WorldWideScience

Sample records for adduct peak elimination

  1. ANALYSIS OF SULFONATES IN AQUEOUS SAMPLES BY ION-PAIR LC/ESI-MS/MS WITH IN-SOURCE CID FOR ADDUCT PEAK ELIMINATION

    OUYANG,S.; VAIRAVAMURTHY,M.A.

    1999-06-13

    Determination of low-molecular-weight organic sulfonates (e.g. taurine and cysteic acid) in aqueous solutions is important in many applications of biological, environmental and pharmaceutical sciences. These compounds are difficult to be determined by commonly used reversed-phase liquid chromatographic separation combined with UV-Visible detection because of their high solubility and the lack chromophoric moieties. Here the authors report a method combining ion-pair liquid chromatography and electrospray ionization tandem mass spectrometry (IPLC/ESI-MS/MS)for determining sulfonates. The ability of low-molecular-weight sulfonates to form ion-pairs with quaternary ammonium cations in aqueous solutions allowed LC separation with a C{sub 18} column. Detection of the sulfonates was accomplished with ESI-MS that lends a universal mode of mass detection for polar, water soluble compounds. An in-source collision induced dissociation (CID) was applied to eliminate the adduct peaks in mass spectra. Characteristic marker ions showed in the second stage mass spectra lent a method for identifying sulfonates.

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

    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...

  3. The Conjugate Addition- Elimination Reaction of Morita-Baylis-Hillman C- Adducts: A Density Functional Theory Study

    Tan, Davin

    2011-12-01

    The Morita-Baylis-Hillman (MBH) reaction is a very versatile synthetic protocol to synthesize various useful compounds containing several functional groups. MBH acetates and carbonates are highly valued compounds as they have good potential to be precursors for organic synthesis reactions due to their ease of modification and synthesis. This thesis utilizes Density Functional Theory (DFT) calculations to understand the mechanism and selectivity of an unexpected tandem conjugate addition-elimination (CA-E) reaction of allylic alkylated Morita-Baylis-Hillman C- adducts. This synthetic protocol was developed by Prof. Zhi-Yong Jiang and co-workers from Henan University, China. The reaction required the use of sub-stoichiometric amounts of an organic or inorganic Brøndst base as a catalyst and was achieved with excellent yields (96%) in neat conditions. TBD gave the highest yield amongst the organocatalysts and Cs2CO3 gave the highest yield amongst all screened bases. A possible mechanistic pathway was proposed and three different energy profiles were modeled using 1,5,7-triaza-bicyclo-[4.4.0]-dec-5-ene (TBD), Cs2CO3 and CO32- as catalysts. All three models were able to explain the experimental observations, revealing both kinetic and thermodynamic factors influencing the selectivity of the CA-E reaction. CO32- model gave the most promising result, revealing a significant energy difference of 17.9 kcal/mol between the transition states of the two differing pathways and an energy difference of 20.9 kcal/mol between the two possible products. Although TBD modeling did not show significant difference in the transition states of the differing pathways, it revealed an unexpected secondary non-covalent electrostatic interaction, involving the electron deficient C atom of the triaza CN3 moiety of the TBD catalyst and the O atom of a neighboring NO2- group in the intermediate. Subsequent modeling using a similar substrate proved the possibility of this non

  4. Carbanion reactivity, kinetic and equilibrium studies of sigma-adduct formation and elimination in the reactions of 4-nitrobenzofurazan derivatives with nitroalkane anions.

    Asghar, Basim H M; Crampton, Michael R

    2007-05-21

    1H NMR studies are reported of the reactions in [2H(6)]-DMSO of 4-nitrobenzofurazan, 2a, and its 7-chloro- and 7-methoxy-derivatives, 2b and 2c respectively, with anions derived from nitromethane, 3, nitroethane, 4, and 2-nitropropane, 5. The initial reactions result in sigma-adduct formation by carbanion attack at the 5-position of 2a-c and in the case of reaction of 2a with 5 the adduct at the 7-position is also observed. These reactions may be followed by base catalysed elimination of nitrous acid to yield anionic alkene derivatives. Kinetic and equilibrium measurements of these reactions were made spectrophotometrically in methanol. The carbon nucleophilicities of the carbanions decrease in the order 3> 4> 5, as also found in their reactions with benzhydrylium cations, and are much lower than the nucleophilicities of some cyano-substituted carbanions. Comparison with corresponding sigma-adduct forming reactions of 1,3,5-trinitrobenzene, TNB, show that here 2 and TNB have similar electrophilicity, although the value of the intrinsic rate coefficient k(o) = 0.05, for reaction of 2 is rather lower than that, k(o) = 0.20, for the TNB reactions. Literature data suggest that for reaction with a variety of nucleophiles 2 and TNB show similar electrophilicities. Measurements of the rates of elimination of nitrous acid from some 5-adducts in methanol catalysed by methoxide ions are reported. Values of rate constants may be influenced both by steric requirements at the reaction centre and by the electronic effects of the 7-substituent. PMID:17571196

  5. Catalytic diastereoselective tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts by C-C bond cleavage

    Yang, Wenguo

    2012-02-08

    Through the cleavage of the C-C bond, the first catalytic tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts has been presented. Various S N2′-like C-, S-, and P-allylic compounds could be obtained with exclusive E configuration in good to excellent yields. The Michael product could also be easily prepared by tuning the β-C-substituent group of the α-methylene ester under the same reaction conditions. Calculated relative energies of various transition states by DFT methods strongly support the observed chemoselectivity and diastereoselectivity. © 2012 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.

  6. Use of a PBPK model with dose-dependent elimination rates predicts higher peak dioxin exposures than previously estimated

    Emond, C. [NRC, NAS, WA, DC (United States); Michalek, J.E. [Air Force Research Lab., Brooks City-Base, TX (United States); Birnbaum, L.S.; DeVito, M.J. [PKB, ETD, ORD, NHEERL U.S. EPA, RTP, NC (United States)

    2004-09-15

    Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with increased risk for cancer, diabetes and reproductive toxicities in numerous epidemiological studies. Several of these studies base exposure estimates on measurements of blood levels years after the accidental or occupational exposures. Peak exposures have been estimated in these studies assuming a mono or biphasic elimination rate for TCDD, with estimates of half-life ranging from 5 to 12 years. Recent clinical studies suggest that the elimination rate of TCDD is dose dependent. To address this question a physiologically based pharmacokinetic (PBPK) model can be used to predict the concentration of TCDD with a dose-dependent elimination rate. The aims of this study were to validate a dose-dependent elimination rate by using a PBPK model and to adequately predict the concentration of TCDD shortly after the exposure.

  7. Elimination of the artefact peaks in capillary electrophoresis determination of glutamate by using organic solvents in sample preparation.

    Campos, Camila Dalben Madeira; de Campos Braga, Patricia Aparecida; Reyes, Felix Guillermo Reyes; da Silva, José Alberto Fracassi

    2015-11-01

    Focusing on the demand from the food industry for fast and reliable alternative methods to control the quality of food products, we present in this paper a method for amino acid separation and glutamic acid quantification in complex matrices employing capillary electrophoresis with capacitively coupled contactless conductivity detection. We demonstrate by simulation and experimentally the use of organic solvents in sample preparation to prevent peak splitting and increase stacking in capillary electrophoretic separations of amino acids. Additionally, we obtained results for glutamic acid quantification comparable to those obtained via traditional methods used at industrial sites. We tested premium and low-cost samples with large variations in their glutamic acid content, which demonstrated the wide range of applicability of the method presented herein. The results of the proposed capacitively coupled contactless conductivity detection based capillary electrophoresis method agreed with those obtained by an enzymatic detector and ultra high performance liquid chromatography coupled to tandem mass spectrometry, considering a confidence level of 95%. PMID:26332708

  8. Acetaldehyde adducts with hemoglobin.

    Stevens, V.J.; Fantl, W J; Newman, C B; Sims, R V; Cerami, A.; Peterson, C M

    1981-01-01

    Clinical studies on the minor hemoglobins (hemoglobin A1a-c) have suggested that a novel adduct may form in people abusing alcohol. Such patients were found to have an elevated concentration of minor hemoglobins, but normal or subnormal amounts of glycosylated hemoglobin (hemoglobin A1c) as determined by radioimmunoassay, Acetaldehyde, a reactive metabolite of ethanol, was postulated to form adducts with hemoglobin A that change its chromatographic properties. At physiological concentrations,...

  9. MUSIC测向算法的虚假谱峰消除方法研究%Study on Method of Eliminating Spurious Spectral Peak of MUSIC Direction Finding Algorithm

    王仁涛; 李斌; 王毅

    2012-01-01

    在基于均匀线阵的MUSIC测向算法中,单元间距与波长之比大于0.5时,可能会出现虚假谱峰,干扰真实波达方向的判断。现有的一些消除虚假谱峰的方法多适用于主动测向或非均匀阵列,而对被动测向和均匀阵列无法适用。针对这一问题,本文通过分析虚假谱峰的出现原因,提出一种新的通过机械旋转进行虚假谱峰消除的方法——阵列旋转法,并仿真分析验证了该方法的有效性。该方法实现简单,适用范围广,能较好满足实际工程设计需求。%In the MUSIC direction finding algorithm based on uniform linear array, when the ratio of the element spacing to wavelength is more than 0. 5, the spurious spectral peak may occur to interfere direction of real arrival estimation. The available methods of eliminating spurious spectral peak are mainly suitable for active direction find- ing or non-uniform array, not for passive direction finding and uniform array. Aiming at this issue, a novel method of eliminating spurious spectral peak ( array rotating method) by mechanical rotating after analyzing causes for occurrence of spurious spectral peak is presented. The simulated results show effectiveness of this method. The implementation of this method is simply, and it can be widely applied and meet real engineering design requirement.

  10. DNA adducts as molecular dosimeters

    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. Glutathione transferase A4-4 resists adduction by 4-hydroxynonenal.

    Shireman, Laura M; Kripps, Kimberly A; Balogh, Larissa M; Conner, Kip P; Whittington, Dale; Atkins, William M

    2010-12-15

    4-Hydroxy-2-trans-nonenal (HNE) is a lipid peroxidation product that contributes to the pathophysiology of several diseases with components of oxidative stress. The electrophilic nature of HNE results in covalent adduct formation with proteins, fatty acids and DNA. However, it remains unclear whether enzymes that metabolize HNE avoid inactivation by it. Glutathione transferase A4-4 (GST A4-4) plays a significant role in the elimination of HNE by conjugating it with glutathione (GSH), with catalytic activity toward HNE that is dramatically higher than the homologous GST A1-1 or distantly related GSTs. To determine whether enzymes that metabolize HNE resist its covalent adduction, the rates of adduction of these GST isoforms were compared and the functional effects of adduction on catalytic properties were determined. Although GST A4-4 and GST A1-1 have striking structural similarity, GST A4-4 was insensitive to adduction by HNE under conditions that yield modest adduction of GST A1-1 and extensive adduction of GST P1-1. Furthermore, adduction of GST P1-1 by HNE eliminated its activity toward the substrates 1-chloro-2,4-dinitrobenzene (CDNB) and toward HNE itself. HNE effects on GST A4-4 and A1-1 were less significant. The results indicate that enzymes that metabolize HNE may have evolved structurally to resist covalent adduction by it. PMID:20836986

  12. Glutathione transferase A4-4 resists adduction by 4-hydroxynonenal☆

    Shireman, Laura M.; Kripps, Kimberly A.; Balogh, Larissa M.; Conner, Kip P.; Whittington, Dale; Atkins, William M.

    2010-01-01

    4-Hydroxy-2-trans-nonenal (HNE) is a lipid peroxidation product that contributes to the pathophysiology of several diseases with components of oxidative stress. The electrophilic nature of HNE results in covalent adduct formation with proteins, fatty acids and DNA. However, it remains unclear whether enzymes that metabolize HNE avoid inactivation by it. Glutathione transferase A4-4 (GST A4-4) plays a significant role in the elimination of HNE by conjugating it with glutathione (GSH), with catalytic activity toward HNE that is dramatically higher than the homologous GST A1-1 or distantly related GSTs. To determine whether enzymes that metabolize HNE resist its covalent adduction, the rates of adduction of these GST isoforms were compared and the functional effects of adduction on catalytic properties were determined. Although GST A4-4 and GST A1-1 have striking structural similarity, GST A4-4 was insensitive to adduction by HNE under conditions that yield modest adduction of GST A1-1 and extensive adduction of GST P1-1. Furthermore, adduction of GST P1-1 by HNE eliminated its activity toward the substrates 1-chloro- 2,4-dinitrobenzene (CDNB) and toward HNE itself. HNE effects on GST A4-4 and A1-1 were less significant. The results indicate that enzymes that metabolize HNE may have evolved structurally to resist covalent adduction by it. PMID:20836986

  13. Eliminating armaments

    The end of Cold War induced optimistic projections concerning disarmament, elimination of nuclear weapons, elimination of massive inequities - poverty, hatred, racism. All these goals should be achieved simultaneously, but little has been achieved so far

  14. The formation of covalent adducts between benzo[a]pyrenediol epoxide and RNA: Structural analysis by mass spectrometry

    Racemic 7-r,8-t-dihydroxy-9-t,10-t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene was reacted with yeast RNA. Modified nucleosides were isolated and resolved by high-performance liquid chromatography; nine adduct peaks were collected for analysis. The bases in these adducts were identified by comparing their retention time with those of adducts from poly(G), poly(A), and poly(C). These samples gave two major and two minor Guo adducts, four major Ado adducts, and at least four Cyd adducts. The relative efficiencies of adduct formation with the polyribionucleotides were poly(G) > yeast RNA > poly(A) > poly(C). Fluorescence measurements show that emission from Guo adducts is strongly quenched relative to that from Ado adducts. Liquid secondary ion mass spectrometry (LSIMS) of underivatized samples and electron-impact mass spectrometry (EIMS) of permethyl derivatives were used to confirm the base identities and establish the alkylation sites of the RNA adducts. Unique nitrogen-containing hydrocarbon fragments that were observed with all samples by EIMS establish that in each adduct analyzed the C-10 position of the hydrocarbon is linked to the exocyclic amino group of the base. This suggested that the multiple adducts formed with each base are diastereomers derived from cis/trans epoxide ring opening of the (+) and (-) enantiomers of the carcinogen. Major fragmentation pathways resulted in formation of nucleoside, base, ribose, hydrocarbon, and base-hydrocarbon ions

  15. Ultrasensitive isolation, identification and quantification of DNA-protein adducts by ELISA-based RADAR assay.

    Kiianitsa, Kostantin; Maizels, Nancy

    2014-07-01

    Enzymes that form transient DNA-protein covalent complexes are targets for several potent classes of drugs used to treat infectious disease and cancer, making it important to establish robust and rapid procedures for analysis of these complexes. We report a method for isolation of DNA-protein adducts and their identification and quantification, using techniques compatible with high-throughput screening. This method is based on the RADAR assay for DNA adducts that we previously developed (Kiianitsa and Maizels (2013) A rapid and sensitive assay for DNA-protein covalent complexes in living cells. Nucleic Acids Res., 41:e104), but incorporates three key new steps of broad applicability. (i) Silica-assisted ethanol/isopropanol precipitation ensures reproducible and efficient recovery of DNA and DNA-protein adducts at low centrifugal forces, enabling cell culture and DNA precipitation to be carried out in a single microtiter plate. (ii) Rigorous purification of DNA-protein adducts by a procedure that eliminates free proteins and free nucleic acids, generating samples suitable for detection of novel protein adducts (e.g. by mass spectroscopy). (iii) Identification and quantification of DNA-protein adducts by direct ELISA assay. The ELISA-based RADAR assay can detect Top1-DNA and Top2a-DNA adducts in human cells, and gyrase-DNA adducts in Escherichia coli. This approach will be useful for discovery and characterization of new drugs to treat infectious disease and cancer, and for development of companion diagnostics assays for individualized medicine. PMID:24914050

  16. Hafnium tetrachloride adducts with aminophenols

    Adducts of hafnium tetrachloride with aminophenols of a general composition of HfCl4x4L have been obtained by addition of ethyl acetate solutions of hafnium tetrachloride with solutions of o-aminophenol in dioxan, m-aminophenol in ethyl acetate and n-aminophenol in dioxan at a ratio Hf/L=1/2. In the investigated adducts, aminophenols are connected to hafnium both through an oxygen atom and a nitrogen atom, the latter's coordination being preferable. A thermal investigation of synthesized complexes has determined the quantity of heat evolving on addition of 4 moles of aminophenol to 1 mole of crystalline hafnium tetrachloride

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

    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

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

    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 ...

  19. DNA adducts-chemical addons

    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.

  20. DNA adducts-chemical addons.

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

    2015-04-01

    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

  1. The boron trifluoride nitromethane adduct

    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.

  2. 'Peak oil' or 'peak demand'?

    This article reports a workshop which addressed several energy issues like the objectives and constraints of energy mix scenarios, the differences between the approaches in different countries, the cost of new technologies implemented for this purposes, how these technologies will be developed and marketed, which will be the environmental and societal acceptability of these technical choices. Different aspects and issues have been more precisely presented and discussed: the peak oil, development of shale gases and their cost (will non conventional hydrocarbons modify the peak oil and be socially accepted?), energy efficiency (its benefits, its reality in France and other countries, its position in front of the challenge of energy transition), and strategies in the transport sector (challenges for mobility, evolution towards a model of sustainable mobility)

  3. Formation of adduct of cerium (4) thenoyltrifluoroacetonate

    Adduct formation of thenoyltrifluoroacetonate of Ce(4) [Ce(TTFA)4] with seven nitrogen- and oxygen-containing donor additional ligands is studied using the methods of IR-spectroscopy, derivatography, X-ray phase analysis. The presence of formation of Ce(TTFA)4 adducts with phosphorus-containing additional ligands tributyl phosphate (TBP), trioctylphosphine oxide (TOPO), triphenylphosphine oxide (TPPO); α, α'-dipyridyl (Dipy) and o-phenanthroline (Phen) is established. The adduct Ce(TTFA)4 stable to reduction is formed with Dipy, and in the case of Phen, TBP, TOPO, TPPO in the process of adduct formation the reduction of Ce(4) to Ce(3) takes place

  4. DNA adducts-chemical addons

    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...

  5. Bilateral failure of adduction following orbital decompression.

    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.

  6. Hydrogen abstraction reactions by amide electron adducts

    Electron reactions with a number of peptide model compounds (amides and N-acetylamino acids) in aqueous glasses at low temperature have been investigated using ESR spectroscopy. The radicals produced by electron attachment to amides, RC(OD)NDR', are found to act as hydrogen abstracting agents. For example, the propionamide electron adduct is found to abstract from its parent propionamide. Electron adducts of other amides investigated show similar behavior except for acetamide electron adduct which does not abstract from its parent compound, but does abstract from other amides. The tendency toward abstraction for amide electron adducts are compared to electron adducts of several carboxylic acids, ketones, aldehydes and esters. The comparison suggests the hydrogen abstraction tendency of the various deuterated electron adducts (DEAs) to be in the following order: aldehyde DEA > acid DEA = approximately ester DEA > ketone DEA > amide DEA. In basic glasses the hydrogen abstraction ability of the amide electron adducts is maintained until the concentration of base is increased sufficiently to convert the DEA to its anionic form, RC(O-)ND2. In this form the hydrogen abstracting ability of the radical is greatly diminished. Similar results were found for the ester and carboxylic acid DEA's tested. (author)

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

    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.

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

    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. The authors 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. (authors)

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

    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

  10. 32P-adduct assay: Comparative recoveries of structurally diverse DNA adducts in the various enhancement procedures

    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

  11. Glutathione transferase A4-4 resists adduction by 4-hydroxynonenal☆

    Shireman, Laura M.; Kripps, Kimberly A.; Balogh, Larissa M.; Conner, Kip P.; Whittington, Dale; Atkins, William M.

    2010-01-01

    4-Hydroxy-2-trans-nonenal (HNE) is a lipid peroxidation product that contributes to the pathophysiology of several diseases with components of oxidative stress. The electrophilic nature of HNE results in covalent adduct formation with proteins, fatty acids and DNA. However, it remains unclear whether enzymes that metabolize HNE avoid inactivation by it. Glutathione transferase A4-4 (GST A4-4) plays a significant role in the elimination of HNE by conjugating it with glutathione (GSH), with cat...

  12. Sperm DNA oxidative damage and DNA adducts.

    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

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

    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

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

    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....

  15. How Ordinary Elimination Became Gaussian Elimination

    Grcar, Joseph F

    2009-01-01

    Newton, in an unauthorized textbook, described a process for solving simultaneous equations that later authors applied specifically to linear equations. This method - that Newton did not want to publish, that Euler did not recommend, that Legendre called "ordinary," and that Gauss called "common" - is now named after Gauss: "Gaussian'" elimination. (One suspects, he would not be amused.) Gauss's name became associated with elimination through the adoption, by professional computers, of a specialized notation that Gauss devised for his own least squares calculations. The notation allowed elimination to be viewed as a sequence of arithmetic operations that were repeatedly optimized for hand computing and eventually were described by matrices.

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

    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-...

  17. Benzo(a)pyrene diolepoxide-DNA adducts detected by synchronous fluorescence spectrophotometry.

    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...

  18. New adducts of Lapachol with primary amines

    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)

  19. STUDY ON GMA-DNA ADDUCTS

    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.

  20. Fluorescence spectroscopy in the analysis of deoxyribonucleic acid (DNA) adducts

    An important first step in the initiation of carcinogenesis by polycyclic aromatic hydrocarbons (PAH), is the formation of a covalently bound adduct between the metabolized PAH and one or more deoxyribonucleic acid bases. In vivo concentrations of these adducts are typically ∼1 adducted base per 108 normal DNA base pairs. In this paper methods of generating high resolution fluorescence spectra of adducts at these levels are described. Methods of overcoming factors such as photochemistry and nonphotochemical hole burning which limit detection limits are described. By generating line narrowed fluorescence spectra, it is possible to spectrally distinguish between various adduct possibilities

  1. 32P-postlabelling methods for cyclic DNA adducts.

    Watson, W P; Crane, A E; Steiner, S

    1993-01-01

    32P-Postlabelling procedures coupled with HPLC have been developed to detect and measure a range of cyclic DNA adducts formed by bifunctional genotoxic agents. The methods are based on reverse-phase HPLC, particularly column-switching HPLC, to enrich adduct 3'-monophosphates before labelling. Following 3'-dephosphorylation of the 3'5'-[5'-32P]bisphosphates with nuclease P1, the resulting 5'-[32P]monophosphate adducts are resolved, identified and characterized by co-chromatography with synthetic reference standards. The procedures have been applied to a number of cyclic adducts including those formed by chloroacetaldehyde, glycidaldehyde and malonaldehyde. In general, labelling efficiencies measured as chromatographed 5'-[32P]monophosphates were in the range 30-40%. However, the values for the malonaldehyde deoxyguanosine adduct were much lower. The techniques have been applied to studies on the formation of DNA adducts in the skin of male C3H mice treated cutaneously with glycidaldehyde. The HPLC-32P-postlabelling analysis of epidermal DNA hydrolysates indicated that a single major cyclic adduct was formed by reaction with deoxyadenosine residues in mouse skin DNA. The adduct was identified as a hydroxymethyl ethenodeoxyadenosine adduct by comparison with a synthetic standard. This adduct was highly fluorescent and it was possible to make quantitative comparisons of the amounts of adduct determined by either HPLC-32P-postlabelling or HPLC-fluorescence detection. PMID:8225493

  2. Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose

    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 (R2 = 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 (kel) indicating that the diHOPrVal adduct was chemically stable. Then, we measured the second-order rate constant (kval) for the reaction of glycidol with N-terminal valine in rat and human hemoglobin in in vitro experiments with whole blood. The kval 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 kval 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. • diHOPrVal is considered

  3. Characterization of glycidol-hemoglobin adducts as biomarkers of exposure and in vivo dose

    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

  4. Acetaldehyde Adducts in Alcoholic Liver Disease

    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.

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

    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

  6. Benzo(a)pyrenediolepoxide-hemoglobin adducts and 3-hydroxy-benzo(a)pyrene urinary excretion profiles in rats subchronically exposed to benzo(a)pyrene.

    Bouchard, M; Viau, C

    1995-01-01

    The time profiles of benzo(a)pyrenediolepoxide (BaPDE)-hemoglobin (Hb) adduct formation and 3-hydroxybenzo(a)pyrene (3-OHBaP) urinary excretion were studied in male Sprague-Dawley rats exposed to daily benzo(a)pyrene (BaP) intraperitoneal doses of 1.25, 6.25, and 31.25 mumol/kg administered Tuesday to Friday for 4 consecutive weeks. Blood was withdrawn weekly, on Tuesdays, prior to dosing. Twenty-four-hour urine samples were collected on Mondays (following 72 h without treatment) and Thursdays. Analytes were quantified by high performance liquid chromatography (HPLC)/fluorescence. Exposure to BaP resulted in the accumulation of BaPDE-Hb adducts, reaching an average of 1.2 +/- 0.3, 8.3 +/- 1.9, and 38.2 +/- 6.1 pmol/g Hb for the 1.25, 6.25, and 31.25 mumol/kg per day doses after 4 weeks of treatment. The expected saw tooth excretion profile of 3-OHBaP was observed, with peaks on Thursdays and troughs on Mondays, and showed a progressive rise on both Mondays and Thursdays. Increase in Monday values with time suggested a possible increase in BaP body burden during exposure. To verify this aspect further, the urinary excretion kinetic of 3-OHBaP following acute intraperitoneal dosing (31.25 mumol/kg) was determined. Urine samples were collected at frequent timed intervals for up to 164 h post-dosing. Two-step elimination was observed, the second step having a half-life of 25 h, presumably linked to the slow release of BaP accumulated in fatty tissues upon repeated treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8534197

  7. Covered Clause Elimination

    Heule, Marijn; Biere, Armin

    2010-01-01

    Generalizing the novel clause elimination procedures developed in [M. Heule, M. J\\"arvisalo, and A. Biere. Clause elimination procedures for CNF formulas. In Proc. LPAR-17, volume 6397 of LNCS, pages 357-371. Springer, 2010.], we introduce explicit (CCE), hidden (HCCE), and asymmetric (ACCE) variants of a procedure that eliminates covered clauses from CNF formulas. We show that these procedures are more effective in reducing CNF formulas than the respective variants of blocked clause elimination, and may hence be interesting as new preprocessing/simplification techniques for SAT solving.

  8. USCIS Backlog Elimination

    Department of Homeland Security — USCIS is streamlining the way immigration benefits are delivered. By working smarter and eliminating redundancies, USCIS is bringing a business model to government....

  9. Peak flow meter (image)

    A peak flow meter is commonly used by a person with asthma to measure the amount of air that can be ... become narrow or blocked due to asthma, peak flow values will drop because the person cannot blow ...

  10. Mutagenesis by site-specific arylamine adducts in plasmid DNA: Enhancing replication of the adducted strand alters mutation frequency

    Site specifically modified plasmids were used to determine the mutagenic effects of single arylamine adducts in bacterial cells. A synthetic heptadecamer bearing a single N-(guanin-8-yl)-2-aminofluorene (AF) or N-(guanin-8-yl)-2-(acetylamino)fluorene (AAF) adduct was used to introduce the adducts into a specific site in plasmid DNA that contained a 17-base single-stranded region complementary to the modified oligonucleotide. Following transformation of bacterial cells with the adduct-bearing DNA, putative mutants were detected by colony hybridization techniques that allowed unbiased detection of all mutations at or near the site of the adduct. The site-specific AF or AAF adducts were also placed into plasmid DNA that contained uracil residues on the strand opposite that bearing the lesions. The presence of uracil in one strand of the DNA decreases the ability of the bacterial replication system to use the uracil-containing strand, thereby favoring the use of the strand bearing the adducts. In a comparison of the results obtained with site specifically modified DNA, either with or without uracil, the presence of the uracil increased the mutation frequencies of the AF adduct by >7-fold to 2.9% and of the AAF adduct by >12-fold to 0.75%. The AF adduct produced primarily single-base deletions in the absence of uracil but only base substitutions in the uracil-containing constructs. The AAF adduct produced mutations only in the uracil-containing DNA, which included both frame shifts and base substitutions. Mutations produced by both adducts were SOS dependent

  11. Role of retinoic acid in the modulation of benzo(a)pyrene-DNA adducts in human hepatoma cells: Implications for cancer prevention

    Carcinogen-DNA adducts could lead to mutations in critical genes, eventually resulting in cancer. Many studies have shown that retinoic acid (RA) plays an important role in inducing cell apoptosis. Here we have tested the hypothesis that levels of carcinogen-DNA adducts can be diminished by DNA repair and/or by eliminating damaged cells through apoptosis. Our results showed that the levels of total DNA adducts in HepG2 cells treated with benzo(a)pyrene (BP, 2 μM) + RA (1 μM) were significantly reduced compared to those treated with BP only (P = 0.038). In order to understand the mechanism of attenuation of DNA adducts, further experiments were performed. Cells were treated with BP (4 μM) for 24 h to initiate DNA adduct formation, following which the medium containing BP was removed, and fresh medium containing 1 μM RA was added. The cells were harvested 24 h after RA treatment. Interestingly, the levels of total DNA adducts were lower in the BP/RA group (390 ± 34) than those in the BP/DMSO group (544 ± 33), P = 0.032. Analysis of cell apoptosis showed an increase in BP + RA group, compared to BP or RA only groups. Our results also indicated that attenuation of BP-DNA adducts by RA was not primarily due to its effects on CYP1A1 expression. In conclusion, our results suggest a mechanistic link between cellular apoptosis and DNA adduct formation, phenomena that play important roles in BP-mediated carcinogenesis. Furthermore, these results help understand the mechanisms of carcinogenesis, especially in relation to the chemopreventive properties of nutritional apoptosis inducers.

  12. Elimination of eliminativisms

    Davor Pecnjak

    2002-06-01

    Full Text Available In this article, the author examines two kinds of eliminativisms in the philosophy of mind – eliminative materialism and functional eliminativism. He shows that mature neuroscience has to explain phenomena which are denoted by the concepts »perception«, »mind« or »consciousness« and that these concepts are not introduced as explanations of something. Consciousness, for example, is a factual phenomenon that should be explained and cannot be eliminated, by eliminative materialism or by functional eliminativism, as an explanandum and as a fact.

  13. Forecasting peak ozone levels

    Simpson, R.W.; Layton, A.P.

    1983-01-01

    Box-Jenkins (1970) time series models are used to predict peak afternoon O3 levels. Data sets from three monitoring stations in Brisbane, Queensland, Australia, are used in the analysis, one of the stations being inner-city and the others being outer-city. It is found that univariate models using only the peak O3 data-set at a site to predict future peak O3 levels are unsatisfactory. However bivariate models using peak O3 data from one site to predict peak O3 levels at another site yield good results. However it is clear that these results only arise because the O3 is formed in a well mixed layer over the region leading to a high degree of correlation between O3 peaks throughout the region. 15 references.

