3'UTR; treatments interfering with this interaction reduced β2B-tubulin mRNA axonal localization and expression, depleted dynamic microtubules and the growth cone periphery, and impaired neuron migration. These results identify APC as a platform binding functionally-related protein and RNA networks, and suggest a self-organizing model for the microtubule to localize synthesis of its own subunits. PMID:25036633

  6. 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

  7. 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

  8. Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells.

    PubMed

    Olsen, Anders Krüger; Coskun, Mehmet; Bzorek, Michael; Kristensen, Michael Holmsgaard; Danielsen, Erik Thomas; Jørgensen, Steffen; Olsen, Jørgen; Engel, Ulla; Holck, Susanne; Troelsen, Jesper Thorvald

    2013-06-01

    Wnt signaling is often constitutively active in colorectal cancer cells. The expression of the intestinal specific transcription factor CDX2 is found to be transiently decreased in invasive cells at the tumor/stroma interface. A recent ChIP-Seq study has indicated that several Wnt signaling-related genes are regulated by CDX2. The aim was to investigate the role of decreased CDX2 level on the expression of APC, AXIN2 and GSK3β in migrating colon cancer cells at the invasive front. CDX2-bound promoter and enhancer regions from APC, AXIN2 and GSK3β were analyzed for gene regulatory activity and the expression pattern of APC and GSK3β at the invasive front was evaluated by immunohistochemical procedures. Transfection of intestinal and non-intestinal cell lines demonstrated that CDX2 activated APC and AXIN2 promoter activities via intestinal cell-specific enhancer elements. Suppressed CDX2 expression was associated with endogenous downregulation of APC and AXIN2 expression in Caco-2 cells but did not affect GSK3β expression. Furthermore, elevated levels of nuclear β-catenin and reduced levels of cytoplasmic APC were correlated to a low CDX2 expression in migrating colon cancer cells in vivo. These results suggest that a low CDX2 level has influence on the Wnt signaling in invasive colon cancer cells possibly promoting cellular migration. PMID:23393221

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Oncogenic mutations in adenomatous polyposis coli (Apc) activate mechanistic target of rapamycin complex 1 (mTORC1) in mice and zebrafish

    PubMed Central

    Valvezan, Alexander J.; Huang, Jian; Lengner, Christopher J.; Pack, Michael; Klein, Peter S.

    2014-01-01

    Truncating mutations in adenomatous polyposis coli (APC) are strongly linked to colorectal cancers. APC is a negative regulator of the Wnt pathway and constitutive Wnt activation mediated by enhanced Wnt–β-catenin target gene activation is believed to be the predominant mechanism responsible for APC mutant phenotypes. However, recent evidence suggests that additional downstream effectors contribute to APC mutant phenotypes. We previously identified a mechanism in cultured human cells by which APC, acting through glycogen synthase kinase-3 (GSK-3), suppresses mTORC1, a nutrient sensor that regulates cell growth and proliferation. We hypothesized that truncating Apc mutations should activate mTORC1 in vivo and that mTORC1 plays an important role in Apc mutant phenotypes. We find that mTORC1 is strongly activated in apc mutant zebrafish and in intestinal polyps in Apc mutant mice. Furthermore, mTORC1 activation is essential downstream of APC as mTORC1 inhibition partially rescues Apc mutant phenotypes including early lethality, reduced circulation and liver hyperplasia. Importantly, combining mTORC1 and Wnt inhibition rescues defects in morphogenesis of the anterior-posterior axis that are not rescued by inhibition of either pathway alone. These data establish mTORC1 as a crucial, β-catenin independent effector of oncogenic Apc mutations and highlight the importance of mTORC1 regulation by APC during embryonic development. Our findings also suggest a new model of colorectal cancer pathogenesis in which mTORC1 is activated in parallel with Wnt/β-catenin signaling. PMID:24092877

  15. Alterations in K-ras, APC and p53-multiple genetic pathway in colorectal cancer among Indians.

    PubMed

    Malhotra, Pooja; Anwar, Mumtaz; Nanda, Neha; Kochhar, Rakesh; Wig, Jai Dev; Vaiphei, Kim; Mahmood, Safrun

    2013-06-01

    The incidence of colorectal cancer (CRC) is increasing rapidly in Asian countries during the past few decades, but no comprehensive analysis has been done to find out the exact cause of this disease. In this study, we investigated the frequencies of mutations and expression pattern of K-ras, APC (adenomatosis polyposis coli) and p53 in tumor, adjoining and distant normal mucosa and to correlate these alterations with patients clinicopathological parameters as well as with the survival. Polymerase chain reaction (PCR)-restriction digestion was used to detect mutations in K-ras and PCR-SSCP (Single Strand Conformation Polymorphism) followed by DNA sequencing was used to detect mutations in APC and p53 genes. Immunohistochemistry was used to detect the expression pattern of K-ras, APC and p53 proteins. The frequencies of mutations of K-ras, APC and p53 in 30 tumor tissues samples were 26.7 %, 46.7 % and 20 %, respectively. Only 3.3 % of tumors contained mutations in all the three genes. The most common combination of mutation was APC and p53 whereas mutation in both p53 and K-ras were extremely rare. There was no association between the mutations and expression pattern of K-ras, APC and p53 (p>0.05). In Indians, the frequency of alterations of K-ras and APC is similar as in Westerns, whereas the frequency of p53 mutation is slightly lower. The lack of multiple mutations in tumor specimens suggests that these genetic alterations might have independent influences on CRC development and there could be multiple alternative genetic pathways to CRC in our present study cohort. PMID:23526092

  16. Promoter methylation of APC and RAR-β genes as prognostic markers in non-small cell lung cancer (NSCLC).

    PubMed

    Feng, Hongxiang; Zhang, Zhenrong; Qing, Xin; Wang, Xiaowei; Liang, Chaoyang; Liu, Deruo

    2016-02-01

    Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-β promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-β promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P=0.391). RAR-β promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P=0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P=0.046) and nodal status (P=0.019) in non-tumor samples, and with smoking (P=0.004) in tumor samples. RAR-β promoter methylation was found associated with age (P=0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log-rank P=0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P=0.012), as were N1 positive lymph node number (P=0.025) and N2 positive lymph node number (P=0.06). Our study shows that RAR-β methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients. PMID:26681652

  17. Study of Cyclin Proteolysis in Anaphase-Promoting Complex (APC) Mutant Cells Reveals the Requirement for APC Function in the Final Steps of the Fission Yeast Septation Initiation Network

    PubMed Central

    Chang, Louise; Morrell, Jennifer L.; Feoktistova, Anna; Gould, Kathleen L.

