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Sample records for aminofluorene-modified dg adduct

  1. Compact DG modules and Gorenstein DG algebras

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    When the base connected cochain DG algebra is cohomologically bounded, it is proved that the difference between the amplitude of a compact DG module and that of the DG algebra is just the projective dimension of that module. This yields the unboundedness of the cohomology of non-trivial regular DG algebras. When A is a regular DG algebra such that H(A) is a Koszul graded algebra, H(A) is proved to have the finite global dimension. And we give an example to illustrate that the global dimension of H(A) may be infinite, if the condition that H(A) is Koszul is weakened to the condition that A is a Koszul DG algebra. For a general regular DG algebra A, we give some equivalent conditions for the Gorensteiness. For a finite connected DG algebra A, we prove that Dc(A) and Dc(Aop) admit Auslander-Reiten triangles if and only if A and Aop are Gorenstein DG algebras. When A is a non-trivial regular DG algebra such that H(A) is locally finite, Dc(A) does not admit Auslander-Reiten triangles. We turn to study the existence of Auslander-Reiten triangles in Dlbf(A) and Dlbf(Aop) instead, when A is a regular DG algebra.

  2. Chemistry and Biology of Aflatoxin-DNA Adducts

    Energy Technology Data Exchange (ETDEWEB)

    Stone, Michael P.; Banerjee, Surajit; Brown, Kyle L.; Egli, Martin (Vanderbilt)

    2012-03-27

    Aspergillus flavus is a fungal contaminant of stored rice, wheat, corn, and other grainstuffs, and peanuts. This is of concern to human health because it produces the mycotoxin aflatoxin B{sub 1} (AFB{sub 1}), which is genotoxic and is implicated in the etiology of liver cancer. AFB{sub 1} is oxidized in vivo by cytochrome P450 to form aflatoxin B{sub 1} epoxide, which forms an N7-dG adduct (AFB{sub 1}-N7-dG) in DNA. The latter rearranges to a formamidopyrimidine (AFB{sub 1}-FAPY) derivative that equilibrates between {alpha} and {beta} anomers of the deoxyribose. In DNA, both the AFB{sub 1}-N7-dG and AFB{sub 1}-{beta}-FAPY adducts intercalate above the 5'-face of the damaged guanine. Each produces G {yields} T transversions in Escherichia coli, but the AFB{sub 1}-{beta}-FAPY adduct is more mutagenic. The Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) provides a model for understanding error-prone bypass of the AFB{sub 1}-N7-dG and AFB{sub 1}-{beta}-FAPY adducts. It bypasses the AFB{sub 1}-N7-dG adduct, but it conducts error-prone replication past the AFB{sub 1}-FAPY adduct, including mis-insertion of dATP, consistent with the G {yields} T mutations characteristic of AFB{sub 1} mutagenesis in E. coli. Crystallographic analyses of a series of binary and ternary complexes with the Dpo4 polymerase revealed differing orientations of the N7-C8 bond of the AFB{sub 1}-N7-dG adduct as compared to the N{sup 5}-C8 bond in the AFB{sub 1}-{beta}-FAPY adduct, and differential accommodation of the intercalated AFB{sub 1} moieties within the active site. These may modulate AFB{sub 1} lesion bypass by this polymerase.

  3. Formation of 1,4-dioxo-2-butene-derived adducts of 2′-deoxyadenosine and 2′-deoxycytosine in oxidized DNA

    OpenAIRE

    Chen, Bingzi; Vu, Choua C.; Byrns, Michael C.; Peter C. Dedon; Peterson, Lisa A.

    2006-01-01

    Oxidation of deoxyribose in DNA produces a variety of electrophilic residues that are capable of reacting with nucleobases to form adducts such as M1dG, the pyrimidopurinone adduct of dG. We now report that deoxyribose oxidation in DNA leads to the formation of oxadiazabicyclo(3.3.0)octaimine adducts of dC and dA. We previously demonstrated that these adducts arise in reactions of nucleosides and DNA with trans-1,4-dioxo-2-butene, the β-elimination product of the 2-phosphoryl-1,4-dioxobutane ...

  4. Optimal DG placement in deregulated electricity market

    Energy Technology Data Exchange (ETDEWEB)

    Gautam, Durga; Mithulananthan, Nadarajah [Electric Power System Management, Energy Field of Study, Asian Institute of Technology, P.O. Box 4, Klong Luang, Pathumthani 12120 (Thailand)

    2007-10-15

    This paper presents two new methodologies for optimal placement of distributed generation (DG) in an optimal power flow (OPF) based wholesale electricity market. DG is assumed to participate in real time wholesale electricity market. The problem of optimal placement, including size, is formulated for two different objectives, namely, social welfare maximization and profit maximization. The candidate locations for DG placement are identified on the basis of locational marginal price (LMP). Obtained as lagrangian multiplier associated with active power flow equation for each node, LMP gives the short run marginal cost (SRMC) of electricity. Consumer payment, evaluated as a product of LMP and load at each load bus, is proposed as another ranking to identify candidate nodes for DG placement. The proposed rankings bridges engineering aspects of system operation and economic aspects of market operation and act as good indicators for the placement of DG, especially in a market environment. In order to provide a scenario of variety of DGs available in the market, several cost characteristics are assumed. For each DG cost characteristic, an optimal placement and size is identified for each of the objectives. The proposed methodology is tested in a modified IEEE 14 bus test system. (author)

  5. Bypass of Aflatoxin B[subscript 1] Adducts by the Sulfolobus solfataricus DNA Polymerase IV

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Surajit; Brown, Kyle L.; Egli, Martin; Stone, Michael P. (Vanderbilt)

    2012-07-18

    Aflatoxin B{sub 1} (AFB{sub 1}) is oxidized to an epoxide in vivo, which forms an N7-dG DNA adduct (AFB{sub 1}-N7-dG). The AFB{sub 1}-N7-dG can rearrange to a formamidopyrimidine (AFB{sub 1}-FAPY) derivative. Both AFB{sub 1}-N7-dG and the {beta}-anomer of the AFB{sub 1}-FAPY adduct yield G {yields} T transversions in Escherichia coli, but the latter is more mutagenic. We show that the Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) bypasses AFB{sub 1}-N7-dG in an error-free manner but conducts error-prone replication past the AFB{sub 1}-FAPY adduct, including misinsertion of dATP, consistent with the G {yields} T mutations observed in E. coli. Three ternary (Dpo4-DNA-dNTP) structures with AFB{sub 1}-N7-dG adducted template:primers have been solved. These demonstrate insertion of dCTP opposite the AFB{sub 1}-N7-dG adduct, and correct vs incorrect insertion of dATP vs dTTP opposite the 5'-template neighbor dT from a primed AFB{sub 1}-N7-dG:dC pair. The insertion of dTTP reveals hydrogen bonding between the template N3 imino proton and the O{sup 2} oxygen of dTTP, and between the template T O{sup 4} oxygen and the N3 imino proton of dTTP, perhaps explaining why this polymerase does not efficiently catalyze phosphodiester bond formation from this mispair. The AFB{sub 1}-N7-dG maintains the 5'-intercalation of the AFB{sub 1} moiety observed in DNA. The bond between N7-dG and C8 of the AFB{sub 1} moiety remains in plane with the alkylated guanine, creating a 16{sup o} inclination of the AFB{sub 1} moiety with respect to the guanine. A binary (Dpo4-DNA) structure with an AFB{sub 1}-FAPY adducted template:primer also maintains 5'-intercalation of the AFB{sub 1} moiety. The {beta}-deoxyribose anomer is observed. Rotation about the FAPY C5-N{sup 5} bond orients the bond between N{sup 5} and C8 of the AFB{sub 1} moiety out of plane in the 5'-direction, with respect to the FAPY base. The formamide group extends in the 3'-direction. This improves

  6. Formation of 1,4-dioxo-2-butene-derived adducts of 2'-deoxyadenosine and 2'-deoxycytidine in oxidized DNA.

    Science.gov (United States)

    Chen, Bingzi; Vu, Choua C; Byrns, Michael C; Dedon, Peter C; Peterson, Lisa A

    2006-08-01

    Oxidation of deoxyribose in DNA produces a variety of electrophilic residues that are capable of reacting with nucleobases to form adducts such as M(1)dG, the pyrimidopurinone adduct of dG. We now report that deoxyribose oxidation in DNA leads to the formation of oxadiazabicyclo(3.3.0)octaimine adducts of dC and dA. We previously demonstrated that these adducts arise in reactions of nucleosides and DNA with trans-1,4-dioxo-2-butene, the beta-elimination product of the 2-phosphoryl-1,4-dioxobutane residue arising from 5'-oxidation of deoxyribose in DNA, and with cis-1,4-dioxo-2-butene, a metabolite of furan. Treatment of DNA with enediyne antibiotics capable of oxidizing the 5'-position of deoxyribose (calicheamicin and neocarzinostatin) led to a concentration-dependent formation of oxadiazabicyclo(3.3.0)octaimine adducts of dC and dA, while the antibiotic bleomycin, which is capable of performing only 4-oxidation of deoxyribose, did not give rise to the adducts. The nonspecific DNA oxidant, gamma-radiation, also produced the adducts that represented approximately 0.1% of the 2-phosphoryl-1,4-dioxobutane residues formed during the irradiation. These results suggest that the oxadiazabicyclo(3.3.0)octaimine adducts of dC and dA could represent endogenous DNA lesions arising from oxidative stresses that also give rise to other DNA adducts. PMID:16918236

  7. Line narrowing spectroscopic studies of DNA-carcinogen adducts and DNA-dye complexes

    International Nuclear Information System (INIS)

    Laser-induced fluorescence line narrowing and non-line narrowing spectroscopic methods were applied to conformational studies of stable DNA adducts of the 7β, 8α-dihydoxy-9α, l0α-epoxy-7,8,9, 10-tetrahydrobenzo[α]pyrene (anti-BPDE). Stereochemically distinct (+)-trans-, (-)-trans-, (+)-cis- and (-)-cis adducts of anti-BPDE bound to exocyclic amino group of the central guanine in an 11-mer oligonucleotide, exist in a mixture of conformations in frozen aqueous buffer matrices. The (+)-trans adduct adopts primarily an external conformation with a smaller fraction ( ∼ 25 %) exists in a partially base-stacked conformation. Both cis adducts were found to be intercalated with significant π-π stacking interactions between the pyrenyl residues and the bases. Conformations of the trans-adduct of (+)-anti -BPDE in 11-mer oligonucleotides were studied as a function of flanking bases. In single stranded form the adduct at G2 or G3 (5 ft-flanking, base guanine) adopts a conformation with strong, interaction with the bases. In contrast, the adduct with a 5ft-flanking, thymine exists in a primarily helixexternal conformation. Similar differences were observed in the double stranded oligonucleotides. The nature of the 3ft-flanking base has little influence on the conformational equilibrium of the (+)-trans-anti BPDE-dG adduct. The formation and repair of BPDE-N2-dG in DNA isolated from the skin of mice treated topically with benzo[α]pyrene (BP) was studied. Low-temperature fluorescence spectroscopy of the intact DNA identified the major adduct as (+)-trans-anti-BPDE-N-dG, and the minor adduct fraction consisted mainly of (+)-cis-anti-BPDE-N2-dG

  8. Line narrowing spectroscopic studies of DNA-carcinogen adducts and DNA-dye complexes

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Myungkoo

    1995-12-06

    Laser-induced fluorescence line narrowing and non-line narrowing spectroscopic methods were applied to conformational studies of stable DNA adducts of the 7{beta}, 8{alpha}-dihydoxy-9{alpha}, l0{alpha}-epoxy-7,8,9, 10-tetrahydrobenzo[{alpha}]pyrene (anti-BPDE). Stereochemically distinct (+)-trans-, ({minus})-trans-, (+)-cis- and ({minus})-cis adducts of anti-BPDE bound to exocyclic amino group of the central guanine in an 11-mer oligonucleotide, exist in a mixture of conformations in frozen aqueous buffer matrices. The (+)-trans adduct adopts primarily an external conformation with a smaller fraction ( {approximately} 25 %) exists in a partially base-stacked conformation. Both cis adducts were found to be intercalated with significant {pi}-{pi} stacking interactions between the pyrenyl residues and the bases. Conformations of the trans-adduct of (+)-anti -BPDE in 11-mer oligonucleotides were studied as a function of flanking bases. In single stranded form the adduct at G{sub 2} or G{sub 3} (5 ft-flanking, base guanine) adopts a conformation with strong, interaction with the bases. In contrast, the adduct with a 5ft-flanking, thymine exists in a primarily helixexternal conformation. Similar differences were observed in the double stranded oligonucleotides. The nature of the 3ft-flanking base has little influence on the conformational equilibrium of the (+)-trans-anti BPDE-dG adduct. The formation and repair of BPDE-N{sup 2}-dG in DNA isolated from the skin of mice treated topically with benzo[{alpha}]pyrene (BP) was studied. Low-temperature fluorescence spectroscopy of the intact DNA identified the major adduct as (+)-trans-anti-BPDE-N-dG, and the minor adduct fraction consisted mainly of (+)-cis-anti-BPDE-N{sup 2}-dG.

  9. In Vitro Bypass of the Major Malondialdehyde- and Base Propenal-Derived DNA Adduct by Human Y-family DNA Polymerases κ, ι, and Rev1†

    OpenAIRE

    Maddukuri, Leena; Robert L Eoff; Choi, Jeong-Yun; Rizzo, Carmelo J.; Guengerich, F. Peter; Marnett, Lawrence J.

    2010-01-01

    3-(2′-Deoxy-β-d-erythro-pentofuranosyl)pyrimido-[1,2-a]purin-10(3H)-one (M1dG) is the major adduct derived from the reaction of DNA with the lipid peroxidation product malondialdehyde and the DNA peroxidation product base propenal. M1dG is mutagenic in Escherichia coli and mammalian cells, inducing base-pair substitutions (M1dG → A and M1dG → T) and frameshift mutations. Y-family polymerases may contribute to the mutations induced by M1dG in vivo. Previous reports described the bypass of M1dG...

  10. DNA adducts as molecular dosimeters

    International Nuclear Information System (INIS)

    There is compelling evidence that DNA adducts play an important role in the actions of many pulmonary carcinogens. During the last ten years sensitive methods (antibodies and 32P-postlabeling) have been developed that permit detection of DNA adducts in tissues of animals or humans exposed to low levels of some genotoxic carcinogens. This capability has led to approaches designed to more reliably estimate the shape of the dose-response curve in the low dose region for a few carcinogens. Moreover, dosimetry comparisions can, in some cases, be made between animals and humans which help in judging the adequacy of animal models for human risk assessments. There are several points that need to be considered in the evaluation of DNA adducts as a molecular dosimeter. For example, DNA adduct formation is only one of many events that are needed for tumor development and some potent carcinogens do not form DNA adducts; i.e., TCDD. Other issues that need to be considered are DNA adduct heterogeneity, DNA repair, relationship of DNA adducts to somatic mutation and cell specificity in DNA adduct formation and persistence. Molecular epidemiology studies often require quantitation of adducts in cells such as lymphocytes which may or may not be reliable surrogates for adduct concentrations in target issues. In summary, accurate quantitation of low levels of DNA adducts may provide data useful in species to species extrapolation of risk including the development of more meaningful human monitoring programs

  11. Dietary and lifestyle determinants of malondialdehyde DNA adducts in a representative sample of the Florence City population.

    Science.gov (United States)

    Saieva, Calogero; Peluso, Marco; Palli, Domenico; Cellai, Filippo; Ceroti, Marco; Selvi, Valeria; Bendinelli, Benedetta; Assedi, Melania; Munnia, Armelle; Masala, Giovanna

    2016-07-01

    Malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, is a mutagenic and carcinogenic compound that can react with DNA to form several types of DNA adducts including the deoxyguanosine adduct (M1dG). The aim of this cross-sectional study was to evaluate the association between individual dietary and lifestyle habits and M1dG levels, measured in peripheral leukocytes in a large representative sample of the general population of Florence City (Italy). Selected anthropometric measurements, detailed information on dietary and lifestyle habits and blood samples were available for 313 adults of the Florence City Sample enrolled in the frame of European Prospective Investigation into Cancer and nutrition (EPIC) study. A multivariate regression analysis adjusted for selected individual characteristics possibly related to M1dG levels (sex, age, BMI, smoke, physical activity level, education level, total caloric intake and a Mediterranean dietary score) was performed to estimate the association between these parameters and M1dG levels. M1dG levels were significantly higher in women (P = 0.014) and lower in moderately active or active subjects (P = 0.037).We also found a significant inverse association with the Modified Mediterranean dietary score (P for trend = 0.049), particularly evident for the highest categories of adherence. Our results indicate that M1dG levels can be modulated by selected individual characteristics such as gender, physical activity and a Mediterranean dietary pattern.

  12. Stability Analysis for Operation of DG Units in Smart Grids

    DEFF Research Database (Denmark)

    Pouresmaeil, Edris; Shaker, Hamid Reza; Mehrasa, Majid;

    2015-01-01

    This paper presents a multifunction control strategy for the stable operation of Distributed Generation (DG) units during grid integration. The proposed control model is based on Direct Lyapunov Control (DLC) theory and provides a stable region for the appropriate operation of DG units during grid...... integration. Using DLC technique in DG technology can provide the continuous injection of maximum active power in fundamental frequency from the DG source to the grid, compensating all reactive power and harmonic current components of grid-connected loads through the integration of DG link into the grid....... Application of this concept can guarantee to reduce the stress on the grid during the energy demand peak. Simulation results are presented to demonstrate the proficiency and performance of the proposed DLC technique in DG technology....

  13. Alcohol, Aldehydes, Adducts and Airways.

    Science.gov (United States)

    Sapkota, Muna; Wyatt, Todd A

    2015-11-05

    Drinking alcohol and smoking cigarettes results in the formation of reactive aldehydes in the lung, which are capable of forming adducts with several proteins and DNA. Acetaldehyde and malondialdehyde are the major aldehydes generated in high levels in the lung of subjects with alcohol use disorder who smoke cigarettes. In addition to the above aldehydes, several other aldehydes like 4-hydroxynonenal, formaldehyde and acrolein are also detected in the lung due to exposure to toxic gases, vapors and chemicals. These aldehydes react with nucleophilic targets in cells such as DNA, lipids and proteins to form both stable and unstable adducts. This adduction may disturb cellular functions as well as damage proteins, nucleic acids and lipids. Among several adducts formed in the lung, malondialdehyde DNA (MDA-DNA) adduct and hybrid malondialdehyde-acetaldehyde (MAA) protein adducts have been shown to initiate several pathological conditions in the lung. MDA-DNA adducts are pre-mutagenic in mammalian cells and induce frame shift and base-pair substitution mutations, whereas MAA protein adducts have been shown to induce inflammation and inhibit wound healing. This review provides an insight into different reactive aldehyde adducts and their role in the pathogenesis of lung disease.

  14. Base-Displaced Intercalated Structure of the N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone DNA Adduct.

    Science.gov (United States)

    Politica, Dustin A; Malik, Chanchal K; Basu, Ashis K; Stone, Michael P

    2015-12-21

    3-Nitrobenzanthrone (3-NBA), an environmental mutagen found in diesel exhaust and a suspected carcinogen, undergoes metabolic reduction followed by reaction with DNA to form aminobenzanthrone (ABA) adducts, with the major alkylation product being N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (C8-dG-ABA). Site-specific synthesis of the C8-dG-ABA adduct in the oligodeoxynucleotide 5'-d(GTGCXTGTTTGT)-3':5'-d(ACAAACACGCAC)-3'; X = C8-dG-ABA adduct, including codons 272-275 of the p53 gene, has allowed for investigation into the structural and thermodynamic properties of this adduct. The conformation of the C8-dG-ABA adduct was determined using NMR spectroscopy and was refined using molecular dynamics (MD) calculations restrained by experimentally determined interproton distance restraints obtained from NOE experiments. The refined structure revealed that the C8-dG-ABA adduct formed a base-displaced intercalated conformation. The adducted guanine was shifted into the syn conformation about the glycosidic bond. The 5'- and 3'-neighboring base pairs remained intact. While this facilitated π-stacking interactions between the ABA moiety and neighboring bases, the thermal melting temperature (Tm) of the adduct-containing duplex showed a decrease of 11 °C as compared to the corresponding unmodified oligodeoxynucleotide duplex. Overall, in this sequence, the base-displaced intercalated conformation of the C8-dG-ABA lesion bears similarity to structures of other arylamine C8-dG adducts. However, in this sequence, the base-displaced intercalated conformation for the C8-dG-ABA adduct differs from the conformation of the N(2)-dG-ABA adduct reported by de los Santos and co-workers, in which it is oriented in the minor groove toward the 5' end of the duplex, with the modified guanine remaining in the anti conformation about the glyosidic torsion angle, and the complementary base remaining within the duplex. The results are discussed in relationship to differences between the C8-d

  15. Short circuit analysis of distribution system with integration of DG

    DEFF Research Database (Denmark)

    Su, Chi; Liu, Zhou; Chen, Zhe;

    2014-01-01

    Integration of distributed generation (DG) such as wind turbines into distribution system is increasing all around the world, because of the flexible and environmentally friendly characteristics. However, DG integration may change the pattern of the fault currents in the distribution system and a...... as well. The results in this paper are based on mathematical analysis and simulation study in DIgSILENT PowerFactory....

  16. In vitro bypass of the major malondialdehyde- and base propenal-derived DNA adduct by human Y-family DNA polymerases κ, ι, and Rev1.

    Science.gov (United States)

    Maddukuri, Leena; Eoff, Robert L; Choi, Jeong-Yun; Rizzo, Carmelo J; Guengerich, F Peter; Marnett, Lawrence J

    2010-09-28

    3-(2'-Deoxy-β-d-erythro-pentofuranosyl)pyrimido-[1,2-a]purin-10(3H)-one (M(1)dG) is the major adduct derived from the reaction of DNA with the lipid peroxidation product malondialdehyde and the DNA peroxidation product base propenal. M(1)dG is mutagenic in Escherichia coli and mammalian cells, inducing base-pair substitutions (M(1)dG → A and M(1)dG → T) and frameshift mutations. Y-family polymerases may contribute to the mutations induced by M(1)dG in vivo. Previous reports described the bypass of M(1)dG by DNA polymerases η and Dpo4. The present experiments were conducted to evaluate bypass of M(1)dG by the human Y-family DNA polymerases κ, ι, and Rev1. M(1)dG was incorporated into template-primers containing either dC or dT residues 5' to the adduct, and the template-primers were subjected to in vitro replication by the individual DNA polymerases. Steady-state kinetic analysis of single nucleotide incorporation indicates that dCMP is most frequently inserted by hPol κ opposite the adduct in both sequence contexts, followed by dTMP and dGMP. dCMP and dTMP were most frequently inserted by hPol ι, and only dCMP was inserted by Rev1. hPol κ extended template-primers in the order M(1)dG:dC > M(1)dG:dG > M(1)dG:dT ∼ M(1)dG:dA, but neither hPol ι nor Rev1 extended M(1)dG-containing template-primers. Liquid chromatography-mass spectrometry analysis of the products of hPol κ-catalyzed extension verified this preference in the 3'-GXC-5' template sequence but revealed the generation of a series of complex products in which dAMP is incorporated opposite M(1)dG in the 3'-GXT-5' template sequence. The results indicate that DNA hPol κ or the combined action of hPol ι or Rev1 and hPol κ bypass M(1)dG residues in DNA and generate products that are consistent with some of the mutations induced by M(1)dG in mammalian cells. PMID:20726503

  17. In Vitro Bypass of the Major Malondialdehyde- and Base Propenal-Derived DNA Adduct by Human Y-family DNA Polymerases κ, ι, and Rev1†

    Science.gov (United States)

    2010-01-01

    3-(2′-Deoxy-β-d-erythro-pentofuranosyl)pyrimido-[1,2-a]purin-10(3H)-one (M1dG) is the major adduct derived from the reaction of DNA with the lipid peroxidation product malondialdehyde and the DNA peroxidation product base propenal. M1dG is mutagenic in Escherichia coli and mammalian cells, inducing base-pair substitutions (M1dG → A and M1dG → T) and frameshift mutations. Y-family polymerases may contribute to the mutations induced by M1dG in vivo. Previous reports described the bypass of M1dG by DNA polymerases η and Dpo4. The present experiments were conducted to evaluate bypass of M1dG by the human Y-family DNA polymerases κ, ι, and Rev1. M1dG was incorporated into template-primers containing either dC or dT residues 5′ to the adduct, and the template-primers were subjected to in vitro replication by the individual DNA polymerases. Steady-state kinetic analysis of single nucleotide incorporation indicates that dCMP is most frequently inserted by hPol κ opposite the adduct in both sequence contexts, followed by dTMP and dGMP. dCMP and dTMP were most frequently inserted by hPol ι, and only dCMP was inserted by Rev1. hPol κ extended template-primers in the order M1dG:dC > M1dG:dG > M1dG:dT ∼ M1dG:dA, but neither hPol ι nor Rev1 extended M1dG-containing template-primers. Liquid chromatography−mass spectrometry analysis of the products of hPol κ-catalyzed extension verified this preference in the 3′-GXC-5′ template sequence but revealed the generation of a series of complex products in which dAMP is incorporated opposite M1dG in the 3′-GXT-5′ template sequence. The results indicate that DNA hPol κ or the combined action of hPol ι or Rev1 and hPol κ bypass M1dG residues in DNA and generate products that are consistent with some of the mutations induced by M1dG in mammalian cells. PMID:20726503

  18. Mutagenic properties of the 8-amino-2'-deoxyguanosine DNA adduct in mammalian cells.

    OpenAIRE

    X. Tan; Suzuki, N; Johnson, F; Grollman, A P; Shibutani, S

    1999-01-01

    The DNA adduct 8-amino-2'-deoxyguanosine (8-amino-dG) is found in liver DNA of rats treated with the hepatocarcinogen 2-nitropropane. Site-specifically modified oligodeoxynucleotides were used to explore the mutagenic potential of 8-amino-dG in simian kidney (COS-7) cells. Oligodeoxynucleotides (5'-TCCTCCTX1G2CCTCTC and 5'-TCCTCCTG1X2CCTCTC, X = dG or 8-amino-dG) with the lesion positioned at codon 60 or 61 of the non-coding strand of the human c-Ha- ras1 gene were inserted into single-strand...

  19. The N(2)-Furfuryl-deoxyguanosine Adduct Does Not Alter the Structure of B-DNA.

    Science.gov (United States)

    Ghodke, Pratibha P; Gore, Kiran R; Harikrishna, S; Samanta, Biswajit; Kottur, Jithesh; Nair, Deepak T; Pradeepkumar, P I

    2016-01-15

    N(2)-Furfuryl-deoxyguanosine (fdG) is carcinogenic DNA adduct that originates from furfuryl alcohol. It is also a stable structural mimic of the damage induced by the nitrofurazone family of antibiotics. For the structural and functional studies of this model N(2)-dG adduct, reliable and rapid access to fdG-modified DNAs are warranted. Toward this end, here we report the synthesis of fdG-modified DNAs using phosphoramidite chemistry involving only three steps. The functional integrity of the modified DNA has been verified by primer extension studies with DNA polymerases I and IV from E. coli. Introduction of fdG into a DNA duplex decreases the Tm by ∼1.6 °C/modification. Molecular dynamics simulations of a DNA duplex bearing the fdG adduct revealed that though the overall B-DNA structure is maintained, this lesion can disrupt W-C H-bonding, stacking interactions, and minor groove hydrations to some extent at the modified site, and these effects lead to slight variations in the local base pair parameters. Overall, our studies show that fdG is tolerated at the minor groove of the DNA to a better extent compared with other bulky DNA damages, and this property will make it difficult for the DNA repair pathways to detect this adduct. PMID:26650891

  20. Determination of \\DG by ATLAS and the impact of non-zero \\DG on other Bs studies.

    CERN Document Server

    Smizanska, M

    1998-01-01

    ATLAS can measure \\DG a decay rate difference between the two mass eigenstates of \\Bs - \\aBs system, by analysing an angular-time distribution in the cascade decay \\Bsto. For a luminosity of $10^{33} cm^{-2} s^{-1}$ a maximum likelihood estimate gives a relative error better than 18\\% with a simultaneous measurement of the average \\Bs decay rate and the helicity amplitude parameters. The influence of a non-zero \\DG value is discussed for \\Bs oscillation measurement with flavour specific states and for CP-parity violating asymmetry measurement using tagged \\Bst decays.

  1. CERN High School Teachers Training Programme meets DG

    CERN Multimedia

    Brice, Maximilien

    2014-01-01

    CERN's DG Rolf Heuer met with the participants of the High School Teachers Training Programme on 23 July 2014 for a Q&A Session. Following the interaction, he met with the HST Working Group collaborating on a lesson plan for teaching SESAME in high schools.

  2. Interpreting Europe: mainstreaming gender in DG Research, European Commission

    NARCIS (Netherlands)

    Cavaghan, R.M.

    2015-01-01

    This chapter critically examines the European Commission’s work of governing. Taking the policy programme of Gender Mainstreaming (GM) as an example, Rosalind Cavaghan shows how officials in different units within DG Research interpreted their policy work and the consequences these interpretations s

  3. DNA adducts-chemical addons

    Directory of Open Access Journals (Sweden)

    T R Rajalakshmi

    2015-01-01

    Full Text Available DNA adduct is a piece of DNA covalently bond to a chemical (safrole, benzopyrenediol epoxide, acetaldehyde. This process could be the start of a cancerous cell. When a chemical binds to DNA, it gets damaged resulting in abnormal replication. This could be the start of a mutation and without proper DNA repair, this can lead to cancer. It is this chemical that binds with the DNA is our prime area of concern. Instead of performing the whole body analysis for diagnosing cancer, this test could be carried out for early detection of cancer. When scanning tunneling microscope is used, the DNA results can be obtained earlier. DNA adducts in scientific experiments are used as biomarkers.

  4. DNA adducts-chemical addons

    Science.gov (United States)

    Rajalakshmi, T. R.; AravindhaBabu, N.; Shanmugam, K. T.; Masthan, K. M. K.

    2015-01-01

    DNA adduct is a piece of DNA covalently bond to a chemical (safrole, benzopyrenediol epoxide, acetaldehyde). This process could be the start of a cancerous cell. When a chemical binds to DNA, it gets damaged resulting in abnormal replication. This could be the start of a mutation and without proper DNA repair, this can lead to cancer. It is this chemical that binds with the DNA is our prime area of concern. Instead of performing the whole body analysis for diagnosing cancer, this test could be carried out for early detection of cancer. When scanning tunneling microscope is used, the DNA results can be obtained earlier. DNA adducts in scientific experiments are used as biomarkers. PMID:26015708

  5. The boron trifluoride nitromethane adduct

    Science.gov (United States)

    Ownby, P. Darrell

    2004-02-01

    The separation of the boron isotopes using boron trifluoride·organic-donor, Lewis acid·base adducts is an essential first step in preparing 10B enriched and depleted crystalline solids so vital to nuclear studies and reactor applications such as enriched MgB 2, boron carbide, ZrB 2, HfB 2, aluminum boron alloys, and depleted silicon circuits for radiation hardening and neutron diffraction crystal structure studies. The appearance of this new adduct with such superior properties demands attention in the continuing search for more effective and efficient means of separation. An evaluation of the boron trifluoride nitromethane adduct, its thermodynamic and physical properties related to large-scale isotopic separation is presented. Its remarkably high separation factor was confirmed to be higher than the expected theoretical value. However, the reportedly high acid/donor ratio was proven to be an order of magnitude lower. On-going research is determining the crystal structure of deuterated and 11B enriched 11BF 3·CD 3NO 2 by X-ray and neutron diffraction.

  6. An improved current control scheme for grid-connected DG unit based distribution system harmonic compensation

    DEFF Research Database (Denmark)

    He, Jinwei; Wei Li, Yun; Wang, Xiongfei;

    2013-01-01

    In order to utilize DG unit interfacing converters to actively compensate distribution system harmonics, this paper proposes an enhanced current control approach. It seamlessly integrates system harmonic mitigation capabilities with the primary DG power generation function. As the proposed curren...

  7. Polychlorinated Biphenyls Induce Oxidative DNA Adducts in Female Sprague-Dawley Rats.

    Science.gov (United States)

    Mutlu, Esra; Gao, Lina; Collins, Leonard B; Walker, Nigel J; Hartwell, Hadley J; Olson, James R; Sun, Wei; Gold, Avram; Ball, Louise M; Swenberg, James A

    2016-08-15

    Polychlorinated biphenyls (PCBs) are organic chemicals that were traditionally produced and widely used in industry as mixtures and are presently formed as byproducts of pigment and dye manufacturing. They are known to persist and bioaccumulate in the environment. Some have been shown to induce liver cancer in rodents. Although the mechanism of the toxicity of PCBs is unknown, it has been shown that they increase oxidative stress, including lipid peroxidation. We hypothesized that oxidative stress-induced DNA damage could be a contributor for PCB carcinogenesis and analyzed several DNA adducts in female Sprague-Dawley rats exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and a binary mixture (PCB 126 + 153) for 14, 31, and 53 wks. Eight adducts were measured to profile oxidative DNA lesions, including 8-oxo-deoxyguanosine (8-oxo-dG), 1,N(6)-ethenodeoxyadenosine (1,N(6)-εdA), N(2),3-ethenoguanine (N(2),3-εG), 1,N(2)-ethenodeoxyguanosine (1,N(2)-εdG), as well as malondialdehyde (M1dG), acrolein (AcrdG), crotonaldehyde (CrdG), and 4-hydroxynonenal-derived dG adducts (HNEdG) by LC-MS/MS analysis. Statistically significant increases were observed for 8-oxo-dG and 1,N(6)-εdA concentrations in hepatic DNA of female rats exposed to the binary mixture (1000 ng/kg/day + 1000 μg/kg/day) but not in rats exposed to PCB 126 (1000 ng/kg/day) or PCB 153 (1000 μg/kg/day) for 14 and 31 wks. However, exposure to PCB 126 (1000 ng/kg/day) for 53 wks significantly increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, and M1dG. Exposure to PCB 153 (1000 μg/kg/day) for 53 wks increased 8-oxo-dG, and 1,N(6)-εdA. Exposure to the binary mixture for 53 wks increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, 1,N(2)-εdG, and N(2),3-εG significantly above control groups. Increased hepatic oxidative DNA adducts following exposure to PCB 126, PCB 153, or the binary mixture shows that an increase in DNA damage may play an important role in hepatic toxicity and

  8. Water vapor in the protoplanetary disk of DG Tau

    CERN Document Server

    Podio, L; Codella, C; Cabrit, S; Nisini, B; Dougados, C; Sandell, G; Williams, J P; Testi, L; Thi, W -F; Woitke, P; Meijerink, R; Spaans, M; Aresu, G; Menard, F; Pinte, C

    2013-01-01

    Water is key in the evolution of protoplanetary disks and the formation of comets and icy/water planets. While high excitation water lines originating in the hot inner disk have been detected in several T Tauri stars (TTSs), water vapor from the outer disk, where most of water ice reservoir is stored, was only reported in the closeby TTS TW Hya. We present spectrally resolved Herschel/HIFI observations of the young TTS DG Tau in the ortho- and para- water ground-state transitions at 557, 1113 GHz. The lines show a narrow double-peaked profile, consistent with an origin in the outer disk, and are ~19-26 times brighter than in TW Hya. In contrast, CO and [C II] lines are dominated by emission from the envelope/outflow, which makes H2O lines a unique tracer of the disk of DG Tau. Disk modeling with the thermo-chemical code ProDiMo indicates that the strong UV field, due to the young age and strong accretion of DG Tau, irradiates a disk upper layer at 10-90 AU from the star, heating it up to temperatures of 600 K...

  9. Structural and Functional Analysis of Sulfolobus solfataricus Y-Family DNA Polymerase Dpo4-Catalyzed Bypass of the Malondialdehyde−Deoxyguanosine Adduct

    Energy Technology Data Exchange (ETDEWEB)

    Eoff, Robert L.; Stafford, Jennifer B.; Szekely, Jozsef; Rizzo, Carmelo J.; Egli, Martin; Guengerich, F. Peter; Marnett, Lawrence J.; (Vanderbilt)

    2010-01-12

    Oxidative stress can induce the formation of reactive electrophiles, such as DNA peroxidation products, e.g., base propenals, and lipid peroxidation products, e.g., malondialdehyde. Base propenals and malondialdehyde react with DNA to form adducts, including 3-(2'-deoxy-{beta}-d-erythro-pentofuranosyl)pyrimido[1,2-{alpha}]purin-10(3H)-one (M{sub 1}dG). When paired opposite cytosine in duplex DNA at physiological pH, M{sub 1}dG undergoes ring opening to form N{sup 2}-(3-oxo-1-propenyl)-dG (N{sup 2}-OPdG). Previous work has shown that M{sub 1}dG is mutagenic in bacteria and mammalian cells and that its mutagenicity in Escherichia coli is dependent on induction of the SOS response, indicating a role for translesion DNA polymerases in the bypass of M{sub 1}dG. To probe the mechanism by which translesion polymerases bypass M{sub 1}dG, kinetic and structural studies were conducted with a model Y-family DNA polymerase, Dpo4 from Sulfolobus solfataricus. The level of steady-state incorporation of dNTPs opposite M{sub 1}dG was reduced 260-2900-fold and exhibited a preference for dATP incorporation. Liquid chromatography-tandem mass spectrometry analysis of the full-length extension products revealed a spectrum of products arising principally by incorporation of dC or dA opposite M{sub 1}dG followed by partial or full-length extension. A greater proportion of -1 deletions were observed when dT was positioned 5' of M{sub 1}dG. Two crystal structures were determined, including a 'type II' frameshift deletion complex and another complex with Dpo4 bound to a dC-M{sub 1}dG pair located in the postinsertion context. Importantly, M{sub 1}dG was in the ring-closed state in both structures, and in the structure with dC opposite M{sub 1}dG, the dC residue moved out of the Dpo4 active site, into the minor groove. The results are consistent with the reported mutagenicity of M{sub 1}dG and illustrate how the lesion may affect replication events.

  10. DNA adducts-chemical addons

    OpenAIRE

    T. R. Rajalakshmi; N AravindhaBabu; Shanmugam, K. T.; Masthan, K. M. K.

    2015-01-01

    DNA adduct is a piece of DNA covalently bond to a chemical (safrole, benzopyrenediol epoxide, acetaldehyde). This process could be the start of a cancerous cell. When a chemical binds to DNA, it gets damaged resulting in abnormal replication. This could be the start of a mutation and without proper DNA repair, this can lead to cancer. It is this chemical that binds with the DNA is our prime area of concern. Instead of performing the whole body analysis for diagnosing cancer, this test could b...

  11. Bilateral failure of adduction following orbital decompression.

    OpenAIRE

    Kinsella, F; Kyle, P.; Stansfield, A

    1990-01-01

    We report a case of bilateral complete failure of adduction following bilateral translid antralethmoidal orbital decompression. We believe the probable mechanism is neuropraxia (temporary dysfunction) of the third cranial nerves' supply to the medial recti, owing to these nerves' occupying an anatomically abnormal position. Partial recovery of adduction occurred over the ensuing six months.

  12. Overcurrent protection issues due to the DG connection

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, J.C.; Tourn, D.H.; Amatti, J.C. [Rio Cuarto National University (IPSEP/UNRC), Cordoba (Argentina). Electric Power Systems Protection Institute], E-mail: jcgomez@ing.unrc.edu.ar

    2009-07-01

    The present energy crisis drives to carry to an extreme the use of all the available energy sources, which need to be connected to the network in their closest point. Traditional electric systems are changing their characteristics, in what concerns to structure, operation, and especially on protection methodologies. The new protection problems of the different parts of the system are explained. The solution presents positive and negative aspects that impact the utility and the customer in different ways. A revision about interconnection international standards is presented. The contributions of generators to short circuit currents is analyzed, especially the double fed generator. Philosophy changes are studied, such as: fault current bi directionality, modification of the protection reach, failures of the overcurrent coordination due to current share, etc. Solicitations to DG due to the normal unbalance of distribution systems are also studied. It is analyzed the discrepancy between the customers and utilities regarding the 'islanding operation', presenting the semi-rigid connection. The changes in the coordination methodology fusible-recloser are also studied, proposing a new methodology to check this coordination. Experimental results on 13.2 kV are presented that relate the deionization without zero current, with arc length and with 'network power to DG power ratio'. It is concluded that DG application offers technical-economic advantages so much to the utility as to the user; and that the technology for these new protection approaches is already available, requiring of investments whose justification needs of a specific analysis for each particular case. (author)

  13. Long Term Optimal DG Placement Considering Transmission System Reliability and Load Uncertainty

    Directory of Open Access Journals (Sweden)

    Ali Badri

    2013-06-01

    Full Text Available DG (dispersed generation application has received increasing attention during recent years. The impact of DG on various aspects of distribution system characteristics depends highly on DG location in distribution feeder. This paper presents an optimization method to determine long term optimal DG placement in distribution systems in which system reliability and operational constraints as well as environmental constraints are taken into account. In order to get more realistic results impact of load uncertainty is modeled using normal distribution function. Furthermore, DG transactions with the market and corresponding payoffs are calculated. Despite, most of studies dealing with the problem from cost minimization point of view in a short term period, here DG placement is investigated from long term perspective. To get more accurate results the model considers both DG benefits and costs and the objective function is based on DG profit maximization. Benefits of using DG consist of loss reduction revenue, reducing in costumers' interruption costs, power purchase saving as well as green house gas and fossil fuel reductions. Whereas, the costs consist of initial costs, maintenance and operating costs and DG transition costs as well. The proposed model is simulated on a standard IEEE test system to obtain the results and show the accuracy of the model.

  14. [DNA adducts in human female genital organs].

    Science.gov (United States)

    Postawski, Krzysztof; Przadka-Rabaniuk, Dorota; Monist, Marta; Baranowski, Włodzimierz

    2007-12-01

    DNA adducts, one of genetic damages markers, precede and finally can lead to oncogenic mutations. They appear in genome as a result of DNA bases damages caused by various and numerous environmental factors eg. ultraviolet light, ionic radiation, toxins and also endogenic substances, for example estrogens. It is believed that the creation of DNA adducts is a necessary but insufficient process for the neoplastic transformation of the cell. The following review presents concise knowledge about the DNA adducts creation and their sequels served in healthy and cancerous tissues of the female genital organs, on the base of the available data. PMID:18411923

  15. DG Placement with Considering Reliability Improvement and Power Loss Reduction with GA Method

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadi

    2011-08-01

    Full Text Available Distributed generators are beneficial in reducing the losses effectively compared to other methods of loss reduction. DGs can be implemented for improvement of reliability of system; too In this study optimal DG unit placement using GA is discussed. The optimal size of the DG unit is calculated analytically using approximate reasoning suitable nodes are determined for DG unit placement. Reliability and power loss reduction indices of distribution system nodes are modeled. GA containing a set of rules is used to determine the DG unit placement. DG units are placed with the highest suitability index. Simulation results show the advantage of optimal DG unit placement. Compared to other power loss and reliability improvement techniques, placement it is giving very good reduction not only in power loss but also it is improving reliability improvement.

  16. Large-Signal DG-MOSFET Modelling for RFID Rectification

    Directory of Open Access Journals (Sweden)

    R. Rodríguez

    2016-01-01

    Full Text Available This paper analyses the undoped DG-MOSFETs capability for the operation of rectifiers for RFIDs and Wireless Power Transmission (WPT at microwave frequencies. For this purpose, a large-signal compact model has been developed and implemented in Verilog-A. The model has been numerically validated with a device simulator (Sentaurus. It is found that the number of stages to achieve the optimal rectifier performance is inferior to that required with conventional MOSFETs. In addition, the DC output voltage could be incremented with the use of appropriate mid-gap metals for the gate, as TiN. Minor impact of short channel effects (SCEs on rectification is also pointed out.

  17. Designing a collection layout for DG-CO collections

    CERN Document Server

    Pantic, Radoslav

    2014-01-01

    While CDS is in use for years and contains a very large number of interesting resources (documents, papers, articles, presentations, videos, images, photos, audio files etc), practical and daily use of it has shown some limitations. First of all, the extremely large amount of available resources does not make easy the possibility to focus only on certain specific pre-selected documents. Second, the search capabilities of CDS, while very extended, do not always meet client-specific needs and are not always easy to use by unexperienced external visitors. This document describes an ideal tool to be used by DG-CO (but also potentially other services) to overcome the 2 limitations described above.

  18. 32P-adduct assay: Comparative recoveries of structurally diverse DNA adducts in the various enhancement procedures

    International Nuclear Information System (INIS)

    A (32)P-adduct assay for the measurement of low levels (1 adduct per 10(sup 7) nucleotides) of binding of carcinogens to DNA has been reported previously. In this procedure, DNA is enzymatically hydrolyzed to 3'-monophosphates of normal nucleosides and adducts, which are 5'-(32)P-labeled by T4 polynucleotide kinase and (lambda(32)P)ATP. Labeled adducts are resolved by TLC. Enrichment of adducts by extraction in 1-butanol or digestion with nuclease P1 prior to (32)P-labeling, however, increased the sensitivity of detection for many adducts to a level of 1 per 10(sup 9-10) nucleotides, although adduct recovery particularly in the latter assay depended on the chemical nature of adducts. The observation that chemical structure of an adduct may be detrimental in its recovery in the enzyme- and extraction-mediated enrichment procedures may serve as a probe in the structural characterization of adducts of unknown carcinogens

  19. Product ion studies of diastereomeric benzo[ghi]fluoranthene-2'-deoxynucleoside adducts by electrospray ionization and quadrupole ion trap mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Li Linge [Department of Chemistry, Loyola University, Chicago, IL 60626 (United States); Chang, H.-F. [Department of Biomedical Sciences, University of Rhode Island, Kingston, RI 02881 (United States); Olsen, Kenneth W. [Department of Chemistry, Loyola University, Chicago, IL 60626 (United States); Cho, Bongsup P. [Department of Biomedical Sciences, University of Rhode Island, Kingston, RI 02881 (United States); Chiarelli, M. Paul [Department of Chemistry, Loyola University, Chicago, IL 60626 (United States)]. E-mail: mchiare@luc.edu

    2006-01-31

    The product ion formation characteristics of the protonated molecule ions generated from 10 different deoxynucleoside adducts of benzo[ghi]fluoranthene (B[ghi]F) have been studied using electrospray ionization (ESI) and quadrupole ion trap mass spectrometry to gain a better understanding of the fragmentation mechanisms that govern structure-specific fragmentation. The reaction of the syn- and anti-diastereomers of trans-3,4-dihydroxy-5,5a-tetrahydrobenzo[ghi]fluoranthene with DNA produce four deoxyguanosine, four deoxyadenosine, and two deoxycytidine adducts whose structures differ based on the cis/trans arrangement of the hydroxyl groups and nucleic acids bound to B[ghi]F. Those adducts that have structures where the nucleic acid and 3'-hydroxyl group of B[ghi]F are cis with respect to each other undergo extensive water loss whereas those isomers where the nucleic acid and 3'-hydroxyl group are trans do not. These results are consistent with a mechanism of water loss initiated by a hydrogen-bonding interaction between the charge-bearing proton on a heterocyclic nitrogen atom on the nucleic acid and the 3'-hydroxyl oxygen on the PAH. The dG and dC adducts are observed to undergo more extensive water loss than the dA adducts. Molecular modeling indicates that the larger relative abundances of the product ions formed by water loss for the dG and dC relative to dA are due to stronger hydrogen-bonding interactions prior to fragmentation and the greater stability of the carbocations formed at the C3' carbon after fragmentation.

  20. 78 FR 67013 - Airworthiness Directives; DG Flugzeugbau GmbH Gliders

    Science.gov (United States)

    2013-11-08

    ...; fax: +49 7251 3020 269; Internet: http://www.dg-flugzeugbau.de/index.php?id=1329 ; email: dirks@dg..., call (816) 329-4148. Examining the AD Docket You may examine the AD docket on the Internet at http... Internet at http://www.regulations.gov by searching for and locating it in Docket No....

  1. Multiclass Carcinogenic DNA Adduct Quantification in Formalin-Fixed Paraffin-Embedded Tissues by Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry.

    Science.gov (United States)

    Guo, Jingshu; Yun, Byeong Hwa; Upadhyaya, Pramod; Yao, Lihua; Krishnamachari, Sesha; Rosenquist, Thomas A; Grollman, Arthur P; Turesky, Robert J

    2016-05-01

    DNA adducts are a measure of internal exposure to genotoxicants and an important biomarker for human risk assessment. However, the employment of DNA adducts as biomarkers in human studies is often restricted because fresh-frozen tissues are not available. In contrast, formalin-fixed paraffin-embedded (FFPE) tissues with clinical diagnosis are readily accessible. Recently, our laboratory reported that DNA adducts of aristolochic acid, a carcinogenic component of Aristolochia herbs used in traditional Chinese medicines worldwide, can be recovered quantitatively from FFPE tissues. In this study, we have evaluated the efficacy of our method for retrieval of DNA adducts from archived tissue by measuring DNA adducts derived from four other classes of human carcinogens: polycyclic aromatic hydrocarbons (PAHs), aromatic amines, heterocyclic aromatic amines (HAAs), and N-nitroso compounds (NOCs). Deoxyguanosine (dG) adducts of the PAH benzo[a]pyrene (B[a]P), 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N(2)-B[a]PDE); the aromatic amine 4-aminobiphenyl (4-ABP), N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP); the HAA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP); and the dG adducts of the NOC 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), O(6)-methyl-dG (O(6)-Me-dG) and O(6)-pyridyloxobutyl-dG (O(6)-POB-dG), formed in liver, lung, bladder, pancreas, or colon were recovered in comparable yields from fresh-frozen and FFPE preserved tissues of rodents treated with the procarcinogens. Quantification was achieved by ultraperformance liquid chromatography coupled with electrospray ionization ion-trap multistage mass spectrometry (UPLC/ESI-IT-MS(3)). These advancements in the technology of DNA adduct retrieval from FFPE tissue clear the way for use of archived pathology samples in molecular epidemiology studies designed to assess the causal role of exposure to hazardous chemicals

  2. Sperm DNA oxidative damage and DNA adducts.

    Science.gov (United States)

    Jeng, Hueiwang Anna; Pan, Chih-Hong; Chao, Mu-Rong; Lin, Wen-Yi

    2015-12-01

    The objective of this study was to investigate DNA damage and adducts in sperm from coke oven workers who have been exposed to polycyclic aromatic hydrocarbons. A longitudinal study was conducted with repeated measurements during spermatogenesis. Coke-oven workers (n=112) from a coke-oven plant served the PAH-exposed group, while administrators and security personnel (n=67) served the control. Routine semen parameters (concentration, motility, vitality, and morphology) were analyzed simultaneously; the assessment of sperm DNA integrity endpoints included DNA fragmentation, bulky DNA adducts, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo). The degree of sperm DNA fragmentation was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and sperm chromatin structure assay (SCSA). The PAH-exposed group had a significant increase in bulky DNA adducts and 8-oxo-dGuo compared to the control subjects (Ps=0.002 and 0.045, respectively). Coke oven workers' percentages of DNA fragmentation and denaturation from the PAH-exposed group were not significantly different from those of the control subjects (Ps=0.232 and 0.245, respectively). Routine semen parameters and DNA integrity endpoints were not correlated. Concentrations of 8-oxo-dGuo were positively correlated with percentages of DNA fragmentation measured by both TUNEL and SCSA (Ps=0.045 and 0.034, respectively). However, the concentrations of 8-oxo-dGuo and percentages of DNA fragmentation did not correlate with concentrations of bulky DNA adducts. In summary, coke oven workers with chronic exposure to PAHs experienced decreased sperm DNA integrity. Oxidative stress could contribute to the degree of DNA fragmentation. Bulky DNA adducts may be independent of the formation of DNA fragmentation and oxidative adducts in sperm. Monitoring sperm DNA integrity is recommended as a part of the process of assessing the impact of occupational and environmental toxins on sperm

  3. Hip adduction and abduction strength profiles in elite soccer players

    DEFF Research Database (Denmark)

    Thorborg, Kristian; Serner, Andreas; Petersen, Jesper;

    2011-01-01

    An ipsilateral hip adduction/abduction strength ratio of more than 90%, and hip adduction strength equal to that of the contralateral side have been suggested to clinically represent adequate strength recovery of hip adduction strength in athletes after groin injury. However, to what extent side......-to-side symmetry in isometric hip adduction and abduction strength can be assumed in soccer players remains uncertain....

  4. Hip adduction and abduction strength profiles in elite soccer players

    DEFF Research Database (Denmark)

    Serner, Andreas; Petersen, Jesper; Madsen, Thomas Moller;

    2011-01-01

    An ipsilateral hip adduction/abduction strength ratio of more than 90%, and hip adduction strength equal to that of the contralateral side have been suggested to clinically represent adequate strength recovery of hip adduction strength in athletes after groin injury. However, to what extent side-......-to-side symmetry in isometric hip adduction and abduction strength can be assumed in soccer players remains uncertain....

  5. Ring-Opening of the γ-OH-PdG Adduct Promotes Error-Free Bypass by the Sulfolobus solfataricus DNA Polymerase Dpo4

    OpenAIRE

    Shanmugam, Ganesh; Minko, Irina G.; Banerjee, Surajit; Christov, Plamen P.; Kozekov, Ivan D.; Rizzo, Carmelo J.; Lloyd, R. Stephen; Egli, Martin; Michael P. Stone

    2013-01-01

    Acrolein, a mutagenic aldehyde, reacts with deoxyguanosine (dG) to form 3-(2′-deoxy-β-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a] purin-10(3H)-one (γ-OH-PdG). When placed opposite deoxycytosine (dC) in DNA, γ-OH-PdG undergoes ring-opening to the N 2-(3-oxopropyl)-dG. Ring-opening of the adduct has been hypothesized to facilitate nonmutagenic bypass, particularly by DNA polymerases of the Y family. This study examined the bypass of γ-OH-PdG by Sulfolobus solfataricus ...

  6. New adducts of Lapachol with primary amines

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Mirelly D.F.; Litivack-Junior, Jose T.; Antunes, Roberto V.; Silva, Tania M.S.; Camara, Celso A., E-mail: ccelso@dq.ufrpe.b [Universidade Federal Rural de Pernambuco (UFRPE), Recife, PE (Brazil). Dept. de Quimica

    2011-07-01

    New adducts of lapachol with neat primary aliphatic amines were obtained in a solvent-free reaction in good to reasonable yields (52 to 88%), at room temperature. The new compounds containing a phenazine moiety were obtained from suitable functionalized aminoalkyl compounds, including ethanolamine, 3-propanolamine, 2-methoxy-ethylamine, 3-methoxy-propylamine, n-butylamine and 2-phenetylamine. (author)

  7. STUDY ON GMA-DNA ADDUCTS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective. DNA modification fixed as mutations in the cells may be an essential factor in the initiation step of chemical carcinogenesis. In order to explore the mechanism of gene mutation and cell transformation induced by glycidyl methacrylate (GMA), the current test studied the characteristics of GMA-DNA adducts formation in vitro.Methods. In vitro test, dAMP, dCMP, dGMP, dTMP and calf thymus DNA were allowed to react with GMA (Glycidyl Methacrylate). After the reaction, the mixtures were detected by UV and subjected to reversed-phase HPLC on ultrasphere ODS reversed-phase column, the reaction products were eluted with a linear gradients of methanol (solvent A) and 10mmol/L ammonium formate, pH5.0 (solvent B). The synthesized adducts were then characterized by UV spectroscopy in acid (pH1.0), neutral (pH7.2), alkaline (pH11.0) and by mass spectroscopy.Results. The results showed that GMA could bind with dAMP, dCMP, dGMP and calf thymus DNA by covalent bond, and the binding sites were specific (N6 of adenine, N3 of cytosine). Meanwhile, a main GMA-DNA adduct in the reaction of GMA with calf thymus DNA was confirmed as N3-methacrylate-2-hydroxypropy1-dCMP.Conclusions. GMA can react with DNA and /or deoxynucleotide monophosphate and generate some adducts such as N6-methacrylate-2-hydroxypropyl-dAMP and N3-methacrylate-2-hydroxypropyl-dCMP, ets. Formation of GMA-DNA adducts is an important molecular event in gene mutation and cell transformation induced by GMA.

  8. Passivity-based control technique for integration of DG resources into the power grid

    DEFF Research Database (Denmark)

    Mehrasa, Majid; Adabi, M. Ebrahim; Pouresmaeil, Edris;

    2014-01-01

    This paper deals with a control method for integration of Distributed Generation (DG) sources to the power grid. The proposed control strategy has been designed based on passivity technique and provides compensation for the active, reactive, and harmonic current components of loads during...... the connection of DG link to the grid. The proper switching functions of interfaced converter have been defined based on the passivity method through the achieving space equations and suitable series damping injection. The proposed control plan is completed by setting suitable reference current components...... for the d and q axis in the control loop of DG, which are defined based on the objectives of proposed method. The effectiveness of the proposed control scheme is validated with injection of maximum available power from the DG resources to the power grid, correction of power factor between the grid current...

  9. A control technique for integration of DG units to the electrical networks

    DEFF Research Database (Denmark)

    Pouresmaeil, Edris; Miguel-Espinar, Carlos; Massot-Campos, Miquel;

    2013-01-01

    This paper deals with a multiobjective control technique for integration of distributed generation (DG) resources to the electrical power network. The proposed strategy provides compensation for active, reactive, and harmonic load current components during connection of DG link to the grid...... and utility grid. By setting an appropriate compensation current references from the sensed load currents in control circuit loop of DG, the active, reactive, and harmonic load current components will be compensated with fast dynamic response, thereby achieving sinusoidal grid currents in phase with load...... voltages, while required power of the load is more than the maximum injected power of the DG to the grid. In addition, the proposed control method of this paper does not need a phase-locked loop in control circuit and has fast dynamic response in providing active and reactive power components of the grid...

  10. Placement and Sizing of DG Using PSO&HBMO Algorithms in Radial Distribution Networks

    Directory of Open Access Journals (Sweden)

    M. A.Taghikhani

    2012-09-01

    Full Text Available Optimal placement and sizing of DG in distribution network is an optimization problem with continuous and discrete variables. Many researchers have used evolutionary methods for finding the optimal DG placement and sizing. This paper proposes a hybrid algorithm PSO&HBMO for optimal placement and sizing of distributed generation (DG in radial distri-bution system to minimize the total power loss and improve the voltage profile. The proposed method is tested on a standard 13 bus radial distribution system and simulation results carried out using MATLAB software. The simulation results indicate that PSO&HBMO method can obtain better results than the simple heuristic search method and PSO algorithm. The method has a potential to be a tool for identifying the best location and rating of a DG to be installed for improving voltage profile and line losses reduction in an electrical power system. Moreover, current reduction is obtained in distribution system.

  11. SUPERCONVERGENCE OF DG METHOD FOR ONE-DIMENSIONAL SINGULARLY PERTURBED PROBLEMS

    Institute of Scientific and Technical Information of China (English)

    Ziqing Xie; Zhimin Zhang

    2007-01-01

    The convergence and superconvergence properties of the discontinuous Galerkin (DG) method for a singularly perturbed model problem in one-dimensional setting are studied.By applying the DG method with appropriately chosen numerical traces, the existence and uniqueness of the DG solution, the optimal order L2 error bounds, and 2p+1-order superconvergence of the numerical traces are established. The numerical results indicate that the DG method does not produce any oscillation even under the uniform mesh. Numerical experiments demonstrate that, under the uniform mesh, it seems impossible to obtain the uniform superconvergence of the numerical traces. Nevertheless, thanks to the implementation of the so-called Shishkin-type mesh, the uniform 2p + 1-order superconvergence is observed numerically.

  12. Improved Grid Synchronization Algorithm for DG System using DSRF PLL under Grid disturbances

    OpenAIRE

    R.Godha; Ch.V.S.S.Sailaja

    2014-01-01

    Distributed Generation (DG) System is a small scale electric power generation at or near the user’s facility as opposed to the normal mode of centralized power generation. In order to ensure safe and reliable operation of power system based on DS, grid synchronization algorithm plays a very important role. This paper presents a Double Synchronous Reference Frame (DSRF) phase locked loop (PLL) based on synthesis circuit for grid synchronization of distributed generation (DG) system...

  13. Acetaldehyde Adducts in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Mashiko Setshedi

    2010-01-01

    Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

  14. Covalent adduction of nitrogen mustards to model protein nucleophiles.

    Science.gov (United States)

    Thompson, Vanessa R; DeCaprio, Anthony P

    2013-08-19

    Protein adducts have the potential to serve as unique biomarkers of exposure to compounds of interest. Many xenobiotics (or their metabolites) are electrophilic and therefore reactive with nucleophilic amino acid residues on proteins. Nitrogen mustards are reactive xenobiotics with potential use as chemical warfare agents (CWA) or agents of terrorist attack, in addition to being employed as chemotherapeutic agents. The present study utilized cysteine-, lysine-, and histidine-containing model peptides to characterize in vitro adduction of the nitrogen mustards mechloroethamine (HN-2) and tris-(2-chlorethyl)amine (HN-3) to these nucleophilic amino acid residues by means of liquid chromatography-tandem mass spectrometry. The study assessed the structure of adducts formed, the time course of adduct formation, concentration-response relationships, and temporal stability of adducts. Adduction was hypothesized to occur on all three model peptides via initial formation of a reactive aziridinium intermediate for both mechloroethamine and tris-(2-chlorethyl)amine, followed by covalent adduction to nucleophilic residues. While adduction was found to occur most readily with cysteine, it was also observed at lysine and histidine, demonstrating that adduction by mechloroethamine and tris-(2-chlorethyl)amine is possible at multiple nucleophilic sites. Following solid phase extraction cleanup, adducts formed with mechloroethamine were stable for up to three weeks. Adducts formed with tris-(2-chlorethyl)amine were less stable; however, hydrolyzed secondary adducts were observed throughout the three week period. This study demonstrates that the nitrogen mustards mechloroethamine and tris-(2-chlorethyl)amine form stable adducts with reactive protein nucleophiles other than cysteine. PMID:23859065

  15. Redshift or adduct stabilization -- a computational study of hydrogen bonding in adducts of protonated carboxylic acids

    DEFF Research Database (Denmark)

    Olesen, Solveig Gaarn; Hammerum, Steen

    2009-01-01

    not always yield consistent predictions, as illustrated by the hydrogen bonds formed by the E and Z OH groups of protonated carboxylic acids. The delta-PA and the stabilization of a series of hydrogen bonded adducts indicate that the E OH group forms the stronger hydrogen bonds, whereas the bond length...... carboxylic acids are different. The OH bond length and IR redshift afford the better measure of hydrogen bond strength.......It is generally expected that the hydrogen bond strength in a D-H-A adduct is predicted by the difference between the proton affinities of D and A, measured by the adduct stabilization, and demonstrated by the IR redshift of the D-H bond stretching vibrational frequency. These criteria do...

  16. Toward a self-wired active reconstruction of the hippocampal trisynaptic loop: DG-CA3

    Directory of Open Access Journals (Sweden)

    Gregory J. Brewer

    2013-10-01

    Full Text Available The mammalian hippocampus functions to encode and retrieve memories by transiently changing synaptic strengths, yet encoding in individual subregions for transmission between regions remains poorly understood. Toward the goal of better understanding the coding in the trisynaptic pathway from the dentate gyrus (DG to the CA3 and CA1, we report a novel microfabricated device that divides a micro-electrode array into two compartments of separate hippocampal network subregions connected by axons that grow through 3x10x400 μm tunnels. Gene expression by qPCR demonstrated selective enrichment of separate DG, CA3 and CA1 subregions. Reconnection of DG to CA3 altered burst dynamics associated with marked enrichment of GAD67 in DG and GFAP in CA3. Surprisingly, DG axon spike propagation was preferentially unidirectional to the CA3 region at 0.5 m/s with little reverse transmission. Therefore, select hippocampal subregions intrinsically self-wire in anatomically appropriate patterns and maintain their distinct subregion phenotype without external inputs

  17. Impact of parameter fluctuations on RF stability performance of DG tunnel FET

    Science.gov (United States)

    Sivasankaran, K.; Mallick, P. S.

    2015-08-01

    This paper presents the impact of parameter fluctuation due to process variation on radio frequency (RF) stability performance of double gate tunnel FET (DG TFET). The influence of parameter fluctuation due to process variation leads to DG TFET performance degradation. The RF figures of merit (FoM) such as cut-off frequency (ft), maximum oscillation frequency (fmax) along with stability factor for different silicon body thickness, gate oxide thickness and gate contact alignment are obtained from extracted device parameters through numerical simulation. The impact of parameter fluctuation of silicon body thickness, gate oxide thickness and gate contact alignment was found significant and the result provides design guidelines of DG TFET for RF applications.

  18. Insights into channel potentials and electron quasi-Fermi potentials for DG tunnel FETs

    Science.gov (United States)

    Menka; Bulusu, Anand; Dasgupta, S.

    2015-01-01

    A detailed investigation carried out, with the help of extensive simulations using the TCAD device simulator Sentaurus, with the aim of achieving an understanding of the effects of variations in gate and drain potentials on the device characteristics of a silicon double-gate tunnel field effect transistor (Si-DG TFET) is reported in this paper. The investigation is mainly aimed at studying electrical properties such as the electric potential, the electron density, and the electron quasi-Fermi potential in a channel. From the simulation results, it is found that the electrical properties in the channel region of the DG TFET are different from those for a DG MOSFET. It is observed that the central channel potential of the DG TFET is not pinned to a fixed potential even after the threshold is passed (as in the case of the DG MOSFET); instead, it initially increases and later on decreases with increasing gate voltage, and this is also the behavior exhibited by the surface potential of the device. However, the drain current always increases with the applied gate voltage. It is also observed that the electron quasi-Fermi potential (eQFP) decreases as the channel potential starts to decrease, and there are hiphops in the channel eQFP for higher applied drain voltages. The channel regime resistance is also observed for higher gate length, which has a great effect on the I-V characteristics of the DG TFET device. These channel regime electrical properties will be very useful for determining the tunneling current; thus these results may have further uses in developing analytical current models.

  19. General and Simple Decision Method for DG Penetration Level in View of Voltage Regulation at Distribution Substation Transformers

    Directory of Open Access Journals (Sweden)

    Joon-Ho Choi

    2013-09-01

    Full Text Available A distribution system was designed and operated by considering unidirectional power flow from a utility source to end-use loads. The large penetrations of distributed generation (DG into the existing distribution system causes a variety of technical problems, such as frequent tap changing problems of the on-load tap changer (OLTC transformer, local voltage rise, protection coordination, exceeding short-circuit capacity, and harmonic distortion. In view of voltage regulation, the intermittent fluctuation of the DG output power results in frequent tap changing operations of the OLTC transformer. Thus, many utilities limit the penetration level of DG and are eager to find the reasonable penetration limits of DG in the distribution system. To overcome this technical problem, utilities have developed a new voltage regulation method in the distribution system with a large DG penetration level. In this paper, the impact of DG on the OLTC operations controlled by the line drop compensation (LDC method is analyzed. In addition, a generalized determination methodology for the DG penetration limits in a distribution substation transformer is proposed. The proposed DG penetration limits could be adopted for a simplified interconnection process in DG interconnection guidelines.

  20. Intramolecular Tetrylene Lewis Adducts: Synthesis and Reactivity.

    Science.gov (United States)

    Schneider, Julia; Krebs, Kilian M; Freitag, Sarah; Eichele, Klaus; Schubert, Hartmut; Wesemann, Lars

    2016-07-01

    A series of benzyl(diphenylphosphino) and o-phenyl(diphenlyphosphino) substituted germylenes and plumbylenes were synthesized by nucleophilic substitution between the respective lithium reagent and tetrylene halide. The Lewis pairs were characterized by X-ray crystallography and NMR spectroscopy. The reactivity of the tetrylenes was investigated with respect to azide addition. In the germylene case, the germaniumimide was formed as the kinetically controlled product, which rearranges upon heating to give the phosphinimide. The stannylene and plumbylene derivatives react with adamantylazide to give the azide adducts. 1-Pentene reacts diastereoselectively with the phosphagermirane to give a cyclic addition product. Trimethysilylacetylene shows an addition with the benzylphosphino-substituted germylene and plumbylene to give the cycloheteropentene molecules. The addition product between phenylacetylene and the four membered Ge-P adduct shows after addition at room temperature a 1,4-phenylmigration to give a cyclic phosphine. Alkylnitrene insertion into a Ge-C bond of the alkyne addition product of the phosphagermirane was found in reaction with adamantylazide. PMID:27273819

  1. Synthesis and Photophysical Properties of C60-carbazole Adducts

    Institute of Scientific and Technical Information of China (English)

    YIN ,Gui(尹桂); YIN,Gui; MAO,Xin-Ping(毛新平); MAO,Xin-Ping; SUO,Zhi-Yong(锁志勇); SUO,Zhi-Yong; XU,Zheng(徐正); XU,Zheng

    2001-01-01

    Three C60-cartazole adducts have been synthesized by 1,3-dipolar cycloaddition reaction.Intramolecular energy/electron transfer from carbazole to C60 was observed by steady-state absorption and fluorescence spectra.The fluorescence spectra of these adducts were similau to each other and dependent on the excitation wavelength and solvent.

  2. 18. Adduct detection in human monitoring for carcinogen exposure

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Determination of the covalently bound products (adducts) of carcinogens with DNA or proteins may be used for the monitoring of exposure to these compounds. Protein adducts are generally stable and are not enzymatically repaired, and the use of these for cxposure monitoring is normally carried out with globin or albumin, because

  3. Adducted thumbs : A clinical clue to genetic diagnosis

    NARCIS (Netherlands)

    Verhagen, J. M. A.; Schrander-Stumpel, C. T. R. M.; Blezer, M. M. J.; Weber, J. W.; Schrander, J. J. P.; Rubio-Gozalbo, M. E.; Bakker, J. A.; Stegmann, A. P. A.; Vos, Y. J.; Frints, S. G. M.

    2013-01-01

    Adducted thumbs are an uncommon congenital malformation. It can be an important clinical clue in genetic syndromes, e. g. the L1 syndrome. A retrospective survey was performed including patients with adducted thumbs referred to the Department of Clinical Genetics between 1985 and 2011 by perinatolog

  4. Insertion of dNTPs Opposite the 1,N[superscript 2]-Propanodeoxyguanosine Adduct by Sulfolobus solfataricus P2 DNA Polymerase IV

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yazhen; Musser, Sarah K.; Saleh, Sam; Marnett, Lawrence J.; Egli, Martin; Stone, Michael P. (Vanderbilt)

    2008-08-04

    1,N{sup 2}-Propanodeoxyguanosine (PdG) is a stable structural analogue for the 3-(2'-deoxy-{beta}-d-erythro-pentofuranosyl)pyrimido[1,2-?]purin-10(3H)-one (M{sub 1}dG) adduct derived from exposure of DNA to base propenals and to malondialdehyde. The structures of ternary polymerase-DNA-dNTP complexes for three template-primer DNA sequences were determined, with the Y-family Sulfolobus solfataricus DNA polymerase IV (Dpo4), at resolutions between 2.4 and 2.7 {angstrom}. Three template 18-mer-primer 13-mer sequences, 5'-d(TCACXAAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTT)-3' (template I), 5'-d(TCACXGAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTC)-3' (template II), and 5'-d(TCATXGAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTC)-3' (template III), where X is PdG, were analyzed. With templates I and II, diffracting ternary complexes including dGTP were obtained. The dGTP did not pair with PdG, but instead with the 5'-neighboring template dC, utilizing Watson-Crick geometry. Replication bypass experiments with the template-primer 5?-TCACXAAATCCTTACGAGCATCGCCCCC-3'{center_dot}5'-GGGGGCGATGCTCGTAAGGATTT-3', where X is PdG, which includes PdG in the 5'-CXA-3' template sequence as in template I, showed that the Dpo4 polymerase inserted dGTP and dATP when challenged by the PdG adduct. For template III, in which the template sequence was 5'-TXG-3', a diffracting ternary complex including dATP was obtained. The dATP did not pair with PdG, but instead with the 5'-neighboring T, utilizing Watson-Crick geometry. Thus, all three ternary complexes were of the 'type II' structure described for ternary complexes with native DNA [Ling, H., Boudsocq, F., Woodgate, R., and Yang, W. (2001) Cell 107, 91--102]. The PdG adduct remained in the anti conformation about the glycosyl bond in each of these threee ternary complexes. These results provide insight into how -1

  5. Modeling the conformational preference of the carbon-bonded covalent adduct formed upon exposure of 2'-deoxyguanosine to ochratoxin A.