  14. Are Bragg Peaks Gaussian?

    Hammouda, Boualem

    2014-01-01

    It is common practice to assume that Bragg scattering peaks have Gaussian shape. The Gaussian shape function is used to perform most instrumental smearing corrections. Using Monte Carlo ray tracing simulation, the resolution of a realistic small-angle neutron scattering (SANS) instrument is generated reliably. Including a single-crystal sample with large d-spacing, Bragg peaks are produced. Bragg peaks contain contributions from the resolution function and from spread in the sample structure....

  15. Properties of ferrocene derivative C60 adduct

    Properties of ferrocene derivative C60 adduct were investigated by thermal analyses, x-ray diffraction, 57Fe Moessbauer spectroscopy in order to examine interaction of iron with fullerene. Thermal treatment may be applied to remove organic groups to obtain sample containing C60Fe with C60 arranged in the fcc lattice and iron dispersed between fullerenes. We performed calculations based on the semi-empirical quantum chemistry model P M3 for a few exohedral complexes with Fe at various sites relatively to C60

  16. Eliminating cracking during drying

    Jin, Qiu; Tan, Peng; Schofield, Andrew B.; Xu, Lei

    2013-01-01

    When colloidal suspensions dry, stresses build up and cracks often occur - a phenomenon undesirable for important industries such as paint and ceramics. We demonstrate an effective method which can completely eliminate cracking during drying: by adding emulsion droplets into colloidal suspensions, we can systematically decrease the amount of cracking, and eliminate it completely above a critical droplet concentration. Since the emulsion droplets eventually also evaporate, our technique achiev...

  17. Minding Rachlin's Eliminative Materialism

    McDowell, J. J

    2012-01-01

    Rachlin's teleological behaviorism eliminates the first-person ontology of conscious experience by identifying mental states with extended patterns of behavior, and thereby maintains the materialist ontology of science. An alternate view, informed by brain-based and externalist philosophies of mind, is shown also to maintain the materialist ontology of science, but without eliminating the phenomenology of consciousness. This view implies that to be judged human, machines not only must exhibit...

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

    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

  19. Intramolecular Tetrylene Lewis Adducts: Synthesis and Reactivity.

    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

  20. DNA adduct formation by alachlor metabolites

    The extent of DNA adduct formation by alachlor [ArN(CH2OCH3)C(O)CH2Cl wherein Ar is 2,6-diethylphenyl] and its metabolites is used as a guide to deduce the causal agent(s) in the carcinogenicity of this major herbicide. [14C-phenyl]Alachlor is compared to its two metabolic cleavage products, [14C-phenyl] 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) [ArNHC(O)CH2Cl] and [14C-phenyl]2,6-diethylaniline (DEA) (ArNH2), and to [14C-methoxy]alachlor in various in vitro and in vivo systems. Horseradish peroxidase and hydrogen peroxide activate DEA, but not CEDPA or alachlor, for formation of adducts with calf thymus DNA, which probably involves 2,6-diethylnitrosobenzene (ArNO) as an intermediate. Mouse liver microsomes and NADPH are both required to enhance the binding from each labeled preparation to calf thymus DNA; 4-fold higher labeling is observed from [14C-methoxy]- than from [14C-phenyl]alachlor. This 4-fold preferential DNA labeling from the 14C-methoxy compound is likewise found in the liver of mice treated intraperitoneally. Mouse liver protein and hemoglobin are also labeled, in vivo, with [14C-phenyl]alachlor, -CDEPA and -DEA, and, as with the DNA, the labeling of these proteins is 1.5- to 2-fold higher with [14C-methoxy]alachlor

  1. Tissue differences, dose-response relationship and persistence of DNA adducts in blue mussels (Mytilus edulis L.) exposed to benzo[a]pyrene

    Baltic Sea blue mussels (Mytilus edulis) were experimentally exposed to the genotoxic model substance benzo[a]pyrene (B[a]P) to study DNA adduct formation. The specific aims were (a) to examine where in the mussels the DNA adducts were formed, in gills or digestive gland; (b) to study the dose-response relationship between B[a]P exposure and DNA adduct formation; and (c) to examine the persistence of the formed adducts. A Scope for growth (SFG) study was also run to compare physiological responses of the mussels with the degree of DNA adduct formation. In an initial dose-response experiment, the mussels were exposed to 0, 5, 50, and 100 μg/l of tritium labelled B[a]P under semi-static conditions for 4 days, and thereafter the bioaccumulation of B[a]P and DNA adduct formation in different tissues was determined using liquid scintillation counting and 32P-postlabelling analysis, respectively. In a following exposure-depuration experiment, mussels were exposed to 17 μg/l of radiolabelled B[a]P under semi-static conditions for 6 days. B[a]P accumulation and DNA adduct formation were determined during the exposure, and B[a]P elimination and persistence of DNA adducts were studied during 28 days of depuration in uncontaminated water. The results revealed large tissue differences in DNA adduct formation. DNA adduct levels were not elevated in the digestive gland of the mussels at any exposure concentration (0-100 μg/l), even though the highest B[a]P tissue concentrations were found in the digestive gland (1.0±0.1 mg B[a]P/g tissue dry wt at 100 μg/l, mean±SE, n=12). DNA adducts were on the other hand formed in the gills, with the highest levels found in mussels exposed to 50 and 100 μg B[a]P/l, and a dose dependent increase in adduct levels (from 1.6 to 5.9 nmol adducts/mol nucleotides) from 0 to 50 μg B[a]P/l. In gills, DNA adduct levels increased with time during the 6-day exposure period in the exposure-depuration experiment, and then persisted for at least 2

  2. Lewis Acid-Base Adduct Approach for High Efficiency Perovskite Solar Cells.

    Lee, Jin-Wook; Kim, Hui-Seon; Park, Nam-Gyu

    2016-02-16

    to form an adduct by reacting with the Lewis base. Crystal growth and morphology of perovskite can be controlled by taking advantage of the weak chemical interaction in the adduct. We have successfully fabricated highly reproducible CH3NH3PbI3 perovskite solar cells with PCE as high as 19.7% via adducts of PbI2 with oxygen-donor N,N'-dimethyl sulfoxide. This adduct approach has been found to be generally adopted, where formamidinium lead iodide perovskite, HC(NH2)2PbI3 (FAPbI3), with large grain, high crystallinity, and long-lived carrier lifetime was successfully fabricated via an adduct of PbI2 with sulfur-donor thiourea as Lewis base. The adduct approach proposed in this Account is a very promising methodology to achieve high quality perovskite films with high photovoltaic performance. Furthermore, single crystal growth on the conductive substrate is expected to be possible if we kinetically control the elimination of Lewis base in the adduct. PMID:26797391

  3. Peak Oil, Peak Coal and Climate Change

    Murray, J. W.

    2009-05-01

    Research on future climate change is driven by the family of scenarios developed for the IPCC assessment reports. These scenarios create projections of future energy demand using different story lines consisting of government policies, population projections, and economic models. None of these scenarios consider resources to be limiting. In many of these scenarios oil production is still increasing to 2100. Resource limitation (in a geological sense) is a real possibility that needs more serious consideration. The concept of 'Peak Oil' has been discussed since M. King Hubbert proposed in 1956 that US oil production would peak in 1970. His prediction was accurate. This concept is about production rate not reserves. For many oil producing countries (and all OPEC countries) reserves are closely guarded state secrets and appear to be overstated. Claims that the reserves are 'proven' cannot be independently verified. Hubbert's Linearization Model can be used to predict when half the ultimate oil will be produced and what the ultimate total cumulative production (Qt) will be. US oil production can be used as an example. This conceptual model shows that 90% of the ultimate US oil production (Qt = 225 billion barrels) will have occurred by 2011. This approach can then be used to suggest that total global production will be about 2200 billion barrels and that the half way point will be reached by about 2010. This amount is about 5 to 7 times less than assumed by the IPCC scenarios. The decline of Non-OPEC oil production appears to have started in 2004. Of the OPEC countries, only Saudi Arabia may have spare capacity, but even that is uncertain, because of lack of data transparency. The concept of 'Peak Coal' is more controversial, but even the US National Academy Report in 2007 concluded only a small fraction of previously estimated reserves in the US are actually minable reserves and that US reserves should be reassessed using modern methods. British coal production can be

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

    Olesen, Solveig Gaarn; Hammerum, Steen

    2009-01-01

    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....

  5. Biocatalytic Reductions of Baylis - Hillman Adducts

    A Walton; W Conerly; Y Pompeu; B Sullivan; J Stewart

    2011-12-31

    Baylis-Hillman adducts are highly useful synthetic intermediates; to enhance their value further, we sought enantiocomplementary alkene reductases to introduce chirality. Two solutions emerged: (1) a wild-type protein from Pichia stipitis (OYE 2.6), whose performance significantly outstrips that of the standard enzyme (Saccharomyces pastorianus OYE1), and (2) a series of OYE1 mutants at position 116 (Trp in the wild-type enzyme). To understand how mutations could lead to inverted enantioselectivity, we solved the X-ray crystal structure of the Trp116Ile OYE1 variant complexed with a cyclopentenone substrate. This revealed key protein-ligand interactions that control the orientation of substrate binding above the FMN cofactor.

  6. Towards Measles elimination

    Muscat, Mark; Sciberras, Maria

    2003-01-01

    In many European countries measles is still a cause of great public health concern. Outbreaks of the disease are still occurring because the degree of vaccination coverage required to interrupt transmission has not yet been achieved. Many countries have started to implement measles elimination strategies. These are primarily based on attaining a very high coverage of measles vaccination and strengthening measles surveillance systems.

  7. Minding Rachlin's Eliminative Materialism

    McDowell, J. J.

    2012-01-01

    Rachlin's teleological behaviorism eliminates the first-person ontology of conscious experience by identifying mental states with extended patterns of behavior, and thereby maintains the materialist ontology of science. An alternate view, informed by brain-based and externalist philosophies of mind, is shown also to maintain the materialist…

  8. Elimination of Social Rules.

    O'Toole, Teddy

    The thesis of this document is that arbitrary social rules must be eliminated. Chapters cover: (1) what it is like to be a student whose personal activities are controlled; (2) the necessity of environmental freedom as a prerequisite to successful educational reform; (3) the question of environmental control; (4) the legal history of environmental…

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

    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

  10. Roaming dynamics in radical addition-elimination reactions

    Joalland, Baptiste; Shi, Yuanyuan; Kamasah, Alexander; Suits, Arthur G.; Mebel, Alexander M.

    2014-06-01

    Radical addition-elimination reactions are a major pathway for transformation of unsaturated hydrocarbons. In the gas phase, these reactions involve formation of a transient strongly bound intermediate. However, the detailed mechanism and dynamics for these reactions remain unclear. Here we show, for reaction of chlorine atoms with butenes, that the Cl addition-HCl elimination pathway occurs from an abstraction-like Cl-H-C geometry rather than a conventional three-centre or four-centre transition state. Furthermore, access to this geometry is attained by roaming excursions of the Cl atom from the initially formed adduct. In effect, the alkene π cloud serves to capture the Cl atom and hold it, allowing many subsequent opportunities for the energized intermediate to find a suitable approach to the abstraction geometry. These bimolecular roaming reactions are closely related to the roaming radical dynamics recently discovered to play an important role in unimolecular reactions.

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

    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

  12. Hale Central Peak

    2004-01-01

    19 September 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows some of the mountains that make up the central peak region of Hale Crater, located near 35.8oS, 36.5oW. Dark, smooth-surfaced sand dunes are seen to be climbing up the mountainous slopes. The central peak of a crater consists of rock brought up during the impact from below the crater floor. This autumn image is illuminated from the upper left and covers an area approximately 3 km (1.9 mi) across.

  13. The peak oil debate

    Graefe, Laurel

    2009-01-01

    For the past half-century, a debate has raged over when "peak oil" will occur—the point at which output can no longer increase and production begins to level off or gradually decline. Determining how long the oil supply will last has become even more pressing because the world’s energy supply still relies heavily on oil, and global energy demand is expected to rise steeply over the next twenty years. ; This article seeks to bring the peak oil debate into focus. The author notes that a number ...

  14. Targeting rubella for elimination

    Davendra K Taneja

    2012-01-01

    Full Text Available Rubella is an acute, usually mild viral disease. However, when rubella infection occurs just before conception or during the first 8-10 weeks of gestation, it causes multiple fetal defects in up to 90% of cases, known as Congenital Rubella Syndrome (CRS. It may result in fetal wastage, stillbirths and sensorineural hearing deficit up to 20 weeks of gestation. Rubella vaccine (RA 27/3 is highly effective and has resulted in elimination of rubella and CRS from the western hemisphere and several European countries. Review of several studies documents the duration of protection over 10-21 years following one dose of RA27/3 vaccination, and persistent seropositivity in over 95% cases. Studies in India show seronegativity to rubella among adolescent girls to vary from 10% to 36%. Although due to early age of infection resulting in protection in the reproductive age group, incidence of rubella in India is not very high. However, due to severity of CRS coupled with introduction of RCV in private sector and in some of the states which is likely to lead to sub-optimal coverage and resulting higher risk of rubella during pregnancy in the coming decades, it is imperative to adopt the goal of rubella elimination. As in order to control measles, the country has adopted strategy of delivering second dose of measles through measles campaigns covering children 9 months to 10 years of age in 14 states, it is recommended to synergize efforts for elimination of rubella with these campaigns by replacing measles vaccine by MR or MMR vaccine. Other states which are to give second dose of measles through routine immunization will also have to adopt campaign mode in order to eliminate rubella from the country over 10-20 years. Subsequently, measles vaccine can be replaced by MR or MMR vaccine in the national schedule.

  15. Optimal elimination contest

    Knyazev, Dmitriy

    2013-01-01

    We consider multi-stage elimination contests, where agents’ efforts at different stages generate some output for the organizers. Depending on the output function we characterize the optimal prize structure of the tournament and show that it is almost efficient. We have found that in some cases quite a strange structure turns out to be optimal, under which prizes for agents are smaller at the later stages than at the earlier ones. Sufficient conditions for optimality of such structures ...

  16. Eliminating Perinatal HIV Transmission

    2012-11-26

    In this podcast, CDC’s Dr. Steve Nesheim discusses perinatal HIV transmission, including the importance of preventing HIV among women, preconception care, and timely HIV testing of the mother. Dr. Nesheim also introduces the revised curriculum Eliminating Perinatal HIV Transmission intended for faculty of OB/GYN and pediatric residents and nurse midwifery students.  Created: 11/26/2012 by Division of HIV/AIDS Prevention.   Date Released: 11/26/2012.

  17. Eliminating Rabies in Estonia

    Cliquet, Florence; Robardet, Emmanuelle; Must, Kylli; Laine, Marjana; Peik, Katrin; Picard-Meyer, Evelyne; Guiot, Anne-Laure; Niin, Enel

    2012-01-01

    The compulsory vaccination of pets, the recommended vaccination of farm animals in grazing areas and the extermination of stray animals did not succeed in eliminating rabies in Estonia because the virus was maintained in two main wildlife reservoirs, foxes and raccoon dogs. These two species became a priority target therefore in order to control rabies. Supported by the European Community, successive oral vaccination (OV) campaigns were conducted twice a year using Rabigen® SAG2 baits, beginn...

  18. Peak-interviewet

    Raalskov, Jesper; Warming-Rasmussen, Bent

    Peak-interviewet er en særlig effektiv metode til at gøre ubevidste menneskelige ressourcer bevidste. Fokuspersonen (den interviewede) interviewes om en selvvalgt, personlig succesoplevelse. Terapeuten/coachen (intervieweren) spørger ind til processen, som ledte hen til denne succes. Herved afdæk...

  19. Acetylator genotype-dependent formation of 2-aminofluorene-hemoglobin adducts in rapid and slow acetylator Syrian hamsters congenic at the NAT2 locus.

    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

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

    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...

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

    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

  2. Efforts to Eliminate Illiteracy

    2000-01-01

    FOLLOWING the Chinese women's emancipation movement, the Chinese women's illiteracy elimination drive has also gone through a history of 50 years. Although this task is a huge and arduous one, due to various historical, economic and ideological reasons, the rate of illiteracy amongst Chinese women has declined from 90 percent immediately after the founding of New China in 1949 to the present level of 23 percent. The rate of girls going to school has risen from 20 percent to 96.8 percent. Among

  3. Eliminator of dental calculus

    Šobich, Adam

    2011-01-01

    Bachelor’s thesis is focused on system design of eliminator of dental calculus operating at a frequency of 27 kHz and reaching the intensity of ultrasound on the applicator tip to 5 W/cm2. The work analyzes problems of dental calculus, principle of ultrasonic waves and the physical phenomena occurring in the environment, which it passes. Another part of the work describes the creation of waves using ultrasonic transducer and the amplification of ultrasound in the waveguide. Practical part of ...

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

    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

  5. Single elimination competition

    Fink, T. M. A.; Coe, J. B.; Ahnert, S. E.

    2008-09-01

    We study a simple model of competition in which each player has a fixed strength: randomly selected pairs of players compete, the stronger one wins and the loser is eliminated. We show that the best indicator of future success is not the number of wins but a player's wealth: the accumulated wealth of all defeated players. We calculate the distributions of strength and wealth for two versions of the problem: in the first, the loser is replaced; in the second, the loser is not. The probability of attaining a given wealth is shown to be path-independent. We illustrate our model with the popular game of conkers and discuss an extension to round-robin sports competition.

  6. The Economics of Peak Oil

    Holland, Stephen

    2011-01-01

    Peak oil” refers to the future decline in world production of crude oil and to the accompanying potentially calamitous effects. The peak oil literature typically rejects economic analysis. This chapter, following Holland (2008), argues that economic analysis is indeed appropriate for analyzing oil scarcity since standard economic models can replicate the observed peaks in oil production. Moreover, the emphasis on peak oil is misplaced since peaking is not a good indicator of scarcity, peak o...

  7. Peak reading detector circuit

    The peak reading detector circuit serves for picking up the instants during which peaks of a given polarity occur in sequences of signals in which the extreme values, their time intervals, and the curve shape of the signals vary. The signal sequences appear in measuring the foetal heart beat frequence from amplitude-modulated ultrasonic, electrocardiagram, and blood pressure signals. In order to prevent undesired emission of output signals from, e. g., disturbing intermediate extreme values, the circuit consists of the series connections of a circuit to simulate an ideal diode, a strong unit, a discriminator for the direction of charging current, a time-delay circuit, and an electronic switch lying in the decharging circuit of the storage unit. The time-delay circuit thereby causes storing of a preliminary maximum value being used only after a certain time delay for the emission of the output signal. If a larger extreme value occurs during the delay time the preliminary maximum value is cleared and the delay time starts running anew. (DG/PB)

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

    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.

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

    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

  10. Disease detection and elimination

    In micropropagation, the health status of the donor mother plant and of the plants multiplied from it are among the most critical factors, which determine the success of a tissue culture operation. The indexing of the mother plants for freedom from viral, bacterial, and fungal diseases is a normal procedure in large-scale plant propagation through tissue culture. Plants not originating from pathogen-tested material must be screened for the presence of viruses Laboratories, which do not have in-house facilities to carry out plant indexing, should obtain their indexed stock plants from organizations such as Departments of Agriculture, agricultural universities or privately owned certified germplasm repositories that routinely produce such plant material. Batches of micropropagated plants should be tested for freedom from diseases either in-house or by other laboratories. ELISA has been the most effective method for virus and pathogen detection in plants. Polymerase chain reaction (PCR) and nucleic acid hybridization are more sensitive than ELISA, and can detect pathogens in extremely low amounts. The elimination of most viruses can be achieved by a combination of apical meristem culture and thermotherapy. (author)

  11. Competitive Deprotonation and Superoxide [O2 (-•)] Radical-Anion Adduct Formation Reactions of Carboxamides under Negative-Ion Atmospheric-Pressure Helium-Plasma Ionization (HePI) Conditions.

    Hassan, Isra; Pinto, Spencer; Weisbecker, Carl; Attygalle, Athula B

    2016-03-01

    Carboxamides bearing an N-H functionality are known to undergo deprotonation under negative-ion-generating mass spectrometric conditions. Herein, we report that N-H bearing carboxamides with acidities lower than that of the hydroperoxyl radical (HO-O(•)) preferentially form superoxide radical-anion (O2 (-•)) adducts, rather than deprotonate, when they are exposed to the glow discharge of a helium-plasma ionization source. For example, the spectra of N-alkylacetamides show peaks for superoxide radical-anion (O2 (-•)) adducts. Conversely, more acidic amides, such as N-alkyltrifluoroacetamides, preferentially undergo deprotonation under similar experimental conditions. Upon collisional activation, the O2 (-•) adducts of N-alkylacetamides either lose the neutral amide or the hydroperoxyl radical (HO-O(•)) to generate the superoxide radical-anion (m/z 32) or the deprotonated amide [m/z (M - H)(-)], respectively. For somewhat acidic carboxamides, the association between the two entities is weak. Thus, upon mildest collisional activation, the adduct dissociates to eject the superoxide anion. Superoxide-adduct formation results are useful for structure determination purposes because carboxamides devoid of a N-H functionality undergo neither deprotonation nor adduct formation under HePI conditions. Graphical Abstract ᅟ. PMID:26545766

  12. Competitive Deprotonation and Superoxide [O2 -•] Radical-Anion Adduct Formation Reactions of Carboxamides under Negative-Ion Atmospheric-Pressure Helium-Plasma Ionization (HePI) Conditions

    Hassan, Isra; Pinto, Spencer; Weisbecker, Carl; Attygalle, Athula B.

    2016-03-01

    Carboxamides bearing an N-H functionality are known to undergo deprotonation under negative-ion-generating mass spectrometric conditions. Herein, we report that N-H bearing carboxamides with acidities lower than that of the hydroperoxyl radical (HO-O•) preferentially form superoxide radical-anion (O2 -•) adducts, rather than deprotonate, when they are exposed to the glow discharge of a helium-plasma ionization source. For example, the spectra of N-alkylacetamides show peaks for superoxide radical-anion (O2 -•) adducts. Conversely, more acidic amides, such as N-alkyltrifluoroacetamides, preferentially undergo deprotonation under similar experimental conditions. Upon collisional activation, the O2 -• adducts of N-alkylacetamides either lose the neutral amide or the hydroperoxyl radical (HO-O•) to generate the superoxide radical-anion ( m/z 32) or the deprotonated amide [ m/z (M - H)-], respectively. For somewhat acidic carboxamides, the association between the two entities is weak. Thus, upon mildest collisional activation, the adduct dissociates to eject the superoxide anion. Superoxide-adduct formation results are useful for structure determination purposes because carboxamides devoid of a N-H functionality undergo neither deprotonation nor adduct formation under HePI conditions.

  13. Crystalline guanine adducts of natural and synthetic trioxacarcins suggest a common biological mechanism and reveal a basis for the instability of trioxacarcin A.

    Pröpper, Kevin; Dittrich, Birger; Smaltz, Daniel J; Magauer, Thomas; Myers, Andrew G

    2014-09-15

    X-ray crystallographic characterization of products derived from natural and fully synthetic trioxacarcins, molecules with potent antiproliferative effects, illuminates aspects of their reactivity and mechanism of action. Incubation of the fully synthetic trioxacarcin analog 3, which lacks one of the carbohydrate residues present in the natural product trioxacarcin A (1) as well as oxygenation at C2 and C4 yet retains potent antiproliferative effects, with the self-complimentary duplex oligonucleotide d(AACCGGTT) led to production of a crystalline covalent guanine adduct (6). Adduct 6 is closely analogous to gutingimycin (2), the previously reported guanine adduct derived from incubation of natural trioxacarcin A (1) with duplex DNA, suggesting that 3 and 1 likely share a common basis of cytotoxicity. In addition, we isolated a novel, dark-red crystalline guanine adduct (7) from incubation of trioxacarcin A itself with the self-complimentary duplex oligonucleotide d(CGTATACG). Crystallographic analysis suggests that 7 is an anthraquinone derivative, which we propose arises by a sequence of guanosine alkylation within duplex DNA, depurination, base-catalyzed elimination of the trioxacarcinose A carbohydrate residue, and oxidative rearrangement to form an anthraquinone. We believe that this heretofore unrecognized chemical instability of natural trioxacarcins may explain why trioxacarcin analogs lacking C4 oxygenation exhibit superior chemical stabilities yet, as evidenced by structure 3, retain a capacity to form lesions with duplex DNA. PMID:25176186

  14. Quantitation of DNA Adducts Induced by 1,3-Butadiene

    Sangaraju, Dewakar; Villalta, Peter W.; Wickramaratne, Susith; Swenberg, James; Tretyakova, Natalia

    2014-07-01

    Human exposure to 1,3-butadiene (BD) present in automobile exhaust, cigarette smoke, and forest fires is of great concern because of its potent carcinogenicity. The adverse health effects of BD are mediated by its epoxide metabolites such as 3,4-epoxy-1-butene (EB), which covalently modify genomic DNA to form promutagenic nucleobase adducts. Because of their direct role in cancer, BD-DNA adducts can be used as mechanism-based biomarkers of BD exposure. In the present work, a mass spectrometry-based methodology was developed for accurate, sensitive, and precise quantification of EB-induced N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) DNA adducts in vivo. In our approach, EB-GII adducts are selectively released from DNA backbone by neutral thermal hydrolysis, followed by ultrafiltration, offline HPLC purification, and isotope dilution nanoLC/ESI+-HRMS3 analysis on an Orbitrap Velos mass spectrometer. Following method validation, EB-GII lesions were quantified in human fibrosarcoma (HT1080) cells treated with micromolar concentrations of EB and in liver tissues of rats exposed to sub-ppm concentrations of BD (0.5-1.5 ppm). EB-GII concentrations increased linearly from 1.15 ± 0.23 to 10.11 ± 0.45 adducts per 106 nucleotides in HT1080 cells treated with 0.5-10 μM DEB. EB-GII concentrations in DNA of laboratory rats exposed to 0.5, 1.0, and 1.5 ppm BD were 0.17 ± 0.05, 0.33 ± 0.08, and 0.50 ± 0.04 adducts per 106 nucleotides, respectively. We also used the new method to determine the in vivo half-life of EB-GII adducts in rat liver DNA (2.20 ± 0.12 d) and to detect EB-GII in human blood DNA. To our knowledge, this is the first application of nanoLC/ESI+-HRMS3 Orbitrap methodology to quantitative analysis of DNA adducts in vivo.

  15. Mutational properties of the primary aflatoxin B1-DNA adduct.

    Bailey, E A; Iyer, R S; Stone, M. P.; Harris, T M; Essigmann, J M

    1996-01-01

    The mutagenic activity of the major DNA adduct formed by the liver carcinogen aflatoxin B1 (AFB1) was investigated in vivo. An oligonucleotide containing a single 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua) adduct was inserted into the single-stranded genome of bacteriophage M13. Replication in SOS-induced Escherichia coli yielded a mutation frequency for AFB1-N7-Gua of 4%. The predominant mutation was G --> T, identical to the principal mutation in human liver tumors believ...

  16. Chemistry and Biology of Aflatoxin-DNA Adducts

    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.

  17. Eliminating rabies in Estonia.

    Florence Cliquet

    Full Text Available The compulsory vaccination of pets, the recommended vaccination of farm animals in grazing areas and the extermination of stray animals did not succeed in eliminating rabies in Estonia because the virus was maintained in two main wildlife reservoirs, foxes and raccoon dogs. These two species became a priority target therefore in order to control rabies. Supported by the European Community, successive oral vaccination (OV campaigns were conducted twice a year using Rabigen® SAG2 baits, beginning in autumn 2005 in North Estonia. They were then extended to the whole territory from spring 2006. Following the vaccination campaigns, the incidence of rabies cases dramatically decreased, with 266 cases in 2005, 114 in 2006, four in 2007 and three in 2008. Since March 2008, no rabies cases have been detected in Estonia other than three cases reported in summer 2009 and one case in January 2011, all in areas close to the South-Eastern border with Russia. The bait uptake was satisfactory, with tetracycline positivity rates ranging from 85% to 93% in foxes and from 82% to 88% in raccoon dogs. Immunisation rates evaluated by ELISA ranged from 34% to 55% in foxes and from 38% to 55% in raccoon dogs. The rabies situation in Estonia was compared to that of the other two Baltic States, Latvia and Lithuania. Despite regular OV campaigns conducted throughout their territory since 2006, and an improvement in the epidemiological situation, rabies has still not been eradicated in these countries. An analysis of the number of baits distributed and the funding allocated by the European Commission showed that the strategy for rabies control is more cost-effective in Estonia than in Latvia and Lithuania.

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

    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

  19. Metabolism of aflatoxin B1 and identification of the major aflatoxin B1-DNA adducts formed in cultured human bronchus and colon

    1979-01-01

    Aflatoxin B1 and benzo(a)pyrene were activated by both cultured human bronchus and human colon as measured by binding to cellular DNA and protein. The binding of aflatoxin B1 to DNA was dose dependent, and the level of binding was higher in cultured human bronchus than it was in the colon. When...... found in these two peaks, and the ratio of radioactivity between the peaks was nearly 1. In colonic DNA, the ratio between Structures 1 and 11 was approximately 2. These observations add aflatoxin B1 to the list of chemical procarcinogens metabolized by cultured human tissues and in which the carcinogen-DNA...... adducts are similar to the adducts formed in animal tissue susceptible to the carcinogenic action of aflatoxin B1....

  20. Quantum State Detection Via Elimination

    Ettinger, J M; Hoyer, Peter

    1999-01-01

    We present the view of quantum algorithms as a search-theoretic problem. We show that the Fourier transform, used to solve the Abelian hidden subgroup problem, is an example of an efficient elimination observable which eliminates a constant fraction of the candidate secret states with high probability. Finally, we show that elimination observables do not always exist by considering the geometry of the hidden subgroup states of the dihedral group D_N.

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

    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.)

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

    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....

  3. Make peak flow a habit!

    Checking your peak flow is one of the best ways to control your asthma and to keep it from getting worse. Asthma attacks ... Most times, they build slowly. Checking your peak flow can tell you if an attack is coming, ...

  4. Synthesis of Borinic Acids and Borinate Adducts Using Diisopropylaminoborane.

    Marciasini, Ludovic; Cacciuttolo, Bastien; Vaultier, Michel; Pucheault, Mathieu

    2015-07-17

    In situ formation of aryl Grignard under Barbier condition and diisopropylaminoborane as boron source allows a complete control of the addition onto the boron electrophile. Analytically pure borinic acid derivatives were produced at the gram scale without column chromatography and isolated as borinates adducts, with ethanolamine or 8-hydroxyquinoline, after workup. PMID:26183591

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

    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...

  6. Characterization of trypsin-derived peptides acrylamide-adducted hemoglobin

    Even though there are a number of sources for human exposure to acrylamide, reliable biomarkers of exposure are not available. In an effort to develop such a biomarker, the authors are characterizing peptides derived from trypsin digests of acrylamide-adducted hemoglobin. For this, radiolabeled acrylamide was incubated with this, radiolabeled acrylamide was incubated with purified human hemoglobin (Ao) and decomposition products removed by dialysis. When the adducted hemoglobin was separated by reverse-phase HPLC, radioactivity eluted with the α and β subunits, suggesting covalent binding. Digestion of individual subunits with trypsin followed by reverse phase HPLC, indicated that most of the radioactivity associated with the α subunit co-eluted with a single peptide. Similar results were observed for the β subunit except that significant amounts of radioactivity eluted with the solvent front, suggesting that radioactivity was released by trypsin digestion. Currently, these preparation are under further characterization by electrospray ionization mass spectrometry. This approach will aid in the identification of the adducted will aid in the identification of the adducted peptide and subsequent preparation of an acrylamide-specific antibody

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

    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...