    2001-01-01

    Cytokinesis in eukaryotic cells requires the inactivation of mitotic cyclin-dependent kinase complexes. An apparent exception to this relationship is found in Schizosaccharomyces pombe mutants with mutations of the anaphase-promoting complex (APC). These conditional lethal mutants arrest with unsegregated chromosomes because they cannot degrade the securin, Cut2p. Although failing at nuclear division, these mutants septate and divide. Since septation requires Cdc2p inactivation in wild-type S. pombe, it has been suggested that Cdc2p inactivation occurs in these mutants by a mechanism independent of cyclin degradation. In contrast to this prediction, we show that Cdc2p kinase activity fluctuates in APC cut mutants due to Cdc13/cyclin B destruction. In APC-null mutants, however, septation and cutting do not occur and Cdc13p is stable. We conclude that APC cut mutants are hypomorphic with respect to Cdc13p degradation. Indeed, overproduction of nondestructible Cdc13p prevents septation in APC cut mutants and the normal reorganization of septation initiation network components during anaphase. PMID:11533255

  18. 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

  19. 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

  20. Molecular analysis of the APC gene in 71 Israeli families: 17 novel mutations.

    PubMed

    Gavert, Nancy; Yaron, Yuval; Naiman, Tova; Bercovich, Dani; Rozen, Paul; Shomrat, Ruth; Legum, Cyril; Orr-Urtreger, Avi

    2002-06-01

    Familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. This study included 71 Israeli families referred for molecular analysis of the APC gene. Analysis was performed by the protein truncation test (PTT) of exon 15, and if negative, by direct sequencing of exon 1 to 14. Mutations were found in 36 (50.7%) probands. Mutation detection rates depended on the pattern of referral, such that among the 40 probands referred from the Service for Hereditary Cancer the mutation detection rate was 70%, whereas among the 31 probands referred by other gastroenterologists detection rate was significantly lower (25.8%). Of the 36 mutations detected, 21 were within exon 15, 13 within exons 1 to 14 and 2 were newly-described splicing mutations in introns 9 and 14. A relatively high proportion of the mutations was detected in exon 9 (6/36), five of them newly described. Altogether, we describe here 17 new mutations. Within the two major ethnic groups in Israel, patients of Ashkenazi and non-Ashkenazi origin, there was no significant differences in the mutation detection rate or the distribution of mutations within the APC gene. No founder mutation was detected in any of these populations. Our data confirm that higher detection rates may be expected in patients referred by clinical services specializing in hereditary colon cancer. These results further underscore the importance of complete analysis of all exons and exon/intron boundaries, in order to achieve maximal detection rate in patients suspected of FAP. PMID:12007223

  1. Kinesin-2 and Apc function at dendrite branch points to resolve microtubule collisions.

    PubMed

    Weiner, Alexis T; Lanz, Michael C; Goetschius, Daniel J; Hancock, William O; Rolls, Melissa M

    2016-01-01

    In Drosophila neurons, kinesin-2, EB1 and Apc are required to maintain minus-end-out dendrite microtubule polarity, and we previously proposed they steer microtubules at branch points. Motor-mediated steering of microtubule plus ends could be accomplished in two ways: 1) by linking a growing microtubule tip to the side of an adjacent microtubule as it navigates the branch point (bundling), or 2) by directing a growing microtubule after a collision with a stable microtubule (collision resolution). Using live imaging to distinguish between these two mechanisms, we found that reduction of kinesin-2 did not alter the number of microtubules that grew along the edge of the branch points where stable microtubules are found. However, reduction of kinesin-2 or Apc did affect the number of microtubules that slowed down or depolymerized as they encountered the side of the branch opposite to the entry point. These results are consistent with kinesin-2 functioning with Apc to resolve collisions. However, they do not pinpoint stable microtubules as the collision partner as stable microtubules are typically very close to the membrane. To determine whether growing microtubules were steered along stable ones after a collision, we analyzed the behavior of growing microtubules at dendrite crossroads where stable microtubules run through the middle of the branch point. In control neurons, microtubules turned in the middle of the crossroads. However, when kinesin-2 was reduced some microtubules grew straight through the branch point and failed to turn. We propose that kinesin-2 functions to steer growing microtubules along stable ones following collisions. PMID:26785384

  2. Apc-driven colon carcinogenesis in Pirc rat is strongly reduced by polyethylene glycol.

    PubMed

    Femia, Angelo Pietro; Becherucci, Caterina; Crucitta, Stefania; Caderni, Giovanna

    2015-11-01

    Polyethylene glycol (PEG) is one of the most powerful agents in reducing chemically induced carcinogenesis in rat colon. However, contrasting results in Min mice dampened the enthusiasm on this potentially strong and virtually safe, cancer chemopreventing agent. Pirc (F344/NTac-Apc (am1137) ) rats carrying a germline heterozygous mutation in the Apc gene, spontaneously develop multiple tumours in the colon thus modelling both familial adenomatous polyposis (FAP) and sporadic colorectal cancer (CRC). Given this similarity, we thought that these rats could be appropriate to test the efficacy of PEG 8000 in reducing carcinogenesis. Pirc male rats aged one month were treated with 5% PEG in drinking water for 2 or 6 months. Precancerous lesions were dramatically reduced after 2 months of PEG treatment (Mucin depleted foci (MDF)/colon were 99 ± 17 and 12 ± 8 in Controls and PEG-treated rats, respectively; p < 0.001; mean ± SD). Similarly, colon tumors were significantly reduced after 6 months of treatment (tumors/rat were 8.1 ± 2.3 and 3.6 ± 2.2 in Controls and PEG-treated rats, respectively; p < 0.05; mean ± SD). Colon proliferation, a parameter correlated to cancer risk, was also significantly lower in PEG-treated rats than in Controls, while apoptosis was not significantly affected. In conclusion, PEG markedly reduces colon carcinogenesis in Pirc rats mutated in Apc; we thus suggest that PEG may be used as chemopreventive agent to reduce cancer risk in FAP and CRC patients. PMID:25912754

  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. PMID:24398672

  4. PLK1 regulates spindle formation kinetics and APC/C activation in mouse zygote.

    PubMed

    Baran, Vladimir; Brzakova, Adela; Rehak, Pavol; Kovarikova, Veronika; Solc, Petr

    2016-06-01

    Polo-like kinase 1 (PLK1) is involved in essential events of cell cycle including mitosis in which it participates in centrosomal microtubule nucleation, spindle bipolarity establishment and cytokinesis. Although PLK1 function has been studied in cycling cancer cells, only limited data are known about its role in the first mitosis of mammalian zygotes. During the 1-cell stage of mouse embryo development, the acentriolar spindle is formed and the shift from acentriolar to centrosomal spindle formation progresses gradually throughout the preimplantation stage, thus providing a unique possibility to study acentriolar spindle formation. We have shown previously that PLK1 activity is not essential for entry into first mitosis, but is required for correct spindle formation and anaphase onset in 1-cell mouse embryos. In the present study, we extend this knowledge by employing quantitative confocal live cell imaging to determine spindle formation kinetics in the absence of PLK1 activity and answer the question whether metaphase arrest at PLK1-inhibited embryos is associated with low anaphase-promoting complex/cyclosome (APC/C) activity and consequently high securin level. We have shown that inhibition of PLK1 activity induces a delay in onset of acentriolar spindle formation during first mitosis. Although these PLK1-inhibited 1-cell embryos were finally able to form a bipolar spindle, not all chromosomes were aligned at the metaphase equator. PLK1-inhibited embryos were arrested in metaphase without any sign of APC/C activation with high securin levels. Our results document that PLK1 controls the onset of spindle assembly and spindle formation, and is essential for APC/C activation before anaphase onset in mouse zygotes. PMID:26174739

  5. 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

  6. STS-34 crewmembers sit in M1-13 APC during emergency egress training at KSC

    NASA Technical Reports Server (NTRS)

    1989-01-01

    STS-34 crewmembers sit in M1-13 Armored Personnel Carrier (APC) during emergency egress training at KSC's shuttle landing facility (SLF) prior to terminal countdown demonstration test (TCDT) activities. Wearing launch and entry suits (LESs), are (from left) Mission Specialist (MS) Ellen S. Baker, MS Shannon W. Lucid, Commander Donald E. Williams (right side, in back), MS Franklin R. Chang-Diaz, and Pilot Michael J. McCulley (holding headset). View provided by KSC with alternate number KSC-89PC-871.