    Science.gov (United States)

    Sharma, Purshotam; Manderville, Richard A; Wetmore, Stacey D

    2013-05-20

    The conformational flexibility of the C8-linked guanine adduct formed from attachment of ochratoxin A (OTA) was analyzed using a systematic computational approach and models ranging from the nucleobase to the adducted DNA helix. A focus was placed on the influence of the C8-modification of 2'-deoxyguanosine (dG) on the preferred relative arrangement of the nucleobase and the C8-substituent and, more importantly, the anti/syn conformational preference with respect to the glycosidic bond. Although OTA is twisted with respect to the base in the nucleobase model, addition of the deoxyribose sugar induces a further twist and restricts rotation about the C-C linkage due to close contacts between OTA and the sugar. The nucleoside model preferentially adpots a syn orientation (by 10-20 kJ mol(-1) depending on the OTA conformation) due to the presence of an O5'-H···N3 interaction. However, when this hydrogen bond is eliminated, which better mimics the DNA environment, a small (simulations and free energy analysis predict that both syn- and anti-conformations of OTB-dG are equally stable in helices when paired opposite cytosine. These results indicate that the adduct will likely adopt a syn conformation in an isolated nucleoside and nucleotide, while a mixture of syn and anti conformations will be observed in DNA duplexes. Since the syn conformation could stabilize base mismatches upon DNA replication or Z-DNA structures with varied biological outcomes, future computational and experimental work should elucidate the consequences of the conformational preference of this potentially harmful DNA lesion.

  6. Adducted thumbs: a clinical clue to genetic diagnosis.

    Science.gov (United States)

    Verhagen, J M A; Schrander-Stumpel, C T R M; Blezer, M M J; Weber, J W; Schrander, J J P; Rubio-Gozalbo, M E; Bakker, J A; Stegmann, A P A; Vos, Y J; Frints, S G M

    2013-03-01

    Adducted thumbs are an uncommon congenital malformation. It can be an important clinical clue in genetic syndromes, e.g. the L1 syndrome. A retrospective survey was performed including patients with adducted thumbs referred to the Department of Clinical Genetics between 1985 and 2011 by perinatologists, (child) neurologists or paediatricians, in order to evaluate current knowledge on the genetic etiology of adducted thumbs. Twenty-five patients were included in this survey. Additional features were observed in 88% (22/25). In 25% (4/16) of the patients with adducted thumbs and congenital hydrocephalus L1CAM gene mutations were identified. One patient had a mosaic 5p13 duplication. Recommendations are made concerning the evaluation and genetic workup of patients with adducted thumbs. PMID:23220544

  7. Tracing kinematical and physical asymmetries in the jet from DG Tauri B

    NARCIS (Netherlands)

    Podio, L.; Eislöffel, J.; Melnikov, S.; Hodapp, K. W.; Bacciotti, F.

    2011-01-01

    Context. Jets from young stars can be highly asymmetric and have multiple velocity components. Aims. To clarify the origin of jet asymmetries and constrain the launch mechanism, we study as a test case the physical and kinematical structure of the prototypical asymmetric flow emitted by DG Tau B. Me

  8. HiCoDG: A Hierarchical Data-Gathering Scheme Using Cooperative Multiple Mobile Elements

    Directory of Open Access Journals (Sweden)

    Duc Van Le

    2014-12-01

    Full Text Available In this paper, we study mobile element (ME-based data-gathering schemes in wireless sensor networks. Due to the physical speed limits of mobile elements, the existing data-gathering schemes that usemobile elements can suffer from high data-gathering latency. In order to address this problem, this paper proposes a new hierarchical and cooperative data-gathering (HiCoDG scheme that enables multiple mobile elements to cooperate with each other to collect and relay data. In HiCoDG, two types of mobile elements are used: the mobile collector (MC and the mobile relay (MR. MCs collect data from sensors and forward them to the MR, which will deliver them to the sink. In this work, we also formulated an integer linear programming (ILP optimization problem to find the optimal trajectories for MCs and the MR, such that the traveling distance of MEs is minimized. Two variants of HiCoDG, intermediate station (IS-based and cooperative movement scheduling (CMS-based, are proposed to facilitate cooperative data forwarding from MCs to theMR. An analytical model for estimating the average data-gathering latency in HiCoDG was also designed. Simulations were performed to compare the performance of the IS and CMS variants, as well as a multiple traveling salesman problem (mTSP-based approach. The simulation results show that HiCoDG outperformsmTSP in terms of latency. The results also show that CMS can achieve the lowest latency with low energy consumption.

  9. HiCoDG: a hierarchical data-gathering scheme using cooperative multiple mobile elements.

    Science.gov (United States)

    Van Le, Duc; Oh, Hoon; Yoon, Seokhoon

    2014-12-17

    In this paper, we study mobile element (ME)-based data-gathering schemes in wireless sensor networks. Due to the physical speed limits of mobile elements, the existing data-gathering schemes that use mobile elements can suffer from high data-gathering latency. In order to address this problem, this paper proposes a new hierarchical and cooperative data-gathering (HiCoDG) scheme that enables multiple mobile elements to cooperate with each other to collect and relay data. In HiCoDG, two types of mobile elements are used: the mobile collector (MC) and the mobile relay (MR). MCs collect data from sensors and forward them to the MR, which will deliver them to the sink. In this work, we also formulated an integer linear programming (ILP) optimization problem to find the optimal trajectories for MCs and the MR, such that the traveling distance of MEs is minimized. Two variants of HiCoDG, intermediate station (IS)-based and cooperative movement scheduling (CMS)-based, are proposed to facilitate cooperative data forwarding from MCs to the MR. An analytical model for estimating the average data-gathering latency in HiCoDG was also designed. Simulations were performed to compare the performance of the IS and CMS variants, as well as a multiple traveling salesman problem (mTSP)-based approach. The simulation results show that HiCoDG outperforms mTSP in terms of latency. The results also show that CMS can achieve the lowest latency with low energy consumption.

  10. Comparing DG and Nedelec finite element discretisations of the second-order time-domain Maxwell equation

    NARCIS (Netherlands)

    Sármány, D.; Botchev, M.A.; Vegt, van der J.J.W.; Verwer, J.G.

    2009-01-01

    This article compares the discontinuous Galerkin finite element method (DG-FEM) with the $H(\\mathrm{curl})$-conforming FEM in the discretisation of the second-order time-domain Maxwell equations with possibly nonzero conductivity term. While DG-FEM suffers from an increased number of degrees of free

  11. Structural and biochemical impact of C8-aryl-guanine adducts within the NarI recognition DNA sequence: influence of aryl ring size on targeted and semi-targeted mutagenicity

    OpenAIRE

    Sproviero, Michael; Verwey, Anne M.R.; Rankin, Katherine M.; Witham, Aaron A.; Soldatov, Dmitriy V.; Richard A. Manderville; Fekry, Mostafa I.; Sturla, Shana J.; Sharma, Purshotam; Wetmore, Stacey D.

    2014-01-01

    Chemical mutagens with an aromatic ring system may be enzymatically transformed to afford aryl radical species that preferentially react at the C8-site of 2′-deoxyguanosine (dG). The resulting carbon-linked C8-aryl-dG adduct possesses altered biophysical and genetic coding properties compared to the precursor nucleoside. Described herein are structural and in vitro mutagenicity studies of a series of fluorescent C8-aryl-dG analogues that differ in aryl ring size and are representative of auth...

  12. The knee adduction moment during gait is associated with the adduction angle measured during computer-assisted total knee arthroplasty.

    Science.gov (United States)

    Roda, Richard D; Wilson, Janie L Astephen; Wilson, David A J; Richardson, Glen; Dunbar, Michael J

    2012-06-01

    Computer-assisted surgery can be used to measure 3-dimensional knee function during arthroplasty surgery; however, it is unknown if the movement of the knee measured during surgery is related to the in vitro, dynamic state of the knee joint, specifically the knee adduction moment during gait, which has been related to implant migration. The purpose of this study was to determine if the preoperative adduction moment is correlated with the knee abduction/adduction angle measured intraoperatively. A statistically significant correlation was found between the mean (r(2) = 0.59; P = .001) and peak (r(2) = 0.53; P = .003) preoperative knee adduction moment and the mean abduction/adduction angle measured intraoperatively. The association found in this study suggests the potential for incorporating functional information that relates to surgical outcome into surgical decision making using computer-assisted surgery.

  13. Protein adduct formation as a molecular mechanism in neurotoxicity.

    Science.gov (United States)

    Lopachin, Richard M; Decaprio, Anthony P

    2005-08-01

    Chemicals that cause nerve injury and neurological deficits are a structurally diverse group. For the majority, the corresponding molecular mechanisms of neurotoxicity are poorly understood. Many toxicants (e.g., hepatotoxicants) of other organ systems and/or their oxidative metabolites have been identified as electrophiles and will react with cellular proteins by covalently binding nucleophilic amino acid residues. Cellular toxicity occurs when adduct formation disrupts protein structure and/or function, which secondarily causes damage to submembrane organelles, metabolic pathways, or cytological processes. Since many neurotoxicants are also electrophiles, the corresponding pathophysiological mechanism might involve protein adduction. In this review, we will summarize the principles of covalent bond formation that govern reactions between xenobiotic electrophiles and biological nucleophiles. Because a neurotoxicant can form adducts with multiple nucleophilic residues on proteins, the challenge is to identify the mechanistically important adduct. In this regard, it is now recognized that despite widespread chemical adduction of tissue proteins, neurotoxicity can be mediated through binding of specific target nucleophiles in key neuronal proteins. Acrylamide and 2,5-hexanedione are prototypical neurotoxicants that presumably act through the formation of protein adducts. To illustrate both the promise and the difficulty of adduct research, these electrophilic chemicals will be discussed with respect to covalent bond formation, suspected protein sites of adduction, and proposed mechanisms of neurotoxicity. The goals of future investigations are to identify and quantify specific protein adducts that play a causal role in the generation of neurotoxicity induced by electrophilic neurotoxicants. This is a challenging but critical objective that will be facilitated by recent advances in proteomic methodologies. PMID:15901921

  14. Heat-treatment of hook made of DG20Mn steel%DG20Mn钢吊钩热处理工艺探讨

    Institute of Scientific and Technical Information of China (English)

    辛永木

    2011-01-01

    The traditional heat treatment process of low carbon alloy steel DG20Mn is normalizing after forging according to the prescription. In production the mechanical property is sometimes disqualification. The mechanical property of the steel by brine quenching and high-temperature tempering is much higher than that of normalizing, this is caused of the transformation of sorbite in the workpiece surface layer, and the transformation of fine pearlite in the subsurface layer after the quenching and tempering,accordingly grain refine , the mechanical property of the steel is improved, thus can meet the application requirement of the lifting hooks.%按照标准规定低碳合金钢DG20Mn的热处理为锻后正火.在生产中,工件正火后检测连体试棒时有力学性能不合格现象.该材料经调质后获得的综合力学性能比正火要高很多,这是由于在调质过程中,工件表层产生索氏体,而内层的珠光体比正火组织细小,从而提高钢的力学性能,满足了起重吊钩使用要求.

  15. DNA adduct measurements in zebra mussels, Dreissena polymorpha, Pallas

    International Nuclear Information System (INIS)

    The purpose of this study was to examine PAH accumulation and bulky DNA adduct formation in the digestive gland of zebra mussels exposed in their habitat or in controlled laboratory conditions to complex mixture of PAH. DNA adducts were measured using a 32P-postlabelling protocol with nuclease P1 enrichment adapted from Reddy and Randerath [Reddy, M.V., Randerath, K., 1986. Nuclease P1-mediated enhancement of sensitivity of 32P-postlabelling test for structurally diverse DNA adducts. Carcinogenesis 7, 1543-1551]. Specimens collected in the upper part of the Seine estuary were shown to accumulate higher levels of PAH (up to 1.6 μg g-1 dry weight) in comparison to individuals from the reference site (0.053 μg g-1 dry weight). The former exhibited elevated levels of DNA adducts (up to 4.0/108 nucleotides) and higher diversity of individual adducts with five distinct spots being specifically detected in individuals originating from the Seine estuary. Zebra mussels exposed for 5 days to 0.01% (v/v) of organic extract of sediment from the Seine estuary were shown to accumulate high amounts of PAH (up to 138 μg g-1 dry weight) but exhibited relatively low levels of DNA adducts. Exposure to benzo[a]pyrene led to a dose-dependent accumulation of B[a]P (up to 7063 μg g-1 dry weight) and a clear induction of DNA adduct formation in the digestive gland of mussels (up to 1.13/108 nucleotides). Comparisons with other bivalves exposed to the same model PAH, revealed similar levels of adducts and comparable adduct profiles with a main adduct spot and a second faint one. This study clearly demonstrated that zebra mussels are able to biotransform B[a]P and probably other PAH into reactive metabolites with DNA-binding activity. This work also demonstrated the applicability of the nuclease P1 enhanced 32P-postlabelling method for bulky adduct detection in the digestive gland of zebra mussels. DNA adduct measurement in zebra mussels could be a suitable biomarker to monitor PAH

  16. Fos-like immunoreactivity in Siberian hamster brain during initiation of torpor-like hypothermia induced by 2DG.

    Science.gov (United States)

    Park, Jin Ho; Dark, John

    2007-08-01

    Systemic 2-deoxy-d-glucose (2DG) produces pronounced torpor-like hypothermia (notSiberian hamster. Siberian hamsters are heterothermic, naturally undergoing photoperiod-dependent torpor during winter-like photoperiods. Fos was used to identify neural structures activated during the initiation of torpor-like hypothermia induced by 2DG treatment. The Fos-like immunoreactivity (Fos-li) in the area postrema and nucleus of the solitary tract that predominantly characterizes other 2DG-induced responses was absent during 2DG-induced torpor in the present experiment. Fos-li was seen in a number of forebrain and hindbrain sites during entry into hypothermia, but the densest Fos-li was found in the parvocellular portion of the paraventricular nucleus. Fos-li in the medial nucleus of the amygdala and the dorsal lateral septum also distinguished 2DG-induced torpor from other 2DG-induced behaviors. The possible involvement of neuropeptide Y pathways during 2DG-induced expression of reversible hypothermia is discussed.

  17. A combined ADER-DG and PML approach for simulating wave propagation in unbounded domains

    KAUST Repository

    Amler, Thomas

    2012-09-19

    In this work, we present a numerical approach for simulating wave propagation in unbounded domains which combines discontinuous Galerkin methods with arbitrary high order time integration (ADER-DG) and a stabilized modification of perfectly matched layers (PML). Here, the ADER-DG method is applied to Bérenger’s formulation of PML. The instabilities caused by the original PML formulation are treated by a fractional step method that allows to monitor whether waves are damped in PML region. In grid cells where waves are amplified by the PML, the contribution of damping terms is neglected and auxiliary variables are reset. Results of 2D simulations in acoustic media with constant and discontinuous material parameters are presented to illustrate the performance of the method.

  18. DG-FEM solution for nonlinear wave-structure interaction using Boussinesq-type equations

    DEFF Research Database (Denmark)

    Engsig-Karup, Allan Peter; Hesthaven, Jan; Bingham, Harry B.;

    2008-01-01

    waters within the breaking limit. To demonstrate the current applicability of the model both linear and mildly nonlinear test cases are considered in two horizontal dimensions where the water waves interact with bottom-mounted fully reflecting structures. It is established that, by simple symmetry......We present a high-order nodal Discontinuous Galerkin Finite Element Method (DG-FEM) solution based on a set of highly accurate Boussinesq-type equations for solving general water-wave problems in complex geometries. A nodal DG-FEM is used for the spatial discretization to solve the Boussinesq...... equations in complex and curvilinear geometries which amends the application range of previous numerical models that have been based on structured Cartesian grids. The Boussinesq method provides the basis for the accurate description of fully nonlinear and dispersive water waves in both shallow and deep...

  19. The Bipolar X-Ray Jet of the Classical T Tauri Star DG Tau

    CERN Document Server

    Guedel, M; Bacciotti, F; Bary, J S; Briggs, K R; Cabrit, S; Carmona, A; Codella, C; Dougados, C; Eisloeffel, J; Gueth, F; Guenther, H M; Herczeg, G; Kundurthy, P; Matt, S P; Mutel, R L; Ray, T; Schmitt, J H M M; Schneider, P C; Skinner, S L; van Boekel, R

    2011-01-01

    We report on new X-ray observations of the classical T Tauri star DG Tau. DG Tau drives a collimated bi-polar jet known to be a source of X-ray emission perhaps driven by internal shocks. The rather modest extinction permits study of the jet system to distances very close to the star itself. Our initial results presented here show that the spatially resolved X-ray jet has been moving and fading during the past six years. In contrast, a stationary, very soft source much closer (~ 0.15-0.2") to the star but apparently also related to the jet has brightened during the same period. We report accurate temperatures and absorption column densities toward this source, which is probably associated with the jet base or the jet collimation region.

  20. 3-D numerical simulations of rotating jets. The case of the DG Tau microjet

    Science.gov (United States)

    Cerqueira, A. H.; de Gouveia Dal Pino, E. M.

    2004-11-01

    We here present results of three-dimensional Smoothed Particle hydro and magnetohydrodynamics simulations of rotating jets, also including the effects of radiative cooling, precession and velocity variability. Using initial conditions and parameters which are particularly suitable for the DG Tau microjet, we have been able to approximately reproduce its complex knotty morphology and kinematics. We have also obtained radial velocity maps which are in good agreement with the data obtained by Bacciotti et al., thus indicating that their interpretation that the DG Tau microjet is rotating is correct. Finally, we have found that a magnetic field of the order of ≈0.5 mG is sufficient to collimate the jet against the lateral expansion that is caused by the centrifugal forces.

  1. 3-D numerical simulations of rotating jets: The case of the DG Tau microjet

    CERN Document Server

    Cerqueira, A H; Cerqueira, Adriano H.; Pino, Elisabete M. de Gouveia Dal

    2004-01-01

    We here present results of three-dimensional Smoothed Particle hydro and magnetohydrodynamics simulations of rotating jets, also including the effects of radiative cooling, precession and velocity variability. Using initial conditions and parameters which are particularly suitable for the DG Tau microjet, we have been able to approximately reproduce its complex knotty morphology and kinematics. We have also obtained radial velocity maps which are in good agreement with the data obtained by Bacciotti et al., thus indicating that their interpretation that the DG Tau microjet is rotating is correct. Finally, we have found that a magnetic field of the order of ~ 0.5 mG is sufficient to collimate the jet against the lateral expansion that is caused by the centrifugal forces.

  2. Predicted rotation signatures in MHD disc winds and comparison to DG Tau observations

    CERN Document Server

    Pesenti, N; Cabrit, S; Ferreira, J; Casse, F; García, P; O'Brien, D

    2004-01-01

    Motivated by the first detections of rotation signatures in the DG Tau jet (Bacciotti et al. 2002), we examine possible biases affecting the relation between detected rotation signatures and true azimuthal velocity for self-similar MHD disc winds, taking into account projection, convolution as well as excitation gradients effects. We find that computed velocity shifts are systematically smaller than the true underlying rotation curve. When outer slower streamlines dominate the emission, we predict observed shifts increasing with transverse distance to the jet axis, opposite to the true rotation profile. Determination of the full transverse rotation profile thus requires high angular resolution observations ( 50) are ruled out for the medium-velocity component in the DG Tau jet.

  3. Predicted rotation signatures in MHD disc winds and comparison to DG Tau observations.

    Science.gov (United States)

    Pesenti, N.; Dougados, C.; Cabrit, S.; Ferreira, J.; Casse, F.; Garcia, P.; O'Brien, D.

    2004-03-01

    Motivated by the first detections of rotation signatures in the DG Tau jet (Bacciotti et al. \\cite{bacciotti2002}), we examine possible biases affecting the relation between detected rotation signatures and true azimuthal velocity for self-similar MHD disc winds, taking into account projection, convolution as well as excitation gradients effects. We find that computed velocity shifts are systematically smaller than the true underlying rotation curve. When outer slower streamlines dominate the emission, we predict observed shifts increasing with transverse distance to the jet axis, opposite to the true rotation profile. Determination of the full transverse rotation profile thus requires high angular resolution observations ( 50) are ruled out for the medium-velocity component in the DG Tau jet.

  4. Early optical follow-up of the nearby active star DG CVn during its 2014 superflare

    CERN Document Server

    Caballero-Garcia, M D; Jelinek, M; Castro-Tirado, A J; Cwiek, A; Claret, A; Opiela, R; Zarnecki, A F; Gorosabel, J; Oates, S R; Cunniffe, R; Jeong, S; Hudec, R; Sokolov, V V; Makarov, D I; Tello, J C; Lara-Gil, O; Kubanek, P; Guziy, S; Bai, J; Fan, Y; Wang, C; Park, I H

    2015-01-01

    DG CVn is a binary system in which one of the components is an M type dwarf ultra fast rotator, only three of which are known in the solar neighborhood. Observations of DG CVn by the Swift satellite and several ground-based observatories during its super-flare event on 2014 allowed us to perform a complete hard X-ray - optical follow-up of a super-flare from the red-dwarf star. The observations support the fact that the super-flare can be explained by the presence of (a) large active region(s) on the surface of the star. Such activity is similar to the most extreme solar flaring events. This points towards a plausible extrapolation between the behaviour from the most active red-dwarf stars and the processes occurring in the Sun.

  5. Improved Grid Synchronization Algorithm for DG System using DSRF PLL under Grid disturbances

    Directory of Open Access Journals (Sweden)

    R.Godha

    2014-11-01

    Full Text Available Distributed Generation (DG System is a small scale electric power generation at or near the user’s facility as opposed to the normal mode of centralized power generation. In order to ensure safe and reliable operation of power system based on DS, grid synchronization algorithm plays a very important role. This paper presents a Double Synchronous Reference Frame (DSRF phase locked loop (PLL based on synthesis circuit for grid synchronization of distributed generation (DG system under grid disturbances aimed to provide an estimation of the angular frequency and both the positive and negative sequences of the fundamental component of an unbalanced three-phase signal. The design of this PLL is based on a complete description of the source voltage involving both positive and negative sequences in stationary coordinates and considering the angular frequency as an uncertain parameter.

  6. Combined effect of CVR and penetration of DG in the voltage profile and losses of lowvoltage secondary distribution networks

    Science.gov (United States)

    Bokhari, Abdullah

    Demarcations between traditional distribution power systems and distributed generation (DG) architectures are increasingly evolving as higher DG penetration is introduced in the system. The concerns in existing electric power systems (EPSs) to accommodate less restrictive interconnection policies while maintaining reliability and performance of power delivery have been the major challenge for DG growth. In this dissertation, the work is aimed to study power quality, energy saving and losses in a low voltage distributed network under various DG penetration cases. Simulation platform suite that includes electric power system, distributed generation and ZIP load models is implemented to determine the impact of DGs on power system steady state performance and the voltage profile of the customers/loads in the network under the voltage reduction events. The investigation designed to test the DG impact on power system starting with one type of DG, then moves on multiple DG types distributed in a random case and realistic/balanced case. The functionality of the proposed DG interconnection is designed to meet the basic requirements imposed by the various interconnection standards, most notably IEEE 1547, public service commission, and local utility regulation. It is found that implementation of DGs on the low voltage secondary network would improve customer's voltage profile, system losses and significantly provide energy savings and economics for utilities. In a network populated with DGs, utility would have a uniform voltage profile at the customers end as the voltage profile becomes more concentrated around targeted voltage level. The study further reinforced the concept that the behavior of DG in distributed network would improve voltage regulation as certain percentage reduction on utility side would ensure uniform percentage reduction seen by all customers and reduce number of voltage violations.

  7. Optimal DG Source Allocation for Grid Connected Distributed Generation with Energy Storage System

    OpenAIRE

    S. Ezhilarasan; P. Palanivel; S. Sambath

    2015-01-01

    This study proposes an Energy Management System (EMS) for allocation of DG source in a grid connected hybrid power system. Modeling and simulation for EMS is implemented using MATLAB/SIMULINK package. The objective of proposed EMS for micro grid is to optimize the fuel cost, improving the energy utilization efficiency and to manage the peak load demand by scheduling the generation according to the availability of the fuel. The proposed intelligent energy management system is designed to optim...

  8. Numerical solution of linear models in economics: The SP-DG model revisited

    OpenAIRE

    T. Andrade, G. Faria, V. Leite, F. Verona, M. Viegas; Afonso, O.; P.B. Vasconcelos

    2007-01-01

    In general, complex and large dimensional models are needed to solve real economic problems. Due to these characteristics, there is either no analytical solution for them or they are not attainable. As a result, solutions can be only obtained through numerical methods. Thus, the growing importance of computers in Economics is not surprising. This paper focuses on an implementation of the SP-DG model, using Matlab,developed by the students as part of the Computational Economics course. We also...

  9. Infrared spectroscopy of fullerene C60/anthracene adducts

    CERN Document Server

    Garcia-Hernandez, D A; Manchado, A

    2013-01-01

    Recent Spitzer Space Telescope observations of several astrophysical environments such as Planetary Nebulae, Reflection Nebulae, and R Coronae Borealis stars show the simultaneous presence of mid-infrared features attributed to neutral fullerene molecules (i.e., C60) and polycyclic aromatic hydrocarbons (PAHs). If C60 fullerenes and PAHs coexist in fullerene-rich space environments, then C60 may easily form adducts with a number of different PAH molecules; at least with catacondensed PAHs. Here we present the laboratory infrared spectra (~2-25 um) of C60 fullerene and anthracene Dies-Alder mono- and bis-adducts as produced by sonochemical synthesis. We find that C60/anthracene Diels-Alder adducts display spectral features strikingly similar to those from C60 (and C70) fullerenes and other unidentified infrared emission features. Thus, fullerene-adducts - if formed under astrophysical conditions and stable/abundant enough - may contribute to the infrared emission features observed in fullerene-containing circu...

  10. Quantitation of DNA adducts by stable isotope dilution mass spectrometry

    OpenAIRE

    Tretyakova, Natalia; Goggin, Melissa; Janis, Gregory

    2012-01-01

    Exposure to endogenous and exogenous chemicals can lead to the formation of structurally modified DNA bases (DNA adducts). If not repaired, these nucleobase lesions can cause polymerase errors during DNA replication, leading to heritable mutations potentially contributing to the development of cancer. Due to their critical role in cancer initiation, DNA adducts represent mechanism-based biomarkers of carcinogen exposure, and their quantitation is particularly useful for cancer risk assessment...

  11. Multiple DNA adducts in lymphocytes of smokers and nonsmokers determined by 32P-postlabeling analysis

    International Nuclear Information System (INIS)

    Identification of DNA adducts in peripheral lymphocytes could serve as a means of monitoring human exposure to potential genotoxic agents. In the study, DNA from peripheral lymphocytes of smokers and nonsmokers was examined for adducts by the P1 nuclease 32P-post-labeling technique. Thin layer chromatography (TLC) maps from both groups revealed multiple DNA adducts which ranged from no adducts for one individual to six adducts for a different individual. The total DNA adduct concentrations were approximately one adduct in 10 to the seventh-10 to the eighth power normal nucleotides. Comparison of the adduct TLC profiles revealed individual variation in both pattern and level of DNA adducts. The type and amount of adduct was not influenced by smoking history and remained unchanged in four out of six subjects who were resampled after a one month interval. One adduct detected in lymphocyte DNA co-migrated on TLC with an adduct derived by in vitro incubation of lymphocytes with benzo(a)pyrene (B(a)P). The 3H-nucloside values were consistent with values obtained by 32P-postlabeling of the same sample (correlation coefficient of 0.88). No relationship was apparent between the capacity of lymphocytes to form a (3H)-B(a)P-derived adduct in vitro and the concentration of the adduct, or total adducts present in untreated lymphocytes

  12. Placement of DG and Capacitor for Loss Reduction, Reliability and Voltage Improvement in Distribution Networks Using BPSO

    Directory of Open Access Journals (Sweden)

    Reza Baghipour

    2012-11-01

    Full Text Available This paper presents multi-objective function for optimally determining the size and location of distributed generation (DG and capacitor in distribution systems for power loss minimization, reliability and voltage improvement. The objective function proposed in this paper includes reliability index, active power loss index, DG's and capacitor's investment cost index and voltage profile index which is minimized using binary particle swarm optimization algorithm (BPSO. The effectiveness of the proposed method is examined in the 10 and 33 bus test systems and comparative studies are conducted before and after DG and capacitor installation in the test systems. Results illustrate significant losses reduction and voltage profile and reliability improvement with presence of DG unit and capacitor.

  13. Cisplatin adducts on a GGG sequence within a DNA duplex studied by NMR spectroscopy and molecular dynamics simulations.

    Science.gov (United States)

    Téletchéa, Stéphane; Skauge, Tormod; Sletten, Einar; Kozelka, Jirí

    2009-11-16

    The antitumor drug cisplatin(cis-[PtCl2(NH3)2]) reacts with cellular DNA to form GG intrastrand adducts between adjacent guanines as predominant lesions. GGG sites have been shown to be hotspots of platination. To study the structural perturbation induced by binding of cisplatin to two adjacent guanines of a GGG trinucleotide,we examined here the decanucleotide duplex d[(G1C2C3G*4 G*5 G6T7-C8G9C10).d(G11C12G13A14C15C16C17G18-G19C20)] (dsCG*G*G) intrastrand cross-linked at the G* guanines by cis-{Pt(NH3)2}2+ using NMR spectroscopy and molecular dynamics (MD) simulations.The NMR spectra of dsCG*G*G were found to be similar to those of previously characterized DNA duplexes cross-linked by cisplatin at apyG*G*X site (py=pyrimidine; X=C,T, A). This similarity of NMR spectra indicates that the base at the 3'-side of the G*G*-Pt cross-link does not affect the structure to a large extent. An unprecedented reversible isomerization between the duplex dsCG*G*G (bearing a G*4 G*5 -Pt chelate) and duplex dsGG*G*T (bearing a G*5 G*6 -Pt chelate)was observed, which yielded a 40:60 equilibrium between the two intrastrand GG-Pt cross-links. No formation of interstrand cross-links was observed.NMR spectroscopic data of dsCG*G*G indicated that the deoxyribose of the 5'-G* adopts an N-type conformation, and the cytidines C3, C15,and C16 have average phase angles intermediate between S and N. The NMR spectroscopic chemical shifts of dsGG*G*T showed some fundamental differences to those of pyG*G*-platinum adducts but were in agreement with the NMR spectra reported previously for the DNA duplexes crosslinked at an AG*G*C sequence by cisplatin or oxaliplatin. The presence of apurine instead of a pyrimidine at the 5'-side of the G*G* cross-link seems therefore to affect the structure of the XG* step significantly. PMID:19813235

  14. Covalent thiol adducts arising from reactive intermediates of cocaine biotransformation.

    Science.gov (United States)

    Schneider, Kevin J; DeCaprio, Anthony P

    2013-11-18

    Exposure to cocaine results in the depletion of hepatocellular glutathione and macromolecular protein binding in humans. Such cocaine-induced responses have generally been attributed to oxidative stress and reactive metabolites resulting from oxidative activation of the cocaine tropane nitrogen. However, little conclusive data exists on the mechanistic pathways leading to protein modification or the structure and specificity of cocaine-derived adduction products. We now report a previously uncharacterized route of cocaine bioactivation leading to the covalent adduction of biological thiols, including cysteine and glutathione. Incubation of cocaine with biological nucleophiles in an in vitro biotransformation system containing human liver microsomes identified a monooxygenase-mediated event leading to the oxidation of, and subsequent sulfhydryl addition to, the cocaine aryl moiety. Adduct structures were confirmed using ultra-high performance liquid chromatography coupled to high resolution, high mass accuracy mass spectrometry. Examination of assays containing transgenic bactosomes expressing single human cytochrome P450 isoforms determined the role of P450s 1A2, 2C19, and 2D6 in the oxidation process resulting in adduct formation. P450-catalyzed aryl epoxide formation and subsequent attack by free nucleophilic moieties is consistent with the resulting adduct structures, mechanisms of formation, and the empirical observation of multiple structural and stereo isomers. Analogous adduction mechanisms were maintained across all sulfhydryl-containing nucleophile models examined; N-acetylcysteine, glutathione, and a synthetic cysteine-containing hexapeptide. Predictive in silico calculations of molecular reactivity and electrophilicity/nucleophilicity were compared to the results of in vitro assay incubations in order to better understand the adduction process using the principles of hard and soft acid and base (HSAB) theory. This study elucidated a novel metabolic

  15. Partitioning of knee joint internal forces in gait is dictated by the knee adduction angle and not by the knee adduction moment.

    Science.gov (United States)

    Adouni, M; Shirazi-Adl, A

    2014-05-01

    Medial knee osteoarthritis is a debilitating disease. Surgical and conservative interventions are performed to manage its progression via reduction of load on the medial compartment or equivalently its surrogate measure, the external adduction moment. However, some studies have questioned a correlation between the medial load and adduction moment. Using a musculoskeletal model of the lower extremity driven by kinematics-kinetics of asymptomatic subjects at gait midstance, we aim here to quantify the relative effects of changes in the knee adduction angle versus changes in the adduction moment on the joint response and medial/lateral load partitioning. The reference adduction rotation of 1.6° is altered by ±1.5° to 3.1° and 0.1° or the knee reference adduction moment of 17Nm is varied by ±50% to 25.5Nm and 8.5Nm. Quadriceps, hamstrings and tibiofemoral contact forces substantially increased as adduction angle dropped and diminished as it increased. The medial/lateral ratio of contact forces slightly altered by changes in the adduction moment but a larger adduction rotation hugely increased this ratio from 8.8 to a 90 while in contrast a smaller adduction rotation yielded a more uniform distribution. If the aim in an intervention is to diminish the medial contact force and medial/lateral load ratio, a drop of 1.5° in adduction angle is much more effective (causing respectively 12% and 80% decreases) than a reduction of 50% in the adduction moment (causing respectively 4% and 13% decreases). Substantial role of changes in adduction angle is due to the associated alterations in joint nonlinear passive resistance. These findings explain the poor correlation between knee adduction moment and tibiofemoral compartment loading during gait suggesting that the internal load partitioning is dictated by the joint adduction angle.

  16. Nodal DG-FEM solution of high-order Boussinesq-type equations

    DEFF Research Database (Denmark)

    Engsig-Karup, Allan Peter; Hesthaven, Jan S.; Bingham, Harry B.;

    2006-01-01

    We present a discontinuous Galerkin finite element method (DG-FEM) solution to a set of high-order Boussinesq-type equations for modelling highly nonlinear and dispersive water waves in one and two horizontal dimensions. The continuous equations are discretized using nodal polynomial basis...... and convergence of the model with both h (grid size) and p (order) refinement are verified for the linearized equations, and calculations are provided for two nonlinear test cases in one horizontal dimension: harmonic generation over a submerged bar; and reflection of a steep solitary wave from a vertical wall...

  17. The kinematic relationship between disk and jet in the DG Tauri system

    CERN Document Server

    Testi, L; Sargent, A I; Ray, T P; Eislöffel, J

    2002-01-01

    We present high angular resolution millimeter wavelength continuum and 13CO(2-1) observations of the circumstellar disk surrounding the TTauri star DG Tauri. We show that the velocity pattern in the inner regions of the disk is consistent with Keplerian rotation about a central 0.67 Msun star. The disk rotation is also consistent with the toroidal velocity pattern in the initial channel of the optical jet, as inferred from HST spectra of the first de-projected 100 AU from the source. Our observations support the tight relationship between disk and jet kinematics postulated by the popular magneto-centrifugal models for jet formation and collimation.

  18. An adaptive control strategy of converter based DG to maintain protection coordination in distribution system

    DEFF Research Database (Denmark)

    Su, Chi; Liu, Zhou; Chen, Zhe;

    2014-01-01

    of network protection devices. As a protection measure commonly used in distribution network, recloser-fuse coordination could suffer from this impact. Research work has been conducted to deal with this problem by modifying the control strategy of the DG converters during faults. These solutions generally...... reduce the current output from the converters during faults so as to mitigate the influence on protection coordination. However, converter current reduction may not be necessary for all types of faults. This paper proposes a converter control strategy with adaptivity to different fault types and also non......-fault voltage drop events. This control strategy is validated by simulations in DIgSILENT PowerFactory....

  19. Organocatalytic removal of formaldehyde adducts from RNA and DNA bases

    Science.gov (United States)

    Karmakar, Saswata; Harcourt, Emily M.; Hewings, David S.; Lovejoy, Alexander F.; Kurtz, David M.; Ehrenschwender, Thomas; Barandun, Luzi J.; Roost, Caroline; Alizadeh, Ash A.; Kool, Eric T.

    2015-09-01

    Formaldehyde is universally used to fix tissue specimens, where it forms hemiaminal and aminal adducts with biomolecules, hindering the ability to retrieve molecular information. Common methods for removing these adducts involve extended heating, which can cause extensive degradation of nucleic acids, particularly RNA. Here, we show that water-soluble bifunctional catalysts (anthranilates and phosphanilates) speed the reversal of formaldehyde adducts of mononucleotides over standard buffers. Studies with formaldehyde-treated RNA oligonucleotides show that the catalysts enhance adduct removal, restoring unmodified RNA at 37 °C even when extensively modified, while avoiding the high temperatures that promote RNA degradation. Experiments with formalin-fixed, paraffin-embedded cell samples show that the catalysis is compatible with common RNA extraction protocols, with detectable RNA yields increased by 1.5-2.4-fold using a catalyst under optimized conditions and by 7-25-fold compared with a commercial kit. Such catalytic strategies show promise for general use in reversing formaldehyde adducts in clinical specimens.

  20. Isolation, identification, and assay of [3H]-porfiromycin adducts of EMT6 mouse mammary tumor cell DNA: effects of hypoxia and dicumarol on adduct patterns.

    Science.gov (United States)

    Tomasz, M; Hughes, C S; Chowdary, D; Keyes, S R; Lipman, R; Sartorelli, A C; Rockwell, S

    1991-07-01

    [3H]-(N-la-methyl) Porfiromycin (POR) was employed to detect and identify the radiolabeled mono- and bis-adducts formed in living EMT6 mouse mammary tumor cells under different conditions. To provide authentic standard adducts, calf-thymus DNA was treated with POR under reductive activation, then digested to nucleosides and POR-nucleoside adducts. The three major adducts formed were isolated by HPLC and authenticated. Two were mono-adducts, composed of deoxyguanosine linked at its N2-position to C-1 of POR and of 10-decarbamoyl POR. The third was a bis-adduct, in which POR was crosslinked to two deoxyguanosines at their N2-positions. DNA from [3H]-POR treated EMT6 cells was digested an analyzed by HPLC. DNA-associated label was located in thymidine and in two mono-adducts and one bis-adduct identical to those described above. Label in thymidine resulted from N-demethylation of POR and reincorporation of label into new thymidylate residues. Adducts were formed more abundantly in hypoxia than in air. In addition, the mono-adduct to crosslink ratios were different, approximately 1:1 and 2:1 for hypoxic and aerobic cells, respectively. The different patterns of alkylation in air and hypoxia may be related to the greater toxicity of POR in hypoxia. When cells were treated simultaneously with POR and dicumarol, adduct levels were lower, and a new, unknown adduct was observed primarily under hypoxia; these changes may be related to the altered toxicity of POR in the presence of dicumarol. The HPLC assay detected simultaneously the full array of stable mono- and bis-adducts in DNA with good sensitivity (greater than or equal to 2 x 10(6) adducts/nucleotide) and excellent reproducibility. This assay should be generally applicable to all cells and tissues when MC or POR with high specific radioactivity can be employed. PMID:1714285

  1. Application of the DG-1199 methodology to the ESBWR and ABWR.

    Energy Technology Data Exchange (ETDEWEB)

    Kalinich, Donald A.; Gauntt, Randall O.; Walton, Fotini

    2010-09-01

    Appendix A-5 of Draft Regulatory Guide DG-1199 'Alternative Radiological Source Term for Evaluating Design Basis Accidents at Nuclear Power Reactors' provides guidance - applicable to RADTRAD MSIV leakage models - for scaling containment aerosol concentration to the expected steam dome concentration in order to preserve the simplified use of the Accident Source Term (AST) in assessing containment performance under assumed design basis accident (DBA) conditions. In this study Economic and Safe Boiling Water Reactor (ESBWR) and Advanced Boiling Water Reactor (ABWR) RADTRAD models are developed using the DG-1199, Appendix A-5 guidance. The models were run using RADTRAD v3.03. Low Population Zone (LPZ), control room (CR), and worst-case 2-hr Exclusion Area Boundary (EAB) doses were calculated and compared to the relevant accident dose criteria in 10 CFR 50.67. For the ESBWR, the dose results were all lower than the MSIV leakage doses calculated by General Electric/Hitachi (GEH) in their licensing technical report. There are no comparable ABWR MSIV leakage doses, however, it should be noted that the ABWR doses are lower than the ESBWR doses. In addition, sensitivity cases were evaluated to ascertain the influence/importance of key input parameters/features of the models.

  2. Novel 2DG-based harmine derivatives for targeted cancer therapy

    Science.gov (United States)

    Wang, Aqin; Chen, Yuqi; Chen, Wei R.; Gu, Yueqing

    2013-02-01

    Harmine is a beta-carboline alkaloid from the plant Peganum harmala. These alkaloids were stimulated by their promising antitumor activities in the recent years. In this study, we designed and synthesized two harmine derivatives #1and #2 modified at position-9 of harmine with ethyl and phenylpropyl, respectively. To improve the tumor targeting capability, #1' and #2' were synthesized by conjugating 2-amino-2-deoxy-D-glucose (2DG) to the derivatives #1 and #2, respectively. The MTT assays of all these compounds in vitro against L02, HepG2 showed all compounds had low toxicity to normal cells (L02) and significantly enhanced carcinoma cell inhibitory rate compared to harmine. Cytotoxicity against liver cancer cell lines of compound #1' #2' is higher than #1 #2, and even the compound #2' is better than positive drug 5-FU. The compound #2', a novel 2DG-based harmine derivatives, could become a promising drug for targeted cancer therapy and combination therapy with other antitumor drugs.

  3. UNUSUALLY STABLE ADDUCT BETWEEN METHANOLYZED AMOXICILLIN OR AMPICILLIN AND THEIR DIKETOPIPERAZINE DERIVATIVES.

    Science.gov (United States)

    Kosińska, Katarzyna; Frański, Rafał; Frańska, Magdalena

    2016-01-01

    Amoxicillin and ampicillin were subjected to methanolysis. As expected, the methanolysis products were observed by HPLC-ESI-MS. Besides these products, diketopiperazine derivatives were also detected. Additionally, unusually stable adduct formed between the products of methanolysis and diketopiperazine derivatives was also identified. Analogical adducts were detected when ethanolysis was performed instead of methanolysis. HPLC-ESI-MS analysis of the separated adducts confirmed that the adducts were composed of methanolysis products and diketopiperazine derivatives.

  4. Environmental, Dietary, Maternal, and Fetal Predictors of Bulky DNA Adducts in Cord Blood

    DEFF Research Database (Denmark)

    Pedersen, Marie; Mendez, Michelle A; Schoket, Bernadette;

    2015-01-01

    BACKGROUND: Bulky DNA adducts reflect genotoxic exposures, have been associated with lower birth weight, and may predict cancer risk. OBJECTIVE: We selected factors known or hypothesized to affect in utero adduct formation and repair and examined their associations with adduct levels in neonates....

  5. [sup 129]I Moessbauer spectroscopic study of metallocene-iodine adducts

    Energy Technology Data Exchange (ETDEWEB)

    Nakashima, Satoru (Dept. of Chemistry, Faculty of Science, Hiroshima Univ. (Japan)); Sakai, Hiroshi (Dept. of Chemistry, Faculty of Science, Hiroshima Univ. (Japan)); Watanabe, Masanobu (Dept. of Chemistry, Coll. of Arts and Sciences, Univ. of Tokyo (Japan)); Maeda, Yutaka (Research Reactor Inst., Kyoto Univ., Osaka (Japan))

    1994-05-01

    A [sup 129]I Moessbauer spectroscopic study of iodine adducts of ferrocenophane, biruthenocene, and osmocene is reported. The spectra show the existence of iodine bonded to the central metals of metallocenes in addition to triiodide anions. The valence state of iron in the ferrocenophane-iodine adduct is the same as those of ruthenium and osmium in their adducts. (orig.)

  6. Active harmonic filtering using current-controlled, grid-connected DG units with closed-loop power control

    DEFF Research Database (Denmark)

    He, Jinwei; Li, Yun Wei; Blaabjerg, Frede;

    2014-01-01

    The increasing application of nonlinear loads may cause distribution system power quality issues. In order to utilize distributed generation (DG) unit interfacing converters to actively compensate harmonics, this paper proposes an enhanced current control approach, which seamlessly integrates...... voltage detection are not necessary for the proposed harmonic compensation method. Moreover, a closed-loop power control scheme is employed to directly derive the fundamental current reference without using any phase-locked loops (PLL). The proposed power control scheme effectively eliminates the impacts...... of steady-state fundamental current tracking errors in the DG units. Thus, an accurate power control is realized even when the harmonic compensation functions are activated. In addition, this paper also briefly discusses the performance of the proposed method when DG unit is connected to a grid...

  7. Design & Performance Analysis of DG-MOSFET for Reduction of Short Channel Effect over Bulk MOSFET at 20nm

    Directory of Open Access Journals (Sweden)

    Ankita Wagadre

    2014-07-01

    Full Text Available An aggressive scaling of conventional MOSFETs channel length reduces below 100nm and gate oxide thickness below 3nm to improved performance and packaging density. Due to this scaling short channel effect (SCEs like threshold voltage, Subthreshold slope, ON current and OFF current plays a major role in determining the performance of scaled devices. The double gate (DG MOSFETS are electro-statically superior to a single gate (SG MOSFET and allows for additional gate length scaling. Simulation work on both devices has been carried out and presented in paper. The comparative study had been carried out for threshold voltage (VT, Subthreshold slope (Sub VT, ION and IOFF Current. It is observed that DG MOSFET provide good control on leakage current over conventional Bulk (Single Gate MOSFET. The VT (Threshold Voltage is 2.7 times greater than & ION of DG MOSFET is 2.2 times smaller than the conventional Bulk (Single Gate MOSFET.

  8. Triphosgene mediated chlorination of Baylis-Hillman adducts

    Indian Academy of Sciences (India)

    Narender Reddy Thatikonda; Naga Sesha Sai Pavan Kumar Chebolu; Mahendar Budde; Jayathirtha Rao Vaidya

    2012-03-01

    An efficient method for the preparation of allyl chlorides from Baylis-Hillman adducts has been developed using triphosgene/pyridine system. This method is best illustrated by its advantages like operational simplicity, excellent yields, short reaction time, simple procedure and stereoselectivity.

  9. Stability, accumulation and cytotoxicity of an albumin-cisplatin adduct

    DEFF Research Database (Denmark)

    Møller, Charlotte; Tastesen, Hanne Sørup; Gammelgaard, Bente;

    2010-01-01

    The accumulation and cytotoxicity of a 10 µmol L¿¹ equimolar human serum albumin-cisplatin adduct (HSA-Pt) was investigated in suspension Ehrlich Ascites Tumor Cells (EATC) and adherent Ehrlich Lettré Ascites Cells (Lettré). HSA-Pt did not induce apoptosis nor was it taken up by the cells to any ...

  10. CARCINOGEN-DNA ADDUCTS: INTRODUCTION, LITERATURE SUMMARY, AND RECOMMENDATIONS

    Science.gov (United States)

    The report summarizes the literature concerning adducts formed by xenobiotics with DNA and/or protein and discusses their feasibility as a monitoring tool for use in exposure and risk assessment. The report is divided into three segments. The first segment provides an introductio...

  11. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Directory of Open Access Journals (Sweden)

    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  12. Genome-wide genetic screen identified the link between dG9a and epidermal growth factor receptor signaling pathway in vivo.

    Science.gov (United States)

    Shimaji, Kouhei; Konishi, Takahiro; Yoshida, Hideki; Kimura, Hiroshi; Yamaguchi, Masamitsu

    2016-08-01

    G9a is one of the histone H3 Lys 9 (H3K9) specific methyltransferases first identified in mammals. Drosophila G9a (dG9a) has been reported to induce H3K9 dimethylation in vivo, and the target genes of dG9a were identified during embryonic and larval stages. Although dG9a is important for a variety of developmental processes, the link between dG9a and signaling pathways are not addressed yet. Here, by genome-wide genetic screen, taking advantage of the rough eye phenotype of flies that over-express dG9a in eye discs, we identified 16 genes that enhanced the rough eye phenotype induced by dG9a over-expression. These 16 genes included Star, anterior open, bereft and F-box and leucine-rich repeat protein 6 which are components of epidermal growth factor receptor (EGFR) signaling pathway. When dG9a over-expression was combined with mutation of Star, differentiation of R7 photoreceptors in eye imaginal discs as well as cone cells and pigment cells in pupal retinae was severely inhibited. Furthermore, the dG9a over-expression reduced the activated ERK signals in eye discs. These data demonstrate a strong genetic link between dG9a and the EGFR signaling pathway. PMID:27343629

  13. Unstructured nodal DG-FEM solution of high-order Boussinesq-type equations

    DEFF Research Database (Denmark)

    Engsig-Karup, Allan Peter

    2007-01-01

    of today, the high-order Boussinesq equations represent the most advanced set of Boussinesq-type equations capable of modelling nonlinear and dispersive waves from shallow to deep water without the practical limitations of classical Boussinesq-type equations. The high-order Boussinesq equations constitute...... time-dependent linear system; and the numerical treatment of high-order and cross-differential derivatives. The suggested solution strategy of the current work is based on a collocation approach where the DG-FEM is used to approximate spatial derivatives and the boundary conditions are imposed weakly...... using a symmetry technique. Since collocation methods are prone to aliasing errors, various anti-aliasing strategies are applied for the stabilization of the models. A practical and relatively straightforward discretization is applied, which is based on a simple treatment of slip boundary conditions...

  14. Impact of Parameter Variations and Optimization on DG-PNIN Tunnel FET

    Directory of Open Access Journals (Sweden)

    Priya Jhalani

    2014-04-01

    Full Text Available The downscaling of conventional MOSFETs has come to its fundamental limits. TFETs are very attractive devices for low power applications because of their low off-current and potential for smaller sub threshold slope. In this paper, the impact of various parameter variations on the performance of a DG-PNIN Tunnel field effect transistor is investigated. In this work, variations in gate oxide material, source doping, channel doping, drain doping, pocket doping and body thickness are studied and all these parameters are optimized as performance boosters to give better current characteristics parameters. After optimization with all these performance boosters, the device has shown improved performance with increased on-current and reduced threshold voltage and the Ion/Ioff ratio is > 106 .

  15. Locating the Launching Region of T Tauri Winds: The Case of DG Tauri

    Science.gov (United States)

    Anderson, Jeffrey M.; Li, Zhi-Yun; Krasnopolsky, Ruben; Blandford, Roger D.

    2003-06-01

    It is widely believed that T Tauri winds are driven magnetocentrifugally from accretion disks close to the central stars. The exact launching conditions are uncertain. We show that a general relation exists between the poloidal and toroidal velocity components of a magnetocentrifugal wind at large distances and the rotation rate of the launching surface, independent of the uncertain launching conditions. We discuss the physical basis of this relation and verify it by using a set of numerically determined large-scale wind solutions. Both velocity components are in principle measurable from spatially resolved spectra, as has been done for the extended low-velocity component (LVC) of the DG Tauri wind by Bacciotti et al. For this particular source, we infer that the spatially resolved LVC originates from a region on the disk extending from ~0.3 to ~4.0 AU from the star, which is consistent with, and a refinement over, the rough estimate of Bacciotti et al.

  16. DOMAIN DECOMPOSITION FOR POROELASTICITY AND ELASTICITY WITH DG JUMPS AND MORTARS

    KAUST Repository

    GIRAULT, V.

    2011-01-01

    We couple a time-dependent poroelastic model in a region with an elastic model in adjacent regions. We discretize each model independently on non-matching grids and we realize a domain decomposition on the interface between the regions by introducing DG jumps and mortars. The unknowns are condensed on the interface, so that at each time step, the computation in each subdomain can be performed in parallel. In addition, by extrapolating the displacement, we present an algorithm where the computations of the pressure and displacement are decoupled. We show that the matrix of the interface problem is positive definite and establish error estimates for this scheme. © 2011 World Scientific Publishing Company.

  17. Quantification of Carnosine-Aldehyde Adducts in Human Urine.

    Science.gov (United States)

    da Silva Bispo, Vanderson; Di Mascio, Paolo; Medeiros, Marisa

    2014-10-01

    Lipid peroxidation generates several reactive carbonyl species, including 4-hydroxy-2-nonenal (HNE), acrolein (ACR), 4-hydroxy-2-hexenal (HHE) and malondialdehyde. One major pathwayof aldehydes detoxification is through conjugation with glutathione catalyzed by glutathione-S-transferases or, alternatively, by conjugation with endogenous histidine containing dipeptides, such as carnosine (CAR). In this study, on-line reverse-phase high-performance liquid chromatography (HPLC) separation with tandem mass spectrometry detection was utilized for the accurate quantification of CAR- ACR, CAR-HHE and CAR-HNE adducts in human urinary samples from non-smokers young adults. Standard adducts were prepared and isolated by HPLC. The results showed the presence of a new product from the reaction of CAR with ACR. This new adduct was completely characterized by HPLC/MS-MSn, 1H RMN, COSY and HSQC. The new HPLC/MS/MS methodology employing stable isotope-labeled internal standards (CAR-HHEd5 and CAR-HNEd11) was developed for adducts quantification. This methodology permits quantification of 10pmol CAR-HHE and 1pmol of CAR-ACR and CAR-HNE. Accurate determinations in human urine sample were performed and showed 4.65±1.71 to CAR-ACR, 5.13±1.76 to CAR-HHE and 5.99±3.19nmol/mg creatinine to CAR-HNE. Our results indicate that carnosine pathways can be an important detoxification route of a, ß -unsaturated aldehydes. Moreover, carnosine adducts may be useful as redox stress indicator. PMID:26461323

  18. 2'-Deoxythymidine Adducts from the Anti-HIV Drug Nevirapine

    Directory of Open Access Journals (Sweden)

    M. Matilde Marques

    2013-04-01

    Full Text Available Nevirapine (NVP is a non-nucleoside reverse transcriptase inhibitor (NNRTI used against HIV-1. Currently, NVP is the most widely used anti-HIV drug in developing countries, both in combination therapy and to prevent mother-to-child transmission of HIV. Despite its efficacy against HIV, NVP produces a variety of toxic responses, including hepatotoxicity and skin rash. It is also associated with increased incidences of hepatoneoplasias in rodents. In addition, epidemiological data suggest that NNRTI use is a risk factor for non-AIDS-defining cancers in HIV-positive patients. Current evidence supports the involvement of metabolic activation to reactive electrophiles in NVP toxicity. NVP metabolism includes oxidation to 12-hydroxy-NVP; subsequent Phase II sulfonation produces an electrophilic metabolite, 12-sulfoxy-NVP, capable of reacting with DNA to yield covalent adducts. Since 2’-deoxythymidine (dT adducts from several alkylating agents are regarded as having significant mutagenic/carcinogenic potential, we investigated the formation of NVP-dT adducts under biomimetic conditions. Toward this goal, we initially prepared and characterized synthetic NVP-dT adduct standards using a palladium-mediated Buchwald-Hartwig coupling strategy. The synthetic standards enabled the identification, by LC-ESI-MS, of 12-(2'-deoxythymidin-N3-yl-nevirapine (N3-NVP-dT in the enzymatic hydrolysate of salmon testis DNA reacted with 12-mesyloxy-NVP, a synthetic surrogate for 12-sulfoxy-NVP. N3-NVP-dT, a potentially cytotoxic and mutagenic DNA lesion, was also the only dT-specific adduct detected upon reaction of dT with 12-mesyloxy-NVP. Our data suggest that N3-NVP-dT may be formed in vivo and play a role in the hepatotoxicity and/or putative hepatocarcinogenicity of NVP.

  19. Developement of serum-free media in CHO-DG44 cells using a central composite statistical design

    OpenAIRE

    Parampalli, Ananth; Eskridge, Kent; Smith, Leonard; Meagher, Michael M.; Mowry, Mark C.; Subramanian, Anuradha

    2007-01-01

    A serum free medium was developed for the production of recombinant antibody against Botulinum A (BoNTA) using dihydrofolate reductase deficient Chinese Hamster Ovary Cells (CHO-DG44) in suspension culture. An initial control basal medium was prepared, which was similar in composition to HAM’s F12: IMDM (1:1) supplemented with insulin, transeferrin, selenium and a lipid mixture. The vitamin concentration of the basal medium was twice that of HAM’s F12: IMDM (1:1). CHO-DG44 cells expressing S2...

  20. Environmental air pollution and DNA adducts in Copenhagen bus drivers - effect of GSTM1 and NAT2 genotypes on adduct level

    DEFF Research Database (Denmark)

    Nielsen, Per Sabro; de Pater, Nettie; Okkels, Henrik;

    1996-01-01

    (smokers and non-smokers). PAH-DNA adducts were determined by 32P-postlabelling with the butanol enrichment procedure. The bus drivers answered a comprehensive questionnaire on passive smoking, residential area, diet and other potential confounding variables. A significantly higher adduct level...... rural controls (0.074 fmol/microg DNA, n = 60, P smoking and diet. The effect of the metabolizing enzymes, GSTM1 and NAT2, on adduct levels was investigated. No statistically significant effects...

  1. Photochemistry of psoralen-DNA adducts, biological effects of psoralen-DNA adducts, applications of psoralen-DNA photochemistry

    International Nuclear Information System (INIS)

    This thesis consists of three main parts and totally eight chapters. In Part I, The author will present studies on the photochemistry of psoralen-DNA adducts, specifically, the wavelength dependencies for the photoreversals of thymidine-HMT (4'-hydroxymethyl-4, 5', 8-trimenthylpsoralen) monoadducts and diadduct and the same adducts incorporated in DNA helices and the wavelength dependecies for the photocrossslinking of thymidine-HMT monoadducts in double-stranded helices. In Part II, The author will report some biological effects of psoralen-DNA adducts, i.e., the effects on double-stranded DNA stability, DNA structure, and transcription by E. coli and T7 RNA polymerases. Finally, The author will focus on the applications of psoralen-DNA photochemistry to investigation of protein-DNA interaction during transcription, which includes the interaction of E. coli and T7 RNA polymerases with DNA in elongation complexes arrested at specific psoralen-DNA adduct sites as revealed by DNase I footprinting experiments. 123 refs., 52 figs., 12 tabs

  2. Immunochemical detection of sulfur mustard-adducts with DNA and proteins: Exploratory research on adducts with proteins

    NARCIS (Netherlands)

    Schans, G.P. van der; Noort, D.; Mars-Groenendijk, R.H.; Dijk-Knijnenburg, H.C.M. van; Fidder, A.; Jong, L.P.A. de; Benschop, H.P.

    2000-01-01

    We have developed two modes of a standard operating procedure (SOP) for immunochemical detection of sulfur mustard adducts to DNA in human blood and skin. In the shortened mode data could be generated within 9 h after in vitro exposure of human blood to > 1 μM sulfur mustard. The sensitive mode allo

  3. Chloroethyinitrosourea-derived ethano cytosine and adenine adducts are substrates for escherichia coli glycosylases excising analogous etheno adducts

    Energy Technology Data Exchange (ETDEWEB)

    Guliaev, Anton B.; Singer, B.; Hang, Bo

    2004-05-05

    Exocyclic ethano DNA adducts are saturated etheno ring derivatives formed mainly by therapeutic chloroethylnitrosoureas (CNUs), which are also mutagenic and carcinogenic. In this work, we report that two of the ethano adducts, 3,N{sup 4}-ethanocytosine (EC) and 1,N{sup 6}-ethanoadenine (EA), are novel substrates for the Escherichia coli mismatch-specific uracil-DNA glycosylase (Mug) and 3-methyladenine DNA glycosylase II (AlkA), respectively. It has been shown previously that Mug excises 3,N{sup 4}-ethenocytosine ({var_epsilon}C) and AlkA releases 1,N{sup 6}-ethenoadenine ({var_epsilon}A). Using synthetic oligonucleotides containing a single ethano or etheno adduct, we found that both glycosylases had a {approx}20-fold lower excision activity toward EC or EA than that toward their structurally analogous {var_epsilon}C or {var_epsilon}A adduct. Both enzymes were capable of excising the ethano base paired with any of the four natural bases, but with varying efficiencies. The Mug activity toward EC could be stimulated by E. coli endonuclease IV and, more efficiently, by exonuclease III. Molecular dynamics (MD) simulations showed similar structural features of the etheno and ethano derivatives when present in DNA duplexes. However, also as shown by MD, the stacking interaction between the EC base and Phe 30 in the Mug active site is reduced as compared to the {var_epsilon}C base, which could account for the lower EC activity observed in this study.

  4. Photochemistry of psoralen-DNA adducts, biological effects of psoralen-DNA adducts, applications of psoralen-DNA photochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yun-bo

    1988-03-01

    This thesis consists of three main parts and totally eight chapters. In Part I, The author will present studies on the photochemistry of psoralen-DNA adducts, specifically, the wavelength dependencies for the photoreversals of thymidine-HMT (4'-hydroxymethyl-4, 5', 8-trimenthylpsoralen) monoadducts and diadduct and the same adducts incorporated in DNA helices and the wavelength dependecies for the photocrossslinking of thymidine-HMT monoadducts in double-stranded helices. In Part II, The author will report some biological effects of psoralen-DNA adducts, i.e., the effects on double-stranded DNA stability, DNA structure, and transcription by E. coli and T7 RNA polymerases. Finally, The author will focus on the applications of psoralen-DNA photochemistry to investigation of protein-DNA interaction during transcription, which includes the interaction of E. coli and T7 RNA polymerases with DNA in elongation complexes arrested at specific psoralen-DNA adduct sites as revealed by DNase I footprinting experiments. 123 refs., 52 figs., 12 tabs.

  5. 32P-postlabeling DNA adduct assay: cigarette smoke-induced dna adducts in the respiratory and nonrespiratory rat tissues. Book chapter

    International Nuclear Information System (INIS)

    An analysis of the tissue DNA adducts in rats by the sensitive (32)p-postlabeling assay showed one to eight detectable DNA adducts in lung, trachea, larynx, heart and bladder of the sham controls. Chronic exposure of animals to mainstream cigarette smoke showed a remarkable enhancement of most adducts in the lung and heart DNA. Since cigarette smoke contains several thousand chemicals and a few dozen of them are known or potential carcinogens, the difference between the DNA adducts of nasal and the other tissues may reflect the diversity of reactive constituents and their differential absorption in different tissues. In comparison to the lung DNA adducts, the adducts in nasal DNA were less hydrophobic. Identity of the predominant adducts was further investigated by comparison with several reference DNA adducts from 10 PAH and aromatic amines. Since some of these chemicals are present in cigarette smoke, the results suggest that these constituents of cigarette smoke may not be directly responsible for formation of DNA adducts in the lung and heart of the smoke-exposed animals

  6. A Study of incentives to increase the use of DG in Colombia based on a System Dynamics modeling

    Directory of Open Access Journals (Sweden)

    S. B. Carvajal-Quintero

    2011-07-01

    Full Text Available This paper presents a study regarding the introduction of distributed generation (DG within the Colombian power system by considering commercial, environmental and technical incentives. Environmental and commercial incentives were quantified by studying international precedents for implementing DG. Technical incentives were quantified by taking into consideration the remuneration received by generator agents providing automatic generation control (AGC, since this is the only ancillary service recognized in Colombia. A system dynamics model was built to evaluate the complete proposal. The study found that the current incentives proposed in Colombian regulation, such as tax breaks, are insufficient to cover total costs. Moreover, environmental incentives can be an efficient way of promoting renewable energy use in Colombia to achieve more generating capacity with lower pollution indices. Similarly, technical incentives, in conjunction with environmental incentives, can further improve DG growth in Colombia. The diffusion of DG thus becomes an additional tool for the operator of the interconnected system for controlling voltage and improving the quality and security of electrical power systems.

  7. EMG evaluation of hip adduction exercises for soccer players

    DEFF Research Database (Denmark)

    Serner, Andreas; Jakobsen, Markus Due; Andersen, Lars Louis;

    2014-01-01

    traditional and two new hip adduction exercises. Additionally, to analyse muscle activation of gluteals and abdominals. MATERIALS AND METHODS: 40 healthy male elite soccer players, training >5 h a week, participated in the study. Muscle activity using surface electromyography (sEMG) was measured bilaterally...... for the adductor longus during eight hip adduction strengthening exercises and peak EMG was normalised (nEMG) using an isometric maximal voluntary contraction (MVC) as reference. Furthermore, muscle activation of the gluteus medius, rectus abdominis and the external abdominal obliques was analysed during...... the exercises. RESULTS: There were large differences in peak nEMG of the adductor longus between the exercises, with values ranging from 14% to 108% nEMG (pEMG results for the gluteals...

  8. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    International Nuclear Information System (INIS)

    Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates

  9. NEW HYDROGENOXALATO ADDUCTS AND MALONATO COMPLEX: SYNTHESIS AND SPECTROSCOPIC STUDIES

    Directory of Open Access Journals (Sweden)

    MOUHAMADOU BIRAME DIOP

    2014-08-01

    Full Text Available Two new hydrogenoxalato and one malonato adduct and complex have been synthesized and studied by infrared and NMR spectroscopies. The suggested structures are discrete, the hydrogenoxalate behaving as a monodentate ligand or only involved in hydrogen bonding, the environment around the tin (IV centre being tetrahedral or trigonal bipyramidal. The malonate anion is a monodentate ligand. In all the suggested structures, when extra hydrogen bonds are considered, supramolecular architectures are obtained.

  10. PHOSPHATO AND PHOSPHONATO ADDUCTS: SYNTHESIS AND SPECTROSCOPIC STUDY

    Directory of Open Access Journals (Sweden)

    Mouhamadou Birame Diop

    2014-05-01

    Full Text Available Two new adducts have been synthesized and studied by infrared and NMR spectroscopy. The suggested structures are discrete or of infinite chain type with a phosphate behaving as a bidentate ligand, a phosphonate acting as a monodentate ligand, the environments around the tin centre being tetrahedral or trigonal bipyramidal. In all the studied compounds, supramolecular architectures are obtained when hydrogen bonds are considered.

  11. Formation and persistence of arylamine DNA adducts in vivo.

    OpenAIRE

    Beland, F A; Kadlubar, F F

    1985-01-01

    Aromatic amines are urinary bladder carcinogens in man and induce tumors at a number of sites in experimental animals including the liver, mammary gland, intestine, and bladder. In this review, the particular pathways involved in the metabolic activation of aromatic amines are considered as well as the specific DNA adducts formed in target and nontarget tissue. Particular emphasis is placed on the following compounds: 1-naphthylamine, 2-naphthylamine, 4-aminobiphenyl, 4-acetylaminobiphenyl, 4...

  12. Ion Pairs or Neutral Molecule Adducts? Cooperativity in Hydrogen Bonding

    Science.gov (United States)

    DeKock, Roger L.; Schipper, Laura A.; Dykhouse, Stephanie C.; Heeringa, Lee P.; Brandsen, Benjamin M.

    2009-01-01

    We performed theoretical studies on the systems NH[subscript 3] times HF times mH[subscript 2]O, NH[subscript 3] times HCl times mH[subscript 2]O, with m = 0, 1, 2, and 6. The molecules with m = 0 form hydrogen-bonded adducts with little tendency to form an ion-pair structure. The molecule NH[subscript 3] times HCl times H[subscript 2]O cannot be…

  13. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bin, E-mail: binli@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Eyer, Peter, E-mail: peter.eyer@lrz.uni-muenchen.de [Walther-Straub-Institut Für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, 80336 München (Germany); Eddleston, Michael, E-mail: M.Eddleston@ed.ac.uk [Clinical Pharmacology Unit, University of Edinburgh, Edinburgh (United Kingdom); Jiang, Wei, E-mail: wjiang@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Schopfer, Lawrence M., E-mail: lmschopf@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Lockridge, Oksana, E-mail: olockrid@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States)

    2013-06-15

    Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates.

  14. Seasonal variations in levels of DNA adducts and X-spots in human populations living in different parts of Poland.

    OpenAIRE

    Grzybowska, E; Hemminki, K; Choraźy, M

    1993-01-01

    White blood cell DNA adducts were measured in coke oven workers, in residents from the area next to the coke oven in Silesia, Poland (highly industrialized region), and in residents from the rural area of Poland using the 32P-postlabeling technique. This method detected aromatic adducts including adducts formed by polycyclic aromatic hydrocarbons (PAHs). Highest levels of adducts in DNA were seen in the group of coke battery workers (6.9 adducts/10(8) nucleotides). Seasonal variations in leve...

  15. Diagnosis and dosimetry of exposure to sulfur mustard: Development of a standard operating procedure for mass spectrometric analysis of haemoglobin adducts - Exploratory research on albumin and keratin adducts

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Hulst, A.G.; Jong, L.P.A. de; Benschop, H.P.

    2000-01-01

    Experiments were carried out to develop a standard operating procedure for analysis of sulfur mustard adducts to the N-terminal valine in haemoglobin and to explore adduct formation with albumin and keratin. In the first approach, gas chromatography-negative chemical ionization/mass spectrometry (GC

  16. Diagnosis and dosimetry of exposure to sulfur mustard: Development of a standard operating procedure for hemoglobin adducts: Exploratory research on albumin and keratin adducts

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Jong, L.P.A. de; Schans, G.P. van der; Benschop, H.P.

    2000-01-01

    A standard operating procedure (SOP) for determination of the sulfur mustard adduct to the N-terminal valine in hemoglobin was developed. By using this SOP, it was found that the Nterminal valine adduct in globin of hairless guinea pigs and marmosets which had been exposed to sulfur mustard (0.5 LD5

  17. Analysis of high-k spacer on symmetric underlap DG-MOSFET with Gate Stack architecture

    Science.gov (United States)

    Das, Rahul; Chakraborty, Shramana; Dasgupta, Arpan; Dutta, Arka; Kundu, Atanu; Sarkar, Chandan K.

    2016-09-01

    This paper shows the systematic study of underlap double gate (U-DG) NMOSFETs with Gate Stack (GS) under the influence of high-k spacers. In highly scaled devices, underlap is used at the Source and Drain side so as to reduce the short channel effects (SCE's), however, it significantly reduces the on current due to the increased channel resistance. To overcome these drawbacks, the use of high-k spacers is projected as one of the remedies. In this paper, the analog performance of the devices is studied on the basis of parameters like transconductance (gm), transconductance generation factor (gm/Id) and intrinsic gain (gmro). The RF performance is analyzed on the merits of intrinsic capacitance (Cgd, Cgs), resistance (Rgd, Rgs), transport delay (τm), inductance (Lsd), cutoff frequency (fT), and the maximum frequency of oscillation (fmax). The circuit performance of the devices are studied by implementing the device as the driver MOSFET in a Single Stage Common Source Amplifier. The Gain Bandwidth Product (GBW) has been analyzed from the frequency response of the circuit.

  18. Locating the Launching Region of T Tauri Winds The Case of DG Tau

    CERN Document Server

    Anderson, J M; Krasnopolsky, R; Blandford, R D; Anderson, Jeffrey M.; Li, Zhi-Yun; Krasnopolsky, Ruben; Blandford, Roger

    2003-01-01

    It is widely believed that T Tauri winds are driven magnetocentrifugally from accretion disks close to the central stars. The exact launching conditions are uncertain. We show that a general relation exists between the poloidal and toroidal velocity components of a magnetocentrifugal wind at large distances and the rotation rate of the launching surface, independent of the uncertain launching conditions. We discuss the physical basis of this relation and verify it using a set of numerically-determined large-scale wind solutions. Both velocity components are in principle measurable from spatially resolved spectra, as has been done for the extended low-velocity component (LVC) of the DG Tau wind by Bacciotti et al. For this particular source, we infer that the spatially resolved LVC originates from a region on the disk extending from $\\sim 0.3$ to $\\sim 4.0\\AU$ from the star, which is consistent with, and a refinement over, the previous rough estimate of Bacciotti et al.