  8. Triphosgene mediated chlorination of Baylis-Hillman adducts

    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. Detection of protein adduction derived from dauricine by alkaline permethylation.

    Xie, Honglei; Liu, Yuyang; Peng, Ying; Zhao, Dongmei; Zheng, Jiang

    2016-06-01

    Dauricine is a bisbenzylisoquinoline alkaloid derivative and has shown multiple pharmacological properties. Despite this, our previous study demonstrated that dauricine induced severe lung toxicity in experimental animals. Metabolic activation of dauricine to the corresponding quinone methide intermediate is suggested to play an important role in dauricine-induced cytotoxicity. Protein adduction derived from the reactive intermediate is considered to initiate the process of the toxicity. In the present study, we developed an alkaline permethylation- and mass spectrometry-based approach to detect dauricine-derived protein adduction. Protein samples were permethylated in the presence of NaOH and CH3I at 80 °C, followed by LC-MS/MS analysis. A thioether product was produced in the reaction. Not only does this technique quantify dauricine-derived protein adduction but also it tells the nature of the interaction between the target proteins and the reactive intermediate of dauricine. The recovery, precision, limit of detection, limit of quantity, and method detection limit were found to be 102.8 %±1.7 %, 1.89 %, 1.32 fmol/mL, 4.93 fmol/mL and 3.37 fmol/mL respectively. The surrogate recovery and surrogate RSD values were 81.5-103.0 % and 2.59 %, respectively. This analytical method has proven sensitive, selective, reliable, and feasible to assess total protein adduction derived from dauricine, and will facilitate the mechanistic investigation of dauricine and other bisbenzylisoquinoline toxicities. Graphical Abstract Alkaline permethylation of dauricine derived protein adduct. PMID:27071763

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

    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

  11. Study on peak shape fitting method in radon progeny measurement

    Alpha spectrum measurement is one of the most important methods to measure radon progeny concentration in environment. However, the accuracy of this method is affected by the peak tailing due to the energy losses of alpha particles. This article presents a peak shape fitting method that can overcome the peak tailing problem in most situations. On a typical measured alpha spectrum curve, consecutive peaks overlap even their energies are not close to each other, and it is difficult to calculate the exact count of each peak. The peak shape fitting method uses combination of Gaussian and exponential functions, which can depict features of those peaks, to fit the measured curve. It can provide net counts of each peak explicitly, which was used in the Kerr method of calculation procedure for radon progeny concentration measurement. The results show that the fitting curve fits well with the measured curve, and the influence of the peak tailing is reduced. The method was further validated by the agreement between radon equilibrium equivalent concentration based on this method and the measured values of some commercial radon monitors, such as EQF3220 and WLx. In addition, this method improves the accuracy of individual radon progeny concentration measurement. Especially for the 218Po peak, after eliminating the peak tailing influence, the calculated result of 218Po concentration has been reduced by 21 %. (authors)

  12. Study on peak shape fitting method in radon progeny measurement.

    Yang, Jinmin; Zhang, Lei; Abdumomin, Kadir; Tang, Yushi; Guo, Qiuju

    2015-11-01

    Alpha spectrum measurement is one of the most important methods to measure radon progeny concentration in environment. However, the accuracy of this method is affected by the peak tailing due to the energy losses of alpha particles. This article presents a peak shape fitting method that can overcome the peak tailing problem in most situations. On a typical measured alpha spectrum curve, consecutive peaks overlap even their energies are not close to each other, and it is difficult to calculate the exact count of each peak. The peak shape fitting method uses combination of Gaussian and exponential functions, which can depict features of those peaks, to fit the measured curve. It can provide net counts of each peak explicitly, which was used in the Kerr method of calculation procedure for radon progeny concentration measurement. The results show that the fitting curve fits well with the measured curve, and the influence of the peak tailing is reduced. The method was further validated by the agreement between radon equilibrium equivalent concentration based on this method and the measured values of some commercial radon monitors, such as EQF3220 and WLx. In addition, this method improves the accuracy of individual radon progeny concentration measurement. Especially for the (218)Po peak, after eliminating the peak tailing influence, the calculated result of (218)Po concentration has been reduced by 21 %. PMID:25920795

  13. 32P-postlabeling DNA adduct assay: cigarette smoke-induced dna adducts in the respiratory and nonrespiratory rat tissues. Book chapter

    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

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

    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

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

    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.

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

    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.

  17. Increasing Ubiquitin Ion Resistance to Unfolding in the Gas Phase Using Chloride Adduction: Preserving More "Native-Like" Conformations Despite Collisional Activation.

    Wagner, Nicole D; Kim, Doyong; Russell, David H

    2016-06-01

    Electrospray ionization (ESI) of ubiquitin from acidified (0.1%) aqueous solution produces abundant ubiquitin-chloride adduct ions, [M + nH + xCl]((n - x)+), that upon mild heating react via elimination of neutral HCl. Ion mobility collision cross section (CCS) measurements show that ubiquitin ions retaining chloride adducts exhibit CCS values similar to those of the "native-state" of the protein. Coupled with results from recent molecular dynamics (MD) simulations for the evolution of a salt-containing electrospray droplet, this study provides a more complete picture for how the presence of salts affects the evolution of protein conformers in the final stages of dehydration of the ESI process and within the instrument. PMID:27137645

  18. THE PEAK LATENCY OF ORBITAL PRESACCADIC SPIKE POTENTIAL WITH HORIZONTAL EYE MOVEMENTS

    单扬; MarkL.Moster; RichardA.Roemer[

    1996-01-01

    Purpose.To investigate the peak latency of the orbital presaccedic spike potential (SP) with horizontal eyemovement in normals.Methods. Orbital SP was recorded in 28 normal subjects from 8 electrodes around the eyes with Pz as the reference while performing 5°,10°,20°,30° and 40° horizontal saccedes to visual targets. SP peak latencywas measured from SP onset to SP peak on averaged data aligned on SP peak.Re,Its. Significant main effects on SP peak latency are found for saccade size (P0. 05). No significant main effect on SP peak htency is found for eye (P>0. 05). SP peak latency increases with increasing saccade size from 5° to 40°. SP peak latency is longer with saccades back to center than away from center, and with abducting saccades than with adducting saccades. SP peak latency differs at the electrode sites with an order from shorter to longer as follows; innercanth° (IC); inferior orbit (IO); outer canthus (OC); superior orbit (SO).Conclusions. The effects on the peak latency of orbital SP can be explained by the saccade dynamic property, volume conduction as weft as physiologic and anatomic factors of the eyes and orbits. The peak latency of orbital SP can be used to reflect the temporal characteristics of ocular motor units controlling saccedic eye movement.

  19. Decoupling approximation design using the peak to peak gain

    Sultan, Cornel

    2013-04-01

    Linear system design for accurate decoupling approximation is examined using the peak to peak gain of the error system. The design problem consists in finding values of system parameters to ensure that this gain is small. For this purpose a computationally inexpensive upper bound on the peak to peak gain, namely the star norm, is minimized using a stochastic method. Examples of the methodology's application to tensegrity structures design are presented. Connections between the accuracy of the approximation, the damping matrix, and the natural frequencies of the system are examined, as well as decoupling in the context of open and closed loop control.

  20. Elimination Theory for Tropical Varieties

    Sturmfels, Bernd; Tevelev, Jenia

    2007-01-01

    Tropical algebraic geometry offers new tools for elimination theory and implicitization. We determine the tropicalization of the image of a subvariety of an algebraic torus under any homomorphism from that torus to another torus.

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

    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...

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

    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

  3. SEM-EDX STUDIES OF CHITOSAN DERIVATIVES-METAL ADDUCTS

    Galo Cárdenas; Edelio Taboada; Armando Bravo; S. Patricia Miranda

    2003-01-01

    Chitosan was obtained from shrimps shells (pleuroncodes monodon) using chemical methods. A series of chitosan (QS)charged with solution of copper, cobalt, nickel and mercury ions were prepared at room temperature using the batch method. N-3,5-diethylamino benzoyl chitosan (QDAB); N,O-dimercapto succinate chitosan (QNOT) and 4-aminobenzoate chitosan (QAB) derivatives were prepared. The chitosan metal adducts with Cu, Co, Ni and Hg ions and derivatives maximum loading is discussed. Chitosan and...

  4. Tunable degradation of maleimide-thiol adducts in reducing environments

    Baldwin, Aaron D.; Kiick, Kristi L.

    2011-01-01

    Addition chemistries are widely used in preparing biological conjugates, and in particular, maleimide-thiol adducts have been widely employed. Here we show that the resulting succinimide thioether formed by a Michael type addition of a thiol to N-ethylmaleimide (NEM), generally accepted as stable, can in fact undergo retro and exchange reactions in the presence of other thiol compounds at physiological pH and temperature, offering a novel strategy for controlled release. Model studies (1H NMR...

  5. Protein modification by acrolein: Formation and stability of cysteine adducts

    Cai, Jian; Bhatnagar, Aruni; Pierce, William M.

    2009-01-01

    The toxicity of the ubiquitous pollutant and endogenous metabolite, acrolein, is due in part to covalent protein modifications. Acrolein reacts readily with protein nucleophiles via Michael addition and Schiff base formation. Potential acrolein targets in protein include the nucleophilic side chains of cysteine, histidine, and lysine residues as well as the free amino terminus of proteins. Although cysteine is the most acrolein-reactive residue, cysteine-acrolein adducts are difficult to iden...

  6. PHOSPHATO AND PHOSPHONATO ADDUCTS: SYNTHESIS AND SPECTROSCOPIC STUDY

    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.

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

    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.

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

    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…

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

    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...

  10. High resolution mass spectrometry based profiling of diet-related deoxyribonucleic acid adducts.

    Hemeryck, Lieselot Y; Decloedt, Anneleen I; Vanden Bussche, Julie; Geboes, Karen P; Vanhaecke, Lynn

    2015-09-10

    Exposure of DNA to endo- and exogenous DNA binding chemicals can result in the formation of DNA adducts and is believed to be the first step in chemically induced carcinogenesis. DNA adductomics is a relatively new field of research which studies the formation of known and unknown DNA adducts in DNA due to exposure to genotoxic chemicals. In this study, a new UHPLC-HRMS(/MS)-based DNA adduct detection method was developed and validated. Four targeted DNA adducts, which all have been linked to dietary genotoxicity, were included in the described method; O(6)-methylguanine (O(6)-MeG), O(6)-carboxymethylguanine (O(6)-CMG), pyrimidopurinone (M1G) and methylhydroxypropanoguanine (CroG). As a supplementary tool for DNA adductomics, a DNA adduct database, which currently contains 123 different diet-related DNA adducts, was constructed. By means of the newly developed method and database, all 4 targeted DNA adducts and 32 untargeted DNA adducts could be detected in different DNA samples. The obtained results clearly demonstrate the merit of the described method for both targeted and untargeted DNA adduct detection in vitro and in vivo, whilst the diet-related DNA adduct database can distinctly facilitate data interpretation. PMID:26388482

  11. Formation and persistence of DNA adducts of anticancer drug ellipticine in rats

    Ellipticine is an antineoplastic agent, whose mode of antitumor and/or toxic side effects is based on DNA intercalation, inhibition of topoisomerase II and formation of DNA adducts mediated by cytochromes P450 and peroxidases. We investigated the formation and persistence of DNA adducts generated in rat, the animal model mimicking the bioactivation of ellipticine in human. Using 32P-postlabeling, ellipticine-DNA adducts were found in liver, kidney, lung, spleen, heart and brain of female and male rats exposed to ellipticine (4, 40 and 80 mg/kg body weight, i.p.). The two major adducts were identical to the deoxyguanosine adducts generated in DNA by 13-hydroxy- and 12-hydroxyellipticine in vitro as confirmed by HPLC of the isolated adducts. At four post-treatment times (2 days, 2, 10 and 32 weeks) DNA adducts in rats treated with 80 mg/kg of ellipticine were analyzed in each tissue to study their long-term persistence. In all organs maximal adduct levels were found 2 days after administration. At all time points highest total adduct levels were in liver (402 adducts/108 nucleotides after 2 days and 3.6 adducts/108 nucleotides after 32 weeks), kidney and lung followed by spleen, heart and brain. Total adduct levels decreased over time to 0.8-8.3% of the initial levels till the latest time point and showed a biphasic profile, a rapid loss during the first 2 weeks was followed by a much slower decline till 32 weeks. These results, the first characterization of persistence of ellipticine-DNA adducts in vivo, are necessary to evaluate genotoxic side effects of ellipticine

  12. Improved Peak Detection and Deconvolution of Native Electrospray Mass Spectra from Large Protein Complexes

    Lu, Jonathan; Trnka, Michael J.; Roh, Soung-Hun; Robinson, Philip J. J.; Shiau, Carrie; Fujimori, Danica Galonic; Chiu, Wah; Burlingame, Alma L.; Guan, Shenheng

    2015-12-01

    Native electrospray-ionization mass spectrometry (native MS) measures biomolecules under conditions that preserve most aspects of protein tertiary and quaternary structure, enabling direct characterization of large intact protein assemblies. However, native spectra derived from these assemblies are often partially obscured by low signal-to-noise as well as broad peak shapes because of residual solvation and adduction after the electrospray process. The wide peak widths together with the fact that sequential charge state series from highly charged ions are closely spaced means that native spectra containing multiple species often suffer from high degrees of peak overlap or else contain highly interleaved charge envelopes. This situation presents a challenge for peak detection, correct charge state and charge envelope assignment, and ultimately extraction of the relevant underlying mass values of the noncovalent assemblages being investigated. In this report, we describe a comprehensive algorithm developed for addressing peak detection, peak overlap, and charge state assignment in native mass spectra, called PeakSeeker. Overlapped peaks are detected by examination of the second derivative of the raw mass spectrum. Charge state distributions of the molecular species are determined by fitting linear combinations of charge envelopes to the overall experimental mass spectrum. This software is capable of deconvoluting heterogeneous, complex, and noisy native mass spectra of large protein assemblies as demonstrated by analysis of (1) synthetic mononucleosomes containing severely overlapping peaks, (2) an RNA polymerase II/α-amanitin complex with many closely interleaved ion signals, and (3) human TriC complex containing high levels of background noise.

  13. Decay kinetics of nicotine/NNK-DNA adducts in vivo studied by accelerator mass spectrometry

    The decay kinetics of nicotine-DNA adducts and NNK-DNA adducts in mice liver after single dosing was studied by accelerator mass spectrometry (AMS). The decay is characterized by a two-stage process. The half-lives of nicotine-DNA adducts are 1.3 d (4-24 h) and 7.0 d (1-21 d), while for NNK-DNA adducts are 0.7 d (4-24 h) and 18.0 d (1-21 d). The relatively faster decay of nicotine-DNA adducts suggests that the genotoxicity of nicotine is weaker than that of NNK. The in vitro study shows that the metabolization of nicotine is necessary for the final formation of nicotine-DNA adducts, and nicotine Δ1'(5') iminium ion is a probable metabolite species that binds to DNA molecule covalently

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

    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

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

    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

  16. Methods of Cut-Elimination

    Baaz, Matthias

    2011-01-01

    This is the first book on cut-elimination in first-order predicate logic from an algorithmic point of view. Instead of just proving the existence of cut-free proofs, it focuses on the algorithmic methods transforming proofs with arbitrary cuts to proofs with only atomic cuts (atomic cut normal forms, so-called ACNFs). The first part investigates traditional reductive methods from the point of view of proof rewriting. Within this general framework, generalizations of Gentzen's and Sch\\"utte-Tait's cut-elimination methods are defined and shown terminating with ACNFs of the original proof. M

  17. Detection of Adriamycin–DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations

    Coldwell, Kate E.; Cutts, Suzanne M.; Ognibene, Ted J.; Henderson, Paul T; Phillips, Don R.

    2008-01-01

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin–DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin–DNA adducts/104 bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin–DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We...

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

    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.

  19. Knee adduction moment and medial contact force - facts about their correlation during gait

    Kutzner, Ines; Trepczynski, Adam; Heller, Markus O.; Bergmann, Georg

    2013-01-01

    The external knee adduction moment is considered a surrogate measure for the medial tibiofemoral contact force and is commonly used to quantify the load reducing effect of orthopedic interventions. However, only limited and controversial data exist about the correlation between adduction moment and medial force. The objective of this study was to examine whether the adduction moment is indeed a strong predictor for the medial force by determining their correlation during gait. Instrumented kn...

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

    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.

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

    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...

  2. Benzene hemoglobin adducts in mice and rats: Characterization of formation and physiological modeling

    Benzene is a myelotoxin and a human leukemogen. Humans are exposed to this compound, both occupationally and environmentally. This study was conducted to determine whether formation of benzene-derived adducts with blood hemoglobin (Hb) can be used as a biomarker of exposure to benzene. B6C3F1 mice and F344/N rats were given 0.1 to 10,000 mumol [14C]benzene/kg body wt, orally. Twenty-four hours later, animals were euthanized, and globin was isolated from blood samples. The globin was analyzed by liquid scintillation spectrometry for the presence of [14C]benzene-derived adducts. Hb adduct formation was linear with respect to dose for amounts of up to 500 mumol [14C]benzene/kg body wt, for both rodent species. Within this linear dose-response range, mice formed adducts from [14C]benzene approximately 3.5 times less efficiently [0.022 +/- 0.010 (pmol adducts/mg globin)/(mumol/kg body wt dose)] than did rats [0.076 +/- 0.014 (pmol adducts)/(mumol/kg body wt dose)]. Benzene-derived Hb adducts also accumulated linearly when mice and rats were given up to three daily doses of 500 mumol [14C]benzene/kg body wt. These data were used to develop a physiological model for benzene-derived Hb adduct formation. Both first-order and saturable pathways for adduct formation were incorporated. The results showed that the model simulated the levels of Hb adducts in both mice and rats after oral exposures to benzene and predicted the levels of Hb adducts present after inhalation exposure. These studies suggest that Hb adducts might be useful biomarkers for human exposures to benzene

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

    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.

  4. Phosphoryl chloride-methanol adducts: Matrix isolation infrared and DFT studies

    Ramanathan, N.; Sankaran, K.

    2013-12-01

    The adducts of phosphoryl chloride (POCl3) and methanol (CH3OH) were studied using matrix isolation infrared spectroscopy and DFT calculations. The 1:1 POCl3:CH3OH binary adduct was generated in a nitrogen matrix at low temperatures and studied using infrared spectroscopy. Formation of the adduct was evidenced by the shifts in the vibrational frequencies of the modes involving POCl3 and CH3OH sub-molecules. The structures, vibrational frequencies and stabilization energies of the adducts were computed at B3LYP/aug-cc-pVDZ level of theory. Our computations located two minima for POCl3:CH3OH adducts on the potential energy surface. However, only one adduct was experimentally identified in the matrix at low temperatures, which was the structure corresponding to the global minimum. The computed vibrational frequencies of the adduct agreed well with the observed experimental frequencies. Atoms In Molecules (AIM) analysis was performed to understand the nature of the interactions in these adducts. Natural Bond Orbital (NBO) analysis was performed to understand the effect of charge-transfer interactions on the stability of adducts.

  5. Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin

    Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM–DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was biopsied between 6 h and 21 days. Formation of SM DNA adducts was dose-dependent with a maximum immediately after exposure. However, adducts were persistent and still detectable 21 days post-exposure. The time-dependent formation of DNA adducts was also found to be correlated with the appearance of apoptotic cells. This temporal correlation suggests that these two early events are responsible for the severity of the damage to the skin. Besides, SM–DNA adducts were also detected in areas located next to contaminated zone, thus suggesting that SM diffuses in skin. Altogether, this work provides for the first time a clear picture of SM-induced genotoxicity using DNA adducts as a marker. - Highlights: • Sulfur mustard adducts are formed in DNA after skin exposure. • DNA damage formation is an early event in the pathological process of skin burn. • The amount of SM–DNA adducts is maximal at the earliest time point investigated. • Adducts are still detected 3 weeks after exposure. • Sulfur mustard diffuses in skin especially when large doses are applied

  6. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    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.

  7. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single (14C)-Labeled Therapeutic Dose

    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 (14C)-labeled therapeutic (20 mg) dose, ∼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-N2-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/109 nucleotides. No (14C)-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 α-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 ∼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.

  8. Peak Oil and other threatening peaks-Chimeras without substance

    Radetzki, Marian, E-mail: marian@radetzki.bi [Lulea University of Technology (Sweden)

    2010-11-15

    The Peak Oil movement has widely spread its message about an impending peak in global oil production, caused by an inadequate resource base. On closer scrutiny, the underlying analysis is inconsistent, void of a theoretical foundation and without support in empirical observations. Global oil resources are huge and expanding, and pose no threat to continuing output growth within an extended time horizon. In contrast, temporary or prolonged supply crunches are indeed plausible, even likely, on account of growing resource nationalism denying access to efficient exploitation of the existing resource wealth.

  9. Peak Oil and other threatening peaks. Chimeras without substance

    Radetzki, Marian [Luleaa University of Technology (Sweden)

    2010-11-15

    The Peak Oil movement has widely spread its message about an impending peak in global oil production, caused by an inadequate resource base. On closer scrutiny, the underlying analysis is inconsistent, void of a theoretical foundation and without support in empirical observations. Global oil resources are huge and expanding, and pose no threat to continuing output growth within an extended time horizon. In contrast, temporary or prolonged supply crunches are indeed plausible, even likely, on account of growing resource nationalism denying access to efficient exploitation of the existing resource wealth. (author)

  10. Peak Oil and other threatening peaks-Chimeras without substance

    The Peak Oil movement has widely spread its message about an impending peak in global oil production, caused by an inadequate resource base. On closer scrutiny, the underlying analysis is inconsistent, void of a theoretical foundation and without support in empirical observations. Global oil resources are huge and expanding, and pose no threat to continuing output growth within an extended time horizon. In contrast, temporary or prolonged supply crunches are indeed plausible, even likely, on account of growing resource nationalism denying access to efficient exploitation of the existing resource wealth.

  11. Electricity Portfolio Management: Optimal Peak / Off-Peak Allocations

    Huisman, Ronald; Mahieu, Ronald; Schlichter, Felix

    2007-01-01

    textabstractElectricity purchasers manage a portfolio of contracts in order to purchase the expected future electricity consumption profile of a company or a pool of clients. This paper proposes a mean-variance framework to address the concept of structuring the portfolio and focuses on how to allocate optimal positions in peak and off-peak forward contracts. It is shown that the optimal allocations are based on the difference in risk premiums per unit of day-ahead risk as a measure of relati...

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

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

    1996-01-01

    rural controls (0.074 fmol/microg DNA, n = 60, P < 0.001). No significant influence on adduct levels was demonstrated from potential confounders, including smoking and diet. The effect of the metabolizing enzymes, GSTM1 and NAT2, on adduct levels was investigated. No statistically significant effects...... levels of exposure to urban air pollution and indicated that these adducts might be helpful as a means of classifying better different exposure groups for epidemiological studies. Furthermore, it demonstrated the ability of 32P-postlabelling to discern small differences in low exposure to ambient air...

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

    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

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

    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

  15. EMG evaluation of hip adduction exercises for soccer players

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

    2014-01-01

    INTRODUCTION: Exercise programmes are used in the prevention and treatment of adductor-related groin injuries in soccer; however, there is a lack of knowledge concerning the intensity of frequently used exercises. OBJECTIVE: Primarily to investigate muscle activity of adductor longus during six...... 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...

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

    Judge Bryan S; James Laura P; Green Jody L; Heard Kennon J; Zolot Liza; Rhyee Sean; Dart Richard C

    2011-01-01

    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 ...

  17. Effect of the diaminocyclohexane carrier ligand on platinum adduct formation, repair, and lethality

    Platinum compounds with the diaminocyclohexane (dach) carrier ligand are of particular interest because cell lines that have developed resistance to platinum compounds in general often retain sensitivity to dach-platinum compounds, suggesting that the dach carrier ligand affects the formation, repair, or lethality of platinum-DNA adducts. The effect of the dach ligand on platinum adduct formation was assessed by using the (HaeIII-HindIII)146 fragment of pBR322 treated to give equal amounts of dach- or ethylene-diamine-platinum adducts. The sites of adduct formation were mapped by digestion with Escherichia coli ABC excinuclease. There were no significant effects of the dach carrier ligand on the types or sites of platinum adduct formation. The effect of the dach ligand on platinum adduct repair was determined by using synthetic oligomers designed to have single, specific platinum adducts. These data suggest that if the carrier ligand has any effect on the repair of platinum adducts, it is more likely to exert that effect on the repair of platinum monoadducts or GNG diadducts rather than on the more abundant AG or GG diadducts. [14C]Thiourea incorporation was used to quantitate the rate of monoadduct to diadduct conversion. Finally, the effect of the dach ligand on platinum adduct lethality was assessed by determining the effect of dach- and en-platinum adducts on the transformation efficiency of pBR322 into a repair-deficient (recA- uvrA-) strain of E. coli. These data suggest that the dach carrier ligand can significantly affect the ability of platinum-DNA adducts to block essential processes such as replication and transcription

  18. Metabolic activation of the antibacterial agent triclocarban by cytochrome P450 1A1 yielding glutathione adducts.

    Schebb, Nils Helge; Muvvala, Jaya B; Morin, Dexter; Buckpitt, Alan R; Hammock, Bruce D; Rice, Robert H

    2014-07-01

    Triclocarban (3,4,4'-trichlorocarbanilide; TCC) is an antibacterial agent used in personal care products such as bar soaps. Small amounts of chemical are absorbed through the epidermis. Recent studies show that residues of reactive TCC metabolites are bound covalently to proteins in incubations with keratinocytes, raising concerns about the potential toxicity of this antimicrobial agent. To obtain additional information on metabolic activation of TCC, this study characterized the reactive metabolites trapped as glutathione conjugates. Incubations were carried out with (14)C-labeled TCC, recombinant CYP1A1 or CYP1B1, coexpressed with cytochrome P450 reductase, glutathione-S-transferases (GSH), and an NADPH-generating system. Incubations containing CYP1A1, but not 1B1, led to formation of a single TCC-GSH adduct with a conversion rate of 1% of parent compound in 2 hours. Using high-resolution mass spectrometry and diagnostic fragmentation, the adduct was tentatively identified as 3,4-dichloro-3'-glutathionyl-4'-hydroxycarbanilide. These findings support the hypothesis that TCC is activated by oxidative dehalogenation and oxidation to a quinone imine. Incubations of TCDD-induced keratinocytes with (14)C-TCC yielded a minor radioactive peak coeluting with TCC-GSH. Thus, we conclude that covalent protein modification by TCC in TCDD-induced human keratinocyte incubations is mainly caused by activation of TCC by CYP1A1 via a dehalogenated TCC derivative as reactive species. PMID:24733789

  19. Shape-based peak identification for ChIP-Seq

    Evans Steven N; Hower Valerie; Pachter Lior

    2011-01-01

    Abstract Background The identification of binding targets for proteins using ChIP-Seq has gained popularity as an alternative to ChIP-chip. Sequencing can, in principle, eliminate artifacts associated with microarrays, and cheap sequencing offers the ability to sequence deeply and obtain a comprehensive survey of binding. A number of algorithms have been developed to call "peaks" representing bound regions from mapped reads. Most current algorithms incorporate multiple heuristics, and despite...

  20. Surveillance considerations for malaria elimination

    Barclay Victoria C; Smith Rachel A; Findeis Jill L

    2012-01-01

    Abstract Constant malaria monitoring and surveillance systems have been highlighted as critical for malaria elimination. The absence of robust monitoring and surveillance systems able to respond to outbreaks in a timely manner undeniably contributed to the failure of the last global attempt to eradicate malaria. Today, technological advances could allow for rapid detection of focal outbreaks and improved deployment of diagnostic and treatment supplies to areas needing support. However, optimi...

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

    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

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

    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...

  3. DNA adducts in marine mussel Mytilus galloprovincialis living in polluted and unpolluted environments

    A generally applicable 32-P post-labelling assay was used to examine for the presence of DNA adducts in mussels experimentally exposed to known carcinogens and in mussels collected from sites impacted by wastewaters. Mussels exposed to seawater artificially polluted with 2-aminofluorene showed exclusively an adduct which was identified as dG-C8-2-aminofluorene. Under the same experimental conditions, Diesel-2 oil did not induce any detectable adducts. When mussel digestive gland DNA was collected and analyzed from one unpolluted site, two moderately impacted sites, and one site heavily impacted by cannery wastewaters, mussel DNA from the unpolluted and only one moderately polluted site showed the presence of 6 to 10 adducts. This indicates they were not related to the pollution. This was further supported by the absence of dose-related adducts. Clear evidence for the presence of pollution-related DNA adducts was, however, found in juvenile mussels collected from an oil refinery site. One major and three minor adducts were detected in these mussels with no adducts detected in juvenile mussels from an unpolluted site. Results indicate that while mussels are capable of metabolizing 2-aminofluorene to a DNA binding species, the environmental pollutants may be metabolized only selectively. Further, the mussel digestive gland DNA also contained DNA modifications which are unrelated to pollutants and their presence appeared to be sex and season dependent

  4. Hubbert's Peak -- A Physicist's View

    McDonald, Richard

    2011-04-01

    Oil, as used in agriculture and transportation, is the lifeblood of modern society. It is finite in quantity and will someday be exhausted. In 1956, Hubbert proposed a theory of resource production and applied it successfully to predict peak U.S. oil production in 1970. Bartlett extended this work in publications and lectures on the finite nature of oil and its production peak and depletion. Both Hubbert and Bartlett place peak world oil production at a similar time, essentially now. Central to these analyses are estimates of total ``oil in place'' obtained from engineering studies of oil reservoirs as this quantity determines the area under the Hubbert's Peak. Knowing the production history and the total oil in place allows us to make estimates of reserves, and therefore future oil availability. We will then examine reserves data for various countries, in particular OPEC countries, and see if these data tell us anything about the future availability of oil. Finally, we will comment on synthetic oil and the possibility of carbon-neutral synthetic oil for a sustainable future.

  5. Fullerene–Carbene Lewis Acid–Base Adducts

    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.

  6. Discriminate Modelling of Peak and Off-Peak Motorway Capacity

    Hashim Mohammed Alhassan

    2013-02-01

    Full Text Available Traffic theory is concerned with the movement of discrete objects in real time over a finite network in 2 Dimensions. It is compatible with or dependent on fundamental diagram of traffic. Without question traffic flow is an essential quantitative parameter that is used in planning, designs and roadway improvements.  Road capacity is significant because it is an important indicator of road performance and can point road managers in the right road maintenance and traffic management direction. In this paper four direct empirical capacity measurement methods have been considered. To test the efficacy of each method, data for peak period, off-peak and transition to peak have been used. The headway and the volume methods lack predictive capability and are suitable only for current assessment of flow rates.  The product limit method is weak in its predictive capability in view of the arbitrariness in the selection of the capacity value. It is also an extreme value method; hence not all volume data can be used with this method. The fundamental diagram method has good predictive capability and furnishes capacity values consistent with the standard of the facility. Unlike other methods, it does not rely on bottleneck conditions to deliver the capacity value.  The paper concluded that each method is uniquely suited to prevailing conditions and can be so employed.