  7. 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

  8. 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

  9. 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

  10. New origin firing is inhibited by APC/CCdh1 activation in S-phase after severe replication stress

    PubMed Central

    Ercilla, Amaia; Llopis, Alba; Feu, Sonia; Aranda, Sergi; Ernfors, Patrik; Freire, Raimundo; Agell, Neus

    2016-01-01

    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/CCdh1 is activated upon severe replication stress. Activation of APC/CCdh1 prevents new origin firing and induces permanent arrest in S-phase. Moreover, Rad51-mediated homologous recombination is also impaired under these conditions. APC/CCdh1 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/CCdh1 activity correlated with an increase in genomic instability. Taken together, our results define a new APC/CCdh1 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

  11. The ubiquitin ligase APC(Cdh1) is required to maintain genome integrity in primary human cells.

    PubMed

    Engelbert, D; Schnerch, D; Baumgarten, A; Wäsch, R

    2008-02-01

    Ensuring precise DNA replication and chromosome segregation is essential during cell division in order to provide genomic stability and avoid malignant growth. Proteolytic control of cell cycle regulators by the anaphase-promoting complex, activated by Cdh1 (APC(Cdh1)), is responsible for a stable G1 phase after mitotic exit allowing accurate preparation for DNA replication in the following S phase. APC(Cdh1) target proteins are frequently upregulated in tumor cells and the inactivation of human Cdh1 might interfere with genome integrity by target stabilization. Here we show that APC(Cdh1) is required for maintaining genomic integrity in primary human cells. Lentiviral-delivered strong and stable suppression of Cdh1 by RNA interference (RNAi) causes aberrant accumulation of several APC(Cdh1) target proteins, such as cyclin A, B, Aurora A or Plk1, which control accurate and equal distribution of the genetic information to daughter cells. This induces a premature and prolonged S phase, mitotic-entry delay and defects in chromosome separation and cytokinesis. Cell cycle deregulation by stable knockdown of Cdh1 leads to activation of p53/p21 and genomic instability, which is further increased by codepletion of p53. Thus, stabilization of APC(Cdh1) targets may initiate aberrant DNA replication and chromosome separation, and trigger a p53 response by deregulating G1 in primary human cells. PMID:17700535

  12. 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

  13. 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

  14. 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

    2016-01-01

    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

  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. 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.

  17. Comprehensive proteome analysis of an Apc mouse model uncovers proteins associated with intestinal tumorigenesis.

    PubMed

    Hung, Kenneth E; Faca, Vitor; Song, Kenneth; Sarracino, David A; Richard, Larissa Georgeon; Krastins, Bryan; Forrester, Sara; Porter, Andrew; Kunin, Alexandra; Mahmood, Umar; Haab, Brian B; Hanash, Samir M; Kucherlapati, Raju

    2009-03-01

    Tumor-derived proteins may occur in the circulation as a result of secretion, shedding from the cell surface, or cell turnover. We have applied an in-depth comprehensive proteomic strategy to plasma from intestinal tumor-bearing Apc mutant mice to identify proteins associated with tumor development. We used quantitative tandem mass spectrometry of fractionated mouse plasma to identify differentially expressed proteins in plasma from intestinal tumor-bearing Apc mutant mice relative to matched controls. Up-regulated proteins were assessed for the expression of corresponding genes in tumor tissue. A subset of proteins implicated in colorectal cancer were selected for further analysis at the tissue level using antibody microarrays, Western blotting, tumor immunohistochemistry, and novel fluorescent imaging. We identified 51 proteins that were elevated in plasma with concordant up-regulation at the RNA level in tumor tissue. The list included multiple proteins involved in colon cancer pathogenesis: cathepsin B and cathepsin D, cullin 1, Parkinson disease 7, muscle pyruvate kinase, and Ran. Of these, Parkinson disease 7, muscle pyruvate kinase, and Ran were also found to be up-regulated in human colon adenoma samples. We have identified proteins with direct relevance to colorectal carcinogenesis that are present both in plasma and in tumor tissue in intestinal tumor-bearing mice. Our results show that integrated analysis of the plasma proteome and tumor transcriptome of genetically engineered mouse models is a powerful approach for the identification of tumor-related plasma proteins. PMID:19240248

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Increased variability in Apc(Min)/+ intestinal tissue can be measured with microultrasound.

    PubMed

    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

  4. 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. PMID:27126000

  5. 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

  6. Testing models of the APC tumor suppressor/β-catenin interaction reshapes our view of the destruction complex in Wnt signaling.

    PubMed

    Yamulla, Robert J; Kane, Eric G; Moody, Alexandra E; Politi, Kristin A; Lock, Nicole E; Foley, Andrew V A; Roberts, David M

    2014-08-01

    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

  7. Identification of five novel modifier loci of ApcMin harbored in the BXH14 recombinant inbred strain

    PubMed Central

    Siracusa, Linda D.

    2012-01-01

    Every year thousands of people in the USA are diagnosed with small intestine and colorectal cancers (CRC). Although environmental factors affect disease etiology, uncovering underlying genetic factors is imperative for risk assessment and developing preventative therapies. Familial adenomatous polyposis is a heritable genetic disorder in which individuals carry germ-line mutations in the adenomatous polyposis coli (APC) gene that predisposes them to CRC. The Apc Min mouse model carries a point mutation in the Apc gene and develops polyps along the intestinal tract. Inbred strain background influences polyp phenotypes in Apc Min mice. Several Modifier of Min (Mom) loci that alter tumor phenotypes associated with the Apc Min mutation have been identified to date. We screened BXH recombinant inbred (RI) strains by crossing BXH RI females with C57BL/6J (B6) Apc Min males and quantitating tumor phenotypes in backcross progeny. We found that the BXH14 RI strain harbors five modifier loci that decrease polyp multiplicity. Furthermore, we show that resistance is determined by varying combinations of these modifier loci. Gene interaction network analysis shows that there are multiple networks with proven gene–gene interactions, which contain genes from all five modifier loci. We discuss the implications of this result for studies that define susceptibility loci, namely that multiple networks may be acting concurrently to alter tumor phenotypes. Thus, the significance of this work resides not only with the modifier loci we identified but also with the combinations of loci needed to get maximal protection against polyposis and the impact of this finding on human disease studies. Abbreviations:APCadenomatous polyposis coliGWASgenome-wide association studiesQTLquantitative trait lociSNPsingle-nucleotide polymorphism. PMID:22637734

  8. Lycopene synergistically enhances quinacrine action to inhibit Wnt-TCF signaling in breast cancer cells through APC.

    PubMed

    Preet, Ranjan; Mohapatra, Purusottam; Das, Dipon; Satapathy, Shakti R; Choudhuri, Tathagata; Wyatt, Michael D; Kundu, Chanakya N