  19. Time-Dependent MHD Shocks and Line Emission: The Case of the DG Tau Jet

    CERN Document Server

    Massaglia, S; Bodo, G

    2005-01-01

    The line emission from a growing number of Herbig-Haro jets can be observed and resolved at angular distances smaller than a few arcseconds from the central source. The interpretation of this emission is problematic, since the simplest model of a cooling jet cannot sustain it. It has been suggested that what one actually observes are shocked regions with a filling factor of $\\sim 1%$. In this framework, up to now, comparisons with observations have been based on stationary shock models. Here we introduce for the first time the self-consistent dynamics of such shocks and we show that considering their properties at different times, i.e. locations, we can reproduce observational data of the DG Tau microjet. In particular, we can interpret the spatial behavior of the [SII]6716/6731 and [NII]/[OI]6583/6300 line intensity ratios adopting a set of physical parameters that yield values of mass loss rates and magnetic fields consistent with previous estimates. We also obtain the values of the mean ionization fraction...

  20. Tracing kinematical and physical asymmetries in the jet from DG Tau B

    CERN Document Server

    Podio, Linda; Melnikov, Stanislav; Hodapp, Klaus W; Bacciotti, Francesca

    2010-01-01

    Stellar jets can be highly asymmetric and have multiple velocity components. To clarify the origin of jet asymmetries and constrain their launch mechanism we study the physical and kinematical structure of the flow emitted by DG Tau B. The analysis of deep spectra taken at the KECK telescope allows us to infer the physical properties (the electron and total density, ne and nh, the ionisation fraction, xe, and the temperature, te) and the spatial distribution of the velocity components in the two jet lobes. The presence of dust grains in the jet is investigated by estimating the gas-phase abundance of calcium with respect to its solar value. At the base of the jet the lines are broad (~100 km/s) and up to three velocity components are detected. At 5" from the source, however, only the denser and more excited high velocity components survive and the lines are narrower (~10-30 km/s). The jet is strongly asymmetric both in velocity and in its physical structure. The red lobe, slower (~140 km/s) and more collimate...

  1. Potential Opponent for 18FDG: Gd3+-DTPA-DG: A New Synthetic MRI Contrast Agent

    Directory of Open Access Journals (Sweden)

    Mehdi Shafiee Ardestani

    2010-05-01

    Full Text Available Glucose mediated imaging tools have recently be-come an area of research interest in the field of nuclear medicine, especially Positron Emission Tomography (PET imaging. The difficulties in the use, preparation and cost of radioactively-labeled glycosylated compounds led to the research and development in this present study of a new gadolinium-labeled glucose that does not have a radioactive half-life or difficulties in its synthesis and utilization. Based on the structure of fluorodeoxyglucose (18FDG, a new compound consisting of a D-glucose conjugated to a well-known chelator DTPA was synthesized, labeled with Gd3+ and examined in vitro and in vivo. The results showed a good anti-cancer potency for the prepared complex. Gd3+ -DTPA-DG did not produce any significant alteration in the blood glucose level and was also phosphorylated by hexokinase enzyme. In vitro relaxation times T1 and T2 were determined and compared with a standard compound Magnevist®. Finally, imaging studies were performed in tumor-bearing mice and the tumor areas were shown successfully. This compound may have great potential in the future in radio-oncology.

  2. Optimal DG Source Allocation for Grid Connected Distributed Generation with Energy Storage System

    Directory of Open Access Journals (Sweden)

    S. Ezhilarasan

    2015-05-01

    Full Text Available This study proposes an Energy Management System (EMS for allocation of DG source in a grid connected hybrid power system. Modeling and simulation for EMS is implemented using MATLAB/SIMULINK package. The objective of proposed EMS for micro grid is to optimize the fuel cost, improving the energy utilization efficiency and to manage the peak load demand by scheduling the generation according to the availability of the fuel. The proposed intelligent energy management system is designed to optimize the availability of energy to the load according to the level of priority and to manage the power flow. The developed management system performance was assessed using a hybrid system having PV panels, Wind Turbine (WT, battery and biomass gasifier. Real time field test has been conducted and the parameters i.e., solar irradiance, temperature, wind speed are gathered from 4.05 KW off grid and 2.0 KW On grid Solar Photovoltaic systems (SPV system and wind turbine. The dynamic behavior of the proposed model is examined under different operating conditions. The simulation results of proposed EMS using fuzzy logic expert system shows the minimization on the operating cost and emission level of micro grid by optimal scheduling of power generation and maintains the State of Charge (SOC of batteries in desired value which improves the battery life. The proposed multi objective intelligent energy management system aims to minimize the operational cost and the environmental impact of a micro grid.

  3. Cool, warm and hot outflows from CTTS: The FUV view of DG Tau

    Directory of Open Access Journals (Sweden)

    Schneider P. C.

    2014-01-01

    Full Text Available Classical T Tauri stars (CTTSs drive strong outflows with temperatures from about 103 K up to a few 106 K. These outflows regulate the angular momentum balance and are therefore tightly related to the accretion process. However, the outflow driving and heating mechanisms are not well understood. We present new HST data of the “prototypical” jet-driving CTTS DG Tau tracing the low-temperature outflow with fluorescently excited far-UV molecular hydrogen emission and the high-temperature part with C IV emission. We find that the spatial distribution of the low-temperature plasma is V-shaped consistent with molecular disk-wind models. Low-velocity shocks (vshock ~ 30 km s−1 are probably the pumping source for the FUV H2 lines. The hot plasma (T > 105 K is located close to the jet axis at a distance of 40 AU from the driving source and spatially offset from standard (optical jet-tracers like [S II] or [O I]. It does not show any hints for proper-motion contrasting typical jet properties. The high-temperature plasma is unlikely caused by a hot stellar wind and we propose that the stationary heating is caused by internal shocks or magnetic reconnection.

  4. Long-Slit Spectroscopy of Parsec-Scale Jets from DG Tauri

    Science.gov (United States)

    Oh, Heeyoung; Pyo, Tae-Soo; Yuk, In-Soo; Park, Byeong-Gon

    2015-04-01

    We present the observational results from optical long-slit spectroscopy of parsec-scale jets of DG Tau. From HH 158 and HH 702, the optical emission lines of Hα, OI λλ6300, 6363, NII λλ6548, 6584, and SII λλ6716, 6731 were obtained. The kinematics and physical properties (electron density, electron temperature, ionization fraction, and mass-loss rate) are investigated along the blueshifted jet up to 650 arcsec distance from the source. For the HH 158, the radial velocity range is -50 to -250 km s^{-1}. The proper motion of knots is 0.196 - 0.272 arcsec yr^{-1}. The electron density is ˜10^{4} cm^{-3} close to the star and decreases to ˜10^{2} cm^{-3} at 14 arcsec away from the star. Ionization fraction indicates that the gas is almost neutral in the vicinity of the source. It increases up to over 0.4 along the distance. The HH 702 is located at 650 arcsec from the source. It shows ˜ -80 km s^{-1} in the radial velccity. Its line ratios are similar to those at knot C of HH 158. The mass-loss rate is estimated about ˜ 10^{-7} M_{⊙} yr^{-1}, which is similar with the values from previous studies.

  5. Improved Grid Synchronization Algorithm for DG System using and UH PLL under Grid disturbances

    Directory of Open Access Journals (Sweden)

    R.Godha

    2014-12-01

    Full Text Available Distributed Generation (DG System is a small scale electric power generation at or near the user’s facility as opposed to the normal mode of centralized power generation. In order to ensure safe and reliable operation of power system based on DS, grid synchronization algorithm plays a very important role. Unbalanced Harmonic (UH based phase locked loop (PLL aimed to provide an estimation of the angular frequency and both the positive and negative sequences of the fundamental component of an unbalanced threephase signal. The UH PLL does not require transformation of variables into synchronous reference frame coordinates. Therefore, the proposed scheme is not based on the phase angle detection. Instead the angular frequency is detected and used for synchronization purposes. The design of this PLL is based on a complete description of the source voltage involving both positive and negative sequences in stationary coordinates and considering the angular frequency as an uncertain parameter. Therefore UHPLL is intended to perform properly under severe unbalanced conditions and to be robust against angular frequency variations, sags and swells in the three-phase utility voltage signal.

  6. Results and limits in the 1-D analytical modeling for the asymmetric DG SOI MOSFET

    Directory of Open Access Journals (Sweden)

    O. Cobianu

    2008-05-01

    Full Text Available This paper presents the results and the limits of 1-D analytical modeling of electrostatic potential in the low-doped p type silicon body of the asymmetric n-channel DG SOI MOSFET, where the contribution to the asymmetry comes only from p- and n-type doping of polysilicon used as the gate electrodes. Solving Poisson's equation with boundary conditions based on the continuity of normal electrical displacement at interfaces and the presence of a minimum electrostatic potential by using the Matlab code we have obtained a minimum potential with a slow variation in the central zone of silicon with the value pinned around 0.46 V, where the applied VGS voltage varies from 0.45 V to 0.95 V. The paper states clearly the validity domain of the analytical solution and the important effect of the localization of the minimum electrostatic potential value on the potential variation at interfaces as a function of the applied VGS voltage.

  7. [Expression of human IL-35-IgG4 (Fc) fusion protein in CHO/DG44 cells].

    Science.gov (United States)

    Tang, Jing; Gao, Wenda; Zhang, Qing; Zhang, Dawei; Chen, Yang; He, Bo; Liu, Quansheng

    2009-01-01

    We constructed the eukaryotic expression vector of human IL-35-IgG4 (Fc)-pOptiVEC-TOPO by gene recombination technique and expressed the fusion protein human IL-35-IgG4 (Fc) in CHO/DG44 cells. The two components of the newly discovered cytokine human IL-35, EBI3 and IL-12p35, were amplified by PCR from the cDNA library derived from the KG-I cells after LPS induction. The two PCR-amplified cDNA fragments of human IL-35 were linked by over-lapping PCR and then cloned into the IgG4 (Fc)-pOptiVEC-TOPO vector. The constructed plasmid with the recombinant cDNA IL-35-IgG4 (Fc) was verified by restriction enzyme digestion analysis, PCR and DNA sequencing. The verified plasmid with the recombinant cDNA was transfected into CHO/DG44 cells using Lipofectamine 2000. The success of the transfection was examined and confirmed by RT-PCR. After selection in alpha-MEM (-) medium, the IL-35-Ig G4 (Fc) positive CHO/DG44 clones were chosen and the media from these positive clones were collected to be used to purify the fusion protein. The positive CHO/DG44 clones were further cultured in increasing concentrations of MTX and the expression levels of the fusion protein IL-35-Ig G4 (Fc) were repetitively induced by MTX-induced gene amplification. The IL-35-IgG4 (Fc) fusion protein was purified from the media collected from the positive CHO/DG44 clones by protein G affinity chromatography and then identified by SDS-PAGE and Western blotting. The results showed that one protein band was found to match well with the predicted relative molecular mass of human IL-35-IgG4 (Fc) and this protein could specifically bind to anti-human IgG4 (Fc) monoclonal antibody. In conclusion, our study successfully established an IL-35-IgG4 (Fc) positive DG44 cell line which could stably express IL-35-IgG4 (Fc) fusion protein.

  8. Human Biomonitoring of DNA Adducts by Ion Trap Multistage Mass Spectrometry.

    Science.gov (United States)

    Guo, Jingshu; Turesky, Robert J

    2016-01-01

    Humans are continuously exposed to hazardous chemicals in the environment. These chemicals or their electrophilic metabolites can form adducts with genomic DNA, which can lead to mutations and the initiation of cancer. The identification of DNA adducts is required for understanding exposure and the etiological role of a genotoxic chemical in cancer risk. The analytical chemist is confronted with a great challenge because the levels of DNA adducts generally occur at spectrometry has emerged as an important technique to screen for DNA adducts because of the high level sensitivity and selectivity, particularly when employing multi-stage scanning (MS(n) ). The product ion spectra provide rich structural information and corroborate the adduct identities even at trace levels in human tissues. Ion trap technology represents a significant advance in measuring DNA adducts in humans. © 2016 by John Wiley & Sons, Inc. PMID:27584705

  9. Fast repair of oxidizing OH adducts of DNA by hydroxycinnamic acid derivatives. A pulse radiolytic study

    International Nuclear Information System (INIS)

    Using pulse radiolytic techniques, it has been demonstrated that the interactions of oxidizing OH adducts of DNA (ssDNA and dsDNA), polyA and polyG with hydroxycinnamic acid derivatives proceed via an electron transfer process (k=5-30x108 dm3 mol-1 s-1). In addition, the rates for fast repair of OH adducts of dAMP, polyA and DNA (ssDNA and dsDNA) are slower than the corresponding rates for the rest OH adducts of DNA constituents. The slower rates for repair of oxidizing OH adducts of dAMP may be the rate determining step during the interaction of hydroxycinnamic acid derivatives with OH adducts of DNA containing the varieties of OH adducts of DNA constituents

  10. Zinc acetylacetonate hydrate adducted with nitrogen donor ligands: Synthesis, spectroscopic characterization, and thermal analysis

    Science.gov (United States)

    Brahma, Sanjaya; Shivashankar, S. A.

    2015-12-01

    We report synthesis, spectroscopic characterization, and thermal analysis of zinc acetylacetonate complex adducted by nitrogen donor ligands, such as pyridine, bipyridine, and phenanthroline. The pyridine adducted complex crystallizes to monoclinic crystal structure, whereas other two adducted complexes have orthorhombic structure. Addition of nitrogen donor ligands enhances the thermal property of these complexes as that with parent metal-organic complex. Zinc acetylacetonate adducted with pyridine shows much higher volatility (106 °C), decomposition temperature (202 °C) as that with zinc acetylacetonate (136 °C, 220 °C), and other adducted complexes. All the adducted complexes are thermally stable, highly volatile and are considered to be suitable precursors for metal organic chemical vapor deposition. The formation of these complexes is confirmed by powder X-ray diffraction, Fourier transform infrared spectroscopy, mass spectroscopy, and elemental analysis. The complexes are widely used as starting precursor materials for the synthesis of ZnO nanostructures by microwave irradiation assisted coating process.

  11. Structure of adducts of isoindolo[2,1-a]benzimidazole derivatives with maleimides

    Science.gov (United States)

    Korolev, Oleksandr; Yegorova, Tatyana; Levkov, Igor; Malytskyy, Volodymyr; Shishkin, Oleg; Zubatyuk, Roman; Palamarchuk, Genadiy; Vedrenne, Marc; Baltas, Michel; Voitenko, Zoia

    2015-03-01

    The selectivity of formation and some mechanistic insights during the synthesis of substituted isoindolo[2,1-a]benzimidazoles are discussed. Furthermore, the reactions of the obtained products with maleimides were carried out. Two types rearrangement adducts together with intermediate Michael type adducts were isolated. The influence of the reaction conditions and reagents ratio is discussed. Specific spectral criteria for the identification of the Michael type adducts are indicated.

  12. Metabolism of the Antibacterial Triclocarban by Human Epidermal Keratinocytes to Yield Protein Adducts

    OpenAIRE

    Schebb, Nils Helge; Buchholz, Bruce A.; Hammock, Bruce D.; Rice, Robert H.

    2012-01-01

    Previous studies of triclocarban suggest that its biotransformation could yield reactive metabolites that form protein adducts. Since the skin is the major route of triclocarban exposure, present work examined this possibility in cultured human keratinocytes. The results provide evidence for considerable biotransformation and protein adduct formation when cytochrome P450 activity is induced in the cells by TCDD, a model Ah receptor ligand. Since detecting low adduct levels in cells and tissue...

  13. Structural aspects of adducts of N-phthaloylglycine and its derivatives

    Science.gov (United States)

    Barooah, Nilotpal; Sarma, Rupam J.; Batsanov, Andrei S.; Baruah, Jubaraj B.

    2006-06-01

    N-phthaloylglycine forms 2:1 adduct with 1,3-dihydroxybenzene and 1:2 adduct with 2-aminopyrimidine. Whereas N-phthaloylglycine form salts with 2,6-diaminopyridine and with 8-hydroxyquinoline. The 1:1 adduct of N, N'-bis(glycinyl)pyromellitic diimide with dimethylsulphoxide, 2-aminopyrimidine and 4,4'-dihydroxybiphenyl are prepared and characterised. The reaction of N, N'-bis(glycinyl)pyromellitic diimide with 2,6-diaminopyridine gives corresponding salt.

  14. Detection and characterization of human serum antibodies to polycyclic aromatic hydrocarbon diol-epoxide DNA adducts.

    OpenAIRE

    Newman, M J; Light, B A; Weston, A; Tollurud, D; Clark, J L; Mann, D L; Blackmon, J P; Harris, C C

    1988-01-01

    The presence of serum antibodies to the diol-epoxide DNA adducts of representative polycyclic aromatic hydrocarbons (PAH), chrysene, benz[a]anthracene and benzo[a]pyrene, was determined by ELISA using serum samples obtained from normal healthy individuals. Antibodies that reacted against PAH adducted-DNA, but not against PAH-adducted protein, were found in the serum of approximately 40% of the test individuals. Specificity analysis of the antibodies demonstrated that serological cross-reactio...

  15. Market and regulatory incentives for cost efficient integration of DG in the electricity system. IMPROGRES project final report

    Energy Technology Data Exchange (ETDEWEB)

    Nieuwenhout, F.D.J.; Jansen, J.C.; Van der Welle, A.J. [ECN Policy Studies, Petten (Netherlands); Olmos, L.; Cossent, R.; Gomez, T. [Universidad Pontificia Comillas, Madrid (Spain); Poot, J.; Bongaerts, M. [Liander, Duiven (Netherlands); Trebolle, D. [Union Fenosa Distribucion, Madrid (Spain); Doersam, B. [MVV Energie, Mannheim (Germany); Bofinger, S.; Gerhardt, N. [Fraunhofer Institute for Wind Energy and Energy System Technology, IWES, Bremerhaven (Germany); Jacobsen, H.; Ropenus, S.; Schroeder, S. [Risoe National Laboratory for Sustainable Energy, Technical University of Denmark DTU, Roskilde (Denmark); Auer, H.; Weissensteiner, L.; Prueggler, W.; Obersteiner, C.; Zach, K. [Energy Economics Group EEG, Vienna University of Technology, Vienna (Austria)

    2010-05-15

    Achieving the European target of 20% reduction of greenhouse gases in 2020 relies for a major part on increasing the share of renewable electricity generation, and more efficient fossil fuel based generation in combined heat and power installations. Most of these renewable and CHP generators are smaller in size than conventional power plants and are therefore usually connected to distribution grids instead of transmission grids. Different support schemes for renewable energy sources (RES) have been successfully implemented and have resulted in a rapid growth of distributed generation (DG). IMPROGRES scenario analysis shows that the installed capacity of DG in the EU-25 is expected to increase from 201 GW in 2008 to about 317 GW in 2020. A large part of this increase will be made up of more variable and less controllable renewable energy sources like wind and photovoltaics.

  16. Four-leg parallel Z-source inverter based DG systems to enhance the grid performance under unbalanced conditions

    DEFF Research Database (Denmark)

    Gajanayake, C.J.; Teodorescu, Remus; Blaabjerg, Frede;

    2007-01-01

    is proposed based on interleaved carriers to reduce the output current ripple. Separate controllers are designed in stationary reference frame for the AC side of each inverter. The AC side controller is designed using a combination of p resonance and negative feedback time delay. The combined controller would......This paper presents a DG system based on four-leg parallel Z-source inverters in integrating a renewable generation system into the grid. Particularly, four-leg distribution schemes give flexibility into the DG system by supporting other functions of power distribution like control of zero sequence...... deliver good reference tracking and harmonic rejection properties. Another controller is designed for the DC side Z-source impedance network to mitigate the fluctuations in the renewable source. The whole system is driven from a higher level controller that would generate current references to operate...

  17. Flicker and thermal noise in an n-channel underlap DG FinFET in a weak inversion region

    International Nuclear Information System (INIS)

    We propose an analytical model for drain current and inversion charge in the subthreshold region for an underlap DG FinFET by using the minimum channel potential method, i.e., the virtual source. The flicker and thermal noise spectral density models are also developed using these charge and current models expression. The model is validated with already published experimental results of flicker noise for DG FinFETs. For an ultrathin body, the degradation of effective mobility and variation of the scattering parameter are considered. The effect of device parameters like gate length Lg and underlap length Lun on both flicker and thermal noise spectral densities are also analyzed. Increasing Lg and Lun, increases the effective gate length, which reduces drain current, resulting in decreased flicker and thermal noise density. A decrease of flicker noise is observed for an increase of frequency, which indicates that the device can be used for wide range of frequency applications. (semiconductor devices)

  18. ANFIS-based approach to studying subthreshold behavior including the traps effect for nanoscale thin-film DG MOSFETs

    International Nuclear Information System (INIS)

    A fuzzy framework based on an adaptive network fuzzy inference system (ANFIS) is proposed to evaluate the relative degradation of the basic subthreshold parameters due to hot-carrier effects for nanoscale thin-film double-gate (DG) MOSFETs. The effect of the channel length and thickness on the resulting degradation is addressed, and 2-D numerical simulations are used for the elaboration of the training database. Several membership function shapes are developed, and the best one in terms of accuracy is selected. The predicted results agree well with the 2-D numerical simulations and can be efficiently used to investigate the impact of the interface fixed charges and quantum confinement on nanoscale DG MOSFET subthreshold behavior. Therefore, the proposed ANFIS-based approach offers a simple and accurate technique to study nanoscale devices, including the hot-carrier and quantum effects. (semiconductor devices)

  19. ANFIS-based approach to studying subthreshold behavior including the traps effect for nanoscale thin-film DG MOSFETs

    Institute of Scientific and Technical Information of China (English)

    T.Bentrcia; F.Djeffal; E.Chebaaki

    2013-01-01

    A fuzzy framework based on an adaptive network fuzzy inference system (ANFIS) is proposed to evaluate the relative degradation of the basic subthreshold parameters due to hot-carrier effects for nanoscale thin-film double-gate (DG) MOSFETs.The effect of the channel length and thickness on the resulting degradation is addressed,and 2-D numerical simulations are used for the elaboration of the training database.Several membership function shapes are developed,and the best one in terms of accuracy is selected.The predicted results agree well with the 2-D numerical simulations and can be efficiently used to investigate the impact of the interface fixed charges and quantum confinement on nanoscale DG MOSFET subthreshold behavior.Therefore,the proposed ANFIS-based approach offers a simple and accurate technique to study nanoscale devices,including the hot-carrier and quantum effects.

  20. Synthesis and Characterization of the Adducts of Bis(O-ethyldithiocarbonatocopper(II with Substituted Pyridines

    Directory of Open Access Journals (Sweden)

    Gurpreet Kour

    2013-01-01

    Full Text Available Monomeric five coordinated adducts of bis(O-ethyldithiocarbonatocopper(II of general formula [Cu(C2H5OCS22(L], [L = 2-, 3-, 4-methylpyridines and 2-, 3-, 4-ethylpyridines] have been synthesized and characterized by elemental analysis, i.r. and electronic spectroscopy, magnetic and conductivity measurements. Analytical results show that the adducts have 1 : 1 stoichiometry. The adducts were found to be paramagnetic and their magnetic moments at room temperature lie within the 1.81–1.94 B.M. range and this indicates the presence of one unpaired electron. All the adducts have distorted square pyramidal geometry.

  1. Correlation between Quadriceps Endurance and Adduction Moment in Medial Knee Osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Soon-Hyuck Lee

    Full Text Available It is not clear whether the strength or endurance of thigh muscles (quadriceps and hamstring is positively or negatively correlated with the adduction moment of osteoarthritic knees. This study therefore assessed the relationships between the strength and endurance of the quadriceps and hamstring muscles and adduction moment in osteoarthritic knees and evaluated predictors of the adduction moment. The study cohort comprised 35 patients with unilateral medial osteoarthritis and varus deformity who were candidates for open wedge osteotomy. The maximal torque (60°/sec and total work (180°/sec of the quadriceps and hamstring muscles and knee adduction moment were evaluated using an isokinetic testing device and gait analysis system. The total work of the quadriceps (r = 0.429, P = 0.037 and hamstring (r = 0.426, P = 0.045 muscles at 180°/sec each correlated with knee adduction moment. Preoperative varus deformity was positively correlated with adduction moment (r = 0.421, P = 0.041. Multiple linear regression analysis showed that quadriceps endurance at 180°/sec was the only factor independently associated with adduction moment (β = 0.790, P = 0.032. The adduction moment of osteoarthritic knees correlated with the endurance, but not the strength, of the quadriceps muscle. However, knee adduction moment did not correlate with the strength or endurance of the hamstring muscle.

  2. General and Simple Decision Method for DG Penetration Level in View of Voltage Regulation at Distribution Substation Transformers

    OpenAIRE

    Joon-Ho Choi; Hyun-Koo Kang; Seong-Soo Cho; Won-Wook Jung; Chul-Min Chu; Il-Keun Song

    2013-01-01

    A distribution system was designed and operated by considering unidirectional power flow from a utility source to end-use loads. The large penetrations of distributed generation (DG) into the existing distribution system causes a variety of technical problems, such as frequent tap changing problems of the on-load tap changer (OLTC) transformer, local voltage rise, protection coordination, exceeding short-circuit capacity, and harmonic distortion. In view of voltage regulation, the intermitten...

  3. A locally p-adaptive approach for Large Eddy Simulation of compressible flows in a DG framework

    CERN Document Server

    Tugnoli, Matteo; Bonaventura, Luca; Restelli, Marco

    2016-01-01

    We investigate the possibility of reducing the computational burden of LES models by employing local polynomial degree adaptivity in the framework of a high order DG method. A novel degree adaptation technique especially featured to be effective for LES applications is proposed and its effectiveness is compared to that of other criteria already employed in the literature. The resulting locally adaptive approach allows to achieve significant reductions in computational cost of representative LES computations.

  4. Fenpropathrin biodegradation pathway in Bacillus sp. DG-02 and its potential for bioremediation of pyrethroid-contaminated soils.

    Science.gov (United States)

    Chen, Shaohua; Chang, Changqing; Deng, Yinyue; An, Shuwen; Dong, Yi Hu; Zhou, Jianuan; Hu, Meiying; Zhong, Guohua; Zhang, Lian-Hui

    2014-03-12

    The widely used insecticide fenpropathrin in agriculture has become a public concern because of its heavy environmental contamination and toxic effects on mammals, yet little is known about the kinetic and metabolic behaviors of this pesticide. This study reports the degradation kinetics and metabolic pathway of fenpropathrin in Bacillus sp. DG-02, previously isolated from the pyrethroid-manufacturing wastewater treatment system. Up to 93.3% of 50 mg L(-1) fenpropathrin was degraded by Bacillus sp. DG-02 within 72 h, and the degradation rate parameters qmax, Ks, and Ki were determined to be 0.05 h(-1), 9.0 mg L(-1), and 694.8 mg L(-1), respectively. Analysis of the degradation products by gas chromatography-mass spectrometry led to identification of seven metabolites of fenpropathrin, which suggest that fenpropathrin could be degraded first by cleavage of its carboxylester linkage and diaryl bond, followed by degradation of the aromatic ring and subsequent metabolism. In addition to degradation of fenpropathrin, this strain was also found to be capable of degrading a wide range of synthetic pyrethroids including deltamethrin, λ-cyhalothrin, β-cypermethrin, β-cyfluthrin, bifenthrin, and permethrin, which are also widely used insecticides with environmental contamination problems with the degradation process following the first-order kinetic model. Bioaugmentation of fenpropathrin-contaminated soils with strain DG-02 significantly enhanced the disappearance rate of fenpropathrin, and its half-life was sharply reduced in the soils. Taken together, these results depict the biodegradation mechanisms of fenpropathrin and also highlight the promising potentials of Bacillus sp. DG-02 in bioremediation of pyrethroid-contaminated soils.

  5. In vitro screening of 50 highly prescribed drugs for thiol adduct formation--comparison of potential for drug-induced toxicity and extent of adduct formation.

    Science.gov (United States)

    Gan, Jinping; Ruan, Qian; He, Bing; Zhu, Mingshe; Shyu, Wen C; Humphreys, W Griffith

    2009-04-01

    Reactive metabolite formation has been associated with drug-induced liver, skin, and hematopoietic toxicity of many drugs that has resulted in serious clinical toxicity, leading to clinical development failure, black box warnings, or, in some cases, withdrawal from the market. In vitro and in vivo screening for reactive metabolite formation has been proposed and widely adopted in the pharmaceutical industry with the aim of minimizing the property and thus the risk of drug-induced toxicity (DIT). One of the most common screening methods is in vitro thiol trapping of reactive metabolites. Although it is well-documented that many hepatotoxins form thiol adducts, there is no literature describing the adduct formation potential of safer drugs that are widely used. The objective of this study was to quantitatively assess the thiol adduct formation potential of 50 drugs (10 associated with DIT and 40 not associated) and document apparent differences in adduct formation between toxic and safer drugs. Dansyl glutathione was used as a trapping agent to aid the quantitation of adducts following in vitro incubation of drugs with human liver microsomes in the presence and absence of NADPH. Metabolic turnover of these drugs was also monitored by LC/UV. Overall, 15 out of the 50 drugs screened formed detectable levels of thiol adducts. There were general trends toward more positive findings in the DIT group vs the non-DIT group. These trends became more marked when the relative amount of thiol adducts was taken into account and improved further when dose and total daily reactive metabolite burdens were considered. In conclusion, there appears to be a general trend between the extent of thiol adduct formation and the potential for DIT, which would support the preclinical measurement and minimization of the property through screening of thiol adduct formation as part of an overall discovery optimization paradigm. PMID:19253935

  6. A new approach for optimum DG placement and sizing based on voltage stability maximization and minimization of power losses

    International Nuclear Information System (INIS)

    Highlights: • A new algorithm is proposed for optimum DG placement and sizing.• I2R losses minimization and voltage stability maximization is considered in fitness function.• Bus voltage stability and line stability is considered in voltage stability maximization.• Multi-objective PSO is used to solve the problem.• Proposed method is compared with analytical and grid search algorithm. - Abstract: Distributed Generation (DG) placement on the basis of minimization of losses and maximization of system voltage stability are two different approaches, discussed in research. In the new proposed algorithm, a multi-objective approach is used to combine the both approaches together. Minimization of power losses and maximization of voltage stability due to finding weakest voltage bus as well as due to weakest link in the system are considered in the fitness function. Particle Swarm Optimization (PSO) algorithm is used in this paper to solve the multi-objective problem. This paper will also compare the propose method with existing DG placement methods. From results, the proposed method is found more advantageous than the previous work in terms of voltage profile improvement, maximization of system loadability, reduction in power system losses and maximization of bus and line voltage stability. The results are validated on 12-bus, 30-bus, 33-bus and 69-bus radial distribution networks and also discussed in detailed

  7. KINEMATICS OF THE OUTFLOW FROM THE YOUNG STAR DG TAU B: ROTATION IN THE VICINITIES OF AN OPTICAL JET

    Energy Technology Data Exchange (ETDEWEB)

    Zapata, Luis A.; Lizano, Susana; Rodríguez, Luis F.; Loinard, Laurent; Tafoya, Daniel [Centro de Radioastronomía y Astrofísica, UNAM, Apdo. Postal 3-72 (Xangari), 58089 Morelia, Mich. (Mexico); Ho, Paul T. P. [Academia Sinica Institute of Astronomy and Astrophysics, Taipei, Taiwan (China); Fernández-López, Manuel, E-mail: lzapata@crya.unam.mx [Astronomy Department, University of Illinois, 1002 West Green Street, Urbana, IL 61801 (United States)

    2015-01-10

    We present {sup 12}CO(2-1) line and 1300 μm continuum observations made with the Submillimeter Array of the young star DG Tau B. We find, in the continuum observations, emission arising from the circumstellar disk surrounding DG Tau B. The {sup 12}CO(2-1) line observations, on the other hand, revealed emission associated with the disk and the asymmetric outflow related with this source. Velocity asymmetries about the flow axis are found over the entire length of the flow. The amplitude of the velocity differences is of the order of 1-2 km s{sup –1} over distances of about 300-400 AU. We interpret them as a result of outflow rotation. The sense of the outflow and disk rotation is the same. Infalling gas from a rotating molecular core cannot explain the observed velocity gradient within the flow. Magneto-centrifugal disk winds or photoevaporated disk winds can produce the observed rotational speeds if they are ejected from a Keplerian disk at radii of several tens of AU. Nevertheless, these slow winds ejected from large radii are not very massive, and cannot account for the observed linear momentum and angular momentum rates of the molecular flow. Thus, the observed flow is probably entrained material from the parent cloud. DG Tau B is a good laboratory to model in detail the entrainment process and see if it can account for the observed angular momentum.

  8. DgSMC-B code: A robust and autonomous direct simulation Monte Carlo code for arbitrary geometries

    Science.gov (United States)

    Kargaran, H.; Minuchehr, A.; Zolfaghari, A.

    2016-07-01

    In this paper, we describe the structure of a new Direct Simulation Monte Carlo (DSMC) code that takes advantage of combinatorial geometry (CG) to simulate any rarefied gas flows Medias. The developed code, called DgSMC-B, has been written in FORTRAN90 language with capability of parallel processing using OpenMP framework. The DgSMC-B is capable of handling 3-dimensional (3D) geometries, which is created with first-and second-order surfaces. It performs independent particle tracking for the complex geometry without the intervention of mesh. In addition, it resolves the computational domain boundary and volume computing in border grids using hexahedral mesh. The developed code is robust and self-governing code, which does not use any separate code such as mesh generators. The results of six test cases have been presented to indicate its ability to deal with wide range of benchmark problems with sophisticated geometries such as airfoil NACA 0012. The DgSMC-B code demonstrates its performance and accuracy in a variety of problems. The results are found to be in good agreement with references and experimental data.

  9. Influence of Underlap on Gate Stack DG-MOSFET for analytical study of Analog/RF performance

    Science.gov (United States)

    Kundu, Atanu; Dasgupta, Arpan; Das, Rahul; Chakraborty, Shramana; Dutta, Arka; Sarkar, Chandan K.

    2016-06-01

    In this paper, the characteristics of 18 nm Underlap Double Gate (U-DG) NMOSFET with gate stack, (GS) are presented. The high-k dielectric as gate insulator under consideration is Hafnium Dioxide (HfO2). The SiO2 padding reduces the effect of scattering at the silicon and oxide interface. The ratio of on current to off current is used for optimizing the underlap length. The Analog and RF performance comparison are shown in this paper considering the drain current (Id), the transconductance (gm), the intrinsic gain (gmRo), the intrinsic capacitances (Cgs, Cgd), the intrinsic resistances (Rgs, Rgd), the transport delay (τm), the intrinsic inductance (Hsd), the unity current gain cut-off frequency (fT) and the maximum frequency of oscillation (fmax). RF parameters are extracted using the Non Quasi Static (NQS) model of the U-DG MOSFET. The performance of single stage amplifiers using the devices is also analyzed. The sharpest transition is shown in case of U-DG-GS MOSFET with optimized underlap length and enhancement in the intrinsic capacitances and resistances, and unity Gain Bandwidth product in case of devices with GS.

  10. Group 13 Superacid Adducts of [PCl2N]3.

    Science.gov (United States)

    Tun, Zin-Min; Heston, Amy J; Panzner, Matthew J; Scionti, Vincenzo; Medvetz, Doug A; Wright, Brian D; Johnson, Nicholas A; Li, Linlin; Wesdemiotis, Chrys; Rinaldi, Peter L; Youngs, Wiley J; Tessier, Claire A

    2016-04-01

    Irrespective of the order of the addition of reagents, the reactions of [PCl2N]3 with MX3 (MX3 = AlCl3, AlBr3, GaCl3) in the presence of water or gaseous HX give the air- and light-sensitive superacid adducts [PCl2N]3·HMX4. The reactions are quantitative when HX is used. These reactions illustrate a Lewis acid/Brønsted acid dichotomy in which Lewis acid chemistry can become Brønsted acid chemistry in the presence of adventitious water or HX. The crystal structures of all three [PCl2N]3·HMX4 adducts show that protonation weakens the two P-N bonds that flank the protonated nitrogen atom. Variable-temperature NMR studies indicate that exchange in solution occurs in [PCl2N]3·HMX4, even at lower temperatures than those for [PCl2N]3·MX3. The fragility of [PCl2N]3·HMX4 at or near room temperature and in the presence of light suggests that such adducts are not involved directly as intermediates in the high-temperature ring-opening polymerization (ROP) of [PCl2N]3 to give [PCl2N]n. Attempts to catalyze or initiate the ROP of [PCl2N]3 with the addition of [PCl2N]3·HMX4 at room temperature or at 70 °C were not successful. PMID:26974866

  11. Metabolites and DNA adduct formation from flavoenzyme-activated porfiromycin.

    Science.gov (United States)

    Pan, S S; Iracki, T

    1988-08-01

    Porfiromycin was reductively metabolized by NADPH cytochrome P-450 reductase and xanthine oxidase under anaerobic conditions. The production of metabolites varied with the pH and the contents of the reaction buffer. In Tris buffer, two major metabolites were produced at pH 7.5 and above, whereas one major metabolite was produced at pH 6.5. The three major metabolites were separated and isolated by HPLC. Identification by californium-252 plasma desorption mass spectrometry showed that the two major metabolites from pH 7.5 were (trans) and (cis)-forms of 7-amino-1-hydroxyl-2-methylaminomitosene and the major metabolite from pH 6.5 was 7-amino-2-methylaminomitosene. All three major metabolites showed substitutions at the C-1 position. DNA was alkylated readily by enzyme-activated porfiromycin. Digestion of porfiromycin-alkylated DNA by DNase, snake venom phosphodiesterase, and alkaline phosphatase resulted in an insoluble nuclease-resistant fraction and a soluble fraction. The nuclease-resistant fraction reflected a high content of cross-linked adducts. Upon HPLC analysis, the solubilized fraction contained two monofunctionally linked porfiromycin adducts and a possibly cross-linked dinucleotide. The major adduct was isolated by HPLC and identified by NMR, as N2-(2'-deoxyguanosyl)-7-amino-2-methylaminomitosene. The N2 position of deoxyguanosine appeared as the major monofunctional alkylating site for DNA alkylation by porfiromycin. Thus, mitomycin C and porfiromycin (which differs from mitomycin C only by the addition of a methyl group to the aziridine nitrogen) share the same enzymatic activating mechanism that leads to the formation of the same types of metabolites and the same specificity of DNA alkylation. PMID:3412325

  12. Lack of Involvement of CEP Adducts in TLR Activation and in Angiogenesis

    Science.gov (United States)

    Gounarides, John; Cobb, Jennifer S.; Zhou, Jing; Cook, Frank; Yang, Xuemei; Yin, Hong; Meredith, Erik; Rao, Chang; Huang, Qian; Xu, YongYao; Anderson, Karen; De Erkenez, Andrea; Liao, Sha-Mei; Crowley, Maura; Buchanan, Natasha; Poor, Stephen; Qiu, Yubin; Fassbender, Elizabeth; Shen, Siyuan; Woolfenden, Amber; Jensen, Amy; Cepeda, Rosemarie; Etemad-Gilbertson, Bijan; Giza, Shelby; Mogi, Muneto; Jaffee, Bruce; Azarian, Sassan

    2014-01-01

    Proteins that are post-translationally adducted with 2-(ω-carboxyethyl)pyrrole (CEP) have been proposed to play a pathogenic role in age-related macular degeneration, by inducing angiogenesis in a Toll Like Receptor 2 (TLR2)-dependent manner. We have investigated the involvement of CEP adducts in angiogenesis and TLR activation, to assess the therapeutic potential of inhibiting CEP adducts and TLR2 for ocular angiogenesis. As tool reagents, several CEP-adducted proteins and peptides were synthetically generated by published methodology and adduction was confirmed by NMR and LC-MS/MS analyses. Structural studies showed significant changes in secondary structure in CEP-adducted proteins but not the untreated proteins. Similar structural changes were also observed in the treated unadducted proteins, which were treated by the same adduction method except for one critical step required to form the CEP group. Thus some structural changes were unrelated to CEP groups and were artificially induced by the synthesis method. In biological studies, the CEP-adducted proteins and peptides failed to activate TLR2 in cell-based assays and in an in vivo TLR2-mediated retinal leukocyte infiltration model. Neither CEP adducts nor TLR agonists were able to induce angiogenesis in a tube formation assay. In vivo, treatment of animals with CEP-adducted protein had no effect on laser-induced choroidal neovascularization. Furthermore, in vivo inactivation of TLR2 by deficiency in Myeloid Differentiation factor 88 (Myd88) had no effect on abrasion-induced corneal neovascularization. Thus the CEP-TLR2 axis, which is implicated in other wound angiogenesis models, does not appear to play a pathological role in a corneal wound angiogenesis model. Collectively, our data do not support the mechanism of action of CEP adducts in TLR2-mediated angiogenesis proposed by others. PMID:25343517

  13. Lack of involvement of CEP adducts in TLR activation and in angiogenesis.

    Directory of Open Access Journals (Sweden)

    John Gounarides

    Full Text Available Proteins that are post-translationally adducted with 2-(ω-carboxyethylpyrrole (CEP have been proposed to play a pathogenic role in age-related macular degeneration, by inducing angiogenesis in a Toll Like Receptor 2 (TLR2-dependent manner. We have investigated the involvement of CEP adducts in angiogenesis and TLR activation, to assess the therapeutic potential of inhibiting CEP adducts and TLR2 for ocular angiogenesis. As tool reagents, several CEP-adducted proteins and peptides were synthetically generated by published methodology and adduction was confirmed by NMR and LC-MS/MS analyses. Structural studies showed significant changes in secondary structure in CEP-adducted proteins but not the untreated proteins. Similar structural changes were also observed in the treated unadducted proteins, which were treated by the same adduction method except for one critical step required to form the CEP group. Thus some structural changes were unrelated to CEP groups and were artificially induced by the synthesis method. In biological studies, the CEP-adducted proteins and peptides failed to activate TLR2 in cell-based assays and in an in vivo TLR2-mediated retinal leukocyte infiltration model. Neither CEP adducts nor TLR agonists were able to induce angiogenesis in a tube formation assay. In vivo, treatment of animals with CEP-adducted protein had no effect on laser-induced choroidal neovascularization. Furthermore, in vivo inactivation of TLR2 by deficiency in Myeloid Differentiation factor 88 (Myd88 had no effect on abrasion-induced corneal neovascularization. Thus the CEP-TLR2 axis, which is implicated in other wound angiogenesis models, does not appear to play a pathological role in a corneal wound angiogenesis model. Collectively, our data do not support the mechanism of action of CEP adducts in TLR2-mediated angiogenesis proposed by others.

  14. Fullerene–Carbene Lewis Acid–Base Adducts

    KAUST Repository

    Li, Huaping

    2011-08-17

    The reaction between a bulky N-heterocylic carbene (NHC) and C60 leads to the formation of a thermally stable zwitterionic Lewis acid-base adduct that is connected via a C-C single bond. Low-energy absorption bands with weak oscillator strengths similar to those of n-doped fullerenes were observed for the product, consistent with a net transfer of electron density to the C60 core. Corroborating information was obtained using UV photoelectron spectroscopy, which revealed that the adduct has an ionization potential ∼1.5 eV lower than that of C60. Density functional theory calculations showed that the C-C bond is polarized, with a total charge of +0.84e located on the NHC framework and -0.84e delocalized on the C 60 cage. The combination of reactivity, characterization, and theoretical studies demonstrates that fullerenes can behave as Lewis acids that react with C-based Lewis bases and that the overall process describes n-doping via C-C bond formation. © 2011 American Chemical Society.

  15. High-performance liquid chromatography for analysis of 32P-Postlabeled DNA adducts

    OpenAIRE

    Zeisig, Magnus

    1996-01-01

    High-Performance Liquid Chromatography for Analysis of 32P-Postlabeled DNA Adducts Magnus Zeisig Center for Nutrition and Toxicology, Department of Bioscience at Novum, Karolinska Institutet, Novum, S-141 57 Huddinge, SwedenThe formation of DNA adducts, i.e. the covalent binding of chemicals and chemical groups to DNA,isbelieved to be an important step in chemical carciwg...

  16. Yield of photo-adduct formation of LOV domains from Chlamydomonas reinhardtii by picosecond laser excitation

    International Nuclear Information System (INIS)

    The photo-excitation of flavin mononucleotide (FMN) in the wild-type light, oxygen and voltage sensitive (LOV) domains of the blue-light photoreceptors phototropin causes the formation of an intermediate flavin-C(4a)-cysteinyl adduct. The adduct formation due to picosecond laser pulse exaction (wavelength 400nm) is studied on wild-type LOV1 and LOV2 domains of the phototropin phot from Chlamydomonas reinhardtii. The efficiency of adduct formation is probed by detection of the fluorescence signals caused by time-separated picosecond excitation pulses since FMN is fluorescent and the formed adduct is non-fluorescent. Quantum yields of adduct formation of φAd∼0.06 are determined for excitation with intense single-pulses of energy densities, wL, comparable to or larger than the saturation energy density, wsat,S0, of ground-state population depletion. Under repetitive picosecond pulse excitation conditions the efficiency of adduct formation rises with decreasing picosecond pulse energy density and approaches for wLsat,S0 the continuous blue-light exposure quantum yields of adduct formation in the range from φAd=0.5-0.9. Picosecond laser pulse induced energy deposition in the LOV domains causing protein conformational changes is discussed as main origin of the intensity dependent reduction of the efficiency of adduct-formation

  17. Specific plant DNA adducts as molecular biomarkers of genotoxic atmospheric environments.

    Science.gov (United States)

    Weber-Lotfi, F; Obrecht-Pflumio, S; Guillemaut, P; Kleinpeter, J; Dietrich, A

    2005-03-01

    The general purpose of this study was to determine whether the formation of DNA addition products ('adducts') in plants could be a valuable biomarker of genotoxic air pollution. Plants from several species were exposed to ambient atmosphere at urban and suburban sites representative of different environmental conditions. The levels of NO2 and of the quantitatively major genotoxic air pollutants benzene, toluene, and xylene were monitored in parallel with plant exposure. DNA adducts were measured in bean (Phaseolus vulgaris), rye-grass (Lolium perenne), and tobacco (Nicotiana tabacum) seedlings by means of the [32P]-postlabeling method. Whereas, no correlation was found between the levels of the major genotoxic air pollutants and the total amounts of DNA adducts, individual analyses revealed site-specific and plant species-specific adduct responses, both at the qualitative and quantitative level. Among these, the amount of a specific rye-grass DNA adduct (rgs1) correlated with benzene/toluene/xylene levels above a threshold. For further characterization, rye-grass seedlings were treated in controlled conditions with benzene, toluene, xylene or their derivatives. On the other hand, in vitro DNA adduct formation assays were developed involving benzene, toluene, xylene, or their derivatives, and plant microsomes or purified peroxidase. Although in some cases, these approaches produced specific adduct responses, they failed to generate the rgs1 DNA adduct, which appeared to be characteristic for on-site test-plant exposure. Our studies have thus identified an interesting candidate for further analysis of environmental biomarkers of genotoxicity.

  18. Immunochemical detection of sulfur mustard adducts with keratins in the stratum corneum of human skin

    NARCIS (Netherlands)

    Schans, G.P. van der; Noort, D.; Mars-Groenendijk, R.H.; Fidder, A.; Chau, L.F.; Jong, L.P.A. de; Benschop, H.P.

    2002-01-01

    As part of a program to develop methods for diagnosis of exposure to chemical warfare agents, we developed immunochemical methods for detection of adducts of sulfur mustard to keratin in human skin. Three partial sequences of keratins containing glutamine or asparagine adducted with a 2-hydroxyethyl

  19. Resistance to Nucleotide Excision Repair of Bulky Guanine Adducts Opposite Abasic Sites in DNA Duplexes and Relationships between Structure and Function.

    Directory of Open Access Journals (Sweden)

    Zhi Liu

    Full Text Available The nucleotide excision repair of certain bulky DNA lesions is abrogated in some specific non-canonical DNA base sequence contexts, while the removal of the same lesions by the nucleotide excision repair mechanism is efficient in duplexes in which all base pairs are complementary. Here we show that the nucleotide excision repair activity in human cell extracts is moderate-to-high in the case of two stereoisomeric DNA lesions derived from the pro-carcinogen benzo[a]pyrene (cis- and trans-B[a]P-N2-dG adducts in a normal DNA duplex. By contrast, the nucleotide excision repair activity is completely abrogated when the canonical cytosine base opposite the B[a]P-dG adducts is replaced by an abasic site in duplex DNA. However, base excision repair of the abasic site persists. In order to understand the structural origins of these striking phenomena, we used NMR and molecular spectroscopy techniques to evaluate the conformational features of 11mer DNA duplexes containing these B[a]P-dG lesions opposite abasic sites. Our results show that in these duplexes containing the clustered lesions, both B[a]P-dG adducts adopt base-displaced intercalated conformations, with the B[a]P aromatic rings intercalated into the DNA helix. To explain the persistence of base excision repair in the face of the opposed bulky B[a]P ring system, molecular modeling results suggest how the APE1 base excision repair endonuclease, that excises abasic lesions, can bind productively even with the trans-B[a]P-dG positioned opposite the abasic site. We hypothesize that the nucleotide excision repair resistance is fostered by local B[a]P residue-DNA base stacking interactions at the abasic sites, that are facilitated by the absence of the cytosine partner base in the complementary strand. More broadly, this study sets the stage for elucidating the interplay between base excision and nucleotide excision repair in processing different types of clustered DNA lesions that are substrates of

  20. Liquid chromatography-thermospray mass spectrometry of DNA adducts formed with mitomycin C, porfiromycin and thiotepa.

    Science.gov (United States)

    Musser, S M; Pan, S S; Callery, P S

    1989-07-14

    High-performance liquid chromatography (HPLC) and thermospray mass spectrometry were combined for the analysis of DNA adducts formed from the interaction of the anticancer drugs mitomycin C, porfiromycin and thiotepa with calf thymus DNA. The adducts formed from reaction of mitomycin C and porfiromycin with DNA were separated from unmodified nucleosides by HPLC on a C18 column and identified by thermospray mass spectrometry. Thiotepa DNA adducts readily depurinated from DNA and were chromatographed and identified by thermospray liquid chromatography-mass spectrometry as the modified bases without the ribose moiety attached. The utility of thermospray mass spectrometry for the identification of microgram quantities of nucleoside adducts and depurinated base adducts of these anticancer drugs was demonstrated. PMID:2504760

  1. DNA adducts in marine mussel and fresh water fishes living in polluted and unpolluted environments

    International Nuclear Information System (INIS)

    32P-postlabeling analysis of DNA adducts in the digestive gland of marine mussel Mytilus galloprovincialis from polluted and unpolluted sites near Rovinj, Northern Adriatic, revealed that majority of adducts are caused by natural environmental factors rather than by man-made chemicals. The only pollutant-specific adducts were observed in a mussel exposed to seawater experimentally polluted with aminofluorene, and in a population of mussel living at a site heavily polluted with a waste waters of an oil refinery. Fresh water fish species Leuciscus cephalus, Barbus barbus, Abramis brama and Rutilus pigus virgo living in a polluted Sava River, Yugoslavia, or in its unpolluted tributary Korana River, have induced in their livers qualitatively identical and quantitatively similar DNA adducts. These DNA adducts had a species-specific patterns and their appearance was seasonally-dependent

  2. Exposure of bus and taxi drivers to urban air pollutants as measured by DNA and protein adducts

    DEFF Research Database (Denmark)

    Hemminki, K.; Zhang, L.F.; Krüger, J.;

    1994-01-01

    Urinary 1-hydroxypyrene, lymphocyte DNA adducts, serum protein-bound PAH and hemoglobin-bound alkene adducts were analysed from 4 groups of non-smoking men: urban and suburban bus drivers, taxi drivers and suburban controls. The only differences between the groups were in DNA adducts between subu...

  3. Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG uptake is highest in hypoxic tumor regions.

    Directory of Open Access Journals (Sweden)

    Erica C Nakajima

    Full Text Available Intratumoral metabolic heterogeneity may increase the likelihood of treatment failure due to the presence of a subset of resistant tumor cells. Using a head and neck squamous cell carcinoma (HNSCC xenograft model and a real-time fluorescence imaging approach, we tested the hypothesis that tumors are metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose uptake within the tumor.Cal33 cells were grown as xenograft tumors (n = 16 in nude mice after identification of this cell line's metabolic response to hypoxia. Tumor uptake of fluorescent markers identifying hypoxia, glucose import, or vascularity was imaged simultaneously using fluorescent molecular tomography. The variability of intratumoral 2-deoxyglucose (IR800-2-DG concentration was used to assess tumor metabolic heterogeneity, which was further investigated using immunohistochemistry for expression of key metabolic enzymes. HNSCC tumors in patients were assessed for intratumoral variability of (18F-fluorodeoxyglucose ((18F-FDG uptake in clinical PET scans.IR800-2-DG uptake in hypoxic regions of Cal33 tumors was 2.04 times higher compared to the whole tumor (p = 0.0001. IR800-2-DG uptake in tumors containing hypoxic regions was more heterogeneous as compared to tumors lacking a hypoxic signal. Immunohistochemistry staining for HIF-1α, carbonic anhydrase 9, and ATP synthase subunit 5β confirmed xenograft metabolic heterogeneity. We detected heterogeneous (18F-FDG uptake within patient HNSCC tumors, and the degree of heterogeneity varied amongst tumors.Hypoxia is associated with increased intratumoral metabolic heterogeneity. (18F-FDG PET scans may be used to stratify patients according to the metabolic heterogeneity within their tumors, which could be an indicator of prognosis.

  4. 2-DG induced modulation of chromosomal DNA profile, cell survival, mutagenesis and gene conversion in x-irradiated yeast

    International Nuclear Information System (INIS)

    Effect of post-irradiation modulation in presence of 2-deoxy-D-glucose and yeast extract, on chromosomal DNA profile, cell survival, reverse mutation (ILV+) and gene conversion (TRP+), were studied in x-irradiated stationary phase yeast cells (diploid strain D7 of Saccharomyces cerevisiae). The damage and repair in chromosomal DNA bands, resolved by using contour clamped homogeneous electric pulsed-field gel electrophoresis (PFGE) technique, was estimated by calculating intensity ratio, Ρn (Ρn=In/It; where In is the intensity of nth band in a lane and It is the sum of intensities of all bands and the well in the lane). The data indicate linear correlation between relative compactness (τ) of a chromosome [chromosome size (Kb)/length of synaptonemal complex (μm)[ and DNA damage and repair. The chromosome repair kinetics were biphasic, showing initial decrease followed by an increase in Ρn. Variations were observed among different chromosomes with respect to DNA damage, repair and post-irradiation repair modulation. 2-DG inhibited both components of chromosomal DNA repair and also repair of potentially lethal damage but enhanced frequencies of mutants. Relatively the effects on revertants were greater in cells irradiated with lower doses (50 Gy) of x-rays and post-irradiation incubation in presence of phosphate buffer having 2-DG (50 mM) and glucose (10 mM). Yeast extract increased frequencies of revertants and convertants thus promoting error-prone DNA repair. Yeast extract in combination with 2-DG showed complex effects on chromosomal DNA repair and enhanced mutagenesis further. (author). 35 refs., 8 figs., 1 tab

  5. Roles of DgBRC1 in regulation of lateral branching in chrysanthemum (Dendranthema ×grandiflora cv. Jinba).

    Science.gov (United States)

    Chen, Xiaoli; Zhou, Xiaoyang; Xi, Lin; Li, Junxiang; Zhao, Ruiyan; Ma, Nan; Zhao, Liangjun

    2013-01-01

    The diverse plasticity of plant architecture is largely determined by shoot branching. Shoot branching is an event regulated by multiple environmental, developmental and hormonal stimuli through triggering lateral bud response. After perceiving these signals, the lateral buds will respond and make a decision on whether to grow out. TCP transcriptional factors, BRC1/TB1/FC1, were previously proven to be involved in local inhibition of shoot branching in Arabidopsis, pea, tomato, maize and rice. To investigate the function of BRC1, we isolated the BRC1 homolog from chrysanthemum. There were two transcripts of DgBRC1 coming from two alleles in one locus, both of which complemented the multiple branches phenotype of Arabidopsis brc1-1, indicating that both are functionally conserved. DgBRC1 was mainly expressed in dormant axillary buds, and down-regulated at the bud activation stage, and up-regulated by higher planting densities. DgBRC1 transcripts could respond to apical auxin supply and polar auxin transport. Moreover, we found that the acropetal cytokinin stream promoted branch outgrowth whether or not apical auxin was present. Basipetal cytokinin promoted outgrowth of branches in the absence of apical auxin, while strengthening the inhibitory effects on lower buds in the presence of apical auxin. The influence of auxin and strigolactons (SLs) on the production of cytokinin was investigated, we found that auxin locally down-regulated biosynthesis of cytokinin in nodes, SLs also down-regulated the biosynthesis of cytokinin, the interactions among these phytohormones need further investigation. PMID:23613914

  6. Double-grid finite-difference frequency-domain (DG-FDFD) method for scattering from chiral objects

    CERN Document Server

    Alkan, Erdogan; Elsherbeni, Atef

    2013-01-01

    This book presents the application of the overlapping grids approach to solve chiral material problems using the FDFD method. Due to the two grids being used in the technique, we will name this method as Double-Grid Finite Difference Frequency-Domain (DG-FDFD) method. As a result of this new approach the electric and magnetic field components are defined at every node in the computation space. Thus, there is no need to perform averaging during the calculations as in the aforementioned FDFD technique [16]. We formulate general 3D frequency-domain numerical methods based on double-grid

  7. Structural phase transitions and adduct release in calcium borohydride

    Energy Technology Data Exchange (ETDEWEB)

    Paolone, A.; Palumbo, O.; Rispoli, P.; Miriametro, A.; Cantelli, R.; Luedtke, A.; Rönnebro, E.; Chandra, D.

    2011-09-01

    Ca(BH4)2 compounds were investigated above room temperature by anelastic spectroscopy (AS) and concomitant measurements of thermogravimetry and mass spectrometry (TGA/MS). Both AS and TGA/MS indicate that even after a thermal treatment at 125 °C for 20 h, a non-negligible residual of THF adduct is still present in the sample, which can be removed on a subsequent thermal treatment at temperatures lower than 250 °C. Above 250 °C dehydrogenation takes place. Moreover, AS sensitively detects the occurrence of the α → α’ structural phase transition around 180 °C, and the α’ → β transformation, which is completed around 330 °C. Finally, we also show that both transitions are irreversible and are not accompanied by a latent heat.

  8. A Design of Intelligent Vehicle's Control System Based on MC9S12DG128%基于MC9S12DG128的智能车的控制系统的设计

    Institute of Scientific and Technical Information of China (English)

    周杰; 詹灯辉

    2011-01-01

    This article introduces one kind intelligent vehicle control system based on the photoelectric sensor and the real-time way recognition algorithm. This system takes 16 micro processing chip MC9S12DG128 as a core. It realizes the control intelligence vehicle to follow in the mark process independently sensor signal gathering and the real-time processing, the motor-driven, changes functions servo control. In the article, it realizes in view of the design in essential electric circuit and the algorithm has carried on the detailed elaboration, and gives the experiment to debug the result.%本文介绍了一种基于光电传感器及实时路径识别算法的智能车控制系统,该系统以16位微处理芯片MC9S12DG128为核心,实现了控制智能车自主循迹过程中的传感器信号采集及实时处理、电机驱动、转向舵机控制等功能,文中针对设计中的关键电路及算法实现进行了详细阐述,并给出了实验调试结果.

  9. 基于MC9S12DG256的汽车ABS液压控制系统设计%Design of vehicle ABS hydraulic control system based on Mcgs12DG256

    Institute of Scientific and Technical Information of China (English)

    张搏; 安悦

    2012-01-01

    Through the deep analysis of the structure principle and the working characteristics of vehicle ABS system, design a vehicle ABS hydraulic control system based on the microcontroller Freescale company production MC9S12DG256, based on the adjustment of brake pressure control, makes the braking process more smoothly, to improve ABS system hydraulic brake precision and reliability, has very extensive application prospect.%通过对汽车ABS系统的结构原理及工作特点的深入分析,设计了基于Freescale公司生产的MC9S12DG256微处理器的汽车ABS液压控制系统,通过对制动压力的调节控制,使得制动过程更加的平稳,提高了ABS系统液压制动精度和可靠性,具有非常广泛的应用前景。

  10. Hemoglobin adducts of N-substituted aryl compounds in exposure control and risk assessment.

    Science.gov (United States)

    Neumann, H G; Birner, G; Kowallik, P; Schütze, D; Zwirner-Baier, I

    1993-03-01

    Arylamines, nitroarenes, and azo dyes yield a common type of metabolite, the nitroarene, which produces a hydrolyzable adduct with protein and is closely related to the critical, ultimate toxic and genotoxic metabolite. The target dose as measured by hemoglobin adducts in erythrocytes reflects not only the actual uptake from the environment but also an individual's capacity for metabolic activation and is therefore an improved dosimeter for human exposure. The usefulness of hemoglobin adducts in molecular epidemiology is now widely recognized. With regard to risk assessment, many questions need to be answered. The described experiments in rats address some of these questions. The relationship between binding to hemoglobin in erythrocytes and to proteins in plasma has been found to vary considerably for a number of diamines. The fraction of hydrolyzable adducts out of the total protein adducts formed also varies in both compartments. This indicates that the kind of circulating metabolites and their availability in different compartments is compound specific. This has to do with the complex pattern of competing metabolic pathways, and the role of N-acetylation and deacetylation is emphasized. An example of nonlinear dose dependence adds to the complexity. Analysis of hemoglobin adducts reveals interesting insights into prevailing pathways, which not only apply to the chemical, but may also be useful to assess an individual's metabolic properties. In addition, it is demonstrated that the greater part of erythrocytes and benzidine-hemoglobin adducts are eliminated randomly in rats, i.e., following first-order kinetics.

  11. Inhibition of nitrobenzene-induced DNA and hemoglobin adductions by dietary constituents

    Energy Technology Data Exchange (ETDEWEB)

    Li Hongli; Cheng Yan; Wang Haifang; Sun Hongfang; Liu Yuanfang E-mail: yliu@pku.edu.cn; Liu Kexin; Peng Shixiang

    2003-03-01

    Nitrobenzene (NB), a widely used industrial chemical, is a likely human carcinogen. Many dietary constituents can suppress the DNA-adduction, acting as the inhibitors of cancer. In this study, we investigated the inhibitory effects of vitamin C (VC), vitamin E (VE), tea polyphenols (TP), garlic squeeze, curcumin, and grapestone extract on NB-DNA and NB-hemoglobin (Hb) adductions in mice using an ultrasensitive method of accelerator mass spectrometry (AMS) with {sup 14}C-labelled nitrobenzene. All of these dietary constituents showed their inhibitory effects on DNA or Hb adduction. VC, VE, TP and grapestone extract could efficaciously inhibit the adductions by 33-50%, and all of these six agents could inhibit Hb adduction by 30-64%. We also investigated resveratrol, curcumin, VC and VE as inhibitors of NB-DNA adduction in vitro using liquid scintillation counting technique. These agents in the presence of NADPH and S9 components also pronouncedly blocked DNA adduction in a dose-dependent profile. Our study suggests that these seven constituents may interrupt the process of NB-induced chemical carcinogenesis.

  12. Detection and characterization of human serum antibodies to polycyclic aromatic hydrocarbon diol-epoxide DNA adducts

    Energy Technology Data Exchange (ETDEWEB)

    Newman, M.J.; Light, B.A.; Weston, A.; Tollurud, D.; Clark, J.L.; Mann, D.L.; Blackmon, J.P.; Harris, C.C.

    1988-07-01

    The presence of serum antibodies to the diol-epoxide DNA adducts of representative polycyclic aromatic hydrocarbons (PAH), chrysene, benz(a)anthracene and benzo(a)pyrene, was determined by ELISA using serum samples obtained from normal healthy individuals. Antibodies that reacted against PAH adducted-DNA, but not against PAH-adducted protein, were found in the serum of approximately 40% of the test individuals. Specificity analysis of the antibodies demonstrated that serological cross-reactions between the benzo(a)pyrene and the chrysene diol-epoxide adducts were present. Similar cross-reactivity between the benz(a)anthracene and the chrysene adducts was observed. Sera containing antibodies that were apparently specific for each of the three PAH-DNA adducts were also identified. The presence of antibodies to PAH-DNA adducts indicates both past exposure to these carcinogenic PAH and their metabolic activation to the DNA damaging metabolites. These antibodies may prove to be useful in both retrospective and prospective epidemiological studies of various diseases associated with PAH exposure.

  13. Use of the /sup 32/P-postlabeling method to detect DNA adducts of 2-amino-3-methylimidazolo(4,5-f)quinoline (IQ) in monkeys fed IQ: identification of the N-(deoxyguanosin-8-yl)-IQ adduct

    Energy Technology Data Exchange (ETDEWEB)

    Snyderwine, E.G.; Yamashita, K.; Adamson, R.H.; Sato, S.; Nagao, M.; Sugimura, T.; Thorgeirsson, S.S.

    1988-10-01

    Eight DNA adducts of 2-amino-3-methylimidazolo(4,5-f)-quinoline (IQ) were found by the standard /sup 32/P-postlabeling method in livers from male Cynomolgus monkeys fed IQ (5 days/week, 3 weeks, 20 mg/kg, nasal-gastric intubation). The IQ-DNA adduct fingerprints observed in monkeys were identical to those observed in rats that received IQ (0.03%) in the diet for 2 weeks. The C8-guanine-IQ adduct was identified by comigration with the synthetic 3',5'-bisphosphate derivative of N(-deoxyguanosin-8-yl)-IQ. DNA modified in vitro with N-hydroxy-IQ showed seven adducts, including the C8-guanine-IQ adduct, that were identical to those found in monkeys and rats. Thus it appears that N-hydroxy-IQ, the reactive metabolite of IQ, was responsible for all adducts found in vivo, except one. In order to detect adducts in other organs that were present at lower levels, the intensification (ATP-deficient) method for /sup 32/P-postlabeling was used. Five of the adducts detected under standard conditions, including the C8-guanine-IQ adduct, were also detected under intensification conditions. The total level of DNA-IQ adducts was highest in the liver, followed by the kidney, colon and stomach, and bladder. The adduct patterns were identical in all organs examined. The results indicate that IQ is potentially genotoxic in primates and therefore a likely human carcinogen.

  14. 32P analysis of DNA adducts in tissues of benzene-treated rats

    International Nuclear Information System (INIS)

    Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, liver, and mammary gland of Sprague-Dawley rats following chronic, high-dose administration of benzene. The carcinogenic activity of benzene is thought to be caused by activation to toxic metabolites that can interact with DNA, forming covalent adducts. A nuclease P1-enhanced 32P-postlabeling assay, having a sensitivity limit of 1 adduct in 10(9-10) DNA nucleotides, was found suitable for measuring aromatic DNA adducts derived in vitro from catechol, benzenetriol (BT), phenol, hydroquinone (HQ), and benzoquinone (BQ), potential metabolites of benzene. When DNA specimens isolated from tissues of female Sprague-Dawley rats at 24 hr after an oral gavage dose of 200 to 500 mg/kg, 5 days/week, in olive oil (3 mL/kg) for 1 day, 1 week, 5 weeks, and 10 weeks were analyzed by the 32P-postlabeling procedure, no aromatic adducts were detected unequivocally with DNA samples of liver, kidney, bone marrow, and mammary gland. With Zymbal gland DNA, three weak spots at levels totaling four lesions per 10(9) DNA nucleotides were seen only after 10 weeks of treatment, and these adducts did not correspond chromatographically to major adducts in vitro from the above specified compounds. Consequently, this finding requires confirmatory experiments. This distinct adduct pattern may relate to tumor induction in this organ following benzene administration. Our results also indicate that DNA adducts derived from catechol, BT, phenol, HQ, and BQ are either not formed in vivo with benzene or formed at levels below the detection limit of 1 adduct per 10(9-10) DNA nucleotides

  15. Determinants of 4-aminobiphenyl-DNA adducts in bladder cancer biopsies.

    Science.gov (United States)

    Airoldi, Luisa; Orsi, Federica; Magagnotti, Cinzia; Coda, Renato; Randone, Donato; Casetta, Giovanni; Peluso, Marco; Hautefeuille, Agnes; Malaveille, Christian; Vineis, Paolo

    2002-05-01

    Exposure to 4-aminobiphenyl (4-ABP) is an important determinant of urinary bladder cancer in humans. We have analyzed by gas chromatography-mass spectrometry the DNA adducts of 4-ABP in 75 bladder cancer biopsies. The purpose was to understand whether smoking, N-acetyltransferase 2 (NAT2) polymorphism, diet or tumor grade were determinants of 4-ABP-DNA levels. 4-ABP-DNA adducts were above the detection limit of 0.1 fmol/microg DNA for 37/75 patients. Overall the level of adducts was 2.7 +/- 0.7 (mean +/- SE) fmol/microg DNA (86 +/- 22 adducts/10(8) normal nucleotides, mean +/- SE). A strong association with grade was observed. In the group of patients with detectable 4-ABP-DNA adducts the odds ratio for having a tumor grade of 2 or 3 was respectively 4.3 (95% CI 0.8-21.9) and 6 (1.3-27.5), compared with grade 1. A non-statistically significant association was found between adduct levels and the deduced slow acetylator phenotype in grades 2 and 3. The intake of fruit and vegetables produced a lower frequency of detectable adducts, though the association was not statistically significant. Detectable 4-ABP-DNA adducts were clearly associated with current smoking in higher tumor grades (grade 3 versus grades 1 + 2, odds ratios 10.4; 95% CI 1.7-63.1). Overall, our findings indicate that higher levels of DNA adducts characterize more invasive tumors (higher tumor grades). This seems to be facilitated by smoking and contrasted by the intake of fruit and vegetables. PMID:12016161

  16. Kinematics of the Outflow From The Young Star DG Tau B: Rotation in the vicinities of an optical jet

    CERN Document Server

    Zapata, Luis A; Rodriguez, Luis F; Ho, Paul T P; Loinard, Laurent; Fernandez-Lopez, Manuel; Tafoya, Daniel

    2014-01-01

    We present $^{12}$CO(2-1) line and 1300 $\\mu$m continuum observations made with the Submillimeter Array (SMA) of the young star DG Tau B. We find, in the continuum observations, emission arising from the circumstellar disk surrounding DG Tau B. The $^{12}$CO(2-1) line observations, on the other hand, revealed emission associated with the disk and the asymmetric outflow related with this source. Velocity asymmetries about the flow axis are found over the entire length of the flow. The amplitude of the velocity differences is of the order of 1 -- 2 km s$^{-1}$ over distances of about 300 -- 400 AU. We interpret them as a result of outflow rotation. The sense of the outflow and disk rotation is the same. Infalling gas from a rotating molecular core cannot explain the observed velocity gradient within the flow. Magneto-centrifugal disk winds or photoevaporated disk winds can produce the observed rotational speeds if they are ejected from a keplerian disk at radii of several tens of AU. Nevertheless, these slow wi...

  17. HST/STIS spectroscopy of the optical outflow from DG Tau structure and kinematics on sub-arcsecond scales

    CERN Document Server

    Bacciotti, F; Ray, T P; Eislöffel, J; Solf, J; Camezind, M; Bacciotti, Francesca; Mundt, Reinhard; Ray, Thomas P.; Eisloeffel, Jochen; Solf, Josef; Camezind, Max

    2000-01-01

    We have carried out a spatio-kinematic study of the outflow from the classical T Tauri star DG Tau using the Space Telescope Imaging Spectrograph (STIS) on board the Hubble Space Telescope (HST). A series of seven spatially offset long-slit spectra spaced by 0.07'' were obtained along the axis of the outflow to build up a 3-D intensity-velocity ``cube'' in various forbidden emission lines (FELs) and Ha. Here we present high spatial resolution synthetic line images close to the star in distinct radial velocity intervals (from ~ +50 km/s to ~ -450 km/s in four bins, each ~ 125 km/s wide). The lowest velocity emission is also examined in finer detail (from +60 km/s to -70 km/s in five bins ~ 25 km/s wide). We have found that the highest velocity and most highly collimated component, i.e. the jet, can be traced from DG Tau to a distance D ~ 0.7''. The jet is on the axis of a pear-shaped limb-brightened bubble which extends between 0.4'' and 1.5'' from the source and which we interpret as a bow shock. Other conden...