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

    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

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

    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

  9. Depurinating estrogen-DNA adducts, generators of cancer initiation: their minimization leads to cancer prevention.

    Cavalieri, Ercole L; Rogan, Eleanor G

    2016-12-01

    Estrogens can initiate cancer by reacting with DNA. Specific metabolites of endogenous estrogens, the catechol estrogen-3,4-quinones, react with DNA to form depurinating estrogen-DNA adducts. Loss of these adducts leaves apurinic sites in the DNA, generating mutations that can lead to the initiation of cancer. A variety of endogenous and exogenous factors can disrupt estrogen homeostasis, which is the normal balance between estrogen activating and protective enzymes. In fact, if estrogen metabolism becomes unbalanced and generates excessive catechol estrogen 3,4-quinones, formation of depurinating estrogen-DNA adducts increases and the risk of initiating cancer is greater. The levels of depurinating estrogen-DNA adducts are high in women diagnosed with breast cancer and those at high risk for the disease. High levels of depurinating estrogen-DNA adducts before the presence of breast cancer indicates that adduct formation is a critical factor in breast cancer initiation. Women with thyroid or ovarian cancer also have high levels of estrogen-DNA adducts, as do men with prostate cancer or non-Hodgkin lymphoma. Depurinating estrogen-DNA adducts are initiators of many prevalent types of human cancer. These findings and other discoveries led to the recognition that reducing the levels of estrogen-DNA adducts could prevent the initiation of human cancer. The dietary supplements N-acetylcysteine and resveratrol inhibit formation of estrogen-DNA adducts in cultured human breast cells and in women. These results suggest that the two supplements offer an approach to reducing the risk of developing various prevalent types of human cancer. Graphical abstract Major metabolic pathway in cancer initiation by estrogens. PMID:26979321

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

    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

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

    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.

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

    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...

  13. Measuring nonlocal Lagrangian peak bias

    Biagetti, Matteo; Desjacques, Vincent; Paranjape, Aseem

    2013-01-01

    In the Lagrangian approach to halo clustering, nonlocal bias can be generated either in the initial conditions or by the subsequent gravitational motions. Here, we investigate nonlocal Lagrangian bias contributions involving gradients of the linear density field, for which we have predictions from the excursion set peak formalism. We reformulate this approach in order to explicitly take into account the variable describing the crossing of the collapse barrier. This enables us to write down a bias expansion which includes all the bias terms, including the nonlocal ones. Having checked that the model furnishes a reasonable fit to the halo mass function, we extend the 1-point cross-correlation technique of Musso, Paranjape & Sheth (2012) to bias contributions that are chi-squared distributed. We validate the method with numerical realizations of peaks of Gaussian random fields before applying it to N-body simulations. We focus on the lowest (quadratic) order nonlocal bias factors predicted by the excursion s...

  14. Causality and the Doppler Peaks

    Turok, Neil

    1996-01-01

    Could cosmic structure have formed by the action of causal physics within the standard hot big bang, or was a prior period of inflation required? Recently there has been some discussion of whether causal sources could reproduce the pattern of Doppler peaks of the standard scale-invariant adiabatic theory. This paper gives a rigorous definition of causality, and a causal decomposition of a general source. I present an example of a simple causal source which mimics the standard adiabatic theory...

  15. Power peaking nuclear reliability factors

    The Calculational Nuclear Reliability Factor (CNRF) assigned to the limiting power density calculated in reactor design has been determined. The CNRF is presented as a function of the relative power density of the fuel assembly and its radial local. In addition, the Measurement Nuclear Reliability Factor (MNRF) for the measured peak hot pellet power in the core has been evaluated. This MNRF is also presented as a function of the relative power density and radial local within the fuel assembly

  16. Surveillance considerations for malaria elimination

    Barclay Victoria C

    2012-08-01

    Full Text Available Abstract Constant malaria monitoring and surveillance systems have been highlighted as critical for malaria elimination. The absence of robust monitoring and surveillance systems able to respond to outbreaks in a timely manner undeniably contributed to the failure of the last global attempt to eradicate malaria. Today, technological advances could allow for rapid detection of focal outbreaks and improved deployment of diagnostic and treatment supplies to areas needing support. However, optimizing diffusion activities (e.g., distributing vector controls and medicines, as well as deploying behaviour change campaigns requires networks of diverse scholars to monitor, learn, and evaluate data and multiple organizations to coordinate their intervention activities. Surveillance systems that can gather, store and process information, from communities to national levels, in a centralized, widely accessible system will allow tailoring of surveillance and intervention efforts. Different systems and, thus reactions, will be effective in different endemic, geographical or socio-cultural contexts. Investing in carefully designed monitoring technologies, built for a multiple-acter, dynamic system, will help to improve malaria elimination efforts by improving the coordination, timing, coverage, and deployment of malaria technologies.

  17. Can Cognitive Explanations Be Eliminated?

    Hakkarainen, Kai

    The purpose of article is to analyze the arguments of Bruno Latour and Steve Woolgar aimed at eliminating `superfluous' cognitive explanations from discussion of scientific activity. They proposed to a ten-year moratorium on cognitive explanations of scientific activity and promised to reassess explanation in terms of cognition after this period of time if some aspects of scientific inquiry would not be accounted by sociological explanations. Intensive laboratory studies of scientific practice indicated that scientific thinking is not based on mental processes alone but relies on external tools and instruments. On the basis of these kinds of observations, they rejected all cognitive explanations of scientific inquiry. By building on sociocultural theories of cognition, the present study makes the case that the use of conceptual tools significantly transforms cognitive processes. It is concluded that the failure to appreciate cognitive explanations reflects a far toon arrow and non-social concept of cognition: Even after the ten-year moratorium there appears to be many good reasons to reassess the proposal of eliminating cognitive explanations altogether.

  18. Drivers of peak sales for pharmaceutical brands

    Fischer, Marc; Leeflang, Peter S. H.; Verhoef, Peter C.

    2010-01-01

    Peak sales are an important metric in the pharmaceutical industry. Specifically, managers are focused on the height-of-peak-sales and the time required achieving peak sales. We analyze how order of entry and quality affect the level of peak sales and the time-to-peak-sales of pharmaceutical brands.

  19. Structural phase transitions and adduct release in calcium borohydride

    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.

  20. SEM-EDX STUDIES OF CHITOSAN DERIVATIVES-METAL ADDUCTS

    Galo Cárdenas

    2003-12-01

    Full Text Available Chitosan was obtained from shrimps shells (pleuroncodes monodon using chemical methods. A series of chitosan (QScharged with solution of copper, cobalt, nickel and mercury ions were prepared at room temperature using the batch method. N-3,5-diethylamino benzoyl chitosan (QDAB; N,O-dimercapto succinate chitosan (QNOT and 4-aminobenzoate chitosan (QAB derivatives were prepared. The chitosan metal adducts with Cu, Co, Ni and Hg ions and derivatives maximum loading is discussed. Chitosan and derivatives containing copper were analyzed by SEM to find out the morphology of the polymers. Chitosan-Cu and derivatives charged, QDAB-Ni and QDAB-Hg were analyzed by EDX to verify the presence of the metal in the polymeric chain

  1. Characterization of DNA adducts with fourier transform mass spectrometry

    The sensitive detection and unambiguous structural characterization of modified nucleic acid constituents is vital for understanding the nature of DNA modification induced by carcinogenic agents. Fourier transform mass spectrometry (FTMS) combined with matrix-assisted laser desorption provides a powerful technique for examining picomole quantities of modified nucleosides, nucleotides, and oligonucleotides. The structures of these modified biomolecules can be probed in detail with a variety of gas phase processes, including collision-induced dissociation, ion-molecule reactions such as deuterium exchange, and selective cationization reactions. Each of these processes provides a wealth of structural information which can be used to not only identify the adduct present, but also determine its exact site of attachment to the nucleic acid constituent, thereby providing isomeric differentiation. This FTMS technique has been applied to the examination of DNA damage induced by high energy (x-rays) as well as low energy radiation (far ultraviolet)

  2. Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics.

    Sparrow, Janet R

    2016-04-26

    Although currently available treatment options for age-related macular degeneration (AMD) are limited, particularly for atrophic AMD, the identification of predisposing genetic variations has informed clinical studies addressing therapeutic options such as complement inhibitors and anti-inflammatory agents. To lower risk of early AMD, recommended lifestyle interventions such as the avoidance of smoking and the intake of low glycemic antioxidant-rich diets have largely followed from the identification of nongenetic modifiable factors. On the other hand, the challenge of understanding the complex relationship between aging and cumulative damage leading to AMD has fueled investigations of the visual cycle adducts that accumulate in retinal pigment epithelial (RPE) cells and are a hallmark of aging retina. These studies have revealed properties of these compounds that provide insights into processes that may compromise RPE and could contribute to disease mechanisms in AMD. This work has also led to the design of targeted therapeutics that are currently under investigation. PMID:27071115

  3. 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

    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.

  4. Synthesis and mutagenesis of the butadiene-derived N3 2'-deoxyuridine adducts.

    Fernandes, Priscilla H; Hackfeld, Linda C; Kozekov, Ivan D; Hodge, Richard P; Lloyd, R Stephen

    2006-07-01

    1,3-Butadiene is a known carcinogen and mutagen that acts through a variety of metabolic intermediates that react with DNA, forming stable and unstable lesions on dG, dA, dC, and dT. The N3 2'-deoxyuridine adducts are a highly stable, stereoisomeric mixture of adducts derived from the reaction of cytosine with the monoepoxide metabolite of butadiene, followed by spontaneous deamination. In this study, the phosphoramidites and subsequent oligodeoxynucleotides containing the N3 2'-deoxyuridine adducts have been constructed and characterized. Using a single-stranded shuttle vector DNA, the mutagenic potential of these adducts has been tested following replication in mammalian cells. Replication past the N3 2'-deoxyuridine adducts was found to be highly mutagenic with an overall mutation yield of approximately 97%. The major mutations that were observed were C to T transitions and C to A transversions. In vitro, these adducts posed a complete block to both the Klenow fragment of Escherichia coli polymerase I and polymerase epsilon, while these lesions significantly blocked polymerase delta. These data suggested a possible involvement of bypass polymerases in the in vivo replication of these lesions. Overall, these findings indicate that the N3 2'-deoxyuridine adducts are highly mutagenic lesions that may contribute to butadiene-mediated carcinogenesis. PMID:16841966

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

    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.

  6. Seasonal and intertidal impact on DNA adduct levels in gills of blue mussels (Mytilus edulis L.)

    The aim of this study was to elucidate possible seasonal variation in DNA adduct levels in blue mussels (Mytilus edulis), and to investigate the impact of intertidal exposure on the DNA adduct levels, i.e. to explore if DNA adduct levels in mussels in the intertidal zone differ from those in the subtidal zone. Blue mussels were deployed separately in the intertidal and subtidal zone at a contaminated and a reference site in Iceland, and sampled regularly during one year. Gill DNA adduct levels were found to be higher in mussels in the intertidal zone compared to the subtidal zone at the contaminated site, the difference being largest in winter. Total PAH tissue levels were also higher in mussels in the intertidal zone. Seasonal variation was observed in both DNA adduct and PAH tissue levels in mussels at the contaminated site, with lower levels from the time of transplantation in summer to autumn, maximum levels in winter, which decreased to lower levels again in spring and summer the following year. DNA adducts and PAH levels were low or below the detection limits in mussels at the reference site at all times, both in the intertidal and subtidal zone. - Gill DNA adduct and total PAH tissue levels were higher in mussels in the intertidal than subtidal zone, and higher in winter than summer

  7. Seasonal and intertidal impact on DNA adduct levels in gills of blue mussels (Mytilus edulis L.)

    Skarpheoinsdottir, Halldora [Institute of Applied Environmental Research, Laboratory for Aquatic Ecotoxicology, Stockholm University, 106 91 Stockholm (Sweden)]. E-mail: halldora@itm.su.se; Ericson, Gunilla [Institute of Applied Environmental Research, Laboratory for Aquatic Ecotoxicology, Stockholm University, 106 91 Stockholm (Sweden); Halldorsson, Halldor P. [Institute of Biology, University of Iceland, Askja, Sturlugata 7, 101 Reykjavik (Iceland); University of Iceland, Sandgeroei Marine Centre, Garoevegur 1, 245 Sandgeroei (Iceland); Svavarsson, Joerundur [Institute of Biology, University of Iceland, Askja, Sturlugata 7, 101 Reykjavik (Iceland); University of Iceland, Sandgeroei Marine Centre, Garoevegur 1, 245 Sandgeroei (Iceland)

    2005-07-15

    The aim of this study was to elucidate possible seasonal variation in DNA adduct levels in blue mussels (Mytilus edulis), and to investigate the impact of intertidal exposure on the DNA adduct levels, i.e. to explore if DNA adduct levels in mussels in the intertidal zone differ from those in the subtidal zone. Blue mussels were deployed separately in the intertidal and subtidal zone at a contaminated and a reference site in Iceland, and sampled regularly during one year. Gill DNA adduct levels were found to be higher in mussels in the intertidal zone compared to the subtidal zone at the contaminated site, the difference being largest in winter. Total PAH tissue levels were also higher in mussels in the intertidal zone. Seasonal variation was observed in both DNA adduct and PAH tissue levels in mussels at the contaminated site, with lower levels from the time of transplantation in summer to autumn, maximum levels in winter, which decreased to lower levels again in spring and summer the following year. DNA adducts and PAH levels were low or below the detection limits in mussels at the reference site at all times, both in the intertidal and subtidal zone. - Gill DNA adduct and total PAH tissue levels were higher in mussels in the intertidal than subtidal zone, and higher in winter than summer.

  8. The Sacramento Peak fast microphotometer

    Arrambide, M. R.; Dunn, R. B.; Healy, A. W.; Porter, R.; Widener, A. L.; November, L. J.; Spence, G. E.

    1984-01-01

    The Sacramento Peak Observatory Fast Microphotometer translates an optical system that includes a laser and photodiode detector across the film to scan the Y direction. A stepping motor moves the film gate in the X direction. This arrangement affords high positional accuracy, low noise (0.002 RMS density units), modest speed (5000 points/second), large dynamic range (4.5 density units), high stability (0.005 density units), and low scattered light. The Fast Microphotometer is interfaced to the host computer by a 6502 microprocessor.

  9. 32P analysis of DNA adducts in tissues of benzene-treated rats

    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

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

    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

  11. Polycyclic aromatic hydrocarbon-DNA adducts and survival among women with breast cancer

    Polycyclic aromatic hydrocarbons (PAH) are mammary carcinogens in animal studies, and a few epidemiologic studies have suggested a link between elevated levels of PAH-DNA adducts and breast cancer incidence. An association between PAH-DNA adducts and survival among breast cancer cases has not been previously reported. We conducted a survival analysis among women with newly diagnosed invasive breast cancer between 1996 and 1997, enrolled in the Long Island Breast Cancer Study Project. DNA was isolated from blood samples that were obtained from cases shortly after diagnosis and assayed for PAH-DNA adducts using ELISA. Among the 722 cases with PAH-DNA adduct measurements, 97 deaths (13.4%) from all causes and 54 deaths (7.5%) due to breast cancer were reported to National Death Index (NDI) by December 31, 2002. Using Cox proportional hazards models and controlling for age at diagnosis, we did not find evidence that all-cause mortality (hazard ratio (HR)=0.88; 95% confidence interval (CI): 0.57-1.37), or breast cancer mortality (HR=1.20; 95% CI: 0.63-2.28) was strongly associated with detectable PAH-DNA adduct levels compared with non-detectable adducts; additionally, no dose-response association was observed. Among a subgroup with treatment data (n=520), adducts were associated with over a two-fold higher mortality among those receiving radiation, but mortality for adducts was reduced among hormone therapy users. Results from this large population-based study do not provide strong support for an association between detectable PAH-DNA adducts and survival among women with breast cancer, except perhaps among those receiving radiation treatment

  12. Inhaled cigarette smoke induces the formation of DNA adducts in lungs of rats

    Cigarette smoking causes a variety of adverse human health effects, including lung cancer. The molecular events associated with smoke-induced carcinogenesis are thought to be related in part to the genotoxic activities of the chemicals associated with smoke. The purpose of this investigation was to determine the molecular dosimetry of compounds in cigarette smoke in lungs of rats exposed by inhalation. These studies investigated the effects of exposure mode, sex, and time (adduct persistence) on the level of DNA adducts. Male and female F344/N rats were exposed 6 hr/day, 5 days/week for 22 days to cigarette smoke by nose-only intermittent (NOI), nose-only continuous (NOC), or whole-body continuous (WBC) exposures. Separate groups of rats were sham-exposed nose-only (NOS) or whole-body (WBS) to filtered air. All smoke exposure modes yielded daily smoke exposure concentration X time products of 600 mg particulate.hr/m3 for the first week and 1200 mg particulate.hour/m3 thereafter. Groups of rats were killed at 18 hr and 3 weeks after the 22-day exposure period and DNA adducts in lung tissues were quantified by the 32P-postlabeling method. There were significant (p less than 0.05) increases in levels of clearly resolved lung DNA adducts in male and female rats exposed to smoke compared to sham-exposed rats. There were no significant effects of exposure mode or sex on lung DNA adducts. Mean levels (+/- SE) of clearly resolved lung DNA adducts for both sexes combined in NOI, NOC, WBC, NOS, and WBS groups were 50 +/- 4, 52 +/- 6, 52 +/- 7, 21 +/- 6, and 22 +/- 4 adducts per 10(9) bases, respectively. Levels of clearly resolved DNA adducts were significantly less in lungs of rats killed 3 weeks after exposure and had declined to near control levels, suggesting that smoke-induced adducts are repaired by lung DNA repair enzymes

  13. DNA-nicotine adduction of lung and liver of mice exposed to passive smoking studied by AMS

    The author presents the measurement of adduction of mice lung or liver DNA with nicotine by accelerator mass spectrometry (AMS). Mice were exposed in a toxicity infecting chamber filled up with cigarette smoke for a period of time of simulate the exposure of mice to passive smoking. The dose of nicotine inhaled by mice was determined. The results of AMS showed, when the dose of inhaled nicotine ranged from 33 μg/kg to 330 μg/kg, the adducts number of lung DNA was 103-104 adducts/1012 nucleotides, and the adducts increased linearly with increasing dose of nicotine; the adducts number of liver DNA reached to 104-105 adducts/1012 nucleotides, when the dose of nicotine ranged from 99 μg/kg to 330 μg/kg, and the adducts increased vigorously as dose of nicotine increased. Comparing the DNA adducts levels of the same nicotine dose, liver DNA adducts were more than lung DNA adducts. This study also suggested that the other components of cigarette smoke have synergic effect on the formation of nicotine derived DNA adducts

  14. Economic effects of peak oil

    Assuming that global oil production peaked, this paper uses scenario analysis to show the economic effects of a possible supply shortage and corresponding rise in oil prices in the next decade on different sectors in Germany and other major economies such as the US, Japan, China, the OPEC or Russia. Due to the price-inelasticity of oil demand the supply shortage leads to a sharp increase in oil prices in the second scenario, with high effects on GDP comparable to the magnitude of the global financial crises in 2008/09. Oil exporting countries benefit from high oil prices, whereas oil importing countries are negatively affected. Generally, the effects in the third scenario are significantly smaller than in the second, showing that energy efficiency measures and the switch to renewable energy sources decreases the countries' dependence on oil imports and hence reduces their vulnerability to oil price shocks on the world market. - Highlights: ► National and sectoral economic effects of peak oil until 2020 are modelled. ► The price elasticity of oil demand is low resulting in high price fluctuations. ► Oil shortage strongly affects transport and indirectly all other sectors. ► Global macroeconomic effects are comparable to the 2008/2009 crisis. ► Country effects depend on oil imports and productivity, and economic structures.

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

    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.

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

    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.

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

    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

  18. Test Bias and the Elimination of Racism

    Sedlacek, William E.

    1977-01-01

    Three types of test bias are discussed: content bias, atmosphere bias, and use bias. Use bias is considered the most important. Tests reflect the bias in society, and eliminating test bias means eliminating racism and sexism in society. A six-stage model to eliminate racism and sexism is presented. (Author)

  19. Improved Peak Detection and Deconvolution of Native Electrospray Mass Spectra from Large Protein Complexes.

    Lu, Jonathan; Trnka, Michael J; Roh, Soung-Hun; Robinson, Philip J J; Shiau, Carrie; Fujimori, Danica Galonic; Chiu, Wah; Burlingame, Alma L; Guan, Shenheng

    2015-12-01

    Native electrospray-ionization mass spectrometry (native MS) measures biomolecules under conditions that preserve most aspects of protein tertiary and quaternary structure, enabling direct characterization of large intact protein assemblies. However, native spectra derived from these assemblies are often partially obscured by low signal-to-noise as well as broad peak shapes because of residual solvation and adduction after the electrospray process. The wide peak widths together with the fact that sequential charge state series from highly charged ions are closely spaced means that native spectra containing multiple species often suffer from high degrees of peak overlap or else contain highly interleaved charge envelopes. This situation presents a challenge for peak detection, correct charge state and charge envelope assignment, and ultimately extraction of the relevant underlying mass values of the noncovalent assemblages being investigated. In this report, we describe a comprehensive algorithm developed for addressing peak detection, peak overlap, and charge state assignment in native mass spectra, called PeakSeeker. Overlapped peaks are detected by examination of the second derivative of the raw mass spectrum. Charge state distributions of the molecular species are determined by fitting linear combinations of charge envelopes to the overall experimental mass spectrum. This software is capable of deconvoluting heterogeneous, complex, and noisy native mass spectra of large protein assemblies as demonstrated by analysis of (1) synthetic mononucleosomes containing severely overlapping peaks, (2) an RNA polymerase II/α-amanitin complex with many closely interleaved ion signals, and (3) human TriC complex containing high levels of background noise. Graphical Abstract ᅟ. PMID:26323614

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

    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.

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

    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.

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

    Veglia, Fabrizio; Loft, Steffen; Matullo, Giuseppe; Peluso, Marco; Munnia, Armelle; Perera, Frederica; Phillips, David H; Tang, Deliang; Autrup, Herman; Raaschou-Nielsen, Ole; Tjønneland, Anne; Vineis, Paolo

    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). The...

  3. 4-Aminobiphenyl-DNA adducts and p53 mutations in bladder cancer.

    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

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

    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.

  5. Fast repair activities of quercetin and rutin toward dGMP hydroxyl radical adducts

    The repair activities and mechanisms of both quercetin and rutin towards the oxidizing deoxyguanosine monophosphate (d GMP) hydroxyl radical adduct were investigated with pulse radiolytic technique. On pulse irradiation of nitrous oxide saturated 2 mm d GMP aqueous solution containing 0.1 mm quercetin, the transient absorption spectrum of the d GMP hydroxyl radical adduct decays with the formation of phenoxyl radical of quercetin within tens of microseconds. It indicates that there is a repair reaction between d GMP hydroxyl radical adduct and quercetin. The repair activity of rutin towards hydroxyl radical adducts of d GMP was also observed. The rate constants of the repair reactions were calculated to be 3.05x108 and 1.31x108 M-1 s-1for quercetin and rutin, respectively. This result together with our previous studies demonstrated that non-enzymatic, fast repair is a universal repair mechanism of phenolic antioxidants.

  6. Development of methods to measure hemoglobin adducts by gel electrophoresis - Preliminary results

    Chemical adducts formed on blood hemoglobin may be a useful biomarker for assessing human exposures to these compounds. This paper reports preliminary results in the development of methods to measure such adducts that may be generally applicable for a wide variety of chemicals. Male F344/N rats were intraperitoneally injected with 14C-BaP dissolved in corn oil. Twenty-four hours later, the rats were sacrificed. Blood samples were collected and globin was isolated. Globin protein was then cleaved into peptide fragments using cyanogen bromide and the fragments separated using 2-dimensional gel electrophoresis. The results showed that the adducted 14C-globin fragments migrated to different areas of the gel than did unadducted fragments. Further research is being conducted to develop methods that will allow quantitation of separated adducted globin fragments from human blood samples without the use of a radiolabel. (author)

  7. Steam generator snubber elimination program

    Hydraulic snubbers are used in Steam Generator (SG) upper support systems because of the snubbers ability to accommodate the large thermal movement of the SG during plant heatup and cooldown while providing restraint to the Reactor Coolant Loop (RCL) for dynamic events such as postulated pipe ruptures and earthquakes. Due to the complexity of the design of the SG upper support system, several factors can significantly affect the performance of the hydraulic snubbers and contribute to the continuing need to monitor and test the functionality of the snubbers. In some cases, snubber malfunctions have caused extended plant outages. Recent advancements in computer technology have made it economically feasible to perform the engineering analyses required to eliminate all of the SG snubbers. Similar to the SG snubber reduction programs started in the 1980s, this paper presents a process of implementing load reduction techniques and taking advantage of component reserve margins. Non-linear time history analyses are required for seismic and pipe rupture loadings to more accurately predict the behavior of the RCL and loads on the primary components. Even without considering the ALARA savings, the payback period to implement a full SG snubber removal program is typically less than two fuel cycles. (author)

  8. Ultrasensitive isolation, identification and quantification of DNA–protein adducts by ELISA-based RADAR assay

    Kiianitsa, Kostantin; Maizels, Nancy

    2014-01-01

    Enzymes that form transient DNA–protein covalent complexes are targets for several potent classes of drugs used to treat infectious disease and cancer, making it important to establish robust and rapid procedures for analysis of these complexes. We report a method for isolation of DNA–protein adducts and their identification and quantification, using techniques compatible with high-throughput screening. This method is based on the RADAR assay for DNA adducts that we previously developed (Kiia...

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

    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 ...

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

    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.

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

    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 ...

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

    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...

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

    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...

  14. Adducts of Amine with Dimeric Rhodium(II) Tetracarboxylates - Formation of Nitrogenous Chiral Center

    Rhodium(II) tetracarboksylates Rh2(RCO2)4 (1a) are able to produce various complexes with organic ligands, like the 1:1 and 2:1 adducts containing axially bonded ligands (1b), or the compounds with rearranged dirhodium core (1c). The solution of dirhodium(II) tetracarboxylate and a ligand usually contains a mixture of adducts, due to ligand exchange and different equilibriums between species. However, application of nuclear magnetic resonance measurements at reduced temperature allows often observing the signals of all species in the solution. Ligands containing nitrogen atom were the subject of our previous investigation. It was found that dirhodium salts are able to form both 1:1 and 2:1 adducts with an amine, depending on reagents ratio. The present investigations are devoted to the amines with general formula NRR'R', is the amines having potential nitrogenous chiral center. An amine with three various substituents NRR'R' is formally a chiral molecule, but in the solution the molecule forms racemic mixture due to fast pyramidal inversion at the nitrogen atom. However, dirhodium(II) tetracarboxylates bonding the amine acts as an agent freezing pyramidal inversion at nitrogen atom, and results in formation of a new, nitrogenous chiral center in the adduct. Thus, the chiral dirhodium salt (4R)-Rh2[(CF3)(OCH3)(Ph)CO2]4 forms with benzyl-ethyl-methylamine five adducts: (4R)/(S), (4R)/(R) (1:1 adducts) and (R)/(4R)/(R), (R)/(4R)/(S), (S)/(4R)/(S) (2:1 adducts). All these diastereoisomers were detected by means of low temperature NMR (253 K). Similar effect was observed for the adducts with methyl-(1-phenylethyl)- amine, PhCH(NHCH3)CH3, having both nitrogenous and carbon chiral centers. (author)

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

    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 ...

  16. Supercritical fluid extraction (SFE) of actinide complexes. Communication 1. SFE of uranyl trifluoroacetylacetonate adduct with pyridine

    Comparison of some methods of ascertaining the solubility of metal complexes in supercritical carbon dioxide (SC-CO2) was made. It is shown that solubility of uranyl trifluoroacetylacetonate adduct with pyridine exceeds 100 g/l (36 mg of uranium per ml) of SC-CO2 under the pressure of 300 atm and temperature of 60 deg C. Partial degrading of the uranyl trifluoroacetylacetonate adduct with pyridine is pointed out

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

    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 ...

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

    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...

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

    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...

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

    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...

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

    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

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

    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...

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

    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...

  4. Implications of acetaldehyde-derived DNA adducts for understanding alcohol-related carcinogenesis.

    Balbo, Silvia; Brooks, Philip J

    2015-01-01

    Among various potential mechanisms that could explain alcohol carcinogenicity, the metabolism of ethanol to acetaldehyde represents an obvious possible mechanism, at least in some tissues. The fundamental principle of genotoxic carcinogenesis is the formation of mutagenic DNA adducts in proliferating cells. If not repaired, these adducts can result in mutations during DNA replication, which are passed on to cells during mitosis. Consistent with a genotoxic mechanism, acetaldehyde does react with DNA to form a variety of different types of DNA adducts. In this chapter we will focus more specifically on N2-ethylidene-deoxyguanosine (N2-ethylidene-dG), the major DNA adduct formed from the reaction of acetaldehyde with DNA and specifically highlight recent data on the measurement of this DNA adduct in the human body after alcohol exposure. Because results are of particular biological relevance for alcohol-related cancer of the upper aerodigestive tract (UADT), we will also discuss the histology and cytology of the UADT, with the goal of placing the adduct data in the relevant cellular context for mechanistic interpretation. Furthermore, we will discuss the sources and concentrations of acetaldehyde and ethanol in different cell types during alcohol consumption in humans. Finally, in the last part of the chapter, we will critically evaluate the concept of carcinogenic levels of acetaldehyde, which has been raised in the literature, and discuss how data from acetaldehyde genotoxicity are and can be utilized in physiologically based models to evaluate exposure risk. PMID:25427902

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

    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.