    2013-02-01

    We previously reported that quinacrine (QC) has anticancer activity against breast cancer cells. Here, we examine the mechanism of action of QC and its ability to inhibit Wnt-TCF signaling in two independent breast cancer cell lines. QC altered Wnt-TCF signaling components by increasing the levels of adenomatous polyposis coli (APC), DAB2, GSK-3β and axin and decreasing the levels of β-catenin, p-GSK3β (ser 9) and CK1. QC also reduced the activity of the Wnt transcription factor TCF/LEF and its downstream targets cyclin D1 and c-MYC. Using a luciferase-based Wnt-TCF transcription factor assay, it was shown that APC levels were inversely associated with TCF/LEF activity. Induction of apoptosis and DNA damage was observed after treatment with QC, which was associated with increased expression of APC. The effects induced by QC depend on APC because the inhibition of Wnt-TCF signaling by QC is lost in APC-knockdown cells, and consequently, the extent of apoptosis and DNA damage caused by QC is reduced compared with parental cells. Because we previously showed that QC inhibits topoisomerase, we examined the effect of another topoisomerase inhibitor, etoposide, on Wnt signaling. Interestingly, etoposide treatment also reduced TCF/LEF activity, β-catenin and cyclin D1 levels commensurate with induction of DNA damage and apoptosis. Lycopene, a plant-derived antioxidant, synergistically increased QC activity and inhibited Wnt-TCF signaling in cancer cells without affecting the MCF-10A normal breast cell line. Collectively, the data suggest that QC-mediated Wnt-TCF signal inhibition depends on APC and that the addition of lycopene synergistically increases QC anticancer activity. PMID:23129580

  9. Peptide-MHC-I from Endogenous Antigen Outnumber Those from Exogenous Antigen, Irrespective of APC Phenotype or Activation

    PubMed Central

    Sei, Janet J.; Haskett, Scott; Kaminsky, Lauren W.; Lin, Eugene; Truckenmiller, Mary E.; Bellone, Clifford J.; Buller, R. Mark; Norbury, Christopher C.

    2015-01-01

    Naïve anti-viral CD8+ T cells (TCD8+) are activated by the presence of peptide-MHC Class I complexes (pMHC-I) on the surface of professional antigen presenting cells (pAPC). Increasing the number of pMHC-I in vivo can increase the number of responding TCD8+. Antigen can be presented directly or indirectly (cross presentation) from virus-infected and uninfected cells, respectively. Here we determined the relative importance of these two antigen presenting pathways in mousepox, a natural disease of the mouse caused by the poxvirus, ectromelia (ECTV). We demonstrated that ECTV infected several pAPC types (macrophages, B cells, and dendritic cells (DC), including DC subsets), which directly presented pMHC-I to naïve TCD8+ with similar efficiencies in vitro. We also provided evidence that these same cell-types presented antigen in vivo, as they form contacts with antigen-specific TCD8+. Importantly, the number of pMHC-I on infected pAPC (direct presentation) vastly outnumbered those on uninfected cells (cross presentation), where presentation only occurred in a specialized subset of DC. In addition, prior maturation of DC failed to enhance antigen presentation, but markedly inhibited ECTV infection of DC. These results suggest that direct antigen presentation is the dominant pathway in mice during mousepox. In a broader context, these findings indicate that if a virus infects a pAPC then the presentation by that cell is likely to dominate over cross presentation as the most effective mode of generating large quantities of pMHC-I is on the surface of pAPC that endogenously express antigens. Recent trends in vaccine design have focused upon the introduction of exogenous antigens into the MHC Class I processing pathway (cross presentation) in specific pAPC populations. However, use of a pantropic viral vector that targets pAPC to express antigen endogenously likely represents a more effective vaccine strategy than the targeting of exogenous antigen to a limiting pAPC

  10. 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

  11. Peptide-MHC-I from Endogenous Antigen Outnumber Those from Exogenous Antigen, Irrespective of APC Phenotype or Activation.

    PubMed

    Sei, Janet J; Haskett, Scott; Kaminsky, Lauren W; Lin, Eugene; Truckenmiller, Mary E; Bellone, Clifford J; Buller, R Mark; Norbury, Christopher C

    2015-06-01

    Naïve anti-viral CD8+ T cells (TCD8+) are activated by the presence of peptide-MHC Class I complexes (pMHC-I) on the surface of professional antigen presenting cells (pAPC). Increasing the number of pMHC-I in vivo can increase the number of responding TCD8+. Antigen can be presented directly or indirectly (cross presentation) from virus-infected and uninfected cells, respectively. Here we determined the relative importance of these two antigen presenting pathways in mousepox, a natural disease of the mouse caused by the poxvirus, ectromelia (ECTV). We demonstrated that ECTV infected several pAPC types (macrophages, B cells, and dendritic cells (DC), including DC subsets), which directly presented pMHC-I to naïve TCD8+ with similar efficiencies in vitro. We also provided evidence that these same cell-types presented antigen in vivo, as they form contacts with antigen-specific TCD8+. Importantly, the number of pMHC-I on infected pAPC (direct presentation) vastly outnumbered those on uninfected cells (cross presentation), where presentation only occurred in a specialized subset of DC. In addition, prior maturation of DC failed to enhance antigen presentation, but markedly inhibited ECTV infection of DC. These results suggest that direct antigen presentation is the dominant pathway in mice during mousepox. In a broader context, these findings indicate that if a virus infects a pAPC then the presentation by that cell is likely to dominate over cross presentation as the most effective mode of generating large quantities of pMHC-I is on the surface of pAPC that endogenously express antigens. Recent trends in vaccine design have focused upon the introduction of exogenous antigens into the MHC Class I processing pathway (cross presentation) in specific pAPC populations. However, use of a pantropic viral vector that targets pAPC to express antigen endogenously likely represents a more effective vaccine strategy than the targeting of exogenous antigen to a limiting pAPC

  12. The 20-year history of the evolution of air pollution control legislation in the U.S.A.

    NASA Astrophysics Data System (ADS)

    Schulze, Richard H.

    Over the past 20 years, the U.S. Congress has passed four acts relating to clean air. The 1970 act set out a comprehensive plan for federal-state partnership to require all areas in the country to meet National Ambient Air Quality Standards. In 1977, the act was amended and expanded, both to address many of the problems encountered in the 1970 act and to reorient the law to limit significantly emissions of any sort, even if there were no currently identified health-related reasons. In 1986, the Emergency Planning and Community Right-to-know Act was passed, as an amendment to a solid waste law, in response to the desire to prevent chemical release tragedies. After 10 years of effort, Congress finally passed the 1990 Clean Air Act amendments which require a number of new programs aimed at curbing urban ozone, rural acid rain, stratospheric ozone, toxic air pollutant emissions and vehicle emissions, and establishing a new, uniform national permit system. This paper discusses some of the consequences of the various acts and suggests ways that others might learn from our 20 years of experience. Certain programs have worked quite well, while some alternatives could have improved other programs.

  13. 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.

  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. 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.

  16. 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

    ... 164,500 103,400 -61,100 -37.14 Coeur D'Alene Basin Commission 98,400 104,300 5,900 6.00 Total... administration, water and waste. Only the smaller Coeur D'Alene Basin Commission showed any increase. Based...

  17. 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.