  18. Physical properties of the jet from DG Tauri on sub-arcsecond scales with HST/STIS

    CERN Document Server

    Maurri, L; Podio, L; Eislöffel, J; Ray, T P; Mundt, R; Locatelli, U; Coffey, D

    2014-01-01

    We derive the physical properties at the base of the jet from DG Tau both along and across the flow and as a function of velocity. We analysed seven optical spectra of the DG Tau jet, taken with the Hubble Space Telescope Imaging Spectrograph. The spectra were obtained by placing a long-slit parallel to the jet axis and stepping it across the jet width. The resulting position-velocity diagrams in optical forbidden emission lines allowed access to plasma conditions via calculation of emission line ratios. We find at the base of the jet high electron density, $n_e \\sim $ 10$^5$, and very low ionisation, $x_e \\sim 0.02-0.05$, which combine to give a total density up to $n_H \\sim $ 3 10$^6$. This analysis confirms previous reports of variations in plasma parameters along the jet, (i.e. decrease in density by several orders of magnitude, increase of $x_e$ from 0.05 to a plateau at 0.7 downstream at 2$''$ from the star). Furthermore, a spatial coincidence is revealed between sharp gradients in the total density and...

  19. Flicker and thermal noise in an n-channel underlap DG FinFET in a weak inversion region

    Institute of Scientific and Technical Information of China (English)

    Sudhansu Kumar Pati; Hemant Pardeshi; Godwin Raj; N Mohankumar; Chandan Kumar Sarkar

    2013-01-01

    We propose an analytical model for drain current and inversion charge in the subthreshold region for an underlap DG FinFET by using the minimum channel potential method,i.e.,the virtual source.The flicker and thermal noise spectral density models are also developed using these charge and current models expression.The model is validated with already published experimental results of flicker noise for DG FinFETs.For an ultrathin body,the degradation of effective mobility and variation of the scattering parameter are considered.The effect of device parameters like gate length Lg and underlap length Lun on both flicker and thermal noise spectral densities are also analyzed.Increasing Lg and Lun,increases the effective gate length,which reduces drain current,resulting in decreased flicker and thermal noise density.A decrease of flicker noise is observed for an increase of frequency,which indicates that the device can be used for wide range of frequency applications.

  20. Moessbauer studies of mercury(II) salt adducts of (2)ferrocenophane derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masanobu; Ichikawa, Hajime; Motoyama, Izumi; Sano, Hirotoshi (Tokyo Metropolitan Univ. (Japan). Faculty of Science)

    1983-11-01

    Various adducts of mercuric salts with (2)ferrocenophane and 1,1,2,2-tetramethyl(2)ferrocenophane, were prepared by treating HgX/sub 2/ (X=Cl/sup -/, I/sup -/, CN/sup -/) with the (2)ferrocenophane derivatives in ether. The adducts were studied by Moessbauer spectroscopy and other physicochemical measurements. Anomalously large quadrupole splitting values of the adducts (about 3.10-3.30 mms/sup -1/ at 78 K) suggest the presence of a strong direct interaction between the Fe and Hg atoms.

  1. Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53

    Science.gov (United States)

    Denissenko, Mikhail F.; Pao, Annie; Tang, Moon-Shong; Pfeifer, Gerd P.

    1996-10-01

    Cigarette smoke carcinogens such as benzo[a]pyrene are implicated in the development of lung cancer. The distribution of benzo[a]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated HeLa cells and bronchial epithelial cells was mapped at nucleotide resolution. Strong and selective adduct formation occurred at guanine positions in codons 157, 248, and 273. These same positions are the major mutational hotspots in human lung cancers. Thus, targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.

  2. Analysis of hemoglobin adducts from acrylamide, glycidamide, and ethylene oxide in paired mother/cord blood samples from Denmark

    DEFF Research Database (Denmark)

    von Stedingk, Hans; Vikström, Anna C; Rydberg, Per;

    2011-01-01

    for analysis of Hb adducts by liquid chromatography-mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide.......20-0.73) for glycidamide, and 0.43 (range 0.17-1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38-0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together...... of the measured adducts in cord blood with gestational age was observed, which may reflect the gestational age-related change of the cord blood Hb composition toward a higher content of adult Hb. The results suggest that the Hb adduct levels measured in cord blood reflect the exposure to the fetus during...

  3. The inverse agonist DG172 triggers a PPARβ/δ-independent myeloid lineage shift and promotes GM-CSF/IL-4-induced dendritic cell differentiation.

    Science.gov (United States)

    Lieber, Sonja; Scheer, Frithjof; Finkernagel, Florian; Meissner, Wolfgang; Giehl, Gavin; Brendel, Cornelia; Diederich, Wibke E; Müller-Brüsselbach, Sabine; Müller, Rolf

    2015-02-01

    The stilbene derivative (Z)-2-(2-bromophenyl)-3-{[4-(1-methylpiperazine)amino]phenyl}acrylonitrile (DG172) was developed as a highly selective inhibitory peroxisome proliferator-activated receptor (PPAR)β/δ ligand. Here, we describe a novel PPARβ/δ-independent, yet highly specific, effect of DG172 on the differentiation of bone marrow cells (BMCs). DG172 strongly augmented granulocyte-macrophage-colony-stimulating factor (GM-CSF)-induced differentiation of primary BMCs from Ppard null mice into two specific populations, characterized as mature (CD11c(hi)MHCII(hi)) and immature (CD11c(hi)MHCII(lo)) dendritic cells (DCs). IL-4 synergized with DG172 to shift the differentiation from MHCII(lo) cells to mature DCs in vitro. The promotion of DC differentiation occurred at the expense of differentiation to granulocytic Gr1(+)Ly6B(+) cells. In agreement with these findings, transcriptome analyses showed a strong DG172-mediated repression of genes encoding neutrophilic markers in both differentiating wild-type and Ppard null cells, while macrophage/DC marker genes were up-regulated. DG172 also inhibited the expression of transcription factors driving granulocytic differentiation (Cebpe, Gfi1, and Klf5), and increased the levels of transcription factors promoting macrophage/DC differentiation (Irf4, Irf8, Spib, and Spic). DG172 exerted these effects only at an early stage of BMC differentiation induced by GM-CSF, did not affect macrophage-colony-stimulating factor-triggered differentiation to macrophages and had no detectable PPARβ/δ-independent effect on other cell types tested. Structure-function analyses demonstrated that the 4-methylpiperazine moiety in DG172 is required for its effect on DC differentiation, but is dispensable for PPARβ/δ binding. Based on these data we developed a new compound, (Z)-2-(4-chlorophenyl)-3-[4-(4-methylpiperazine-1-yl)phenyl]acrylonitrile (DG228), which enhances DC differentiation in the absence of significant PPARβ/δ binding. PMID

  4. Second vowel formant relationship to adduction: A preliminary study

    Science.gov (United States)

    Hanrahan, Kevin G.

    The relationship between the vocal tract and the larynx in the formation of vowels has been debated for decades. Vowels were first thought to have been formed in the larynx; then later it was believed that they were formed solely in the vocal tract. In the 1960s Fant formalized this belief into the Source-Filter Theory of Vowel Formation. The theory was interpreted by voice teachers to mean that the larynx had very little to do with the formation of vowels, and this interpretation has dominated voice teaching for decades. Recent research, however, is now suggesting that the larynx and the vocal tract are interactive with each other, meaning that a change of muscular function in the larynx will create a change of resonator function in the vocal tract, and vice versa. This conclusion is drawn mainly on the work of Titze, Story, Laukkanen, et.al. They have found that a relationship exists between laryngeal function and the first vowel formant (F1). When examining research on the second vowel formant (F2), this author discovered that there may be a relationship between F2 and adduction. Therefore, based on present evidence, it was hypothesized that an elevated frequency of F2 corresponded to an increase in adduction. The hypothesis was examined by comparing the resonance output and glottal closure between vowels where F2 was elevated and vowels without modification of F2. Subjects were asked to sing [i], [a], and [u] at a medium dynamic level on D4, G#4, and D5 for the female subjects and an octave below for the male subjects, once using a "generic" version of the vowel, meaning what they considered a "nice, easy, and generic" version of the vowel to be, and then again modifying the vowel to increase the frequency of the upper harmonics. Electroglottogram, pitch, intensity, and formant data were collected and compared. An increase in the frequency of F2 corresponded to an increase in the Closed Quotient (CQ), the length of time the vocal folds are closed, in a few

  5. Recent progress in quantitative analysis of DNA adducts of nephrotoxin aristolochic acid

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Aristolochic acid (AA), a mixture of structure-related nitrophenanthrene carboxylic acid derivatives derived from Aristolochia spp, is associated with nephrotoxin and carcinogen. AA-DNA adducts induced by reductive metabolic activation of AA were detected in tissues of animals and in patients exposed to AA. The DNA adducts were generally used as biomarkers in toxicological study of AA. In this short review, quantitative analysis of AA-DNA adducts in various in vitro and in vivo systems by using 32P-postlabelling assay, HPLC-UV, HPLC-radiation monitor, HPLC-FLD, HPLC-ESI/MS and UPLC-MS/MS methods is discussed. The distribution of AA-DNA adducts in various tissues is also summarized.

  6. Glottal configuration, acoustic, and aerodynamic changes induced by variation in suture direction in arytenoid adduction procedures.

    Science.gov (United States)

    Inagi, Katsuhide; Connor, Nadine P; Suzuki, Tatsutoshi; Ford, Charles N; Bless, Diane M; Nakajima, Masami

    2002-10-01

    Arytenoid adduction is a phonosurgical procedure in which the arytenoid cartilages are approximated to reduce posterior glottal gap size and improve voice. Voice outcomes following arytenoid adduction are not always optimal. The goal of this study was to systematically vary suture direction and force of pull on the arytenoid cartilages in a human excised laryngeal model to determine the optimal combination of factors for reducing glottal gap and improving voice. Several factors demonstrated significant effects. Changes in suture direction and force of pull affected glottal configuration in both the horizontal and vertical planes. Increased force of pull on the muscular process resulted in increased adduction of the vocal process for all suture directions. Changes in suture direction and force of pull also affected acoustic and aerodynamic measures of induced voice. Therefore, voice outcomes can be optimized with arytenoid adduction if the vocal fold plane is accurately adjusted.

  7. 4-Aminobiphenyl-DNA adducts and p53 mutations in bladder cancer.

    Science.gov (United States)

    Martone, T; Airoldi, L; Magagnotti, C; Coda, R; Randone, D; Malaveille, C; Avanzi, G; Merletti, F; Hautefeuille, A; Vineis, P

    1998-02-01

    Epidemiologic studies have suggested that smokers of air-cured tobacco (rich in arylamines) are at higher risk of bladder cancer than smokers of flue-cured tobacco. The risk has been shown to be modulated by the N-acetyltransferase genotype. We analyzed the biopsies of 45 patients with bladder cancer. p53 mutations were sought by direct sequencing, and 4-aminobiphenyl-DNA adducts were measured by negative ion gas chromatography-mass spectrometry. 4-Aminobiphenyl-DNA adducts were higher in smokers of air-cured tobacco and in current smokers, but no relationship with the number of cigarettes smoked was found. Adducts were higher in more advanced histologic grades of tumors. No pattern was evident for p53 mutations. Seven of 9 mutations occurred in grade 3 tumors. No association was found between 4-ABP adducts and GSTM1 or NAT2 genetic polymorphisms. PMID:9466649

  8. Methods for synthesizing alane without the formation of adducts and free of halides

    Science.gov (United States)

    Zidan, Ragaiy; Knight, Douglas A; Dinh, Long V

    2013-02-19

    A process is provided to synthesize an alane without the formation of alane adducts as a precursor. The resulting product is a crystallized .alpha.-alane and is a highly stable product and is free of halides.

  9. NEW THIO S2- ADDUCTS WITH ANTIMONY (III AND V HALIDE: SYNTHESIS AND INFRARED STUDY

    Directory of Open Access Journals (Sweden)

    HASSAN ALLOUCH

    2013-12-01

    Full Text Available Five new S2- adducts with SbIII and SbV halides have been synthesized and studied by infrared. Discrete structures have been suggested, the environment around the antimony being tetrahedral, trigonal bipyramidal or octahedral.

  10. DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis

    DEFF Research Database (Denmark)

    Veglia, Fabrizio; Loft, Steffen; Matullo, Giuseppe;

    2008-01-01

    Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk...... in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies....... In the pooled analysis, a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% confidence interval 1-28%; using the weighted mean difference method, 0.15 SD, units higher adducts in cases than in controls...

  11. Effects of Metal Ion Adduction on the Gas-Phase Conformations of Protein Ions

    OpenAIRE

    Flick, Tawnya G.; Merenbloom, Samuel I.; Williams, Evan R.

    2013-01-01

    Changes in protein ion conformation as a result of nonspecific adduction of metal ions to the protein during electrospray ionization (ESI) from aqueous solutions were investigated using traveling wave ion mobility spectrometry (TWIMS). For all proteins examined, protein cations (and in most cases anions) with nonspecific metal ion adducts are more compact than the fully protonated (or deprotonated) ions with the same charge state. Compaction of protein cations upon nonspecific metal ion bindi...

  12. Determinants of the variability of aflatoxin-albumin adduct levels in Ghanaians.

    Science.gov (United States)

    Dash, B; Afriyie-Gyawu, E; Huebner, H J; Porter, W; Wang, J S; Jolly, P E; Phillips, T D

    2007-01-01

    Hepatocellular carcinoma (HCC) is a multifactorial disease with various host and environmental factors involved in its etiology. Of these, aflatoxin exposure has been established as an important risk factor in the development of HCC; the presence of aflatoxin-albumin (AA) adducts in the blood serves as a valuable biomarker of human exposure. In this study, the relationship between a variety of different HCC host factors and the incidence of AA adduct levels was examined in a Ghanaian population at high risk for HCC. These factors included age, gender, hepatitis virus B (HVB) and hepatitis C virus (HCV) status, and genetic polymorphisms in both microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GSTs). Blood samples were analyzed for AA adducts and HBV and HCV status. GSTM1 and GSTT1 deletion polymorphisms and mEH exon 3 and exon 4 single-nucleotide polymorphisms (SNPs) were determined from urine samples. In univariate analysis, age, HBV and HVC status, and GSTT1 and mEH exon 3 genotypes were not associated with AA adduct levels. However, mean adduct levels were significantly higher in both females and individuals typed heterozygous for mEH exon 4 (vs. wild types). Stratification analysis also showed that gender along with mEH exon 4 genotype and HBV status had a significant effect on adduct levels. Both females typed HBsAg+ and males with mEH exon 4 heterozygote genotypes showed significantly higher adduct levels as compared to the HBsAg- and wild types, respectively. Understanding the relationships between these host factors and the variability in aflatoxin-adduct levels may help in identifying susceptible populations in developing countries and for targeting specific public health interventions for the prevention of aflatoxicoses in populations with HCC and chronic liver diseases. PMID:17162498

  13. NMR solution structures of adducts derived from the binding of polycyclic aromatic diol epoxides to DNA

    Energy Technology Data Exchange (ETDEWEB)

    Cosman, M.; Patel, D.J. [Memorial Sloan Kettering Cancer Center, New York, NY (United States). Cellular Biochemistry and Biophysics Program; Hingerty, B.E. [Oak Ridge National Lab., TN (United States). Health and Safety Research Div.; Amin, S. [American Health Foundation, Valhalla, NY (United States); Broyde, S.; Geacintov, N.E. [New York Univ., NY (United States)

    1995-12-31

    Site-specifically modified oligonucleotides were derived from the reactions of stereoisomeric polycyclic aromatic diol epoxide metabolite model compounds with oligonucleotides of defined base composition and sequence. The NMR solution structures of ten different adducts studied so far are briefly described, and it is shown that stereochemical factors and the nature of the oligonucleotide context of the complementary strands, exert a powerful influence on the conformational features of these adducts.

  14. Haemoglobin adducts formed by aromatic amines in smokers: sources of inter-individual variability.

    OpenAIRE

    Ronco, G.; Vineis, P; Bryant, M S; Skipper, P. L.; Tannenbaum, S R

    1990-01-01

    In a previous study we found that aromatic amines, particularly 4-aminobiphenyl, formed haemoglobin adducts at higher concentrations in the blood of smokers compared to non-smokers. We re-analyse here data on haemoglobin adducts of 14 aromatic amines in order to ascertain if the inter-individual variability left unexplained by tobacco smoking could be attributed to differences in individual metabolic patterns. For this purpose we computed residuals from analysis of variance in order to adjust...

  15. Hemoglobin adducts of aromatic amines: associations with smoking status and type of tobacco.

    OpenAIRE

    Bryant, M S; Vineis, P; Skipper, P. L.; Tannenbaum, S R

    1988-01-01

    Hemoglobin adducts of 15 aromatic amines were determined in nonsmokers and smokers of blond- or black-tobacco cigarettes living in Turin, Italy. The subjects were all males age 55 or less and were representative of the population previously examined in a case/control study of bladder cancer. 4-Aminobiphenyl adduct levels were found to be significantly different in the three groups, and the differences were approximately proportional to the relative risk of each group. Adjustment for age and c...

  16. Effect of Laterally Wedged Insoles on the External Knee Adduction Moment across Different Reference Frames.

    Directory of Open Access Journals (Sweden)

    Satoshi Yamaguchi

    Full Text Available Biomechanical effects of laterally wedged insoles are assessed by reduction in the knee adduction moment. However, the degree of reduction may vary depending on the reference frame with which it is calculated. The purpose of this study was to clarify the effect of reference frame on the reduction in the knee adduction moment by laterally wedged insoles.Twenty-nine healthy participants performed gait trials with a laterally wedged insole and with a flat insole as a control. The knee adduction moment, including the first and second peaks and the angular impulse, were calculated using four different reference frames: the femoral frame, tibial frame, laboratory frame and the Joint Coordinate System.There were significant effects of reference frame on the knee adduction moment first and second peaks (P < 0.001 for both variables, while the effect was not significant for the angular impulse (P = 0.84. No significant interaction between the gait condition and reference frame was found in either of the knee adduction moment variables (P = 0.99 for all variables, indicating that the effects of laterally wedged insole on the knee adduction moments were similar across the four reference frames. On the other hand, the average percent changes ranged from 9% to 16% for the first peak, from 16% to 18% for the second peak and from 17% to 21% for the angular impulse when using the different reference frames.The effects of laterally wedged insole on the reduction in the knee adduction moment were similar across the reference frames. On the other hand, Researchers need to recognize that when the percent change was used as the parameter of the efficacy of laterally wedged insole, the choice of reference frame may influence the interpretation of how laterally wedged insoles affect the knee adduction moment.

  17. Structural Elucidation of a Carnosine-Acrolein Adduct and its Quantification in Human Urine Samples.

    Science.gov (United States)

    Bispo, Vanderson S; de Arruda Campos, Ivan P; Di Mascio, Paolo; Medeiros, Marisa H G

    2016-01-01

    Aldehydes accumulate in inflammation, during myocardial infarction and have been associated with pain symptoms. One pathway of aldehyde detoxification is the conjugation with carnosine. A 3-methylpyridinium carnosine adduct from the reaction of carnosine and acrolein was characterized using extensive spectroscopic measurements. The adduct with urinary concentrations of 1.82 ± 0.68 nmol/mg of creatinine is one of the most abundant acrolein metabolites in urine and opens promising therapeutic strategies for carnosine. PMID:26783107

  18. Structural Elucidation of a Carnosine-Acrolein Adduct and its Quantification in Human Urine Samples

    OpenAIRE

    Vanderson S. Bispo; Ivan P. de Arruda Campos; Paolo Di Mascio; Medeiros, Marisa H. G.

    2016-01-01

    Aldehydes accumulate in inflammation, during myocardial infarction and have been associated with pain symptoms. One pathway of aldehyde detoxification is the conjugation with carnosine. A 3-methylpyridinium carnosine adduct from the reaction of carnosine and acrolein was characterized using extensive spectroscopic measurements. The adduct with urinary concentrations of 1.82 ± 0.68 nmol/mg of creatinine is one of the most abundant acrolein metabolites in urine and opens promising therapeutic s...

  19. Surgical treatment of thumb adduction contracture in children with infantile cerebral palsy

    OpenAIRE

    Vladimir Alexandrovich Novikov; Valery Vladimirovich Umnov

    2015-01-01

    The purpose of the work is to evaluate the effectiveness of different methods of surgical treatment of thumb adduction contracture in children with infantile cerebral palsy.Materials and methods.The present study is based on diagnostic results of children with infantile cerebral palsy with affected upper limb. The main criterion for selection of patients was the presence of thumb adduction contracture, the absence of significant positive outcome in a patient after conservative treatment, the ...

  20. Formation and characterization of covalent guanosine adducts with electrochemistry—liquid chromatography–mass spectrometry ☆

    OpenAIRE

    Plattner, Sabine; Erb, Robert; Pitterl, Florian; Brouwer, Hendrik-Jan; Oberacher, Herbert

    2012-01-01

    Chemicals can interact with the genetic material giving rise to the formation of covalent adducts. These alterations can lead to adverse consequences, including cancer, reproductive impairment, development anomalies, or genetic diseases. In search for an assay allowing identification of hazardous compounds that might form covalent adducts with nucleic acids, electrochemistry (EC)/liquid chromatography (LC)/mass spectrometry (MS) is presented. EC/LC/MS is a purely instrumental approach. EC is ...

  1. DNA adducts in target and nontarget tissues of 3,2'-dimethyl-4-aminobiphenyl in rats.

    OpenAIRE

    Shirai, T; Tada, M; Kojima, M; Hasegawa, R.; Masui, T.; Ito, N.

    1994-01-01

    3,2'-Dimethyl-4-aminobiphenyl (DMAB) is a potent carcinogenic aromatic amine which demonstrates multiorgan tropism in rats. Using polyclonal antibodies against DMAB-DNA adducts, an immunohistochemical procedure as well as an ELISA were applied to investigate the relationship between DMAB-DNA adduct formation and tumorigenicity. Dose-related nuclear staining was observed 24 hr after application of the carcinogen but specificity in terms of sites of tumor development was lacking. No observable ...

  2. Comparison of DNA adducts from exposure to complex mixtures in various human tissues and experimental systems

    OpenAIRE

    Lewtas, Joellen; Mumford, Judy; Everson, Richard B; Hulka, Barbara; Wilcosky, Tim; Kozumbo, Walter; Thompson, Claudia; George, Michael; Dobiáš, Lubomir; Šrám, Radim; Li, Xueming; Gallagher, Jane

    1993-01-01

    DNA adducts derived from complex mixtures of polycyclic aromatic compounds emitted from tobacco smoke are compared to industrial pollution sources (e.g., coke ovens and aluminum smelters), smoky coal burning, and urban air pollution. Exposures to coke oven emissions and smoky coal, both potent rodent skin tumor initiators and lung carcinogens in humans, result in high levels of DNA adducts compared to tobacco smoke in the in vitro calf thymus DNA model system, in cultured lymphocytes, and in ...

  3. DNA adducts as a measure of lung cancer risk in humans exposed to polycyclic aromatic hydrocarbons.

    OpenAIRE

    Kriek, E; van Schooten, F.J.; Hillebrand, M J; van Leeuwen, F E; Den Engelse, L; De Looff, A J; Dijkmans, A P

    1993-01-01

    Workers in the coking, foundry, and aluminum industry can be exposed to high concentrations of polycyclic aromatic hydrocarbons (PAHs) and are at increased risk for lung cancer, as are cigarette smokers. In recent years several studies on workers in the foundry and coking industries have been reported. In these studies, white blood cell(WBC) DNA was used for analysis of PAH-DNA adducts. Theoretically, DNA adduct formation is a more relevant biological parameter for assessing exposure risk tha...

  4. Albumin Adducts of Electrophilic Benzene Metabolites in Benzene-Exposed and Control Workers

    OpenAIRE

    Lin, Yu-Sheng; Vermeulen, Roel; Tsai, Chin H.; Waidyanatha, Suramya; Lan, Qing; Rothman, Nathaniel; Smith, Martyn T.; Zhang, Luoping; Shen, Min; Li, Guilan; Yin, Songnian; Kim, Sungkyoon; Rappaport, Stephen M.

    2006-01-01

    Background Metabolism of benzene produces reactive electrophiles, including benzene oxide (BO), 1,4-benzoquinone (1,4-BQ), and 1,2-benzoquinone (1,2-BQ), that are capable of reacting with blood proteins to produce adducts. Objectives The main purpose of this study was to characterize relationships between levels of albumin adducts of these electrophiles in blood and the corresponding benzene exposures in benzene-exposed and control workers, after adjusting for important covariates. Because se...

  5. A Z-source Inverter Based Flexible DG System with P+resonance and Repetitive Controllers for Power Quality Improvement of a Weak Grid

    DEFF Research Database (Denmark)

    Gajanayake, C.J.; Vilathgamuwa, D.M.; Loh, P.C.;

    2007-01-01

    , the utility has an obligation to deliver a quality supply to consumers. Interestingly, with the increase in energy demand and penetration of renewable sources, generation units popularly known as Distributed Generators (DGs) are increasingly connected at the distribution level. Most of these sources...... functions of the power distribution like harmonics and unbalance mitigation etc. Moreover, some of these DG sources have large operating ranges demanding special converters with wide operating range. Being a single stage buck-boost inverter, recently proposed Z-source inverter is a good candidate for future...... DG systems. Considering these factors, this paper presents the controller design for a Z-source inverter based DG system to improve the power quality of distribution systems. To improve the reference tracking and to eliminate harmonics, a p+resonance and repetitive controller designed using a simple...

  6. High order WENO and DG methods for time-dependent convection-dominated PDEs: A brief survey of several recent developments

    Science.gov (United States)

    Shu, Chi-Wang

    2016-07-01

    For solving time-dependent convection-dominated partial differential equations (PDEs), which arise frequently in computational physics, high order numerical methods, including finite difference, finite volume, finite element and spectral methods, have been undergoing rapid developments over the past decades. In this article we give a brief survey of two selected classes of high order methods, namely the weighted essentially non-oscillatory (WENO) finite difference and finite volume schemes and discontinuous Galerkin (DG) finite element methods, emphasizing several of their recent developments: bound-preserving limiters for DG, finite volume and finite difference schemes, which address issues in robustness and accuracy; WENO limiters for DG methods, which address issues in non-oscillatory performance when there are strong shocks, and inverse Lax-Wendroff type boundary treatments for finite difference schemes, which address issues in solving complex geometry problems using Cartesian meshes.

  7. Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers.

    OpenAIRE

    Harris, C. C.; Vahakangas, K.; Newman, M J; Trivers, G E; Shamsuddin, A; Sinopoli, N; Mann, D L; Wright, W. E.

    1985-01-01

    Coke oven workers are exposed to high levels of carcinogenic polycyclic aromatic hydrocarbons, including benzo[a]pyrene (B[a]P), and are at increased risk of lung cancer. Since B[a]P is enzymatically activated to 7 beta,8 alpha-dihydroxy(9 alpha, 10 alpha)epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE) that forms adducts with DNA, the presence of these adducts was measured in DNA from peripheral blood lymphocytes by synchronous fluorescence spectrophotometry and enzyme radioimmunoassay. App...

  8. Abacavir forms novel cross-linking abacavir protein adducts in patients.

    Science.gov (United States)

    Meng, Xiaoli; Lawrenson, Alexandre S; Berry, Neil G; Maggs, James L; French, Neil S; Back, David J; Khoo, Saye H; Naisbitt, Dean J; Park, B Kevin

    2014-04-21

    Abacavir (ABC), a nucleoside-analogue reverse transcriptase inhibitor, is associated with severe hypersensitivity reactions that are thought to involve the activation of CD8+ T cells in a HLA-B*57:01-restricted manner. Recent studies have claimed that noncovalent interactions of ABC with HLA-B*57:01 are responsible for the immunological reactions associated with ABC. However, the formation of hemoglobin-ABC aldehyde (ABCA) adducts in patients exposed to ABC suggests that protein conjugation might represent a pathway for antigen formation. To further characterize protein conjugation reactions, we used mass spectrometric methods to define ABCA modifications in patients receiving ABC therapy. ABCA formed a novel intramolecular cross-linking adduct on human serum albumin (HSA) in patients and in vitro via Michael addition, followed by nucleophilic adduction of the aldehyde with a neighboring protein nucleophile. Adducts were detected on Lys159, Lys190, His146, and Cys34 residues in the subdomain IB of HSA. Only a cysteine adduct and a putative cross-linking adduct were detected on glutathione S-transferase Pi (GSTP). These findings reveal that ABC forms novel types of antigens in all patients taking the drug. It is therefore vital that the immunological consequences of such pathways of haptenation are explored in the in vitro models that have been used by various groups to define new mechanisms of drug hypersensitivity exemplified by ABC. PMID:24571427

  9. Sperm DNA adducts impair fertilization during ICSI but not during IVF.

    Directory of Open Access Journals (Sweden)

    Piotr Widłak

    2008-04-01

    Full Text Available Many studies emphasize the influence of the status of spermatozoal nucleus on fertilization, mainly with regard to DNA fragmentation. This study was undertaken to analyze the influence of DNA adducts content in spermatozoa on fertilization during assisted reproduction. Ovarian hyperstimulation, oocyte retrieval and laboratory work-up in 61 IVF (in vitro fertilization and 118 ICSI (intracytoplasmic sperm injection first cycles were performed according to the same protocol. Semen analysis was made according to WHO Manual (1999. DNA adducts assay in spermatozoa was performed by 32Ppostlabeling method. In total 331 fertilizable oocytes were obtained during IVF and 659 during ICSI. Both groups differed significantly by sperm count, motility and morphology but not by the concentration of DNA adducts in spermatozoa (0.0306 +/- 0.0217 in IVF versus 0.0373 +/- 0.0321 in ICSI. The fertilization rate during IVF was significantly influenced by sperm count (p=0.0002 and motility (p=0.0037 but not by DNA adducts concentration (p=0.30528, whereas during ICSI was positively influenced by sperm motility (p=0.04669 and negatively by DNA adducts concentration (p=0.00796. DNA adducts concentration in spermatozoa significantly negatively influences fertilization rate during ICSI, but not during IVF.

  10. Effects of metal ion adduction on the gas-phase conformations of protein ions.

    Science.gov (United States)

    Flick, Tawnya G; Merenbloom, Samuel I; Williams, Evan R

    2013-11-01

    Changes in protein ion conformation as a result of nonspecific adduction of metal ions to the protein during electrospray ionization (ESI) from aqueous solutions were investigated using traveling wave ion mobility spectrometry (TWIMS). For all proteins examined, protein cations (and in most cases anions) with nonspecific metal ion adducts are more compact than the fully protonated (or deprotonated) ions with the same charge state. Compaction of protein cations upon nonspecific metal ion binding is most significant for intermediate charge state ions, and there is a greater reduction in collisional cross section with increasing number of metal ion adducts and increasing ion valency, consistent with an electrostatic interaction between the ions and the protein. Protein cations with the greatest number of adducted metal ions are no more compact than the lowest protonated ions formed from aqueous solutions. These results show that smaller collisional cross sections for metal-attached protein ions are not a good indicator of a specific metal-protein interaction in solution because nonspecific metal ion adduction also results in smaller gaseous protein cation cross sections. In contrast, the collisional cross section of α-lactalbumin, which specifically binds one Ca(2+), is larger for the holo-form compared with the apo-form, in agreement with solution-phase measurements. Because compaction of protein cations occurs when metal ion adduction is nonspecific, elongation of a protein cation may be a more reliable indicator that a specific metal ion-protein interaction occurs in solution.

  11. The use of an artificial nucleotide for polymerase-based recognition of carcinogenic O6-alkylguanine DNA adducts.

    Science.gov (United States)

    Wyss, Laura A; Nilforoushan, Arman; Williams, David M; Marx, Andreas; Sturla, Shana J

    2016-08-19

    Enzymatic approaches for locating alkylation adducts at single-base resolution in DNA could enable new technologies for understanding carcinogenesis and supporting personalized chemotherapy. Artificial nucleotides that specifically pair with alkylated bases offer a possible strategy for recognition and amplification of adducted DNA, and adduct-templated incorporation of an artificial nucleotide has been demonstrated for a model DNA adduct O(6)-benzylguanine by a DNA polymerase. In this study, DNA adducts of biological relevance, O(6)-methylguanine (O(6)-MeG) and O(6)-carboxymethylguanine (O(6)-CMG), were characterized to be effective templates for the incorporation of benzimidazole-derived 2'-deoxynucleoside-5'-O-triphosphates ( BENZI: TP and BIM: TP) by an engineered KlenTaq DNA polymerase. The enzyme catalyzed specific incorporation of the artificial nucleotide BENZI: opposite adducts, with up to 150-fold higher catalytic efficiency for O(6)-MeG over guanine in the template. Furthermore, addition of artificial nucleotide BENZI: was required for full-length DNA synthesis during bypass of O(6)-CMG. Selective incorporation of the artificial nucleotide opposite an O(6)-alkylguanine DNA adduct was verified using a novel 2',3'-dideoxy derivative of BENZI: TP. The strategy was used to recognize adducts in the presence of excess unmodified DNA. The specific processing of BENZI: TP opposite biologically relevant O(6)-alkylguanine adducts is characterized herein as a basis for potential future DNA adduct sequencing technologies. PMID:27378785

  12. Identification of Rosmarinic Acid-Adducted Sites in Meat Proteins in a Gel Model under Oxidative Stress by Triple TOF MS/MS.

    Science.gov (United States)

    Tang, Chang-Bo; Zhang, Wan-Gang; Wang, Yao-Song; Xing, Lu-Juan; Xu, Xing-Lian; Zhou, Guang-Hong

    2016-08-24

    Triple TOF MS/MS was used to identify adducts between rosmarinic acid (RosA)-derived quinones and meat proteins in a gel model under oxidative stress. Seventy-five RosA-modified peptides responded to 67 proteins with adduction of RosA. RosA conjugated with different amino acids in proteins, and His, Arg, and Lys adducts with RosA were identified for the first time in meat. A total of 8 peptides containing Cys, 14 peptides containing His, 48 peptides containing Arg, 64 peptides containing Lys, and 5 peptides containing N-termini that which participated in adduction reaction with RosA were identified, respectively. Seventy-seven adduction sites were subdivided into all adducted proteins including 2 N-terminal adduction sites, 3 Cys adduction sites, 4 His adduction sites, 29 Arg adduction sites, and 39 Lys adduction sites. Site occupancy analyses showed that approximately 80.597% of the proteins carried a single RosA-modified site, 14.925% retained two sites, 1.492% contained three sites, and the rest 2.985% had four or more sites. Large-scale triple TOF MS/MS mapping of RosA-adducted sites reveals the adduction regulations of quinone and different amino acids as well as the adduction ratios, which clarify phenol-protein adductions and pave the way for industrial meat processing and preservation. PMID:27486909

  13. Developement of serum-free media in CHO-DG44 cells using a central composite statistical design.

    Science.gov (United States)

    Parampalli, Ananth; Eskridge, Kent; Smith, Leonard; Meagher, Michael M; Mowry, Mark C; Subramanian, Anuradha

    2007-05-01

    A serum free medium was developed for the production of recombinant antibody against Botulinum A (BoNTA) using dihydrofolate reductase deficient Chinese Hamster Ovary Cells (CHO-DG44) in suspension culture. An initial control basal medium was prepared, which was similar in composition to HAM's F12: IMDM (1:1) supplemented with insulin, transeferrin, selenium and a lipid mixture. The vitamin concentration of the basal medium was twice that of HAM's F12: IMDM (1:1). CHO-DG44 cells expressing S25 antibody grew from 2 x 10(5) cells to maximum cell density of 1.04 x 10(6) cells/ml after 5 days in this control medium. A central composite design was used to identify optimal levels and interaction among five groups of medium components. These five groups were glutamine, Essential Amino Acids (EAA), Non Essential Amino Acids (NEAA), Insulin, Transferrin, Selenium (ITS), and lipids. Fifty experiments were carried out in four batches, with two controls in each batch. There was little effect of ITS and Lipid concentrations over the range studied, and glutamine concentration showed a strong interaction with EAA. The optimal concentrations of the variables studied were 2.5 mM Glutamine, 7.4 mM (2x) EAA, 1.4 mM (0.5x) NEAA, 1x ITS supplement, 0.7x Lipids supplement. The maximum viable cell density attained in the optimized medium was 1.4 x 10(6) cells/ml, a 35% improvement over the control culture, while the final antibody titer attained was 22 +/- 3.4 mug/mL, a 50% improvement.

  14. Diazoalkane addition reaction on the fullerene dimer C120O and characterization of the resulting mono-adduct.

    Directory of Open Access Journals (Sweden)

    Uwe Ritter

    2008-06-01

    Full Text Available A mono-adduct of the fullerene dimer C120O was prepared via a diazoalkane addition reaction to obtain rod-like analogue of[60]PCBM opening the possibility to make photovoltaic and photosensitive layers of supra-molecular and anisotropic order.The mono-adduct was obtained as a mixture containing five isomers. The structure of the mono-adduct was verified bymass-, IR-, and 1H-NMR-spectroscopies. The mono-adduct is readily soluble in common fullerene solvents and shows abroader and stronger optical absorption than [60]PCBM. The mono-adduct features a similar acceptor strength as [60]PCBMand [70]PCBM, is stable in air below 150 °C and in nitrogen below 500 °C. The mono-adduct is expected to be a valuablematerial for photovoltaic and photosensitive applications.

  15. Revisiting the stability of endo/exo Diels-Alder adducts between cyclopentadiene and 1,4-benzoquinone

    Energy Technology Data Exchange (ETDEWEB)

    Tormena, Claudio F. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Quimica. Dept. de Quimica Organica; Lacerda Junior, Valdemar [Universidade Federal do Espirito Santo (UFES), Vitoria, ES (Brazil). Centro de Ciencias Exatas. Dept. de Quimica; Oliveira, Kleber T. de [Universidade Federal do ABC (UFABC), Santo Andre, SP (Brazil). Centro de Ciencias Naturais e Humanas

    2010-07-01

    In this work it is presented a detailed theoretical analysis of the relative stability of endo/exo Diels-Alder adducts formed by the reaction between cyclopentadiene (1) and 1,4-benzoquinone (2). The intrinsic reaction coordinate (IRC) showed the existence of only one transition state for the reaction studied, for both endo 3 and exo 4 adducts. The energies of both adducts were obtained at high level of theory (CBS-Q) confirming that the endo adduct is more stable than exo, which is in the opposite way to the observed in reactions that usually follow Alder's rule. An electronic structure analysis was performed through NBO methodology, indicating that the attractive delocalization interaction predominates over the steric repulsive interaction in the endo adducts. In summary, for the studied cycloaddition reaction the endo adduct is the thermodynamic and kinetic product, which can be also confirmed by experimental data mentioned in this work. (author)

  16. Transplatin-conjugated triplex-forming oligonucleotides form adducts with both strands of DNA.

    Science.gov (United States)

    Campbell, Meghan A; Miller, Paul S

    2009-12-01

    Triplex-forming oligonucleotides (TFOs) can bind to polypurine x polypyrimidine tracts in DNA and, as a consequence, perturb the normal functioning of a targeted gene. The effectiveness of such antigene TFOs can potentially be enhanced by covalent attachment of the TFO to its DNA target. Here, we report that attachment of N-7-platinated guanine nucleosides to the 3'- and/or 5'-ends of oligopyrimidine TFOs enables these TFOs to form highly stable adducts with target DNA deoxyguanosines or deoxyadenosines that are adjacent to the TFO binding site. Such adduct formation stably anchors the TFO to its target. Depending on the sequences adjacent to the TFO binding site, adduct formation can occur on either strand of the DNA. Adduct formation by 3',5'-bis-platinated TFOs can result in the formation of an interstrand cross-link between both strands of the DNA duplex. Formation of the adducts, which could be reversed by treatment with sodium cyanide, was dependent upon the ability of the TFO to bind to DNA and appeared to occur at a rate slower than that at which the TFO bound to the DNA duplex. The extent of adduct formation at 37 degrees C by platinated deoxyribo-TFOs diminished as the pH was increased from 6.5 to 7.4. In contrast, high levels (approximately 86%) of adduct formation by platinated 2'-O-methylribo-TFOs were observed at both pH 6.5 and pH 7.4. Platinated 2'-O-methylribo-TFOs were also shown to bind to plasmid DNA and inhibit transcription in vitro, and to inhibit plasmid replication in E. coli cells. These results suggest that platinum-conjugated TFOs may be good candidates for use as antigene agents. PMID:19950917

  17. Silver adducts of four-branched histidine rich peptides exhibit synergistic antifungal activity.

    Science.gov (United States)

    Leng, Qixin; Woodle, Martin C; Liu, Yijia; Mixson, A James

    2016-09-01

    Previously, a four branched histidine-lysine rich peptide, H3K4b, was shown to demonstrate selective antifungal activity with minimal antibacterial activity. Due to the potential breakdown from proteases, H3K4b was further evaluated in the current study by varying the D- and l-amino acid content in its branches. Whereas analogues of H3K4b that selectively replaced l-amino acids (H3k4b, h3K4b) had improved antifungal activity, the all d-amino acid analogue, h3k4b, had reduced activity, suggesting that partial breakdown of the peptide may be necessary. Moreover, because histidines form coordination bonds with the silver ion, we examined whether silver adducts can be formed with these branched histidine-lysine peptides, which may improve antifungal activity. For Candida albicans, the silver adduct of h3K4b or H3k4b reduced the MIC compared to peptide and silver ions alone by 4- and 5-fold, respectively. For Aspergillus fumigatus, the silver adducts showed even greater enhancement of activity. Although the silver adducts of H3k4b or h3K4b showed synergistic activity, the silver adduct with the all l-amino acid H3K4b surprisingly showed the greatest synergistic and growth inhibition of A. fumigatus: the silver adduct of H3K4b reduced the MIC compared to the peptide and silver ions alone by 30- and 26-fold, respectively. Consistent with these antifungal efficacy results, marked increases in free oxygen radicals were produced with the H3K4b and silver combination. These studies suggest that there is a balance between stability and breakdown for optimal antifungal activity of the peptide alone and for the peptide-silver adduct. PMID:27387239

  18. Simultaneous detection of multiple DNA adducts in human lung samples by isotope-dilution UPLC-MS/MS.

    Science.gov (United States)

    Monien, Bernhard H; Schumacher, Fabian; Herrmann, Kristin; Glatt, Hansruedi; Turesky, Robert J; Chesné, Christophe

    2015-01-01

    Recent studies have demonstrated that various DNA adducts can be detected in human tissues and fluids using liquid chromatography connected to tandem mass spectrometry (LC-MS/MS). However, the utility of a single DNA adduct as a biomarker in risk assessment is debatable because humans are exposed to many genotoxicants. We established a method to measure DNA adducts derived from 16 ubiquitous genotoxicants and developed an analytical technique for their simultaneous quantification by ultra performance liquid chromatography (UPLC)-MS/MS. Methods for the enrichment of the analytes from DNA hydrolysates and chromatographic separation preceding mass spectrometric analysis were optimized, and the resultant technique was used for the simultaneous analysis of the 16 DNA adducts in human lung biopsy specimens. Eleven adducts (formed by benzo[a]pyrene, 1-methylpyrene, 4-aminobiphenyl, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 1-methoxy-3-indolylmethylglucosinolate, 5-hydroxymethylfurfural, and malondialdehyde) were not detected in any tissue sample (limits of detection: 0.02-7.1 adducts/10(8) nucleosides). 3,N(4)-etheno-2'-deoxycytidine and 1,N(6)-etheno-2'-deoxyadenosine, formed from 2,3-epoxyaldehydes of endogenous lipid peroxidation products, were present in all subjects (16.9-115.3 and 27.2-179/10(8) nucleosides, respectively). The same was true for N(2)-(trans-methylisoeugenol-3'-yl)-2'-deoxyguanosine, the major adduct of methyleugenol (1.7-23.7/10(8) nucleosides). A minor adduct of methyleugenol and two adducts of furfuryl alcohol were detected in several pulmonary specimens. Taken together, we developed a targeted approach for the simultaneous mass spectrometric analyses of 16 DNA adducts, which can be easily extended by adducts formed from other mutagens. The method allowed one to detect adducts of furfuryl alcohol and methyleugenol in samples of human lung. PMID:25423194

  19. Simultaneous Detection of Multiple DNA Adducts in Human Lung Samples by Isotope-Dilution UPLC-MS/MS

    OpenAIRE

    Monien, Bernhard H.; Schumacher, Fabian; Herrmann, Kristin; Glatt, Hansruedi; Turesky, Robert J.; Chesné, Christophe

    2014-01-01

    Recent studies have demonstrated that various DNA adducts can be detected in human tissues and fluids using liquid chromatography connected to tandem mass spectrometry (LC-MS/MS). However, the utility of a single DNA adduct as a biomarker in risk assessment is debatable because humans are exposed to many genotoxicants. We established a method to measure DNA adducts derived from 16 ubiquitous genotoxicants and developed an analytical technique for their simultaneous quantification by ultra per...

  20. A multi-dimensional high-order DG-ALE method based on gas-kinetic theory with application to oscillating bodies

    Science.gov (United States)

    Ren, Xiaodong; Xu, Kun; Shyy, Wei

    2016-07-01

    This paper presents a multi-dimensional high-order discontinuous Galerkin (DG) method in an arbitrary Lagrangian-Eulerian (ALE) formulation to simulate flows over variable domains with moving and deforming meshes. It is an extension of the gas-kinetic DG method proposed by the authors for static domains (X. Ren et al., 2015 [22]). A moving mesh gas kinetic DG method is proposed for both inviscid and viscous flow computations. A flux integration method across a translating and deforming cell interface has been constructed. Differently from the previous ALE-type gas kinetic method with piecewise constant mesh velocity at each cell interface within each time step, the mesh velocity variation inside a cell and the mesh moving and rotating at a cell interface have been accounted for in the finite element framework. As a result, the current scheme is applicable for any kind of mesh movement, such as translation, rotation, and deformation. The accuracy and robustness of the scheme have been improved significantly in the oscillating airfoil calculations. All computations are conducted in a physical domain rather than in a reference domain, and the basis functions move with the grid movement. Therefore, the numerical scheme can preserve the uniform flow automatically, and satisfy the geometric conservation law (GCL). The numerical accuracy can be maintained even for a largely moving and deforming mesh. Several test cases are presented to demonstrate the performance of the gas-kinetic DG-ALE method.

  1. Optimization of the source/drain extension region profile for suppression of short channel effects in sub-50 nm DG MOSFETs with high-κ gate dielectrics

    Science.gov (United States)

    Kranti, Abhinav; Armstrong, G. Alastair

    2006-12-01

    In the present paper, we propose a new scaling theory to model short channel effects (SCEs) in nanoscale double gate (DG) SOI MOSFETs, addressing two important technological issues—source/drain extension (SDE) region engineering and high-κ gate dielectrics. The impact of SDE region engineering through the optimization of lateral source/drain doping gradient and spacer width on SCEs is extensively analysed in DG devices with high-κ gate dielectrics, using the analytical model and 2D device simulations. Novel technology dependent scaling parameters, i.e., spacer-to-gradient ratio (ρ) and effective channel length (Leff), are proposed for source/drain-engineered DG MOSFETs, and their significance in minimizing SCEs in high-κ gate dielectrics is discussed in detail. Results show that the optimal spacer-to-gradient ratio should be increased with the permittivity of high-κ dielectrics in order to maintain SCEs to an acceptable level. The results of the analytical model confirm well with simulated data over the entire range of spacer widths, doping gradients, high-κ gate dielectrics and effective channel lengths. The present work provides valuable design insights in the performance of nanoscale source/drain-engineered DG SOI devices with high-κ gate dielectrics and serves as an accurate tool to optimize important device parameters aiding technology development.

  2. Formation of metal-ion adducts and evidence for surface-catalyzed ionization in electrospray analysis of pharmaceuticals and pesticides

    Science.gov (United States)

    Thurman, E.M.; Ferrer, I.

    2002-01-01

    The formation of metal ion adducts in liquid chromatography/mass spectrometry positive-ion electrospray analysis of pharmaceuticals and pesticides was investigated. The evidence of surface-catalyzed ionization in the electrospray analysis was also studied. Both positive and negative ion mass spectrometry were used for the analysis of the products. It was found that the sodium adducts formed in the analysis included single, double, and triple sodium adducts. Adduction was found to occur by attachment of the metal ion to carboxyl, carbonyl and aromatic pi electrons of the molecule.

  3. Physical properties of the jet from DG Tauri on sub-arcsecond scales with HST/STIS

    Science.gov (United States)

    Maurri, L.; Bacciotti, F.; Podio, L.; Eislöffel, J.; Ray, T. P.; Mundt, R.; Locatelli, U.; Coffey, D.

    2014-05-01

    Context. Stellar jets are believed to play a key role in star formation, but the question of how they originate is still being debated. Aims: We derive the physical properties at the base of the jet from DG Tau both along and across the flow and as a function of velocity. Methods: We analysed seven optical spectra of the DG Tau jet, taken with the Hubble Space Telescope Imaging Spectrograph. The spectra were obtained by placing a long-slit parallel to the jet axis and stepping it across the jet width. The resulting position-velocity diagrams in optical forbidden emission lines allowed access to plasma conditions via calculation of emission line ratios. In this way, we produced a 3D map (2D in space and 1D in velocity) of the jet's physical parameters i.e. electron density ne, hydrogen ionisation fraction xe, and total hydrogen density nH. The method used is a new version of the BE-technique. Results: A fundamental improvement is that the new diagnostic method allows us to overcome the upper density limit of the standard [S ii] diagnostics. As a result, we find at the base of the jet high electron density, ne ~ 105, and very low ionisation, xe ~ 0.02-0.05, which combine to give a total density up to nH ~ 3 × 106. This analysis confirms previous reports of variations in plasma parameters along the jet, (i.e. decrease in density by several orders of magnitude, increase of xe from 0.05 to a plateau at 0.7 downstream at 2'' from the star). Furthermore, a spatial coincidence is revealed between sharp gradients in the total density and supersonic velocity jumps. This strongly suggests that the emission is caused by shock excitation. No evidence was found of variations in the parameters across the jet, within a given velocity interval. The position-velocity diagrams indicate the presence of both fast accelerating gas and slower, less collimated material. We derive the mass outflow rate, Ṁj, in the blue-shifted lobe in different velocity channels, that contribute to a

  4. Targeted mutations induced by a single acetylaminofluorene DNA adduct in mammalian cells and bacteria

    International Nuclear Information System (INIS)

    Mutagenic specificity of 2-acetylaminofluorene (AAF) has been established in mammalian cells and several strains of bacteria by using a shuttle plasmid vector containing a single N-(deoxyguanosin-8-yl)acetylaminofluorene (C8-dG-AAF) adduct. The nucleotide sequence of the gene conferring tetracycline resistance was modified by conservative codon replacement so as to accommodate the sequence d(CCTTCGCTAC) flanked by two restriction sites, Bsm I and Xho I. The corresponding synthetic oligodeoxynucleotide underwent reaction with 2-(N-acetoxy-N-acetylamino)-fluorene (AAAF), forming a single dG-AAF adduct. This modified oligodeoxynucleotide was hybridized to its complementary strand and ligated between the Bsm I and Xho I sites of the vector. Plasmids containing the C8-dG-AAF adduct were used to transfect simian virus 40-transformed simian kidney (COS-1) cells and to transform several AB strains of Escherichia coli. Colonies containing mutant plasmides were detected by hybridization to 32P-labeled oligodeoxynucleotides. Presence of the single DNA adduct increased the mutation frequency by 8-fold in both COS cells and E. coli. Over 80% of mutations detected in both systems were targeted and represented G x C → C x G or G x C → T x A transversions or single nucleotide deletions. The authors conclude that modification of a deoxyguanosine residue with AAF preferentially induces mutations targeted at this site when a plasmid containing a single C8-dG-AAF adduct is introduced into mammalian cells or bacteria

  5. Serine Protease Catalysis: A Computational Study of Tetrahedral Intermediates and Inhibitory Adducts.

    Science.gov (United States)

    Ngo, Phong D; Mansoorabadi, Steven O; Frey, Perry A

    2016-08-01

    Peptide boronic acids and peptidyl trifluoromethyl ketones (TFKs) inhibit serine proteases by forming monoanionic, tetrahedral adducts to serine in the active sites. Investigators regard these adducts as analogs of monoanionic, tetrahedral intermediates. Density functional theory (DFT) calculations and fractional charge analysis show that tetrahedral adducts of model peptidyl TFKs are structurally and electrostatically very similar to corresponding tetrahedral intermediates. In contrast, the DFT calculations show the structures and electrostatic properties of analogous peptide boronate adducts to be significantly different. The peptide boronates display highly electrostatically positive boron, with correspondingly negative ligands in the tetrahedra. In addition, the computed boron-oxygen and boron-carbon bond lengths in peptide boronates (which are identical or very similar to the corresponding bonds in a peptide boronate adduct of α-lytic protease determined by X-ray crystallography at subangstrom resolution) are significantly longer than the corresponding bond lengths in model tetrahedral intermediates. Since protease-peptidyl TFKs incorporate low-barrier hydrogen bonds (LBHBs) between an active site histidine and aspartate, while the protease-peptide boronates do not, these data complement the spectroscopic and chemical evidence for the participation of LBHBs in catalysis by serine proteases. Moreover, while the potency of these classes of inhibitors can be correlated to the structures of the peptide moieties, the present results indicate that the strength of their bonds to serine contribute significantly to their inhibitory properties. PMID:27387593

  6. Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity.

    Science.gov (United States)

    James, Laura; Yan, Ke; Pence, Lisa; Simpson, Pippa; Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda; Kearns, Gregory; Beger, Richard

    2015-01-01

    Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts) and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; pacetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury.

  7. DNA isolation and sample preparation for quantification of adduct levels by accelerator mass spectrometry.

    Science.gov (United States)

    Dingley, Karen H; Ubick, Esther A; Vogel, John S; Ognibene, Ted J; Malfatti, Michael A; Kulp, Kristen; Haack, Kurt W

    2014-01-01

    Accelerator mass spectrometry (AMS) is a highly sensitive technique used for the quantification of adducts following exposure to carbon-14- or tritium-labeled chemicals, with detection limits in the range of one adduct per 10(11)-10(12) nucleotides. The protocol described in this chapter provides an optimal method for isolating and preparing DNA samples to measure isotope-labeled DNA adducts by AMS. When preparing samples, special precautions must be taken to avoid cross-contamination of isotope among samples and produce a sample that is compatible with AMS. The DNA isolation method described is based upon digestion of tissue with proteinase K, followed by extraction of DNA using Qiagen isolation columns. The extracted DNA is precipitated with isopropanol, washed repeatedly with 70 % ethanol to remove salt, and then dissolved in water. DNA samples are then converted to graphite or titanium hydride and the isotope content measured by AMS to quantify adduct levels. This method has been used to reliably generate good yields of uncontaminated, pure DNA from animal and human tissues for analysis of adduct levels.

  8. Foot rotation--a potential target to modify the knee adduction moment.

    Science.gov (United States)

    Teichtahl, A J; Morris, M E; Wluka, A E; Baker, R; Wolfe, R; Davis, S R; Cicuttini, F M

    2006-05-01

    Isolating the particular joints/limb segments associated with knee adductor moment variability may provide clinically important data that could help to identify strategies to reduce medial tibiofemoral joint load. The aim of this study was to examine whether or not foot and thigh rotation during human locomotion are significant determinants of knee adductor moment variability. Three-dimensional gait analyses were performed on 32 healthy adult women (mean age 54+/-12 years, mean BMI 25+/-4 kg m(-2)) with radiologically normal knees. The relationships between foot rotation, thigh rotation and the external knee adduction moment were examined during early and late-stance phases of the gait cycle. The degree of foot rotation correlated significantly with the magnitude of the peak knee adduction moment during late stance (r=0.40, p=0.024). No significant associations were apparent between thigh rotation and the peak knee adduction moment. The association between foot rotation and the knee adduction moment in this study suggests that women who walk with external rotation at the foot reduce their knee adduction moment during late stance. This result implies that changes in foot kinematics can modify the medial tibiofemoral load during gait, which may be important in the prevention and management of knee osteoarthritis.

  9. Characterization of model peptide adducts with reactive metabolites of naphthalene by mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Nathalie T Pham

    Full Text Available Naphthalene is a volatile polycyclic aromatic hydrocarbon generated during combustion and is a ubiquitous chemical in the environment. Short term exposures of rodents to air concentrations less than the current OSHA standard yielded necrotic lesions in the airways and nasal epithelium of the mouse, and in the nasal epithelium of the rat. The cytotoxic effects of naphthalene have been correlated with the formation of covalent protein adducts after the generation of reactive metabolites, but there is little information about the specific sites of adduction or on the amino acid targets of these metabolites. To better understand the chemical species produced when naphthalene metabolites react with proteins and peptides, we studied the formation and structure of the resulting adducts from the incubation of model peptides with naphthalene epoxide, naphthalene diol epoxide, 1,2-naphthoquinone, and 1,4-naphthoquinone using high resolution mass spectrometry. Identification of the binding sites, relative rates of depletion of the unadducted peptide, and selectivity of binding to amino acid residues were determined. Adduction occurred on the cysteine, lysine, and histidine residues, and on the N-terminus. Monoadduct formation occurred in 39 of the 48 reactions. In reactions with the naphthoquinones, diadducts were observed, and in one case, a triadduct was detected. The results from this model peptide study will assist in data interpretation from ongoing work to detect peptide adducts in vivo as markers of biologic effect.

  10. Inhibition of nicotine-DNA adduct formation by polyphenolic compounds in vitro

    Institute of Scientific and Technical Information of China (English)

    CHENG Yan; WANG Hai-Fang; SUN Hong-Fang; LI Hong-Li

    2004-01-01

    Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine], a major alkaloid in tobacco products, has proven to be a potential genotoxic compound. Some polyphenolic compounds can suppress the DNA adduction, and hence act as the potential inhibitors of carcinogenesis. In this study, the inhibitory effects of three polyphenolic compounds, curcumin (diferuloylmethane), resveratrol (trans-3, 5, 4-trihydroxystilbene) and tea polyphenols, on the nicotine-DNA adduction have been investigated in vitro using radiolabelled nicotine and liquid scintillation counting (LSC) technique. Also, the inhibition mechanism of these chemopreventive agents in regard to the activity of the biotransformation enzymes, including cytochrome P450 (CYP450), cytochrome b5 (CYb5) and glutathione S-transferase (GST), has been studied. The results demonstrated that these three polyphenols induced marked dose-dependent decrease in nicotine-DNA adducts as compared with the controls. The elimination rate of adducts reached above 46% at the highest dose for all the three agents with 51.6% for resveratrol. Correspondingly, three polyphenols all suppressed CYP450 and CYb5, whereas curcumin and resveratrol induced GST. We may arrive at a point that the three polyphenols are beneficial to prevent the nicotine adduct formation, and thus may be used to block the potential carcinogenesis induced by nicotine.

  11. Diviseurs de la forme 2D-G sans sections et rang de la multiplication dans les corps finis (Divisors of the form 2D-G without sections and bilinear complexity of multiplication in finite fields)

    CERN Document Server

    Randriam, Hugues

    2011-01-01

    Let X be an algebraic curve, defined over a perfect field, and G a divisor on X. If X has sufficiently many points, we show how to construct a divisor D on X such that l(2D-G)=0, of essentially any degree such that this is compatible the Riemann-Roch theorem. We also generalize this construction to the case of a finite number of constraints, l(k_i.D-G_i)=0, where |k_i|\\leq 2. Such a result was previously claimed by Shparlinski-Tsfasman-Vladut, in relation with the Chudnovsky-Chudnovsky method for estimating the bilinear complexity of the multiplication in finite fields based on interpolation on curves; unfortunately, as noted by Cascudo et al., their proof was flawed. So our work fixes the proof of Shparlinski-Tsfasman-Vladut and shows that their estimate m_q\\leq 2(1+1/(A(q)-1)) holds, at least when A(q)\\geq 5. We also fix a statement of Ballet that suffers from the same problem, and then we point out a few other possible applications.

  12. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

    Directory of Open Access Journals (Sweden)

    Judge Bryan S

    2011-03-01

    Full Text Available Abstract Background Acetaminophen-cysteine adducts (APAP-CYS are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. Methods Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated. Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. Results Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20 nmol/ml, Trial 2- 0.1 (0.09 nmol/ml and Trial 3- 0.3 (0.12 nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml. No subject had detectable APAP

  13. 32P-postlabelling analysis of dibenz[a,j]acridine-DNA adducts in mice: identification of proximate metabolites.

    Science.gov (United States)

    Talaska, G; Roh, J; Schamer, M; Reilman, R; Xue, W; Warshawsky, D

    1995-03-30

    N-Heterocyclic polynuclear aromatics are widely-occurring environmental pollutants formed during the pyrolysis of nitrogen-containing organic chemicals. Dibenz[a,j]acridine (DBA), a member of this class, has been shown to be a skin carcinogen in mice. We undertook studies to determine the organ distribution of DBA-DNA adducts and to identify the DBA metabolites which lead to the formation of carcinogen-DNA adducts in vivo. DBA and its metabolites, trans-DBA-1,2-dihydrodiol (DBA-1,2-DHD) trans-DBA-3,4-dihydrodiol (DBA-3,4-DHD) and trans-DBA-5,6-dihydrodiol (DBA-5,6-DHD), were topically applied on mice. DNA was isolated using enzyme-solvent extraction methods, and analyzed for carcinogen-DNA adducts using 32P-postlabelling. In skin, DBA produced two distinct adducts (Adducts 1 and 2). The same two adducts were seen when DBA-3,4-DHD was applied. In addition, the total adduct level elicited by DBA-3,4-DHD was twice that of the parent compound. Two adducts (Adducts 3 and 4) were also seen in mouse skin when DBA-5,6-DHD was applied, but these differed chromatographically from adducts seen with DBA. However, when DBA-3,4-DHD was applied and analyzed using sensitive nuclease P1 32P-postlabelling, all four adducts could be detected. These results suggest that the major route of DBA activation to DNA-binding species in skin is through formation of DBA-3,4-DHD and subsequent metabolism of this compound to a bay-region diol-epoxide. However, we postulate that another activation pathway may proceed through a bis-dihydrodiol-epoxide.

  14. Atomic-Resolution Structure of an N(5) Flavin Adduct in D-Arginine Dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Guoxing; Yuan, Hongling; Wang, Siming; Gadda, Giovanni; Weber, Irene T. (GSU)

    2011-09-06

    D-Arginine dehydrogenase (DADH) catalyzes the flavin-dependent oxidative deamination of D-arginine and other D-amino acids to the corresponding imino acids. The 1.07 {angstrom} atomic-resolution structure of DADH crystallized with D-leucine unexpectedly revealed a covalent N(5) flavin adduct, instead of the expected iminoleucine product in the active site. This acyl adduct has been successfully reproduced by photoreduction of DADH in the presence of 4-methyl-2-oxopentanoic acid (ketoleucine). The iminoleucine may be released readily because of weak interactions in the binding site, in contrast to iminoarginine, converted to ketoleucine, which reacts with activated FAD to form the covalently linked acyl adduct.

  15. Atomic-resolution structure of an N5 flavin adduct in D-arginine dehydrogenase.

    Science.gov (United States)

    Fu, Guoxing; Yuan, Hongling; Wang, Siming; Gadda, Giovanni; Weber, Irene T

    2011-07-26

    D-Arginine dehydrogenase (DADH) catalyzes the flavin-dependent oxidative deamination of D-arginine and other D-amino acids to the corresponding imino acids. The 1.07 Å atomic-resolution structure of DADH crystallized with D-leucine unexpectedly revealed a covalent N(5) flavin adduct, instead of the expected iminoleucine product in the active site. This acyl adduct has been successfully reproduced by photoreduction of DADH in the presence of 4-methyl-2-oxopentanoic acid (ketoleucine). The iminoleucine may be released readily because of weak interactions in the binding site, in contrast to iminoarginine, converted to ketoleucine, which reacts with activated FAD to form the covalently linked acyl adduct. PMID:21707047

  16. Development of sandwich ELISAs for the detection of aromatic diisocyanate adducts.

    Science.gov (United States)

    Lemons, Angela R; Bledsoe, Toni A; Siegel, Paul D; Beezhold, Donald H; Green, Brett J

    2013-11-29

    Diisocyanates (dNCOs) are highly reactive low molecular weight chemicals commonly used in the manufacturing industry. Occupational exposures to dNCOs have been shown to elicit allergic sensitization and occupational asthma. Among the most commonly used dNCOs in industry are the aromatic dNCOs, toluene diisocyanate (TDI) and methylene diphenyl diisocyanate (MDI). This study aimed to develop enzyme linked immunosorbent assays (ELISA) utilizing aromatic dNCO-specific monoclonal antibodies (mAbs) for the detection of aromatic dNCO adducts. Two sandwich ELISAs were developed. The first sandwich ELISA utilized mAb 60G2 along with an anti-human serum albumin (HSA) polyclonal antibody. This assay detected MDI-, 2,4- and 2,6-TDI-HSA adducts with limits of detection (LOD) of 2.67, characterization of aromatic dNCO adducts as well as in biomonitoring occupational and environmental dNCO exposures. PMID:24012971

  17. DFT Study on the Co-Xe Bond in the HCo(CO3Xe Adduct

    Directory of Open Access Journals (Sweden)

    Tamás Kégl

    2014-01-01

    Full Text Available The metal-xenon interaction has been studied in hydrido-cobalt-carbonyl complexes by means of density functional methods. The method of choice has been selected after testing various functionals including dispersion correction on the bond dissociation enthalpy of Xe in the Cr(CO5Xe adduct. In general, the long range corrected versions of popular gradient-corrected functionals performed well. In particular, LC-mPWPW91 resulted in a perfect match with available experimental data; therefore this functional was selected for the computation of HCo(CO3Xe adducts. For HCo(CO3Xe two isomers have been located; the structure with CS symmetry has proved to be more stable by 5.3 kcal/mol than the C3V adduct in terms of free energy. The formation of HCo(CO3Xe is, however, endergonic by 3.5 kcal/mol for the CS isomer.

  18. Multi-epoch Sub-arcsecond [Fe II] Spectroimaging of the DG Tau Outflows with NIFS. I. First data epoch

    CERN Document Server

    White, Marc C; Bicknell, Geoffrey V; Salmeron, Raquel; Beck, Tracy L

    2014-01-01

    Investigating the outflows emanating from young stellar objects (YSOs) on sub-arcsecond scales provides important clues to the nature of the underlying accretion-ejection process occurring near the central protostar. We have investigated the structures and kinematics of the outflows driven by the YSO DG Tauri, using the Near-infrared Integral Field Spectrograph (NIFS) on Gemini North. The blueshifted outflow shows two distinct components in [Fe II] 1.644 micron emission, which are separated using multi-component line fitting. A stationary recollimation shock is observed, in agreement with previous X-ray and FUV observations. The presence of this shock indicates that the innermost streamlines of the high-velocity component are launched at a very small radius, 0.01-0.15 AU, from the central star. The jet accelerates and expands downstream of the recollimation shock; the 'acceleration' is likely a sign of velocity variations in the jet. No evidence of rotation is found, and we compare this non-detection to previ...

  19. A Very Bright, Very Hot, and Very Long Flaring Event from the M Dwarf Binary System DG CVn

    CERN Document Server

    Osten, Rachel A; Drake, Stephen A; Krimm, Hans; Page, Kim; Gazeas, Kosmas; Kennea, Jamie; Oates, Samantha; Page, Mathew; de Miguel, Enrique; Novák, Rudolf; Apeltauer, Tomas; Gehrels, Neil

    2016-01-01

    On April 23, 2014, the Swift satellite responded to a hard X-ray transient detected by its Burst Alert Telescope, which turned out to be a stellar flare from a nearby, young M dwarf binary DG~CVn. We utilize observations at X-ray, UV, optical, and radio wavelengths to infer the properties of two large flares. The X-ray spectrum of the primary outburst can be described over the 0.3-100 keV bandpass by either a single very high temperature plasma or a nonthermal thick-target bremsstrahlung model, and we rule out the nonthermal model based on energetic grounds. The temperatures were the highest seen spectroscopically in a stellar flare, at T$_{X}$ of 290 MK. The first event was followed by a comparably energetic event almost a day later. We constrain the photospheric area involved in each of the two flares to be $>$10$^{20}$ cm$^{2}$, and find evidence from flux ratios in the second event of contributions to the white light flare emission in addition to the usual hot, T$\\sim$10$^{4}$K blackbody emission seen in ...

  20. HST\\/STIS Spectroscopy of the Optical Outflow from DG Tau Indications for Rotation in the Initial Jet Channel

    CERN Document Server

    Bacciotti, F; Mundt, R; Eislöffel, J; Solf, J

    2002-01-01

    We have carried out a kinematical, high angular resolution (~ 0".1) study of the jet from DG Tau within 0."5 from the source (or 110 AU along this flow). We analysed line profiles extracted from a set of seven spectra taken with STIS on board the Hubble Space Telescope, with the slits parallel to the jet axis but displaced transversely every 0".07. For the flow of moderate velocity (-70 km/s), we have found systematic differences in the radial velocities of lines emitted on alternate sides of the jet axis. The results are corrected for the effects due to uneven illumination of the slit. The relative Doppler shifts range from 5 to 20 km/s. If this is interpreted as rotation, the flow is then rotating clockwise looking from the jet towards the source and the derived toroidal velocities are in the range 6 - 15 km/s. Using recent estimates of the mass loss rate, one obtains for the considered velocity regime, an angular momentum flux of ~ 3.8x10E-5 M_sun/yr AU km/s. Our findings may constitute the first detection...

  1. Formation of melamium adducts by pyrolysis of thiourea or melamine/NH4 Cl mixtures.

    Science.gov (United States)

    Braml, Nicole E; Sattler, Andreas; Schnick, Wolfgang

    2012-02-01

    Pyrolysis of prominent precursor compounds for the synthesis of carbon nitride type materials (e.g., melamine, thiourea) have been studied in detail. Molecular adducts containing monoprotonated melamium C(6)N(11)H(10)(+) and melaminium HC(3)N(3)(NH(2))(3)(+) ions, respectively, have been identified as intermediates. The adduct C(6)N(11)H(10)Cl·0.5NH(4)Cl was obtained by the reaction of melamine C(3)N(3)(NH(2))(3) with NH(4)Cl at 450 °C. During the pyrolysis of thiourea, guanidinium thiocyanate was initially formed and subsequently the melamium thiocyanate melamine adduct C(6)N(11)H(10)SCN·2C(3)N(3)(NH(2))(3) was isolated at 300 °C. A second melaminium thiocyanate melamine adduct with the formula HC(3)N(3)(NH(2))(3)SCN·2C(3)N(3)(NH(2))(3) represents an intermediary reaction product that is best accessible at low pressures. The crystal structures of the compounds were solved by single-crystal XRD. Unequivocal proton localization at the C(6)N(11)H(10)(+) ion was established. A typical intramolecular and interannular hydrogen bridge and other characteristic hydrogen-bonding motifs were identified. Additionally, the adducts were investigated by solid-state NMR spectroscopy. Our study provides detailed insight into the thermal condensation of thiourea by identifying and characterizing key intermediates involved in the condensation process leading to carbon nitride type materials. Furthermore, factors promoting the formation of melamium adduct phases over melem are discussed. PMID:22223531

  2. "Danger" conditions increase sulfamethoxazole-protein adduct formation in human antigen-presenting cells.