  6. Scavenging of Toxic Acrolein by Resveratrol and Hesperetin and Identification of Adducts.

    Wang, Weixin; Qi, Yajing; Rocca, James R; Sarnoski, Paul J; Jia, Aiqun; Gu, Liwei

    2015-11-01

    The objective of this study was to investigate the ability of resveratrol and hesperetin to scavenge acrolein at pH 7.4 and 37 °C. About 6.4 or 5.2% of acrolein remained after reaction with resveratrol or hesperetin for 12 h at equimolar concentrations. An acrolein-resveratrol adduct and two acrolein-hesperetin adducts were isolated. Their structures were elucidated using mass and NMR spectroscopy. Acrolein reacted with resveratrol at the C-2 and C-3 positions through nucleophilic addition and formed an additional heterocyclic ring. Two similar monoacrolein-conjugated adducts were identified for hesperetin. Spectroscopic data suggested each acrolein-hesperetin adduct was a mixture of four stereoisomers due to the existence of two chiral carbon atoms. Yield of adducts was low at pH 5.4 but increased at pH 7.4 and 8.4. Higher pH also promoted the formation of diacrolein adducts. Results suggest that resveratrol and hesperetin exert health benefits in part through neutralizing toxic acrolein in vivo. PMID:26457480

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

    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

  8. Neurofeedback training for peak performance

    Marek Graczyk

    2014-11-01

    Full Text Available [b]aim[/b]. One of the applications of the Neurofeedback methodology is peak performance in sport. The protocols of the neurofeedback are usually based on an assessment of the spectral parameters of spontaneous EEG in resting state conditions. The aim of the paper was to study whether the intensive neurofeedback training of a well-functioning Olympic athlete who has lost his performance confidence after injury in sport, could change the brain functioning reflected in changes in spontaneous EEG and event related potentials (ERPs. [b]case study[/b]. The case is presented of an Olympic athlete who has lost his performance confidence after injury in sport. He wanted to resume his activities by means of neurofeedback training. His QEEG/ERP parameters were assessed before and after 4 intensive sessions of neurotherapy. Dramatic and statistically significant changes that could not be explained by error measurement were observed in the patient. [b]conclusion[/b]. Neurofeedback training in the subject under study increased the amplitude of the monitoring component of ERPs generated in the anterior cingulate cortex, accompanied by an increase in beta activity over the medial prefrontal cortex. Taking these changes together, it can be concluded that that even a few sessions of neurofeedback in a high performance brain can significantly activate the prefrontal cortical areas associated with increasing confidence in sport performance.

  9. Peak Detection Using Wavelet Transform

    Omar Daoud

    2014-07-01

    Full Text Available A new work based-wavelet transform is designed to o vercome one of the main drawbacks that found in the present new technologies. Orthogonal Frequency Divi sion Multiplexing (OFDMis proposed in the literature to enhance the multimedia resolution. Ho wever, the high peak power (PAPR values will obstr uct such achievements. Therefore, a new proposition is found in this work, making use of the wavelet transforms methods, and it is divided into three ma in stages; de-noising stage, thresholding stage and then the replacement stage. In order to check the system stages validity; a mat hematical model has been built and its checked afte r using a MATLAB simulation. A simulated bit error ra te (BER achievement will be compared with our previously published work, where an enhancement fro m 8×10 -1 to be 5×10 -1 is achieved. Moreover, these results will be compared to the work found in the l iterature, where we have accomplished around 27% PAPR extra reduction. As a result, the BER performance has been improved for the same bandwidth occupancy. Moreover and due to the de-noise stage, the verification rate ha s been improved to reach 81%. This is in addition t o the noise immunity enhancement.

  10. Elimination of Onchocerciasis from Mexico.

    Mario A Rodríguez-Pérez

    Full Text Available Mexico is one of the six countries formerly endemic for onchocerciasis in Latin America. Transmission has been interrupted in the three endemic foci of that country and mass drug distribution has ceased. Three years after mass drug distribution ended, post-treatment surveillance (PTS surveys were undertaken which employed entomological indicators to check for transmission recrudescence.In-depth entomologic assessments were performed in 18 communities in the three endemic foci of Mexico. None of the 108,212 Simulium ochraceum s.l. collected from the three foci were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA, resulting in a maximum upper bound of the 95% confidence interval (95%-ULCI of the infective rate in the vectors of 0.035/2,000 flies examined. This is an order of magnitude below the threshold of a 95%-ULCI of less than one infective fly per 2,000 flies tested, the current entomological criterion for interruption of transmission developed by the international community. The point estimate of seasonal transmission potential (STP was zero, and the upper bound of the 95% confidence interval for the STP ranged from 1.2 to 1.7 L3/person/season in the different foci. This value is below all previous estimates for the minimum transmission potential required to maintain the parasite population.The results from the in-depth entomological post treatment surveillance surveys strongly suggest that transmission has not resumed in the three foci of Mexico during the three years since the last distribution of ivermectin occurred; it was concluded that transmission remains undetectable without intervention, and Onchocerca volvulus has been eliminated from Mexico.

  11. Fabrication techniques to eliminate postweld heat treatment

    Postweld heat treatments to reduce residual stresses (stress relief operations) have been a common practice in the pressure vessel industry for a large number of years. A suitable heat treatment operation can, in particular for low alloy steels, have additional beneficial effects, i.e. a reduction in peak hardness values in the heat-affected zone, an improvement in weld metal properties, and a lowering of the adverse effects of the welding process on the mechanical properties of the parent material adjacent to the weld metal. However, continuing studies in the field of brittle fracture, improved parent materials, and more sophisticated nondestructive testing techniques have led to the elimination of such a practice in ever-increasing thickness ranges and types of material. For instance, the recently issued BS 5500 compared with BS 1113 (1969) lifts the thickness limit requiring stress relief in certain circumstances from 19 to 35mm for C steels. With respect to materials the CEGB has stated that as a result of successful operational experience it will no longer be necessary to postweld heat treat butt welds in 2 1/4 Cr-1Mo tubes of certain dimensions. Despite this trend, over a period of years a number of instances have arisen where, because of some factor, postweld heat treatment, although perhaps desirable, is not possible. This Paper describes several such examples. It must be noted that the examples quoted consist of relatively important and major items. It has been necessary within the confines of this Paper to condense the reports. It is hoped that no significant factors have been omitted. (author)

  12. Pre-Peak and Post-Peak Rock Strain Characteristics During Uniaxial Compression by 3D Digital Image Correlation

    Munoz, H.; Taheri, A.; Chanda, E. K.

    2016-07-01

    A non-contact optical method for strain measurement applying three-dimensional digital image correlation (3D DIC) in uniaxial compression is presented. A series of monotonic uniaxial compression tests under quasi-static loading conditions on Hawkesbury sandstone specimens were conducted. A prescribed constant lateral-strain rate to control the applied axial load in a closed-loop system allowed capturing the complete stress-strain behaviour of the rock, i.e. the pre-peak and post-peak stress-strain regimes. 3D DIC uses two digital cameras to acquire images of the undeformed and deformed shape of an object to perform image analysis and provides deformation and motion measurements. Observations showed that 3D DIC provides strains free from bedding error in contrast to strains from LVDT. Erroneous measurements due to the compliance of the compressive machine are also eliminated. Furthermore, by 3D DIC technique relatively large strains developed in the post-peak regime, in particular within localised zones, difficult to capture by bonded strain gauges, can be measured in a straight forward manner. Field of strains and eventual strain localisation in the rock surface were analysed by 3D DIC method, coupled with the respective stress levels in the rock. Field strain development in the rock samples, both in axial and shear strain domains suggested that strain localisation takes place progressively and develops at a lower rate in pre-peak regime. It is accelerated, otherwise, in post-peak regime associated with the increasing rate of strength degradation. The results show that a major failure plane, due to strain localisation, becomes noticeable only long after the peak stress took place. In addition, post-peak stress-strain behaviour was observed to be either in a form of localised strain in a shearing zone or inelastic unloading outside of the shearing zone.

  13. Novel pyrano and vinylphenol adducts of deoxyanthocyanidins in sorghum sourdough.

    Bai, Yunpeng; Findlay, Brandon; Maldonado, Alma Fernanda Sanchez; Schieber, Andreas; Vederas, John C; Gänzle, Michael G

    2014-11-26

    This study determined the fate of deoxyanthocyanidins in sorghum sourdoughs. Sourdoughs prepared from the red sorghum variety Town were fermented with the caffeic acid-decarboxylating strains Lactobacillus plantarum FUA3171 and the decarboxylase negative L. casei FUA3166. Deoxyanthocyanidins were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Apigeninidin and methoxyapigeninidin were the major deoxyanthocyanidins prior to fermentation. During fermentation, novel deoxyanthocyanidins were formed. Purification by preparative LC, followed by NMR analysis and high-resolution MS identified two of the compounds as 6-deoxyanthocyanidin-vinylphenol and pyrano-3-deoxyanthocyanidin. To identify pathways for their formation, sorghum was fermented with single strains, L. plantarum or L. casei. 6-Deoxyanthocyanidin-vinylphenol and pyrano-3-deoxyanthocyanidin were formed only during fermentation with L. plantarum FUA3171, indicating a role of vinylphenol in their formation. Chemical synthesis confirmed that 6-deoxyanthocyanidin-vinylphenol and pyrano-3-deoxyanthocyanidin are formed from apigeninidin with vinylphenol but not with p-coumaric acid as reactants. In conclusion, the products of microbial decarboxylation of hydroxycinnamic acids convert apigeninidin and methoxyapigeninidin to pyrano-3-deoxyanthocyanidins and vinylphenol adducts. PMID:25370078

  14. Peak Strain in Regressing Finocyl Port Propellant Grainsunder Pressure Loading

    Himanshu Shekhar

    2007-03-01

    Full Text Available Finite element analysis (FEM has been conducted for case-bonded finocyl port propellantcross section under pressure loading conditions during burning. Peak strain is found todecrease in course of burning, hence, analysis of any intermediate configuration in courseof burning is not required for assessing margin of safety in finocyl port propellant grains.The Power Law proposed1 has also been used to predict peak strain. Variation in strainsobtained by FEM and using the Power Law is found to be matching closely with findingsreported in CPIA (Chemical Propulsion Information Agency publications. Extension indomain of power law to regressing pressurised finocyl port propellant grain eliminates dependenceon time-consuming computer- intensive FEM computations without compromising the accuracyof results.

  15. Mapping residual transmission for malaria elimination.

    Reiner, Robert C; Le Menach, Arnaud; Kunene, Simon; Ntshalintshali, Nyasatu; Hsiang, Michelle S; Perkins, T Alex; Greenhouse, Bryan; Tatem, Andrew J; Cohen, Justin M; Smith, David L

    2015-01-01

    Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections . In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show 'malariogenic potential', a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination. PMID:26714110

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

    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.

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

    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

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

    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...

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

    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

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

    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

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

    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.

  2. Peak-flow characteristics of Virginia streams

    Austin, Samuel H.; Krstolic, Jennifer L.; Wiegand, Ute

    2011-01-01

    Peak-flow annual exceedance probabilities, also called probability-percent chance flow estimates, and regional regression equations are provided describing the peak-flow characteristics of Virginia streams. Statistical methods are used to evaluate peak-flow data. Analysis of Virginia peak-flow data collected from 1895 through 2007 is summarized. Methods are provided for estimating unregulated peak flow of gaged and ungaged streams. Station peak-flow characteristics identified by fitting the logarithms of annual peak flows to a Log Pearson Type III frequency distribution yield annual exceedance probabilities of 0.5, 0.4292, 0.2, 0.1, 0.04, 0.02, 0.01, 0.005, and 0.002 for 476 streamgaging stations. Stream basin characteristics computed using spatial data and a geographic information system are used as explanatory variables in regional regression model equations for six physiographic regions to estimate regional annual exceedance probabilities at gaged and ungaged sites. Weighted peak-flow values that combine annual exceedance probabilities computed from gaging station data and from regional regression equations provide improved peak-flow estimates. Text, figures, and lists are provided summarizing selected peak-flow sites, delineated physiographic regions, peak-flow estimates, basin characteristics, regional regression model equations, error estimates, definitions, data sources, and candidate regression model equations. This study supersedes previous studies of peak flows in Virginia.

  3. A Brief Discussion of eliminating Grammatical Ambiguity

    张俊

    2014-01-01

    As we all know that one kind of language structure has more than one meaning,to be called ambiguity.Generally thought,the grammatical ambiguity is quite complex in English,and this article pays attention to eliminating English grammatical ambiguity and making the shallow analysis on the three kinds of strategies of eliminating ambiguity.

  4. On the decay of peak 3 in the glow curve of TLD-100

    It was suggested that the ratio peak 3/peak 5 can be used to estimate the time elapsed between the irradiation and readout of a personal dosimeter of TLD-100.. Horowitz and Yossian[2] claim that this statement might be wrong since Moscovitch did not study the effect of the time between prior readout and the irradiation. The possible fading of unfilled traps can also affect the peak 3/peak 5 ratio. We measured the ratio peak 3/(peak 4 + peak 5) and found that it depends actually on the time between the prior readout and the last readout (the sum of the pre-irradiation and post-irradiation times) as can be seen in table 1. This observation eliminates the possibility of measuring the elapsed time after irradiation. The decay of peak 3/(peak 4 + peak 5) for short pre-irradiation time can be plotted as signal vs. log(t) (figure 1) as was done by Moscovitch. However this functional form has no physical meaning and if exponential decay was looked for it was found to be composed of the sum of two exponential terms (figure 2), indicating that probably peak 3 is composed of two kinds of traps

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

    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. PMID:24623226

  6. Induction of stable protein-deoxyribonucleic acid adducts in Chinese hamster cell chromatin by ultraviolet light

    Ultraviolet (uv)-light-mediated formation of protein-DNA adducts in Chinese hamster cell chromatin was investigated in an attempt to compare chromatin alterations induced in vitro with those observed in vivo. Three independent methods of analysis indicated stable protein-DNA associations: a membrane filter assay which retained DNA on the filter in the presence of high salt-detergent; a Sepharose 4B column assay in which protein eluted coincident with DNA; and a CsCl density gradient equilibrium assay which showed both protein and DNA banding at densities other than their respective native densities. Treatment of the irradiated chromatin with DNase provided further evidence that protein--DNA and not protein-protein adducts were being observed in the column assay. There is a fluence-dependent response of protein-DNA adduct formation when the chromatin is irradiated at low ionic strength and is linear for protein over the range studied. When the chromatin is exposed to differing conditions of pH, ionic strength, or divalent metal ion concentration, the quantity of adduct formed upon uv irradiation varies. Susceptibility to adduct formation can be partially explained in terms of the condensation state of the chromatin and other factors such as rearrangement, denaturation, and dissociation of the chromatin components. Besides providing information on the biological significance of these types of uv-induced lesions, this technique may be useful as a probe of chromatin structure

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

    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.

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

    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

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

    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

  10. On the trail of double peak hydrographs

    Martínez-Carreras, Núria; Hissler, Christophe; Gourdol, Laurent; Klaus, Julian; Juilleret, Jérôme; François Iffly, Jean; McDonnell, Jeffrey J.; Pfister, Laurent

    2016-04-01

    A double peak hydrograph features two peaks as a response to a unique rainfall pulse. The first peak occurs at the same time or shortly after the precipitation has started and it corresponds to a fast catchment response to precipitation. The delayed peak normally starts during the recession of the first peak, when the precipitation has already ceased. Double peak hydrographs may occur for various reasons. They can occur (i) in large catchments when lag times in tributary responses are large, (ii) in urban catchments where the first peak is often caused by direct surface runoff on impervious land cover, and the delayed peak to slower subsurface flow, and (iii) in non-urban catchments, where the first and the delayed discharge peaks are explained by different runoff mechanisms (e.g. overland flow, subsurface flow and/or deep groundwater flow) that have different response times. Here we focus on the third case, as a formal description of the different hydrological mechanisms explaining these complex hydrological dynamics across catchments with diverse physiographic characteristics is still needed. Based on a review of studies documenting double peak events we have established a formal classification of catchments presenting double peak events based on their regolith structure (geological substratum and/or its weathered products). We describe the different hydrological mechanisms that trigger these complex hydrological dynamics across each catchment type. We then use hydrometric time series of precipitation, runoff, soil moisture and groundwater levels collected in the Weierbach (0.46 km2) headwater catchment (Luxembourg) to better understand double peak hydrograph generation. Specifically, we aim to find out (1) if the generation of a double peak hydrograph is a threshold process, (2) if the hysteretic relationships between storage and discharge are consistent during single and double peak hydrographs, and (3) if different functional landscape units (the hillslopes

  11. A new control strategy for tracking peak power in a wind or wave energy system

    Rao, S. Srinivasa; Murthy, B.K. [Department of Electrical Engineering, National Institute of Technology, Warangal 506 004, Andhra Pradesh (India)

    2009-06-15

    This paper proposes a novel control strategy for tracking peak power in a wind or wave energy system using a squirrel cage induction generator. It eliminates wind speed measurement or estimation and uses a simple scalar technique by exploiting the cubic nature of the power curve. The method works even when air velocity is varying dynamically. (author)

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

    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

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

    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.

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

    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

  15. Cut elimination in multifocused linear logic

    Guenot, Nicolas; Brock-Nannestad, Taus

    2015-01-01

    We study cut elimination for a multifocused variant of full linear logic in the sequent calculus. The multifocused normal form of proofs yields problems that do not appear in a standard focused system, related to the constraints in grouping rule instances in focusing phases. We show that cut...... elimination can be performed in a sensible way even though the proof requires some specific lemmas to deal with multifocusing phases, and discuss the difficulties arising with cut elimination when considering normal forms of proofs in linear logic....

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

    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.

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

    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

  18. The Origin of Weak Lensing Convergence Peaks

    Liu, Jia; Haiman, Zoltan

    2016-01-01

    Weak lensing convergence peaks are a promising tool to probe nonlinear structure evolution at late times, providing additional cosmological information beyond second-order statistics. Previous theoretical and observational studies have shown that the cosmological constraints on $\\Omega_m$ and $\\sigma_8$ are improved by a factor of up to ~ 2 when peak counts and second-order statistics are combined, compared to using the latter alone. We study the origin of lensing peaks using observational da...

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

    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.

  20. DNA adducts in marine mussel Mytilus galloprovincialis living in polluted and unpolluted environments. Chapter 12. Book chapter

    A generally applicable (32)P-postlabeling assay was used to examine the presence of DNA adducts in mussels experimentally exposed to known carcinogens and in mussels collected from sites impacted by wastewaters. Mussels exposed to seawater artificially polluted with 2-aminofluorene showed exclusively one adduct which was identified to be dG-C8-2-aminofluorene. Under the same experimental conditions, Diesel-2 oil did not induce any detectable adducts. When mussel digestive gland DNA was collected and analyzed from one unpolluted site, two moderately impacted sites, and one site heavily impacted by cannery wastewaters, mussel DNA from the unpolluted and only one moderately polluted site showed the presence of 6 to 10 adducts. This indicates they were not related to the pollution. This was further supported by the absence of dose-related adducts. Clear evidence for the presence of pollution-related DNA adducts was, however, found in juvenile mussels collected from an oil refinery site. One major and three minor adducts were detected in these mussels with no adducts detected in juvenile mussels from an unpolluted site

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

    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

  2. NanoLC/ESI+ HRMS3 quantitation of DNA adducts induced by 1,3-butadiene.

    Sangaraju, Dewakar; Villalta, Peter W; Wickramaratne, Susith; Swenberg, James; Tretyakova, Natalia

    2014-07-01

    Human exposure to 1,3-butadiene (BD) present in automobile exhaust, cigarette smoke, and forest fires is of great concern because of its potent carcinogenicity. The adverse health effects of BD are mediated by its epoxide metabolites such as 3,4-epoxy-1-butene (EB), which covalently modify genomic DNA to form promutagenic nucleobase adducts. Because of their direct role in cancer, BD-DNA adducts can be used as mechanism-based biomarkers of BD exposure. In the present work, a mass spectrometry-based methodology was developed for accurate, sensitive, and precise quantification of EB-induced N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) DNA adducts in vivo. In our approach, EB-GII adducts are selectively released from DNA backbone by neutral thermal hydrolysis, followed by ultrafiltration, offline HPLC purification, and isotope dilution nanoLC/ESI(+)-HRMS(3) analysis on an Orbitrap Velos mass spectrometer. Following method validation, EB-GII lesions were quantified in human fibrosarcoma (HT1080) cells treated with micromolar concentrations of EB and in liver tissues of rats exposed to sub-ppm concentrations of BD (0.5-1.5 ppm). EB-GII concentrations increased linearly from 1.15 ± 0.23 to 10.11 ± 0.45 adducts per 10(8) nucleotides in HT1080 cells treated with 0.5-10 μM EB. EB-GII concentrations in DNA of laboratory rats exposed to 0.5, 1.0, and 1.5 ppm BD were 0.17 ± 0.05, 0.33 ± 0.08, and 0.50 ± 0.04 adducts per 10(8) nucleotides, respectively [corrected]. We also used the new method to determine the in vivo half-life of EB-GII adducts in rat liver DNA (2.20 ± 0.12 d) and to detect EB-GII in human blood DNA. To our knowledge, this is the first application of nanoLC/ESI(+)-HRMS(3) Orbitrap methodology to quantitative analysis of DNA adducts in vivo. PMID:24867429

  3. Grilled Meat Consumption and PhIP-DNA Adducts in Prostate Carcinogenesis

    Tang, Deliang; Liu, Jason J; Rundle, Andrew; Neslund-Dudas, Christine; Savera, Adnan T.; Bock, Cathryn H.; Nock, Nora L.; Yang, James J.; Rybicki, Benjamin A

    2007-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the major heterocyclic amine generated from cooking meats at high temperatures, and dietary exposures have been shown to induce prostate cancer in rats. PhIP derives its carcinogenic potential through the formation of PhIP-DNA adducts. The purpose of this study was to examine whether self-reported consumption and preparation doneness of grilled meats were associated with PhIP-DNA adduct levels in prostate epithelial cells. The study po...

  4. Quantitative strategies to determine cisplatin adducts with DNA nucleotides in drosofila larvae and tumoral cell cultures

    Full text: The antitumoral effect of cisplatin [cis-diamminodichloroplatinum(II)] in mammals is related to its binding to DNA components. A novel sensitive and selective method is proposed to quantify cisplatin-DNA adducts induced in vivo in somatic cells of Drosophila melanogaster at biologically relevant concentrations. The method uses HPLC-ICPMS in combination with species-specific isotope dilution analysis (cisplatin enriched in 194Pt). For the first time, a cisplatin-DNA adduct is quantified by this approach. The obtained results show the great potential of this system to advance our molecular understanding of the biological effects of cisplatin. (author)

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

    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

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

    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.

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

    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...

  8. ELIMINATION AND IDENTITIES WITH THE INTEGRAL SIGN

    Hongmei LIU; Tianming WANG

    2006-01-01

    In this paper, we aim at using the elimination in Weyl algebra to give an algorithm for proving the identities with integral sign. Then, we test several examples that have been proved by D Zeilberger.

  9. A Dynamic Elimination-Combining Stack Algorithm

    Bar-Nissan, Gal; Suissa, Adi

    2011-01-01

    Two key synchronization paradigms for the construction of scalable concurrent data-structures are software combining and elimination. Elimination-based concurrent data-structures allow operations with reverse semantics (such as push and pop stack operations) to "collide" and exchange values without having to access a central location. Software combining, on the other hand, is effective when colliding operations have identical semantics: when a pair of threads performing operations with identical semantics collide, the task of performing the combined set of operations is delegated to one of the threads and the other thread waits for its operation(s) to be performed. Applying this mechanism iteratively can reduce memory contention and increase throughput. The most highly scalable prior concurrent stack algorithm is the elimination-backoff stack. The elimination-backoff stack provides high parallelism for symmetric workloads in which the numbers of push and pop operations are roughly equal, but its performance d...

  10. Elimination Problems in Infants and Children

    ... inability to digest wheat (CELIAC DISEASE) or milk (LACTOSE INTOLERANCE) can cause these symptoms. Eliminate foods that make ... be an appropriate substitute for infants who have lactose intolerance. No 4. Does your child seem to have ...

  11. The geomorphic structure of the runoff peak

    R. Rigon

    2011-06-01

    Full Text Available This paper develops a theoretical framework to investigate the core dependence of peak flows on the geomorphic properties of river basins. Based on the theory of transport by travel times, and simple hydrodynamic characterization of floods, this new framework invokes the linearity and invariance of the hydrologic response to provide analytical and semi-analytical expressions for peak flow, time to peak, and area contributing to the peak runoff. These results are obtained for the case of constant-intensity hyetograph using the Intensity-Duration-Frequency (IDF curves to estimate extreme flow values as a function of the rainfall return period. Results show that, with constant-intensity hyetographs, the time-to-peak is greater than rainfall duration and usually shorter than the basin concentration time. Moreover, the critical storm duration is shown to be independent of rainfall return period as well as the area contributing to the flow peak. The same results are found when the effects of hydrodynamic dispersion are accounted for. Further, it is shown that, when the effects of hydrodynamic dispersion are negligible, the basin area contributing to the peak discharge does not depend on the channel velocity, but is a geomorphic propriety of the basin. As an example this framework is applied to three watersheds. In particular, the runoff peak, the critical rainfall durations and the time to peak are calculated for all links within a network to assess how they increase with basin area.

  12. Practical load management - Peak shaving using photovoltaics

    This article takes a look at how photovoltaic (PV) power generation can be used in a practical way to meet peak demands for electricity. Advice is provided on how photovoltaics can provide peak load 'shaving' through the correlation between its production and the peak loads encountered during the day. The situation regarding feed-in tariffs in Italy is discussed, as are further examples of installations in Germany and Austria. Further, an initiative of the American Southern California Edison utility is discussed which foresees the installation of large PV plant on the roofs of commercial premises to provide local generation of peak energy and thus relieve demands on their power transportation network.

  13. NMR solvent peak suppression by piecewise polynomial truncated singular value decomposition methods

    A new modified singular value decomposition method, piecewise polynomial truncated SVD (PPTSVD), which was originally developed to identify discontinuity of the earth's radial density function, has been used for large solvent peak suppression and noise elimination in nuclear magnetic resonance (NMR) signal processing. PPTSVD consists of two algorithms of truncated SVD (TSVD) and L1 problems. In TSVD, some unwanted large solvent peaks and noise are suppressed with a certain soft threshold value, whereas signal and noise in raw data are resolved and eliminated in L1 problem. These two algorithms were systematically programmed to produce high quality of NMR spectra, including a better solvent peak suppression with good spectral line shapes and better noise suppression with a higher signal to noise ratio value up to 27% spectral enhancement, which is applicable to multidimensional NMR data processing

  14. Elimination of Lymphatic Filariasis in Southern India

    Sanjay Pattanshetty; Ashwini Kumar; Ravi Kumar; Rao, Chythra R.; Sanjeev Badiger; Rashmi R; Sneha Kamath

    2010-01-01

    BackgroundLymphatic filariasis is an important public health problem in India. Inspite of National filarial control programme (NFCP) being in place for lymphatic filariasis (LF) elimination, several important issues need to be addressed. There is uncertainty about the coverage and compliance to treatment in order to achieve elimination. Method A community based cross-sectional study was conducted as per the National Vector Borne Disease Control Programme (NVBDCP) directions. The study includ...

  15. Algorithms and implementations for differential elimination

    Wittkopf, Allan

    2004-01-01

    The 1)rimary focus of this work is the design and implementation of efficient differential elimination algorithms. Such algorithms use a finite number of differentiations and eliminations to simplify over-determined systems of ordinary and partial differential equations (ODE and PDE) to a more tractable form. They can be used in exact solution methods for ODE and PDE systems, as a preprocessor for numerical solution of these systems, and for reduction of nonlinear PDE to linear PDE. Different...

  16. Adduct formation in LC-ESI-MS of nonylphenol ethoxylates: mass spectrometrical, theoretical and quantitative analytical aspects

    The analysis of nonylphenol ethoxylate (A9PEOn) surfactants with LC-ESI-MS was investigated in a detailed study of the formation of different types of adducts. Part of the observations was explained by calculating their relative stabilities using molecular dynamics techniques. Strong differences in adduct formation behaviour were found for different oligomers. Beside the common sodium adducts, surfactant dimer adducts [2 x A9PEO1,2 + Na]+, adducts including a solvent molecule [A9PEO1,2 + MeOH + Na]+ and doubly charged adducts [A9PEO>11 + 2 x Na]2+ were found. Molecular dynamics calculations showed that the A9PEOn molecule wraps itself around the complexing sodium ion in a way that negative electronic charges on oxygen have optimum electrostatic interaction with this ion. van der Waals interactions between alkyl chains are of less importance for the stability of these adducts. Both [2 x A9PEO2,5 + Na]+ dimer and [A9PEO2,5 + Na]+ monomer adducts turned out to be stable from an energetic point of view with adducts of A9PEO5 being more stable than adducts of A9PEO2. Only for the monomer adduct the latter is in accordance with experimental observations. Consequences of the formation of several adducts per A9PEOn oligomer for the quantitative analysis of environmental samples were evaluated. In clean samples, it was found that the presence of short-chain A9PEO1,2 can cause an overestimation of long-chain A9PEO>2. In real environmental extracts, other processes like matrix effects have a stronger influence on the quantitative result, and therefore no significant influence of adduct formation processes could be observed. However, inclusion of [A9PEO1,2 + MeOH + Na]+ adduct signals does improve the detection limits of the two short-chain oligomers. Correct quantitative results are obtained when A9PEO1 and A9PEO2 are quantified separately, and longer oligomers with a molar calibration followed by correction of the average molar weight of the A9PEO>2 in the sample

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

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

    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)

  19. Comparative synchronous fluorescence spectrophotometry and 32P-postlabeling analysis of PAH-DNA adducts in human lung and the relationship to TP53 mutations

    Andreassen, Åshild; Kure, Elin H.; Nielsen, Per Sabro; Autrup, Herman; Haugen, Aage

    )-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 and the...... levels in lung tissue and TP53 mutations....

  20. The maximal forward peak in elastic scattering

    The maximal sharpness of the forward peak in elastic scattering is constrained by unitarity. This is done by minimizing the average of (t). The data are within 15% o/ the maximal sharpness. Our bound and an earlier lower bound on the forward slope constitute a severe restriction on the shape of forward peak. (author)

  1. The Boson peak in supercooled water.

    Kumar, Pradeep; Wikfeldt, K Thor; Schlesinger, Daniel; Pettersson, Lars G M; Stanley, H Eugene

    2013-01-01

    We perform extensive molecular dynamics simulations of the TIP4P/2005 model of water to investigate the origin of the Boson peak reported in experiments on supercooled water in nanoconfined pores, and in hydration water around proteins. We find that the onset of the Boson peak in supercooled bulk water coincides with the crossover to a predominantly low-density-like liquid below the Widom line TW. The frequency and onset temperature of the Boson peak in our simulations of bulk water agree well with the results from experiments on nanoconfined water. Our results suggest that the Boson peak in water is not an exclusive effect of confinement. We further find that, similar to other glass-forming liquids, the vibrational modes corresponding to the Boson peak are spatially extended and are related to transverse phonons found in the parent crystal, here ice Ih. PMID:23771033

  2. Multiscale peak alignment for chromatographic datasets.

    Zhang, Zhi-Min; Liang, Yi-Zeng; Lu, Hong-Mei; Tan, Bin-Bin; Xu, Xiao-Na; Ferro, Miguel

    2012-02-01

    Chromatography has been extensively applied in many fields, such as metabolomics and quality control of herbal medicines. Preprocessing, especially peak alignment, is a time-consuming task prior to the extraction of useful information from the datasets by chemometrics and statistics. To accurately and rapidly align shift peaks among one-dimensional chromatograms, multiscale peak alignment (MSPA) is presented in this research. Peaks of each chromatogram were detected based on continuous wavelet transform (CWT) and aligned against a reference chromatogram from large to small scale gradually, and the aligning procedure is accelerated by fast Fourier transform cross correlation. The presented method was compared with two widely used alignment methods on chromatographic dataset, which demonstrates that MSPA can preserve the shapes of peaks and has an excellent speed during alignment. Furthermore, MSPA method is robust and not sensitive to noise and baseline. MSPA was implemented and is available at http://code.google.com/p/mspa. PMID:22222564

  3. Multiscale peak detection in wavelet space.

    Zhang, Zhi-Min; Tong, Xia; Peng, Ying; Ma, Pan; Zhang, Ming-Jin; Lu, Hong-Mei; Chen, Xiao-Qing; Liang, Yi-Zeng

    2015-12-01

    Accurate peak detection is essential for analyzing high-throughput datasets generated by analytical instruments. Derivatives with noise reduction and matched filtration are frequently used, but they are sensitive to baseline variations, random noise and deviations in the peak shape. A continuous wavelet transform (CWT)-based method is more practical and popular in this situation, which can increase the accuracy and reliability by identifying peaks across scales in wavelet space and implicitly removing noise as well as the baseline. However, its computational load is relatively high and the estimated features of peaks may not be accurate in the case of peaks that are overlapping, dense or weak. In this study, we present multi-scale peak detection (MSPD) by taking full advantage of additional information in wavelet space including ridges, valleys, and zero-crossings. It can achieve a high accuracy by thresholding each detected peak with the maximum of its ridge. It has been comprehensively evaluated with MALDI-TOF spectra in proteomics, the CAMDA 2006 SELDI dataset as well as the Romanian database of Raman spectra, which is particularly suitable for detecting peaks in high-throughput analytical signals. Receiver operating characteristic (ROC) curves show that MSPD can detect more true peaks while keeping the false discovery rate lower than MassSpecWavelet and MALDIquant methods. Superior results in Raman spectra suggest that MSPD seems to be a more universal method for peak detection. MSPD has been designed and implemented efficiently in Python and Cython. It is available as an open source package at . PMID:26514234

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

    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.