  18. MONITORING AND MODELING METHODS FOR DEVELOPING AIR POLLUTION CONTROL STRATEGIES: A CASE STUDY IN THE NORTHWEST CZECH REPUBLIC

    EPA Science Inventory

    Scientists from the United States and the Czech Republic recently completed a study to investigate the ambient air quality impact of industrial and motor vehicle sources in Teplice. ir pollution measurements made from 1992 through 1993 provide data on ambient concentrations of su...

  19. METHODS DEVELOPMENT FOR ASSESSING AIR POLLUTION CONTROL BENEFITS. VOLUME I. EXPERIMENTS IN THE ECONOMICS OF AIR POLLUTION EPIDEMIOLOGY

    EPA Science Inventory

    The volume employs the analytical and empirical methods of economics to develop hypotheses on disease etiologies and to value labor productivity and consumer losses due to air pollution-induced mortality and morbidity. In the mortality work, 1970 city-wide mortality rates for maj...

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. A novel GSK3-regulated APC:Axin interaction regulates Wnt signaling by driving a catalytic cycle of efficient βcatenin destruction

    PubMed Central

    Pronobis, Mira I; Rusan, Nasser M; Peifer, Mark

    2015-01-01

    APC, a key negative regulator of Wnt signaling in development and oncogenesis, acts in the destruction complex with the scaffold Axin and the kinases GSK3 and CK1 to target βcatenin for destruction. Despite 20 years of research, APC's mechanistic function remains mysterious. We used FRAP, super-resolution microscopy, functional tests in mammalian cells and flies, and other approaches to define APC's mechanistic role in the active destruction complex when Wnt signaling is off. Our data suggest APC plays two roles: (1) APC promotes efficient Axin multimerization through one known and one novel APC:Axin interaction site, and (2) GSK3 acts through APC motifs R2 and B to regulate APC:Axin interactions, promoting high-throughput of βcatenin to destruction. We propose a new dynamic model of how the destruction complex regulates Wnt signaling and how this goes wrong in cancer, providing insights into how this multiprotein signaling complex is assembled and functions via multivalent interactions. DOI: http://dx.doi.org/10.7554/eLife.08022.001 PMID:26393419

  5. A novel GSK3-regulated APC:Axin interaction regulates Wnt signaling by driving a catalytic cycle of efficient βcatenin destruction.

    PubMed

    Pronobis, Mira I; Rusan, Nasser M; Peifer, Mark

    2015-01-01

    APC, a key negative regulator of Wnt signaling in development and oncogenesis, acts in the destruction complex with the scaffold Axin and the kinases GSK3 and CK1 to target βcatenin for destruction. Despite 20 years of research, APC's mechanistic function remains mysterious. We used FRAP, super-resolution microscopy, functional tests in mammalian cells and flies, and other approaches to define APC's mechanistic role in the active destruction complex when Wnt signaling is off. Our data suggest APC plays two roles: (1) APC promotes efficient Axin multimerization through one known and one novel APC:Axin interaction site, and (2) GSK3 acts through APC motifs R2 and B to regulate APC:Axin interactions, promoting high-throughput of βcatenin to destruction. We propose a new dynamic model of how the destruction complex regulates Wnt signaling and how this goes wrong in cancer, providing insights into how this multiprotein signaling complex is assembled and functions via multivalent interactions. PMID:26393419

  6. 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

  7. Crop residues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crop residues [e.g., corn (Zea mays) stover and small grain straw] are sometimes excluded when discussing cellulosic energy crops per se, but because of the vast area upon which they are grown and their current role in the development of cellulosic energy systems. This chapter focuses on current cor...

  8. 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. PMID:20720115

  9. 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

  10. 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.

  11. Colon epithelial cell differentiation is inhibited by constitutive c-myb expression or mutant APC plus activated RAS.

    PubMed

    Ramsay, Robert G; Ciznadija, Daniel; Sicurella, Catherine; Reyes, Nancy; Mitchelhill, Ken; Darcy, Phillip K; D'Abaco, Giovanna; Mantamadiotis, Theo

    2005-01-01

    Blocked differentiation is a hallmark of cancer cells and the restoration of differentiation programs in vivo is an actively pursued clinical aim. Understanding the key regulators of cyto-differentiation may focus therapies on molecules that reactivate this process. c-myb expression declines rapidly when human colon cancer epithelial cells are induced to differentiate with the physiologically relevant short-chain fatty acid, sodium butyrate. These cells show increased expression of alkaline phosphatase and cytokeratin 8. Similarly, murine Immorto-epithelial cells derived from wild-type colon cells also show c-myb mRNA declines when induced to differentiate with sodium butyrate. Immorto-cells harboring a single APC mutation are indistinguishable from wild-type cells with regard to differentiation, while addition of activated RAS alone markedly enhances differentiation. In marked contrast, complete differentiation arrest occurs when both APC and RAS are mutated. Expression of MybER, a 4-hydroxytamoxifen-activatable form of c-Myb, blocks differentiation in wildtype and APC mutant Immorto-cell lines as well as LIM1215 human colon carcinoma cells. These data identify two pathways of oncogenic change that lead to retarded epithelial cell differentiation, one involving the presence of a single APC mutation in conjunction with activated RAS or alternatively constitutive c-myb expression. PMID:15684716

  12. 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...

  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. PMID:27418100

  14. FIP200 inhibits β-catenin-mediated transcription by promoting APC-independent β-catenin ubiquitination.

    PubMed

    Choi, J D; Ryu, M; Ae Park, M; Jeong, G; Lee, J-S

    2013-05-01

    Focal adhesion kinase-family-interacting protein of 200 kDa (FIP200) has been shown to regulate multiple cellular functions, including cell adhesion, autophagy, development and proliferation. Furthermore, FIP200 is considered to have tumor-suppressive activity, which may be correlated with its inactivation in human breast cancers, in addition to its role as an important signal transduction node. Herein, we report that FIP200 interacts with the oncoprotein β-catenin. Moreover, FIP200 promotes destabilization of wild-type β-catenin, but not a cancer-causing form of β-catenin, and as a result represses the β-catenin-mediated transcription. FIP200-induced degradation of β-catenin is independent of adenomatous polyposis coli (APC) of the well-established β-catenin destruction complex (glycogen synthase kinase-3β/axin/APC), in a component of β-catenin E3 ubiquitin ligase, β-TrCP-dependent manner. Thus, the APC-independent β-catenin degradation by FIP200 suggests a role for FIP200 in tumor suppression in the presence of APC dysfunction. These findings reveal a new and important function of FIP200 in regulation of the Wnt/β-catenin pathway. PMID:22751121

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Statin Use and Colorectal Adenoma Risk: Results from the Adenoma Prevention with Celecoxib (APC) Trial

    PubMed Central

    Bertagnolli, Monica M.; Hsu, Meier; Hawk, Ernest T.; Eagle, Craig J.; Zauber, Ann G.