    Science.gov (United States)

    Lavergne, S N; Wang, H; Callan, H E; Park, B K; Naisbitt, D J

    2009-11-01

    Antigen-presenting cells (APC) are thought to play an important role in the pathogenesis of drug-induced immune reactions. Various pathological factors can activate APC and therefore influence the immune equilibrium. It is interesting that several diseases have been associated with an increased rate of drug allergy. The aim of this project was to evaluate the impact of such "danger signals" on sulfamethoxazole (SMX) metabolism in human APC (peripheral blood mononuclear cells, Epstein-Barr virus-modified B lymphocytes, monocyte-derived dendritic cells, and two cell lines). APC were incubated with SMX (100 microM-2 mM; 5 min-24 h), in the presence of pathological factors: bacterial endotoxins (lipopolysaccharide and staphylococcal enterotoxin B), flu viral proteins, cytokines [interleukin (IL)-1beta, IL-6, IL-10; tumor necrosis factor-alpha; interferon-gamma; and transforming growth factor-beta], inflammatory molecules (prostaglandin E2, human serum complement, and activated protein C), oxidants (buthionine sulfoximine and H(2)O(2)), and hyperthermia (37.5-39.5 degrees C). Adduct formation was evaluated by enzyme-linked immunosorbent assay and confocal microscopy. SMX-protein adduct formation was time- and concentration-dependent for each cell type tested, in both physiological and danger conditions. A danger environment significantly increased the formation of SMX-protein adducts and significantly shortened the delay for their detection. An additive effect was observed with a combination of danger signals. Dimedone (chemical selectively binding cysteine sulfenic acid) and antioxidants decreased both baseline and danger-enhanced SMX-adduct formation. Various enzyme inhibitors were associated with a significant decrease in SMX-adduct levels, with a pattern varying depending on the cell type and the culture conditions. These results illustrate that danger signals enhance the formation of intracellular SMX-protein adducts in human APC. These findings might be relevant

  3. GSTM1 and XRCC3 Polymorphisms: Effects on Levels of Aflatoxin B1-DNA Adducts

    Institute of Scientific and Technical Information of China (English)

    Xi-dai Long; Yun Ma; Zhou-lin Deng

    2009-01-01

    Objective: Aflatoxin B1 (AFB1), which can cause the formation of AFB1-DNA adducts, is a known human carcinogen. AFB1-exposure individuals with inherited susceptible carcinogen-metabolizing or repairing genotypes may experience an increased risk of genotoxicity. This study was designed to investigate whether the polymorphisms of two genes, the metabolic gene Glutathione S-transferase M1 (GSTM1) and DNA repair gene x-ray repair cross-complementing group 3 (XRCC3), can affect the levels of AFB1-DNA adducts in Guangxi Population (n= 966) from an AFB1-exposure area.Methods: AFB1-DNA adducts were measured by ELISA, and GSTM1 and XRCC3 codon 241 genotypes were identified by PCR-RFLP.Results: The GSTM1-null genotype [adjusted odds ratio (OR) = 2.09; 95% confidence interval (CI) = 1.61(2.71] and XRCC3 genotypes with 241 Met alleles [i.e., XRCC3-TM and -MM, adjusted ORs (95% CI) were 1.43 (1.08(1.89) and 2.42 (1.13(5.22), respectively] were significantly associated with higher levels of AFB1-DNA adducts. Compared with those individuals who did not express any putative risk genotypes as reference (OR = 1), individuals featuring all of the putative risk genotypes did experience a significantly higher DNA-adduct levels (adjusted ORs were 2.87 for GSTM1-null and XRCC3-TM; 5.83 for GSTM1-null and XRCC3-MM). Additionally, there was a positive joint effect between XRCC3 genotypes and long-term AFB1 exposure in the formation of AFB1-DNA adducts.Conclusion: These results suggest that individuals with susceptible genotypes GSTM1-null, XRCC3-TM, or XRCC3-MM may experience an increased risk of DNA damage elicited by AFB1 exposure.

  4. Safrole-DNA adduct in hepatocellular carcinoma associated with betel quid chewing.

    Science.gov (United States)

    Chung, Yu-Ting; Chen, Chiu-Lan; Wu, Cheng-Chung; Chan, Shan-An; Chi, Chin-Wen; Liu, Tsung-Yun

    2008-12-15

    Betel quid chewing, which contributes high concentration of safrole in saliva, is a popular oral habit in Taiwan. Safrole is a documented rodent hepatocarcinogen, yet its hepatocarcinogenic potential in human is not known. Here, we used LC/ESI-ITMS(n) and LC/QTOF-MS confirmed safrole-dGMP as reference standard to detect the safrole-DNA adduct in hepatic tissues from HBsAg-/HCV-seronegative hepatocellular carcinoma patients by (32)P-postlabeling. We first synthesized and confirmed safrole-dGMP by LC/MS. Two isomeric safrole-dGMPs were characterized as N(2)-(trans-isosafrol-3'-yl) deoxyguanosine and N(2)-(safrol-1'-yl) deoxyguanosine. This technique was able to detect hepatic safrole-DNA adduct in mice that were treated with safrole but not sensitive enough to detect safrole-DNA adduct in human samples. Using the nuclease P1 version of the (32)P-postlabeling technique, we detected the presence of safrole-DNA adduct in two out of 28 hepatic tissues from hepatocellular carcinoma patients, and only these two patients had a history of betel quid chewing lasting more than 10 years. From co-chromatography with the mass confirmed safrole-dGMPs, this safrole-DNA adduct was identified as N(2)-(trans-isosafrol-3'-yl) deoxyguanosine. These results suggest that betel quid-containing safrole might be involved in the pathogenesis of hepatocellular carcinoma in human beings and LC/MS has the potential to identify DNA adducts in clinical samples.

  5. Research of high-accurary PWM output in overfrequency based on MC9S12DG128B%基于MC9S12DG128B超频状态下高精度PWM输出的研究

    Institute of Scientific and Technical Information of China (English)

    徐杰

    2011-01-01

    Based on Freescale MC9S12DG128 as the core control unit, designed and implemented the PWM output under over-clocking conditionso The higher precision of the PWM output is,the less of the PWM output value is. And the PWM output pulse amplitude decreases, overelocking can be applied to high precision PWM output system.%以MC9S12DG128作为核心控制单元,利用MC9S12DG128实现了超频条件下的高精度PWM输出。随着输出PWM精度的增加,PWM输出的幅值开始减小,同时PWM输出脉冲幅值减小,超频状态下可应用于高精度PWM输出系统中。

  6. White blood cell DNA adducts and fruit and vegetable consumption in bladder cancer.

    Science.gov (United States)

    Peluso, M; Airoldi, L; Magagnotti, C; Fiorini, L; Munnia, A; Hautefeuille, A; Malaveille, C; Vineis, P

    2000-02-01

    The 'Mediterranean diet', a diet rich in cereals, fruit and vegetables, has been associated with lowering the risk of a variety of cancers of the digestive tract and the bladder. In a previous study, we showed that the high phenolic content these dietary components produce in the urine could be associated with higher antimutagenic properties of the urine and lower arylamine-DNA adducts in exfoliated bladder cells. We have conducted a case-control study on 162 bladder cancer patients and 104 hospital controls. Total aromatic DNA adducts were measured in white blood cells (WBC) of all subjects by (32)P-post-labelling. Genetically based metabolic polymorphisms were analysed by PCR-RFLP (NAT2, GSTM1, GSTT1, GSTP1, COMT and NQO1). All subjects were interviewed about their tobacco use, dietary habits and other risk factors. The odds ratio (OR) for the risk of bladder cancer according to the presence/absence of WBC DNA adducts (detection limit 0.1 RALx10(8)) was 3.7 [95% confidence interval (CI) 2.2-6.3] and a dose-response relationship with levels of adducts was apparent. The association between case/control status and the presence of WBC DNA adducts was significantly stronger in the subjects who consumed fewer portions of fruit or vegetables per day (OR 7.80, 95% CI 3.0-20.30 for 0-1 portions of vegetables) than in the heavy consumers (OR 4.98 for consumers of 2 portions daily, OR 1.97 for consumers of > or =3 portions; similar but lower estimates were found for the intake of fruit). No association was noticed between tobacco smoking and WBC DNA adducts. Only NAT-2, among the several genotypes considered, was associated in a statistically significant way with the risk of bladder cancer (OR 1.72, 95% CI 1.03-2.87) and with the levels of WBC DNA adducts. Our report suggests that fruit and vegetables could protect against bladder cancer by inhibiting the formation of DNA adducts. PMID:10657956

  7. Active Oxygen Radical Scavenging Ability of Water-Soluble β-Alanine C60 Adducts

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Water-soluble β-alanine C60 adducts were synthesized, and the scavenging ability to superoxygen anion radical O2-and hydroxyl radicalOH were studied by autoxidation ofpyrogallol and chemiluminescence, respectively. It was found that β-alanine C60 adducts showed an excellent efficiency in eliminating superoxygen anion radical and hydroxyl radical. The 50% inhibition concentration (IC50) for superoxygen anion radical and hydroxyl radical were 0.15 mg/mL and 0.048 mg/mL, respectively. The difference should be mainly attributed to the different scavenging mechanisms.

  8. Olefin Hydroborations with Diamidocarbene–BH3 Adducts at Room Temperature

    Directory of Open Access Journals (Sweden)

    Dominika N. Lastovickova

    2016-09-01

    Full Text Available An isolable N,N’-diamidocarbene (DAC was previously shown to promote the B–H bond activation of various BH3 complexes. The resultant DAC–BH3 adducts facilitated olefin hydroborations under mild conditions and in the absence of exogenous initiators. The substrate scope for such transformations was further explored and is described herein. While organoboranes were obtained in quantitative yields from various terminal and internal olefins, use of the latter substrates resulted in intramolecular ring-expansion of the newly formed DAC–borane adducts.

  9. Effect of external electric field on Cyclodextrin-Alcohol adducts: A DFT study

    Indian Academy of Sciences (India)

    Kundan Baruah; Pradip Kr Bhattacharyya

    2015-06-01

    Effect of external electric fields on the interaction energy between cyclodextrin and alcohol was analyzed in the light of density functional theory (DFT) and density functional reactivity theory (DFRT). Stability of the cyclodextrin-alcohol adducts was measured in terms of DFT based reactivity descriptor, global hardness, electrophilicity, and energy of the HOMO. Stability of adducts was observed to be sensitive towards the strength as well as direction of the applied external electric field. In addition, reactivity pattern follows the maximum hardness and minimum electrophilicity principles.

  10. Dosimetry by means of DNA and hemoglobin adducts in propylene oxide-exposed rats

    International Nuclear Information System (INIS)

    The main purpose of the study was to establish the relation between exposure dose of propylene oxide (PO) and dose in various tissues of male F344 rats exposed to the compound by inhalation. The animals were exposed to 0, 5, 25, 50, 300, or 500 ppm PO in the air for 3 days (6 h/day) or 4 weeks (6 h/day, 5 days/week). Blood, nasal respiratory epithelium, lung, and liver were collected. 2-Hydroxypropylvaline (HPVal) in hemoglobin was quantified using the N-alkyl Edman method and gas chromatography/tandem mass spectrometry. 7-(2-Hydroxypropyl)guanine (7-HPG) in DNA was quantified using 32P postlabeling. The levels of 7-HPG in DNA of nasal respiratory epithelium and lung increased linearly with concentration as measured both after 3 days and 4 weeks of exposure. Similarly, 7-HPG in liver DNA and HPVal in hemoglobin showed a linear increase with PO concentration in the 3-day exposure group, whereas a deviation from linearity was observed above 300 ppm in the 4-week exposure group. The new results confirm previous observations of a dose difference between tissues with the highest dose present in the nasal respiratory epithelium. The measured adduct levels were used for calculation of adduct increments and corresponding tissue doses per unit of external exposure dose. For this purpose, the buildup of adducts was modeled considering the different kinetics of formation and elimination of adducts with DNA and hemoglobin, respectively, and also considering the increasing body weight of the animals. The half-life of 7-HPG in vivo, as well as tissue doses, could be solved from DNA adduct data at the 3rd and 26th days. Within the range of concentrations where the dose-response curves for adduct formation are linear, the relationship between exposure dose and resulting tissue doses could be based equally well on adduct data from the short-term exposure as on adduct data from the prolonged exposure

  11. Polycyclic Aromatic Hydrocarbon–DNA Adducts and Breast Cancer: A Pooled Analysis

    OpenAIRE

    Gammon, Marilie D.; Sagiv, Sharon K.; Eng, Sybil M.; Shantakumar, Sumitra; Gaudet, Mia M.; Teitelbaum, Susan L; Britton, Julie A.; Terry, Mary Beth; WANG, LIAN WEN; Wang, Qiao; STELLMAN, STEVE D.; Beyea, Jan; Hatch, Maureen; Kabat, Geoffrey C; Wolff, Mary S.

    2004-01-01

    Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with breast cancer in several small studies. The authors’ pooled analysis included 873 cases and 941 controls from a population-based case-control study. Competitive enzyme-linked immunosorbent assay in peripheral mononuclear cells was conducted in 2 rounds, and results were pooled on the basis of round-specific quantiles. The odds ratio for breast cancer was elevated in relation to detectable PAH-DNA adducts (1.29 as comp...

  12. Diagnostic ions for the analysis of phenylalanine adducts of acrylamide and styrene by ESI-QTOF mass spectrometry.

    Science.gov (United States)

    Chu, Fong Lam; Sleno, Lekha; Yaylayan, Varoujan Antranik

    2013-10-30

    To facilitate the detection of acrylamide or styrene adduct of amino acids by mass spectrometry based techniques, phenylalanine was used as a representative amino acid and pyrolysis was employed in conjunction with isotope labeling technique as a microscale sample preparation tool to generate the reaction products. The residues remaining after the pyrolysis of phenylalanine/styrene, phenylalanine/acrylamide, and phenylalanine/glucose mixtures at 250 °C were analyzed by electrospray quadrupole time-of-flight (ESI-QqTOF) mass spectrometry to identify the adducts. The phenylalanine/acrylamide adduct was independently synthesized for confirmation. Characteristic product ions in the tandem mass spectra were found at m/z 191 for the acrylamide adduct and at m/z 262 and 190 for its double-addition product. On the other hand, an ion at m/z 224 was shown to be diagnostic of the styrene adduct. The ability of the m/z 224 ion to predict the presence of styrene adduct in a heated phenylalanine/glucose model system was tested and verified. Detailed isotope labeling analysis of the phenylalanine/glucose model further indicated the formation of a novel adduct that was consistent with the reaction of the Amadori product with styrene. Such diagnostic ions that are needed to develop MS/MS-based screening methodologies may accelerate in the future the detection of Michael-type adducts in food.

  13. Cigarette Smoking, BPDE-DNA Adducts, and Aberrant Promoter Methylations of Tumor Suppressor Genes (TSGs) in NSCLC from Chinese Population.

    Science.gov (United States)

    Jin, Yongtang; Xu, Peiwei; Liu, Xinneng; Zhang, Chunye; Tan, Cong; Chen, Chunmei; Sun, Xiaoyu; Xu, Yingchun

    2016-01-01

    Non-small cell lung cancer (NSCLC) is related to the genetic and epigenetic factors. The goal of this study was to determine association of cigarette smoking and BPDE-DNA adducts with promoter methylations of several genes in NSCLC. Methylation of the promoters of p16, RARβ, DAPK, MGMT, and TIMP-3 genes of tumor tissues from 199 lung cancer patients was analyzed with methylation-specific PCR (MSP), and BPDE-DNA adduct level in lung cancer tissue was obtained by ELISA. Level of BPDE-DNA adduct increased significantly in males, aged people (over 60 years), and smokers; however, no significant difference was found while comparing the BPDE-DNA adduct levels among different tumor types, locations, and stages. Cigarette smoking was also associated with increased BPDE-DNA adducts level (OR = 2.43, p > .05) and increased methylation level in at least 1 gene (OR = 5.22, p smoking also significantly increase the risk of p16 or DAPK methylation (OR = 3.02, p smoking for more than 40 pack-years (OR = 4.21, p smoking is significantly associated with the increase of BPDE-DNA adduct level, promoter hypermethylation of p16 and DAPK genes, while BPDE-DNA adduct was not significantly related to abnormal promoter hypermethylation in TSGs, suggesting that BPDE-DNA adducts and TSGs methylations play independent roles in NSCLC.

  14. Glutathionetransferase activity and PAN-DNA adducts in human placenta as a risk factor for newborn in radioactively contaminated regions

    International Nuclear Information System (INIS)

    It was shown that the higher is the contamination of area the more decreased is GST activity and the more abundant are PAH adducts in placental DNA. Placental glutathionetransferase activity and level of PAH-DNA adducts content in placental tissue are the integral indices of environmental pollution, efficiency of maternal and placental detoxification and a prognostic factor for newborn

  15. Few constraints limit the design of quinone methide-oligonucleotide self-adducts for directing DNA alkylation†

    OpenAIRE

    Rossiter, Clifford S.; Modica, Emilia; Kumar, Dalip; Rokita, Steven E

    2010-01-01

    Nucleotide sequences minimally containing adenosine, cytosine or guanosine are sufficient to form intrastrand oligonucleotide quinone methide self-adducts reversibly for subsequent alkylation of complementary DNA. The general lack of sequence restrictions should now allow for alkylation of most any target of interest although reaction is most efficient when the self-adducts contain guanine residues and do not form hairpin structures.

  16. Bulky carcinogen-DNA adducts and exposure to environmental and occupational sources of polycyclic aromatic hydrocarbons. Influence of susceptibility genotypes on adduct level

    International Nuclear Information System (INIS)

    PAH exposure, whether it is of occupational or environmental origin, is thought to result in an elevated risk of cancer especially in the lungs. DNA damage is considered an important step in the carcinogenic effect of PAH. Hence, methods that elucidate the steps in the carcinogenic process are important to understand the action of PAH. It may prove useful in the exposure assessment and in combination with classical epidemiological methods give better basis for risk estimation. The objective in this thesis was to evaluate the feasibility of the 32P-postlabeling method to detect carcinogen-DNA adducts for assessing exposure to DNA damaging compounds in different occupationally and environmentally exposed groups. The studies included groups, that have an elevated cancer risk due to occupational exposure to PAH. Exposure levels were supposed to be relatively low according to reports on occupational and environmental air quality programs. Another aim was to evaluate the influence of polymorphisms in metabolizing enzyme genes on DNA adduct levels. A third objective was to establish some kind of baseline DNA adduct level for individuals with supposed low exposure, and compare it to the more exposed groups. A fourth aim in these studies was to examine if biomarkers of genotoxic exposure could be useful in epidemiological studies to identify groups at risk and thereby contribute with better exposure estimates in the study of PAH related cancer risk. (EG)

  17. Bulky carcinogen-DNA adducts and exposure to environmental and occupational sources of polycyclic aromatic hydrocarbons. Influence of susceptibility genotypes on adduct level

    Energy Technology Data Exchange (ETDEWEB)

    Sabro Nielsen, P.

    1996-12-31

    PAH exposure, whether it is of occupational or environmental origin, is thought to result in an elevated risk of cancer especially in the lungs. DNA damage is considered an important step in the carcinogenic effect of PAH. Hence, methods that elucidate the steps in the carcinogenic process are important to understand the action of PAH. It may prove useful in the exposure assessment and in combination with classical epidemiological methods give better basis for risk estimation. The objective in this thesis was to evaluate the feasibility of the {sup 32}P-postlabeling method to detect carcinogen-DNA adducts for assessing exposure to DNA damaging compounds in different occupationally and environmentally exposed groups. The studies included groups, that have an elevated cancer risk due to occupational exposure to PAH. Exposure levels were supposed to be relatively low according to reports on occupational and environmental air quality programs. Another aim was to evaluate the influence of polymorphisms in metabolizing enzyme genes on DNA adduct levels. A third objective was to establish some kind of baseline DNA adduct level for individuals with supposed low exposure, and compare it to the more exposed groups. A fourth aim in these studies was to examine if biomarkers of genotoxic exposure could be useful in epidemiological studies to identify groups at risk and thereby contribute with better exposure estimates in the study of PAH related cancer risk. (EG).

  18. Small-Signal Modeling of the PVR-Based AD Scheme and Controller Design for Three-Phase Standalone DG System

    DEFF Research Database (Denmark)

    Shen, Pan; Han, Yang; Lu, Chang;

    2016-01-01

    controllers are based on an enhanced proportional resonant (PR) structure to achieve zero steady-state error, and multi-resonant harmonic compensator (MRHC) plus PR controller to prevent low-order load current harmonics to distort the output voltage. The proposed small-signal model of the islanded DG system...... with multi-loop control strategy in the stationary reference frame is presented. Moreover, an enhanced delay compensation (EDC) scheme based on two integrators of the discrete PR controller is presented to improve stability margins with a higher accuracy compared with the existing methods. Then, a detailed......This paper presents the small-signal state-space modeling and a new multifunctional multi-loop control strategy for three-phase inverter-based islanded DG systems under unbalanced and/or nonlinear load conditions. The proposed control methodology utilizes the parallel virtual resistance (PVR...

  19. Dynamic rupture simulations on complex fault zone structures with off-fault plasticity using the ADER-DG method

    Science.gov (United States)

    Wollherr, Stephanie; Gabriel, Alice-Agnes; Igel, Heiner

    2015-04-01

    In dynamic rupture models, high stress concentrations at rupture fronts have to to be accommodated by off-fault inelastic processes such as plastic deformation. As presented in (Roten et al., 2014), incorporating plastic yielding can significantly reduce earlier predictions of ground motions in the Los Angeles Basin. Further, an inelastic response of materials surrounding a fault potentially has a strong impact on surface displacement and is therefore a key aspect in understanding the triggering of tsunamis through floor uplifting. We present an implementation of off-fault-plasticity and its verification for the software package SeisSol, an arbitrary high-order derivative discontinuous Galerkin (ADER-DG) method. The software recently reached multi-petaflop/s performance on some of the largest supercomputers worldwide and was a Gordon Bell prize finalist application in 2014 (Heinecke et al., 2014). For the nonelastic calculations we impose a Drucker-Prager yield criterion in shear stress with a viscous regularization following (Andrews, 2005). It permits the smooth relaxation of high stress concentrations induced in the dynamic rupture process. We verify the implementation by comparison to the SCEC/USGS Spontaneous Rupture Code Verification Benchmarks. The results of test problem TPV13 with a 60-degree dipping normal fault show that SeisSol is in good accordance with other codes. Additionally we aim to explore the numerical characteristics of the off-fault plasticity implementation by performing convergence tests for the 2D code. The ADER-DG method is especially suited for complex geometries by using unstructured tetrahedral meshes. Local adaptation of the mesh resolution enables a fine sampling of the cohesive zone on the fault while simultaneously satisfying the dispersion requirements of wave propagation away from the fault. In this context we will investigate the influence of off-fault-plasticity on geometrically complex fault zone structures like subduction

  20. The potential of platinum-DNA adduct determination in ex vivo treated tumor fragments for the prediction of sensitivity to cisplatin chemotherapy

    NARCIS (Netherlands)

    Welters, M.J.P.; Braakhuis, B.J.M.; Jacobs-Bergmans, A.J.; Kegel, A.; Baan, R.A.; Vijgh, W.J.F. van der; Fichtinger-Schepman, A.M.J.

    1999-01-01

    Background: Response to cisplatin-therapy is assumed to be related to the formation of platinum (Pt)-DNA adducts. Measurement of these adducts prior to therapy could be of value to improve cisplatin based cancer therapy. Materials and methods: We determined Pt-GG and Pt-AG adduct levels by use of 32

  1. DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening

    Directory of Open Access Journals (Sweden)

    Villoutreix Bruno O

    2009-11-01

    Full Text Available Abstract Background Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Results Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. Conclusion DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

  2. 含分布式电源的配电网固定成本分摊%Allocation of Fixed Costs in Distribution Networks with DG

    Institute of Scientific and Technical Information of China (English)

    黄庆云

    2014-01-01

    提出一种含分布式电源的固定成本分摊方法。由于分布式电源的引入,配电网络的固定成本分摊发生了改变。通过流跟踪技术及贡献因子理论,对引入分布式电源后的配电网固定成本进行了分摊研究。该方法首先考虑将固定成本在有功无功间进行分摊,然后按用户类型将有功无功成本比例分摊给负荷和电源,最后将其分摊至单个负荷及电源。并用一个含分布式电源的简单配电系统的计算实例证明方法的正确及可行。%This paper proposed a method for the allocation of fixed costs in distribution networks with DG. The introduction of DG makes the allocation of fixed costs of the whole distribution networks to be changed. Based on tracing the power flow and the theory of the contribution factor,this paper tries to allocate the fixed costs in distribution networks with DG. Firstly,the fixed costs of the distribution network are allocated to the active and reactive costs. Secondly, the active and reactive costs are allocated to the loads and generators according to the comparison. Finally, the costs are allocated to each load and generators. The paper use a simple distribution networks with DG to calculate prove the validity and feasibility of this method.

  3. Pengaruh Edukasi Gizi Terhadap Pengetahuan, Pola Makan Dan Kadar Glukosa Darah Pasien Diabetes Melitus Tipe 2 RSUD Lanto??? Dg Pasewang Jeneponto

    OpenAIRE

    Dr. Dra Nurhaedar Jafar, Apt, M.Kes

    2007-01-01

    The phenomenon of diabetes mellitus from year to year an increasing number. One major factor is the lack of knowledge in conducting therapy in patients with diabetes mellitus diit so may lead to increased blood sugar levels. The aim of this study was to determine the effect of nutrition education to increase the knowledge, dietary compliance and uncontrolled blood sugar levels Type 2 Diabetes Mellitus Outpatient in Lanto Dg Pasewang Public Hospital Jeneponto. The design of this research was ...

  4. Local tsunami early warning: the case of Rhodes island, Greece, and the NEARTOWARN (EU-DG ECHO) prevention project

    Science.gov (United States)

    Papadopoulos, Gerassimos; Argyris, Ilias; Fokaefs, Anna

    2013-04-01

    Local, that is near-field, tsunamis occur in the global ocean including the Mediterranean Sea and its connected seas. For such tsunamis the first wave has very short travel time of arrival (less than 30 min.) to the closest coastal zone thus making the early warning a very difficult task. An efficient, end-to-end early tsunami warning system in local conditions should fulfill the condition that the time needed for the earthquake detection, plus the time needed for the warning message transmission to the authorities and afterwards to the general public and/or other task groups, plus the time needed for response and real evacuation is less than the travel time of the first wave. In the physiographic conditions of the Mediterranean Sea it is extremely hard to satisfy such a condition unless the total time needed to response in early warning is drastically minimized. The project Near-Field Tsunami Warning and Emergency Planning (NEARTOWARN, which is supported by the EU DG-ECHO prevention programme, aims, among others, to establish a system in Rhodes island, Greece, with the purpose to meet needs for local early tsunami warning. To minimize the time for emergency in less than 30 sec, seismic alert devices (SED's) make the core component of the system. SED's are activated and send alerting signals as soon as a P-phase of seismic wave is detected in the near-field but for a predetermined threshold of ground motion. Then, emergency starts while SED's activate remotely other devices, such as computers with data bases of pre-calculated tsunami simulations, surveillance cameras etc. The system is completed with tide-gauges, simulated tsunami scenarios and emergency planning supported by a Geographical Management System. Rhodes island in Dodecanese, South Aegean Sea, Greece, has been selected as a test-area for the development of the prototype system given that it was hit by large tsunamigenic earthquakes several times in the past.

  5. Adduct formation of ionic and nanoparticular silver with amino acids and glutathione

    Energy Technology Data Exchange (ETDEWEB)

    Blaske, Franziska; Stork, Lisa; Sperling, Michael; Karst, Uwe, E-mail: uk@uni-muenster.de [University of Muenster, Institute of Inorganic and Analytical Chemistry (Germany)

    2013-09-15

    To investigate the interaction of ionic and nanoparticular silver with amino acids and small peptides, an electrospray ionization time-of-flight mass spectrometry method was developed. Monomeric and oligomeric silver adducts were formed with amino acids including cysteine (Cys), methionine, histidine, lysine, or the tripeptide glutathione (GSH). The obtained spectra for ionic silver show clusters in different ratios between Ag{sup +} and the reaction partners (X) including [Ag{sub n}X{sub m} - (n + 1)H]{sup -} (n = 1-4, m = 1-3). Regarding Cys, adduct clusters up to n = 5 and m = 4 were observed as well. Considering silver-GSH interactions, even doubly charged oligomers occur generating [Ag{sub (a+1)}GSH{sub a} - (a + 3)H]{sup 2-} (a = 5-7) and [Ag{sub b}GSH{sub b} - (b + 2)H]{sup 2-} (b = 4-8) ions. {sup 1}H NMR data of free GSH compared to that after treatment with Ag{sup +} confirm sulfur-metal interactions due to changing chemical shifts for the protons located adjacent to the thiol group. Density functional theory calculations for silver-GSH clusters may explain the formation of experimentally recorded large clusters due to cooperative effects between silver and carboxylic acid side chains. Both sets of experiments indicate the presence of these adducts in the liquid phase. For silver nanoparticles, the respective data confirm the release of silver ions and the subsequent adduct formation.

  6. Correlation between the knee adduction torque and medial contact force for a variety of gait patterns.

    Science.gov (United States)

    Zhao, Dong; Banks, Scott A; Mitchell, Kim H; D'Lima, Darryl D; Colwell, Clifford W; Fregly, Benjamin J

    2007-06-01

    The external knee adduction torque has been proposed as a surrogate measure for medial compartment load during gait. However, a direct link between these two quantities has not been demonstrated using in vivo measurement of medial compartment load. This study uses in vivo data collected from a single subject with an instrumented knee implant to evaluate this link. The subject performed five different overground gait motions (normal, fast, slow, wide, and toe-out) with simultaneous collection of instrumented implant, video motion, and ground reaction data. For each trial, the knee adduction torque was measured externally while the total axial force applied to the tibial insert was measured internally. Based on data collected from the same subject performing treadmill gait under fluoroscopic motion analysis, a regression equation was developed to calculate medial contact force from the implant load cell measurements. Correlation analyses were performed for the stance phase and entire gait cycle to quantify the relationship between the knee adduction torque and both the medial contact force and the medial to total contact force ratio. When the entire gait cycle was analyzed, R(2) for medial contact force was 0.77 when all gait trials were analyzed together and between 0.69 and 0.93 when each gait trial was analyzed separately (p knee adduction torque is highly correlated with medial compartment contact force and medial to total force ratio during gait.

  7. New adduct of abietane-type diterpene from Salvia leriifolia Benth.

    Science.gov (United States)

    Hussain, Amjad; Adhikari, Achyut; Iqbal Choudhary, M; Ayatollahi, Syed Abdulmajid; Atta-Ur-Rahman

    2016-07-01

    A new adduct of abietane-type diterpene, salvialeriicone (1), was isolated from Salvia leriifolia Benth., along with a new chemical entity nor-abietane diterpene, 2-isopropyl-8,8-dimethyl-7,8-dihydrophenanthrene-1,4,5(6H)-trione (2). Their structures were determined using mass spectrometry, and 1D- and 2D-NMR spectroscopy. PMID:27266891

  8. 40 CFR 721.3700 - Fatty acid, ester with styrenated phenol, ethylene oxide adduct.

    Science.gov (United States)

    2010-07-01

    ... phenol, ethylene oxide adduct. 721.3700 Section 721.3700 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.3700 Fatty acid, ester with styrenated phenol... chemical substance identified generically as fatty acid, ester with styrenated phenol, ethylene...

  9. Sigma-Adducts of pteridines and 3-deazapteridines : structure and reactivity

    NARCIS (Netherlands)

    Nagel, A.

    1978-01-01

    In the introduction of this thesis the reactions of pteridines and pyrido[2,3- b ]-pyrazines with nucleophiles are reviewed. In the following chapters the results of an NMR investigation on the formation of σ-adducts between these azaaromatic ring systems and nitrogen nucleophiles, especially KNH

  10. Lysine adducts between methyltetrahydrophthalic anhydride and collagen in guinea pig lung.

    Science.gov (United States)

    Jönsson, B A; Wishnok, J S; Skipper, P L; Stillwell, W G; Tannenbaum, S R

    1995-11-01

    The formation of adducts between methyltetrahydrophthalic anhydride (MTHPA), an important industrial chemical and potent allergen, and collagen from guinea pig lung tissue was investigated. Collagen peptides were obtained from the lung tissue by homogenization, defatting, washing, and digestion with collagenase. In experiments in vitro, lung tissue was exposed to 8.4 mumol (50 microCi) of 14C MTHPA. The amount of adducts was 97 nmol MTHPA/g of wet tissue as determined from the bound radioactivity. In a study in vivo, four guinea pigs were injected intratracheally with 8.4 mumol of 14C MTHPA each. The amount of adducts was 0-1.2 nmol MTHPA/g of wet tissue (determined by bound radioactivity). N epsilon-methyltetrahydrophthaloyl-L-lysine (MTHPL) was synthesized and characterized by NMR, UV, and mass spectrometry (MS). A method to analyze MTHPL, after derivatization with methanol and pentafluorobenzoyl chloride, using gas chromatography-MS was developed. Analysis of Pronase-digested MTHPA-exposed lung tissue showed a concentration of 19 nmol MTHPL/g wet lung in vitro and between 0 and 0.15 nmol MTHPL/g wet lung in vivo. Thus, 20% in vitro and 12-15% in vivo of the bound radioactivity was found as adducts with lysine. These results are a first step toward studies of allergenic epitopes in proteins and methods for biological monitoring of exposure to acid anhydrides.

  11. Eccentric hip adduction and abduction strength in elite soccer players and matched controls

    DEFF Research Database (Denmark)

    Thorborg, Kristian; Couppé, C; Petersen, J;

    2011-01-01

    Eccentric hip adduction and abduction strength plays an important role in the treatment and prevention of groin injuries in soccer players. Lower extremity strength deficits of less than 10% on the injured side, compared to the uninjured side, have been suggested as the clinical milestone before...

  12. Cisplatin-DNA adduct formation in rat spermatozoa and its effect on fetal development

    NARCIS (Netherlands)

    Hooser, S.T.; Dijk-Knijnenburg, C.M. van; Waalkens-Berendsen, I.D.H.; Smits-van Prooije, A.E.; Snoeij, N.J.; Baan, R.A.; Fichtinger-Schepman, M.J.

    2000-01-01

    Exposure of males to some genotoxic chemicals causes DNA damage in spermatozoa resulting in embryotoxicity and developmental defects in their offspring. This study demonstrates that cisplatin-DNA adducts could be measured in spermatozoa following treatment with the antineoplastic drug, cisplatin. Th

  13. Ambulatory measurement of the knee adduction moment in patients with osteoarthritis of the knee

    NARCIS (Netherlands)

    Noort, van den J.C.; Esch, van der M.; Steultjens, M.P.M.; Dekker, J.; Schepers, H.M.; Veltink, P.H.

    2013-01-01

    High knee joint-loading increases the risk and progression of knee osteoarthritis (OA). Mechanical loading on the knee is reflected in the external knee adduction moment (KAdM) that can be measured during gait with laboratory-based measurement systems. However, clinical application of these systems

  14. The knee adduction moment measured with an instrumented force shoe in patients with knee osteoarthritis

    NARCIS (Netherlands)

    Noort, van den Josien C.; Esch, van der Martin; Steultjens, Martijn P.M.; Dekker, Joost; Schepers, H. Martin; Veltink, Peter H.; Harlaar, Jaap

    2012-01-01

    The external knee adduction moment (KAdM) during gait is an important parameter in patients with knee osteoarthritis (OA). KAdM measurement is currently restricted to instruments only available in gait laboratories. However, ambulatory movement analysis technology, including instrumented force shoes

  15. New adduct of abietane-type diterpene from Salvia leriifolia Benth.

    Science.gov (United States)

    Hussain, Amjad; Adhikari, Achyut; Iqbal Choudhary, M; Ayatollahi, Syed Abdulmajid; Atta-Ur-Rahman

    2016-07-01

    A new adduct of abietane-type diterpene, salvialeriicone (1), was isolated from Salvia leriifolia Benth., along with a new chemical entity nor-abietane diterpene, 2-isopropyl-8,8-dimethyl-7,8-dihydrophenanthrene-1,4,5(6H)-trione (2). Their structures were determined using mass spectrometry, and 1D- and 2D-NMR spectroscopy.

  16. Conformational, IR spectroscopic and electronic properties of conium alkaloids and their adducts with C60 fullerene

    Science.gov (United States)

    Zabolotnyi, M. A.; Prylutskyy, Yu I.; Poluyan, N. A.; Evstigneev, M. P.; Dovbeshko, G. I.

    2016-08-01

    Conformational, IR spectroscopic and electronic properties of the components of Conium alkaloids (Conium maculatum) in aqueous environment were determined by model calculations and experiment. With the help of FT-IR spectroscopy the possibility of formation of an adduct between γ-coniceine alkaloid and C60 fullerene was demonstrated, which is important for further application of conium analogues in biomedical purposes.

  17. DNA adducts induced by in vitro activation of extracts of diesel and biodiesel exhaust particles

    Science.gov (United States)

    AbstractContext: Biodiesel and biodiesel-blend fuels offer a renewable alternative to petroleum diesel, but few data are available concerning the carcinogenic potential of biodiesel exhausts. Objectives: We compared the formation of covalent DNA adducts by the in vitro metabol...

  18. Electroluminescent TCC, C3dg and fB/Bb epitope assays for profiling complement cascade activation in vitro using an activated complement serum calibration standard.

    Science.gov (United States)

    van Vuuren, B Jansen; Bergseth, G; Mollnes, T E; Shaw, A M

    2014-01-15

    Electroluminescent assays for epitopes on the complement components C3dg, terminal complement complex (TCC) and factor B/Bb (fB/Bb) have been developed with capture and detection antibodies to produce detection limits C3dg=91±9ng/mL, TCC=3±0.1ng/mL and fB=55.7±0.1ng/mL. The assay performance was assessed against a series of zymosan and heat aggregated IgG (HAIgG) in vitro activations of complement using a calibrated activated complement serum (ACS) as calibration standard. The ACS standard was stable within 20% accuracy over a 6-month period with freeze-thaw cycles as required. Differential activation of the complement cascade was observed for TCC showing a pseudo-first order formation half-life of 3.5h after activation with zymosan. The C3dg activation fragment indicates a 10% total activation for both activation agents. The kinetic-epitope analysis for fB indicates that the capture epitope is on the fB/Bb protein fragment which can then become covered by the formation of C3bBb or C3bBbP complexes during the time course of the cascade.

  19. Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity.

    Directory of Open Access Journals (Sweden)

    Laura James

    Full Text Available Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; p<0.001, glycodeoxycholic acid (R=0.581; p<0.001, and glycochenodeoxycholic acid (R=0.571; p<0.001. Variability in bile acids was greater among hospitalized children receiving low doses of acetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury.

  20. Role of CYP1B1 in PAH-DNA adduct formation and breast cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Russell, Marion L.; Muller, A.P.; Caleffi, M.; Eschiletti, J.; Graudenz, M.; Sohn, Michael D.

    2010-04-01

    This study investigated the hypothesis that increased exposure to polycyclic aromatic hydrocarbons (PAHs) increases breast cancer risk. PAHs are products of incomplete burning of organic matter and are present in cigarette smoke, ambient air, drinking water, and diet. PAHs require metabolic transformation to bind to DNA, causing DNA adducts, which can lead to mutations and are thought to be an important pre-cancer marker. In breast tissue, PAHs appear to be metabolized to their cancer-causing form primarily by the cytochrome P450 enzyme CYP1B1. Because the genotoxic impact of PAH depends on their metabolism, we hypothesized that high CYP1B1 enzyme levels result in increased formation of PAH-DNA adducts in breast tissue, leading to increased development of breast cancer. We have investigated molecular mechanisms of the relationship between PAH exposure, CYP1B1 expression and breast cancer risk in a clinic-based case-control study. We collected histologically normal breast tissue from 56 women (43 cases and 13 controls) undergoing breast surgery and analyzed these specimens for CYP1B1 genotype, PAH-DNA adducts and CYP1B1 gene expression. We did not detect any difference in aromatic DNA adduct levels of cases and controls, only between smokers and non-smokers. CYP1B1 transcript levels were slightly lower in controls than cases, but the difference was not statistically significant. We found no correlation between the levels of CYP1B1 expression and DNA adducts. If CYP1B1 has any role in breast cancer etiology it might be through its metabolism of estrogen rather than its metabolism of PAHs. However, due to the lack of statistical power these results should be interpreted with caution.

  1. Quantitative analysis of positional isomers of triacylglycerols via electrospray ionization tandem mass spectrometry of sodiated adducts.

    Science.gov (United States)

    Herrera, Lisandra Cubero; Potvin, Michael A; Melanson, Jeremy E

    2010-09-01

    Herein we report a reversed-phase high-performance liquid chromatography tandem mass spectrometry (RP-HPLC/MS/MS) method for the analysis of positional isomers of triacylglycerols (TAGs) in vegetable oils. The fragmentation behavior of [M + X](+) ions (X = NH(4), Li, Na or Ag) was studied on a quadrupole-time-of-flight (Q-TOF) mass spectrometer under low-energy collision-induced dissociation (CID) conditions. Mass spectra that were dependent on the X(+) ion and the nature and position of the acyl substituents were observed for four pairs of 'AAB/ABA'-type TAGs, namely PPO/POP, OOP/OPO, LLO/LOL and OOL/OLO (where P is 16:0, palmitic acid; O is 18:1, oleic acid; and L is 18:2, linoleic acid). For the majority of [M + X](+) adducts, the loss of the fatty acid in the outer positions (sn-1 or sn-3) was favored over the loss in the central position (sn-2), which enabled the determination of the fractional abundance of the isomers. Ratios of the intensity of fragment ions at various AAB/ABA compositions produced linear calibration curves with positive slopes, comparable to those obtained traditionally by ESI-MS/MS of [M + NH(4)](+) adducts. The only exceptions were the [M + Ag](+) adducts of the PPO/POP system, which produced calibration curves with negative slopes. Sodium adducts provided the most consistent level of isomeric discrimination for the TAGs studied and also offered the most convenience in that they required no additive to the mobile phase. Therefore, calibration curve data derived from [M + Na](+) adducts were applied to the quantification of TAG regioisomers in sunflower and olive oils. The regiospecific analysis showed that palmitic acid was typically located at positions sn-1 or sn-3, whereas unsaturated fatty acids, oleic and linoleic acids were mostly found at the sn-2 position. PMID:20814981

  2. Screening for DNA Alkylation Mono and Cross-Linked Adducts with a Comprehensive LC-MS(3) Adductomic Approach.

    Science.gov (United States)

    Stornetta, Alessia; Villalta, Peter W; Hecht, Stephen S; Sturla, Shana J; Balbo, Silvia

    2015-12-01

    A high-resolution/accurate-mass DNA adductomic approach was developed to investigate anticipated and unknown DNA adducts induced by DNA alkylating agents in biological samples. Two new features were added to a previously developed approach to significantly broaden its scope, versatility, and selectivity. First, the neutral loss of a base (guanine, adenine, thymine, or cytosine) was added to the original methodology's neutral loss of the 2'-deoxyribose moiety to allow for the detection of all DNA base adducts. Second, targeted detection of anticipated DNA adducts based on the reactivity of the DNA alkylating agent was demonstrated by inclusion of an ion mass list for data dependent triggering of MS(2) fragmentation events and subsequent MS(3) fragmentation. Additionally, untargeted screening of the samples, based on triggering of an MS(2) fragmentation event for the most intense ions of the full scan, was included for detecting unknown DNA adducts. The approach was tested by screening for DNA mono and cross-linked adducts in purified DNA and in DNA extracted from cells treated with PR104A, an experimental DNA alkylating nitrogen mustard prodrug currently under investigation for the treatment of leukemia. The results revealed the ability of this new DNA adductomic approach to detect anticipated and unknown PR104A-induced mono and cross-linked DNA adducts in biological samples. This methodology is expected to be a powerful tool for screening for DNA adducts induced by endogenous or exogenous exposures.

  3. Preparation and Evaluation of Aromatic Amine-Epoxidized Sunflower Free Fatty Acid Adducts As Corrosion Inhibitors in Curable Varnishes

    International Nuclear Information System (INIS)

    Five aromatic amines [o-, m- and p- Toluidine (o-T, m-T and p-T), p- anizidine (p-A) and p- chloroaniline (p-ClA)] were reacted with epoxidized sunflower free fatty acid (ESFA) under severe conditions of inert atmosphere and high temperature. The produced adducts were characterized physically, chemically and by IR spectroscopic analysis. Acid value and oxiran content of the prepared adducts were determined to confirm the participation of carboxylic groups and epoxy groups respectively in the reaction of ESFA with aromatic amines. The prepared adducts of (o-T-ESFA, m-T-ESFA, p-T-ESFA, p-A-ESFA and p-ClA-ESFA) were evaluated as corrosion inhibitors of mild steel in epoxy acrylate oligomer formulations curable by electron beam irradiation. Different concentrations of the prepared aromatic adducts were added in varnish formulations. Physical and mechanical measurements were carried out, in addition to corrosion resistance tests and weight loss of coated steel panels. The efficiency of adducts in varnishes formulation were determined, in which it was found that, the varnish formulations containing the prepared aromatic amine adducts could protect steel from corrosion. Superior corrosion inhibition efficiency was found for the varnish formula containing 0.6% p-A-ESFA adduct. The corrosion inhibition efficiency of the prepared aromatic amine in epoxy acrylate oligomer varnishes follows the order: p-A-ESFA > p-T-ESFA > m-T-ESFA > o-T-ESFA > p-ClA-ESFA

  4. Lifestyle, Environmental, and Genetic Predictors of Bulky DNA Adducts in a Study Population Nested within a Prospective Danish Cohort

    DEFF Research Database (Denmark)

    Eriksen, K. T.; Sørensen, M.; Autrup, H.;

    2010-01-01

    Danish cohort. At enrollment, blood samples were collected and information on lifestyle, including dietary and smoking habits, obtained. Previously, bulky DNA adducts were measured in 245 individuals who developed lung cancer and 255 control members of the cohort. Of these 500 individuals, data on 375...... found between dietary factors or smoking and DNA adduct levels. Further, the results showed no prominent associations between any of 12 genetic polymorphisms and adduct levels. Overall, our study showed only few associations between dietary, environmental, and genetic factors and levels of bulky DNA...

  5. Modulatory effects of essential oils from spices on the formation of DNA adduct by aflatoxin B1 in vitro.

    Science.gov (United States)

    Hashim, S; Aboobaker, V S; Madhubala, R; Bhattacharya, R K; Rao, A R

    1994-01-01

    Essential oils from common spices such as nutmeg, ginger, cardamom, celery, xanthoxylum, black pepper, cumin, and coriander were tested for their ability to suppress the formation of DNA adducts by aflatoxin B1 in vitro in a microsomal enzyme-mediated reaction. All oils were found to inhibit adduct formation very significantly and in a dose-dependent manner. The adduct formation appeared to be modulated through the action on microsomal enzymes, because an effective inhibition on the formation of activated metabolite was observed with each oil. The enzymatic modulation is perhaps due to the chemical constituents of the oils, and this could form a basis for their potential anticarcinogenic roles. PMID:8058527

  6. Elimination technique for alkali metal ion adducts from an electrospray ionization process using an on-line ion suppressor

    OpenAIRE

    NOZAKI, Kazuyoshi; TARUI, Akira; OSAKA, Issey; Kawasaki, Hideya; ARAKAWA, Ryuichi; 荒川, 隆一

    2010-01-01

    The effects of an on-line ion suppressor device on alkali metal ion adduct formations of the model compound tacrolimus were investigated. The base peak ion in the positive ion ESI-MS spectrum of tacrolimus was a sodium ion adduct, [M+Na]+. On the other hand, an ammonium ion adduct, [M+NH4]+, was the base peak ion in the full-scan mass spectrum of tacrolimus with a cation-exchange suppressor resin, and both [M+Na]+ and [M+K]+ were eliminated. These results indicate that the combination of an o...

  7. 4 July 2013- European Commission DG CONNECT Director-General R. Madelin, signing the guest book with CERN Director-General R. Heuer and visiting CMS experimental area with Collaboration Deputy Spokesperson J. Varela.

    CERN Multimedia

    Maximilien Brice

    2013-01-01

    4 July 2013- European Commission DG CONNECT Director-General R. Madelin, signing the guest book with CERN Director-General R. Heuer and visiting CMS experimental area with Collaboration Deputy Spokesperson J. Varela.

  8. Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) representative H. Ikukawa visiting ATLAS experiment with Collaboration Spokesperson P. Jenni, KEK representative T. Kondo and Advisor to CERN DG J. Ellis on 15 May 2007.

    CERN Multimedia

    Maximilien Brice

    2007-01-01

    Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) representative H. Ikukawa visiting ATLAS experiment with Collaboration Spokesperson P. Jenni, KEK representative T. Kondo and Advisor to CERN DG J. Ellis on 15 May 2007.

  9. NEARTOWARN: A new EU-DG ECHO-supported project for the near-field tsunami early warning

    Science.gov (United States)

    Papadopoulos, G. A.

    2012-04-01

    The early warning for near-field (local) tsunamis, with travel times of no more than about 30 min. from the tsunami source to the closest coastal zones, is today a hot topic of great importance in the international effort to reduce the loss of human lives and to mitigate other tsunami risks. Particularly, in the Mediterranean region earthquakes, and more rarely volcanic eruptions and landslides, produce near-field tsunamis threatening nearly all the coastal zones but mainly those in the Hellenic Arc and Trench (South Peloponnese, Cyclades, Crete, Rhodes, SW Turkey), in the Corinth Gulf (Central Greece), in the Messina strait and the east Sicily (Italy) in the Ligurian Sea, the Algeria and the Balearic islands, in the west Mediterranean basin, and the Cyprus-Lebanon area in the easternmost Mediterranean. The North East Atlantic and Mediterranean Tsunami Warning System (NEAMTWS), which is under construction with the supervision of the Intergovernmental Oceanographic Commission, is oriented to issue warnings only in regional scales, that is for about 1 hour of tsunami propagation time. For near-field warning it is unrealistic to rely on a unique system for the entire basin. Instead, several local systems working on the basis of some joint principles but with local adjustements is the most promising solution. This is exactly the aim of the new project NEARToWARN (Near-field Tsunami Warning) which is supported by the EU DG-ECHO. Partnership includes the National Observatory of Athens (Coordinator, Greece), the University of Bologna (Italy), the University of Cyprus, the ACRI-ST (Sophia-Antipolis, France), the University of Cantabria (Spain) and the Municipility of Rhodes. The main concept is to develop a prototype local early tsunami warning system. To minimize the time for emergency in less than 30 sec, seismic alert devices (SED's) make the core component of the system. SED's are activated and send alerting signals as soon as a P-phase of seismic wave is detected in

  10. Phosphatase activity in commercial spleen exonuclease decreases the recovery of benzo[a]pyrene and N-hydroxy-2-naphthylamine DNA adducts by 32P-postlabeling.

    Science.gov (United States)

    Adams, S P; Laws, G M; Selden, J R; Nichols, W W

    1994-05-15

    Spleen exonuclease, which degrades nucleic acids into single 3'-nucleotides, is used in the detection of DNA adducts by 32P-postlabeling. Contamination of the exonuclease with phosphatase activity can reduce the recovery of benzo[a]pyrene and N-hydroxy-2-naphthylamine DNA adducts by 32P-postlabeling. Four preparations of spleen exonuclease containing varying levels of phosphatase activity (2-naphthylamine DNA adducts. Surprisingly, recovery of these DNA adducts was nearly 10 times greater using nuclease P1 than when using 1-butanol extraction for adduct enrichment, since arylamine DNA adducts have previously been reported to be poorly detected by 32P-postlabeling after nuclease P1 treatment. Our data indicate that the hydrolysis of DNA by spleen exonuclease may be an important source of variability in both qualitative and quantitative analysis of adducts by 32P-postlabeling. PMID:8059938

  11. Homologs of the Xenopus developmental gene DG42 are present in zebrafish and mouse and are involved in the synthesis of Nod-like chitin oligosaccharides during early embryogenesis.

    Science.gov (United States)

    Semino, C E; Specht, C A; Raimondi, A; Robbins, P W

    1996-05-14

    The Xenopus developmental gene DG42 is expressed during early embryonic development, between the midblastula and neurulation stages. The deduced protein sequence of Xenopus DG42 shows similarity to Rhizobium Nod C, Streptococcus Has A, and fungal chitin synthases. Previously, we found that the DG42 protein made in an in vitro transcription/translation system catalyzed synthesis of an array of chitin oligosaccharides. Here we show that cell extracts from early Xenopus and zebrafish embryos also synthesize chitooligosaccharides. cDNA fragments homologous to DG42 from zebrafish and mouse were also cloned and sequenced. Expression of these homologs was similar to that described for Xenopus based on Northern and Western blot analysis. The Xenopus anti-DG42 antibody recognized a 63-kDa protein in extracts from zebrafish embryos that followed a similar developmental expression pattern to that previously described for Xenopus. The chitin oligosaccharide synthase activity found in extracts was inactivated by a specific DG42 antibody; synthesis of hyaluronic acid (HA) was not affected under the conditions tested. Other experiments demonstrate that expression of DG42 under plasmid control in mouse 3T3 cells gives rise to chitooligosaccharide synthase activity without an increase in HA synthase level. A possible relationship between our results and those of other investigators, which show stimulation of HA synthesis by DG42 in mammalian cell culture systems, is provided by structural analyses to be published elsewhere that suggest that chitin oligosaccharides are present at the reducing ends of HA chains. Since in at least one vertebrate system hyaluronic acid formation can be inhibited by a pure chitinase, it seems possible that chitin oligosaccharides serve as primers for hyaluronic acid synthesis.

  12. PARP1 impact on DNA repair of platinum adducts: preclinical and clinical read-outs.

    Science.gov (United States)

    Olaussen, Ken A; Adam, Julien; Vanhecke, Elsa; Vielh, Philippe; Pirker, Robert; Friboulet, Luc; Popper, Helmut; Robin, Angélique; Commo, Fréderic; Thomale, Jürgen; Kayitalire, Louis; Filipits, Martin; Le Chevalier, Thierry; André, Fabrice; Brambilla, Elisabeth; Soria, Jean-Charles

    2013-05-01

    Evaluation of DNA repair proteins might provide meaningful information in relation to prognosis and chemotherapy efficacy in Non-Small Cell Lung Cancer (NSCLC) patients. The role of Poly(ADP-Ribose) Polymerase (PARP) in DNA repair of platinum adducts has not been firmly established. We used a DNA repair functional test based on antibody recognition of cisplatin intrastrand platinum adducts on DNA. We evaluated the effect of PARP inhibition on DNA repair functionality in a panel of cisplatin cell lines treated by the clinical-grade pharmacological inhibitor CEP8983 (a 4-methoxy-carbazole derivate) and the commercially available inhibitor PJ34 (phenanthridinone). We determined PARP1 protein expression in whole tumor sections from the International Adjuvant Lung cancer Trial (IALT)-bio study and tested a 3-marker PARP1/MSH2/ERCC1 algorithm combining PARP1 tumor status with previously published data. Chemosensitivity of cisplatin in NSCLC cell lines was correlated with the accumulation of cisplatin DNA adducts (P=0.0004). Further, the pharmacological inhibition of PARP induced a 1.7 to 2.3-fold increase in platinum adduct accumulation (24h) in A549 cell line suggesting a slow-down of platinum DNA-adduct repair capacity. In parallel, PARP1 inhibition increased the sensitivity to cisplatin treatment. In patient samples, PARP1 expression levels did not influence patient survival or the effect of platinum-based post-operative chemotherapy in the global IALT-bio population (interaction P=0.79). Among cases with high expression of all three markers (triple positive), untreated patients had prolonged survival with a median DFS of 7.8 years, (HR=0.34, 95%CI [0.19-0.61], adjusted P=0.0003) compared to triple negative patients (1.4 years). Remarkably, triple positive patients suffered from a detrimental effect (4.9-year reduction of median DFS) by post-operative cisplatin-based chemotherapy (HR=1.79, 95%CI [1.01-3.17], adjusted P=0.04, chemotherapy vs. control). Combinatorial

  13. Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA.

    Science.gov (United States)

    Chen, Fangyi; Tang, Qi; Bian, Ke; Humulock, Zachary T; Yang, Xuedong; Jost, Marco; Drennan, Catherine L; Essigmann, John M; Li, Deyu

    2016-04-18

    The AlkB protein is a repair enzyme that uses an α-ketoglutarate/Fe(II)-dependent mechanism to repair alkyl DNA adducts. AlkB has been reported to repair highly susceptible substrates, such as 1-methyladenine and 3-methylcytosine, more efficiently in ss-DNA than in ds-DNA. Here, we tested the repair of weaker AlkB substrates 1-methylguanine and 3-methylthymine and found that AlkB prefers to repair them in ds-DNA. We also discovered that AlkB and its human homologues, ABH2 and ABH3, are able to repair the aforementioned adducts when the adduct is present in a mismatched base pair. These observations demonstrate the strong adaptability of AlkB toward repairing various adducts in different environments. PMID:26919079

  14. Large eccentric strength increase using the Copenhagen Adduction exercise in football

    DEFF Research Database (Denmark)

    Ishøi, L; Sørensen, C N; Kaae, N M;

    2016-01-01

    Hip adductor injuries are frequent in football, and players with low adductor strength appear to be at increased risk of injury. High adductor muscle activity has been shown in the Copenhagen Adduction exercise (CA); however, an associated strength gain has not been investigated. This study aims...... to examine the eccentric hip adduction strength (EHAD) gain using the CA in-season. Two U-19 sub-elite football teams, including 24 football players, were randomized to either an 8-week supervised progressive training program in addition to the usual training (intervention) or to continue training as usual...... (control). EHAD, eccentric hip abduction strength (EHAB), and side-bridge endurance were measured using reliable test procedures at baseline and follow-up by a blinded tester. There was a significant interaction between group and time on EHAD, EHAB, and EHAD/EHAB ratio (P 

  15. AlkB recognition of a bulky DNA base adduct stabilized by chemical cross-linking

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    E.coli AlkB is a direct DNA/RNA repair protein that oxidatively reverses N1 alkylated purines and N3 alkylated pyrimidines to regular bases.Previous crystal structures have revealed N1-methyl adenine(1-meA) recognition by AlkB and a unique base flipping mechanism,but how the AlkB active site can accommodate bulky base adducts is largely unknown.Employing a previously developed chemical cross-linking technique,we crystallized AlkB with a duplex DNA containing a caged thymine base(cagedT).The structure revealed a flexible hairpin lid and a reorganized substrate recognition loop used by AlkB to accommodate cagedT.These observations demonstrate,at the molecular level,how bulky DNA adducts may be recognized and processed by AlkB.

  16. Diastereoselective synthesis of substituted 2-amino-1,3-propanediols from Morita-Baylis-Hillman adducts

    Energy Technology Data Exchange (ETDEWEB)

    Paioti, Paulo H.S.; Rezende, Patricia; Coelho, Fernando [Laboratorio de Sintese de Produtos Naturais e Farmacos, Instituto de Quimica, Universidade Estadual de Campinas (UNICAMP), SP (Brazil)

    2012-07-01

    We report herein a new diastereoselective approach to substituted 2-amino-1,3-propanediols with anti relative stereochemistry from Morita-Baylis-Hillman (MBH) adducts. These structural moieties have been used as intermediates for the synthesis of several compounds with relevant pharmacological and commercial interest. In this strategy, substituted anti 2-amino-1,3-propanediols were readily prepared via ozonolysis of allylic diols obtained from MBH adducts, followed by a diastereoselective reductive amination of the substituted 2-oxo-1,3-propanediols. To demonstrate the synthetic utility of these aminodiols, they were transformed into substituted oxazolidine-2-ones, which were also used in the indirect determination of the relative stereochemistry of the aminodiols. (author)

  17. Polycyclic aromatic hydrocarbon-DNA adducts in cervix of women infected with carcinogenic human papillomavirus types: An immunohistochemistry study

    Energy Technology Data Exchange (ETDEWEB)

    Pratt, M. Margaret [Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD (United States)], E-mail: prattm@mail.nih.gov; Sirajuddin, Paul; Poirier, Miriam C. [Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD (United States); Schiffman, Mark [Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD (United States); Glass, Andrew G.; Scott, David R.; Rush, Brenda B. [Northwest Kaiser Permanente, Portland, OR (United States); Olivero, Ofelia A. [Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD (United States); Castle, Philip E. [Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD (United States)

    2007-11-01

    Among women infected with carcinogenic human papillomavirus (HPV), there is a two- to five-fold increased risk of cervical precancer and cancer in women who smoke compared to those who do not smoke. Because tobacco smoke contains carcinogenic polycyclic aromatic hydrocarbons (PAHs), it was of interest to examine human cervical tissue for PAH-DNA adduct formation. Here, we measured PAH-DNA adduct formation in cervical biopsies collected in follow-up among women who tested positive for carcinogenic HPV at baseline. A semi-quantitative immunohistochemistry (IHC) method using antiserum elicited against DNA modified with r7,t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) was used to measure nuclear PAH-DNA adduct formation. Cultured human cervical keratinocytes exposed to 0, 0.153, or 0.331 {mu}M BPDE showed dose-dependent increases in r7,t8,t9-trihydroxy-c-10-(N{sup 2}deoxyguanosyl)-7,8,9, 10-tetrahydro-benzo[a]pyrene (BPdG) adducts. For BPdG adduct analysis, paraffin-embedded keratinocytes were stained by IHC with analysis of nuclear color intensity by Automated Cellular Imaging System (ACIS) and, in parallel cultures, extracted DNA was assayed by quantitative BPDE-DNA chemiluminescence immunoassay (CIA). For paraffin-embedded samples from carcinogenic HPV-infected women, normal-appearing cervical squamous epithelium suitable for scoring was found in samples from 75 of the 114 individuals, including 29 cases of cervical precancer or cancer and 46 controls. With a lower limit of detection of 20 adducts/10{sup 8} nucleotides, detectable PAH-DNA adduct values ranged from 25 to 191/10{sup 8} nucleotides, with a median of 75/10{sup 8} nucleotides. PAH-DNA adduct values above 150/10{sup 8} nucleotides were found in eight samples, and in three samples adducts were non-detectable. There was no correlation between PAH-DNA adduct formation and either smoking or case status. Therefore, PAH-DNA adduct formation as measured by this methodology did not appear

  18. Pulse radiolysis study of reaction of bull serum albumin electron adduct with oxygen. Polychromatic kinetics of reaction with adsorbed oxygen

    International Nuclear Information System (INIS)

    By the method of pulse radiolysis the reaction of bull serum albumin electron adduct with oxygen is investigated. As pulsed radiation source electron linear accelerators with particle energy of 8.0 and 4.5 MeV and pulse time of 40 ns and 2.2 μs, respectively have been used. It is assumed that the disappearance of protein electron adduct occurs in the course of its interaction with oxygen adsorbed on protein globular molecule

  19. Efficient CO2 capture by tertiary amine-functionalized ionic liquids through Li+-stabilized zwitterionic adduct formation

    OpenAIRE

    Yang, Zhen-zhen; He, Liang-Nian

    2014-01-01

    Highly efficient CO2 absorption was realized through formation of zwitterionic adducts, combining synthetic strategies to ionic liquids (ILs) and coordination. The essence of our strategy is to make use of multidentate cation coordination between Li+ and an organic base. Also PEG-functionalized organic bases were employed to enhance the CO2-philicity. The ILs were reacted with CO2 to form the zwitterionic adduct. Coordination effects between various lithium salts and neutral ligands, as well ...

  20. Modulation of the Effect of Prenatal PAH Exposure on PAH-DNA Adducts in Cord Blood by Plasma Antioxidants

    OpenAIRE

    Kelvin, Elizabeth A.; Edwards, Susan; Jedrychowski, Wieslaw; Schleicher, Rosemary L.; Camann, David; Tang, Deliang; Perera, Frederica P.

    2009-01-01

    The fetus is more susceptible than the adult to the effects of certain carcinogens, such as polycyclic aromatic hydrocarbons (PAH). Nutritional factors, including antioxidants, have been shown to have a protective effect on carcinogen-DNA adducts and cancer risk in adults. We investigated whether the effect of prenatal airborne PAH exposure, measured by personal air monitoring during pregnancy, on the level of PAH-DNA adducts in a baby's cord blood is modified by the concentration of micronut...

  1. Contribution of artifacts to N-methylated piperazine cyanide adduct formation in vitro from N-alkyl piperazine analogs.

    Science.gov (United States)

    Zhang, Minli; Resuello, Christina M; Guo, Jian; Powell, Mark E; Elmore, Charles S; Hu, Jun; Vishwanathan, Karthick

    2013-05-01

    In the liver microsome cyanide (CN)-trapping assays, piperazine-containing compounds formed significant N-methyl piperazine CN adducts. Two pathways for the N-methyl piperazine CN adduct formation were proposed: 1) The α-carbon in the N-methyl piperazine is oxidized to form a reactive iminium ion that can react with cyanide ion; 2) N-dealkylation occurs followed by condensation with formaldehyde and dehydration to produce N-methylenepiperazine iminium ion, which then reacts with cyanide ion to form the N-methyl CN adduct. The CN adduct from the second pathway was believed to be an artifact or metabonate. In the present study, a group of 4'-N-alkyl piperazines and 4'-N-[¹³C]methyl-labeled piperazines were used to determine which pathway was predominant. Following microsomal incubations in the presence of cyanide ions, a significant percentage of 4'-N-[¹³C]methyl group in the CN adduct was replaced by an unlabeled natural methyl group, suggesting that the second pathway was predominant. For 4'-N-alkyl piperazine, the level of 4'-N-methyl piperazine CN adduct formation was limited by the extent of prior 4'-N-dealkylation. In a separate study, when 4'-NH-piperaziens were incubated with potassium cyanide and [¹³C]-labeled formaldehyde, 4'-N-[¹³C]methyl piperazine CN-adduct was formed without NADPH or liver microsome suggesting a direct Mannich reaction is involved. However, when [¹³C]-labeled methanol or potassium carbonate was used as the one-carbon donor, 4'-N-[¹³C]methyl piperazine CN adduct was not detected without liver microsome or NADPH present. The biologic and toxicological implications of bioactivation via the second pathway necessitate further investigation because these one-carbon donors for the formation of reactive iminium ions could be endogenous and readily available in vivo. PMID:23431111

  2. Benzo(a)pyrene-albumin adducts in humans exposed to polycyclic aromatic hydrocarbons in an industrial area of Poland.

    OpenAIRE

    Kure, E H; Andreassen, A; Ovrebø, S; Grzybowska, E; Fiala, Z; Strózyk, M; Chorazy, M; Haugen, A

    1997-01-01

    OBJECTIVES: The interaction of benzo(a)pyrene with serum albumin was measured in an attempt to identify the actual exposure and to evaluate albumin adduct measurements as biomarkers for exposure monitoring. METHODS: Benzo(a)pyrene-diol-epoxide (BPDE)-albumin adducts were measured by competitive enzyme linked immunosorbent assay (ELISA) in plasma of coke oven plant workers from three plants and from people living in a highly industrialised area of Silesia in Poland. Due to the high air concent...

  3. Significant Positive Correlation of Plasma BPDE-Albumin Adducts to Urinary 1-Hydroxypyrene in Coke Oven Workers

    Institute of Scientific and Technical Information of China (English)

    HONG WANG; TANG-CHUN WU; XIAO-BO YANG; AI-LIN LIU; HONG-YAN ZHEN; LIANG GUO; HUA-SHAN LIANG; YONG-YI BI; YUN BAI; YONG-WEN CHEN

    2007-01-01

    Objective To investigate the application of BPDE-albumin adducts as monitoring biomarkers for coke oven workers exposed to polycyclic aromatic hydrocarbons(PAHs)and to explore possible relationship between BPDE-albumin adducts and urinary 1-hydroxypyrene (1-OHP)levels in them.Methods Thirty-seven coke oven workers from a coke plant and 47 controls without the occupational exposure to PAHs were recruited in this study.The levels of plasma BPDE-albumin adducts and urinary 1-OHP were analyzed using high performance liquid chromatography.Results The median levels of BPDE-albumin adducts(42.10 fmol/mg albumin)and urinary 1-OHP(5.46 μmol/mol creatinine)were significantly higher in coke oven workers than in controls(14.16 fmol/mg albumin,2.96 μmol/mol creatinine,respectively;P<0.01).Multiple logistic regression analysis showed that coke oven workers were at higher risk of having BPDE-albumin adduct levels above 25.30 prnol/mg albumin(OR=1.79,P<0.01)and urinary 1-OHP levels above 4.13 μmol/mol creatinine(OR=2.45,P<0.05).There was a positive correlation between the levels of BPDE-albumin adducts and urinary 1-OHP in all subjects(rs=0.349,P<0.01).Conclusion BPDE-albumin adduct is a useful biomarker for monitoring long-term exposure to PAHs,and plasma BPDE-albumin adducts level is significantly correlated to urinary 1-OHP levels in coke oven workers.

  4. The 1:1 adduct of caffeine and 2-(1,3-dioxoisoindolin-2-ylacetic acid

    Directory of Open Access Journals (Sweden)

    Moazzam H. Bhatti

    2011-09-01

    Full Text Available In the crystal structure of the title adduct [systematic name: 2-(1,3-dioxoisoindolin-2-ylacetic acid–1,3,7-trimethyl-1,2,3,6-tetrahydro-7H-purine-2,6-dione (1/1], C8H10N4O2·C10H7NO4, the components are linked by an O—H...N hydrogen-bond and no proton transfer occurs.

  5. Rearrangement mechanism of the sodium adducts of Fmoc protected amino acids

    Institute of Scientific and Technical Information of China (English)

    DU Jintang; LI Yanmei; ZHU Zhentai; CHEN Yi; ZHAO Yufen

    2003-01-01

    The cationized 9-fluorenylmethoxycarbonyl (Fmoc) protected amino acidswere analyzed by the electrospray ionization tandem mass spectrometry (ESI-MS/MS). A rearrangement reaction leading to the C-terminal hydroxyl group transfer was observed. The sodium adducts of Fmoc-OH was formed. A possible rearrangement mechanism was proposed. The rearrangement reaction depended on the Fmoc group, metal ions and metal ion radius. It was shown that the Fmoc group has a strong affinity to the hydroxyl group in the gas phase.

  6. Free flow electrophoresis separation and AMS quantitation of {sup 14}C-naphthalene-protein adducts

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, Bruce A., E-mail: bbuchholz@llnl.go [Center for AMS, LLNL, 7000 East Avenue, Livermore, CA 94551 (United States); Haack, Kurt W.; Sporty, Jennifer L. [Center for AMS, LLNL, 7000 East Avenue, Livermore, CA 94551 (United States); Buckpitt, Alan R.; Morin, Dexter [Department of Molecular Biosciences, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States)

    2010-04-15

    Naphthalene is a volatile aromatic hydrocarbon to which humans are exposed from a variety of sources including mobile air sources and cigarette smoke. Naphthalene produces dose-(concentration)dependent injury to airway epithelial cells of murine lung which is observed at concentrations well below the current occupational exposure standard. Toxicity is dependent upon the cytochrome P450 mediated metabolic activation of the parent substrate to unstable metabolites which become bound covalently to tissue proteins. Nearly 70 proteins have been identified as forming adducts with reactive naphthalene metabolites using in vitro systems but very little work has been conducted in vivo because reasonably large amounts (100 muCi) of {sup 14}C labeled parent compound must be administered to generate detectable adduct levels on storage phosphor screens following separation of labeled proteins by 2D gel electrophoresis. The work described here was done to provide proof of concept that protein separation by free flow electrophoresis followed by AMS detection of protein fractions containing protein bound reactive metabolites would provide adducted protein profiles in animals dosed with trace quantities of labeled naphthalene. Mice were administered 200 mg/kg naphthalene intraperitoneally at a calculated specific activity of 2 DPM/nmol (1 pCi/nmol) and respiratory epithelial tissue was obtained by lysis lavage 4 h post injection. Free flow electrophoresis (FFE) separates proteins in the liquid phase over a large pH range (2.5-11.5) using low molecular weight acids and bases to modify the pH. The apparatus separates fractions into standard 96-well plates that can be used in other protein analysis techniques. The buffers of the fractions have very high carbon content, however, and need to be dialyzed to yield buffers compatible with {sup 14}C-AMS. We describe the processing techniques required to couple FFE to AMS for quantitation of protein adducts.

  7. uvrC gene function has no specific role in repair of N-2-aminofluorene adducts.