  5. Situational restriction of elevation in adduction relieved by faden on the medial rectus

    R Muralidhar

    2016-01-01

    Full Text Available We describe a patient with situational restriction of elevation in adduction in his left eye. Clinical examination pointed to instability of the left medial rectus pulley. This was corrected by Faden on the medial rectus. The importance of this relatively new concept in identifying and treating orbital pulley instability is discussed.

  6. Bulky DNA adducts in white blood cells: a pooled analysis of 3600 subjects

    Ricceri, F.; Godschalk, R. W.; Peluso, M.; Philips, D. H.; Agudo, A.; Georgiadis, P.; Loft, S.; Tjonneland, A.; Raaschau-Nielsen, O.; Palli, D.; Perera, F.; Vermeulen, R.; Taioli, E.; Šrám, Radim; Munnia, A.; Rosa, F.; Allione, A.; Matullo, G.; Vineis, P.

    2010-01-01

    Roč. 19, č. 12 (2010), s. 3174-3181. ISSN 1055-9965 Grant ostatní: European Union ECNIS(XE) FOOD-CT-2005-513943 Institutional research plan: CEZ:AV0Z50390512 Keywords : DNA adducts * biomarkers of exposure * air pollution Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 4.190, year: 2010

  7. Two food-borne heterocyclic amines: Metabolism and DNA adduct formation of amino-alpha-carbolines

    Frederiksen, Hanne

    2005-01-01

    -adducts have also 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...

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

    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

  9. DNA adducts and atherosclerotic: A study of accidental and sudden death males in the Czech Republic

    Binková, Blanka; Šmerhovský, Zdeněk; Strejc, P.; Boubelík, O.; Stávková, Zdena; Chvátalová, Irena; Šrám, Radim

    č. 501 (2002), s. 115-128. ISSN 0027-5107 R&D Projects: GA MŽP SI/340/1/97 Institutional research plan: CEZ:AV0Z5039906 Keywords : atherosclerosis * DNA-adducts * GSTM1 and CYP1A1 polymorphism Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.158, year: 2002

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

    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

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

    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...

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

    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 ...

  13. Adducts compounds of lanthanides (III) trifluoreacetates and yttrium and the N,N - dimenthylformamide

    Some studies on lanthanides, f transition elements, and yttrium are presented. Adducts of lanthanides trifluoroacetates and N,N -dimethylformamide are described. The characterization of complexes from elementar analysis, conductance measurements, X-ray patterns, vibrational, electronics and fluorescence spectra are analysed. (M.J.C.)

  14. Simulation of Solid-Liquid Equilibrium in a Ternary System with Adduct Compounds

    Malijevská, I.; Sedláková, Zuzana

    Kuala Lumpur : -, 2007, s. 150-151. [Asian Chemical Congress (12ACC) 2007 /12./. Kuala Lumpur (MY), 23.08.2007-25.08.2007] Institutional research plan: CEZ:AV0Z40720504 Keywords : solid-liquid equilibrium * adduct * ternary system Subject RIV: CF - Physical ; Theoretical Chemistry

  15. Structural analysis and aggregation propensity of reduced and nonreduced glycated insulin adducts.

    Alavi, Parnian; Yousefi, Reza; Amirghofran, Sara; Karbalaei-Heidari, Hamid Reza; Moosavi-Movahedi, Ali Akbar

    2013-06-01

    The milieu within pancreatic β cells represents a favorable environment for glycation of insulin. Therefore, in this study, insulin samples were individually subjected to glycation under reducing and nonreducing conditions. As monitored by ortho-phthalaldehyde and fluorescamine assays, the reduced glycated insulin adduct demonstrates extensively higher level of glycation than the nonreduced glycated counterpart. Also, gel electrophoresis experiments suggest a significant impact of glycation under a reducing system on the level of insulin oligomerization. Furthermore, reduced and nonreduced glycated insulin adducts respectively exhibit full and partial resistance against dithiothreitol-induced aggregation. The results of thioflavin T and Congo red assays suggest the existence of a significant quantity of amyloid-like entities in the sample of reduced glycated insulin adduct. Both fluorescence and far-ultraviolet circular dichroism studies respectively suggest that the extents of unfolding and secondary structural alteration were closely correlated to the level of insulin glycation. Moreover, the surface tension of two glycated insulin adducts was inversely correlated to their glycation extents and to the quantity of exposed hydrophobic patches. Overall, the glucose-modified insulin molecules under reducing and nonreducing systems display different structural features having significant consequences on aggregation behaviors and surface tension properties. The particular structural constraints of glycated insulin may reduce the binding interaction of this hormone to its receptor which is important for both insulin function and clearance. PMID:23584594

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

    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

  17. Noni juice reduces lipid peroxidation-derived DNA adducts in heavy smokers.

    Wang, Mian-Ying; Peng, Lin; Jensen, Claude J; Deng, Shixin; West, Brett J

    2013-03-01

    Food plants provide important phytochemicals which help improve or maintain health through various biological activities, including antioxidant effects. Cigarette smoke-induced oxidative stress leads to the formation of lipid hydroperoxides (LOOHs) and their decomposition product malondialdehyde (MDA), both of which cause oxidative damage to DNA. Two hundred forty-five heavy cigarette smokers completed a randomized, double-blind, placebo-controlled clinical trial designed to investigate the effect of noni juice on LOOH- and MDA-DNA adducts in peripheral blood lymphocytes (PBLs). Volunteers drank noni juice or a fruit juice placebo every day for 1 month. DNA adducts were measured by (32)P postlabeling analysis. Drinking 29.5-118 mL of noni juice significantly reduced adducts by 44.6-57.4%. The placebo, which was devoid of iridoid glycosides, did not significantly influence LOOH- and MDA-DNA adduct levels in current smokers. Noni juice was able to mitigate oxidative damage of DNA in current heavy smokers, an activity associated with the presence of iridoids. PMID:24804023

  18. Redox and catalytic reactions of adducts of DNA with osmium tetroxide complexes on mercury electrodes

    Havran, Luděk; Fojta, Miroslav; Jelen, František; Paleček, Emil

    Bratislava : Comenius University, 2001. s. 22. [International Symposium on BIOELECTROCHEMISTRY and BIOENERGETICS /16./. 01.06.2001-06.06.2001, Bratislava] Institutional research plan: CEZ:AV0Z5004920 Keywords : mercury electrodes * osmium tetroxide * adducts of DNA Subject RIV: BO - Biophysics

  19. Hemoglobin adducts of epoxybutene in workers occupationally exposed to 1,3-butadiene

    Begemann, P.; Šrám, Radim; Neumann, H. G.

    2001-01-01

    Roč. 74, - (2001), s. 680-687. ISSN 0340-5761 Grant ostatní: EU(XC) CIPA-CT93-0228 Institutional research plan: CEZ:AV0Z5039906 Keywords : biomonitoring * hemoglobin adducts Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 1.558, year: 2001

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

    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

  1. Peroxidase-catalyzed formation of (deoxy)guanosine adducts by Sudan I

    Dračínský, Martin; Semanská, M.; Cvačka, Josef; Martínek, V.; Stiborová, M.

    Brno : Masaryk University, 2009. C32-C32. ISBN 978-80-86441-40-5. [Central European NMR Meeting. NMR Valtice /24./. 26.04.2009-29.04.2009, Valtice] Institutional research plan: CEZ:AV0Z40550506 Keywords : Sudan I * DNA adducts * NMR Subject RIV: CC - Organic Chemistry

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

    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.

  3. Body elimination attitude family resemblance in Kuwait.

    Al-Fayez, Ghenaim; Awadalla, Abdelwahid; Arikawa, Hiroko; Templer, Donald I; Hutton, Shane

    2009-12-01

    The purpose of the present study was to determine the family resemblance of attitude toward body elimination in Kuwaiti participants. This study was conceptualized in the context of the theories of moral development, importance of cleanliness in the Muslim religion, cross-cultural differences in personal hygiene practices, previous research reporting an association between family attitudes and body elimination attitude, and health implications. The 24-item Likert-type format Body Elimination Attitude Scale-Revised was administered to 277 Kuwaiti high school students and 437 of their parents. Females scored higher, indicating greater disgust, than the males. Moreover, sons' body elimination attitude correlated more strongly with fathers' attitude (r = .85) than with that of the mothers (r = .64). Daughters' attitude was similarly associated with the fathers' (r = .89) and the mothers' attitude (r = .86). The high correlations were discussed within the context of Kuwait having a collectivistic culture with authoritarian parenting style. The higher adolescent correlations, and in particular the boys' correlation with fathers than with mothers, was explained in terms of the more dominant role of the Muslim father in the family. Public health and future research implications were suggested. A theoretical formulation was advanced in which "ideal" body elimination attitude is relative rather than absolute, and is a function of one's life circumstances, one's occupation, one's culture and subculture, and the society that one lives in. PMID:22029659

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

    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

  5. Reserve, peak and new load capacity

    Ensuring reserve, peak and new load capacity in a deregulated market was the subject of this discussion paper. The problem arises from the fact that both reserve (capacity for outages) and peak capacities (capacity for maximum load demand on the system) are dictated by the most severe contingency considerations that can befall the system. As reserve or peak capacity may only be minimally used, the cost of electricity generated is extremely expensive, and the marketplace may resist investment in peak capacity without adequate financial incentives. The preferred approach would be to implement a competitive bidding system for the provision of reserve and peak power. Issues that require consideration to efficiently providing adequate reserve, peak and new load capacity, and to ensure system reliability were reviewed. Among these were greater transparency of information, timely and accurate forecasting of load, and sufficient lead time with respect to the provision of additional capacity. Pricing signals to consumers to motivate them to change their demand profiles and consumption patterns may also be important to increase market liquidity. As far as the provision of new capacity is concerned, the system must send early pricing signals to create investment interest. There is also a need to promote reserve and peak power sources that do not strain emission limits

  6. The Origin of Weak Lensing Convergence Peaks

    Liu, Jia

    2016-01-01

    Weak lensing convergence peaks are a promising tool to probe nonlinear structure evolution at late times, providing additional cosmological information beyond second-order statistics. Previous theoretical and observational studies have shown that the cosmological constraints on $\\Omega_m$ and $\\sigma_8$ are improved by a factor of up to ~ 2 when peak counts and second-order statistics are combined, compared to using the latter alone. We study the origin of lensing peaks using observational data from the 154 deg$^2$ Canada-France-Hawaii Telescope Lensing Survey. We found that while high peaks (with height $\\kappa$ >3.5 $\\sigma_\\kappa$, where $\\sigma_\\kappa$ is the r.m.s. of the convergence $\\kappa$) are typically due to one single massive halo of ~$10^{15}M_\\odot$, low peaks ($\\kappa$ ~ their virial radii), compared with ~0.25 virial radii for halos linked with high peaks, hinting that low peaks are more immune to baryonic processes whose impact is confined to the inner regions of the dark matter halos. Our fi...

  7. Elimination of Ideas and Professional Socialisation

    Gravengaard, Gitte; Rimestad, Lene

    2012-01-01

    potential news stories are eliminated by the editor at the daily newsroom meetings. The elimination of ideas for news stories are not just eliminations; they are also corrections of culturally undesirable behaviour producing and reproducing the proper perception of an important object of knowledge......This article investigates and interprets social and cultural production and reproduction as we turn our attention to an important part of routinised practice in the newsroom: the early newsroom meetings. These meetings are essential sites for the building of the craft ethos and professional vision....... Our aim is to study how this building of expertise takes place at meetings with a particular focus on the decision-making process concerning ideas for new news stories. In order to do this, we perform linguistic analysis of news production practices, as we investigate how the journalists' ideas for...

  8. Looking for High Energy Peaked Blazars

    Costamante, L.; Ghisellini, G.; Celotti, A.; Giommi, P.; Padovani, P.; Tagliaferri, G.; Wolter, A.; Chiaberge, M.; Fossati, G; Pian, E.; L. Maraschi(INAF National Institute for Astrophysics, I-00136 Rome, Italy); Tavecchio, F.; Treves, A.

    2000-01-01

    Blazars can be classified on the basis of their overall Spectral Energy Distribution (SED). BL Lac objects are usually divided in LBL or HBL (Low or High energy peaked BL Lacs), according to the peak frequency of the synchrotron emission, if in the optical or UV-soft-X band respectively. FSRQs instead are characterized by synchrotron peaks mainly at IR-optical frequencies, similarly to LBLs. Here we report on recent BeppoSAX observations which are unveiling the high energy branch of the range...

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

    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

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

    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.

  11. Peak load arrangements : Assessment of Nordel guidelines

    2009-07-01

    Two Nordic countries, Sweden and Finland, have legislation that empowers the TSO to acquire designated peak load resources to mitigate the risk for shortage situations during the winter. In Denmark, the system operator procures resources to maintain a satisfactory level of security of supply. In Norway the TSO has set up a Regulation Power Option Market (RKOM) to secure a satisfactory level of operational reserves at all times, also in winter with high load demand. Only the arrangements in Finland and Sweden fall under the heading of Peak Load Arrangements defined in Nordel Guidelines. NordREG has been invited by the Electricity Market Group (EMG) to evaluate Nordel's proposal for 'Guidelines for transitional Peak Load Arrangements'. The EMG has also financed a study made by EC Group to support NordREG in the evaluation of the proposal. The study has been taken into account in NordREG's evaluation. In parallel to the EMG task, the Swedish regulator, the Energy Markets Inspectorate, has been given the task by the Swedish government to investigate a long term solution of the peak load issue. The Swedish and Finnish TSOs have together with Nord Pool Spot worked on finding a harmonized solution for activation of the peak load reserves in the market. An agreement accepted by the relevant authorities was reached in early January 2009, and the arrangement has been implemented since 19th January 2009. NordREG views that the proposed Nordel guidelines have served as a starting point for the presently agreed procedure. However, NordREG does not see any need to further develop the Nordel guidelines for peak load arrangements. NordREG agrees with Nordel that the market should be designed to solve peak load problems through proper incentives to market players. NordREG presumes that the relevant authorities in each country will take decisions on the need for any peak load arrangement to ensure security of supply. NordREG proposes that such decisions should be

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

    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

  13. Dynamics of Hydrogen Elimination from Unsaturated Hydrocarbons

    Cromwell, Evan Francis

    State-of-the-art laser and molecular beam techniques are used to study the dynamics of H_2 elimination from 1,4-cyclohexadiene and ethylene. Information on the transition state configurations and the dynamics of the dissociation processes for these reactions is reported. A brief introduction to these studies is presented in Chapter I. An ultrahigh-brightness laser system, developed to study the spectroscopy and dynamics of molecules and clusters from the vacuum ultraviolet (VUV) and extreme ultraviolet (XUV) to the near infra-red spectral regions is described in Chapter II. The laser utilizes pulse amplification of a single-mode ring dye laser, frequency doubling, and four-wave mixing in a pulsed jet. Pulse energies of > 120mJ in the visible, >35mJ in the uv, >15mJ in the infra-red and > 10^{11} photons/pulse in the VUV-XUV have been obtained. The bandwidth of the laser has been measured to be 91MHz in the visible and 210MHz in the XUV. In Chapter III a comprehensive study of the dynamics of H_2 elimination from 1,4- and 1,3-cyclohexadiene is reported. Rotational and vibrational quantum state distributions as well as translation energy distributions for the H_2 product are measured. State specific detection of H_2 is accomplished with a transform limited vuv-xuv laser system via (1 + 1) REMPI. Rate constants for the H_2 elimination and 1,4 to 1,3 isomerization reactions are derived. A (v, J) correlation for H _2 with {bf v}| {bf J} primarily is observed from anisotropy in the Doppler profiles. A clear picture of the transition state configuration of 1,4-cyclohexadiene is provided from the information obtained. A study of the dynamics of H_2 elimination from ethylene is presented in the last Chapter. A complete H_2 product energy distribution is obtained. The distribution of energy in H_2 product from the dissociation of 1,1-d_2 ethylene is also presented. Two separate H_2 elimination channels are observed, a 1,1 elimination and a 1,2 elimination, in the

  14. Ten years left to eliminate blinding trachoma

    Haddad D.

    2010-09-01

    Full Text Available n 1997, the World Health Organization formed the Global Alliance to Eliminate Blinding Trachoma by 2020 (GET 2020, a coalition of governmental, non-governmental, research, and pharmaceutical partners. In 1998, the World Health Assembly urged member states to map blinding trachoma in endemic areas, implement the SAFE strategy (which stands for surgery for trichiasis, antibiotics, facial-cleanliness and environmental change, such as clean water and latrines and collaborate with the global alliance in its work to eliminate blinding trachoma.

  15. Noise elimination algorithm for modal analysis

    Bao, X. X., E-mail: baoxingxian@upc.edu.cn [Department of Naval Architecture and Ocean Engineering, China University of Petroleum (East China), Qingdao 266580 (China); Li, C. L. [Key Laboratory of Marine Geology and Environment, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071 (China); Xiong, C. B. [The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China)

    2015-07-27

    Modal analysis is an ongoing interdisciplinary physical issue. Modal parameters estimation is applied to determine the dynamic characteristics of structures under vibration excitation. Modal analysis is more challenging for the measured vibration response signals are contaminated with noise. This study develops a mathematical algorithm of structured low rank approximation combined with the complex exponential method to estimate the modal parameters. Physical experiments using a steel cantilever beam with ten accelerometers mounted, excited by an impulse load, demonstrate that this method can significantly eliminate noise from measured signals and accurately identify the modal frequencies and damping ratios. This study provides a fundamental mechanism of noise elimination using structured low rank approximation in physical fields.

  16. Recognizing, Confronting, and Eliminating Workplace Bullying.

    Berry, Peggy Ann; Gillespie, Gordon L; Fisher, Bonnie S; Gormley, Denise K

    2016-07-01

    Workplace bullying (WPB) behaviors negatively affect nurse productivity, satisfaction, and retention, and hinder safe patient care. The purpose of this article is to define WPB, differentiate between incivility and WPB, and recommend actions to prevent WPB behaviors. Informed occupational and environmental health nurses and nurse leaders must recognize, confront, and eliminate WPB in their facilities and organizations. Recognizing, confronting, and eliminating WPB behaviors in health care is a crucial first step toward sustained improvements in patient care quality and the health and safety of health care employees. PMID:27053288

  17. Noise elimination algorithm for modal analysis

    Modal analysis is an ongoing interdisciplinary physical issue. Modal parameters estimation is applied to determine the dynamic characteristics of structures under vibration excitation. Modal analysis is more challenging for the measured vibration response signals are contaminated with noise. This study develops a mathematical algorithm of structured low rank approximation combined with the complex exponential method to estimate the modal parameters. Physical experiments using a steel cantilever beam with ten accelerometers mounted, excited by an impulse load, demonstrate that this method can significantly eliminate noise from measured signals and accurately identify the modal frequencies and damping ratios. This study provides a fundamental mechanism of noise elimination using structured low rank approximation in physical fields

  18. Species difference in radioactivity elimination from liver parenchymal cells after injection of radiolabeled proteins

    Mukai, Takahiro E-mail: mukai@net.nagasaki-u.ac.jp; Arano, Yasushi; Nishida, Koyo; Sasaki, Hitoshi; Akizawa, Hiromichi; Ogawa, Kazuma; Ono, Masahiro; Saji, Hideo; Nakamura, Junzo

    1999-04-01

    To elucidate the cause for the different levels of hepatic radioactivity among mammals after injection of protein radiopharmaceuticals, the metabolism of radiolabeled proteins and the fate of their radiometabolites in the parenchymal cells of rat liver were investigated and compared with those of mice. We used galactosyl-neoglycoalbumin (NGA) as a carrier protein, and NGA was labeled with {sup 111}In via 1-(4-isothiocyanatobenzyl)ethylenediaminetetraacetic acid (SCN-Bz-EDTA) or 1-[p-(5-maleimidopentyl)aminobenzyl]ethylenediaminetetraacetic acid (EMCS-Bz-EDTA) and with {sup 125}I via direct iodination. All radiolabeled NGAs exhibited rapid accumulation in liver parenchymal cells after intravenous injection into rats. Radioactivity was eliminated following NGA-{sup 125}I injection at similar rates from rat and mouse liver. In contrast, both {sup 111}In-labeled NGAs demonstrated much slower elimination of radioactivity in rat when compared with mouse liver. Analyses of radioactivity in bile and liver indicated that both SCN-Bz-EDTA and EMCS-Bz-EDTA rendered mono-amino acid adducts as the final radiometabolites, which were generated in rat liver within 1 h postinjection. Subcellular distribution studies suggested that these radiometabolites were copurified with lysosome in rat liver. Because similar results were observed in mice previously, the difference between rats and mice in radioactivity elimination from liver parenchymal cells would be predominantly attributable to the different efflux rate of the {sup 111}In-labeled metabolites from the lysosome between these species. Such differences in the efflux rates of radiometabolites from the lysosome among mammals may also account for the different hepatic radioactivity levels of radiolabeled proteins between animal and clinical studies.

  19. Peak Vegetation Growth 1996 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 1996 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  20. Peak Vegetation Growth 2004 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 2004 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  1. Peak Vegetation Growth 1994 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 1994 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  2. Peak Vegetation Growth 1995 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 1995 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  3. Peak Vegetation Growth 1990 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 1990 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  4. Peak Vegetation Growth 1993 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 1993 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  5. Peak Vegetation Growth 2002 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 2002 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  6. Peak Vegetation Growth 1997 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 1997 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  7. Osteoporosis: Peak Bone Mass in Women

    ... Bone Health for Lupus Patients Bone Health and Anorexia Nervosa Partner Resources Screening Tests and Immunizations Guidelines for ... calcium. Physical Activity. Girls and boys and young adults who exercise regularly generally achieve greater peak bone ...

  8. Peak Vegetation Growth 1992 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 1992 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  9. Cosmic Microwave Background Acoustic Peak Locations

    Pan, Zhen; Mulroe, Brigid; Narimani, Ali

    2016-01-01

    The Planck collaboration has measured the temperature and polarization of the cosmic microwave background well enough to determine the locations of eight peaks in the temperature (TT) power spectrum, five peaks in the polarization (EE) power spectrum and twelve extrema in the cross (TE) power spectrum. The relative locations of these extrema give a striking, and beautiful, demonstration of what we expect from acoustic oscillations in the plasma; e.g., that EE peaks fall half way between TT peaks. We expect this because the temperature map is predominantly sourced by temperature variations in the last scattering surface, while the polarization map is predominantly sourced by gradients in the velocity field, and the harmonic oscillations have temperature and velocity 90 degrees out of phase. However, there are large differences in expectations for extrema locations from simple analytic models vs. numerical calculations. Here we quantitatively explore the origin of these differences in gravitational potential tr...

  10. Peak Vegetation Growth 1999 - Direct Download

    U.S. Geological Survey, Department of the Interior — This map layer is a grid map of 1999 peak vegetation growth for Alaska and the conterminous United States. The nominal spatial resolution is 1 kilometer and the map...

  11. Tectonics, Climate and Earth's highest peaks

    Robl, Jörg; Prasicek, Günther; Hergarten, Stefan

    2016-04-01

    Prominent peaks characterized by high relief and steep slopes are among the most spectacular morphological features on Earth. In collisional orogens they result from the interplay of tectonically driven crustal thickening and climatically induced destruction of overthickened crust by erosional surface processes. The glacial buzz-saw hypothesis proposes a superior status of climate in limiting mountain relief and peak altitude due to glacial erosion. It implies that peak altitude declines with duration of glacial occupation, i.e., towards high latitudes. This is in strong contrast with high peaks existing in high latitude mountain ranges (e.g. Mt. St. Elias range) and the idea of peak uplift due to isostatic compensation of spatially variable erosional unloading an over-thickened orogenic crust. In this study we investigate landscape dissection, crustal thickness and vertical strain rates in tectonically active mountain ranges to evaluate the influence of erosion on (latitudinal) variations in peak altitude. We analyze the spatial distribution of serval thousand prominent peaks on Earth extracted from the global ETOPO1 digital elevation model with a novel numerical tool. We compare this dataset to crustal thickness, thickening rate (vertical strain rate) and mean elevation. We use the ratios of mean elevation to peak elevation (landscape dissection) and peak elevation to crustal thickness (long-term impact of erosion on crustal thickness) as indicators for the influence of erosional surface processes on peak uplift and the vertical strain rate as a proxy for the mechanical state of the orogen. Our analysis reveals that crustal thickness and peak elevation correlate well in orogens that have reached a mechanically limited state (vertical strain rate near zero) where plate convergence is already balanced by lateral extrusion and gravitational collapse and plateaus are formed. On the Tibetan Plateau crustal thickness serves to predict peak elevation up to an altitude

  12. Bayesian Peak Picking for NMR Spectra

    Cheng, Yichen

    2014-02-01

    Protein structure determination is a very important topic in structural genomics, which helps people to understand varieties of biological functions such as protein-protein interactions, protein–DNA interactions and so on. Nowadays, nuclear magnetic resonance (NMR) has often been used to determine the three-dimensional structures of protein in vivo. This study aims to automate the peak picking step, the most important and tricky step in NMR structure determination. We propose to model the NMR spectrum by a mixture of bivariate Gaussian densities and use the stochastic approximation Monte Carlo algorithm as the computational tool to solve the problem. Under the Bayesian framework, the peak picking problem is casted as a variable selection problem. The proposed method can automatically distinguish true peaks from false ones without preprocessing the data. To the best of our knowledge, this is the first effort in the literature that tackles the peak picking problem for NMR spectrum data using Bayesian method.

  13. Helping System Engineers Bridge the Peaks

    Rungta, Neha; Tkachuk, Oksana; Person, Suzette; Biatek, Jason; Whalen, Michael W.; Castle, Joseph; Castle, JosephGundy-Burlet, Karen

    2014-01-01

    In our experience at NASA, system engineers generally follow the Twin Peaks approach when developing safety-critical systems. However, iterations between the peaks require considerable manual, and in some cases duplicate, effort. A significant part of the manual effort stems from the fact that requirements are written in English natural language rather than a formal notation. In this work, we propose an approach that enables system engineers to leverage formal requirements and automated test generation to streamline iterations, effectively "bridging the peaks". The key to the approach is a formal language notation that a) system engineers are comfortable with, b) is supported by a family of automated V&V tools, and c) is semantically rich enough to describe the requirements of interest. We believe the combination of formalizing requirements and providing tool support to automate the iterations will lead to a more efficient Twin Peaks implementation at NASA.

  14. Peaking Capacity in Restructured Power Systems

    Doorman, Gerard

    2000-01-01

    The theme of this thesis is the supply of capacity during peak demand in restructured power systems. There are a number of reasons why there is uncertainty about whether an enegyonly electricity market (where generators are only paid for the energy produced) is able to ensure uninterrupted supply during peak load conditions.Much of the public debate in Europe has been about the present surplus generation capacity. However, in a truly competitive environment, it is hard to believe that seldom ...

  15. Forward-peaked scattering of polarized light.

    Clark, Julia P; Kim, Arnold D

    2014-11-15

    Polarized light propagation in a multiple scattering medium is governed by the vector radiative transfer equation. We analyze the vector radiative transfer equation in asymptotic limit of forward-peaked scattering and derive an approximate system of equations for the Stokes parameters, which we call the vector Fokker-Planck approximation. The vector Fokker-Planck approximation provides valuable insight into several outstanding issues regarding the forward-peaked scattering of polarized light such as the polarization memory phenomenon. PMID:25490484

  16. Comparison of five portable peak flow meters

    Glaucia Nency Takara; Gualberto Ruas; Bruna Varanda Pessoa; Luciana Kawakami Jamami; Valéria Amorim Pires Di Lorenzo; Mauricio Jamami

    2010-01-01

    OBJECTIVE: To compare the measurements of spirometric peak expiratory flow (PEF) from five different PEF meters and to determine if their values are in agreement. Inaccurate equipment may result in incorrect diagnoses of asthma and inappropriate treatments. METHODS: Sixty-eight healthy, sedentary and insufficiently active subjects, aged from 19 to 40 years, performed PEF measurements using Air Zone®, Assess®, Galemed®, Personal Best® and Vitalograph® peak flow meters. The highest value record...

  17. Cosmic microwave background acoustic peak locations

    Pan, Z.; Knox, L.; Mulroe, B.; Narimani, A.

    2016-07-01

    The Planck collaboration has measured the temperature and polarization of the cosmic microwave background well enough to determine the locations of eight peaks in the temperature (TT) power spectrum, five peaks in the polarization (EE) power spectrum and 12 extrema in the cross (TE) power spectrum. The relative locations of these extrema give a striking, and beautiful, demonstration of what we expect from acoustic oscillations in the plasma; e.g. that EE peaks fall half way between TT peaks. We expect this because the temperature map is predominantly sourced by temperature variations in the last scattering surface, while the polarization map is predominantly sourced by gradients in the velocity field, and the harmonic oscillations have temperature and velocity 90 deg out of phase. However, there are large differences in expectations for extrema locations from simple analytic models versus numerical calculations. Here, we quantitatively explore the origin of these differences in gravitational potential transients, neutrino free-streaming, the breakdown of tight coupling, the shape of the primordial power spectrum, details of the geometric projection from three to two dimensions, and the thickness of the last scattering surface. We also compare the peak locations determined from Planck measurements to expectations under the Λ cold dark matter model. Taking into account how the peak locations were determined, we find them to be in agreement.