    2010-01-01

    Background Statins are widely prescribed for cardiovascular disease prevention, and also commonly used in patients at high risk for colorectal cancer (CRC). We report the results of a planned secondary analysis of the relationship between statin use and colorectal adenoma risk in a large chemoprevention trial. Methods The Adenoma Prevention with Celecoxib (APC) trial randomized 2035 adenoma patients to receive placebo (679 patients), 200 mg celecoxib twice daily (685 patients), or 400 mg celecoxib twice daily (671 patients). The study collected complete medical history and medication use data, and performed colonoscopic surveillance to 5 years after study enrollment. Effects of statin use on newly detected adenomas and cardiovascular adverse events were analyzed as time-dependent variables by multivariable Cox regression. Results Statins were used by 36% (N=730) of APC trial participants. When adjusted for covariates including cardioprotective aspirin use, age, and sex, participants on the placebo arm who used statins at any time had no benefit over 5 years compared to never users (Risk Ratio (RR) 1.24; 95% confidence interval (CI) (0.99-1.56); p=0.065). Statin use for >3 years increased adenoma risk over 5 years (RR 1.39; 95%CI 1.04-1.86; p=0.024). For all comparisons of patients treated with celecoxib, adenoma detection rates for statin users and non-users were equivalent. Consistent with their use in patients at high risk, cardiovascular serious adverse events were more common among statin users. Conclusions For patients at high risk of CRC, statins do not protect against colorectal neoplasms and may even increase the risk of developing colorectal adenomas. PMID:20403998

  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. 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

  3. Loss of heterozygosity of the APC and MCC genes in squamous cell carcinoma of the head and neck

    SciTech Connect

    Nogueira, C.P.; Afridi, N.A.; Licameli, G.

    1994-09-01

    Squamous cell carcinoma of the head and neck offers a unique opportunity to study genetic mechanisms in human tumorigenesis. Two types of premalignant lesions can be identified clinically, suggesting a multistep process. The majority of the lesions are easy to identify and access. Despite these advantages, possible genetic models for these cancers remain relatively unexplored. Loss of heterozygosity of the tumor suppressor genes APC (adenomatous polyposis coli) and MCC (mutated in colon cancer) was investigated in 24 squamous cell carcinomas of the head and neck. Three sites were analyzed by assays based on the polymerase chain reaction: two RFLPs in the APC gene (Rsa I on exon 11; Ssp I on the 3{prime} untranslated region) and an insertion/deletion in exon 10 of the MCC gene. Sixty three percent of the individuals were informative for at least one marker. Loss of heterozygosity (LOH) was observed in 33% of the tumors, either at the APC or MCC locus. Two out of 11 informative tumors (18%) showed LOH on the APC gene. Three out of seven informative tumors (43%) showed LOH on the MCC gene. These results suggest that inactivation of the APC, MCC and/or a linked gene on chromosome 5q plays a important role in squamous cell carcinoma of the head and neck. The data is in agreement with another study, which detected 25% of loss of heterozygosity in the chromosomal region 5q by using microsatellite markers. These values are much lower than the ones observed in esophageal cancer, a closely related type of tumor, with the same etiology. This may be attributed to differences in the biology of these two cancers.

  4. Liver-targeted disruption of Apc in mice activates β-catenin signaling and leads to hepatocellular carcinomas

    PubMed Central

    Colnot, S.; Decaens, T.; Niwa-Kawakita, M.; Godard, C.; Hamard, G.; Kahn, A.; Giovannini, M.; Perret, C.

    2004-01-01

    Although inappropriate activation of the Wnt/β-catenin pathway has been implicated in the development of hepatocellular carcinoma (HCC), the role of this signaling in liver carcinogenesis remains unclear. To investigate this issue, we constructed a mutant mouse strain, Apclox/lox, in which exon 14 of the tumor-suppressor gene adenomatous polyposis coli (Apc) is flanked by loxP sequences. i.v. injection of adenovirus encoding Cre recombinase (AdCre) at high multiplicity [109 plaque-forming units (pfu) per mouse] inactivated the Apc gene in the liver and resulted in marked hepatomegaly, hepatocyte hyperplasia, and rapid mortality. β-Catenin signaling activation was demonstrated by nuclear and cytoplasmic accumulation of β-catenin in the hepatocytes and by the induction of β-catenin target genes (glutamine synthetase, glutamate transporter 1, ornithine aminotransferase, and leukocyte cell-derived chemotaxin 2) in the liver. To test a long-term oncogenic effect, we inoculated mice with lower doses of AdCre (0.5 × 109 pfu per mouse), compatible with both survival and persistence of β-catenin-activated cells. In these conditions, 67% of mice developed HCC. β-Catenin signaling was strongly activated in these Apc-inactivated HCCs. The HCCs were well, moderately, or poorly differentiated. Indeed, their histological and molecular features mimicked human HCC. Thus, deletion of Apc in the liver provides a valuable model of human HCC, and, in this model, activation of the Wnt/β-catenin pathway by invalidation of Apc is required for liver tumorigenesis. PMID:15563600

  5. Targeted apc;twist double-mutant mice: a new model of spontaneous osteosarcoma that mimics the human disease.

    PubMed

    Entz-Werlé, Natacha; Choquet, Philippe; Neuville, Agnès; Kuchler-Bopp, Sabine; Clauss, François; Danse, Jean-Marc; Simo-Noumbissie, Pauline; Guérin, Eric; Gaub, Marie-Pierre; Freund, Jean-Noel; Boehm, Nelly; Constantinesco, André; Lutz, Patrick; Guenot, Dominique; Perrin-Schmitt, Fabienne

    2010-01-01

    TWIST and adenomatosis polyposis coli (APC) are critical signaling factors in normal bone development. In previous studies examining a homogeneously treated cohort of pediatric osteosarcoma patients, we reported the frequent and concurrent loss of both TWIST and APC genes. On these bases, we created a related animal model to further explore the oncogenic cooperation between these two genes. We performed intercrosses between twist-null/+ and Apc1638N/+ mice and studied their progeny. The Apc1638N/+;twistnull/+ mice developed bone abnormalities observed by macroscopic skeletal analyses and in vivo imaging. Complementary histologic, cellular, and molecular analyses were used to characterize the identified bone tumors, including cell culture and immunofluorescence of bone differentiation markers. Spontaneous localized malignant bone tumors were frequently identified in Apc1638N/+;twist-null/+ mice by in vivo imaging evaluation and histologic analyses. These tumors possessed several features similar to those observed in human localized osteosarcomas. In particular, the murine tumors presented with fibroblastic, chondroblastic, and osteoblastic osteosarcoma histologies, as well as mixtures of these subtypes. In addition, cellular analyses and bone differentiation markers detected by immunofluorescence on tumor sections reproduced most murine and human osteosarcoma characteristics. For example, the early bone differentiation marker Runx2, interacting physically with hypophosphorylated pRb, was undetectable in these murine osteosarcomas, whereas phosphorylated retinoblastoma was abundant in the osteoblastic and chondroblastic tumor subtypes. These characteristics, similar to those observed in human osteosarcomas, indicated that our animal model may be a powerful tool to further understand the development of localized osteosarcoma. PMID:21151473

  6. Targeted Apc;Twist Double-Mutant Mice: A New Model of Spontaneous Osteosarcoma That Mimics the Human Disease123

    PubMed Central

    Entz-Werlé, Natacha; Choquet, Philippe; Neuville, Agnès; Kuchler-Bopp, Sabine; Clauss, François; Danse, Jean-Marc; Simo-Noumbissie, Pauline; Guérin, Eric; Gaub, Marie-Pierre; Freund, Jean-Noel; Boehm, Nelly; Constantinesco, André; Lutz, Patrick; Guenot, Dominique; Perrin-Schmitt, Fabienne