    OpenAIRE

    Bichara, M; Fuchs, R P

    1987-01-01

    In Escherichia coli, plasmid DNA modified with N-2-aminofluorene adducts survived equally well in wild-type, uvrA, or uvrB strains. Increased sensitivity was found in uvrC and uvrD strains. Moreover, N-2-aminofluorene-mediated toxicity in the uvrC background was reversed when an additional uvrA mutation was introduced into the strain.

  8. Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother-newborns

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, Marie, E-mail: mpedersen@creal.cat [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark); Halldorsson, Thorhallur I., E-mail: lur@ssi.dk [Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland Reykjavik (Iceland); Center for Fetal Programming, Department of Epidemiology, Statens Serum Institute, Copenhagen (Denmark); Autrup, Herman, E-mail: ha@mil.au.dk [School of Public Health, Department of Environmental and Occupational Medicine, Aarhus University, Aarhus (Denmark); Brouwer, Abraham, E-mail: Bram.Brouwer@bds.nl [BioDetection Systems B.V., Amsterdam (Netherlands); Besselink, Harrie, E-mail: Harrie.Besselink@bds.nl [BioDetection Systems B.V., Amsterdam (Netherlands); Loft, Steffen, E-mail: stl@sund.ku.dk [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark); Knudsen, Lisbeth E., E-mail: liek@sund.ku.dk [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark)

    2012-06-01

    Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006-2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX){sup Registered-Sign} bioassay, {sup 32}P-postlabelling technique and cytokinesis-block MN assay. Maternal preference for meats with dark surface were significantly associated with higher bulky DNA adducts in both maternal ({beta} 95%CI; 0.46 (0.08, 0.84)) and cord blood ({beta} 95%CI; 0.46 (0.05, 0.86)) before and after adjustment for potential confounders. No other significant associations between the 18 dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA adducts appear to be captured by a FFQ while potential associations for other biomarkers might be more complex or need larger sample size.

  9. Triple helix-forming oligonucleotides target psoralen adducts to specific chromosomal sequences in human cells.

    OpenAIRE

    Oh, D H; Hanawalt, P C

    1999-01-01

    The ability to target photochemical adducts to specific genomic DNA sequences in cells is useful for studying DNA repair and mutagenesis in intact cells, and also as a potential mode of gene-specific therapy. Triple helix-forming DNA oligonucleotides linked to psoralen (psoTFOs) were designed to deliver UVA-induced psoralen photoadducts to two distinct sequences within the human interstitial collagenase gene. A primer extension assay demonstrated that the appropriate psoTFO selectively damage...

  10. Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother–newborns

    International Nuclear Information System (INIS)

    Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006–2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX)® bioassay, 32P-postlabelling technique and cytokinesis-block MN assay. Maternal preference for meats with dark surface were significantly associated with higher bulky DNA adducts in both maternal (β 95%CI; 0.46 (0.08, 0.84)) and cord blood (β 95%CI; 0.46 (0.05, 0.86)) before and after adjustment for potential confounders. No other significant associations between the 18 dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA adducts appear to be captured by a FFQ while potential associations for other biomarkers might be more complex or need larger sample size.

  11. Benzo(a)pyrene diolepoxide-DNA adducts detected by synchronous fluorescence spectrophotometry.

    OpenAIRE

    Vahakangas, K.; Trivers, G; Rowe, M.; Harris, C. C.

    1985-01-01

    Using benzo(a)pyrene (BP) as a model carcinogen we are currently applying a fluorescence technique to detect the very low levels of carcinogen-DNA adducts in human populations due to environmental exposure. In synchronous fluorescence spectrophotometry for detection of BP-diol epoxide-DNA, excitation and emission wavelengths are scanned simultaneously with a fixed wavelength difference (delta lambda) of 34 nm. Compared to conventional fluorescence methods only one peak emerges because excitat...

  12. DFT study on adduct reaction paths of GaN MOCVD growth

    Institute of Scientific and Technical Information of China (English)

    SHI; JunCao; ZUO; Ran; MENG; SuCi

    2013-01-01

    The adduct reaction paths for GaN growth by metal organic chemical vapor deposition (MOCVD) were studied by quantum chemical calculations employing density functional theory (DFT). Five possible adduct reaction paths with or without the ex-cess NH3were proposed and the corresponding potential energy surfaces were calculated. From the calculation results, it is concluded that after the formation of DMGNH2from TMG:NH3, the further decomposition paths have very slim probability because of the high energy barriers; whereas the oligomerization pathway to form oligomers [DMGNH2]x(x=2, 3) is probable,because of zero energy barrier. Since the oligomers tend to further polymerize, the nanoparticles are easily formed through this path. When NH3is in excess, TMG:NH3 tends to combine with the second NH3to form two new complexes: the coordination-bonded compound H3N:TMG:NH3and the hydrogen-bonded compound TMG:NH3 NH3. The formation of hydrogen-bonded compound TMG:NH3 NH3 will be more probable because of the lower energy than H3N:TMG:NH3. By comparing the potential energy surfaces in five adduct reaction paths, we postulate that, under the growth conditions of GaN MOCVD, the formation of hydrogen-bonded compound TMG:NH3 NH3 followed by the reversible decomposition may be the main reaction path for GaN thin film growth; while the adduct oligomerization path to generate oligomers [DMGNH2]2 and [DMGNH2]3might be the main reaction path for nanoparticles formation.

  13. SOME NEW SULFATO AND HYDROGENOSULFATO ADDUCTS: SYNTHESIS, INFRARED AND MÖSSBAUER STUDIES

    Directory of Open Access Journals (Sweden)

    Alain Wattiaux

    2010-07-01

    Full Text Available Eight organotin (IV (mainly sulfato adducts have been synthesized and studied by spectroscopic methods. While considering the anionic component, the suggested structures are discrete; supramolecular architectures are obtained with secondary interactions through NH----Cl and NH----O hydrogen bonds while considering the cations, the anions behaving as monochelating, bridging or monocoordinating ligands, the environment around the tin (IV centre being octahedral. Tetrahedral SnMe2Cl2 has been characterized spectroscopically.

  14. Thermogravimetric and calorimetric study of cadmium iodide adducts with cyclic ureas

    International Nuclear Information System (INIS)

    Adducts of general formula CdI2·nL [n=1 and 2; L: ethyleneurea (eu) and propyleneurea (pu)] were synthesized by a solid state route and characterized by elemental analysis, infrared spectroscopy, thermogravimetry and reaction solution calorimetry. The infrared results shown that eu and pu coordinate through oxygen atom. All adducts release the ligand molecules in a single mass loss step, suggesting that, in the bisadducts, both ligand molecules are in equivalent coordination sites, exhibiting similar bond enthalpies. For all thermogravimetric curves, the first mass loss step is associated with the release of ligand molecules and the second one with the sublimation of cadmium iodide: CdI2·nL(s)→CdI2(s)+nL(g); CdI2(s)→CdI2(g). The observed thermal stability trend is: CdI2·eu (228 deg. C) > CdI2·pu (213 deg. C) > CdI2·2pu (200) > CdI2·2eu (186 deg. C). The standard molar reaction enthalpy in condensed phase: CdI2(cr)+nL(cr)=CdI2·nL(cr); ΔrHmθ, were obtained from reaction-solution calorimetry, to give the following values for mono and bisadducts: -7.16 and -27.61, -4.99 and -9.07 kJ mol-1 for eu and pu adducts, respectively. Decomposition (ΔDHmθ) and lattice (ΔMHmθ) enthalpies, as well as the mean cadmium-oxygen bond dissociation enthalpy, D(Cd-O), were calculated for all adducts

  15. Preparation and characterization of the adducts between lanthanide methanesulfonates and thioxane oxide

    International Nuclear Information System (INIS)

    The preparation and characterization of the adduct between lanthanide methanesulphonates and thioxane oxide are presented. The compounds characterization by conductance measurements, X-ray powder patterns, infrared, visible and fluorescence spectra, TG, DTG and DTA curves was made. According to the X-ray patterns, three isomorphous series were obtained: a-La-Gd b-Tb-Dy and c-Ho-Lu, Y. (M.J.C.)

  16. Signal transduction in light–oxygen–voltage receptors lacking the adduct-forming cysteine residue

    Science.gov (United States)

    Yee, Estella F.; Diensthuber, Ralph P.; Vaidya, Anand T.; Borbat, Peter P.; Engelhard, Christopher; Freed, Jack H.; Bittl, Robert; Möglich, Andreas; Crane, Brian R.

    2015-01-01

    Light–oxygen–voltage (LOV) receptors sense blue light through the photochemical generation of a covalent adduct between a flavin-nucleotide chromophore and a strictly conserved cysteine residue. Here we show that, after cysteine removal, the circadian-clock LOV-protein Vivid still undergoes light-induced dimerization and signalling because of flavin photoreduction to the neutral semiquinone (NSQ). Similarly, photoreduction of the engineered LOV histidine kinase YF1 to the NSQ modulates activity and downstream effects on gene expression. Signal transduction in both proteins hence hinges on flavin protonation, which is common to both the cysteinyl adduct and the NSQ. This general mechanism is also conserved by natural cysteine-less, LOV-like regulators that respond to chemical or photoreduction of their flavin cofactors. As LOV proteins can react to light even when devoid of the adduct-forming cysteine, modern LOV photoreceptors may have arisen from ancestral redox-active flavoproteins. The ability to tune LOV reactivity through photoreduction may have important implications for LOV mechanism and optogenetic applications. PMID:26648256

  17. 32P-postlabelling analysis of DNA adducted with urinary mutagens from smokers of black tobacco.

    Science.gov (United States)

    Peluso, M; Castegnaro, M; Malaveille, C; Talaska, G; Vineis, P; Kadlubar, F; Bartsch, H

    1990-08-01

    In order to characterize the tobacco-derived mutagens excreted in the urine of tobacco smokers, 32P-postlabelling techniques were used to examine DNA adducts formed from these mutagens with calf thymus DNA in the presence of a metabolic activation system (rat liver S9, Aroclor 1254-induced, with or without acetyl coenzyme A). Using either nuclease P1 or butanol extraction procedures, four-six and three spots, respectively, were reproducibly found on the autoradiograms in the case of the urine extract from two smokers of black tobacco. Using the urinary extract from a non-smoker, only three faint spots were detected after nuclease P1 enrichment. DNA adducts produced in smokers' urine were then compared with those formed by four N-hydroxyarylamines, N-hydroxy-2-amino-3,8-dimethyl-3H-imidazo[4,5-f]quinoxaline, N-hydroxy-2-amino-3-methyl-imidazo[4,5-f]quinoxaline, N-hydroxy-2-naphthylamine and N-hydroxy-4-aminobiphenyl. Visual inspection revealed that none of the reference aromatic amines contributed to the adduct pattern produced by the urinary mutagen(s). However, primary aromatic amines are mainly implicated as urinary mutagens because: (i) they produce frameshift mutations in Salmonella typhimurium strains, (ii) they are easily extractable with blue cotton and (iii) their mutagenicity is abolished by a nitrite treatment procedure for deamination. PMID:2387016

  18. Protein adducts of the prostate carcinogen PhIP in children

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence Livermore National Laboratory

    2004-02-20

    Prostate cancer is the second leading cause of cancer death in men in the United States. few epidemiology studies have indicated that exposure to PhIP, a rodent prostate carcinogen formed in meat during cooking, may be an important risk factor for prostate cancer in humans. Therefore, a highly sensitive biomarker assay is urgently needed to clarify the role of PhIP in prostate cancer. The goal of this project is to develop an assay that can be used to more accurately quantify human exposure to PhIP and potential prostate cancer risk. Our hypothesis is that an Accelerator Mass Spectrometry-based method can be developed to measure protein adducts of PhIP in the blood of humans. This will provide a measure of the internal dose, as well as the capacity for carcinogen bioactivation to a form that can initiate the cancer process. Towards this goal, we have characterized an adduct formed by PhIP in vitro with the amino acid cysteine. This adduct should provide a biomarker of dietary PhIP exposure and potential prostate cancer risk that could be used to identify individuals for prevention and for monitoring the effect chemoprevention strategies.

  19. Molecular structures of five adducts assembled from p-dimethylaminobenzaldehyde and organic acids

    Science.gov (United States)

    Jin, Shouwen; Wang, Lanqing; Liu, Hui; Liu, Li; Zhang, Huan; Wang, Daqi; Li, Minghui; Guo, Jianzhong; Guo, Ming

    2016-07-01

    Five adducts 1-5 derived from p-dimethylaminobenzaldehyde have been prepared and characterized by X-ray diffraction analysis, IR, mp, and elemental analysis. Of the five adducts two are organic salts (1, and 2) and the other three (3-5) are cocrystals. In salts 1, and 2, the L molecules are protonated. The supramolecular architectures of the adducts 1-5 involve extensive intermolecular N-H⋯O, O-H⋯O, O-H⋯S, and C-H⋯O hydrogen bonds as well as other non-covalent interactions. The role of weak and strong non-covalent interactions in the crystal packing is ascertained. The complexes displayed 2D/3D framework structure for the synergistic effect of the various non-covalent interactions. The results presented herein tell that the strength and directionality of the N-H⋯O, O-H⋯O, and O-H⋯S hydrogen bonds between organic acids and p-dimethylaminobenzaldehyde are sufficient to bring about the formation of binary cocrystals or organic salts.

  20. Carbofuran poisoning detected by mass spectrometry of butyrylcholinesterase adduct in human serum.

    Science.gov (United States)

    Li, He; Ricordel, Ivan; Tong, Larry; Schopfer, Lawrence M; Baud, Frédéric; Mégarbane, Bruno; Maury, Eric; Masson, Patrick; Lockridge, Oksana

    2009-03-01

    Carbofuran is a pesticide whose acute toxicity is due to inhibition of acetylcholinesterase. Butyrylcholinesterase (BChE) in plasma is inhibited by carbofuran and serves as a biomarker of poisoning by carbofuran. The goal was to develop a method to positively identify poisoning by carbofuran. Sera from an attempted murder and an attempted suicide were analyzed for the presence of carbofuran adducts on BChE. The BChE from 1 ml of serum was rapidly purified on a 0.2 ml procainamide-Sepharose column. Speed was essential because the carbofuran-BChE adduct decarbamylates with a half-life of about 2 h. The partially purified BChE was boiled to denature the protein, thus stopping decarbamylation and making the protein vulnerable to digestion with trypsin. The labeled peptide was partially purified by HPLC before analysis by LC/MS/MS in the multiple reaction monitoring mode on the QTRAP 2000 mass spectrometer. Carbofuran was found to be covalently bound to Ser 198 of human BChE in serum samples from two poisoning cases. Multiple reaction monitoring triggered MS/MS spectra positively identified the carbofuran-BChE adduct. In conclusion a mass spectrometry method to identify carbofuran poisoning in humans has been developed. The method uses 1 ml of serum and detects low-level exposure associated with as little as 20% inhibition of plasma butyrylcholinesterase.

  1. Surgical treatment of thumb adduction contracture in children with infantile cerebral palsy

    Directory of Open Access Journals (Sweden)

    Владимир Александрович Новиков

    2015-06-01

    Full Text Available The purpose of the work is to evaluate the effectiveness of different methods of surgical treatment of thumb adduction contracture in children with infantile cerebral palsy.Materials and methods.The present study is based on diagnostic results of children with infantile cerebral palsy with affected upper limb. The main criterion for selection of patients was the presence of thumb adduction contracture, the absence of significant positive outcome in a patient after conservative treatment, the impossibility of active thumb abduction more than 30° and the instability of the first metacarpophalangeal joint. Total we examined and treated 9 patients with spastic types of cerebral palsy.Results and conclusions.We evaluated the results of the following types of surgical treatment: release of adductor pollisis muscle, release of adductor pollisis muscle and tendon shortening of m.abductor pollicis longus, release of adductor pollisis muscle and tendon transfer of m.extensor indicis in the tendon m. abductor pollicis longus, the fixation of the first metacarpophalangeal joint with extramedullary plate. Based on these data, we were able to confirm the effectiveness of surgical treatment of thumb adduction contracture.

  2. Suicide of EMT-6 tumor cells by decays from radioactively-labelled sensitizer adducts

    International Nuclear Information System (INIS)

    Nitroaromatic radiosensitizers become metabolically bound preferentially to hypoxic cells and at least 10/sup 9/ adducts/cell can be tolerated as non-toxic. EMT-6 tumor cells have been incubated in hypoxia in the presence of /sup 3/H-Misonidazole and /sup 125/I-Azomycin Riboside for various times and the amount of /sup 3/H or /sup 125/I bound/cell was determined. Cells were stored as monolayers at 250C for up to 96 hr to accumulate radioactive decays and transferred at various times to 370C for colony-forming assays. No radiation inactivation was measured in cells which had incorporated at least 10/sup 6/ /sup 3/H or 10/sup 5/ /sup 125/I atoms. Previous studies had shown that -- 1% of MISO adducts to EMT-6 cells was associated with cellular DNA. These data indicate that the radiation-induced damage produced by these quantities of bound /sup 3/H or /sup 125/I causes little or not cell inactivation. The results of current studies to measure the colony-forming ability of sensitizer-labelled cells which have been stored in liquid nitrogen to facilitate the accumulation of more decays will be reported. These data suggest that a ''sensitizer-adduct suicide technique'' as a hypoxic cell selective adjunct to other cancer therapies is not feasible. These data are also instructive for those who attempt to develop radiolabelled ''tumor specific'' antibodies for therapeutic purposes

  3. Supramolecular Adducts of Cucurbit[7]uril and Amino Acids in the Gas Phase

    Science.gov (United States)

    Kovalenko, Ekaterina; Vilaseca, Marta; Díaz-Lobo, Mireia; Masliy, A. N.; Vicent, Cristian; Fedin, Vladimir P.

    2016-02-01

    The complexation of the macrocyclic cavitand cucurbit[7]uril (Q7) with a series of amino acids (AA) with different side chains (Asp, Asn, Gln, Ser, Ala, Val, and Ile) is investigated by ESI-MS techniques. The 1:1 [Q7 + AA + 2H]2+ adducts are observed as the base peak when equimolar Q7:AA solutions are electrosprayed, whereas the 1:2 [Q7 + 2AA + 2H]2+ dications are dominant when an excess of the amino acid is used. A combination of ion mobility mass spectrometry (IM-MS) and DFT calculations of the 1:1 [Q7 + AA + 2H]2+ (AA = Tyr, Val, and Ser) adducts is also reported and proven to be unsuccessful at discriminating between exclusion or inclusion-type conformations in the gas phase. Collision induced dissociation (CID) revealed that the preferred dissociation pathways of the 1:1 [Q7 + AA + 2H]2+ dications are strongly influenced by the identity of the amino acid side chain, whereas ion molecule reactions towards N-butylmethylamine displayed a common reactivity pattern comprising AA displacement. Special emphasis is given on the differences between the gas-phase behavior of the supramolecular adducts with amino acids (AA = Asp, Asn, Gln, Ser, Ala, Val, and Ile) and those featuring basic (Lys and Arg) and aromatic (Tyr and Phe) side chains.

  4. Differential repair of platinum-DNA adducts in human bladder and testicular tumor continuous cell lines

    International Nuclear Information System (INIS)

    The formation and removal of four platinum-DNA adducts were immunochemically quantitated in cultured cells derived from a human bladder carcinoma cell line (RT112) and from two lines derived from germ cell tumors of the testis (833K and SUSA), following exposure in vitro to 16.7 microM (5 micrograms/ml) cisplatin. RT112 cells were least sensitive to the drug and were proficient in the repair of all four adducts, whereas SUSA cells, which were 5-fold more sensitive, were deficient in the repair of DNA-DNA intrastrand cross-links in the sequences pApG and pGpG. Despite expressing a similar sensitivity to SUSA cells, 833K cells were proficient in the repair of all four adducts, although less so than the RT112 bladder tumor cells. In addition, SUSA cells were unable to repair DNA-DNA interstrand cross-links whereas 50-85% of these lesions were removed in RT112 and 833K cells 24 h following drug exposure. It is possible that the inability of SuSa cells to repair platinated DNA may account for their hypersensitivity to cisplatin

  5. Role of Scaphoid in the Abduction and Adduction Movements of Wrist Joint

    Directory of Open Access Journals (Sweden)

    Sadik I Shaikh

    2013-06-01

    Full Text Available Background: Being a carpal bone scaphoid has an important role in wrist movements. Wrist joint is a synovial modified ellipsoid joint where movements like flexion, extension and adduction, abduction take place around two axes (transverse and antero-posterior. These movements at the wrist joint are associated with considerable range of movements at the mid carpal joint, as same group of muscles act on both of these joints. Methodology: A study has been done amongst 120 persons at the tertiary care hospital during the period from 2006-07 to detect the important movements of scaphoid bone specially during the abduction and adduction of wrist joint (which occur in association with the intercarpal joints and also to detect whether such movements have any speciality in the population. Results: In fully abducted position, it was 45o among 53.3% subjects and the average among all the subjects was 60o. So, the degree of abduction was 30o. The extent of movement was more in adduction (ie, 1.90 cm - 1.03 cm = 0.87 cm than in abduction (ie, 1.03 cm - 0.72 cm = 0.31cm. Conclusion: It was found in this study that the scaphoid acts as a link bone between the two rows of carpal bones and prevents the buckling of midcarpal joint especially of the capitato- lunate joint interface. [Natl J Med Res 2013; 3(3.000: 253-256

  6. LC-MS/MS screening strategy for unknown adducts to N-terminal valine in hemoglobin applied to smokers and nonsmokers.

    Science.gov (United States)

    Carlsson, Henrik; von Stedingk, Hans; Nilsson, Ulrika; Törnqvist, Margareta

    2014-12-15

    Electrophilically reactive compounds have the ability to form adducts with nucleophilic sites in DNA and proteins, constituting a risk for toxic effects. Mass spectrometric detection of adducts to N-terminal valine in hemoglobin (Hb) after detachment by modified Edman degradation procedures is one approach for in vivo monitoring of exposure to electrophilic compounds/metabolites. So far, applications have been limited to one or a few selected reactive species, such as acrylamide and its metabolite glycidamide. This article presents a novel screening strategy for unknown Hb adducts to be used as a basis for an adductomic approach. The method is based on a modified Edman procedure, FIRE, specifically developed for LC-MS/MS analysis of N-terminal valine adducts in Hb detached as fluorescein thiohydantoin (FTH) derivatives. The aim is to detect and identify a priori unknown Hb adducts in human blood samples. Screening of valine adducts was performed by stepwise scanning of precursor ions in small mass increments, monitoring four fragments common for the FTH derivative of valine with different N-substitutions in the multiple-reaction mode, covering a mass range of 135 Da (m/z 503-638). Samples from six smokers and six nonsmokers were analyzed. Control experiments were performed to compare these results with known adducts and to check for artifactual formation of adducts. In all samples of smokers and nonsmokers, seven adducts were identified, of which six have previously been studied. Nineteen unknown adducts were observed, and 14 of those exhibited fragmentation patterns similar to earlier studied FTH derivatives of adducts to valine. Identification of the unknown adducts will be the focus of future work. The presented methodology is a promising screening tool using Hb adducts to indicate exposure to potentially toxic electrophilic compounds and metabolites.

  7. Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose

    Energy Technology Data Exchange (ETDEWEB)

    Honda, Hiroshi, E-mail: honda.hiroshi@kao.co.jp [R and D Safety Science Research, Kao Corporation, 2606 Akabane, Ichikai-Machi, Haga-Gun, Tochigi 321-3497 (Japan); Törnqvist, Margareta [Department of Materials and Environmental Chemistry, Environmental Chemistry Unit, Stockholm University, SE-106 91 Stockholm (Sweden); Nishiyama, Naohiro [R and D Safety Science Research, Kao Corporation, 2606 Akabane, Ichikai-Machi, Haga-Gun, Tochigi 321-3497 (Japan); Kasamatsu, Toshio, E-mail: kasamatsu.toshio@kao.co.jp [R and D Safety Science Research, Kao Corporation, 2606 Akabane, Ichikai-Machi, Haga-Gun, Tochigi 321-3497 (Japan)

    2014-03-15

    Hemoglobin adducts have been used as biomarkers of exposure to reactive chemicals. Glycidol, an animal carcinogen, has been reported to form N-(2,3-dihydroxy-propyl)valine adducts to hemoglobin (diHOPrVal). To support the use of these adducts as markers of glycidol exposure, we investigated the kinetics of diHOPrVal formation and its elimination in vitro and in vivo. Five groups of rats were orally administered a single dose of glycidol ranging from 0 to 75 mg/kg bw, and diHOPrVal levels were measured 24 h after administration. A dose-dependent increase in diHOPrVal levels was observed with high linearity (R{sup 2} = 0.943). Blood sampling at different time points (1, 10, 20, or 40 days) from four groups administered glycidol at 12 mg/kg bw suggested a linear decrease in diHOPrVal levels compatible with the normal turnover of rat erythrocytes (life span, 61 days), with the calculated first-order elimination rate constant (k{sub el}) indicating that the diHOPrVal adduct was chemically stable. Then, we measured the second-order rate constant (k{sub val}) for the reaction of glycidol with N-terminal valine in rat and human hemoglobin in in vitro experiments with whole blood. The k{sub val} was 6.7 ± 1.1 and 5.6 ± 1.3 (pmol/g globin per μMh) in rat and human blood, respectively, indicating no species differences. In vivo doses estimated from k{sub val} and diHOPrVal levels were in agreement with the area under the (concentration–time) curve values determined in our earlier toxicokinetic study in rats. Our results indicate that diHOPrVal is a useful biomarker for quantification of glycidol exposure and for risk assessment. - Highlight: • Glycidol-hemoglobin adduct (diHOPrVal) was characterized for exposure evaluation. • We studied the kinetics of diHOPrVal formation and elimination in vitro and in vivo. • Dose dependent formation and chemical stability were confirmed in the rat study. • In vivo dose (AUC) of glycidol could be estimated from diHOPrVal levels

  8. Lipid peroxidation-derived etheno-DNA adducts in human atherosclerotic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Jagadeesan [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); De Flora, Silvio [Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa (Italy); Izzotti, Alberto [Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa (Italy); Bartsch, Helmut [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany)]. E-mail: h.bartsch@dkfz.de

    2007-08-01

    Atherosclerosis and cancer are characterized by uncontrolled cell proliferation and share common risk factors, such as cigarette smoking, dietary habits and ageing. Growth of smooth muscle cells (SMCs) in atherosclerotic plaques may result from DNA damage, caused either by exogenous mutagens or by agents endogenously generated due to oxidative stress and lipid peroxidation (LPO). Hydroxy-2-nonenal (HNE), a major LPO product, binds covalently to cellular DNA to form the exocyclic etheno-DNA-base adducts, 1,N {sup 6}-ethenodeoxyadenine ({epsilon}dA) and 3,N {sup 4}-ethenodeoxycytosine ({epsilon}dC). By applying an ultrasensitive {sup 32}P-postlabeling-immunoaffinity method, {epsilon}dA and {epsilon}dC were quantified in abdominal aorta SMCs from 13 atherosclerotic patients and 3 non-smoking subjects without atherosclerotic lesions. The levels of etheno-adducts ranged for {epsilon}dA from 2.3 to 39.6/10{sup 8} dA and for {epsilon}dC from 10.7 to 157.7/10{sup 8} dC, with a high correlation between {epsilon}dA and {epsilon}dC (r = 0.84, P = 0.0001). Etheno-adduct levels were higher in atherosclerotic smokers than in ex-smokers for both {epsilon}dA (means 15.2 versus 7.3, P = 0.06) and {epsilon}dC (71.9 versus 51.6, not significant). {epsilon}dC levels were higher in either ex-smokers (P = 0.03) or smokers (P = 0.07) than in non-smokers. There was a poor correlation between either {epsilon}dA or {epsilon}dC and 8-hydroxy-2'-deoxyguanosine, whereas significant positive correlations were detected with the levels of several postlabeled bulky aromatic DNA adducts. In conclusion, two different types of DNA damage may be involved in atherosclerotic plaque formation and progression: (i) bulky aromatic compounds, to which aorta SMCs are chronically exposed in smokers, can either covalently bind to DNA, induce redox-cycling via quinone intermediates and/or activate local chronic inflammatory processes in the arterial wall; ii) this in turn leads to a self perpetuating

  9. Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Retrorsine, Leading to DNA Adduct Formation In Vivo

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2005-04-01

    Full Text Available Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. The high toxicity of many pyrrolizidine alkaloids has caused considerable loss of free-ranging livestock due to liver and pulmonary lesions. Chronic exposure of toxic pyrrolizidine alkaloids to laboratory animals induces cancer. This investigation studies the metabolic activation of retrorsine, a representative naturally occurring tumorigenic pyrrolizidine alkaloid, and shows that a genotoxic mechanism is correlated to the tumorigenicity of retrorsine. Metabolism of retrorsine by liver microsomes of F344 female rats produced two metabolites, 6, 7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, at a rate of 4.8 ± 0.1 nmol/mg/min, and retrorsine-N-oxide, at a rate of 17.6±0.5 nmol/mg/min. Metabolism was enhanced 1.7-fold by using liver microsomes prepared from dexamethasone-treated rats. DHP formation was inhibited 77% and retrorsine N-oxide formation was inhibited 29% by troleandomycin, a P450 3A enzyme inhibitor. Metabolism of retrorsine with lung, kidney, and spleen microsomes from dexamethasone-treated rats also generated DHP and the N-oxide derivative. When rat liver microsomal metabolism of retrorsine occurred in the presence of calf thymus DNA, a set of DHP-derived DNA adducts was formed; these adducts were detected and quantified by using a previously developed 32P-postlabeling/HPLC method. These same DNA adducts were also found in liver DNA of rats gavaged with retrorsine. Since DHP-derived DNA adducts are suggested to be potential biomarkers of riddelliine-induced tumorigenicity, our results indicate that (i similar to the metabolic activation of riddelliine, the mechanism of retrorsine-induced carcinogenicity in rats is also through a genotoxic mechanism involving DHP; and (ii the set of DHP-derived DNA adducts found in liver DNA of rats gavaged with retrorsine or riddelliine can serve as biomarkers for the

  10. Analysis of hemoglobin adducts from acrylamide, glycidamide, and ethylene oxide in paired mother/cord blood samples from Denmark.

    Science.gov (United States)

    von Stedingk, Hans; Vikström, Anna C; Rydberg, Per; Pedersen, Marie; Nielsen, Jeanette K S; Segerbäck, Dan; Knudsen, Lisbeth E; Törnqvist, Margareta

    2011-11-21

    The knowledge about fetal exposure to acrylamide/glycidamide from the maternal exposure through food is limited. Acrylamide, glycidamide, and ethylene oxide are electrophiles and form adducts with hemoglobin (Hb), which could be used for in vivo dose measurement. In this study, a method for analysis of Hb adducts by liquid chromatography-mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide, and ethylene oxide, were increased in tobacco smokers. Highly significant correlations were found between cord and maternal blood with regard to measured adduct levels of the three compounds. The mean cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27-0.86) for acrylamide, 0.38 (range 0.20-0.73) for glycidamide, and 0.43 (range 0.17-1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38-0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together, these results indicate a similar life span of fetal and maternal erythrocytes. The results showed that the in vivo dose in fetal and maternal blood is about the same and that the placenta gives negligible protection of the fetus to exposure from the investigated compounds. A trend of higher levels of the measured adducts in cord blood with gestational age was observed, which may reflect the gestational age-related change of the cord blood Hb composition toward a higher content of adult Hb. The results suggest that the Hb adduct levels measured in cord blood reflect the exposure to the fetus during the third trimester. The evaluation of the new analytical method showed that it is suitable for monitoring of background exposures of the investigated electrophilic compounds in large

  11. Multi-epoch Sub-arcsecond [Fe II] Spectroimaging of the DG Tau Outflows with NIFS. II. On the Nature of the Bipolar Outflow Asymmetry

    CERN Document Server

    White, Marc C; McGregor, Peter J; Salmeron, Raquel

    2014-01-01

    The origin of bipolar outflow asymmetry in young stellar objects (YSOs) remains poorly understood. It may be due to an intrinsically asymmetric outflow launch mechanism, or it may be caused by the effects of the ambient medium surrounding the YSO. Answering this question is an important step in understanding outflow launching. We have investigated the bipolar outflows driven by the T Tauri star DG Tauri on scales of hundreds of AU, using the Near-infrared Integral Field Spectrograph (NIFS) on Gemini North. The approaching outflow consists of a well-collimated jet, nested within a lower-velocity disc wind. The receding outflow is composed of a single-component bubble-like structure. We analyse the kinemat- ics of the receding outflow using kinetic models, and determine that it is a quasi-stationary bubble with an expanding internal velocity field. We propose that this bubble forms because the receding counterjet from DG Tau is obstructed by a clumpy ambient medium above the circumstellar disc surface, based on...

  12. Photochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA and Formation of DNA Covalent Adducts

    Directory of Open Access Journals (Sweden)

    Peter P. Fu

    2005-04-01

    Full Text Available DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.

  13. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2015-02-01

    Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6 μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response. - Highlights: • PM forms ovarian DNA adducts. • DNA damage marker γH2AX increased by PM exposure. • PM induces ovarian DNA double strand break repair.

  14. Comparative synchronous fluorescence spectrophotometry and 32P-postlabeling analysis of PAH-DNA adducts in human lung and the relationship to TP53 mutations

    DEFF Research Database (Denmark)

    Andreassen, Åshild; Kure, Elin H.; Nielsen, Per Sabro;

    1996-01-01

    Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were studied in human lung from 39 lung cancer patients by synchronous fluorescence spectrophotometric (SFS) and 32P-postlabeling assays. Regression analysis of the samples failed to detect any correlation between benzo[a]pyrene-diolepoxide (BPDE......)-DNA adducts detected by SFS and the BPDE co-migrating spot detected by 32P-postlabeling. We have also analyzed the relationship between adduct levels and TP53 mutations. By postlabeling diagonal radioactive zone (DRZ) adducts were detected in 37 of 39 (95%) lung tissues from lung cancer patients...

  15. Characterization of quinone derived protein adducts and their selective identification using redox cycling based chemiluminescence assay.

    Science.gov (United States)

    Elgawish, Mohamed Saleh; Kishikawa, Naoya; Ohyama, Kaname; Kuroda, Naotaka

    2015-07-17

    The cytotoxic mechanism of many quinones has been correlated to covalent modification of cellular proteins. However, the identification of relevant proteins targets is essential but challenging goals. To better understand the quinones cytotoxic mechanism, human serum albumin (HSA) was incubated in vitro with different concentration of menadione (MQ). In this respect, the initial nucleophilic addition of proteins to quinone converts the conjugates to redox-cycling quinoproteins with altered conformation and secondary structure and extended life span than the short lived, free quinones. The conjugation of MQ with nucleophilic sites likewise, free cysteine as well as ɛ-amino group of lysine residue of HSA has been found to be in concentration dependent manner. The conventional methods for modified proteins identification in complex mixtures are complicated and time consuming. Herein, we describe a highly selective, sensitive, simple, and fast strategy for quinoproteins identification. The suggested strategy exploited the unique redox-cycling capability of quinoproteins in presence of a reductant, dithiothreitol (DTT), to generate reactive oxygen species (ROS) that gave sufficient chemiluminescence (CL) when mixed with luminol. The CL approach is highly selective and sensitive to detect the quinoproteins in ten-fold molar excess of native proteins without adduct enrichment. The approach was also coupled with gel filtration chromatography (GFC) and used to identify adducts in complex mixture of proteins in vitro as well as in rat plasma after MQ administration. Albumin was identified as the main protein in human and rat plasma forming adduct with MQ. Overall, the identification of quinoproteins will encourage further studies of toxicological impact of quinones on human health. PMID:26044383

  16. Determining protein adducts of fipexide: mass spectrometry based assay for confirming the involvement of its reactive metabolite in covalent binding.

    Science.gov (United States)

    Sleno, Lekha; Varesio, Emmanuel; Hopfgartner, Gérard

    2007-01-01

    Fipexide is a nootropic drug, withdrawn from the market due to its idiosyncratic drug reactions causing adverse effects in man. Previous work on its metabolites has identified several potential reactive metabolites which could be implicated in protein binding. Here, we investigated the formation of these metabolites in rat and human hepatocytes. Based on these results, the o-quinone of fipexide (FIP), formed via the demethylenation reaction through a catechol intermediate, was chosen for further investigation. Studies were then pursued in order to relate this metabolite to protein binding, and thus better understand potential mechanisms for the toxicity of the parent compound. An assay was developed for determining the fipexide catechol-cysteine adduct in the microsomal protein fractions following in vitro incubations. This method digests the entire protein fraction into amino acids, followed by the detection of the Cys-metabolite adduct by liquid chromatography/mass spectrometry (LC/MS). We have designed a strategy where drug metabolism taking place in microsomal incubations and involved in protein binding can be assessed after the proteins have been digested, with the detection of the specific amino acid adduct. In this study, the structure of the fipexide adduct was hypothesized using knowledge previously gained in glutathione and N-acetylcysteine trapping experiments. Acetaminophen was used as a positive control for detecting a drug metabolite-cysteine adduct by LC/MS. This approach has the potential to be applicable as a protein-binding assay in early drug discovery without the need for radioactive compounds. PMID:18022964

  17. Safrole-DNA adducts in tissues from esophageal cancer patients: clues to areca-related esophageal carcinogenesis.

    Science.gov (United States)

    Lee, Jang-Ming; Liu, Tsung-Yung; Wu, Deng-Chyang; Tang, Hseau-Chung; Leh, Julie; Wu, Ming-Tsang; Hsu, Hsao-Hsun; Huang, Pei-Ming; Chen, Jin-Shing; Lee, Chun-Jean; Lee, Yung-Chie

    2005-01-01

    Epidemiological studies have demonstrated that areca quid chewing can be an independent risk factor for developing esophageal cancer. However, no studies are available to elucidate the mechanisms of how areca induces carcinogenesis in the esophagus. Since the areca nut in Taiwan contains a high concentration of safrole, a well-known carcinogenic agent, we analyzed safrole-DNA adducts by the 32P-postlabelling method in tissue specimens from esophageal cancer patients. In total, we evaluated 47 patients with esophageal cancer (16 areca chewers and 31 non-chewers) who underwent esophagectomy at the National Taiwan University Hospital between 1996 and 2002. Of the individuals with a history of habitual areca chewing (14 cigarette smokers and two non-smokers), one of the tumor tissue samples and five of the normal esophageal mucosa samples were positive for safrole-DNA adducts. All patients positive for safrole-DNA adducts were also cigarette smokers. Such adducts could not be found in patients who did not chew areca, irrespective of their habits of alcohol consumption or cigarette smoking (psafrole was also tested in vitro in three esophageal cell lines and four cultures of primary esophageal keratinocytes. In two of the esophageal keratinocyte cultures, adduct formation was increased by treatment with safrole after induction of cytochrome P450 by 3-methyl-cholanthrene. This paper provides the first observation of how areca induces esophageal carcinogenesis, i.e., through the genotoxicity of safrole, a component of the areca juice.

  18. A new general pathway for synthesis of reference compounds of N-terminal valine-isocyanate adducts.

    Science.gov (United States)

    Davies, Ronnie; Rydberg, Per; Westberg, Emelie; Motwani, Hitesh V; Johnstone, Erik; Törnqvist, Margareta

    2010-03-15

    Adducts to Hb could be used as biomarkers to monitor exposure to isocyanates. Particularly useful is the measurement of carbamoylation of N-terminal valines in Hb, after detachment as hydantoins. The synthesis of references from the reactive isocyanates, especially diisocyanates, has been problematic due to side reactions and polymerization of the isocyanate starting material. A simpler, safer, and more general method for the synthesis of valine adducts of isocyanates has been developed using N-[(4-nitrophenyl)carbamate]valine methylamide (NPCVMA) as the key precursor to adducts of various mono- and diisocyanates of interest. By reacting NPCVMA with a range of isocyanate-related amines, carbamoylated valines are formed without the use of the reactive isocyanates. The carbamoylated products synthesized here were cyclized with good yields of the formed hydantoins. The carbamoylated derivative from phenyl isocyanate also showed quantitative yield in a test with cyclization under the conditions used in blood. This new pathway for the preparation of N-carbamoylated model compounds overcomes the above-mentioned problems in the synthesis and is a general and simplified approach, which could make such reference compounds of adducts to N-terminal valine from isocyanates accessible for biomonitoring purposes. The synthesized hydantoins corresponding to adducts from isocyanic acid, methyl isocyanate, phenyl isocyanate, and 2,6-toluene diisocyanate were characterized by LC-MS analysis. The background level of the hydantoin from isocyanic acid in human blood was analyzed with the LC-MS conditions developed.

  19. Cysteine amide adduct formation from carboxylic acid drugs via UGT-mediated bioactivation in human liver microsomes.

    Science.gov (United States)

    Harada, H; Toyoda, Y; Endo, T; Kobayashi, M

    2015-10-01

    Although chemical trapping has been widely used to evaluate cytochrome P450-mediated drug bioactivation, thus far, only a few in vitro-trapping studies have been performed on UDP-glucuronosyltransferase (UGT)-mediated drug bioactivation. In this study, we used cysteine (Cys) as trapping agent to gain new insights into the UGT-mediated bioactivation involving acyl glucuronides of carboxylic acid drugs. Diclofenac, ketoprofen and ibuprofen were incubated in human liver microsomes with UDPGA and Cys, followed by analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The N-acyl-Cys amide adduct of diclofenac was characterized by mass analysis and was detectable even in photodiode array analysis. Our data indicated that the formation of such adducts reflects the reactivity of the corresponding acyl glucuronides. In addition, it was suggested that the adduct formation requires an N-terminal Cys moiety with both a free amine and a free thiol group, from the results using various cysteine derivatives. We propose that the S-acyl-Cys thioester adduct can form via transacylation of an acyl glucuronide and can then form to an N-acyl-Cys amide adduct through intramolecular S- to N-acyl rearrangement. This series of the reactions has important implications as a possible bioactivation mechanism for covalent binding of carboxylic acid drugs to macromolecules. PMID:26601426

  20. Determination of DNA adducts by combining acid-catalyzed hydrolysis and chromatographic analysis of the carcinogen-modified nucleobases.

    Science.gov (United States)

    Leung, Elvis M K; Deng, Kailin; Wong, Tin-Yan; Chan, Wan

    2016-01-01

    The commonly used method of analyzing carcinogen-induced DNA adducts involves the hydrolysis of carcinogen-modified DNA samples by using a mixture of enzymes, followed by (32)P-postlabeling or liquid chromatography (LC)-based analyses of carcinogen-modified mononucleotides/nucleosides. In the present study, we report the development and application of a new approach to DNA adduct analysis by combining the H(+)/heat-catalyzed release of carcinogen-modified nucleobases and the use of LC-based methods to analyze DNA adducts. Results showed that heating the carcinogen-modified DNA samples at 70 °C for an extended period of 4 to 6 h in the presence of 0.05% HCl can efficiently induce DNA depurination, releasing the intact carcinogen-modified nucleobases for LC analyses. After optimizing the hydrolysis conditions, DNA samples with C8- and N (2) -modified 2'-deoxyguanosine, as well as N (6) -modified 2'-deoxyadenosine, were synthesized by reacting DNA with 1-nitropyrene, acetaldehyde, and aristolochic acids, respectively. These samples were then hydrolyzed, and the released nucleobase adducts were analyzed using LC-based analytical methods. Analysis results demonstrated a dose-dependent release of target DNA adducts from carcinogen-modified DNA samples, indicating that the developed H(+)/heat-catalyzed hydrolysis method was quantitative. Comparative studies with enzymatic digestion method on carcinogen-modified DNA samples revealed that the two hydrolysis methods did not yield systematically different results.

  1. Hemagglutinin 222D/G polymorphism facilitates fast intra-host evolution of pandemic (H1N1 2009 influenza A viruses.

    Directory of Open Access Journals (Sweden)

    Nora Seidel

    Full Text Available The amino acid substitution of aspartic acid to glycine in hemagglutinin (HA in position 222 (HA-D222G as well as HA-222D/G polymorphism of pandemic (H1N1 2009 influenza viruses (A(H1N1pdm09 were frequently reported in severe influenza in humans and mice. Their impact on viral pathogenicity and the course of influenza has been discussed controversially and the underlying mechanism remained unclarified. In the present study, BALB/c mice, infected with the once mouse lung- and cell-passaged A(H1N1pdm09 isolate A/Jena/5258/09 (mpJena/5258, developed severe pneumonia. From day 2 to 3 or 4 post infection (p.i. symptoms (body weight loss and clinical score continuously worsened. After a short disease stagnation or even recovery phase in most mice, severity of disease further increased on days 6 and 7 p.i. Thereafter, surviving mice recovered. A 45 times higher virus titer maximum in the lung than in the trachea on day 2 p.i. and significantly higher tracheal virus titers compared to lung on day 6 p.i. indicated changes in the organ tropism during infection. Sequence analysis revealed an HA-222D/G polymorphism. HA-D222 and HA-G222 variants co-circulated in lung and trachea. Whereas, HA-D222 variant predominated in the lung, HA-G222 became the major variant in the trachea after day 4 p.i. This was accompanied by lower neutralizing antibody titers and broader receptor recognition including terminal sialic acid α-2,3-linked galactose, which is abundant on mouse trachea epithelial cells. Plaque-purified HA-G222-mpJena/5258 virus induced severe influenza with maximum symptom on day 6 p.i. These results demonstrated for the first time that HA-222D/G quasispecies of A(H1N1pdm09 caused severe biphasic influenza because of fast viral intra-host evolution, which enabled partial antibody escape and minor changes in receptor binding.

  2. A mini-review on Biginelli adducts with notable pharmacological properties

    Directory of Open Access Journals (Sweden)

    Ângelo de Fátima

    2015-05-01

    Full Text Available Since the disclosure of Biginelli reaction by the chemist Pietro Biginelli, functionalized 3,4-dihydropyrimidin-2(1H-ones/thiones (DHPMs have emerged as prototypes for the design of compounds with a broad variety of biological activities. This mini-review describes over 100 Biginelli adducts demonstrated to be promising anticancer, inhibitors of calcium channel, anti-inflammatory, antimicrobial and antioxidant agents. Thus, this compilation presents the most notable in vitro and in vivo results for such fascinating class of organic compounds.

  3. Cisplatin–DNA adducts inhibit translocation of the Ku subunits of DNA-PK

    OpenAIRE

    Turchi, John J.; Henkels, Karen M.; Zhou, Yun

    2000-01-01

    We have determined the effect of cisplatin–DNA damage on the ability of the DNA-dependent protein kinase (DNA-PK) to interact with duplex DNA molecules in vitro. The Ku DNA binding subunits of DNA-PK display a reduced ability to translocate on duplex DNA containing cisplatin–DNA adducts compared to control, undamaged duplex DNA. The decreased rates of translocation resulted in a decrease in the association of the p460 catalytic subunit of DNA-PK (DNA-PKcs) with the Ku–DNA complex. In addition...

  4. Atheroprotective immunization with malondialdehyde-modified LDL is hapten specific and dependent on advanced MDA adducts

    DEFF Research Database (Denmark)

    Gonen, Ayelet; Hansen, Lotte; Turner, William W;

    2014-01-01

    Immunization with homologous malondialdehyde (MDA)-modified LDL (MDA-LDL) leads to atheroprotection in experimental models supporting the concept that a vaccine to oxidation-specific epitopes (OSEs) of oxidized LDL could limit atherogenesis. However, modification of human LDL with OSE to use...... as an immunogen would be impractical for generalized use. Furthermore, when MDA is used to modify LDL, a wide variety of related MDA adducts are formed, both simple and more complex. To define the relevant epitopes that would reproduce the atheroprotective effects of immunization with MDA-LDL, we sought...

  5. STM/STS observation of ferrocene derivative adduct to C60 on HOPG

    International Nuclear Information System (INIS)

    The C60ONCFn cycloadduct (Fn=ferrocene) was prepared in the reaction between C60 and ferrocene oxime, the ferrocene derivative was bound to C60 at the 6-6 bond by a heterocyclic oxygen-nitrogen-carbon ring; the compound was stable in air. The compound dissolved in dichloroethane was deposited on HOPG and observed by UHV STM/STS methods. The molecules of C60ONCFn formed several-microns-long straight chains with clearly visible adducted groups pointing to one side of the chain. The STM/STS observations are discussed within the terms of semiempirical quantum chemical molecular modeling

  6. Lead tetraacetate oxidation of the Diels-Alder adduct of 7-dehydrocholestryl acetate with maleic anhydride

    Directory of Open Access Journals (Sweden)

    MIHAILO LJ. MIHAILOVIC

    2000-03-01

    Full Text Available The Diels-Alder adduct (3, obtained by cycloaddition of 7-dehydrocholesteryl acetate (1 and maleic anhydride (2, was heated at ca. 90°C with a large excess of lead tetraacetate in pyridine solution for 5 h. Under these conditions, compound 3 underwent lactonization with the participation of the olefinic D6-double bond to give two isomeric monolactone derivatives, 9 and 10 (in a total yield of ca. 6%, and the bislactone product 11 (in 11.5% yield. The starting material was recovered in 36% yield.

  7. Shape of the Adduct Formic Acid-Dimethyl Ether: A Rotational Study.

    Science.gov (United States)

    Evangelisti, Luca; Spada, Lorenzo; Li, Weixing; Ciurlini, Anna; Grabow, Jens-Uwe; Caminati, Walther

    2016-05-12

    Formic acid and dimethyl ether are combined in a supersonic expansion to form a molecular adduct with the two subunits held together by a "classical" OH···O hydrogen bond and a bifurcated weak CH2···O hydrogen bond. The rotational spectra of the parent and of two (13)C isotopologues in natural abundance show that the complex has Cs symmetry, with the heavy atom symmetry planes of HCOOH and (CH3)2O perpendicular to each other. PMID:27102727

  8. TRANSPLATIN-CONJUGATED TRIPLEX-FORMING OLIGONUCLEOTIDES FORM ADDUCTS WITH BOTH STRANDS OF DNA

    OpenAIRE

    Campbell, Meghan A.; Miller, Paul S.

    2009-01-01

    Triplex-forming oligonucleotides (TFOs) can bind to polypurine•polypyrimidine tracts in DNA and as a consequence, perturb normal functioning of a targeted gene. The effectiveness of such anti-gene TFOs can potentially be enhanced by covalent attachment of the TFO to its DNA target. Here we report that attachment of N-7-platinated guanine nucleosides to the 3′- and/or 5′-ends of oligopyrimidine TFOs enables these TFOs to form highly stable adducts with target DNA deoxyguanosines or deoxyadenos...

  9. Chlorabietols A-C, Phloroglucinol-Diterpene Adducts from the Chloranthaceae Plant Chloranthus oldhamii.

    Science.gov (United States)

    Xiong, Juan; Hong, Zhi-Lai; Gao, Li-Xin; Shen, Jie; Liu, Shu-Ting; Yang, Guo-Xun; Li, Jia; Zeng, Huaqiang; Hu, Jin-Feng

    2015-11-01

    Three unprecedented phloroglucinol-diterpene adducts, chlorabietols A-C (1-3), were isolated from the roots of the rare Chloranthaceae plant Chloranthus oldhamii. They represent a new class of compounds, featuring an abietane-type diterpenoid coupled with different alkenyl phloroglucinol units by forming a 2,3-dihydrofuran ring. Their structures were elucidated by detailed spectroscopic analysis, molecular modeling studies, and electronic circular dichroism calculations. Compounds 1-3 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 12.6, 5.3, and 4.9 μM, respectively.

  10. Variations on a theme - the evolution of hydrocarbon solids: I. Compositional and spectral modelling - the eRCN and DG models

    CERN Document Server

    Jones, A P

    2015-01-01

    Context. The compositional properties of hydrogenated amorphous carbons are known to evolve in response to the local conditions. Aims. To present a model for low-temperature, amorphous hydrocarbon solids, based on the microphysical properties of random and defected networks of carbon and hydrogen atoms, that can be used to study and predict the evolution of their properties in the interstellar medium. Methods. We adopt an adaptable and prescriptive approach to model these materials, which is based on a random covalent network (RCN) model, extended here to a full compositional derivation (the eRCN model), and a defective graphite (DG) model for the hydrogen poorer materials where the eRCN model is no longer valid. Results. We provide simple expressions that enable the determination of the structural, infrared and spectral properties of amorphous hydrocarbon grains as a function of the hydrogen atomic fraction, XH. Structural annealing, resulting from hydrogen atom loss, results in a transition from H-rich, ali...

  11. Analytical Modeling of Potential Distribution and Threshold Voltage of Gate Underlap DG MOSFETs with a Source/Drain Lateral Gaussian Doping Profile

    Science.gov (United States)

    Singh, Kunal; Kumar, Mirgender; Goel, Ekta; Singh, Balraj; Dubey, Sarvesh; Kumar, Sanjay; Jit, Satyabrata

    2016-04-01

    This paper reports a new two-dimensional (2D) analytical model for the potential distribution and threshold voltage of the short-channel symmetric gate underlap ultrathin DG MOSFETs with a lateral Gaussian doping profile in the source (S)/drain (D) region. The parabolic approximation and conformal mapping techniques have been explored for solving the 2D Poisson's equation to obtain the channel potential function of the device. The effects of straggle parameter (of the lateral Gaussian doping profile in the S/D region), underlap length, gate length, channel thickness and oxide thickness on the surface potential and threshold voltage have been investigated. The loss of switching speed due to the drain-induced barrier lowering (DIBL) has also been reported. The proposed model results have been validated by comparing them with their corresponding TCAD simulation data obtained by using the commercially available 2D ATLAS™ simulation software.

  12. Formation and persistence of sterigmatocystin-DNA adducts in rat liver determined via 32P-postlabeling analysis

    International Nuclear Information System (INIS)

    A 32P-postlabeling method has been employed to detect the in vitro and in vivo modification of DNA by the mycotoxin sterigmatocystin (ST). Dose-dependent ST-DNA adduct formation was detected in the liver of male Fischer 344 rats over a 27-fold range of ST administered. In addition, ST-DNA adducts, formed in rats given a 9 mg/kg dose, were found to persist up to 105 days after treatment at a level of 0.5% of the 2-h value. Loss of these adducts from liver DNA was observed to exhibit a triphasic profile: rapid loss during the first 24 h followed by a slower decline from 1 to 14 days post dosing and an extremely slow decline from day 14 to 105 post treatment. This experimental approach to the study of mycotoxin-DNA interactions permits the quantitative description of DNA modification in ST-treated animals. (Auth.)

  13. Efficient CO2 capture by tertiary amine-functionalized ionic liquids through Li+-stabilized zwitterionic adduct formation

    Directory of Open Access Journals (Sweden)

    Zhen-Zhen Yang

    2014-08-01

    Full Text Available Highly efficient CO2 absorption was realized through formation of zwitterionic adducts, combining synthetic strategies to ionic liquids (ILs and coordination. The essence of our strategy is to make use of multidentate cation coordination between Li+ and an organic base. Also PEG-functionalized organic bases were employed to enhance the CO2-philicity. The ILs were reacted with CO2 to form the zwitterionic adduct. Coordination effects between various lithium salts and neutral ligands, as well as the CO2 capacity of the chelated ILs obtained were investigated. For example, the CO2 capacity of PEG150MeBu2N increased steadily from 0.10 to 0.66 (mol CO2 absorbed per mol of base through the formation of zwitterionic adducts being stabilized by Li+.

  14. Myeloperoxidase - 463A variant reduces benzo(a)pyrene diol epoxide DNA adducts in skin of coal tar treated patients

    Energy Technology Data Exchange (ETDEWEB)

    Rojas, M.; Godschalk, R.; Alexandrov, K.; Cascorbi, I.; Kriek, E.; Ostertag, J.; Van Schooten, F.J.; Bartsch, H. [German Cancer Research Center, Heidelberg (Germany). Div. of Toxicology & Cancer Risk Factors

    2001-07-01

    The skin of atopic dermatitis patients provides an excellent model to study the role of inflammation in benzo(a)pyrene (BaP) activation, since these individuals are often topically treated with ointments containing high concentrations of BaP. The authors determined, by HPLC with fluorescence detection, the BaP diol epoxide (BPDE)-DNA adduct levels in human skin after topical treatment with coal tar and their modulation by the -453G into A myeloperoxidase (MPO) polymorphism, which reduces MPO mRNA expression. The data show for the first time: (i) the in vivo formation of BPDE-DNA adducts in human skin treated with coal tar; (ii) that the MPO-463AA/AG genotype reduced BPDE-DNA adduct levels in human skin.

  15. Optimal Siting and Sizing of Multiple DG Units for the Enhancement of Voltage Profile and Loss Minimization in Transmission Systems Using Nature Inspired Algorithms.

    Science.gov (United States)

    Ramamoorthy, Ambika; Ramachandran, Rajeswari

    2016-01-01

    Power grid becomes smarter nowadays along with technological development. The benefits of smart grid can be enhanced through the integration of renewable energy sources. In this paper, several studies have been made to reconfigure a conventional network into a smart grid. Amongst all the renewable sources, solar power takes the prominent position due to its availability in abundance. Proposed methodology presented in this paper is aimed at minimizing network power losses and at improving the voltage stability within the frame work of system operation and security constraints in a transmission system. Locations and capacities of DGs have a significant impact on the system losses in a transmission system. In this paper, combined nature inspired algorithms are presented for optimal location and sizing of DGs. This paper proposes a two-step optimization technique in order to integrate DG. In a first step, the best size of DG is determined through PSO metaheuristics and the results obtained through PSO is tested for reverse power flow by negative load approach to find possible bus locations. Then, optimal location is found by Loss Sensitivity Factor (LSF) and weak (WK) bus methods and the results are compared. In a second step, optimal sizing of DGs is determined by PSO, GSA, and hybrid PSOGSA algorithms. Apart from optimal sizing and siting of DGs, different scenarios with number of DGs (3, 4, and 5) and PQ capacities of DGs (P alone, Q alone, and P and Q both) are also analyzed and the results are analyzed in this paper. A detailed performance analysis is carried out on IEEE 30-bus system to demonstrate the effectiveness of the proposed methodology.

  16. Optimal Siting and Sizing of Multiple DG Units for the Enhancement of Voltage Profile and Loss Minimization in Transmission Systems Using Nature Inspired Algorithms.

    Science.gov (United States)

    Ramamoorthy, Ambika; Ramachandran, Rajeswari

    2016-01-01

    Power grid becomes smarter nowadays along with technological development. The benefits of smart grid can be enhanced through the integration of renewable energy sources. In this paper, several studies have been made to reconfigure a conventional network into a smart grid. Amongst all the renewable sources, solar power takes the prominent position due to its availability in abundance. Proposed methodology presented in this paper is aimed at minimizing network power losses and at improving the voltage stability within the frame work of system operation and security constraints in a transmission system. Locations and capacities of DGs have a significant impact on the system losses in a transmission system. In this paper, combined nature inspired algorithms are presented for optimal location and sizing of DGs. This paper proposes a two-step optimization technique in order to integrate DG. In a first step, the best size of DG is determined through PSO metaheuristics and the results obtained through PSO is tested for reverse power flow by negative load approach to find possible bus locations. Then, optimal location is found by Loss Sensitivity Factor (LSF) and weak (WK) bus methods and the results are compared. In a second step, optimal sizing of DGs is determined by PSO, GSA, and hybrid PSOGSA algorithms. Apart from optimal sizing and siting of DGs, different scenarios with number of DGs (3, 4, and 5) and PQ capacities of DGs (P alone, Q alone, and P and Q both) are also analyzed and the results are analyzed in this paper. A detailed performance analysis is carried out on IEEE 30-bus system to demonstrate the effectiveness of the proposed methodology. PMID:27057557

  17. Optimal Siting and Sizing of Multiple DG Units for the Enhancement of Voltage Profile and Loss Minimization in Transmission Systems Using Nature Inspired Algorithms

    Science.gov (United States)

    Ramamoorthy, Ambika; Ramachandran, Rajeswari

    2016-01-01

    Power grid becomes smarter nowadays along with technological development. The benefits of smart grid can be enhanced through the integration of renewable energy sources. In this paper, several studies have been made to reconfigure a conventional network into a smart grid. Amongst all the renewable sources, solar power takes the prominent position due to its availability in abundance. Proposed methodology presented in this paper is aimed at minimizing network power losses and at improving the voltage stability within the frame work of system operation and security constraints in a transmission system. Locations and capacities of DGs have a significant impact on the system losses in a transmission system. In this paper, combined nature inspired algorithms are presented for optimal location and sizing of DGs. This paper proposes a two-step optimization technique in order to integrate DG. In a first step, the best size of DG is determined through PSO metaheuristics and the results obtained through PSO is tested for reverse power flow by negative load approach to find possible bus locations. Then, optimal location is found by Loss Sensitivity Factor (LSF) and weak (WK) bus methods and the results are compared. In a second step, optimal sizing of DGs is determined by PSO, GSA, and hybrid PSOGSA algorithms. Apart from optimal sizing and siting of DGs, different scenarios with number of DGs (3, 4, and 5) and PQ capacities of DGs (P alone, Q alone, and  P and Q both) are also analyzed and the results are analyzed in this paper. A detailed performance analysis is carried out on IEEE 30-bus system to demonstrate the effectiveness of the proposed methodology. PMID:27057557

  18. Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters.

    Science.gov (United States)

    Pelz, Kimberly M; Routman, David; Driscoll, Joseph R; Kriegsfeld, Lance J; Dark, John

    2008-01-01

    Siberian hamsters (Phodopus sungorus) have the ability to express daily torpor and decrease their body temperature to approximately 15 degrees C, providing a significant savings in energy expenditure. Daily torpor in hamsters is cued by winterlike photoperiods and occurs coincident with the annual nadirs in body fat reserves and chronic leptin concentrations. To better understand the neural mechanisms underlying torpor, Siberian hamster pups were postnatally treated with saline or MSG to ablate arcuate nucleus neurons that likely possess leptin receptors. Body temperature was studied telemetrically in cold-acclimated (10 degrees C) male and female hamsters moved to a winterlike photoperiod (10:14-h light-dark cycle) (experiments 1 and 2) or that remained in a summerlike photoperiod (14:10-h light-dark cycle) (experiment 3). In experiment 1, even though other photoperiodic responses persisted, MSG-induced arcuate nucleus ablations prevented the photoperiod-dependent torpor observed in saline-treated Siberian hamsters. MSG-treated hamsters tended to possess greater fat reserves. To determine whether reductions in body fat would increase frequency of photoperiod-induced torpor after MSG treatment, hamsters underwent 2 wk of food restriction (70% of ad libitum) in experiment 2. Although food restriction did increase the frequency of torpor in both MSG- and saline-treated hamsters, it failed to normalize the proportion of MSG-treated hamsters undergoing photoperiod-dependent torpor. In experiment 3, postnatal MSG treatments reduced the proportion of hamsters entering 2DG-induced torpor-like hypothermia by approximately 50% compared with saline-treated hamsters (38 vs. 72%). In those MSG-treated hamsters that did become hypothermic, their minimum temperature during hypothermia was significantly greater than comparable saline-treated hamsters. We conclude that 1) arcuate nucleus mechanisms mediate photoperiod-induced torpor, 2) food-restriction-induced torpor may also be

  19. Optimal Siting and Sizing of Multiple DG Units for the Enhancement of Voltage Profile and Loss Minimization in Transmission Systems Using Nature Inspired Algorithms

    Directory of Open Access Journals (Sweden)

    Ambika Ramamoorthy

    2016-01-01

    Full Text Available Power grid becomes smarter nowadays along with technological development. The benefits of smart grid can be enhanced through the integration of renewable energy sources. In this paper, several studies have been made to reconfigure a conventional network into a smart grid. Amongst all the renewable sources, solar power takes the prominent position due to its availability in abundance. Proposed methodology presented in this paper is aimed at minimizing network power losses and at improving the voltage stability within the frame work of system operation and security constraints in a transmission system. Locations and capacities of DGs have a significant impact on the system losses in a transmission system. In this paper, combined nature inspired algorithms are presented for optimal location and sizing of DGs. This paper proposes a two-step optimization technique in order to integrate DG. In a first step, the best size of DG is determined through PSO metaheuristics and the results obtained through PSO is tested for reverse power flow by negative load approach to find possible bus locations. Then, optimal location is found by Loss Sensitivity Factor (LSF and weak (WK bus methods and the results are compared. In a second step, optimal sizing of DGs is determined by PSO, GSA, and hybrid PSOGSA algorithms. Apart from optimal sizing and siting of DGs, different scenarios with number of DGs (3, 4, and 5 and PQ capacities of DGs (P alone, Q alone, and  P and Q both are also analyzed and the results are analyzed in this paper. A detailed performance analysis is carried out on IEEE 30-bus system to demonstrate the effectiveness of the proposed methodology.

  20. Association between plasma BPDE‐Alb adduct concentrations and DNA damage of peripheral blood lymphocytes among coke oven workers

    Science.gov (United States)

    Wang, Hong; Chen, Weihong; Zheng, Hongyan; Guo, Liang; Liang, Huashan; Yang, Xiaobo; Bai, Yun; Sun, Jianya; Su, Yougong; Chen, Yongwen; Yuan, Jing; Bi, Yongyi; Wei, Qingyi; Wu, Tangchun

    2007-01-01

    Objectives Coke oven emissions (COE) containing polycyclic aromatic hydrocarbons (PAHs) can induce both benzo[a]pyrene‐r‐7, t‐8, t‐9,c‐10‐tetrahydotetrol‐albumin (BPDE‐Alb) adducts and DNA damage. However, the relation between these biomarkers for early biological effects is not well documented in coke oven workers. Methods In this study, the authors recruited 207 male workers exposed to COE and 102 controls not exposed to COE in the same steel plant in northern China. They measured BPDE‐Alb adduct concentrations in plasma with reverse‐phase high performance liquid chromatography and DNA damage in peripheral blood lymphocytes with alkaline comet assay. Results The results showed that the median concentration of BPDE‐Alb adducts in the exposed group (34.36 fmol/mg albumin) was significantly higher than that in the control group (21.90 fmol/mg albumin, p = 0.012). The mean Olive tail moment (Olive TM) of DNA damage in the exposed and control groups were 1.20 and 0.63, respectively (p = 0.000). Multivariate logistic regression analysis revealed that the odds ratio (OR) for BPDE‐Alb adduct and Olive TM associated with the exposure were 1.72 (95% CI 1.06 to 2.81) and 1.96 (95% CI 1.20 to 3.19), respectively. These results show significant correlations between the concentrations of BPDE‐Alb adduct and Olive TM levels in exposed group (r = 0.235, p = 0.001) but not in control group (r = 0.093, p = 0.353). Conclusion The results suggest that occupational exposure to COE may induce both BPDE–Alb adducts and DNA damage in the lymphocytes of coke oven workers and that these two markers are useful for monitoring exposure to COE in the workplace. PMID:17449561

  1. Benzene-derived N2-(4-hydroxyphenyl)-deoxyguanosine adduct: UvrABC incision and its conformation in DNA

    Energy Technology Data Exchange (ETDEWEB)

    Hang, Bo; Rodriguez, Ben; Yang, Yanu; Guliaev, Anton B.; Chenna, Ahmed

    2010-06-14

    Benzene, a ubiquitous human carcinogen, forms DNA adducts through its metabolites such as p-benzoquinone (p-BQ) and hydroquinone (HQ). N(2)-(4-Hydroxyphenyl)-2'-deoxyguanosine (N(2)-4-HOPh-dG) is the principal adduct identified in vivo by (32)P-postlabeling in cells or animals treated with p-BQ or HQ. To study its effect on repair specificity and replication fidelity, we recently synthesized defined oligonucleotides containing a site-specific adduct using phosphoramidite chemistry. We here report the repair of this adduct by Escherichia coli UvrABC complex, which performs the initial damage recognition and incision steps in the nucleotide excision repair (NER) pathway. We first showed that the p-BQ-treated plasmid was efficiently cleaved by the complex, indicating the formation of DNA lesions that are substrates for NER. Using a 40-mer substrate, we found that UvrABC incises the DNA strand containing N(2)-4-HOPh-dG in a dose- and time-dependent manner. The specificity of such repair was also compared with that of DNA glycosylases and damage-specific endonucleases of E. coli, both of which were found to have no detectable activity toward N(2)-4-HOPh-dG. To understand why this adduct is specifically recognized and processed by UvrABC, molecular modeling studies were performed. Analysis of molecular dynamics trajectories showed that stable G:C-like hydrogen bonding patterns of all three Watson-Crick hydrogen bonds are present within the N(2)-4-HOPh-G:C base pair, with the hydroxyphenyl ring at an almost planar position. In addition, N(2)-4-HOPh-dG has a tendency to form more stable stacking interactions than a normal G in B-type DNA. These conformational properties may be critical in differential recognition of this adduct by specific repair enzymes.

  2. Acetaminophen-induced liver damage in mice is associated with gender-specific adduction of peroxiredoxin-6

    Directory of Open Access Journals (Sweden)

    Isaac Mohar

    2014-01-01

    Full Text Available The mechanism by which acetaminophen (APAP causes liver damage evokes many aspects drug metabolism, oxidative chemistry, and genetic-predisposition. In this study, we leverage the relative resistance of female C57BL/6 mice to APAP-induced liver damage (AILD compared to male C57BL/6 mice in order to identify the cause(s of sensitivity. Furthermore, we use mice that are either heterozygous (HZ or null (KO for glutamate cysteine ligase modifier subunit (Gclm, in order to titrate the toxicity relative to wild-type (WT mice. Gclm is important for efficient de novo synthesis of glutathione (GSH. APAP (300 mg/kg, ip or saline was administered and mice were collected at 0, 0.5, 1, 2, 6, 12, and 24 h. Male mice showed marked elevation in serum alanine aminotransferase by 6 h. In contrast, female WT and HZ mice showed minimal toxicity at all time points. Female KO mice, however, showed AILD comparable to male mice. Genotype-matched male and female mice showed comparable APAP–protein adducts, with Gclm KO mice sustaining significantly greater adducts. ATP was depleted in mice showing toxicity, suggesting impaired mitochondria function. Indeed, peroxiredoxin-6, a GSH-dependent peroxiredoxin, was preferentially adducted by APAP in mitochondria of male mice but rarely adducted in female mice. These results support parallel mechanisms of toxicity where APAP adduction of peroxiredoxin-6 and sustained GSH depletion results in the collapse of mitochondria function and hepatocyte death. We conclude that adduction of peroxiredoxin-6 sensitizes male C57BL/6 mice to toxicity by acetaminophen.

  3. Troglitazone thiol adduct formation in human liver microsomes: enzyme kinetics and reaction phenotyping.

    Science.gov (United States)

    Gan, Jinping; Qu, Qinling; He, Bing; Shyu, Wen C; Rodrigues, A David; He, Kan

    2008-08-01

    Troglitazone (TGZ) induced hepatotoxicity has been linked to cytochrome P450 (CYP)-catalyzed reactive metabolite formation. Therefore, the kinetics and CYP specificity of reactive metabolite formation were studied using dansyl glutathione (dGSH) as a trapping agent after incubation of TGZ with human liver microsomes (HLM) and recombinant human CYP proteins. CYP2C8 exhibited the highest rate of TGZ adduct (TGZ-dGS) formation, followed by CYP3A4, CYP3A5, and CYP2C19. The involvement of CYP2C8 and CYP3A4 was confirmed with CYP form-selective chemical inhibitors. The impact of TGZ concentration on the rate of TGZ-dGS formation was also evaluated. In this instance, two distinctly different profiles were observed with recombinant CYP3A4 and CYP2C8. It is concluded that both CYP3A4/5 and CYP2C8 play a major role in the formation of TGZ adduct in HLM. However, the contribution of these CYPs varies depending on their relative expression and the concentration of TGZ. PMID:19356091

  4. Formation of BH3 Adducts with Pyridine-2-Methylaminophosphine ligands: An experimental and computational study

    Indian Academy of Sciences (India)

    Harinath Adimulam; Dwijendra P Kukri; Bhabani S Mallik; Tarun K Panda

    2016-01-01

    The reaction of pyridine-2-methylaminophosphine [C5H4N-CH2NHPPh2] (1) and pyridine-2-methylphosphinoselenoic amide [C5H4N-CH2NHP(Se)Ph2] (2) with BH3·SMe2 yields the corresponding adducts [C5H4N(BH3)-CH2NHP(BH3)Ph2] (1a), and [C5H4N(BH3)-CH2NHP(Se)Ph2] (2a), respectively. The solid state structures of both the compounds were established by single crystal X-ray diffraction analysis. The phosphorus and the pyridine nitrogen atoms are coordinated to the boron atom in the case of 1a whereas only pyridine nitrogen atom is attached to the BH3 group in the case of 2a. To understand the nature of P-B/ N-B bonds and to compare the basicities of pyridine nitrogen, amino nitrogen and phosphorus atoms, density functional theoretical (DFT) calculations were performed on the BH3 adducts 1a and 2a. The results are consistent with the experimental results.