  18. Do dark matter halos explain lensing peaks?

    Matilla, José Manuel Zorrilla; Hsu, Daniel; Gupta, Arushi; Petri, Andrea

    2016-01-01

    We have investigated a recently proposed halo-based model, Camelus, for predicting weak-lensing peak counts, and compared its results over a collection of 162 cosmologies with those from N-body simulations. While counts from both models agree for peaks with $\\mathcal{S/N}>1$ (where $\\mathcal{S/N}$ is the ratio of the peak height to the r.m.s. shape noise), we find $\\approx 50\\%$ fewer counts for peaks near $\\mathcal{S/N}=0$ and significantly higher counts in the negative $\\mathcal{S/N}$ tail. Adding shape noise reduces the differences to within $20\\%$ for all cosmologies. We also found larger covariances that are more sensitive to cosmological parameters. As a result, credibility regions in the $\\{\\Omega_m, \\sigma_8\\}$ are $\\approx 30\\%$ larger. Even though the credible contours are commensurate, each model draws its predictive power from different types of peaks. Low peaks, especially those with $23)$. Our results confirm the importance of using a cosmology-dependent covariance with at least a 14\\% improveme...

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

    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

  20. DNA adduct measurements in zebra mussels, Dreissena polymorpha, Pallas. Potential use for genotoxicant biomonitoring of fresh water ecosystems.

    Le Goff, J; Gallois, J; Pelhuet, L; Devier, M H; Budzinski, H; Pottier, D; André, V; Cachot, J

    2006-08-12

    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 microg g(-1) dry weight) in comparison to individuals from the reference site (0.053 microg g(-1) dry weight). The former exhibited elevated levels of DNA adducts (up to 4.0/10(8) 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 microg 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 microg g(-1) dry weight) and a clear induction of DNA adduct formation in the digestive gland of mussels (up to 1.13/10(8) 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

  1. Rabies in South Asia: fighting for elimination.

    Chowdhury, Fazle-Rabbi; Basher, Ariful; Amin, Mohammad R; Hassan, Nazia; Patwary, Mohammad I

    2015-01-01

    South Asia is regarded as the hot spot for the tourist and travelers. Unfortunately, three big countries (India, Pakistan and Bangladesh) of this region belong to top five rabies endemic countries of the world. Around 55,000 people die of rabies every year globally and 45% of them belong to South and South East Asia. Countries are now working on the elimination of rabies by the year 2020. Elimination of animal rabies is the pivotal of controlling human rabies. Dog (primary source) registration, population control and mass vaccination are the different ways of eliminating animal rabies. Pre (for risk groups including travelers) and post-exposure vaccine is the core for controlling human rabies. Post-exposure vaccine consists of nerve tissue vaccine and tissue culture vaccine. Due to low antigenicity and post-vaccine neurological complications all countries of South Asia except Pakistan have phased out the production and use of nerve tissue vaccine. To reduce the cost intramuscular regimen is now largely replaced by intradermal regimen and equine rabies immunoglobulin will probably replace human immunoglobulin in future for category III animal bite. 'SAARC' took initiatives for rabies elimination through 'SAARC development fund' which would hopefully play a vital role in regional collaboration to make the region rabies free. PMID:25858305

  2. Promoting Relationships and Eliminating Violence in Canada

    Pepler, Debra; Craig, Wendy

    2011-01-01

    The Promoting Relationships and Eliminating Violence Network (PREVNet) involves Canadian researchers and national organizations working to promote healthy relationships and prevent bullying. In this paper, we provide the rationale for establishing PREVNet, a description of the work of the network, and an assessment of the success of PREVNet.…

  3. Eliminating Computational Instability In Multibody Simulations

    Watts, Gaines L.

    1994-01-01

    TWOBODY implements improved version of Lagrange multiplier method. Program ultilizes programming technique eliminating computational instability in multibody simulations in which Lagrange multipliers used. In technique, one uses constraint equations, instead of integration, to determine coordinates that are not independent. To illustrate technique, it includes simple mathematical model of solid rocket booster and parachute connected by frictionless swivel. Written in FORTRAN 77.

  4. Enhanced NTRU cryptosystem eliminating decryption failures

    Yao Jun; Zeng Guihua

    2006-01-01

    An enhaned NTRU cryptosystem eliminating decryption failures is proposed without using padding schemes and can resist the oracle model andchosen-ciphertext attacks. Because lattice reduction is the main threat to lattice-based cryptosystems, lattice reductionalgorithms are analyzed to evaluate the security of this scheme. Furthermore, the new scheme remains the advantage of high efficiency of original NTRU.

  5. Tuberculosis elimination: theory and practice in Europe.

    D'Ambrosio, Lia; Dara, Masoud; Tadolini, Marina; Centis, Rosella; Sotgiu, Giovanni; van der Werf, Marieke J; Gaga, Mina; Cirillo, Daniela; Spanevello, Antonio; Raviglione, Mario; Blasi, Francesco; Migliori, Giovanni Battista

    2014-05-01

    Although Europe identified the pathway to tuberculosis (TB) elimination in 1990, no information on programmes for country preparedness is available. A questionnaire investigating TB elimination activities was submitted to 38 national TB programme representatives of low TB incidence (national TB programme, 20 (64.5%) a national plan including TB elimination (13 (41.9%) including targets), 22 (71%) guidelines, 14 (45.2%) a specific budget for TB activities, and 23 (74.2%) TB reference centres. All countries reported having case-based electronic TB surveillance, 19 (61.3%) perform regular supervision, 12 (38.7%) have a monitoring and evaluation plan and five (16.1%) perform modelling. In three countries (9.7%), TB health services are free for insured individuals only. In 22 countries/territories (71%) not all TB drugs were available, while in 12 (38.7%) drug stock-outs have been described. Although high-risk group screening for latent TB infection is performed by the majority of countries, only 6 (19.4%) provided figures on preventive treatment completion rates. Not all elements identified as essential for country preparedness to achieve TB elimination are available in the countries surveyed. PMID:24389868

  6. Limitation of peak fitting and peak shape methods for determination of activation energy of thermoluminescence glow peaks

    Sunta, C M; Piters, T M; Watanabe, S

    1999-01-01

    This paper shows the limitation of general order peak fitting and peak shape methods for determining the activation energy of the thermoluminescence glow peaks in the cases in which retrapping probability is much higher than the recombination probability and the traps are filled up to near saturation level. Right values can be obtained when the trap occupancy is reduced by using small doses or by post-irradiation partial bleaching. This limitation in the application of these methods has not been indicated earlier. In view of the unknown nature of kinetics in the experimental samples, it is recommended that these methods of activation energy determination should be applied only at doses well below the saturation dose.

  7. WaVPeak: Picking NMR peaks through wavelet-based smoothing and volume-based filtering

    Liu, Zhi

    2012-02-10

    Motivation: Nuclear magnetic resonance (NMR) has been widely used as a powerful tool to determine the 3D structures of proteins in vivo. However, the post-spectra processing stage of NMR structure determination usually involves a tremendous amount of time and expert knowledge, which includes peak picking, chemical shift assignment and structure calculation steps. Detecting accurate peaks from the NMR spectra is a prerequisite for all following steps, and thus remains a key problem in automatic NMR structure determination. Results: We introduce WaVPeak, a fully automatic peak detection method. WaVPeak first smoothes the given NMR spectrum by wavelets. The peaks are then identified as the local maxima. The false positive peaks are filtered out efficiently by considering the volume of the peaks. WaVPeak has two major advantages over the state-of-the-art peak-picking methods. First, through wavelet-based smoothing, WaVPeak does not eliminate any data point in the spectra. Therefore, WaVPeak is able to detect weak peaks that are embedded in the noise level. NMR spectroscopists need the most help isolating these weak peaks. Second, WaVPeak estimates the volume of the peaks to filter the false positives. This is more reliable than intensity-based filters that are widely used in existing methods. We evaluate the performance of WaVPeak on the benchmark set proposed by PICKY (Alipanahi et al., 2009), one of the most accurate methods in the literature. The dataset comprises 32 2D and 3D spectra from eight different proteins. Experimental results demonstrate that WaVPeak achieves an average of 96%, 91%, 88%, 76% and 85% recall on 15N-HSQC, HNCO, HNCA, HNCACB and CBCA(CO)NH, respectively. When the same number of peaks are considered, WaVPeak significantly outperforms PICKY. The Author(s) 2012. Published by Oxford University Press.

  8. Electric peak power forecasting by year 2025

    Peak power demand in Kuwait up to the year 2025 was predicted using an artificial neural network (ANN) model. The aim of the study was to investigate the effect of air conditioning (A/C) units on long-term power demand. Five socio-economic factors were selected as inputs for the simulation: (1) gross national product, (2) population, (3) number of buildings, (4) imports of A/C units, and (5) index of industrial production. The study used socio-economic data from 1978 to 2000. Historical data of the first 10 years of the studied time period were used to train the ANN. The electrical network was then simulated to forecast peak power for the following 11 years. The calculated error was then used for years in which power consumption data were not available. The study demonstrated that average peak power rates increased by 4100 MW every 5 years. Various scenarios related to changes in population, the number of buildings, and the quantity of A/C units were then modelled to estimate long-term peak power demand. Results of the study demonstrated that population had the strongest impact on future power demand, while the number of buildings had the smallest impact. It was concluded that peak power growth can be controlled through the use of different immigration policies, increased A/C efficiency, and the use of vertical housing. 7 refs., 2 tabs., 6 figs

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

    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

  10. SYNTHESIS AND INFRARED STUDY OF SOME NEW MOLYBDATO AND HYDROGENOMOLYBDATO ADDUCTS AND COMPLEXES OF COBALT, ZINC, ANTIMONY AND CADMIUM CHLORIDES

    SERIGNE FALLOU POUYE

    2014-01-01

    Full Text Available Five new molybdato (four and hydrogenomolybdato (one adducts and complexes have been synthesized and studied by infrared spectroscopy. The suggested structures are all discrete, the molybdate anion behaving as a trichelating, a monochelating, a bridging, a tetrachelating and a bichelating ligand. The environment around Zn, Co, Cd is tetrahedral or trigonal bipyramidal also for Zn - while being octahedral for Sb. The Cd pentanuclear adduct has a two metallic components structure, a tetranuclear anionic one with a tetrachelating molybdate, the second being a neutral dehydrated adduct component. The suggested structure for the hydrogenomolybdato adduct is discrete, the hydrogenomolybdate being present as a hydrogen bonded dimer behaves as a bridging bidentate ligand. The water molecules can be considered as a coordinating ligand or lattice. When secondary interactions through hydrogen bonds involving the water molecules are considered supramolecular architectures are obtained.

  11. Water-soluble noncovalent adducts of the heterometallic copper subgroup complexes and human serum albumin with remarkable luminescent properties.

    Chelushkin, P S; Krupenya, D V; Tseng, Yu-Jui; Kuo, Ting-Yi; Chou, Pi-Tai; Koshevoy, I O; Burov, S V; Tunik, S P

    2014-01-25

    Novel water-soluble noncovalent adducts of the heterometallic copper subgroup complexes and human serum albumin (HSA) display strong phosphorescence, internalize into HeLa cells and can be used in time-resolved fluorescent imaging. PMID:24296768

  12. Pattern of OH radical reaction with N6,N6-dimethyladenosine. Production of three isomeric OH adducts and their dehydration and ring-opening reactions

    By use of pulse radiolysis with optical and conductance detection, the reactions in aqueous solution of OH radicals by N6,N6-dimethyladenosine (DMAdo) were studied. OH reacts with DMAdo with the rate constant 6.4 x 109 M-1 s-1 by addition to C-4 (35% probability), to C-5 (19%), and to C-8 (30%) and by H abstraction from the methyl or ribose groups (16%). The resulting OH adducts A-4-OH and A-5-OH on the one hand and A-8-OH on the other undergo unimolecular transformation reactions characterized by different rates (at 20 0C) and activation parameters. With A-4-OH and A-5-OH, the transformations involve OH- elimination (dehydration) (k = (4.2-4.9) x 105 s-1) to yield the radical cation DMAdo/sup .+/; with A-8-OH, opening of the imidazole ring occurs (k = 9.5 x 104 s-1). DMAdo/sup .+/ oxidizes N,N,N',N'-tetramethyl-p-phenylenediamine with k = 2.9 x 109 M-1 s-1. The OH- elimination reactions of A-4-OH and A-5-OH are inhibited by protonation of the radicals, which occurs at pH 4-5 and probably involves N6 as the proton acceptor. The elimination of OH- is prevented also by OH-. In contrast, the ring opening reaction that A-8-OH undergoes is enhanced by OH-. A-4-OH, A-5-OH, and A-8-OH and their transformation products differ also with respect to their redox properties. A-4-OH has a low reactivity with O2, whereas A-5-OH and A-8-OH are extremely reactive

  13. Paleomagnetism of the Becker Peak stock

    Miller, B. A.; Housen, B. A.

    2009-12-01

    Paleomagnetic studies of plutonic rocks, although subject to uncertainty due to lack of paleohorizontal control, can provide important constrains of patterns of regional deformation, and can play a role in evaluation of tectonic models and reconstructions. Many plutonic rocks of the Cascades have been well-studied via paleomagnetism, but there are many that lack robust data sets. One such pluton, the Beckler Peak stock, is a late Cretaceous tonalitic stock, with biotite and amphibole K-Ar ages of 93 to 82 Ma (Engels and Crowder, 1971, Yeats and Engels, 1971). The Beckler Peak stock is considered to be a companion body to the larger Mt. Stuart Batholith, but is separated from the Mt. Stuart Batholith by the Evergreen Fault. For this study five paleomagnetic sites were sampled from the Beckler Peak stock near Skykomish, Washington. After low temperature and thermal demagnetization site means were calculated for the four sites where at least two samples survived demagnetization. Unblocking temperatures were indicative of magnetite and hematite as the carriers of remanence. Two of the site means were disregarded due to anomalous directions likely due to sites being from very large slump blocks. The two acceptable site means, along with a Beckler Peak stock site mean from Beck and Noson (1972) and another from Housen et al. (2003) give a stock-wide mean of D = 3.8°, I = 41.9°, k = 32.9, and α95 = 16.2°. This direction is consistent with mean directions for the Mount Stuart batholith determined by Beck and Noson (1972), Beck et al. (1981), and Housen et al. (2003). This directional consistency supports an association between the Beckler Peak stock and the Mt. Stuart Batholith, or at least that these two plutonic bodies were emplaced in the same structural block, and that any post-magnetization deformation (such as rotation and/or tilt associated with the Evergreen Fault) between the Beckler Peak stock and the Mt. Stuart Batholith was minor.

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

    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

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

    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 μM BPDE showed dose-dependent increases in r7,t8,t9-trihydroxy-c-10-(N2deoxyguanosyl)-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/108 nucleotides, detectable PAH-DNA adduct values ranged from 25 to 191/108 nucleotides, with a median of 75/108 nucleotides. PAH-DNA adduct values above 150/108 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 related to the increased risk of

  16. MOSES AND DENNISON PEAK ROADLESS AREAS, CALIFORNIA.

    Goldfarb, Richard J.; Lipton, David A.

    1984-01-01

    A mineral-resource survey was conducted in the Moses and Dennison Peak Roadless Areas, southeastern Sierra Nevada, California. One area within the Moses Roadless Area is classified as having substantiated mineral-resource potential for small base-metal skarn deposits. Additionally, geochemical data indicate probable potential for small base-metal skarn deposits from one locality within Dennison Peak Roadless Area and for small tungsten skarn deposits from a region within Moses Roadless Area. The geologic setting precludes the presence of energy resources.

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

    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 ...

  18. Benzo(a)pyrene-albumin adducts in humans exposed to polycyclic aromatic hydrocarbons in an industrial area of Poland.

    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...

  19. Significant Positive Correlation of Plasma BPDE-Albumin Adducts to Urinary 1-Hydroxypyrene in Coke Oven Workers

    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.

  20. Mass spectrometry-based quantification of myocardial protein adducts with acrolein in an in vivo model of oxidative stress

    Wu, Jianyong; Stevens, Jan F.; Maier, Claudia S.

    2011-01-01

    Acrolein exposure leads to the formation of protein-acrolein adducts. Protein modification by acrolein has been associated with various chronic diseases including cardiovascular and neurodegenerative diseases. Here we report an analytical strategy that enables the quantification of Michael-type protein adducts of acrolein in mitochondrial proteome samples using liquid chromatography in combination with tandem mass spectrometry and selected ion monitoring (LC-MS/MS SRM) analysis. Our approach ...

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

    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

  2. Modulation of the Effect of Prenatal PAH Exposure on PAH-DNA Adducts in Cord Blood by Plasma Antioxidants

    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...

  3. Contribution of artifacts to N-methylated piperazine cyanide adduct formation in vitro from N-alkyl piperazine analogs.

    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

  4. Evidence for phosphorus bonding in phosphorus trichloride-methanol adduct: a matrix isolation infrared and ab initio computational study.

    Joshi, Prasad Ramesh; Ramanathan, N; Sundararajan, K; Sankaran, K

    2015-04-01

    The weak interaction between PCl3 and CH3OH was investigated using matrix isolation infrared spectroscopy and ab initio computations. In a nitrogen matrix at low temperature, the noncovalent adduct was generated and characterized using Fourier transform infrared spectroscopy. Computations were performed at B3LYP/6-311++G(d,p), B3LYP/aug-cc-pVDZ, and MP2/6-311++G(d,p) levels of theory to optimize the possible geometries of PCl3-CH3OH adducts. Computations revealed two minima on the potential energy surface, of which, the global minimum is stabilized by a noncovalent P···O interaction, known as a pnictogen bonding (phosphorus bonding or P-bonding). The local minimum corresponded to a cyclic adduct, stabilized by the conventional hydrogen bonding (Cl···H-O and Cl···H-C interactions). Experimentally, 1:1 P-bonded PCl3-CH3OH adduct in nitrogen matrix was identified, where shifts in the P-Cl modes of PCl3, O-C, and O-H modes of CH3OH submolecules were observed. The observed vibrational frequencies of the P-bonded adduct in a nitrogen matrix agreed well with the computed frequencies. Furthermore, computations also predicted that the P-bonded adduct is stronger than H-bonded adduct by ∼1.56 kcal/mol. Atoms in molecules and natural bond orbital analyses were performed to understand the nature of interactions and effect of charge transfer interaction on the stability of the adducts. PMID:25772403

  5. Haploidization via Chromosome Elimination: Means and Mechanisms.

    Ishii, Takayoshi; Karimi-Ashtiyani, Raheleh; Houben, Andreas

    2016-04-29

    The ability to generate haploids and subsequently induce chromosome doubling significantly accelerates the crop breeding process. Haploids have been induced through the generation of plants from haploid tissues (in situ gynogenesis and androgenesis) and through the selective loss of a parental chromosome set via inter- or intraspecific hybridization. Here, we focus on the mechanisms responsible for this selective chromosome elimination. CENH3, a variant of the centromere-specific histone H3, has been exploited to create an efficient method of haploid induction, and we discuss this approach in some detail. Parallels have been drawn with chromosome-specific elimination, which occurs as a normal part of differentiation and sex determination in many plant and animal systems. PMID:26772657

  6. McGuire snubber elimination program

    An engineering program has been initiated at McGuire Nuclear Stations 1 and 2 to eliminate all existing snubbers. The elimination is achieved by replacing existing snubbers with limit stop pipe supports. The program establishes plant-wide modification procedures for one-to-one substitution under the 10 CFR 50.59 requirement. Nuclear Regulatory Commission (NRC) acceptance is based on the results of both comparison analyses and the hardware implementation of sample piping systems at McGuire nuclear stations. Experimental results obtained on shake table testing and from the NRC sponsored HDR research program are also used to formulate the technical basis and design procedures for plant-wide implementation of the snubber replacement effort. The overall program plan is for nearly 3,000 snubbers to be replaced in phases consistent with the plant scheduled outages. Duke Power estimates the program, when completed, will maintain ALARA, improve reliability, and reduce plant operating costs

  7. Eliminative behaviour of dairy cows at pasture

    Whistance, Lindsay Kay; Sinclair, Liam A.; Arney, David Richard;

    2011-01-01

    Despite a strong avoidance of grazing near dung patches, cattle have traditionally been considered not to avoid bodily contact with faeces, regardless of any risk of disease. Little is understood of the behaviour of pasture-kept dairy cows at the time of defaecation and therefore, the eliminative...... behaviour of 40 Holstein-Friesian cows was observed at pasture for6 heach day between morning and afternoon milking for a total of24 h. Lying (l), standing (s) and walking (w) behaviours were recorded pre, during and post-elimination. Sequences of 3–6 changes in these behaviours were recorded if expressed...... observed events (uppercase letters denote behaviour during defaecation). In all recorded events, 383 stood and 54 walked whilst defaecating (P

  8. Renal elimination of organic anions in cholestasis

    Adriana Mónica Tortes

    2008-01-01

    The disposition of most drugs is highly dependent on specialized transporters.OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells,identified as contributors to xenobiotic and endogenous organic anion secretion.It is well known that cholestasis may cause renal damage.Impairment of kidney function produces modifications in the renal elimination of drugs.Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis.Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters.The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.

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

    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.

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

    Ishøi, L; Sørensen, C N; Kaae, N M; Jørgensen, L B; Hölmich, P; Serner, A

    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...... implemented in-season with an 8-week progressive training program elicited a large significant increase in EHAD, EHAB, and EHAD/EHAB ratio....... 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...

  11. Monitoring the apple polyphenol oxidase-modulated adduct formation of phenolic and amino compounds.

    Reinkensmeier, Annika; Steinbrenner, Katrin; Homann, Thomas; Bußler, Sara; Rohn, Sascha; Rawel, Hashadrai M

    2016-03-01

    Minimally processed fruit products such as smoothies are increasingly coming into demand. However, they are often combined with dairy ingredients. In this combination, phenolic compounds, polyphenoloxidases, and amino compounds could interact. In this work, a model approach is presented where apple serves as a source for a high polyphenoloxidase activity for modulating the reactions. The polyphenoloxidase activity ranged from 128 to 333nakt/mL in different apple varieties. From these, 'Braeburn' was found to provide the highest enzymatic activity. The formation and stability of resulting chromogenic conjugates was investigated. The results show that such adducts are not stable and possible degradation mechanisms leading to follow-up products formed are proposed. Finally, apple extracts were used to modify proteins and their functional properties characterized. There were retaining antioxidant properties inherent to phenolic compounds after adduct formation. Consequently, such interactions may also be utilized to improve the textural quality of food products. PMID:26471529

  12. Preparation, properties and application of lanthanide thenoyltrifluoroacetonate adducts with diaza-15-crown-5

    The interaction of the whole series of lanthanide thenoyltrifluoroacetonates (TTA) with diaza-15-crown-5 (DA15C5) has been studied by conductometric and luminescence methods in aqueous ethanol solutions. The composition of the adducts has been found to be Ln : TA : DA15C5 = 1 : 3 : 1, the logarithms of their conditional stability constants are (2.05 - 2.45) ± (0.04 - 0.06). The mechanism of europium luminescence quenching in the adducts by foreign lanthanide ions has been established. A luminescence method for determination of europium in high purity lanthanide oxides and sulfides and gallium-gadolinium garnet has been worked out with detection limits of 5 x 10-6% and 5 x 10-7% respectively

  13. Greater Hip Extension but Not Hip Abduction Explosive Strength Is Associated With Lesser Hip Adduction and Knee Valgus Motion During a Single-Leg Jump-Cut

    Cronin, Baker; Johnson, Samuel T.; Chang, Eunwook; Pollard, Christine D.; Norcross, Marc F.

    2016-01-01

    Background: The relationships between hip abductor and extensor strength and frontal plane hip and knee motions that are associated with anterior cruciate ligament injury risk are equivocal. However, previous research on these relationships has evaluated relatively low-level movement tasks and peak torque rather than a time-critical strength measure such as the rate of torque development (RTD). Hypothesis: Females with greater hip abduction and extension RTD would exhibit lesser frontal plane hip and knee motion during a single-leg jump-cutting task. Study Design: Descriptive laboratory study. Methods: Forty recreationally active females performed maximal isometric contractions and single-leg jump-cuts. From recorded torque data, hip extension and abduction RTD was calculated from torque onset to 200 ms after onset. Three-dimensional motion analysis was used to quantify frontal plane hip and knee kinematics during the movement task. For each RTD measure, jump-cut biomechanics were compared between participants in the highest (high) and lowest (low) RTD tertiles. Results: No differences in frontal plane hip and knee kinematics were identified between high and low hip abduction RTD groups. However, those in the high hip extension RTD group exhibited lower hip adduction (high, 3.8° ± 3.0°; low, 6.5° ± 3.0°; P = .019) and knee valgus (high, –2.5° ± 2.3°; low, –4.4° ± 3.2°; P = .046) displacements during the jump-cut. Conclusion: In movements such as cutting that are performed with the hip in a relatively abducted and flexed position, the ability of the gluteus medius to control hip adduction may be compromised. However, the gluteus maximus, functioning as a hip abductor, may take on a pivotal role in controlling hip adduction and knee valgus motion during these types of tasks. Clinical Relevance: Training with a specific emphasis on increasing explosive strength of the hip extensors may be a means through which to improve frontal plane hip and knee

  14. Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

    McDaniel, Larry S.; Swiatlo, Edwin

    2016-01-01

    ABSTRACT  Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The pneumococcal conjugate vaccines have significantly reduced invasive disease. However, these vaccines have changed pneumococcal ecology within the human nasopharynx. We suggest that elimination of the pneumococcus from the human nasopharynx can have consequences that should be considered as the next generation of pneumococcal va...

  15. Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

    McDaniel, Larry S; Swiatlo, Edwin

    2016-01-01

    Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The pneumococcal conjugate vaccines have significantly reduced invasive disease. However, these vaccines have changed pneumococcal ecology within the human nasopharynx. We suggest that elimination of the pneumococcus from the human nasopharynx can have consequences that should be considered as the next generation of pneumococcal vaccines is developed. PMID:27222469

  16. Decreased elimination of theophylline after influenza vaccination.

    Renton, K W; Gray, J D; Hall, R. I.

    1980-01-01

    The elimination of theophylline is decreased after vaccination against influenza. In three patients receiving 200 mg of oxtriphylline (equivalent to 128 mg of theophylline) every 6 hours by mouth the serum theophylline levels rose after vaccination, and in four healthy volunteers given the same dose of oxtriphylline 24 hours after vaccination the half-life of theophylline increased by an average of 122%. Two of the three patients showed signs of a toxic reaction to the drug. These results sug...

  17. Challenges for malaria elimination in Brazil.

    Ferreira, Marcelo U; Castro, Marcia C

    2016-01-01

    Brazil currently contributes 42 % of all malaria cases reported in the Latin America and the Caribbean, a region where major progress towards malaria elimination has been achieved in recent years. In 2014, malaria burden in Brazil (143,910 microscopically confirmed cases and 41 malaria-related deaths) has reached its lowest levels in 35 years, Plasmodium falciparum is highly focal, and the geographic boundary of transmission has considerably shrunk. Transmission in Brazil remains entrenched in the Amazon Basin, which accounts for 99.5 % of the country's malaria burden. This paper reviews major lessons learned from past and current malaria control policies in Brazil. A comprehensive discussion of the scientific and logistic challenges that may impact malaria elimination efforts in the country is presented in light of the launching of the Plan for Elimination of Malaria in Brazil in November 2015. Challenges for malaria elimination addressed include the high prevalence of symptomless and submicroscopic infections, emerging anti-malarial drug resistance in P. falciparum and Plasmodium vivax and the lack of safe anti-relapse drugs, the largely neglected burden of malaria in pregnancy, the need for better vector control strategies where Anopheles mosquitoes present a highly variable biting behaviour, human movement, the need for effective surveillance and tools to identify foci of infection in areas with low transmission, and the effects of environmental changes and climatic variability in transmission. Control actions launched in Brazil and results to come are likely to influence control programs in other countries in the Americas. PMID:27206924

  18. Eliminating Electroencephalogram Artefacts Using Independent Component Analysis

    Rashid, Akram; Qureshi, Ijaz Mansoor

    2015-01-01

    The elimination of artefacts from Electroencephalogram(EEG) has an important role many signal and image processing applications. The artefacts are the noises that appears during the acquisition of signals from the patient body. With the presence of these artefacts it become difficult for doctors and technicians to analyse the Electroencephalogram signals efficiently. The aim of this research work is to remove these artefacts using Independent Components Analysis(ICA). The scalp EEG is intensi...

  19. Prime number generation and factor elimination

    Kumar, Vineet

    2014-01-01

    We have presented a multivariate polynomial function termed as factor elimination function,by which, we can generate prime numbers. This function's mapping behavior can explain the irregularities in the occurrence of prime numbers on the number line. Generally the different categories of prime numbers found till date, satisfy the form of this function. We present some absolute and probabilistic conditions for the primality of the number generated by this method. This function is capable of le...

  20. Prizes and Incentives in Elimination Tournaments

    Sherwin Rosen

    1985-01-01

    The role of rewards for maintaining performance incentives in multistage, sequential games of survival is studied. The sequential structure is a statistical design-of-experiments for selecting and ranking contestants. It promotes survival of the fittest and saves sampling costs by early elimination of weaker contenders. Analysis begins with the case where competitors' talents are common knowledge and is extended to cases where talents are unknown. It is shown that extra weight must be placed ...

  1. Eliminating the cost of task set reconfiguration.

    Hunt, Amelia R; Klein, Raymond M

    2002-06-01

    With insufficient time to fully prepare for a switch in task, a deterioration in performance on the first trial of a new task would be expected. The interest of researchers has been captured by the residual switch costs that, surprisingly, remain despite sufficient time to prepare. We used avery simple task to investigate the costs to reaction time and accuracy associated with changing between two different instructional sets every eight trials. Subjects responded to left and right visual targets by making either spatially compatible or incompatible eye movements (Experiment 1) or buttonpress responses (Experiment 2). The subjects were cued as to whether to make the compatible or the incompatible response by the color of a border appearing on the perimeter of the display. In cases in which the subject alternated between making pro- and antisaccades, the large costs to reaction time and accuracy at the short cue-target stimulus onset asynchrony were completely eliminated when sufficient time was provided to prepare for the switch. This complete elimination of residual switch costs was not obtained when the same alternation was applied to manual responses. This pattern of results links residual costs to response selection processes and suggests that they are not a necessary component of the switch process. We propose that the elimination of "stubborn" residual switch costs is rooted in our use of a hypercompatible task (making saccades toward targets) that places minimal demands on response selection. PMID:12184554

  2. DNA adduct formation by ochratoxin A?: A review of the available evidence

    Dekant, Wolfgang

    2005-01-01

    Abstract The mycotoxin ochratoxin A (OTA) is a potent nephrotoxin and renal carcinogen in rodents. However, the mechanism of OTA-induced tumour formation is unknown and conflicting results regarding the potential of OTA to react with DNA have been obtained. While experiments using radiolabelled (3H or 14C) OTA and liquid scintillation counting or accelerator mass spectrometry indicate lack of formation of covalent DNA-adducts, spots detected by 32P-postlabelling have been attribute...

  3. Polyamines stimulate the formation of mutagenic 1,N 2-propanodeoxyguanosine adducts from acetaldehyde

    Theruvathu, Jacob A.; Jaruga, Pawel; Nath, Raghu G.; Dizdaroglu, Miral; Brooks, P. J.