    2010-01-01

    TWIST and adenomatosis polyposis coli (APC) are critical signaling factors in normal bone development. In previous studies examining a homogeneously treated cohort of pediatric osteosarcoma patients, we reported the frequent and concurrent loss of both TWIST and APC genes. On these bases, we created a related animal model to further explore the oncogenic cooperation between these two genes. We performed intercrosses between twist-null/+ and Apc1638N/+ mice and studied their progeny. The Apc1638N/+;twistnull/+ mice developed bone abnormalities observed by macroscopic skeletal analyses and in vivo imaging. Complementary histologic, cellular, and molecular analyses were used to characterize the identified bone tumors, including cell culture and immunofluorescence of bone differentiation markers. Spontaneous localized malignant bone tumors were frequently identified in Apc1638N/+;twist-null/+ mice by in vivo imaging evaluation and histologic analyses. These tumors possessed several features similar to those observed in human localized osteosarcomas. In particular, the murine tumors presented with fibroblastic, chondroblastic, and osteoblastic osteosarcoma histologies, as well as mixtures of these subtypes. In addition, cellular analyses and bone differentiation markers detected by immunofluorescence on tumor sections reproduced most murine and human osteosarcoma characteristics. For example, the early bone differentiation marker Runx2, interacting physically with hypophosphorylated pRb, was undetectable in these murine osteosarcomas, whereas phosphorylated retinoblastoma was abundant in the osteoblastic and chondroblastic tumor subtypes. These characteristics, similar to those observed in human osteosarcomas, indicated that our animal model may be a powerful tool to further understand the development of localized osteosarcoma. PMID:21151473

  7. 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

  8. Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex.

    PubMed

    Kunttas-Tatli, Ezgi; Roberts, David M; McCartney, Brooke M

    2014-11-01

    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

  9. 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

  10. Interaction of APC/C-E3 Ligase with Swi6/HP1 and Clr4/Suv39 in Heterochromatin Assembly in Fission Yeast*S⃞♦

    PubMed Central

    Dubey, Rudra Narayan; Nakwal, Nandni; Bisht, Kamlesh Kumar; Saini, Ashok; Haldar, Swati; Singh, Jagmohan

    2009-01-01

    Heterochromatin assembly in fission yeast is initiated by binding of Swi6/HP1 to the Lys-9-dimethylated H3 followed by spreading via cooperative recruitment of Swi6/HP1. Recruitment of Cohesin by Swi6/HP1 further stabilizes the heterochromatin structure and integrity. Subsequently, polyubiquitylation of Cut2 by anaphase-promoting complex-cyclosome (APC/C)-ubiquitin-protein isopeptide ligase (E3 ligase) followed by degradation of Cut2 releases Cut1, which cleaves the Rad21 subunit of Cohesin, facilitating sister chromatid separation during mitosis. Here, we demonstrate a surprising role of APC/C in assembly of heterochromatin and silencing at mating type, centromere, and ribosomal DNA loci. Coincidentally with the loss of silencing, recruitment of Swi6, H3-Lys-9-Me2, and Clr4 at dg-dh repeats at cen1 and the K region of mat locus is abrogated in mutants cut4, cut9, and nuc2. Surprisingly, both Cut4 and Cut9 are also highly enriched at these regions in wild type and depleted in swi6Δ mutant. Cut4 and Cut9 interact directly with Swi6/HP1 and Clr4, whereas the mutant Cut4 does not, suggesting that a direct physical interaction of APC subunits Cut4 and Cut9 with Swi6 and Clr4 is instrumental in heterochromatin assembly. The silencing defect in APC mutants is causally related to ubiquitylation activity of APC-E3 ligase. Like swi6 mutant, APC mutants are also defective in Cohesin recruitment and exhibit defects like lagging chromosomes, chromosome loss, and aberrant recombination in the mat region. In addition, APC mutants exhibit a bidirectional expression of dh repeats, suggesting a role in the RNA interference pathway. Thus, APC and heterochromatin proteins Swi6 and Clr4 play a mutually cooperative role in heterochromatin assembly, thereby ensuring chromosomal integrity, inheritance, and segregation during mitosis and meiosis. PMID:19117951

  11. 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.

  12. 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...

  13. 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

  14. Five Year Efficacy and Safety Analysis of the Adenoma Prevention with Celecoxib (APC) Trial

    PubMed Central

    Bertagnolli, Monica M.; Eagle, Craig J.; Zauber, Ann G.; Redston, Mark; Breazna, Aurora; Kim, KyungMann; Tang, Jie; Rosenstein, Rebecca B.; Umar, Asad; Bagheri, Donya; Collins, Neal T.; Burn, John; Chung, Daniel C.; Dewar, Thomas; Foley, T. Raymond; Hoffman, Neville; Macrae, Finlay; Pruitt, Ronald E.; Saltzman, John R.; Salzberg, Bruce; Sylwestrowicz, Thomas; Hawk, Ernest T.

    2010-01-01

    The Adenoma Prevention with Celecoxib (APC) Trial examined the efficacy and safety of the Cox-2 inhibitor, celecoxib, for sporadic colorectal adenoma prevention in patients at high risk for colorectal cancer (CRC). The trial randomized 2035 subjects to receive either placebo, celecoxib 200mg twice daily, or celecoxib 400mg twice daily. The primary study safety and efficacy analyses involved three years of treatment. The results showed significant anti-tumor effect, but also indicated increased cardiovascular adverse events in patients treated with celecoxib compared to placebo. A total of 933 patients participated in an extension of the APC Trial, with a planned total treatment and surveillance duration of 5 years. Study medication was stopped early, resulting in a median treatment duration of 3.1 years. Patients treated on the placebo arm had a cumulative adenoma incidence of 68.4% over 5 years of observation. This figure was 59.0% (p<0.0001) for those receiving low dose celecoxib, and 60.1% (p<0.0001) for those receiving high dose celecoxib. The cumulative incidence of advanced adenomas over 5 years was 21.3% of those taking placebo, 12.5% (p<0.0001) of those taking low dose celecoxib and 15.8% (p<0.0001) of those taking high dose celecoxib. Investigator reported treatment emergent adverse events were similar across all treatment groups for categories including renal and hypertensive events and gastrointestinal ulceration and hemorrhage events. For a category composed of cardiovascular and thrombotic events, the risk relative to placebo was 1.6 (95%CI 1.0, 2.5) for those using 200mg BID celecoxib and 1.9 (95%CI 1.2, 3.1) for those using 400mg BID celecoxib. Secondary analysis showed an interaction between a baseline history of atherosclerotic heart disease and study drug use with respect to cardiovascular and thrombotic adverse events (p=0.004). These results confirm the inhibitory effect of celecoxib on colorectal adenoma formation, and provide additional safety

  15. Residual Cap

    NASA Technical Reports Server (NTRS)

    2006-01-01

    10 May 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a summertime view of the south polar residual cap of Mars. In this image, mesas composed largely of solid carbon dioxide are separated from one another by irregularly-shaped depressions. The variation in brightness across this scene is a function of several factors including, but not limited to, varying proportions of dust and solid carbon dioxide, undulating topography, and differences in the roughness of the slopes versus the flat surfaces.