  5. The formation of argpyrimidine, a methylglyoxal-arginine adduct, in the nucleus of neural cells

    International Nuclear Information System (INIS)

    Methylglyoxal (MG) is an endogenous metabolite in glycolysis and forms stable adducts primarily with arginine residues of intracellular proteins. The biological role of this modification in cell function is not known. In the present study, we found that a MG-detoxification enzyme glyoxalase I (GLO1) is mainly expressed in the ventricular zone (VZ) at embryonic day 16 which neural stem and progenitor cells localize. Moreover, immunohistochemical analysis revealed that argpyrimidine, a major MG-arginine adduct, is predominantly produced in cortical plate neurons not VZ during cerebral cortex development and is exclusively located in the nucleus. Immunoblotting experiment showed that the formation of argpyrimidine occurs on some nuclear proteins of cortical neurons. To our knowledge, this is first report of the argpyrimidine formation in the nucleus of neuron. These findings suggest that GLO1, which is dominantly expressed in the embryonic VZ, reduces the intracellular level of MG and suppresses the formation of argpyrimidine in neural stem and progenitor cells. Argpyrimidine may contribute to the neural differentiation and/or the maintenance of the differentiated state via the modification of nuclear proteins.

  6. Fast repair of dAMP hydroxyl radical adduct by verbascoside via electron transfer

    Institute of Scientific and Technical Information of China (English)

    石益民; 王文锋; 姚思德; 林维真; 韩镇辉; 师彦平; 贾忠建; 郑荣梁

    1999-01-01

    DNA damaged by oxygen radicals has been implicated as a causative event in a number of degenerative diseases, including cancer and aging. So it is very impotant to look for ways in which either oxygen radicals are scavenged prior to DNA damage or damaged DNA is repaired to supplement the cells’ inadequate repair capacity. The repair activity and its mechanism of verbaseoside, isolated from Pedicularis species, towards dAMP-OH·was studied with pulse radiolytic technique. On pulse irradiation of nitrous oxide saturated 2 mmol/L dAMP aqueous solution containing verbascoside, the transient absorption spectrum of the hydroxyl adduct of dAMP decayed with the formation of that of the phenoxyl radical of verbascoside well under 100 microseconds after electron pulse irradiation. The result indicated that dAMP hydroxyl adducts can be repaired by verbascoside. The rate constants of the repair reaction was deduced to be 5.9×108 dm3·mol-1·s-1. A deeper understanding of this new repair mechanism will undo

  7. 2-Aminofluorene metabolism and DNA adduct formation by mononuclear leukocytes from rapid and slow acetylator mouse strains.

    Science.gov (United States)

    Levy, G N; Chung, J G; Weber, W W

    1994-02-01

    Following exposure of mice to the arylamine carcinogen 2-aminofluorene, DNA-carcinogen adducts can be found in the target tissues liver and bladder, and also in circulating leukocytes. Evidence is presented here that mouse mononuclear leukocytes (MNL) are capable of metabolizing 2-aminofluorene to DNA-binding metabolites which give rise to the adducts found in the MNL. Both lymphocytes and monocytes were able to acetylate arylamines during 18 h of culture. The degree of acetylation was determined by the N-acetyltransferase genotype of the mice as shown through use of acetylator congenic strains which differ only in the Nat-2 gene. Cultured MNL from rapid acetylator mice (C57BL/6J and A.B6-Natr) produced about twice as much N-acetylaminofluorene from 2-aminofluorene and 6- to 8-fold as much N-acetyl-p-aminobenzoic acid from p-aminobenzoic acid as cells from slow acetylator mice (B6.A-Nat(s) and A/J). Other differences in arylamine metabolism by MNL in culture were observed and shown to be due to genetic factors, currently unidentified, other than N-acetyltransferase. DNA adduct formation following incubation of MNL with the arylamine carcinogen 2-aminofluorene was related to both acetylation capacity and to other genetic metabolic factors in the mouse genome. MNL from rapid acetylator mice with the C57BL/6J background (B6) had 3-fold the DNA adduct levels of cells from the corresponding slow acetylator congenic (B6.A-Nat(s)). Similarly, MNL from rapid acetylator mice with the A/J background (A.B6-Natr) had twice the DNA adduct levels of those from their corresponding slow congenic (A). Adduct levels in MNL from C57BL/6J were nearly the same as those of MNL from A/J, again indicating the involvement of loci other than acetylation in DNA adduct formation. The finding of genetically dependent arylamine carcinogen metabolism and DNA adduct formation in cultured MNL suggests the possibility of using cultured MNL for assessing individual susceptibility to arylamine

  8. Recognition and repair of the CC-1065-(N3-Adenine)-DNA adduct by the UVRABC nuclease

    Energy Technology Data Exchange (ETDEWEB)

    Tang, M.; Lee, C.S.; Doisy, R.; Ross, L.; Needham-VanDevanter, D.R.; Hurley, L.H.

    1988-02-09

    The recognition and repair of the helix-stabilizing and relatively nondistortive CC-1065-(N3-adenine)-DNA adduct by UVRABC nuclease has been investigated both in vivo with phi X174RFI DNA by a transfection assay and in vitro by a site-directed adduct in a 117 base pair fragment from M13mp1. CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis which binds within the minor groove of DNA through N3 of adenine. In contrast to the helix-destabilizing and distortive modifications of DNA caused by ultraviolet light or N-acetoxy-2-(acetylamino)fluorene, CC-1065 increases the melting point of DNA and decreases the S1 nuclease activity. Using a viral DNA-Escherichia coli transfection system, the authors have found that the uvrA, uvrB, and uvrC genes, which code for the major excision repair proteins for UV- and NAAAF-induced DNA damage, are also involved in the repair of CC-1065-DNA adducts. In contrast, the uvrD gene product, which has been found to be involved in the repair of UV damage, has no effect in repairing CC-1065-DNA adducts. Purified UVRA, UVRB, and UVRC proteins must work in concert to incise the drug-modified phi X174RFI DNA. Using a site-directed and multiple CC-1065 modified (MspI-BstNI) 117 base pair fragment from M13mp1, they have found that UVRABC nuclease incises at the eight phosphodiester bond on the 5' side of the CC-1065-DNA adduct on the drug-modified strand. The enzymes do not cut the noncovalently modified strand. The DNA sequence and/or helix-stabilizing effect of multiple adducts may determine the recognition and/or incision of the drug-DNA adduct by UVRABC nuclease. These results are discussed in relation to the structure of the CC-1065-DNA adduct and the effect of drug binding on local DNA structure.

  9. Recognition and repair of the CC-1065-(N3-Adenine)-DNA adduct by the UVRABC nuclease

    International Nuclear Information System (INIS)

    The recognition and repair of the helix-stabilizing and relatively nondistortive CC-1065-(N3-adenine)-DNA adduct by UVRABC nuclease has been investigated both in vivo with phi X174RFI DNA by a transfection assay and in vitro by a site-directed adduct in a 117 base pair fragment from M13mp1. CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis which binds within the minor groove of DNA through N3 of adenine. In contrast to the helix-destabilizing and distortive modifications of DNA caused by ultraviolet light or N-acetoxy-2-(acetylamino)fluorene, CC-1065 increases the melting point of DNA and decreases the S1 nuclease activity. Using a viral DNA-Escherichia coli transfection system, the authors have found that the uvrA, uvrB, and uvrC genes, which code for the major excision repair proteins for UV- and NAAAF-induced DNA damage, are also involved in the repair of CC-1065-DNA adducts. In contrast, the uvrD gene product, which has been found to be involved in the repair of UV damage, has no effect in repairing CC-1065-DNA adducts. Purified UVRA, UVRB, and UVRC proteins must work in concert to incise the drug-modified phi X174RFI DNA. Using a site-directed and multiple CC-1065 modified (MspI-BstNI) 117 base pair fragment from M13mp1, they have found that UVRABC nuclease incises at the eight phosphodiester bond on the 5' side of the CC-1065-DNA adduct on the drug-modified strand. The enzymes do not cut the noncovalently modified strand. The DNA sequence and/or helix-stabilizing effect of multiple adducts may determine the recognition and/or incision of the drug-DNA adduct by UVRABC nuclease. These results are discussed in relation to the structure of the CC-1065-DNA adduct and the effect of drug binding on local DNA structure

  10. Structure of DNA polymerase β with a benzo[c]phenanthrene diol epoxide-adducted template exhibits mutagenic features

    OpenAIRE

    Batra, Vinod K.; Shock, David D.; Prasad, Rajendra; BEARD, WILLIAM A.; Hou, Esther W.; Pedersen, Lars C.; Sayer, Jane M.; Yagi, Haruhiko; Kumar, Subodh; Jerina, Donald M.; Wilson, Samuel H.

    2006-01-01

    We have determined the crystal structure of the human base excision repair enzyme DNA polymerase β (Pol β) in complex with a 1-nt gapped DNA substrate containing a template N2-guanine adduct of the tumorigenic (−)-benzo[c]phenanthrene 4R,3S-diol 2S,1R-epoxide in the gap. Nucleotide insertion opposite this adduct favors incorrect purine nucleotides over the correct dCMP and hence can be mutagenic. The structure reveals that the phenanthrene ring system is stacked with the base pair immediately...

  11. Pulse radiolysis investigation of the reaction of the electronic adduct of bovine serum albumin with oxygen. Polychromatic kinetics of the reaction with adsorbed oxygen

    International Nuclear Information System (INIS)

    The method of pulse radiolysis was used to investigate the reaction of the electronic adduct of bovine serum albumin with oxygen. It was suggested that the disappearance of the electronic adduct of the protein occurs in the course of its interaction with oxygen adsorbed on the globular protein molecule

  12. DIFFERENCES IN DETECTION OF DNA ADDUCTS IN THE 32P-POSTLABELING ASSAY AFTER EITHER 1-BUTANOL EXTRACTION OR NUCLEASE P1 TREATMENT

    Science.gov (United States)

    The use of nuclease Pl treatment and 1-butanol extraction to increase the sensitivity of the 32P-postlabe1ling assay for DNA adducts have been compared. lthough similar results were obtained with the two methods for standard adducts formed with benzo(a)pyrene diol epoxide I, nucl...

  13. Acute and sub-acute effects of repetitive kicking on hip adduction torque in injury-free elite youth soccer players

    DEFF Research Database (Denmark)

    Jensen, Jesper; Bandholm, Thomas; Hölmich, Per;

    2014-01-01

    Hip adduction strength is important for kicking and acceleration in soccer players. Changes in hip adduction strength may therefore have an effect on soccer players' athletic performance. The purpose of this study was to investigate the acute and sub-acute effects of a kicking drill session on hi...

  14. Etheno-DNA adduct formation in rats gavaged with linoleic acid, oleic acid and coconut oil is organ- and gender specific

    International Nuclear Information System (INIS)

    Intake of linoleic acid (LA) increased etheno-DNA adducts induced by lipid peroxidation (LPO) in white blood cells (WBC) of female but not of male volunteers [J. Nair, C.E. Vaca, I. Velic, M. Mutanen, L.M. Valsta, H. Bartsch, High dietary ω-6 polyunsaturated fatty acids drastically increase the formation of etheno-DNA adducts in white blood cells of female subjects, Cancer Epidemiol. Biomarkers Prev. 6 (1997) 597-601]. Etheno-adducts were measured in rats gavaged with LA, oleic acid (OA) and saturated fatty acid rich coconut oil for 30 days. DNA from organs and total WBC was analyzed for 1, N6-ethenodeoxyadenosine (εdA) and 3, N4-ethenodeoxycytidine (εdC) by immunoaffinity/32P-postlabeling. Colon was the most affected target with LA-treatment, where etheno-adducts were significantly elevated in both sexes. In WBC both adducts were elevated only in LA-treated females. Unexpectedly, OA treatment enhanced etheno-adduct levels in prostate 3-9 fold. Our results in rodents confirm the gender-specific increase of etheno-adducts in WBC-DNA, likely due to LPO induced by redox-cycling of 4-hydroxyestradiol. Colon was a target for LPO-derived DNA-adducts in both LA-treated male and female rats, supporting their role in ω-6 PUFA induced colon carcinogenesis

  15. Differences in detection of DNA adducts in the 32P-postlabelling assay after either 1-butanol extraction or nuclease P1 treatment.

    Science.gov (United States)

    Gallagher, J E; Jackson, M A; George, M H; Lewtas, J; Robertson, I G

    1989-04-01

    The use of nuclease P1 treatment and 1-butanol extraction to increase the sensitivity of the 32P-postlabelling assay for DNA adducts have been compared. Although similar results were obtained with the two methods for standard adducts formed with benzo[a]pyrene diol epoxide I (BPDE-I), nuclease P1 treatment resulted in a significant reduction in detection of major adducts from 1-amino-6-nitropyrene (1-amino-6-NP), 1-amino-8-nitropyrene (1-amino-8-NP), 2-aminofluorene (2-AF), 2-naphthylamine (2-NA) and 4-aminobiphenyl (4-ABP) modified DNAs, but not following the 32P-postlabelling analysis of 2-acetylaminofluorene (2-AAF) modified DNA. These results suggest that, at least initially, both modifications of the 32P-postlabelling assay should be used for the detection of unknown adducts or for adducts derived from nitroaromatics and aromatic amines. PMID:2540901

  16. Differences in detection of DNA adducts in the 32P-postlabelling assay after either 1-butanol extraction or nuclease Pl treatment

    International Nuclear Information System (INIS)

    The use of nuclease P1 treatment and 1-butanol extraction to increase the sensitivity of the 32P-postlabelling assay for DNA adducts have been compared. Although similar results were obtained with the two methods for standard adducts formed with benzo(a)pyrene diol epoxide I, nuclease P1 treatment resulted in a significant reduction in detection of major adducts 1-amino-6-nitropyrene, 1-amino-8-nitropyrene, 2-aminofluorene, 2-naphthylamine and 4-aminobiphenyl modified DNAs, but not following the 32P-postlabelling analysis of 2-acetylaminofluorene modified DNA. These results suggest that at least initially, both modications of the 32P-postlabelling assay should be used for the detection of unknown adducts or for adducts derived from nitro-aromatics and aromatic amines

  17. Quantitative comparison between in vivo DNA adduct formation from exposure to selected DNA-reactive carcinogens, natural background levels of DNA adduct formation and tumour incidende in rodent bioassays

    NARCIS (Netherlands)

    Paini, A.; Scholz, G.; Marin-Kuan, M.; Schilter, B.; O'Brien, J.; Bladeren, van P.J.; Rietjens, I.

    2011-01-01

    This study aimed at quantitatively comparing the occurrence/formation of DNA adducts with the carcinogenicity induced by a selection of DNA-reactive genotoxic carcinogens. Contrary to previous efforts, we used a very uniform set of data, limited to in vivo rat liver studies in order to investigate w

  18. Miscoding properties of 1,N{sup 6}-ethanoadenine, a DNA adduct derived from reaction with antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea

    Energy Technology Data Exchange (ETDEWEB)

    Hang, Bo; Guliaev, Anton B.; Chenna, Ahmed; Singer, B.

    2003-03-05

    1,N{sup 6}-Ethanoadenine (EA) is an exocyclic adduct formed from DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). To understand the role of this adduct in the mechanism of mutagenicity or carcinogenicity by BCNU, an oligonucleotide with a site-specific EA was synthesized using phosphoramidite chemistry. We now report the in vitro miscoding properties of EA in translesion DNA synthesis catalyzed by mammalian DNA polymerases (pols) {alpha}, {beta}, {eta} and {iota}. These data were also compared with those obtained for the structurally related exocyclic adduct, 1,N{sup 6}-ethenoadenine ({var_epsilon}A). Using a primer extension assay, both pols {alpha} and {beta} were primarily blocked by EA or {var_epsilon}A with very minor extension. Pol {eta} a member of the Y family of polymerases, was capable of catalyzing a significant amount of bypass across both adducts. Pol {eta} incorporated all four nucleotides opposite EA and {var_epsilon}A, but with differential preferences and mainly in an error-prone manner. Human pol {iota}, a paralog of human pol {eta}, was blocked by both adducts with a very small amount of synthesis past {var_epsilon}A. It incorporated C and, to a much lesser extent, T, opposite either adduct. In addition, the presence of an A adduct, e.g. {var_epsilon}A, could affect the specificity of pol {iota} toward the template T immediately 3 feet to the adduct. In conclusion, the four polymerases assayed on templates containing an EA or {var_epsilon}A showed differential bypass capacity and nucleotide incorporation specificity, with the two adducts not completely identical in influencing these properties. Although there was a measurable extent of error-free nucleotide incorporation, all these polymerases primarily misincorporated opposite EA, indicating that the adduct, similar to {var_epsilon}A, is a miscoding lesion.

  19. Expression of human vascular endothelial growth factor receptor-Fc in DG44 cells and biological activity of expressed product%人血管内皮生长因子受体-Fc在DG44细胞中的表达及其生物活性

    Institute of Scientific and Technical Information of China (English)

    胡伟伟; 范清林; 尼钢钢; 张玲; 黄辉; 宋礼华

    2013-01-01

    Objective To express human vascular endothelial growth factor receptor (VEGFR)-Fc in Chinese hamster ovary(CHO) DG44 cells and determine its biological activity.Methods The sequence VEGFR1D2-VEGFR2D3 encoding the second and the third human immunoglobulin domains of VEGFR2 was synthesized,and fused with human IgG1Fc by overlap PCR to generate VEGFR-Fc fusion gene,which was then subcloned into eukaryotic expression plasmid pD2.The constructed recombinant plasmid pD2-VEGFR-Fc was transfected to DG44 cells in mediation of FreeStyleTM MAX Reagent and OptiPROTM SFM,and a cell line stably expressing VEGFR-Fc protein was screened by MTX pressure screening.The expressed VEGFR-Fc in cell culture supernatant was determined by SDS-PAGE,Western blot and ELISA,then purified through HiTrapTM ProteinA FF column,and determined for activity by using microscopy and endothelial ECV304 cell model.Results The length of PCR product of VEGFR-Fc gene was 1 377 bp.Restriction analysis and sequencing proved that recombinant plasmid pD2-VEGFR-Fc was constructed correctly.VEGFR-Fc protein was detected in culture supernatant of DG44 cells transfected with plasmid pD2-VEGFR-Fc,of which the expression level was 0.5 g / L.After purification by HiTrapTM ProteinA FF column chromatography,the foreign protein in cell culture supernatant was removed effectively.Purified VEGFR-Fc showed specific binding to VEGF and inhibited the growth of ECV304 cells.Conclusion The VEGFR-Fc with biological activity was successfully expressed in DG44 cells,which laid a foundation of further study on its role in angiogenesis inhibition and anticancer therapy.%目的 在中国仓鼠卵巢细胞DG44中表达人血管内皮生长因子受体(vascular endothelial growth factor receptor,VEGFR)-Fc,并检测其生物活性.方法 化学合成人VEGFR1的第2免疫球蛋白结构域(VEGFR1D2)基因和人VEGFR2的第3免疫球蛋白结构域(VEGFR2D3)基因,通过重叠PCR(Overlap PCR)将VEGFR1D2-VEGFR2D3和人IgG1Fc拼接形

  20. Increased levels of etheno-DNA adducts and genotoxicity biomarkers of long-term exposure to pure diesel engine exhaust.

    Science.gov (United States)

    Shen, Meili; Bin, Ping; Li, Haibin; Zhang, Xiao; Sun, Xin; Duan, Huawei; Niu, Yong; Meng, Tao; Dai, Yufei; Gao, Weimin; Yu, Shanfa; Gu, Guizhen; Zheng, Yuxin

    2016-02-01

    Etheno-DNA adducts are biomarkers for assessing oxidative stress. In this study, the aim was to detect the level of etheno-DNA adducts and explore the relationship between the etheno-DNA adducts and genotoxicity biomarkers of the diesel engine exhaust (DEE)-exposed workers. We recruited 86 diesel engine testing workers with long-term exposure to DEE and 99 non-DEE-exposed workers. The urinary mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and etheno-DNA adducts (εdA and εdC) were detected by HPLC-MS/MS and UPLC-MS/MS, respectively. Genotoxicity biomarkers were also evaluated by comet assay and cytokinesis-block micronucleus assay. The results showed that urinary εdA was significantly higher in the DEE-exposed workers (p<0.001), exhibited 2.1-fold increase compared with the non-DEE-exposed workers. The levels of urinary OH-PAHs were positively correlated with the level of εdA among all the study subjects (p<0.001). Moreover, we found that the increasing level of εdA was significantly associated with the increased olive tail moment, percentage of tail DNA, or frequency of micronucleus in the study subjects (p<0.01). No significant association was observed between the εdC level and any measured genotoxicity biomarkers. In summary, εdA could serve as an indicator for DEE exposure in the human population. PMID:26588802

  1. The association between submaximal quadriceps force steadiness and the knee adduction moment during walking in patients with knee osteoarthritis

    DEFF Research Database (Denmark)

    Sørensen, Tina Juul; Langberg, Henning; Aaboe, Jens;

    2011-01-01

    in this population. METHODS: Forty-one patients with knee OA (34 females and 7 males) were included in the study. Submaximal isometric quadriceps force steadiness was measured during a force target-tracking task. Peak knee adduction moments during ambulation were measured using a 3-dimensional gait analysis system...

  2. Pyrrolizidine Alkaloid-Protein Adducts: Potential Non-invasive Biomarkers of Pyrrolizidine Alkaloid-Induced Liver Toxicity and Exposure.

    Science.gov (United States)

    Xia, Qingsu; Zhao, Yuewei; Lin, Ge; Beland, Frederick A; Cai, Lining; Fu, Peter P

    2016-08-15

    Pyrrolizidine alkaloids (PAs) are phytochemicals present in hundreds of plant species from different families widely distributed in many geographical regions around the world. PA-containing plants are probably the most common type of poisonous plants affecting livestock, wildlife, and humans. There have been many large-scale human poisonings caused by the consumption of food contaminated with toxic PAs. PAs require metabolic activation to generate pyrrolic metabolites to exert their toxicity. In this study, we developed a novel method to quantify pyrrole-protein adducts present in the blood. This method involves the use of AgNO3 in acidic ethanol to cleave the thiol linkage of pyrrole-protein (DHP-protein) adducts, and the resulting 7,9-di-C2H5O-DHP is quantified by HPLC-ES-MS/MS multiple reaction monitoring analysis in the presence of a known quantity of isotopically labeled 7,9-di-C2D5O-DHP internal standard. Using this method, we determined that diester-type PAs administered to rats produced higher levels of DHP-protein adducts than other types of PAs. The results suggest that DHP-protein adducts can potentially serve as minimally invasive biomarkers of PA exposure. PMID:27388689

  3. Malabaricone C-containing mace extract inhibits safrole bioactivation and DNA adduct formation both in vitro and in vivo

    NARCIS (Netherlands)

    Martati, E.; Boonpawa, R.; Berg, van den J.H.J.; Paini, A.; Spenkelink, A.; Punt, A.; Vervoort, J.J.M.; Bladeren, van P.J.; Rietjens, I.

    2014-01-01

    Safrole, present in mace and its essential oils, causes liver tumors in rodents at high dose levels due to formation of a DNA reactive 1'-sulfooxysafrole. The present study identifies malabaricone C as a mace constituent able to inhibit safrole DNA adduct formation at the level of sulfotransferase m

  4. Thermodynamics and kinetics of reduction and species conversion at a hydrophobic surface for mitochondrial cytochromes c and their cardiolipin adducts

    International Nuclear Information System (INIS)

    Highlights: • Cytochrome c and its adduct with cardiolipin can be immobilized on a hydrophobic SAM. • Adsorbed cytochrome c and its adduct undergo extensive unfolding and axial ligand substitution. • An equilibrium between a six-coordinated and a five-coordinated form is observed in both cases. • The reduced five-coordinated form is stabilized by cardiolipin binding. • Immobilized cytochrome c exchanges electrons more slowly upon cardiolipin binding. - Abstract: Cytochrome c (cytc) and its adduct with cardiolipin (CL) were immobilized on a hydrophobic SAM-coated electrode surface yielding a construct which mimics the environment experienced by the complex at the inner mitochondrial membrane where it plays a role in cell apoptosis. Under these conditions, both species undergo an equilibrium between a six-coordinated His/His-ligated and a five-coordinated His/- ligated forms stable in the oxidized and in the reduced state, respectively. The thermodynamics of the oxidation-state dependent species conversion were determined by temperature-dependent diffusionless voltammetry experiments. CL binding stabilizes the immobilized reduced His/- ligated form of cytc which was found previously to catalytically reduce dioxygen. Here, this adduct is also found to show pseudoperoxidase activity, catalysing reduction of hydrogen peroxide. These effects would impart CL with an additional role in the cytc-mediated peroxidation leading to programmed cell death. Moreover, immobilized cytc exchanges electrons more slowly upon CL binding possibly due to changes in solvent reorganization effects at the protein-SAM interface

  5. A cobalt(ii) iminoiodane complex and its scandium adduct: mechanistic promiscuity in hydrogen atom abstraction reactions.

    Science.gov (United States)

    Kundu, Subrata; Chernev, Petko; Engelmann, Xenia; Chung, Chan Siu; Dau, Holger; Bill, Eckhard; England, Jason; Nam, Wonwoo; Ray, Kallol

    2016-10-01

    In addition to oxometal [M(n+)[double bond, length as m-dash]O] and imidometal [M(n+)[double bond, length as m-dash]NR] units, transient metal-iodosylarene [M((n-2)+)-O[double bond, length as m-dash]IPh] and metal-iminoiodane [M((n-2)+)-N(R)[double bond, length as m-dash]IPh] adducts are often invoked as a possible "second oxidant" responsible for the oxo and imido group transfer reactivity. Although a few metal-iodosylarene adducts have been recently isolated and/or spectroscopically characterized, metal-iminoiodane adducts have remained elusive. Herein, we provide UV-Vis, EPR, NMR, XAS and DFT evidence supporting the formation of a metal-iminoiodane complex 2 and its scandium adduct 2-Sc. 2 and 2-Sc are reactive toward substrates in the hydrogen-atom and nitrene transfer reactions, which confirm their potential as active oxidants in metal-catalyzed oxidative transformations. Oxidation of para-substituted 2,6-di-tert-butylphenols by 2 and 2-Sc can occur by both coupled and uncoupled proton and electron transfer mechanisms; the exact mechanism depends on the nature of the para substituent. PMID:27465222

  6. Formation of fractals by the self-assembly of interpolymer adducts of polymethacrylic acid with complementary polymers in aqueous solution

    Indian Academy of Sciences (India)

    Kandhasamy Durai Murugan; Arlin Jose Amali; Paramasivam Natarajan

    2012-03-01

    Interpolymer adducts of poly(methacrylic acid), (PMAA), with poly(vinylpyrrolidone) in presence of sodium chloride or potassium chloride form highly ordered fractal patterns in films on glass surface on drying at ambient temperature. The structure, morphology and the conditions under which the formation of fractal patterns occurs were investigated by SEM, EDX and confocal microscopic techniques. Self-organization of PMAA with complementary polymers such as poly(vinylpyrrolidone) is well-known and in the presence of sodium chloride formation of the fractals in films of the adducts is a novel observation. Fractal formation occurs due to the aggregation of interpolymer adducts. The composition of the fractals in the film is studied by EDX and confocal microscopic images of the fluorophores covalently bound to PMAA. In presence of salts, sodium chloride or potassium chloride, micellar like entities of 80 nm size were formed which further aggregate to form fractal patterns. It is suggested that the fractals result from the interpolymer adduct by Diffusion Limited Aggregation mechanism.

  7. A convenient synthesis of 1,5-diarylpyrazoles from Baylis-Hillman adducts using HY-zeolite

    Institute of Scientific and Technical Information of China (English)

    Mohammad; Nikpassand; Manouchehr; Mamaghani; Mohammad; Ali; Zanjanchi; Nosrat; Olah; Mahmoodi; Massomeh; Mirzaeinejad

    2010-01-01

    A facile and convenient protocol was developed for the synthesis of 1,5-diarylpyrazoles using Baylis-Hillman adducts in the presence of HY-zeolite as an efficient recyclable heterogeneous catalyst in reasonable reaction times(1.5-2.5 h) and high yields (78-90%).

  8. Sorocenols G and H, Anti-MRSA Oxygen Heterocyclic Diels-Alder-type Adducts from Sorocea muriculata Roots

    Science.gov (United States)

    Bioassay-guided fractionation of a root extract of Sorocea muriculata led to the isolation and identification of two new oxygen heterocyclic Diels-Alder-type adducts, sorocenols G (1) and H (2), along with lupeol-3-(3'R-hydroxytetradecanoate) and oxyresveratrol. The structures of 1 and 2 were eluci...

  9. Plasma and liver acetaminophen-protein adduct levels in mice after acetaminophen treatment: Dose–response, mechanisms, and clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    McGill, Mitchell R.; Lebofsky, Margitta [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Norris, Hye-Ryun K.; Slawson, Matthew H. [Center for Human Toxicology, University of Utah, Salt Lake City, UT (United States); Bajt, Mary Lynn; Xie, Yuchao; Williams, C. David [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Wilkins, Diana G.; Rollins, Douglas E. [Center for Human Toxicology, University of Utah, Salt Lake City, UT (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2013-06-15

    At therapeutic doses, acetaminophen (APAP) is a safe and effective analgesic. However, overdose of APAP is the principal cause of acute liver failure in the West. Binding of the reactive metabolite of APAP (NAPQI) to proteins is thought to be the initiating event in the mechanism of hepatotoxicity. Early work suggested that APAP-protein binding could not occur without glutathione (GSH) depletion, and likely only at toxic doses. Moreover, it was found that protein-derived APAP-cysteine could only be detected in serum after the onset of liver injury. On this basis, it was recently proposed that serum APAP-cysteine could be used as diagnostic marker of APAP overdose. However, comprehensive dose–response and time course studies have not yet been done. Furthermore, the effects of co-morbidities on this parameter have not been investigated. We treated groups of mice with APAP at multiple doses and measured liver GSH and both liver and plasma APAP-protein adducts at various timepoints. Our results show that protein binding can occur without much loss of GSH. Importantly, the data confirm earlier work that showed that protein-derived APAP-cysteine can appear in plasma without liver injury. Experiments performed in vitro suggest that this may involve multiple mechanisms, including secretion of adducted proteins and diffusion of NAPQI directly into plasma. Induction of liver necrosis through ischemia–reperfusion significantly increased the plasma concentration of protein-derived APAP-cysteine after a subtoxic dose of APAP. While our data generally support the measurement of serum APAP-protein adducts in the clinic, caution is suggested in the interpretation of this parameter. - Highlights: • Extensive GSH depletion is not required for APAP-protein binding in the liver. • APAP-protein adducts appear in plasma at subtoxic doses. • Proteins are adducted in the cell and secreted out. • Coincidental liver injury increases plasma APAP-protein adducts at subtoxic doses

  10. Investigation on the optical and electrical properties of MMTG crystal: A Lewis base adduct

    Science.gov (United States)

    Vetha Potheher, I.; Rajarajan, K.; Vimalan, M.; Tamilselvan, S.; Jeyasekaran, R.; Sagayaraj, P.

    2011-09-01

    The growth of nonlinear optical single crystal of manganese mercury thiocyanate glycol monomethyl ether (MMTG), a Lewis base adduct of manganese mercury thiocyanate (MMTC), is reported. MMTG crystallizes in orthorhombic structure with Pca2 1 space group. The optical band gap energy of the sample is found to be 3.5 eV. The sample is thermally stable up to 145 °C. The grown crystal is characterized by photoluminescence, dielectric, dc conductivity, photoconductivity and SEM studies. From the photoluminescence study, the suitability of the material for blue and green light generation is confirmed. The electric and dielectric response of the grown crystal is studied as a function of temperature and the results are discussed. The dc activation energy of the sample is found to be 0.048 eV.

  11. Two food-borne heterocyclic amines: Metabolism and DNA adduct formation of amino-alpha-carbolines

    DEFF Research Database (Denmark)

    Frederiksen, Hanne

    2005-01-01

    or proteins of animal or vegetable origin, furthermore they are found in many cooked foods, such as fish, meat, and chicken. The specific mutagenicity of the amino-a-carbolines are lower in the Ames Salmonella assay than other heterocyclic amines, but in rodent studies the carcinogenicity of the aminoa, alpha...... been studied. Characteristic for the amino-a-carbolines are that relatively large amounts of these compounds in rat and human hepatic microsomes are activated to potent carcinogenic compounds compared with other heterocyclic amines, but further in vivo studies of the amino-a-carbolines are needed...... to highlight these indications. In this review, the main characteristics with focus on the metabolism and the DNA-adduct formation of the amino-a-carbolines are described and compared with other heterocyclic amines....

  12. A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy.

    Directory of Open Access Journals (Sweden)

    Thu Le Trinh

    Full Text Available AS1411 (previously known as AGRO100 is a 26 nucleotide guanine-rich DNA aptamer which forms a guanine quadruplex structure. AS1411 has shown promising utility as a treatment for cancers in Phase I and Phase II clinical trials without causing major side-effects. AS1411 inhibits tumor cell growth by binding to nucleolin which is aberrantly expressed on the cell membrane of many tumors. In this study, we utilized a simple technique to conjugate a widely-used chemotherapeutic agent, doxorubicin (Dox, to AS1411 to form a synthetic Drug-DNA Adduct (DDA, termed as AS1411-Dox. We demonstrate the utility of AS1411-Dox in the treatment of hepatocellular carcinoma (HCC by evaluating the targeted delivery of Dox to Huh7 cells in vitro and in a murine xenograft model of HCC.

  13. Crystal structure of the bis(cyclohexylammonium succinate succinic acid salt adduct

    Directory of Open Access Journals (Sweden)

    Modou Sarr

    2015-08-01

    Full Text Available The crystal structure of the title salt adduct, 2C6H14N+·C4H4O42−·C4H6O4, consists of two cyclohexylammonium cations, one succcinate dianion and one neutral succinic acid molecule. Succinate dianions and succinic acid molecules are self-assembled head-to-tail through O—H...O hydrogen bonds and adopt a syn–syn configuration, leading to a strand-like arrangement along [101]. The cyclohexylammonium cations have a chair conformation and act as multidentate hydrogen-bond donors linking adjacent strands through intermolecular N—H...O interactions to both the succinate and the succinic acid components. This results in two-dimensional supramolecular layered structures lying parallel to (010.

  14. Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother newborns

    DEFF Research Database (Denmark)

    Pedersen, Marie; Halldorsson, Thorhallur I; Autrup, Herman;

    2012-01-01

    Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei...... (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006-2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet...... was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX)(®) bioassay, (32)P-postlabelling technique and cytokinesis-block MN assay...

  15. Adducts of rare earth hexafluoroacetylacetonates with amino acids. [Eu, Tb, Dy, La, Lu

    Energy Technology Data Exchange (ETDEWEB)

    Karasev, V.E.; Steblevskaya, N.I.; Shchelokov, R.N. (AN SSSR, Vladivostok. Inst. Khimii)

    1983-01-01

    Crystal different-ligand rare earth complexes with hexafluoroacetylacetone and amino acids of m(GFAA)/sub 3/ 2A composition, where m=La, Eu, Tb, Dy, Lu, A-glycine, ..cap alpha..-alanine, ..beta..-alanine, valine, norvaline, asparagine, proline, are extracted for the first time. IR spectroscopic and luminescent methods have been used to characterize compound composition. Amino acid is shown to be a neutral ligand coordinating through oxygen atom of carboxyl group with conservation of betaine structure. Analysis of Stark structure of /sup 5/D/sub 0/-/sup 7/F/sub 1/-transition in luminescence spectra of europium adducts points out monotonous decrease of ..delta..F/sub 1/ parameter from glycine to asparagine: gly > pro > ..cap alpha..-ala > hys > val > ..beta..-ala > Nsub(val) > ast.

  16. Synthesis and crystal structure of a 1:2 adducts of aquatrifluoroboron and triphenylphosphine oxide

    International Nuclear Information System (INIS)

    Crystalline 1:2 adduct of aquatrifluoroboron and triphenylphosphine oxide: 1/2[BF3(Ho)] · Ph3Po(I) was prepared and studied by the method of X-ray diffraction analysis. The crystals are rhombic, space group Fdd2, a = 32.283, b = 20.162, c = 10.191 A, Z = 16. Molecule of [BF3(H2O)] is statistically disordered in reference to axis 2; population of all its atomic positions equals 0.5. Boron atom has a distorted tetrahedral coordination with B-O(w) donor-acceptor bond, its length being 1.568 (9) A. The B-F bond lengths fall within the range 1.378(8)-1.399(9) A

  17. Foot alignments influence the effect of knee adduction moment with lateral wedge insoles during gait.

    Science.gov (United States)

    Sawada, Tomonori; Tokuda, Kazuki; Tanimoto, Kenji; Iwamoto, Yoshitaka; Ogata, Yuta; Anan, Masaya; Takahashi, Makoto; Kito, Nobuhiro; Shinkoda, Koichi

    2016-09-01

    Lateral wedge insoles (LWIs) reduce the peak external knee adduction moment (KAM). However, the efficacy of LWIs is limited in certain individuals for whom they fail to decrease KAM. Possible explanations for a lack of desired LWI response are variations in foot alignments. The purpose of this study was to evaluate whether the immediate biomechanical effects of LWIs depend on individual foot alignments during gait. Fifteen healthy adults participated in this study. Their feet were categorized as normal, pronated, and supinated using the foot posture index. All subjects were subsequently requested to perform a normal gait under barefoot and LWI conditions. A three-dimensional motion analysis system was used to record the kinematic and kinetic data, included peak KAM, KAM impulse (KAAI), center of pressure displacement, and knee-ground reaction force lever arm (KLA). Furthermore, lower limb frontal plane kinematic parameters at the rear foot, ankle, knee, and hip were evaluated. Among all feet, there was no significant difference in the peak KAM and KAAI between the conditions. In contrast, the peak KAM was significantly reduced under the LWI condition relative to the barefoot condition in the normal foot group. Reductions in the peak KAM were correlated with a more lateral center of pressure and reduced KLA. In addition, a reduced KLA was correlated with decreased hip adduction. LWIs significantly reduced the peak KAM in normal feet, indicating that biomechanical effects of LWIs vary between individual foot alignments. Our findings suggest that it is helpful to assess individual foot alignment to ensure adequate insole treatment for patients with knee osteoarthritis.

  18. A fenestration approach to arytenoid adduction for unilateral vocal cord paralysis. Results of 32 cases

    International Nuclear Information System (INIS)

    The objective of this study was to develop and evaluate the voice outcomes of an approach to arytenoid adduction (AA) for unilateral vocal cord paralysis through fenestration of the thyroid ala. Thirty-two patients with unilateral vocal cord paralysis underwent laryngoplasty using an approach to AA performed through fenestration of the thyroid ala combined with type I thyroplasty. Thirty-two patients with unilateral vocal cord paralysis were treated between October 2004 and February 2008. In all cases, maximum phonation time (MPT) and mean airflow rate (MFR) were measured before and after the operation. The voices were analyzed using shimmer and jitter. Two surgical windows were made in the lower part of the thyroid ala. The anterior one was for typical type I thyroplasty and the posterior one was for arytenoid adduction (AA). The locations of the two windows were determined based on three-dimensional computer tomography (3DCT) data. AA was performed by muscular process through the posterior window without releasing the cricothyroid joint. The operations were performed under local anesthesia with sedation. Vocal cord medialization was confirmed endoscopically during the operation. Twenty-nine of the 32 patients achieved an MPT of over 10 s after surgery. The other 3 cases, whose MPTs were 9 s after the operation, had low breathing capacity because of lung disease and normal side vocal cord sulcus. The MFRs, which ranged from 236 to 1908 ml/s before the operation, improved to under 200 ml/s except in 3 patients, whose MFRs were 210 ml/s, 214 ml/s and 216 ml/s. Jitter and shimmer improved significantly after the operation. Perceptual evaluation using the GRBAS scale also improved significantly. Our new procedure simplified the combination of AA and type I thyroplasty because the two treatments can be performed in the same operating field, obtaining good voice improvement. Determination of the surgical approach using 3DCT and endoscopic vocal cord observation may

  19. Direct relationship between radiobiological hypoxia in tumors and monoclonal antibody detection of EF5 cellular adducts.

    Science.gov (United States)

    Lee, J; Siemann, D W; Koch, C J; Lord, E M

    1996-07-29

    While the potential importance of hypoxia in limiting the sensitivity of tumor cells to ionizing radiation has long been appreciated, methods for accurately quantifying the number of radiation-resistant hypoxic cells within tumors have been lacking. We have used the pentafluorinated derivative [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acet amide] of etanidazole (EF5), which binds selectively to hypoxic cells. The adducts formed between EF5 and cellular proteins in the hypoxic cells were detected using the specific monoclonal antibody (MAb), ELK3-51 conjugated to the flurochrome Cy3, and the number of hypoxic cells was quantified by flow cytometry. To verify the validity of this technique for the detection of hypoxic cells, mice bearing KHT sarcomas were treated with various agents to alter tumor oxygenation and hence vary the fraction of radiobiologically hypoxic tumor cells. The percentage of EF5 binding cells was then compared directly with the clonogenic survival of the tumor cells following radiation treatment under the various pretreatment conditions. The results showed that allowing the mice to breathe carbogen (5% CO2/95% O2) prior to irradiation reduced clonogenic cell survival approx. 6-fold and led to an absence of cells binding high levels of EF5. In contrast, pretreating the tumor-bearing animals with either hydralazine, which decreased tumor blood flow, or phenylhydrazine hydrochloride, which made the mice anemic, increased tumor cell survival following irradiation 2- to 4-fold, indicative of an increase in the fraction of hypoxic tumor cells. EF5 measurements made under identical conditions illustrated a shift in the cells in the tumor to high EF5 binding. Our results demonstrate that flow cytometric measurement by fluorescent MAb binding to EF5 adducts may relate directly to radiobiological hypoxia in KHT tumors measured by conventional methods. PMID:8707411

  20. Inhibition of azoxymethane-induced DNA adduct formation by Aloe arborescens var. natalensis.

    Science.gov (United States)

    Shimpo, Kan; Chihara, Takeshi; Beppu, Hidehiko; Ida, Chikako; Kaneko, Takaaki; Hoshino, Motoyuki; Kuzuya, Hiroshi

    2003-01-01

    To clarify the possible mechanisms of inhibition of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in the rat colorectum by freeze-dried whole leaves of Aloe arborescens var. natalensis (Kidachi aloe) (hereinafter referred to as ALOE) and commercial crude aloin (Sigma A-0451; from Curacao aloe) (hereinafter ALOIN), we studied the effects of ALOE and ALOIN on the formation of AOM-induced DNA adducts (O6-methylguanine; O6-MeG) in rats. Male F344 rats (4 weeks old) were fed a basal diet, or experimental diets containing 5%ALOE or 0.25%ALOIN for 5 weeks. All rats were injected s.c. twice with 15 mg/kg AOM, once at the end of week 1, and once at the end of week 2. The animals were sacrificed 6 hours after the second injection to analyze DNA adducts (O6-MeG) in the colorectum. Dietary administration of ALOE significantly inhibited the O6-MeG levels (50% reduction) compared with controls, whereas the O6-MeG levels in the ALOIN-fed rats showed a tendency to decrease (by 30%), although not significantly. In this study, we also measured the enzyme activity and mRNA level of cytochrome (CYP) 2E1, known to be responsible for the activation of AOM, in rat liver. ALOE-fed rats showed significantly reduced CYP2E1 enzymatic activity (27% reduction) compared with controls. On the other hand, the activity in ALOIN-fed rats tended to decrease by 11%, although not significantly. The CYP2E1 mRNA levels in ALOE- and ALOIN-fed rats were slightly reduced (9.7% and 5.2%, respectively). These results may explain, at least in part, the previously observed inhibitory effects of ALOE and ALOIN, especially ALOE on AOM-induced ACF formation in the rat colorectum. PMID:14507246

  1. Isolation and identification of the adducts of mitomycin C and porfiromycin with DNA formed in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chowdary, D.R.

    1989-01-01

    The antitumor antibiotics, mitomycin C (MC) and porfiromycin (PM), are shown to form covalent complexes with DNA in vitro, under reductive activation conditions (both chemical and enzymatic). Three major covalent adducts have been isolated and identified as (1) N{sup 2}-guanine adduct with MC (structure 4a), (2) N{sup 2}-guanine adduct with 10-decarbamoyl mitomycin ((10-DMC); structure 16a), and a bisadduct of MC linked to two Gs at their N{sup 2}-positions (structure 6). The adducts of PM with DNA formed in vitro are analogous (structures 19, 20, and 21). Formation of adducts 6 and 16a in CHO mammalian cells has been shown after exposing them to MC or 10-DMC, whereas formation of crosslink 6 in vivo has been demonstrated after injecting rats with MC. The experiments done in tissue cultures with (1a-{sup 3}H)-polyfiromycin show ({sup 3}H)-label in the unmodified A, G, and T thus suggesting the demethylation of PM to MC in cells. The methyl group containing ({sup 3}H) label was incorporated into nucleosides via de novo purine and thymidylate biosynthesis. A consolidated enzymatic scheme for the hydrolysis of MC-modified DNA has been established and the resistance of such DNA to cleavage by several nucleases has been shown. Thus, only DNase I/SVD/alkaline phosphatase or nuclease P{sub 1}/SVD/alkaline phosphatase combinations can degrade MC-modified DNA into nucleosides. A modified version of {sup 32}P-postlabeling has been developed with in vitro authentic standards and this can be conveniently used in the future to detect MC-modified lesions obtained in vivo. By utilizing the alkaline ethidium bromide fluorescence assay, the crosslinking effect of MC, PM, and 10-DMC has been shown to occur in cells.

  2. Estimativa da entalpia de decomposição (deltaD Hmº de adutos por termogravimetria Estimative of deltaD Hmº for adducts by thermogravimetry

    Directory of Open Access Journals (Sweden)

    Robson Fernandes de Farias

    1998-07-01

    Full Text Available An empirical equation: deltaD HmO = t i/2.2(2-n is obtained and tested for 102 adducts (mainly adducts with zinc group halides. In the equation, t i is the Kelvin temperature of the beginning of the thermal decomposition of the adduct, (obtained by thermogravimetry, and n is the number of ligands. For 1/3 of the tested adducts the difference between experimental and calculated values was less than 5%. For about 1/3 of the adducts that difference exceeds 15%.

  3. Variations on a theme - the evolution of hydrocarbon solids. I. Compositional and spectral modelling - the eRCN and DG models

    Science.gov (United States)

    Jones, A. P.

    2012-04-01

    Context. The compositional properties of hydrogenated amorphous carbons are known to evolve in response to the local conditions. Aims: We present a model for low-temperature, amorphous hydrocarbon solids, based on the microphysical properties of random and defected networks of carbon and hydrogen atoms, that can be used to study and predict the evolution of their properties in the interstellar medium. Methods: We adopt an adaptable and prescriptive approach to model these materials, which is based on a random covalent network (RCN) model, extended here to a full compositional derivation (the eRCN model), and a defective graphite (DG) model for the hydrogen poorer materials where the eRCN model is no longer valid. Results: We provide simple expressions that enable the determination of the structural, infrared and spectral properties of amorphous hydrocarbon grains as a function of the hydrogen atomic fraction, XH. Structural annealing, resulting from hydrogen atom loss, results in a transition from H-rich, aliphatic-rich to H-poor, aromatic-rich materials. Conclusions: The model predicts changes in the optical properties of hydrogenated amorphous carbon dust in response to the likely UV photon-driven and/or thermal annealing processes resulting, principally, from the radiation field in the environment. We show how this dust component will evolve, compositionally and structurally in the interstellar medium in response to the local conditions. Appendices A and B are available in electronic form at http://www.aanda.org

  4. 计及DG与STATCOM的配电网重构优化策略%Optimal reconfiguration of distribution network with DG and STATCOM

    Institute of Scientific and Technical Information of China (English)

    吴忠强; 赵立儒; 贾文静; 吴昌韩

    2016-01-01

    采用一种改进遗传算法(GA)实现配电网重构,其考虑了配电网近期的发展变化,将分布式发电(DG)与静止无功补偿器(STATCOM)引入配电网模型中,探讨它们对配电网重构和提高电能质量的影响.采用十进制与二进制混合编码方式和特殊的交叉与变异操作避免GA不可行解的产生,采用云算法改进交叉率与变异率以提高GA的收敛性.对IEEE 33节点配电网进行仿真,结果表明所提出的改进GA可有效地实现网络重构,DG与STATCOM的引入能有效提高配电网的供电质量和可靠性.

  5. Sub-arcsecond [FeII] spectro-imaging of the DG Tau jet: Periodic bubbles and a dusty disk wind?

    CERN Document Server

    Agra-Amboage, V; Cabrit, S; Reunanen, J

    2011-01-01

    We present SINFONI/VLT observations of the DG Tauri jet in the [FeII] lines with 0.15" angular resolution and R=3000 spectral resolution. We observe an onion-like velocity structure in [FeII] in the blueshifted jet, similar to that observed in optical lines. High-velocity gas at ~-200 km/s is collimated inside a half-opening angle of 4 degrees and medium-velocity gas at ~-100 km/s in a cone with an half-opening angle 14 degrees. Two new axial jet knots are detected in the blue jet, as well as a more distant bubble with corresponding counter-bubble. The periodic knot ejection timescale is revised downward to 2.5 yrs. The redshifted jet is detected only beyond 0.7" from the star, yielding revised constraints on the disk surface density. From comparison to [OI] data we infer iron depletion of a factor 3 at high velocities and a factor 10 at speeds below -100 km/s. The mass-fluxes in each of the medium and high-velocity components of the blueshifted lobe are ~1.6+-0.8x10^-8 Msun/yr, representing 0.02-0.2 of the d...

  6. DNA adducts, benzo(a)pyrene monooxygenase activity, and lysosomal membrane stability in Mytilus galloprovincialis from different areas in Taranto coastal waters (Italy)

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the impact of environmental pollution at different stations along the Taranto coastline (Ionian Sea, Puglia, Italy) using several biomarkers of exposure and the effect on mussels, Mytilus galloprovincialis, collected in October 2001 and October 2002. Five sampling sites were compared with a 'cleaner' reference site in the Aeronautics Area. In this study we also investigated the differences between adduct levels in gills and digestive gland. This Taranto area is the most significant industrial settlement on the Ionian Sea known to be contaminated by polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, heavy metals, etc. Exposure to PAHs was evaluated by measuring DNA adduct levels and benzo(a)pyrene monooxygenase activity (B(a)PMO); DNA adducts were analyzed by 32P-postlabeling with nuclease P1 enhancement in both gills and digestive glands to evaluate differences between DNA adduct levels in the two tissues. B(a)PMO was assayed in the microsomal fraction of the digestive glands as a result of the high expression of P450-metabolizing enzymes in this tissue. Lysosomal membrane stability, a potential biomarker of anthropogenic stress, was also evaluated in the digestive glands of mussels, by measuring the latent activity of β-N-acetylhexosaminidase. Induction of DNA adducts was evident in both tissues, although the results revealed large tissue differences in DNA adduct formation. In fact, gills showed higher DNA adduct levels than did digestive gland. No significant differences were found in DNA adduct levels over time, with both tissues providing similar results in both years. DNA adduct levels were correlated with B(a)PMO activity in digestive gland in both years (r=0.60 in 2001; r=0.73 in 2002). Increases were observed in B(a)PMO activity and DNA adduct levels at different stations; no statistical difference was observed in B(a)PMO activity over the two monitoring campaigns. The membrane labilization period

  7. Investigation of the DNA adducts formed in B6C3F1 mice treated with benzene: Implications for molecular dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Bodell, W.J.; Pathak, D.N.; Levay, G. [Univ. of California, San Francisco, CA (United States)] [and others

    1996-12-01

    We have investigated the formation of DNA adducts in the bone marrow and white blood cells of male B6C3F1 mice treated with benzene using P1-enhanced {sup 32}P-postlabeling. No adducts were detected in the bone marrow of controls or mice treated with various doses of benzene once a day. After twice-daily treatment for 1 to 7 days with benzene, 440 mg/kg, one major (no. 1) and UP to two minor DNA adducts were detected in both the bone marrow and white blood cells. The relative adduct levels in these cells ranged from 0.06 to 1.46 x 10{sup -7}. A significant correlation (r 0.95) between levels of adducts in bone marrow and white blood cells was observed. After a 7-day treatment with benzene, 440 mg/kg twice a day, the number of cells per femur decreased from 1.6 x 10{sup 7} to 0.85 X 10{sup 7}, indicating myelotoxicity. In contrast, administration of benzene once a day produced only a small decrease in bone marrow cellularity. The observed induction of toxicity in bone marrow was paralleled by formation of DNA adducts. In vitro treatment of bone marrow with hydroquinone (HQ) for 24 hr produced the same DNA adducts as found after treatment of mice with benzene, suggesting that HQ is the principal metabolite of benzene leading to DNA adduct formation in vivo. Using {sup 32}P-postlabeling the principal DNA adduct formed in vivo was compared with N{sup 2}-(4-hydroxyphenyl)-2-deoxyguanosine-3-phosphate. The results of this comparison demonstrates that the DNA adduct formed in vivo co-chromatographs with N{sup 2}-(4-hydroxyphenyl)-2-deoxyguanosine-3{prime}-phosphate. These studies indicate that metabolic activation of benzene leads to the formation of DNA adducts in bone marrow and white blood cells and suggest that measurement of DNA adducts in white blood cells may be an indicator of biological effect following benzene exposure. 34 refs., 4 figs., 2 tabs.

  8. Effects of Push-up Exercise with Hip Adduction on the COP Deviation and the Serratus Anterior and L1 Paraspinal Muscles

    OpenAIRE

    Kim, Min-Hee; Yoo, Won-Gyu

    2013-01-01

    [Purpose] This study investigated the effect of push-up exercise with hip adduction on the COP deviation and SA and L1 spinal muscle activation. [Subjects] Twelve males aged 20–30 years were recruited. [Methods] We measured the COP deviation and SA and L1 spinal muscle activities during push-up exercise with and without hip adduction [Results] The COP deviation significantly decreased and the SA and L1 spinal muscles were significantly increased during push-ups with hip adduction when compare...

  9. Absolute configuration, stability, and interconversion of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine valine adducts and their phenylthiohydantoin derivatives

    Directory of Open Access Journals (Sweden)

    Xiao Jiang

    2015-06-01

    Full Text Available Pyrrolizidine alkaloid-containing plants are widespread in the world and probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids require metabolic activation to form dehydropyrrolizidine alkaloids that bind to cellular proteins and DNA leading to hepatotoxicity, genotoxicity, and tumorigenicity. At present, it is not clear how dehydropyrrolizidine alkaloids bind to cellular amino acids and proteins to induced toxicity. We previously reported that reaction of dehydromonocrotaline with valine generated four highly unstable 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP-derived valine (DHP-valine adducts that upon reaction with phenyl isothiocyanate (PITC formed four DHP-valine-PITC adduct isomers. In this study, we report the absolute configuration and stability of DHP-valine and DHP-valine-PITC adducts, and the mechanism of interconversion between DHP-valine-PITC adducts.

  10. SEPARATION AND CHARACTERIZATION OF TETROL METABOLITES OF BENZO[A]PYRENE-DNA ADDUCTS USING HPLC AND SOLID-MATRIX ROOM TEMPERATURE LUMINESCENCE. (R824100)

    Science.gov (United States)

    AbstractFour tetrols of benzo[a]pyrene-DNA adducts were separated using reversed-phase high performance liquid chromatography. Chromatographic fractions containing a given tetrol were readily characterized with solid-matrix room temperature luminescence techniques. So...

  11. The importance of Pyr(6-4)Pyo adducts for survival and mutation induction in mammalian cells

    International Nuclear Information System (INIS)

    The biological consequences of a variety of DNA photoproducts are being studied in Chinese hamster ovary cells. By comparing the rate of induction of resistance to 6-thioguanine following irradiation at 254 nm and 313 nm, the authors find a similar mutation rate at equitoxic doses. Thus, enhanced mutation frequency does not appear to be a consequence of Pyr(6-4)Pyo adducts, which are produced at 254 nm but not at 313 nm. When the level of dimerised photoproducts is measured in a radioimmunoassay, Pyr(6-4)Pyo adducts, which are highly antigenic, are readily detected. By comparing the kinetics of removal of antibody-binding sites following irradiation at 254mn and 313 nm, it is evident that these lesions are repaired at the same rate as cyclobutane dimers

  12. Structure of cis-[Pt(NH3)(2-picoline)]2+ and DNA adduct and its bonding characteristics

    Institute of Scientific and Technical Information of China (English)

    JIA; Muxin; LIU; Kai; YANG; Zuoyin; CHEN; Guangju

    2004-01-01

    Several methods including molecular mechanics, molecular dynamics, ONIOM that combines quantum chemistry with molecular mechanics and standard quantum chemistry are used to study the configuration and electron structures of an adduct of the DNA segment d(ATACATG*G*TACATA)·d(TATGTACCATGTAT) with cis-[Pt(NH3)(2-Picoline)]2+. The investigation shows that the configuration optimized by ONIOM is similar to that determined by NMR. Strong chemical bonds between Pt of the complex and two N7s of neighboring guanines in the DNA duplex and hydrogen bond between the NH3 of the complex and O6 of a nearby guanine have a large impact on the configuration of the adduct. Chemical bonds, the aforementioned hydrogen bond, and the interaction between a methyl of the complex and a methyl of the base in close proximity are critical for the complex to specifically recognize DNA.

  13. Synthesis and activity of novel homodimers of Morita-Baylis-Hillman adducts against Leishmania donovani: A twin drug approach.

    Science.gov (United States)

    da Silva, Wagner A V; Rodrigues, Daniele C; de Oliveira, Ramon G; Mendes, Rhuan K S; Olegário, Tayná R; Rocha, Juliana C; Keesen, Tatjana S L; Lima-Junior, Claudio G; Vasconcellos, Mário L A A

    2016-09-15

    It is reported here the synthesis of novel Homodimers 12-19 of Morita-Baylis-Hillman adducts (MBHA) from one-pot Morita-Baylis-Hillman Reaction (MBHR) between aromatic aldehydes as eletrophiles and ethylene glycol diacrylate as Michael acceptor (35-94% yields) using cheap and green conditions. The bioactivities were evaluated against promastigote form of Leishmania donovani. All homodimers showed to be more potent than corresponding monomers. It is worth highlighting that the halogenated homodimers 17 and 18 (0.50μM) is almost 400 times more active than the corresponding monomer 10 and 1.24 times more potent than the second-line drug amphotericin B (0.62μM). Moreover, the selectivity index to 18 is very high (SIrb>400) far better than amphotericin B (SIrb=18.73). This is the first report of twin drugs strategy applied on Morita-Baylis-Hillman adducts. PMID:27520941

  14. 提高DG接纳能力的配电网动态重构方法%Distribution Network Dynamic Reconfiguration Method for Improving Distribution Network’s Ability of Accepting DG

    Institute of Scientific and Technical Information of China (English)

    易海川; 张彼德; 王海颖; 吴宇; 袁国森; 吕柔睿

    2016-01-01

    随着分布式电源(distributed generation,DG)大量接入配电网,具备组合控制各种DG能力的主动配电网得到了大力发展,加大配电网对DG的接纳能力是主动配电网的一个显著特征。提出了以提高DG接纳能力为目标函数的配电网动态重构方法。首先构建了相应的数学模型,以一天为周期综合考虑风力和光伏2种不同类型的 DG,根据不同时段DG的不同特性,提出了随时段变化的配电网动态重构模型,并用遗传算法对其进行优化,最后以改进的IEEE 33节点系统为例验证了所提模型的有效性。%With a plenty of distributed generation (DG) integrated into distribution network, active distribution networks with combined DG control ability have been vigorously developed. A significant feature of active distribution network is increasing this ability. Distribution network dynamic reconfiguration method was proposed for improving the ability. Firstly, its mathematical model was constructed. Then, dynamic reconfiguration model, considering wind and photovoltaic (PV) DG with different characteristics in different periods, was put forward. Genetic algorithm was utilized to search optimal scheme. Case studies were carried out using a modified IEEE 33-node distribution network. Simulation results showed effectiveness of the proposed model.

  15. UNESCO accolade for former DG

    CERN Multimedia

    2006-01-01

    Former CERN Director General, Herwig Schopper, has been awarded the UNESCO Niels Bohr Gold Medal award. He shares this year's distinction with two other recipients: Sir Martin Rees, Britain's astronomer royal, and Professor Peter Zoller, a central figure in the field of quantum information. Herwig Schopper (left) receiving the 2005 Niels Bohr Gold Medal from Helge Sander, Denmark's Minister of Science, Technology and Innovation. The awards, which took place at the Danish Royal Academy of Science and Letters on 15 November, recognise scientific excellence, concern for the impact of science, and efforts to promote the free exchange of ideas on a broad international scale. Herwig Schopper was Director-General of CERN from 1981 to 1988. Today, he is President of the SESAME Council, the International Centre for Synchrotron Light for Experimental Science and Applications in the Middle East (see Bulletin No. 26/2003). In his opening address at the ceremony, Jens Jørgen Gaardhøje, from the Danish National Commi...

  16. Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother–Child Study (NewGeneris)

    OpenAIRE

    Pedersen, Marie; Schoket, Bernadette; Godschalk, Roger W.; Wright, John; von Stedingk, Hans; Törnqvist, Margareta; Sunyer, Jordi; Nielsen, Jeanette K.; Merlo, Domenico Franco; Mendez, Michelle A.; Meltzer, Helle Margrete; Lukacs, Viktoria; Landström, Anette; Kyrtopoulos, Soterios A; Kovacs, Katalin

    2013-01-01

    Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this associat...

  17. Evaluation of Interindividual Human Variation in Bioactivation and DNA Adduct Formation of Estragole in Liver Predicted by Physiologically Based Kinetic/Dynamic and Monte Carlo Modeling.

    Science.gov (United States)

    Punt, Ans; Paini, Alicia; Spenkelink, Albertus; Scholz, Gabriele; Schilter, Benoit; van Bladeren, Peter J; Rietjens, Ivonne M C M

    2016-04-18

    Estragole is a known hepatocarcinogen in rodents at high doses following metabolic conversion to the DNA-reactive metabolite 1'-sulfooxyestragole. The aim of the present study was to model possible levels of DNA adduct formation in (individual) humans upon exposure to estragole. This was done by extending a previously defined PBK model for estragole in humans to include (i) new data on interindividual variation in the kinetics for the major PBK model parameters influencing the formation of 1'-sulfooxyestragole, (ii) an equation describing the relationship between 1'-sulfooxyestragole and DNA adduct formation, (iii) Monte Carlo modeling to simulate interindividual human variation in DNA adduct formation in the population, and (iv) a comparison of the predictions made to human data on DNA adduct formation for the related alkenylbenzene methyleugenol. Adequate model predictions could be made, with the predicted DNA adduct levels at the estimated daily intake of estragole of 0.01 mg/kg bw ranging between 1.6 and 8.8 adducts in 10(8) nucleotides (nts) (50th and 99th percentiles, respectively). This is somewhat lower than values reported in the literature for the related alkenylbenzene methyleugenol in surgical human liver samples. The predicted levels seem to be below DNA adduct levels that are linked with tumor formation by alkenylbenzenes in rodents, which were estimated to amount to 188-500 adducts per 10(8) nts at the BMD10 values of estragole and methyleugenol. Although this does not seem to point to a significant health concern for human dietary exposure, drawing firm conclusions may have to await further validation of the model's predictions. PMID:26952143

  18. S-adenosyl-L-methionine protection of acetaminophen mediated oxidative stress and identification of hepatic 4-hydroxynonenal protein adducts by mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Brown, James Mike [Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Huntington, WV (United States); Kuhlman, Christopher [Southwest Environmental Health Sciences Center, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona Health Sciences Center, Tucson, AZ (United States); Terneus, Marcus V. [Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Huntington, WV (United States); Labenski, Matthew T. [Southwest Environmental Health Sciences Center, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona Health Sciences Center, Tucson, AZ (United States); Lamyaithong, Andre Benja; Ball, John G. [Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Huntington, WV (United States); Lau, Serrine S. [Southwest Environmental Health Sciences Center, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona Health Sciences Center, Tucson, AZ (United States); Valentovic, Monica A., E-mail: Valentov@marshall.edu [Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Huntington, WV (United States)

    2014-12-01

    Acetaminophen (APAP) hepatotoxicity is protected by S-adenosyl-L-methionine (SAMe) treatment 1 hour (h) after APAP in C57/Bl6 mice. This study examined protein carbonylation as well as mitochondrial and cytosolic protein adduction by 4-hydroxynonenal (4-HNE) using mass spectrometry (MS) analysis. Additional studies investigated the leakage of mitochondrial proteins and 4-HNE adduction of these proteins. Male C57/Bl6 mice (n = 5/group) were divided into the following groups and treated as indicated: Veh (15 ml/kg water, ip), SAMe (1.25 mmol/kg, ip), APAP (250 mg/kg), and SAMe given 1 h after APAP (S + A). APAP toxicity was confirmed by an increase (p < 0.05) in plasma ALT (U/l) and liver weight/10 g body weight relative to the Veh, SAMe and S + A groups 4 h following APAP treatment. SAMe administered 1 h post-APAP partially corrected APAP hepatotoxicity as ALT and liver weight/10 g body weights were lower in the S + A group compared the APAP group. APAP induced leakage of the mitochondrial protein, carbamoyl phosphate synthase-1 (CPS-1) into the cytosol and which was reduced in the S + A group. SAMe further reduced the extent of APAP mediated 4-HNE adduction of CPS-1. MS analysis of hepatic and mitochondrial subcellular fractions identified proteins from APAP treated mice. Site specific 4-HNE adducts were identified on mitochondrial proteins sarcosine dehydrogenase and carbamoyl phosphate synthase-1 (CPS-1). In summary, APAP is associated with 4-HNE adduction of proteins as identified by MS analysis and that CPS-1 leakage was greater in APAP treated mice. SAMe reduced the extent of 4-HNE adduction of proteins as well as leakage of CPS-1. - Highlights: • Acetaminophen (APAP) toxicity protected by S-adenosylmethionine (SAMe) • 4-Hydroxynonenal adducted to sarcosine dehydrogenase • 4-Hydroxynonenal adducted to carbamoyl phosphate synthetase-1 • SAMe reduced APAP mediated CPS-1 mitochondrial leakage.

  19. Synthesis of oxa-bridged derivatives from Diels–Alder bis-adducts of butadiene and 1,2,3,4-tetrahalo-5,5-dimethoxycyclopentadiene

    Directory of Open Access Journals (Sweden)

    Faiz Ahmed Khan

    2010-06-01

    Full Text Available Bis-adducts of 1,2,3,4-tetrahalo-5,5-dimethoxycyclopentadiene and 1,3-butadiene, generated in situ from 3-sulfolene, have been synthesized in excellent yield. Ruthenium catalyzed oxidation of the bis-adducts followed by a one-pot transformation of the resulting α-diketone furnished oxa-bridged compounds. Unambiguous stereochemical assignments of both diastereomeric series are reported.

  20. 32P-post-labelling analysis of DNA adducts formed in the upper gastrointestinal tissue of mice fed bracken extract or bracken spores.

    OpenAIRE

    A. C. Povey; D. Potter; O'Connor, P J

    1996-01-01

    Bracken toxicity to both domestic and laboratory animals is well established and tumours are formed when rodents are treated with either bracken extracts or bracken spores. In this study we have administered bracken spores and extract to mice in order to investigate whether such exposure leads to the formation of DNA adducts. DNA, isolated from the upper gastrointestinal tract and liver, was digested to 3'-nucleotides. Adducts were extracted with butanol, 32P-post-labelled, separated by thin ...

  1. New approaches for synthesis and analysis of adducts to N-terminal valine in hemoglobin from isocyanates, aldehydes, methyl vinyl ketone and diepoxybutane

    OpenAIRE

    Davies, Ronnie

    2009-01-01

    Human exposure to harmful compounds in the environment, from intake via food, occupational exposures or other sources, could have health implications. Exposure to reactive compounds/metabolites can be identified and quantified as hemoglobin (Hb) adducts by mass spectrometry. This thesis aimed at improved synthetic pathways for reference standards, and improved analytical methods for adducts to N-terminal valine in Hb from a range of reactive compounds; isocyanates, aldehydes, methyl vinyl ket...

  2. Effects of alkyl chain length and substituent pattern of fullerene bis-adducts on film structures and photovoltaic properties of bulk heterojunction solar cells.

    Science.gov (United States)

    Tao, Ran; Umeyama, Tomokazu; Kurotobi, Kei; Imahori, Hiroshi

    2014-10-01

    A series of alkoxycarbonyl-substituted dihydronaphthyl-based [60]fullerene bis-adduct derivatives (denoted as C2BA, C4BA, and C6BA with the alkyl chain of ethyl, n-butyl, and n-hexyl, respectively) have been synthesized to investigate the effects of alkyl chain length and substituent pattern of fullerene bis-adducts on the film structures and photovoltaic properties of bulk heterojunction polymer solar cells. The shorter alkyl chain length caused lower solubility of the fullerene bis-adducts (C6BA > C4BA > C2BA), thereby resulting in the increased separation difficulty of respective bis-adduct isomers. The device performance based on poly(3-hexylthiophene) (P3HT) and the fullerene bis-adduct regioisomer mixtures was enhanced by shortening the alkyl chain length. When using the regioisomerically separated fullerene bis-adducts, the devices based on trans-2 and a mixture of trans-4 and e of C4BA exhibited the highest power conversion efficiencies of ca. 2.4%, which are considerably higher than those of the C6BA counterparts (ca. 1.4%) and the C4BA regioisomer mixture (1.10%). The film morphologies as well as electron mobilities of the P3HT:bis-adduct blend films were found to affect the photovoltaic properties considerably. These results reveal that the alkyl chain length and substituent pattern of fullerene bis-adducts significantly influence the photovoltaic properties as well as the film structures of bulk heterojunction solar cells.

  3. Procedures for Analysis of Dried Plasma Using Microsampling Devices to Detect Sulfur Mustard-Albumin Adducts for Verification of Poisoning.

    Science.gov (United States)

    John, Harald; Willoh, Sophia; Hörmann, Philipp; Siegert, Markus; Vondran, Antje; Thiermann, Horst

    2016-09-01

    Incorporation of the chemical warfare agent sulfur mustard (SM) produces a covalent adduct with human serum albumin (HSA) representing an established plasma biomarker of poisoning. Bioanalytical verification requires both plasma generation from whole blood and shipping to specialized laboratories following strict guidelines for complex packaging. These needs often push the infrastructural boundary in crisis regions and war zones. Therefore, we herein originally introduce different reliable bioanalytical procedures using filter paper as well as novel volumetric microsampling tools (Mitra devices and Noviplex DUO cards) to generate dried plasma samples not liable to the shipping constraints. In addition, the Noviplex device enables in-transit separation of plasma from whole blood without the need of a centrifuge. Plasma-loaded and dried devices were subjected to pronase treatment yielding the alkylated dipeptide hydroxyethylthioethyl-CysPro (HETE-CP) derived from the HSA-SM adduct that was detected by microbore liquid chromatography-electrospray ionization tandem-mass spectrometry (μLC-ESI MS/MS). For all devices, samples exposed to SM yielded excellent linearity (0.025-50 μM SM) and good precision (≤13%) and fulfilled forensic quality criteria for ion ratios of qualifying and quantifying product ions. Stability of the HSA-SM adduct in dried and liquid plasma is shown under conditions of three climatic zones (temperate climate, hot and dry climate, and hot and humid climate) for at least 9 days simulating the period of delayed sample shipping. Our results originally document that dried plasma is appropriate for storage and shipping at ambient temperature and that novel microsampling tools are of essential benefit when targeting the HSA-SM adduct for verification analysis. PMID:27482832

  4. Limits of the manipulative-fixed method for measurement of shoulder joint horizontal adduction muscle strength using a handheld dynamometer

    OpenAIRE

    Hirano, Masahiro; Katoh, Munenori

    2015-01-01

    [Purpose] The aim of this study was to verify the limit of isometric muscle strength of shoulder joint horizontal adduction using handheld dynamometer (HHD) manipulated by hand (referred to as the manipulative-fixed method). [Subjects and Methods] The subjects were 33 healthy college students. The examiner was a healthy college student. Shoulder joint horizontal adductor muscle strength was measured using HHD with the subject in the supine position. The belt-fixed and manipulative-fixed metho...