    Location near: 86.7oS, 343.3oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

  16. Metabonomic Profiling Reveals Cancer Chemopreventive Effects of American Ginseng on Colon Carcinogenesis in Apc(Min/+) Mice.

    PubMed

    Xie, Guoxiang; Wang, Chong-Zhi; Yu, Chunhao; Qiu, Yunping; Wen, Xiao-Dong; Zhang, Chun-Feng; Yuan, Chun-Su; Jia, Wei

    2015-08-01

    American ginseng (Panax quinquefolius L.) is one of the most commonly used herbal medicines in the West. It has been reported to possess significant antitumor effects that inhibit the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the cancer chemopreventive effects of American ginseng on the progression of high fat (HF) diet-enhanced colorectal carcinogenesis with a genetically engineered Apc(Min/+) mouse model. The metabolic alterations in sera of experimental mice perturbed by HF diet intervention as well as the American ginseng treatment were measured by gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) analysis. American ginseng treatment significantly extended the life span of the Apc(Min/+) mouse. Significant alterations of metabolites involving amino acids, organic acids, fatty acids, and carbohydrates were observed in Apc(Min/+) mouse in sera, which were attenuated by American ginseng treatment and concurrent with the histopathological improvement with significantly reduced tumor initiation, progression and gut inflammation. These metabolic changes suggest that the preventive effect of American ginseng is associated with attenuation of impaired amino acid, carbohydrates, and lipid metabolism. It also appears that American ginseng induced significant metabolic alterations independent of the Apc(Min/+) induced metabolic changes. The significantly altered metabolites induced by American ginseng intervention include arachidonic acid, linolelaidic acid, glutamate, docosahexaenoate, tryptophan, and fructose, all of which are associated with inflammation and oxidation. This suggests that American ginseng exerts the chemopreventive effects by anti-inflammatory and antioxidant mechanisms. PMID:26136108

  17. Racial variations in frequency and phenotypes of APC and MUTYH mutations in 6,169 individuals undergoing genetic testing

    PubMed Central

    Inra, Jennifer A.; Steyerberg, Ewout W.; Grover, Shilpa; McFarland, Ashley; Syngal, Sapna; Kastrinos, Fay

    2016-01-01

    Purpose To assess whether differences in frequency and phenotype of APC and MUTYH mutations exist among racially/ethnically diverse populations. Methods 6169 individuals with personal and/or family history of colorectal cancer (CRC) and polyps were studied. APC testing involved full sequencing/large rearrangement analysis (FS/LRA); MUTYH involved “panel testing” (for Y165C, G382D mutations), or FS/LRA, performed by Myriad Genetics, a commercial laboratory. Subjects were identified as Caucasian, Asian, African American (AA), or Other. Statistical tests included Chi-Square, Fisher’s Exact, ANOVA and z-approximation. Results 17.5% had pathogenic APC mutations. 4.8% were biallelic MUTYH carriers. 18% were non-Caucasian with >100 adenomas and younger ages of adenoma or CRC diagnosis (p<0.0001) than Caucasians. The overall APC mutation rate was higher in Asians, AAs and Others compared to Caucasians (25.2%, 30.9%, 24%, 15.5%;p<0.0001) but similar in all groups when adjusted for polyp burden. More MUTYH biallelic carriers were Caucasian or Other than Asian or AA (5%, 7%, 2.7%, 0.3%;p<0.0001). Among Caucasians, 5% were biallelic carriers identified by panel testing versus 2% by sequencing/LRA (p=0.002). Among non-Caucasians, 3% undergoing panel testing were biallelic carriers versus 10% identified by sequencing/LRA(p<0.0002). Conclusion Non-Caucasians undergo genetic testing at more advanced stages of polyposis and/or younger ages of CRC/polyp diagnosis. Restricted MUTYH analysis may miss significant numbers of biallelic carriers, particularly in non-Caucasians. PMID:25590978

  18. Sulindac increases the expression of APC mRNA in malignant colonic epithelial cells: an in vitro study.

    PubMed Central

    Schnitzler, M; Dwight, T; Robinson, B G

    1996-01-01

    BACKGROUND--Sulindac is a non-steroidal anti-inflammatory drug which induces regression of colonic polyps in patients with familial adenomatous polyposis. Animal and in vitro studies have shown that both the sulphide metabolite of sulindac, which is able to inhibit cyclo-oxygenase, and the sulphone metabolite, which lacks this ability, are able to inhibit the growth of colonic carcinoma cells. The exact mechanism by which these effects occurs is not known. AIMS--To examine the effect of sulindac sulphide and sulindac sulphone on the expression of APC messenger RNA (mRNA), and on the proliferation of colonic carcinoma cells in vitro. METHODS--The colonic carcinoma cell line LIM 1215 was treated with sulindac sulphide and sulindac sulphone (10 microM or 100 microM) for 24 hours. Total RNA was extracted and APC mRNA was quantitated using competitive reverse transcription polymerase chain reaction. Measurements of cell number, cell proliferation, and prostaglandin E2 concentrations were also made. RESULTS--A significant increase in APC mRNA was observed after treatment with 10 microM of both sulindac sulphide and sulindac sulphone (control: 37.2 (19.7); 10 microM sulindac sulphide: 129 (112.8); 10 microM sulindac sulphone: 207.7 (102.9) pg/(g total RNA) (p < 0.05). Prostaglandin E2 concentrations were significantly reduced after treatment with sulindac sulphide, but not after sulindac sulphone. Both agents produced a dose dependent reduction in cell numbers and cell proliferation, which was more noticeable after treatment with sulindac sulphide. CONCLUSIONS--Both sulindac sulphide and sulindac sulphone inhibit the growth of carcinoma cells in vitro and cause an increase in APC mRNA. The effect of these agents on colonic carcinogenesis is not mediated entirely by means of an inhibition of prostaglandin biosynthesis. Images Figure 1 PMID:8707116

  19. 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

  20. Uncovering the role of APC-Cdh1 in generating the dynamics of S-phase onset

    PubMed Central

    Yuan, Xi; Srividhya, Jeyaraman; De Luca, Thomas; Lee, Ju-hyong E.; Pomerening, Joseph R.

    2014-01-01

    Cdh1, a coactivator of the anaphase-promoting complex (APC), is a potential tumor suppressor. Cdh1 ablation promotes precocious S-phase entry, but it was unclear how this affects DNA replication dynamics while contributing to genomic instability and tumorigenesis. We find that Cdh1 depletion causes early S-phase onset in conjunction with increase in Rb/E2F1-mediated cyclin E1 expression, but reduced levels of cyclin E1 protein promote this transition. We hypothesize that this is due to a weakened cyclin-dependent kinase inhibitor (CKI)–cyclin-dependent kinase 2 positive-feedback loop, normally generated by APC-Cdh1–mediated proteolysis of Skp2. Indeed, Cdh1 depletion increases Skp2 abundance while diminishing levels of the CKI p27. This lowers the level of cyclin E1 needed for S-phase entry and delays cyclin E1 proteolysis during S-phase progression while corresponding to slowed replication fork movement and reduced frequency of termination events. In summary, using both experimental and computational approaches, we show that APC-Cdh1 establishes a stimulus–response relationship that promotes S phase by ensuring that proper levels of p27 accumulate during G1 phase, and defects in its activation accelerate the timing of S-phase onset while prolonging its progression. PMID:24356446