  5. Detection of serum AFB1-lysine adduct in Malaysia and its association with liver and kidney functions.

    Science.gov (United States)

    Mohd Redzwan, S; Rosita, Jamaluddin; Mohd Sokhini, A M; Nurul 'Aqilah, A R; Wang, Jia-Sheng; Kang, Min-Su; Zuraini, Ahmad

    2014-01-01

    Aflatoxin is ubiquitously found in many foodstuffs and produced by Aspergillus species of fungi. Of many aflatoxin metabolites, AFB1 is classified by the International Agency for Research on Cancer (IARC) as group one carcinogen and linked to the development of hepatocellular carcinoma (HCC). The study on molecular biomarker of aflatoxin provides a better assessment on the extent of human exposure to aflatoxin. In Malaysia, the occurrences of aflatoxin-contaminated foods have been documented, but there is a lack of data on human exposure to aflatoxin. Hence, this study investigated the occurrence of AFB1-lysine adduct in serum samples and its association with liver and kidney functions. 5ml fasting blood samples were collected from seventy-one subjects (n=71) for the measurement of AFB1-lysine adduct, albumin, total bilirubin, AST (aspartate aminotransferase), ALT (alanine transaminase), ALP (alkaline phosphatase), GGT (gamma-glutamyl transpeptidase), creatinine and BUN (blood urea nitrogen). The AFB1-lysine adduct was detected in all serum samples (100% detection rate) with a mean of 6.85±3.20pg/mg albumin (range: 1.13-18.85pg/mg albumin). Male subjects (mean: 8.03±3.41pg/mg albumin) had significantly higher adduct levels than female subjects (mean: 5.64±2.46pg/mg albumin) (p6.85pg/mg albumin) had significantly elevated level of total bilirubin (pMalaysia. Given that aflatoxin can pose serious problem to the health, intervention strategies should be implemented to limit/reduce human exposure to aflatoxin. Besides, a study with a big sample size should be warranted in order to assess aflatoxin exposure in the general population of Malaysia.

  6. Specific adduction of plant lipid transfer protein by an allene oxide generated by 9-lipoxygenase and allene oxide synthase

    OpenAIRE

    Bakan, Benedicte; Hamberg, Mats; Perrocheau, Ludivine; Maume, Daniel; Rogniaux, Helene; Tranquet, Olivier; Rondeau, Corinne; Blein, J Pierre; Ponchet, Michel; Marion, Didier

    2006-01-01

    Lipid transfer proteins (LTPs) are ubiquitous plant lipid-binding proteins that have been associated with multiple developmental and stress responses. Although LTPs typically bind fatty acids and fatty acid derivatives in a non-covalent way, studies on the LTPs of barley seeds have identified an abundantly occurring covalently modified form, LTP1b, the lipid ligand of which has resisted clarification. In the present study, this adduct was identified as the {alpha}-ketol 9-hydroxy-10-oxo-12(Z)...

  7. Scapular Notching on Kinematic Simulated Range of Motion After Reverse Shoulder Arthroplasty Is Not the Result of Impingement in Adduction

    OpenAIRE

    Laedermann, Alexandre; Gueorguiev, Boyko; Charbonnier, Caecilia; Stimec, Bojan; Fasel, Jean; Zderic, Ivan; Hagen, Jennifer; Walch, Gilles

    2015-01-01

    Abstract Impingement after reverse shoulder arthroplasty (RSA) is believed to occur from repetitive contact in adduction between the humeral component and the inferior scapular pillar. The primary purpose of this biomechanical study was to confirm the presence of different types of impingement and to examine which daily-life movements are responsible for them. A secondary aim was to provide recommendations on the type of components that would best minimize notching and loss of range of motion...

  8. Induction of somatic mutations but not methylated DNA adducts in λlacZ transgenic mice by dichlorvos

    NARCIS (Netherlands)

    Pletsa, V.; Steenwinkel, M.-J.S.T.; Delft, J.H.M. van; Baan, R.A.; Kyrtopoulos, S.A.

    1999-01-01

    In order to examine the in vivo genotoxic activity of dichlorvos, λlacZ transgenic mice (Muta(TM)Mouse) were treated i.p. with single (4.4 or 11 mg/kg) or multiple (5x11 mg/kg) doses of this agent and sacrificed 4 h or 14 days post-treatment for DNA adduct measurement or mutant frequency analysis, r

  9. Biomonitoring of diesel exhaust-exposed workers. DNA and hemoglobin adducts and urinary 1-hydroxypyrene as markers of exposure

    DEFF Research Database (Denmark)

    Nielsen, Per Sabro; Andreassen, Åshild; Farmer, Peter B.;

    1996-01-01

    the 32P-postlabelling method with butanol and P1 enrichment procedures. Hydroxyethylvaline (HOEtVal) adducts in hemoglobin were measured by gas chromatography-mass spectrometry (GC-MS) and 1-hydroxypyrene (HPU) in urine determined using HPLC analysis. The exposed workers had significantly higher levels....... The study indicated that skin absorption of polycyclic aromatic hydrocarbons (PAH) might be an important factor to consider when studying PAH exposure from air pollution sources....

  10. 99Tcm标记Gd-DTPA-DG及其在裸鼠体内的生物分布%Radio-labeling of Gd-DTPA-DG with 99Tcm and its biodistribution in nude mice

    Institute of Scientific and Technical Information of China (English)

    黄占文; 张伟; 陈跃

    2011-01-01

    Objective To observe the stability and biodistribution of 99 Tcm radio-labeled a paramagnetic deoxy-glucose-type MR contrast agent diethylenetriamine pentaacetic acid-gadolinium salt deoxy-glucose(Gd-DTPA-DG) in tumor-bearing nude mice in vivo. Methods To form 99 Tcm-Gd-DTPA-DG , the labelling conditions such as Gd-DTPA-DG quality, SnCl2 · 2 H2 O dosage , the reaction medium pH value and reaction temperature were optimized by orthogonal experimental design. The radio-labeling efficiency was measured by thin layer chromatography(TLC). The bio-distribution was observed by the tumor and other major organs were taken out from nude mice at 10,30 min and 1, 2,4 , 24 h respectively after caudal vein injection of 99 Tcm-Gd-DTPA-DG. Results When taking 10 mg Gd-DTPA-DG,0. 6 mg SnCl2 · 2H2O,pH<2,adding 37 MBq Na99 TcmO4 ,then reacting in boiling water for 30 min, the radiochemical purity of 99Tcm-Gd-DTPA-DG can reach to 98. 5% and remain 96. 2% placed at room temperature for 6 h. 99TcmGd-DTPA-DG accumulated in the tumor to a higher level than other organ at 2 h,the uptake was about (1. 48±0. 12) %ID/g , and the radio-uptake ratio of tumor to muscle(T/NT)was reached 2. 91. Conclusion 99 Tcm labeled the paramagnetic MR contrast agent Gd-DTPA-DG is feasible. The labeled agent shows excellent tumor targeting in nude mice in vivo. 99 Tcm-Gd-DTPA-DG is potential for a SPECT(single photon emission computed tomography)-MRI dual-modality imaging probes.%目的 探讨锝(99Tcm)标记顺磁性脱氧葡萄糖类MRI对比剂二乙三胺五乙酸-脱氧葡萄糖钆盐(Gd-DTPA-DG)的稳定性及在荷瘤裸鼠体内的生物分布,寻找一种核素与磁共振双模式影像探针.方法 对 Gd-DTPA-DG进行99Tcm标记,并对需要的Gd-DTPA-DG、氯化亚锡(SnCl2·2H2O)用量,pH,温度采用正交实验设计,确定最佳标记条件.采用薄层纸层析法(TLC)分析标记率,体外放置6 h,观察标记物的稳定性.将标记的99Tcm -Gd-DTPA-DG注入裸鼠体内,10、30

  11. Malabaricone C-containing mace extract inhibits safrole bioactivation and DNA adduct formation both in vitro and in vivo.

    Science.gov (United States)

    Martati, Erryana; Boonpawa, Rungnapa; van den Berg, Johannes H J; Paini, Alicia; Spenkelink, Albertus; Punt, Ans; Vervoort, Jacques; van Bladeren, Peter J; Rietjens, Ivonne M C M

    2014-04-01

    Safrole, present in mace and its essential oils, causes liver tumors in rodents at high dose levels due to formation of a DNA reactive 1'-sulfooxysafrole. The present study identifies malabaricone C as a mace constituent able to inhibit safrole DNA adduct formation at the level of sulfotransferase mediated bioactivation. This inhibition was incorporated into physiologically based biokinetic rat and human models. Dosing safrole at 50mg/kg body weight and malabaricone C-containing mace extract at a ratio reflecting the relative presence in mace, and assuming 100% or 1% uptake of malabaricone C-containing mace extract, the model predicted inhibition of 1'-sulfooxysafrole formation for rats and humans by 90% and 100% or 61% and 91%, respectively. To validate the model, mace extract and safrole were co-administered orally to Sprague-Dawley rats. LC-ECI-MS/MS based quantification of DNA adduct levels revealed a significant (psafrole DNA adduct formation by malabaricone C-containing mace extract in the liver of rats exposed to safrole. The data obtained were used to perform a refined risk assessment of safrole. Overall, the results suggest a lower tumor incidence when safrole would be tested within a relevant food matrix containing sulfotransferase inhibitors compared to dosing pure safrole.

  12. Equilibrium Dynamics of β-N-Methylamino-L-Alanine (BMAA) and Its Carbamate Adducts at Physiological Conditions

    Science.gov (United States)

    Zimmerman, David; Goto, Joy J.; Krishnan, Viswanathan V

    2016-01-01

    Elevated incidences of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia complex (ALS/PDC) is associated with β-methylamino-L-alanine (BMAA), a non-protein amino acid. In particular, the native Chamorro people living in the island of Guam were exposed to BMAA by consuming a diet based on the cycad seeds. Carbamylated forms of BMAA are glutamate analogues. The mechanism of neurotoxicity of the BMAA is not completely understood, and BMAA acting as a glutamate receptor agonist may lead to excitotoxicity that interferes with glutamate transport systems. Though the interaction of BMAA with bicarbonate is known to produce carbamate adducts, here we demonstrate that BMAA and its primary and secondary adducts coexist in solution and undergoes a chemical exchange among them. Furthermore, we determined the rates of formation/cleavage of the carbamate adducts under equilibrium conditions using two-dimensional proton exchange NMR spectroscopy (EXSY). The coexistence of the multiple forms of BMAA at physiological conditions adds to the complexity of the mechanisms by which BMAA functions as a neurotoxin. PMID:27513925

  13. Collision-induced dissociation analysis of negative atmospheric ion adducts in atmospheric pressure corona discharge ionization mass spectrometry.

    Science.gov (United States)

    Sekimoto, Kanako; Takayama, Mitsuo

    2013-05-01

    Collision-induced dissociation (CID) experiments were performed on atmospheric ion adducts [M + R](-) formed between various types of organic compounds M and atmospheric negative ions R(-) [such as O2(-), HCO3(-), COO(-)(COOH), NO2(-), NO3(-), and NO3(-)(HNO3)] in negative-ion mode atmospheric pressure corona discharge ionization (APCDI) mass spectrometry. All of the [M + R](-) adducts were fragmented to form deprotonated analytes [M - H](-) and/or atmospheric ions R(-), whose intensities in the CID spectra were dependent on the proton affinities of the [M - H](-) and R(-) fragments. Precursor ions [M + R](-) for which R(-) have higher proton affinities than [M - H](-) formed [M - H](-) as the dominant product. Furthermore, the CID of the adducts with HCO3(-) and NO3(-)(HNO3) led to other product ions such as [M + HO](-) and NO3(-), respectively. The fragmentation behavior of [M + R](-) for each R(-) observed was independent of analyte type (e.g., whether the analyte was aliphatic or aromatic, or possessed certain functional groups). PMID:23479312

  14. Collision-induced dissociation analysis of negative atmospheric ion adducts in atmospheric pressure corona discharge ionization mass spectrometry.

    Science.gov (United States)

    Sekimoto, Kanako; Takayama, Mitsuo

    2013-05-01

    Collision-induced dissociation (CID) experiments were performed on atmospheric ion adducts [M + R](-) formed between various types of organic compounds M and atmospheric negative ions R(-) [such as O2(-), HCO3(-), COO(-)(COOH), NO2(-), NO3(-), and NO3(-)(HNO3)] in negative-ion mode atmospheric pressure corona discharge ionization (APCDI) mass spectrometry. All of the [M + R](-) adducts were fragmented to form deprotonated analytes [M - H](-) and/or atmospheric ions R(-), whose intensities in the CID spectra were dependent on the proton affinities of the [M - H](-) and R(-) fragments. Precursor ions [M + R](-) for which R(-) have higher proton affinities than [M - H](-) formed [M - H](-) as the dominant product. Furthermore, the CID of the adducts with HCO3(-) and NO3(-)(HNO3) led to other product ions such as [M + HO](-) and NO3(-), respectively. The fragmentation behavior of [M + R](-) for each R(-) observed was independent of analyte type (e.g., whether the analyte was aliphatic or aromatic, or possessed certain functional groups).

  15. Effect of Increased Water Intake on Urinary DNA Adduct Levels and Mutagenicity in Smokers: A Randomized Study

    Directory of Open Access Journals (Sweden)

    Inmaculada Buendia Jimenez

    2015-01-01

    Full Text Available The association between fluid intake and bladder cancer risk remains controversial. Very little is known about to which extent the amount of water intake influences the action of excreting toxics upon the urinary system. This proof of concept trial investigates the effect of water intake on mutagenesis in smokers, a high risk population for bladder cancer. Methods. Monocentric randomized controlled trial. Inclusion Criteria. Male subjects aged 2045–45 y/o, smokers, and small drinkers (24-hour urinary volume 700 mOsmol/kg. Outcomes. 4-ABP DNA adducts formation in exfoliated bladder cells in 24-hour urine collection and urinary mutagenicity in 24-hour urine. Test Group. Subjects consumed 1.5 L daily of the study product (EVIAN on top of their usual water intake for 50 days. Control Group. Subjects continued their usual lifestyle habits. Results. 65 subjects were randomized. Mean age was 30 y/o and mean cigarettes per day were 20. A slight decrease in adducts formation was observed between baseline and last visit but no statistically significant difference was demonstrated between the groups. Urinary mutagenicity significantly decreased. The study shows that increasing water intake decreases urinary mutagenicity. It is not confirmed by urinary adducts formation. Further research would be necessary.

  16. Effects of squats accompanied by hip joint adduction on the selective activity of the vastus medialis oblique.

    Science.gov (United States)

    Hyong, In Hyouk

    2015-06-01

    [Purpose] This study evaluated the effective selective activation method of the vastus medialis oblique for knee joint stabilization in patients with patellofemoral pain syndrome. [Subjects and Methods] Fifteen healthy college students (9 males, 6 females); mean age, height, and weight: 22.2 years, 167.8 cm, and 61.4 kg, respectively) participated. The knee angle was held at 60°. Muscle activities were measured once each during an ordinary squat and a squat accompanied by hip joint adduction. The muscle activities of the vastus medialis oblique and vastus lateralis were measured by electromyography for five seconds while maintaining 60° knee flexion. Electromyography signals were obtained at a sampling rate of 1,000 Hz and band pass filtering at 20-50 Hz. The obtained raw root mean square was divided by the maximal voluntary isometric contraction and expressed as a percentage. The selective activity of the vastus medialis oblique was assessed according to the muscle activity ratio of the vastus medialis oblique to the vastus lateralis. [Results] The activity ratio of the vastus medialis oblique was higher during a squat with hip joint adduction than without. [Conclusion] A squat accompanied by hip joint adduction is effective for the selective activation of the vastus medialis oblique. PMID:26180362

  17. Structure and spectromagnetic properties of the superoxide radical adduct of DMPO in water: elucidation by theoretical investigations.

    Science.gov (United States)

    Houriez, Céline; Ferré, Nicolas; Siri, Didier; Tordo, Paul; Masella, Michel

    2010-09-16

    In the field of spin trapping chemistry, the design of more efficient radical traps can be assisted by the development of theoretical methods able to give a quantitative evaluation of the electron paramagnetic resonance (EPR) spectrum features of the spin-adduct radical, even before initiating the experimental work. The superoxide radical adduct of the 5,5-dimethyl-1-pyrroline-N-oxide nitrone (DMPO-OOH) has been reported in a huge number of papers devoted to the study of the oxidative stress. Here, we present for the first time the theoretical study of DMPO-OOH in an explicit water solution, based on the combined QM/MM//MD protocol we recently proposed, featuring a full coupling between the solute and all the explicit water molecules. Our results show that the DMPO-OOH EPR spectrum, whose interpretation is still debated, can be explained in the light of two sites in chemical exchange, in agreement with the most recent experimental data. Moreover, we demonstrate that each site consists of an equilibrium between the two main 5-membered ring conformations of DMPO-OOH. We provide also an analysis of the solvent contribution to the hyperfine coupling constants (hcc's) as well as an exhaustive study of the possible relationship between the hcc's and the main structural characteristics of DMPO-OOH. Our QM/MM//MD protocol appears thus to be an accurate theoretical tool allowing the investigation of the magnetic properties of large nitroxide spin adducts in complex environments. PMID:20722404

  18. A new approach to the synthesis of monomers and polymers incorporating furan/maleimide Diels-Alder adducts

    Science.gov (United States)

    Banella, Maria Barbara; Gioia, Claudio; Vannini, Micaela; Colonna, Martino; Celli, Annamaria; Gandini, Alessandro

    2016-05-01

    The Diels-Alder reaction between furan and maleimide moieties is a well-known and widely used strategy to build bio-based macromolecular structures with peculiar properties. The furan-maleimide adducts are thermally reversible because they can be broken above about 120°C and recombined at lower temperatures. At the moment only the monomers exhibiting the furan or the maleimide moieties on their extremity are used in order to get linear or cross-linked polymeric structures. The innovative idea described here consists in using a monomer bearing two carboxylic acidic groups on its extremities and a furan-maleimide Diels-Alder adduct within its structure. This monomer can give rise to classical polycondensation reactions leading to polymers. These polymers (which are polyesters in the present case) can be broken at high temperatures in correspondence of the furane-maleimide Diels-Alder adduct leading to segments exhibiting furan or maleimide moieties at their extremities, which at lower temperature recombine leading to random or block copolymers.

  19. Effect of Increased Water Intake on Urinary DNA Adduct Levels and Mutagenicity in Smokers: A Randomized Study

    Science.gov (United States)

    Buendia Jimenez, Inmaculada; Richardot, Pascaline; Picard, Pascaline; Lepicard, Eve M.; De Meo, Michel; Talaska, Glenn

    2015-01-01

    The association between fluid intake and bladder cancer risk remains controversial. Very little is known about to which extent the amount of water intake influences the action of excreting toxics upon the urinary system. This proof of concept trial investigates the effect of water intake on mutagenesis in smokers, a high risk population for bladder cancer. Methods. Monocentric randomized controlled trial. Inclusion Criteria. Male subjects aged 2045–45 y/o, smokers, and small drinkers (24-hour urinary volume 700 mOsmol/kg). Outcomes. 4-ABP DNA adducts formation in exfoliated bladder cells in 24-hour urine collection and urinary mutagenicity in 24-hour urine. Test Group. Subjects consumed 1.5 L daily of the study product (EVIAN) on top of their usual water intake for 50 days. Control Group. Subjects continued their usual lifestyle habits. Results. 65 subjects were randomized. Mean age was 30 y/o and mean cigarettes per day were 20. A slight decrease in adducts formation was observed between baseline and last visit but no statistically significant difference was demonstrated between the groups. Urinary mutagenicity significantly decreased. The study shows that increasing water intake decreases urinary mutagenicity. It is not confirmed by urinary adducts formation. Further research would be necessary. PMID:26357419

  20. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to Lactobacillus casei DG CNCM I-1572 and decreasing potentially pathogenic gastro-intestinal microorganisms (ID 2949, 3061, further assessment) pursuant to Article 13

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment related to Lactobacillus casei...... DG CNCM I-1572 and decreasing potentially pathogenic gastro-intestinal microorganisms. The food constituent that is the subject of the health claim, Lactobacillus casei DG CNCM I-1572, is sufficiently characterised. The claimed effect, decreasing potentially pathogenic gastro...... and effect relationship has not been established between the consumption of Lactobacillus casei DG CNCM I-1572 and decreasing potentially pathogenic gastro‑intestinal microorganisms....

  1. Biomarkers of exposure to tobacco smoke and environmental pollutants in mothers and their transplacental transfer to the foetus. Part I: Bulky DNA adducts

    International Nuclear Information System (INIS)

    32P-postlabelling and PAH-ELISA using the antiserum no. 29 were employed to analyze DNA adducts in venous and umbilical cord blood and the placenta of 79 mothers giving birth to 80 living babies in Prague (Czech Republic). Ambient air exposure was measured by stationary measurements of basic air pollutants (PM2.5, c-PAHs) during the entire pregnancy. Tobacco smoke exposure was assessed by questionnaire data and by plasma cotinine levels. The total DNA adduct levels in the lymphocytes of mothers and newborns were elevated by 30-40% (p 8 nucleotides vs. 0.15 ± 0.06 adducts/108 nucleotides) with newborns indicated a 30-40% increase of adducts in mothers. Almost equal PAH-DNA adduct levels were detected by anti-BPDE-DNA ELISA in the placenta of tobacco smoke-exposed and -unexposed mothers. Our results suggest a protective effect of the placental barrier against the genotoxic effect of some tobacco smoke components between the circulation of mother and child. We found a correlation between adduct levels in the blood of mothers and newborns.

  2. Serendipitous compositional and structural diversity in urotropine adducts of binary cadmium xanthates

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Yee Seng; Azizuddin, Aliaa Diyana [Malaya Univ., Kuala Lumpur (Malaysia). Dept. of Chemistry; Campian, Marius V.; Haiduc, Ionel [Babes-Bolyai Univ., Cluj-Napoca (Romania). Dept. of Chemistry; Tiekink, Edward R.T. [Sunway Univ., Bandar Sunway (Malaysia). Centre for Crystalline Material

    2016-05-01

    Three new compounds, Cd(S{sub 2}COMe){sub 2}(hmta) (1), Cd(S{sub 2}COEt){sub 2}(hmta)0.5 (2) and Cd(S{sub 2}COiPr){sub 2}(hmta) (3), have been isolated from a systematic study of adduct formation between Cd(S{sub 2}COR){sub 2}, R = Me, Et and iPr, precursors and potentially polydentate hmta; hmta is urotropine (hexamethylenetetramine). The compounds have been characterised by a variety of spectroscopic techniques including a photoluminescence study in both solution and the solid-state, as well as by thermal methods. Crystallography shows 1 to have μ{sub 2}-bridging hmta leading to a one-dimensional coordination polymer. This framework is essentially repeated in 2 but with a μ{sub 3}-bridging hmta so that Cd(S{sub 2}COEt){sub 2} entities decorate the chain. By contrast, a binuclear zero-dimensional aggregate with terminally bound hmta is found in 3. The influence of steric bulk of the alkyl substituents in Cd(S{sub 2}COR){sub 2} is pivotal in determining the ultimate structural outcome.

  3. Real-Time Knee Adduction Moment Feedback for Gait Retraining Through Visual and Tactile Displays

    KAUST Repository

    Wheeler, Jason W.

    2011-01-01

    The external knee adduction moment (KAM) measured during gait is an indicator of tibiofemoral joint osteoarthritis progression and various strategies have been proposed to lower it. Gait retraining has been shown to be an effective, noninvasive approach for lowering the KAM. We present a new gait retraining approach in which the KAM is fed back to subjects in real-time during ambulation. A study was conducted in which 16 healthy subjects learned to alter gait patterns to lower the KAM through visual or tactile (vibration) feedback. Participants converged on a comfortable gait in just a few minutes by using the feedback to iterate on various kinematic modifications. All subjects adopted altered gait patterns with lower KAM compared with normal ambulation (average reduction of 20.7%). Tactile and visual feedbacks were equally effective for real-time training, although subjects using tactile feedback took longer to converge on an acceptable gait. This study shows that real-time feedback of the KAM can greatly increase the effectiveness and efficiency of subject-specific gait retraining compared with conventional methods. © 2011 American Society of Mechanical Engineers.

  4. SYNTHESIS AND PHARMACOLOGICAL EFFECTS OF BUTADIENE AND CYCLOPENTADIENE ADDUCTS OF METHANDROSTENOLONE IN RATS

    Directory of Open Access Journals (Sweden)

    FAZEL SHAMSA

    2006-06-01

    Full Text Available In this study the reactivity of methandrostenolone or [(17b-17-hydroxy-17-methylandrosta-1, 4-diene-3-one], as a dienophil in a Diels-Alder type cycloaddition reaction was investigated. The purpose of this approach was to investigate whether the 1-dehydro position of methandrostenolone 1 undergoes a cycloaddition reaction with dienes, such as 1, 3 butadiene or cyclopentadiene, and to investigate the biological behavior of the reaction adducts, i.e, compound 3 {(17b-17-hydroxy-17-methyl androsta [1a, 2a] cyclohex 3’, 4-diene-3-one} and compound 4 {(17b-17-hydroxy-17-methyl androsta [1a, 2a] cyclohex (2’,5’ methylene 3’, 4-diene-3-one}, relative to compound 1. The results indicated that thedDiels-Alder reactionddid notpproceed under the usual circumstances of high pressure and temperature, but could proceed in the presence of a Lewis acid (AlCl3. The structures of compounds 3 and 4 were confirmed by spectroscopic methods. The androgenic behavior of compounds 3 and 4 in comparison to compound 1 in the apomorphine test indicated that both compounds were almost devoid of androgenic activity, but prevented apomorphine mediated penile erection in male rats in a similar manner as cyproterone acetate.

  5. Theoretical Investigation of Detailed Thermodynamic Character of Possible Difunctional Adducts Model

    Institute of Scientific and Technical Information of China (English)

    CHANG Guan-Ru; ZHOU Li-Xin; CHEN Dong

    2006-01-01

    The B3LYP/6-31G* level of theory was used to optimize trans-[Pt(NH3)(Am)G-L], where Am = quinoline or thiazole and L is chosen as the model for functional groups of peptide side chains, and for adenine and guanine sites of DNA as the ultimate target of platinum anticancer drugs. Bond dissociating energy and stability energy of complexes are chosen to study detailedly ther- modynamic character of possible difunctional adducts model. In order to investigate the influence of a polarizable environment on the energy of the Pt-L bond formation, we adopt a new bonding energy formula brought forward by Lippard and his coworkers: ΔH(Sol) = ΔH(SCF) + ΔG(Solv), which is quite appropriate to compare with what is found in experimental studies. Our calculated results demonstrate that N-containing ligands are more favored in view of thermodynamics both in gas phrase and in solution. However, it is worthly to be noted that addition of solvation free energies result in moderate correction of bonding energy in relative ordering, and the largest ones both present in imidazole ligand, not in guanine ligand. Finally, the nature of bond is analyzed in terms of partial charges distribution based on NBO population.

  6. Hypervalent Compounds as Ligands: I 3 -Anion Adducts with Transition Metal Pentacarbonyls

    KAUST Repository

    Rogachev, Andrey Yu.

    2013-06-17

    Just a couple of transition metal complexes of the familiar triiodide anion are known. To investigate the bonding in these, as well as isomeric possibilities, we examined theoretically adducts of I3 - with model organometallic fragments, [Cr(CO)5] and [Mn(CO) 5]+. Bonding energy computations were augmented by a Natural Bond Orbital (NBO) perturbation theory analysis and Energy Decomposition Analysis (EDA). The bonding between I3 - and the organometallic fragment is substantial, especially for the electrostatically driven anion-cation case. "End-on" coordination is favored by 5-13 kcal/mol over "side-on" (to the central I of I3 -), with a ∼10 kcal/mol barrier for isomerization. A developing asymmetry in the I-I bonding of "end-on" coordinated I 3 - led us to consider in some detail the obvious fragmentation to a coordinated I- and free I2. While the signs of incipient fragmentation in that direction are there, these is a definite advantage to maintaining some I- to I2 bonding in triiodide complexes. © 2013 American Chemical Society.

  7. Structural basis for recognition of 5'-phosphotyrosine adducts by TDP2

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Ke; Kurahash, Kayo; Gao, Rui; Tsutakawa, Susan E.; Tainer, John A.; Pommier, Yves; Aihara, Hideki

    2012-12-19

    The DNA repair enzyme TDP2 resolves 5'-phosphotyrosyl-DNA adducts, and is responsible for resistance to anti-cancer drugs that target covalent topoisomerase-DNA complexes. TDP2 also participates in key signaling pathways during development and tumorigenesis, and cleaves a protein-RNA linkage during picornavirus replication. The crystal structure of zebrafish TDP2 bound to DNA reveals a deep and narrow basic groove that selectively accommodates the 5'-end of single-stranded DNA in a stretched conformation. The crystal structure of the full-length C. elegans TDP2 shows that this groove can also accommodate an acidic peptide stretch in vitro, with Glu and Asp sidechains occupying the DNA backbone phosphate binding sites. This extensive molecular mimicry suggests a potential mechanism for auto-regulation and how TDP2 may interact with phosphorylated proteins in signaling. Our study provides a framework to interrogate functions of TDP2 and develop inhibitors for chemotherapeutic and antiviral applications.

  8. Quantification of DNA adducts formed in liver, lungs, and isolated lung cells of rats and mice exposed to (14)C-styrene by nose-only inhalation.

    Science.gov (United States)

    Boogaard, P J; de Kloe, K P; Wong, B A; Sumner, S C; Watson, W P; van Sittert, N J

    2000-10-01

    Bronchiolo-alveolar tumors were observed in mice exposed chronically to 160 ppm styrene, whereas no tumors were seen in rats up to concentrations of 1000 ppm. Clara cells, which are predominant in the bronchiolo-alveolar region in mouse lungs but less numerous in rat and human lung, contain various cytochrome P450s, which may oxidize styrene to the rodent carcinogen styrene-7,8-oxide (SO) and other reactive metabolites. Reactive metabolites may form specific DNA adducts and induce the tumors observed in mice. To determine DNA adducts in specific tissues and cell types, rats and mice were exposed to 160 ppm [ring-U-(14)C]styrene by nose-only inhalation for 6 h in a recirculating exposure system. Liver and lungs were isolated 0 and 42 h after exposure. Fractions enriched in Type II cells and Clara cells were isolated from rat and mouse lung, respectively. DNA adduct profiles differed quantitatively and qualitatively in liver, total lung, and enriched lung cell fractions. At 0 and 42 h after exposure, the two isomeric N:7-guanine adducts of SO (measured together, HPEG) were present in liver at 3.0 +/- 0.2 and 1.9 +/- 0.3 (rat) and 1.2 +/- 0.2 and 3.2 +/- 0.5 (mouse) per 10(8) bases. Several other, unidentified adducts were present at two to three times higher concentrations in mouse, but not in rat liver. In both rat and mouse lung, HPEG was the major adduct at approximately 1 per 10(8) bases at 0 h, and these levels halved at 42 h. In both rat Type II and non-Type II cells, HPEG was the major adduct and was about three times higher in Type II cells than in total lung. For mice, DNA adduct levels in Clara cells and non-Clara cells were similar to total lung. The hepatic covalent binding index (CBI) at 0 and 42 h was 0.19 +/- 0.06 and 0.14 +/- 0.03 (rat) and 0. 25 +/- 0.11 and 0.44 +/- 0.23 (mouse), respectively. The pulmonary CBIs, based on tissues combined for 0 and 42 h, were 0.17 +/- 0.04 (rat) and 0.24 +/- 0.04 (mouse). Compared with CBIs for other genotoxicants

  9. gamma-Diketone neuropathy: axon atrophy and the role of cytoskeletal protein adduction.

    Science.gov (United States)

    LoPachin, Richard M; DeCaprio, Anthony P

    2004-08-15

    Multifocal giant neurofilamentous axonal swellings and secondary distal degeneration have been historically considered the hallmark features of gamma-diketone neuropathy. Accordingly, research conducted over the past 25 years has been directed toward discerning mechanisms of axonal swelling. However, this neuropathological convention has been challenged by recent observations that swollen axons were an exclusive product of long-term 2.5-hexanedione (HD) intoxication at lower daily dose-rates (e.g., 175 mg/kg/day); that is, higher HD dose-rates (e.g., 400 mg/kg/day) produced neurological deficits in the absence of axonal swellings. The observation that neurological toxicity can be expressed without axonal swelling suggests that this lesion is not an important pathophysiological event. Instead, several research groups have now shown that axon atrophy is prevalent in nervous tissues of laboratory animals intoxicated over a wide range of HD dose-rates. The well-documented nerve conduction defects associated with axon atrophy, in conjunction with the temporal correspondence between this lesion and the onset of neurological deficits, strongly suggest that atrophy has pathophysiological significance. In this commentary, we present evidence that supports a pathognomonic role for axon atrophy in gamma-diketone neuropathy and suggests that the functional consequences of this lesion mediate the corresponding neurological toxicity. Previous research has demonstrated that HD interacts with proteins via formation of pyrrole adducts. We therefore discuss the possibility that this chemical process is essential to the mechanism of atrophy. Evidence presented in this review suggests that "distal axonopathy" is an inaccurate classification and future nosological schemes should be based on the apparent primacy of axon atrophy. PMID:15289087

  10. Specificity and affinity of phenosafranine protein adduct: Insights from biophysical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Ding Fei [Department of Chemistry, China Agricultural University, Beijing 100193 (China); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Zhang Li; Sun Ye [Department of Chemistry, China Agricultural University, Beijing 100193 (China); Diao Jianxiong [College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193 (China); Yang Xinling [Department of Chemistry, China Agricultural University, Beijing 100193 (China); Sun Ying, E-mail: sunying@cau.edu.cn [College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193 (China); Zhang Li, E-mail: zhli.work@gmail.com [Key Laboratory of Pesticide Chemistry and Application Technology, Ministry of Agriculture, Department of Applied Chemistry, China Agricultural University, Beijing 100193 (China)

    2012-03-15

    Phenosafranine is a toxic and recalcitrant compound, whose capacity to intercalate with double stranded DNA has been shown. In this contribution, a biophysical discuss on the conjugation of phenosafranine with two model proteins human serum albumin (HSA) and lysozyme (Lys) has been identified utilizing a combination of molecular modeling, steady state and time-resolved fluorescence and circular dichroism (CD) approaches. The accurate binding domain of phenosafranine in protein has been characterized from molecular modeling, subdomain IIIA of HSA and Trp-62, Trp-63 and Trp-108 residues of Lys was designated to possess high-affinity for this compound, the dominant forces in the protein-phenosafranine adduct are hydrogen bonds and {pi}-{pi} interactions, but hydrophobic interactions between dye and Lys are also not exclude. The data of fluorescence displayed that the complex of phenosafranine with protein produces quenching through static property, this corroborates the time-resolved fluorescence results that the ground state complex formation with a moderate affinity of 10{sup 4} M{sup -1}. Moreover, via synchronous fluorescence, CD and three-dimensional fluorescence we indicated some extent of polypeptide chain of protein partially unfolding upon conjugation with phenosafranine. Through this work, we anticipate it can supply salient clues on the toxicological action of phenosafranine and other azines, which have analogous configuration with phenosafranine. - Highlights: Black-Right-Pointing-Pointer Our study supply salient clues on the toxicological action of toxic phenosafranine. Black-Right-Pointing-Pointer Phenosafranine is situated within subdomain IIIA, Sudlow's site II on HSA. Black-Right-Pointing-Pointer Trp-62, Trp-63 and Trp-108 residues on the Lys molecule are all close to dye. Black-Right-Pointing-Pointer Static property of the phenosafranine induced quenching of protein Trp fluorescence. Black-Right-Pointing-Pointer Protein spatial structure proved

  11. Some Lewis acid-base adducts involving boron trifluoride as electrolyte additives for lithium ion cells

    Science.gov (United States)

    Nie, Mengyun; Madec, L.; Xia, J.; Hall, D. S.; Dahn, J. R.

    2016-10-01

    Three complexes with boron trifluoride (BF3) as the Lewis acid and different Lewis bases were synthesized and used as electrolyte additives in Li[Ni1/3Mn1/3Co1/3]O2/graphite and Li[Ni0.42Mn0.42Co0.16]O2/graphite pouch cells. Lewis acid-base adducts with a boron-oxygen (Bsbnd O) bond were trimethyl phosphate boron trifluoride (TMP-BF) and triphenyl phosphine oxide boron trifluoride (TPPO-BF). These were compared to pyridine boron trifluoride (PBF) which has a boron-nitrogen (Bsbnd N) bond. The experimental results showed that cells with PBF had the least voltage drop during storage at 4.2 V, 4.4 V and 4.7 V at 40 °C and the best capacity retention during long-term cycling at 55 °C compared to cells with the other additives. Charge-hold-discharge cycling combined with simultaneous electrochemical impedance spectroscopy measurements showed that impedance growth in TMP-BF and TPPO-BF containing cells was faster than cells containing 2%PBF, suggesting that PBF is useful for impedance control at high voltages (>4.4 V). XPS analysis of the SEI films highlighted a specific reactivity of the PBF-derived SEI species that apparently hinders the degradation of both LiPF6 and solvent during formation and charge-hold-discharge cycling. The modified SEI films may explain the improved impedance, the smaller voltage drop during storage and the improved capacity retention during cycling of cells containing the PBF additive.

  12. Observation of an Acryloyl–Thiamin Diphosphate Adduct in the First Step of Clavulanic Acid Biosynthesis

    Science.gov (United States)

    Merski, Matthew

    2011-01-01

    The first committed biosynthetic step toward clavulanic acid, the clinically-important β-lactamase inhibitor, is catalyzed by the thiamin diphosphate (ThDP)-dependent enzyme N2-(2-carboxyethyl)arginine synthase (CEAS). This protein carries out a unique reaction among ThDP-dependent processes in which a C–N bond is formed, and an electrophilic acryloyl–thiazolium intermediate of ThDP is proposed to be involved, unlike the nucleophilic enamine species typically generated by this class of enzymes. Here we present evidence for the existence of the putative acryloyl adduct, and report the unexpected observation of a long-wavelength chromophore (λ = 433 nm), which we attribute to this enzyme bound species. Chemical models were synthesized that both confirm its expected absorption (λ = 310–320 nm), and exclude self-condensation and intramolecular imine formation with the cofactor as its cause. Circular dichroism experiments and others discount charge transfer as a likely explanation for the ~120 nm red shift of the chromophore (~25 kcal). Examples are well-known of charged molecules that exhibit significantly red-shifted UV-visible spectra compared to their neutral forms as, for example, polyene cations and dyes such as indigo and the cyanines. Rhodopsin is the classic biochemical example where the protein (opsin)-bound protonated Schiff base of retinal displays a remarkable range of red-shifted absorptions modulated by the protein environment. Similar tuning of the chromophoric behavior of the enzyme-bound CEAS acryloyl•ThDP species may be occurring. PMID:18052280

  13. Dose-dependent reduction of 3,2'-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib

    International Nuclear Information System (INIS)

    Colon cancer is second leading cause of cancer-related deaths in Western countries. Diet and smoking, which contain aromatic and heterocyclic amines, are major risk factors for colon cancer. Colorectal cancers have a natural history of long latency and therefore provide ample opportunities for effective chemoprevention. 3,2'-Dimethyl-4-aminobiphenyl (DMABP) is an experimental aromatic amine that causes cancer in rat colon and serves as an experimental model for arylamine and heterocyclic amine mutagens derived from diet and smoking. In this study, we investigated the effects of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor on DMABP-induced DNA adduct formation in rat liver and colon. Male F-344 rats (5-week old) were provided free access to modified AIN-76A rat chow containing 0 (control), 500, 1000, or 1500 ppm celecoxib. Two weeks later, the rats received a subcutaneous injection of 100 mg/kg DMABP in peanut oil. Two days after DMABP treatment, the rats were killed and DMABP-derived adducts were analyzed in colon and liver DNA by butanol extraction-mediated 32P-postlabeling. Two major DNA adducts, identified as dG-C8-DMABP and dG-N2-DMABP, were detected in liver and colon of rats treated with DMABP. These DNA adducts were diminished approximately 35-40% with 500 ppm and 65-70% with 1,000 ppm celecoxib. In the colon, no further decline in DNA adducts was observed at 1500 ppm. The same DMABP-DNA adducts also were detected in the liver and were also diminished by celecoxib treatment. The reduction in DMABP-DNA adduct levels in celecoxib-treated animals provides further support for celecoxib as a chemopreventive agent for colorectal cancer

  14. Noncovalent interactions of a benzo[a]pyrene diol epoxide with DNA base pairs: insight into the formation of adducts of (+)-BaP DE-2 with DNA.

    Science.gov (United States)

    Hargis, Jacqueline C; Schaefer, Henry F; Houk, K N; Wheeler, Steven E

    2010-02-01

    Noncovalent complexes of a tumorigenic benzo[a]pyrene diol epoxide with the guanine-cytosine (GC) and adenine-thymine (AT) base pairs have been examined computationally. (+)-BaP DE-2 forms covalent adducts with DNA via nucleophilic attack on the (+)-BaP DE-2 epoxide. Computational results predict five thermodynamically accessible complexes of AT with (+)-BaP DE-2 that are compatible with intact DNA. Among these, two are expected to lead to adenine adducts. In the lowest energy AT...(+)-BaP DE-2 complex, which has a gas-phase interaction energy of -20.9 kcal mol(-1), the exocyclic NH(2) of adenine is positioned for backside epoxide attack and formation of a trans adduct. The most energetically favorable complex leading to formation of a cis ring-opened adduct lies only 0.6 kcal mol(-1) higher in energy. For GC...(+)-BaP DE-2, there are only two thermodynamically accessible complexes. The higher-lying complex, bound in the gas phase by 24.4 kcal mol(-1) relative to separated GC and (+)-BaP DE-2, would lead to a trans ring-opened N(2)-guanine adduct. In the global minimum energy GC...(+)-BaP DE-2 complex, bound by 27.3 kcal mol(-1), the exocyclic NH(2) group of cytosine is positioned for cis epoxide addition. However, adducts of (+)-BaP DE-2 with cytosine are rarely observed experimentally. The paucity of cytosine adducts, despite the predicted thermodynamic stability of this GC...(+)-BaP DE-2 complex, is attributed to the electrostatic destabilization of the benzylic cation intermediate thought to precede cis addition.

  15. Acetylator genotype-dependent formation of 2-aminofluorene-hemoglobin adducts in rapid and slow acetylator Syrian hamsters congenic at the NAT2 locus.

    Science.gov (United States)

    Feng, Y; Rustan, T D; Ferguson, R J; Doll, M A; Hein, D W

    1994-01-01

    Arylamine-hemoglobin adducts are a valuable dosimeter for assessing arylamine exposures and carcinogenic risk. The effects of age, sex, time-course, dose, and acetylator genotype on levels of 2-aminofluorene-hemoglobin adducts were investigated in homozygous rapid (Bio. 82.73/H-Patr) and slow (Bio. 82.73/H-Pats) acetylator hamsters congenic at the polymorphic (NAT2) acetylator locus. Following administration of a single ip dose of [3H]2-aminofluorene, peak 2-aminofluorene-hemoglobin adduct levels were achieved at 12-18 hr and retained a plateau up to 72 hr postinjection in both rapid and slow acetylator congenic hamsters. 2-Aminofluorene-hemoglobin adduct levels did not differ significantly between young (5-6 weeks) and old (32-49 weeks) hamsters or between male and female hamsters within either acetylator genotype. 2-Aminofluorene-hemoglobin adduct levels increased in a dose-dependent manner (r = 0.95, p = 0.0001) and were consistently higher in slow versus rapid acetylator congenic hamsters in studies of both time-course and dose-effect. The magnitude of the acetylator genotype-dependent difference was a function of dose; 2-aminofluorene-hemoglobin adduct levels were 1.5-fold higher in slow acetylator congenic hamsters following a 60 mg/kg 2-aminofluorene dose (p = 0.0013) but 2-fold higher following a 100 mg/kg 2-aminofluorene dose (p < 0.0001). These results show a specific and significant role for NAT2 acetylator genotype in formation of arylamine-hemoglobin adducts, which may reflect the relationship between acetylator genotype and the incidence of different cancers from arylamine exposures. PMID:8291051

  16. An integrated QSAR-PBK/D modelling approach for predicting detoxification and DNA adduct formation of 18 acyclic food-borne α,β-unsaturated aldehydes

    International Nuclear Information System (INIS)

    Acyclic α,β-unsaturated aldehydes present in food raise a concern because the α,β-unsaturated aldehyde moiety is considered a structural alert for genotoxicity. However, controversy remains on whether in vivo at realistic dietary exposure DNA adduct formation is significant. The aim of the present study was to develop physiologically based kinetic/dynamic (PBK/D) models to examine dose-dependent detoxification and DNA adduct formation of a group of 18 food-borne acyclic α,β-unsaturated aldehydes without 2- or 3-alkylation, and with no more than one conjugated double bond. Parameters for the PBK/D models were obtained using quantitative structure–activity relationships (QSARs) defined with a training set of six selected aldehydes. Using the QSARs, PBK/D models for the other 12 aldehydes were defined. Results revealed that DNA adduct formation in the liver increases with decreasing bulkiness of the molecule especially due to less efficient detoxification. 2-Propenal (acrolein) was identified to induce the highest DNA adduct levels. At realistic dietary intake, the predicted DNA adduct levels for all aldehydes were two orders of magnitude lower than endogenous background levels observed in disease free human liver, suggesting that for all 18 aldehydes DNA adduct formation is negligible at the relevant levels of dietary intake. The present study provides a proof of principle for the use of QSAR-based PBK/D modelling to facilitate group evaluations and read-across in risk assessment. - Highlights: • Physiologically based in silico models were made for 18 α,β-unsaturated aldehydes. • Kinetic parameters were determined by in vitro incubations and a QSAR approach. • DNA adduct formation was negligible at levels relevant for dietary intake. • The use of QSAR-based PBK/D modelling facilitates group evaluations and read-across

  17. Non-covalent C-Cl…π interaction in acetylene-carbon tetrachloride adducts: Matrix isolation infrared and ab initio computational studies

    Science.gov (United States)

    Ramanathan, N.; Sundararajan, K.; Vidya, K.; Jemmis, Eluvathingal D.

    2016-03-01

    Non-covalent halogen-bonding interactions between π cloud of acetylene (C2H2) and chlorine atom of carbon tetrachloride (CCl4) have been investigated using matrix isolation infrared spectroscopy and quantum chemical computations. The structure and the energies of the 1:1 C2H2-CCl4 adducts were computed at the B3LYP, MP2 and M05-2X levels of theory using 6-311 ++G(d,p) basis set. The computations indicated two minima for the 1:1 C2H2-CCl4 adducts; with the C-Cl…π adduct being the global minimum, where π cloud of C2H2 is the electron donor. The second minimum corresponded to a C-H…Cl adduct, in which C2H2 is the proton donor. The interaction energies for the adducts A and B were found to be nearly identical. Experimentally, both C-Cl…π and C-H…Cl adducts were generated in Ar and N2 matrixes and characterized using infrared spectroscopy. This is the first report on halogen bonded adduct, stabilized through C-Cl…π interaction being identified at low temperatures using matrix isolation infrared spectroscopy. Atoms in Molecules (AIM) and Natural Bond Orbital (NBO) analyses were performed to support the experimental results. The structures of 2:1 ((C2H2)2-CCl4) and 1:2 (C2H2-(CCl4)2) multimers and their identification in the low temperature matrixes were also discussed.

  18. An integrated QSAR-PBK/D modelling approach for predicting detoxification and DNA adduct formation of 18 acyclic food-borne α,β-unsaturated aldehydes

    Energy Technology Data Exchange (ETDEWEB)

    Kiwamoto, R., E-mail: reiko.kiwamoto@wur.nl; Spenkelink, A.; Rietjens, I.M.C.M.; Punt, A.

    2015-01-01

    Acyclic α,β-unsaturated aldehydes present in food raise a concern because the α,β-unsaturated aldehyde moiety is considered a structural alert for genotoxicity. However, controversy remains on whether in vivo at realistic dietary exposure DNA adduct formation is significant. The aim of the present study was to develop physiologically based kinetic/dynamic (PBK/D) models to examine dose-dependent detoxification and DNA adduct formation of a group of 18 food-borne acyclic α,β-unsaturated aldehydes without 2- or 3-alkylation, and with no more than one conjugated double bond. Parameters for the PBK/D models were obtained using quantitative structure–activity relationships (QSARs) defined with a training set of six selected aldehydes. Using the QSARs, PBK/D models for the other 12 aldehydes were defined. Results revealed that DNA adduct formation in the liver increases with decreasing bulkiness of the molecule especially due to less efficient detoxification. 2-Propenal (acrolein) was identified to induce the highest DNA adduct levels. At realistic dietary intake, the predicted DNA adduct levels for all aldehydes were two orders of magnitude lower than endogenous background levels observed in disease free human liver, suggesting that for all 18 aldehydes DNA adduct formation is negligible at the relevant levels of dietary intake. The present study provides a proof of principle for the use of QSAR-based PBK/D modelling to facilitate group evaluations and read-across in risk assessment. - Highlights: • Physiologically based in silico models were made for 18 α,β-unsaturated aldehydes. • Kinetic parameters were determined by in vitro incubations and a QSAR approach. • DNA adduct formation was negligible at levels relevant for dietary intake. • The use of QSAR-based PBK/D modelling facilitates group evaluations and read-across.

  19. Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a case-control study using a structural equation modeling.

    Directory of Open Access Journals (Sweden)

    Stefano Porru

    Full Text Available DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs and polycyclic aromatic hydrocarbons (PAHs. No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028, whereas XRCC1 Arg 399 (p<0.006 was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001, coffee (p<0.001, cumulative AAs exposure (p = 0.041 and MnSOD (p = 0.009 and a decreased risk by MPO (p<0.008 were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different

  20. Single-stranded oligonucleotide adducts formed by Pt complexes favoring left-handed base canting: steric effect of flanking residues and relevance to DNA adducts formed by Pt anticancer drugs.

    Science.gov (United States)

    Saad, Jamil S; Marzilli, Patricia A; Intini, Francesco P; Natile, Giovanni; Marzilli, Luigi G

    2011-09-01

    Platinum anticancer drug binding to DNA creates large distortions in the cross-link (G*G*) and the adjacent XG* base pair (bp) steps (G* = N7-platinated G). These distortions, which are responsible for anticancer activity, depend on features of the duplex (e.g., base pairing) and of the cross-link moiety (e.g., the position and canting of the G* bases). The duplex structure stabilizes the head-to-head (HH) over the head-to-tail (HT) orientation and right-handed (R) over left-handed (L) canting of the G* bases. To provide fundamental chemical information relevant to the assessment of such duplex effects, we examine (S,R,R,S)-BipPt(oligo) adducts (Bip = 2,2'-bipiperidine with S,R,R,S chiral centers at the N, C, C, and N chelate ring atoms, respectively; oligo = d(G*pG*) with 3'- and/or 5'-substituents). The moderately bulky (S,R,R,S)-Bip ligand favors L canting and slows rotation about the Pt-G* bonds, and the (S,R,R,S)-BipPt(oligo) models provide more useful data than do dynamic models derived from active Pt drugs. All 5'-substituents in (S,R,R,S)-BipPt(oligo) adducts favor the normal HH conformer (∼97%) by destabilizing the HT conformer through clashes with the 3'-G* residue rather than through favorable H-bonding interactions with the carrier ligand in the HH conformer. For all (S,R,R,S)-BipPt(oligo) adducts, the S pucker of the 5'-X residue is retained. For these adducts, a 5'-substituent had only modest effects on the degree of L canting for the (S,R,R,S)-BipPt(oligo) HH conformer. This small flanking 5'-substituent effect on an L-canted HH conformer contrasts with the significant decrease in the degree of R canting previously observed for flanking 5'-substituents in the R-canted (R,S,S,R)-BipPt(oligo) analogues. The present data support our earlier hypothesis that the distortion distinctive to the XG* bp step (S to N pucker change and movement of the X residue) is required for normal stacking and X·X' WC H bonding and to prevent XG* residue clashes.

  1. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  2. Metabolomic profiling unravels DNA adducts in human breast that are formed from peroxidase mediated activation of estrogens to quinone methides.

    Directory of Open Access Journals (Sweden)

    Nilesh W Gaikwad

    Full Text Available Currently there are three major hypotheses that have been proposed for estrogen induced carcinogenicity, however exact etiology remains unknown. Based on the chemical logic, studies were undertaken to investigate if estrogens could generate quinone methides in an oxidative environment which then could cause DNA damage in humans. In presence of MnO2 estrogens were oxidized to quinone methides. Surprisingly quinone methides were found to be stable with t1/2 of 20.8 and 4.5 min respectively. Incubation of estrogens with lactoperoxidase (LPO and H2O2 resulted in formation of respective quinone methides (E1(E2-QM. Subsequent addition of adenine to the assay mixture lead to trapping of E1(E2-QM, resulting in formation of adenine adducts of estrogens, E1(E2-9-N-Ade. Targeted ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS based metabolomic analysis of the breast tissue extracts showed the presence of adenine adducts of estrogens, E1(E2-9-N-Ade, along with other estrogen related metabolites. Identity of E1(E2-N-Ade in LPO assay extracts and breast tissue extracts were confirmed by comparing them to pure synthesized E1(E2-9-N-Ade standards. From these results, it is evident that peroxidase enzymes or peroxidase-like activity in human breast tissue could oxidize estrogens to electrophilic and stable quinone methides in a single step that covalently bind to DNA to form adducts. The error prone repair of the damaged DNA can result in mutation of critical genes and subsequently cancer. This article reports evidence for hitherto unknown estrogen metabolic pathway in human breast, catalyzed by peroxidase, which could initiate cancer.

  3. Estimating the value of the metal-ligand bond dissociation enthalpy (M-L for adducts using empirical equations supported by TG data

    Directory of Open Access Journals (Sweden)

    Farias Robson Fernandes

    1999-01-01

    Full Text Available In this work is presented and tested (for 106 adducts, mainly of the zinc group halides two empirical equations supported in TG data to estimate the value of the metal-ligand bond dissociation enthalpy for adducts: (M-O = t i / g if t i < 420 K and (M-O = (t i / g - 7,75 . 10-2 . t i if t i > 420 K. In this empirical equations, t i is the thermodynamic temperature of the beginning of the thermal decomposition of the adduct, as determined by thermogravimetry, andg is a constant factor that is function of the metal halide considered and of the number of ligands, but is not dependant of the ligand itself. To half of the tested adducts the difference between experimental and calculated values was less than 5%. To about 80% of the tested adducts, the difference between the experimental (calorimetric and the calculated (using the proposed equations values are less than 15%.

  4. The role of reactive oxygen species (ROS and cytochrome P-450 2E1 in the generation of carcinogenic etheno-DNA adducts

    Directory of Open Access Journals (Sweden)

    Kirsten Linhart

    2014-01-01

    Full Text Available Exocyclic etheno-DNA adducts are mutagenic and carcinogenic and are formed by the reaction of lipidperoxidation (LPO products such as 4-hydoxynonenal or malondialdehyde with DNA bases. LPO products are generated either via inflammation driven oxidative stress or via the induction of cytochrome P-450 2E1 (CYP2E1. In the liver CYP2E1 is induced by various compounds including free fatty acids, acetone and ethanol. Increased levels of CYP2E1 and thus, oxidative stress are observed in the liver of patients with non-alcoholic steatohepatitis (NASH as well as in the chronic alcoholic. In addition, chronic ethanol ingestion also increases CYP2E1 in the mucosa of the oesophagus and colon. In all these tissues CYP2E1 correlates significantly with the levels of carcinogenic etheno-DNA adducts. In contrast, in patients with non-alcoholic steatohepatitis (NASH hepatic etheno-DNA adducts do not correlate with CYP2E1 indicating that in NASH etheno-DNA adducts formation is predominately driven by inflammation rather than by CYP2E1 induction. Since etheno-DNA adducts are strong mutagens producing various types of base pair substitution mutations as well as other types of genetic damage, it is strongly believed that they are involved in ethanol mediated carcinogenesis primarily driven by the induction of CYP2E1.

  5. Variation in PAH-related DNA adduct levels among non-smokers: the role of multiple genetic polymorphisms and nucleotide excision repair phenotype.

    Science.gov (United States)

    Etemadi, Arash; Islami, Farhad; Phillips, David H; Godschalk, Roger; Golozar, Asieh; Kamangar, Farin; Malekshah, Akbar Fazel-Tabar; Pourshams, Akram; Elahi, Seerat; Ghojaghi, Farhad; Strickland, Paul T; Taylor, Philip R; Boffetta, Paolo; Abnet, Christian C; Dawsey, Sanford M; Malekzadeh, Reza; van Schooten, Frederik J

    2013-06-15

    Polycyclic aromatic hydrocarbons (PAHs) likely play a role in many cancers even in never-smokers. We tried to find a model to explain the relationship between variation in PAH-related DNA adduct levels among people with similar exposures, multiple genetic polymorphisms in genes related to metabolic and repair pathways, and nucleotide excision repair (NER) capacity. In 111 randomly selected female never-smokers from the Golestan Cohort Study in Iran, we evaluated 21 SNPs in 14 genes related to xenobiotic metabolism and 12 SNPs in eight DNA repair genes. NER capacity was evaluated by a modified comet assay, and aromatic DNA adduct levels were measured in blood by32P-postlabeling. Multivariable regression models were compared by Akaike's information criterion (AIC). Aromatic DNA adduct levels ranged between 1.7 and 18.6 per 10(8) nucleotides (mean: 5.8 ± 3.1). DNA adduct level was significantly lower in homozygotes for NAT2 slow alleles and ERCC5 non-risk-allele genotype, and was higher in the MPO homozygote risk-allele genotype. The sum of risk alleles in these genes significantly correlated with the log-adduct level (r = 0.4, p studies, with large inter-individual variation which could best be explained by a combination of Phase I genes and NER capacity. PMID:23175176

  6. DNA polymerase eta participates in the mutagenic bypass of adducts induced by benzo[a]pyrene diol epoxide in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Alden C Klarer

    Full Text Available Y-family DNA-polymerases have larger active sites that can accommodate bulky DNA adducts allowing them to bypass these lesions during replication. One member, polymerase eta (pol eta, is specialized for the bypass of UV-induced thymidine-thymidine dimers, correctly inserting two adenines. Loss of pol eta function is the molecular basis for xeroderma pigmentosum (XP variant where the accumulation of mutations results in a dramatic increase in UV-induced skin cancers. Less is known about the role of pol eta in the bypass of other DNA adducts. A commonly encountered DNA adduct is that caused by benzo[a]pyrene diol epoxide (BPDE, the ultimate carcinogenic metabolite of the environmental chemical benzo[a]pyrene. Here, treatment of pol eta-deficient fibroblasts from humans and mice with BPDE resulted in a significant decrease in Hprt gene mutations. These studies in mammalian cells support a number of in vitro reports that purified pol eta has error-prone activity on plasmids with site-directed BPDE adducts. Sequencing the Hprt gene from this work shows that the majority of mutations are G>T transversions. These data suggest that pol eta has error-prone activity when bypassing BPDE-adducts. Understanding the basis of environmental carcinogen-derived mutations may enable prevention strategies to reduce such mutations with the intent to reduce the number of environmentally relevant cancers.

  7. Evaluation of a patient-specific cost function to predict the influence of foot path on the knee adduction torque during gait.

    Science.gov (United States)

    Fregly, Benjamin J; Reinbolt, Jeffery A; Chmielewski, Terese L

    2008-02-01

    A large external knee adduction torque during gait has been correlated with the progression of knee osteoarthritis (OA). Though foot path changes (e.g. toeing out) can reduce the adduction torque, no method currently exists to predict whether an optimal foot path exists for a specific patient. This study evaluates a patient-specific optimization cost function to predict how foot path changes influence both adduction torque peaks. Video motion and ground reaction data were collected from a patient with knee OA performing normal, toe out, and wide stance gait. Joint and inertial parameters in a dynamic, 27 degree-of-freedom, full-body gait model were calibrated to the patient's normal gait data. The model was then used in gait optimizations that predicted how the patient's adduction torque peaks would change due to changes in foot path. The cost function tracked the patient's normal gait data using weight factors calibrated to toe out gait and tested using wide stance gait. For both gait motions, the same cost function weights predicted the change in both adduction torque peaks to within 7% error. With further development, this approach may eventually permit the design of patient-specific rehabilitation procedures such as an optimal foot path for patients with knee OA.

  8. Triphenyl phosphine adducts of platinum(IV) and palladium(II) dithiocarbamates complexes: a spectral and in vitro study

    Science.gov (United States)

    Manav, N.; Mishra, A. K.; Kaushik, N. K.

    2004-11-01

    Triphenyl phosphine adducts of dithiocarbamate complexes of platinum(IV) and palladium(II) of the type [Pt(L) 2PPh 3Cl 2] and [Pd(L) 2PPh 3] [L: morpholine dithiocarbamate (L 1), aniline dithiocarbamate (L 2) and N-(methyl, cyclohexyl) dithiocarbamate (L 3)] were prepared and characterized by elemental analysis, electronic, IR, 1H NMR and 13C NMR spectral studies. Thermal studies of the complexes were carried out. In vitro antitumor activity has been screened towards human adenocarcinoma cell lines and showed significant inhibition even at very low concentration.

  9. Mechanism of Translesion Synthesis Past an Equine Estrogen-DNA Adduct by Y-Family DNA Polymerases

    OpenAIRE

    Yasui, Manabu; Suzuki, Naomi; Liu, Xiaoping; Kim, Yoshinori Okamoto Sung Yeon; Laxmi, Y. R. Santosh; Shibutani, Shinya

    2007-01-01

    4-Hydroxyequilenin (4-OHEN)-dC is a major, potentially mutagenic DNA adduct induced by equine estrogens used for hormone replacement therapy. To study the miscoding property of 4-OHEN-dC and the involvement of Y-family human DNA polymerases (pols) η, κ and ι in that process, we incorporated 4-OHEN-dC into oligodeoxynucleotides and used them as templates in primer extension reactions catalyzed by pol η, κ and ι. Pol η inserted dAMP opposite 4-OHEN-dC, accompanied by lesser amounts of dCMP and ...

  10. DNA adduct formation by 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) in rat colon

    OpenAIRE

    Lin, Chun-xing; Mondan, Yasumasa; Umemoto, Atsushi

    2001-01-01

    A food-born carcinogen, 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) induces cancer in the rat colon. The mechanism for colonic DNA adduct formation leading to cancer by IQ was studied using a colostomized F344 rat model. In this model, the transverse colon of the rat was colostomized, which produced a fecal stream-positive proximal colon and a negative distal colon were produced. When IQ (50 mg/kg) was administered into the distal colon of the colostomized rats (n=5), the ratio of the DNA ...

  11. SYNTHESIS AND INFRARED STUDY OF POLYNUCLEAR DABCO ADDUCTS WITH NiCl2 AND CuCl2

    Directory of Open Access Journals (Sweden)

    MAMADOU NDIAYE

    2015-02-01

    Full Text Available The proposed structures for the studied adducts - DABCO.3[NiCl2·2H2O].EtOH and 2DABCO.3CuCl2.4EtOH or 3DABCO. 4CuCl2.5EtOH are discrete with two or three metallic components, the environments around the Nickel centres being octahedral or square planar, while being octahedral , linear or a square based prism around the Copper centres, the DABCO behaving as a monodentate or bridging bidentate ligand or being lattice. Extra intermolecular interactions via hydrogen bonds when considered, may lead to supramolecular architectures.

  12. ()-Garner aldehyde derived Baylis-Hillman adduct: A potential substrate for the synthesis of D- phytosphinosine analogue

    Indian Academy of Sciences (India)

    Gulshan Kumar; Amanpreet Kaur; Vasundhara Singh

    2014-11-01

    A short, facile and efficient synthesis of D-lyxo-phytosphingosine analogue has been achieved. The key steps involved are the Baylis-Hillman reaction of (S)-Garner aldehyde with methyl acrylate to obtain the corresponding adduct as the potential substrate, to which was added decylmagnesium bromide to obtain the E-trisubstituted alkene followed by OsO4/NMO mediated dihydroxylation gave the desired D-lyxophytosphingosine analogue intermediate diol which on acid hydrolysis resulted in the formation of the target molecule in good yield.

  13. Quantification of Carbohydrates and Related Materials Using Sodium Ion Adducts Produced by Matrix-Assisted Laser Desorption Ionization

    Science.gov (United States)

    Ahn, Sung Hee; Park, Kyung Man; Moon, Jeong Hee; Lee, Seong Hoon; Kim, Myung Soo

    2016-09-01

    The utility of sodium ion adducts produced by matrix-assisted laser desorption ionization for the quantification of analytes with multiple oxygen atoms was evaluated. Uses of homogeneous solid samples and temperature control allowed the acquisition of reproducible spectra. The method resulted in a direct proportionality between the ion abundance ratio I([A + Na]+)/I([M + Na]+) and the analyte concentration, which could be used as a calibration curve. This was demonstrated for carbohydrates, glycans, and polyether diols with dynamic range exceeding three orders of magnitude.

  14. DNA adduct formation and oxidative stress in colon and liver of Big Blue rats after dietary exposure to diesel particles

    DEFF Research Database (Denmark)

    Dybdahl, Marianne; Risom, Lotte; Møller, Peter;

    2003-01-01

    Exposure to diesel exhaust particles (DEP) via the gastrointestinal route may impose risk of cancer in the colon and liver. We investigated the effects of DEP given in the diet to Big Blue rats by quantifying a panel of markers of DNA damage and repair, mutation, oxidative damage to proteins...... in liver accompanied by enhanced vitamin C levels. In plasma, we found no significant effects on oxidative damage to proteins and lipids, antioxidant enzymes or vitamin C levels. Our data indicate that gastrointestinal exposure to DEP induces DNA adducts and oxidative stress resulting in DNA strand breaks...

  15. Rotação do jato em DG tau próximo à região de sua formação: análise comparativa das velocidades radiais simuladas e observadas

    Science.gov (United States)

    Cerqueira, A. H.; de Gouveia dal Pino, E. M.

    2003-08-01

    Os modelos magneto-centrífugos utilizados para explicar a formação dos jatos Herbig-Haro assumem a presença de um disco de acresção em rotação kepleriana na base de lançamento do jato. Neste cenário, o jato transmite a informação da rotação do disco para regiões distantes da fonte central, além da superfície de Alfvén, na região de colimação inicial do jato. Recentemente, Bacciotti et al. (2002, ApJ, 537, L49) obtiveram pela primeira vez uma evidência observacional de rotação em um jato HH, o jato em DG Tau, em regiões próximas da fonte central, compatível (qualitativa e quantitativamente) com o esperado a partir dos modelos magneto-centrífugos para a produção e colimação inicial de jatos HH. No presente trabalho, apresentamos mapas de velocidade radial, obtidos através de simulações numéricas tri-dimensionais SPH, para um jato com características semelhantes ao jato em DG Tau, objetivando uma comparação com os mapas de velocidade radiais obtidos por Bacciotti et al.. Nossos resultados, embora preliminares, indicam que a inclusão de efeitos como a precessão, evidenciada em DG Tau (Dougados et al. 2000, A&A, 357, L61) devem ser levadas em consideração na análise da presença de rotação não só em DG Tau mas em qualquer sistema, com o uso das velocidades radias observadas. A ausência de um grau elevado de simetria axial (quebrada, por exemplo, pela precessão do eixo do jato; ou pela presença de uma superfície interna de trabalho, ou seja, um bow shock interno), implica também em uma maior complexidade nos mapas, com conseqüências relevantes para suas interpretações.

  16. Dynamic topologic analysis of distribution network based on on-line switch and DG states%基于在线开关状态和DG角色的动态配电网拓扑分析

    Institute of Scientific and Technical Information of China (English)

    楼宗明; 章坚民; 庄晓丹; 钟一俊; 张亚东; 陆献传

    2014-01-01

    Under the comprehensive CIM based modeling, a novel topologic method is presented which divides the distribution network into series of topologic islands according to the types of switches and DGs and their operation states in the networks. According to the structure of design state of the distribution network, the static topologic analysis prepares and stores a lots of sub-trees of topologic islands with their own power supply points in one terminal of bi-directional switches or DG as the main power supply source. Based on the real time states of switches and the role of DG, the dynamic topologic analysis makes the logic reasoning to form a dynamic topologic tree of the distribution networks with the quick assembly of suitable sub-tree of topologic islands which can be directly used for further power flow calculation to meet the real time requirement of on-line mathematic operation. Through the comparison of this algorithm and traditional CIM analysis, this paper verifies the efficiency of the algorithm.%采用 CIM 表示法对配电网综合建模,提出一种基于开关类型及状态、DG 角色的配电网拓扑岛分解方法。根据配电网设计态结构,静态拓扑分析准备和储存了大量的以双向开关某一端口和DG为功率注入点的拓扑岛子树。动态拓扑分析基于开关状态、DG 角色,对各种情况进行逻辑判断,并选择已储存的合适的拓扑岛子树的快速组装形成动态拓扑树,该拓扑结构可直接用于后续潮流计算,满足在线运算的实时性。通过该算法与传统CIM分析的比较,验证了算法的高效性。

  17. Biomarkers for Exposure to Ambient Air Pollution - Comparison of Carcinogen-DNA Adduct Levels with Other Exposure Markers and Markers for Oxidative Stress

    DEFF Research Database (Denmark)

    Autrup, Herman; Daneshvar, Bahram; Dragsted, Lars Ove;

    1999-01-01

    Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts....../10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96...... nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative...

  18. Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress

    DEFF Research Database (Denmark)

    Autrup, H; Daneshvar, B; Dragsted, L O;

    1999-01-01

    Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts....../10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96...... nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative...

  19. Biomarkers for exposure to ambient air pollution - Comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress

    DEFF Research Database (Denmark)

    Autrup, Herman; Daneshvar, Bahram; Dragsted, Lars Ove;

    1999-01-01

    Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts....../10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0.......96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/mu g albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative...

  20. SYNTHESIS OF THE FULLY PROTECTED PHOSPHORAMIDITE OF THE BENZENE-DNA ADDUCT, N2- (4-HYDROXYPHENYL)-2'-DEOXYGUANOSINE AND INCORPORATION OF THE LATER INTO DNA OLIGOMERS

    Energy Technology Data Exchange (ETDEWEB)

    Chenna, Ahmed; Gupta, Ramesh C.; Bonala, Radha R.; Johnson, Francis; Huang, Bo

    2008-06-09

    N2-(4-Hydroxyphenyl)-2'-deoxyguanosine-5'-O-DMT-3'-phosphoramidite has been synthesized and used to incorporate the N2-(4-hydroxyphenyl)-2'-dG (N2-4-HOPh-dG) into DNA, using solid-state synthesis technology. The key step to obtaining the xenonucleoside is a palladium (Xantphos-chelated) catalyzed N2-arylation (Buchwald-Hartwig reaction) of a fully protected 2'-deoxyguanosine derivative by 4-isobutyryloxybromobenzene. The reaction proceeded in good yield and the adduct was converted to the required 5'-O-DMT-3'-O-phosphoramidite by standard methods. The latter was used to synthesize oligodeoxynucleotides in which the N2-4-HOPh-dG adduct was incorporated site-specifically. The oligomers were purified by reverse-phase HPLC. Enzymatic hydrolysis and HPLC analysis confirmed the presence of this adduct in the oligomers.