    2005-01-01

    Alcoholic beverage consumption is associated with an increased risk of upper gastrointestinal cancer. Acetaldehyde (AA), the first metabolite of ethanol, is a suspected human carcinogen, but the molecular mechanisms underlying AA carcinogenicity are unclear. In this work, we tested the hypothesis that polyamines could facilitate the formation of mutagenic α-methyl-γ-hydroxy-1,N 2-propano-2′-deoxyguanosine (Cr-PdG) adducts from biologically relevant AA concentrations. We found that Cr-PdG addu...

  4. Formation of an adduct between fosfomycin and glutathione: a new mechanism of antibiotic resistance in bacteria.

    Arca, P; Rico, M; Braña, A F; Villar, C J; Hardisson, C; Suárez, J E

    1988-01-01

    Plasmid-borne resistance to fosfomycin in bacteria is due to modification of the antibiotic molecule by a glutathione S-transferase that catalyzes the formation of a covalent bond between the sulfhydryl residue of the cysteine in glutathione and the C-1 of fosfomycin. This reaction results in opening of the epoxide ring of the antibiotic to form an inactive adduct, the structure of which was confirmed by nuclear magnetic resonance. Dialyzed extracts prepared from resistant Escherichia coli st...

  5. Loss of Dermatan-4-Sulfotransferase 1 Function Results in Adducted Thumb-Clubfoot Syndrome

    Dündar, Munis; Müller, Thomas; Zhang, Qi; Pan, Jing; Steinmann, Beat; Vodopiutz, Julia; Gruber, Robert; Sonoda, Tohru; Krabichler, Birgit; Utermann, Gerd; Baenziger, Jacques U.; Zhang, Lijuan; Janecke, Andreas R.

    2009-01-01

    Adducted thumb-clubfoot syndrome is an autosomal-recessive disorder characterized by typical facial appearance, wasted build, thin and translucent skin, congenital contractures of thumbs and feet, joint instability, facial clefting, and coagulopathy, as well as heart, kidney, or intestinal defects. We elucidated the molecular basis of the disease by using a SNP array-based genome-wide linkage approach that identified distinct homozygous nonsense and missense mutations in CHST14 in each of fou...

  6. DFT study on adduct reaction paths of GaN MOCVD growth

    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.

  7. Triple helix-forming oligonucleotides target psoralen adducts to specific chromosomal sequences in human cells.

    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...

  8. Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother–newborns

    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.

  9. SOME NEW SULFATO AND HYDROGENOSULFATO ADDUCTS: SYNTHESIS, INFRARED AND MÖSSBAUER STUDIES

    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.

  10. Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother-newborns

    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.

  11. Thermogravimetric and calorimetric study of cadmium iodide adducts with cyclic ureas

    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

  12. Free flow electrophoresis separation and AMS quantitation of {sup 14}C-naphthalene-protein adducts

    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.

  13. Preparation and characterization of the adducts between lanthanide methanesulfonates and thioxane oxide

    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.)

  14. uvrC gene function has no specific role in repair of N-2-aminofluorene adducts.

    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.

  15. 32P-Postlabelling/HPLC analysis of various styrene-induced DNA adducts in mice

    Koskinen, M.; Vodička, Pavel; Vodičková, L.; Hemminki, K.

    2001-01-01

    Roč. 6, č. 3 (2001), s. 175-189. ISSN 1354-750X R&D Projects: GA ČR GA313/99/1460 Grant ostatní: GA-(EU) QLK4-1999-01368 Institutional research plan: CEZ:AV0Z5039906 Keywords : DNA adducts Subject RIV: EA - Cell Biology Impact factor: 1.118, year: 2001

  16. Kinetics of formation of specific styrene oxide adducts in double-stranded DNA

    Koskinen, M.; Vodičková, L.; Vodička, Pavel; Warner, S. C.; Hemminki, K.

    2001-01-01

    Roč. 138, č. 2 (2001), s. 111-124. ISSN 0009-2797 R&D Projects: GA ČR GA313/99/1460 Grant ostatní: EU(XC) QLK4-1999-01368 Institutional research plan: CEZ:AV0Z5039906 Keywords : biomonitoring * DNA adducts Subject RIV: EA - Cell Biology Impact factor: 1.706, year: 2001

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

    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 ...

  18. The 1:1 adduct of caffeine and 2-(1,3-dioxoisoindolin-2-ylacetic acid

    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.

  19. Hitting Hotspots: Spatial Targeting of Malaria for Control and Elimination

    Bousema, T.; Griffin, J.T.; Sauerwein, R.W.; Smith, D.L.; Churcher, T.S.; Takken, W.; Ghani, A.; Drakeley, C.; Gosling, R.

    2012-01-01

    Current malaria elimination guidelines are based on the concept that malaria transmission becomes heterogeneous in the later phases of malaria elimination [1]. In the pre-elimination and elimination phases, interventions have to be targeted to entire villages or towns with higher malaria incidence u

  20. Role of Scaphoid in the Abduction and Adduction Movements of Wrist Joint

    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

  1. Protein adducts of the prostate carcinogen PhIP in children

    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.

  2. The reversibility of the glutathionyl-quercetin adduct spreads oxidized quercetin-induced toxicity

    Quercetin is one of the most prominent dietary antioxidants. During its antioxidant activity, quercetin becomes oxidized into its o-quinone/quinone methide QQ. QQ is toxic since it instantaneously reacts with thiols of, e.g., proteins. In cells, QQ will initially form an adduct with glutathione (GSH), giving GSQ. We have found that GSQ is not stable; it dissociates continuously into GSH and QQ with a half life of 2 min. Surprisingly, GSQ incubated with 2-mercapto-ethanol (MSH), a far less reactive thiol, results in the conversion of GSQ into the MSH-adduct MSQ. A similar conversion of GSQ into relatively stable protein thiol-quercetin adducts is expected. With the dithiol dihydrolipoic acid (L(SH)2), quercetin is formed out of GSQ. These results indicate that GSQ acts as transport and storage of QQ. In that way, the initially highly focussed toxicity of QQ is dispersed by the formation of GSQ that finally spreads QQ-induced toxicity, probably even over cells

  3. Molecular structures of five adducts assembled from p-dimethylaminobenzaldehyde and organic acids

    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.

  4. Suicide of EMT-6 tumor cells by decays from radioactively-labelled sensitizer adducts

    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

  5. Differential repair of platinum-DNA adducts in human bladder and testicular tumor continuous cell lines

    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

  6. 32P-postlabelling analysis of DNA adducted with urinary mutagens from smokers of black tobacco.

    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

  7. Real estate price peaks: a comparative overview

    Röhner, B M

    2006-01-01

    First, we emphasize that the real estate price peaks which are currently under way in many industrialized countries (one important exception is Japan) share many of the characteristics of previous historical price peaks. In particular, we show that: (i) In the present episode real price increases are, at least for now, of the same order of magnitude as in previous episodes, typically of the order of 80 percent to 100 percent. (ii) Historically, price peaks turned out to be symmetrical with respect to the peak; soft landing, i.e. an upgoing phase followed by a plateau, has rarely (if ever) been observed. (iii) The inflated demand is mainly boosted by investors and high-income buyers. (iv) In the present as well as in previous episodes, the main engines in the upgoing phase have been the hot markets which developed in major cities such as London, Los Angeles, New York, Paris, San Francisco or Sydney. In our conclusion, we propose a prediction for real estate prices in the West of the United States over the peri...

  8. Facility Location with Double-peaked Preferences

    Filos-Ratsikas, Aris; Li, Minming; Zhang, Jie;

    2015-01-01

    ; this makes the problem essentially more challenging. As our main contribution, we present a simple truthful-in-expectation mechanism that achieves an approximation ratio of 1+b=c for both the social and the maximum, cost, where b is the distance of the agent from the peak and c is the minimum cost of...

  9. APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

    Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24 h. In cultures where APE1 expression was reduced by ∼80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons

  10. APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

    Kim, Hyun-Suk [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Guo, Chunlu; Thompson, Eric L. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Jiang, Yanlin [Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Kelley, Mark R. [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Vasko, Michael R. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Lee, Suk-Hee, E-mail: slee@iu.edu [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States)

    2015-09-15

    Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24 h. In cultures where APE1 expression was reduced by ∼80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons.

  11. Determining peak stress history using acoustic emissions

    As part of the test program at the Nevada Test Site, there is a need for determining the peak stress induced by explosions in tuff. Standard techniques make use of various gages grouted into the tuff prior to the test. These are difficulties in interpreting the output of these gages and there is always the chance that the gage will not survive long enough to allow a stress determination to be made. As an alternative, we have been testing a passive technique for determining peak stress as a function of distance from a test. Using core samples retrieved from the vicinity of an explosion, we have tested for the existence of a threshold stress for the onset of acoustic emissions, the Kaiser effect (Kaiser 1950). From laboratory results it is known that for many rock types, the previously applied peak stress can be detected by restressing a sample while monitoring acoustic emissions. An abrupt onset for acoustic emission activity typically occurs at a stress state close to the previous peak. The point of this work was to determine if the Kaiser effect occurred in tuff and, if so, whether it could be used to determine the peak stresses induced by an explosion. On the basis of four tests it is only possible to draw tentative conclusions. There does seem to be enough evidence of the existence and stress dependence of the Kaiser effect in the tuff to allow hope for the use of this technique in studying past stress states. In future tests the saturation state of the samples should be carefully controlled. Tests should be done on variously oriented subcores from a main core to determine the other components of the in situ stress tensor. If the components are indeed decoupled, as these few tests indicate, then a complete stress determination can be made this way. It would be interesting to use the same technique to try and determine in situ stresses in tuff. 7 refs., 6 figs

  12. The peak in anomalous magnetic viscosity

    Anomalous magnetic viscosity, where the magnetization as a function of time exhibits non-monotonic behaviour, being seen to increase, reach a peak, and then decrease, is observed on recoil lines in bulk amorphous ferromagnets, for certain magnetic prehistories. A simple geometrical approach based on the motion of the state line on the Preisach plane gives a theoretical framework for interpreting non-monotonic behaviour and explains the origin of the peak. This approach gives an expression for the time taken to reach the peak as a function of the applied (or holding) field. The theory is applied to experimental data for bulk amorphous ferromagnet alloys of composition Nd60−xFe30Al10Dyx, x = 0, 1, 2, 3 and 4, and it gives a reasonable description of the observed behaviour. The role played by other key magnetic parameters, such as the intrinsic coercivity and fluctuation field, is also discussed. When the non-monotonic behaviour of the magnetization of a number of alloys is viewed in the context of the model, features of universal behaviour emerge, that are independent of alloy composition. - Highlights: • Development of a simple geometrical model based on the Preisach model which gives a complete explanation of the peak in the magnetic viscosity. • Geometrical approach is extended by considering equations that govern the motion of the state line. • The model is used to deduce the relationship between the holding field and the time it takes to reach the peak. • The model is tested with experimental results for a range of Nd–Fe–Al–Dy bulk amorphous ferromagnets. • There is good agreement between the model and the experimental data

  13. Lipid peroxidation-derived etheno-DNA adducts in human atherosclerotic lesions

    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

  14. Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Retrorsine, Leading to DNA Adduct Formation In Vivo

    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

  15. The global cost of eliminating avoidable blindness

    Kirsten L Armstrong

    2012-01-01

    Full Text Available Aims : To complete an initial estimate of the global cost of eliminating avoidable blindness, including the investment required to build ongoing primary and secondary health care systems, as well as to eliminate the ′backlog′ of avoidable blindness. This analysis also seeks to understand and articulate where key data limitations lie. Materials and Methods : Data were collected in line with a global estimation approach, including separate costing frameworks for the primary and secondary care sectors, and the treatment of backlog. Results : The global direct health cost to eliminate avoidable blindness over a 10-year period from 2011 to 2020 is estimated at $632 billion per year (2009 US$. As countries already spend $592 billion per annum on eye health, this represents additional investment of $397.8 billion over 10 years, which is $40 billion per year or $5.80 per person for each year between 2010 and 2020. This is concentrated in high-income nations, which require 68% of the investment but comprise 16% of the world′s inhabitants. For all other regions, the additional investment required is $127 billion. Conclusions : This costing estimate has identified that low- and middle-income countries require less than half the additional investment compared with high-income nations. Low- and middle-income countries comprise the greater investment proportion in secondary care whereas high-income countries require the majority of investment into the primary sector. However, there is a need to improve sector data. Investment in better data will have positive flow-on effects for the eye health sector.

  16. Redundancy Elimination in DTN via ACK Mechanism

    Xiqing Zhang

    2015-08-01

    Full Text Available The traditional routing protocols for delay tolerant networks (DTN usually take the strategy of spreading multiple copies of one message to the networks. When one copy reaches destination, the transmission of other copies not only waste the bandwidth but also deprive other messages of the opportunities for transmission. This paper brings up a mechanism to eliminate the redundant copies. By adding an acknowledge field to the packet header to delete redundant copies, it can degrade the network overhead while improve the delivery ratio. Simulation results confirm that the proposed method can improve the performance of epidemic and Spray and Wait routing protocol.

  17. Prolonged midazolam elimination half-life.

    Dundee, J W; Collier, P S; Carlisle, R J; Harper, K. W.

    1986-01-01

    The pharmacokinetics of a fixed dose of midazolam (0.3 mg kg-1 i.v.) were studied in detail in 115 healthy patients or volunteers and nine were found with a prolonged elimination half-life. A further 102 patients had an abbreviated pharmacokinetic study, of whom five showed a similar abnormality. Defective hepatic metabolism of midazolam may be a factor in the aetiology of what appears to be a true phenomenon, occurring in 6% of over 200 fit subjects given a standard dose of the drug.

  18. Elimination of Sexual Discrimination in English Study

    蒋小文

    2008-01-01

    Gender discrimination is a social attitude that is re- flected in language. The representation of gender discrimination in the English language has a variety of forms, and can be eliminated by vari- ous means. English teachers are supposed to observe these phenomenon, avoiding using sexual prejudical words and helping students to learn to use neuter words so that they can communicate with English native speakers effortlessly without hurting the latter. This thesis is tending to talk about the ways of removing sexism in English study.

  19. The Doppler peaks from a generic defect

    Magueijo, J

    1996-01-01

    We investigate which of the exotic Doppler peak features found for textures and cosmic strings are generic novelties pertaining to defects. We find that the ``out of phase'' texture signature is an accident. Generic defects, when they generate a secondary peak structure similar to inflation, apply to it an additive shift. It is not necessary for this shift to be ``out of phase''. We also show which factors are responsible for the absence of secondary oscillations found for cosmic strings. Within this general analysis we finally consider the conditions under which topological defects and inflation can be confused. It is argued that only \\Omega=1 inflation and a defect with a horizon size coherence length have a chance to be confused. Any other inflationary or defect model always differ distinctly. (To appear in the proceedings of the XXXIth Moriond meeting, ``Microwave Background Anisotropies'')

  20. After Acoustic Peaks What's Next in CMB?

    Cooray, A R

    2002-01-01

    The advent of high signal-to-noise cosmic microwave background (CMB) anisotropy experiments has allowed detailed studies on the power spectrum of temperature fluctuations. The existence of acoustic oscillations in the anisotropy power spectrum is now established with the detection of the first two, and possibly the third, peaks. Beyond the acoustic peak structure, we consider cosmological and astrophysical information that can be extracted by pushing anisotropy observations to fine angular scales with higher resolution instruments. At small scales, a variety of contributions allow the use of CMB photons as a probe of the large scale structure: we outline possible studies related to understanding detailed physical properties such as the distribution of dark matter, baryons and pressure, and ways to measure the peculiar, transverse and rotational velocities of virialized halos such as galaxy clusters. Beyond the temperature, we consider several useful aspects of the CMB polarization and comment on an ultimate g...

  1. A small dim infrared maritime target detection algorithm based on local peak detection and pipeline-filtering

    Wang, Bin; Dong, Lili; Zhao, Ming; Xu, Wenhai

    2015-12-01

    In order to realize accurate detection for small dim infrared maritime target, this paper proposes a target detection algorithm based on local peak detection and pipeline-filtering. This method firstly extracts some suspected targets through local peak detection and removes most of non-target peaks with self-adaptive threshold process. And then pipeline-filtering is used to eliminate residual interferences so that only real target can be retained. The experiment results prove that this method has high performance on target detection, and its missing alarm rate and false alarm rate can basically meet practical requirements.

  2. The accuracy of portable peak flow meters.

    Miller, M. R.; Dickinson, S A; Hitchings, D J

    1992-01-01

    BACKGROUND: The variability of peak expiratory flow (PEF) is now commonly used in the diagnosis and management of asthma. It is essential for PEF meters to have a linear response in order to obtain an unbiased measurement of PEF variability. As the accuracy and linearity of portable PEF meters have not been rigorously tested in recent years this aspect of their performance has been investigated. METHODS: The response of several portable PEF meters was tested with absolute standards of flow ge...

  3. EVALUATING CONGESTION PRICING IMPACTS UNDER PEAK SPREADING

    Wolff, Carolyn; Vilain, Pierre

    2007-01-01

    The paper involves an econometric analysis of congestion pricing at the bridges and tunnels operated by the Port Authority of New York and New Jersey (PANYNJ). Using a fixed effects model, we pool all facilities to evaluate the impacts of the congestion pricing structure in effect since March 2001. We find significant impacts for autos, but need to confront a counter-intuitive finding: cash paying vehicles, who do not benefits from off-peak discounts, are also estimated to be impacted. Using ...

  4. Peak reduction technique in commutative algebra

    Shpilrain, Vladimir; Yu, Jie-Tai

    1999-01-01

    The "peak reduction" method is a powerful combinatorial technique with applications in many different areas of mathematics as well as theoretical computer science. It was introduced by Whitehead, a famous topologist and group theorist, who used it to solve an important algorithmic problem concerning automorphisms of a free group. Since then, this method was used to solve numerous problems in group theory, topology, combinatorics, and probably in some other areas as well. In this paper, we giv...

  5. Probing Cosmology with Weak Lensing Peak Counts

    Kratochvil, Jan M; May, Morgan

    2009-01-01

    We propose counting peaks in weak lensing (WL) maps, as a function of their height, to probe models of dark energy and to constrain cosmological parameters. Because peaks can be identified in two-dimensional WL maps directly, they can provide constraints that are free from potential selection effects and biases involved in identifying and determining the masses of galaxy clusters. We have run cosmological N-body simulations to produce WL convergence maps in three models with different constant values of the dark energy equation of state parameter, w=-0.8, -1, and -1.2, with a fixed normalization of the primordial power spectrum (corresponding to present-day normalizations of sigma8=0.742, 0.798, and 0.839, respectively). By comparing the number of WL peaks in 8 convergence bins in the range of -0.1 < kappa < 0.2, in multiple realizations of a single simulated 3x3 degree field, we show that the first (last) pair of models can be distinguished at the 95% (85%) confidence level. A survey with depth and are...

  6. Revisiting Twomey's approximation for peak supersaturation

    B. J. Shipway

    2015-04-01

    Full Text Available Twomey's seminal 1959 paper provided lower and upper bound approximations to the estimation of peak supersaturation within an updraft and thus provides the first closed expression for the number of nucleated cloud droplets. The form of this approximation is simple, but provides a surprisingly good estimate and has subsequently been employed in more sophisticated treatments of nucleation parametrization. In the current paper, we revisit the lower bound approximation of Twomey and make a small adjustment that can be used to obtain a more accurate calculation of peak supersaturation under all potential aerosol loadings and thermodynamic conditions. In order to make full use of this improved approximation, the underlying integro-differential equation for supersaturation evolution and the condition for calculating peak supersaturation are examined. A simple rearrangement of the algebra allows for an expression to be written down that can then be solved with a single lookup table with only one independent variable for an underlying lognormal aerosol population. While multimodal aerosol with N different dispersion characteristics requires 2N+1 inputs to calculate the activation fraction, only N of these one-dimensional lookup tables are needed. No additional information is required in the lookup table to deal with additional chemical, physical or thermodynamic properties. The resulting implementation provides a relatively simple, yet computationally cheap, physically based parametrization of droplet nucleation for use in climate and Numerical Weather Prediction models.

  7. Uncertainty in peak cooling load calculations

    Dominguez-Munoz, Fernando; Cejudo-Lopez, Jose M.; Carrillo-Andres, Antonio [Grupo de Energetica, ETS Ingenieros Industriales, Universidad de Malaga, Calle Dr. Ortiz Ramos, 29071 Malaga (Spain)

    2010-07-15

    Peak cooling loads are usually calculated at early stages of the building project, when large uncertainties affect the input data. Uncertainties arise from a variety of sources like the lack of information, random components and the approximate nature of the building mathematical model. Unfortunately, these uncertainties are normally large enough to make the result of the calculation very dependent on starting assumptions about the value of input data. HVAC engineers deal with uncertainties through worst-case scenarios and/or safety factors. In this paper, a new approach is proposed based on stochastic simulation methods. Uncertainty bands are applied to the input data and propagated through the building model in order to determine their impact on the peak cooling load. The result of this calculation is a probability distribution that quantifies the whole range of possible peak loads and the probability of each interval. The stochastic solution is compared with the conventional one, and a global sensitivity analysis is undertaken to identify the most important uncertainties. (author)

  8. Revisiting Twomey's approximation for peak supersaturation

    B. J. Shipway

    2014-10-01

    Full Text Available Twomey's seminal 1959 paper provided lower and upper bound approximations to the estimation of peak supersaturation within an updraft and thus provides the first closed expression for the number of nucleated cloud droplets. The form of this approximation is simple, but provides a surprisingly good estimate and has subsequently been employed in more sophisticated treatments of nucleation parametrization. In the current paper, we revisit the lower bound approximation of Twomey and make a small adjustment which can be used to obtain a more accurate calculation of peak supersaturation under all potential aerosol loadings and thermodynamic conditions. In order to make full use of this improved approximation, the underlying integro-differential equation for supersaturation evolution and the condition for calculating peak supersaturation are examined. A simple rearrangement of the algebra allows for an expression to be written down which can then be solved with a single lookup table with only one independent variable for an underlying lognormal aerosol population. Multimode aerosol with only N different dispersion characteristics require only N of these one-dimensional lookup tables. No additional information is required in the lookup table to deal with additional chemical, physical or thermodynamic properties. The resulting implementation provides a relatively simple, yet computationally cheap and very accurate physically-based parametrization of droplet nucleation for use in climate and NWP models.

  9. [Fast spectral modeling based on Voigt peaks].

    Li, Jin-rong; Dai, Lian-kui

    2012-03-01

    Indirect hard modeling (IHM) is a recently introduced method for quantitative spectral analysis, which was applied to the analysis of nonlinear relation between mixture spectrum and component concentration. In addition, IHM is an effectual technology for the analysis of components of mixture with molecular interactions and strongly overlapping bands. Before the establishment of regression model, IHM needs to model the measured spectrum as a sum of Voigt peaks. The precision of the spectral model has immediate impact on the accuracy of the regression model. A spectrum often includes dozens or even hundreds of Voigt peaks, which mean that spectral modeling is a optimization problem with high dimensionality in fact. So, large operation overhead is needed and the solution would not be numerically unique due to the ill-condition of the optimization problem. An improved spectral modeling method is presented in the present paper, which reduces the dimensionality of optimization problem by determining the overlapped peaks in spectrum. Experimental results show that the spectral modeling based on the new method is more accurate and needs much shorter running time than conventional method. PMID:22582612

  10. METing SUSY on the Z peak

    Barenboim, G.; Bernabeu, J.; Vives, O. [Universitat de Valencia, Departament de Fisica Teorica, Burjassot (Spain); Universitat de Valencia-CSIC, Parc Cientific U.V., IFIC, Paterna (Spain); Mitsou, V.A.; Romero, E. [Universitat de Valencia-CSIC, Parc Cientific U.V., IFIC, Paterna (Spain)

    2016-02-15

    Recently the ATLAS experiment announced a 3 σ excess at the Z-peak consisting of 29 pairs of leptons together with two or more jets, E{sub T}{sup miss} > 225 GeV and HT > 600 GeV, to be compared with 10.6 ± 3.2 expected lepton pairs in the Standard Model. No excess outside the Z-peak was observed. By trying to explain this signal with SUSY we find that only relatively light gluinos, m{sub g} or similar 400 GeV decaying predominantly to Z-boson plus a light gravitino, such that nearly every gluino produces at least one Z-boson in its decay chain, could reproduce the excess. We construct an explicit general gauge mediation model able to reproduce the observed signal overcoming all the experimental limits. Needless to say, more sophisticated models could also reproduce the signal, however, any model would have to exhibit the following features: light gluinos, or heavy particles with a strong production cross section, producing at least one Z-boson in its decay chain. The implications of our findings for the Run II at LHC with the scaling on the Z peak, as well as for the direct search of gluinos and other SUSY particles, are pointed out. (orig.)

  11. An alternative interpretation for cosmic ray peaks

    Kim, Doojin

    2015-01-01

    We propose an alternative mechanism based upon dark matter (DM) interpretation for anomalous peak signatures in cosmic ray measurements, assuming an extended dark sector with two DM species. This is contrasted with previous effort to explain various line-like cosmic-ray excesses in the context of DM models where the relevant DM candidate directly annihilates into Standard Model (SM) particles. The heavier DM is assumed to annihilate to an on-shell intermediate state. As the simplest choice, it decays directly into the lighter DM along with an unstable particle which in turn decays to a pair of SM states corresponding to the interesting cosmic anomaly. We show that a sharp continuum energy peak can be readily generated under the proposed DM scenario, depending on dark sector particle mass spectra. Remarkably, such a peak is robustly identified as half the mass of the unstable particle. Furthermore, other underlying mass parameters are analytically related to the shape of energy spectrum. We apply this idea to ...

  12. Ten Reasons to Take Peak Oil Seriously

    Robert J. Brecha

    2013-02-01

    Full Text Available Forty years ago, the results of modeling, as presented in The Limits to Growth, reinvigorated a discussion about exponentially growing consumption of natural resources, ranging from metals to fossil fuels to atmospheric capacity, and how such consumption could not continue far into the future. Fifteen years earlier, M. King Hubbert had made the projection that petroleum production in the continental United States would likely reach a maximum around 1970, followed by a world production maximum a few decades later. The debate about “peak oil”, as it has come to be called, is accompanied by some of the same vociferous denials, myths and ideological polemicizing that have surrounded later representations of The Limits to Growth. In this review, we present several lines of evidence as to why arguments for a near-term peak in world conventional oil production should be taken seriously—both in the sense that there is strong evidence for peak oil and in the sense that being societally unprepared for declining oil production will have serious consequences.

  13. Deuterium-labeling method for the assignment of histidine nuclear magentic resonance peaks of proteins

    A tritium labelling method involving differential tritium exchange at the C-2 H position of histidines and 1H NMR of differentially deuterated proteins can be a general method for the assignment of the histidine NMR peaks. In the present report this method is modified by replacing the tritium with deuterium, which eliminates ambiguities arising from the tritium isotope effect. In the deuterium labelling method, differentially deuterated proteins are cleaved by trypsin into smaller peptides each containing a single histidine residue, which are separated by chromatography. The method was applied to the Bence Hones dimer Ak which contains two histidine residues in the constant domain of each of the light chains. The decay of the NMR peaks with time allowed the assignment of one peak to His189 and the other to His198

  14. In vitro hemoglobin adduct formation in blood from rats, mice and humans using 14C-phenol

    Hemoglobin (Hb) adducts may be useful biomarkers of exposures to chemicals. The mechanisms of Hb adduct formation were studied to enable better extrapolations of rodent studies to human exposure situations. Resuspended red blood cells (RBC) obtained from male F344/N rats, B6C3F1 mice and humans were incubated with 50 nmoles 14C-phenol/ml for 60 min in the presence of liver S9 from each species. Globin was isolated and analyzed for bound 14C. 14C-Phenol-derived Hb adduct levels from rat, mouse and human RBC incubations were 1.66 ± 0.02, 0.82 ± 0.09, and 0.58 ± 0.10 pmoles of adducts/mg globin (X ± SE; n=3-6), respectively. Preincubating RBC with maleimide, a sulfhydryl blocker, reduced adduct formation in rat, mouse and human RBC by 22.4 ± 2.7, 62.1 ± 3.8, and 1.40 ± 0.02%, respectively. RBC incubation with maleimide and subsequent measurement of free sulfhydryls in isolated globin showed that maleimide was able to bind to only 36.4 ± 4.4, 59.1 ± 3.6 and 21.4 ± 1.2 of the cysteine (Cys) sulfhydryls in Hb from rats, mice and humans, respectively. These studies suggest that humans are less efficient in forming Hb adducts than rodents. Also, the contribution of Cys binding to the total adducts formed on Hb may be greater in rodents than humans, due to the accessibility of Hb

  15. Photochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA and Formation of DNA Covalent Adducts

    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.

  16. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

    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

  17. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

    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.

  18. Eliminating Major Tornadoes in Tornado Alley

    Tao, R.

    2015-03-01

    In my recent paper, I propose that major tornadoes in Tornado Alley can be eliminated by building east-west ranged walls, 300 meter high and 50 meter wide. The work has received much attention, but some meteorologists are against the idea, claiming that the major tornadoes in Tornado Alley are not related to the collisions between northbound warm air flow and southbound cold air flow because supercells are not at the collision front. In this talk, we will show that wind tunnel experiments and airplane wing tip vortices clearly demonstrate that vortices produced by air mass collisions are usually not at the collision front because of the extremely volatile condition over there; they are either near the ends or at side of the collision fronts. When the warm and moist wind collides with the cold wind violently in Tornado Alley, similarly, the supercell storms cannot be right at the collision fronts, but are near the ends or at sides of the collision fronts. While only a small portion of vortices in the warm air side may have a chance to develop into tornadoes, the major tornadoes in Tornado Alley indeed start from the air mass clashes. If we can weaken such violent air mass collisions, we will eliminate the major tornadoes in Tornado Alley. The work is supported in part by Naval Research Lab.

  19. The OBE Elimination in Piping Design

    The Operating Basis Earthquake (OBE) and Safe Shutdown Earthquake (SSE) have been considered in the design of nuclear power facilities as required by Appendix A to 10 CFR Part 100. However, it is believed that the elimination of the OBE from the design of nuclear facilities would be necessary for plant optimization since the OBE criterion is too rigid and has excessive conservatism. Studies indicate that alternative piping designs can exhibit reliability and safety levels equal to or greater than the current analysis methods. The alternative rules for the Earthquake Engineering Criteria have been issued by the Appendix S to 10 CFR 50. In the System 80+ Design, the USNRC reviewed the alternate analysis methods which were proposed to eliminate the OBE based on the EPRI-URD and concluded that those were acceptable as stated in the NUREG-1462. In the Korean Next Generation Reactor (KNGR) developed as an ALWR, a typical piping model was selected to include ASME Classes 1, 2 and 3 piping and was analyzed according to the current method as well as the alternate analysis method, specified in NUREG-1462, for comparison

  20. Elimination of Lymphatic Filariasis in Southern India

    Sanjay Pattanshetty

    2010-12-01

    Full Text Available BackgroundLymphatic filariasis is an important public health problem in India. Inspite of National filarial control programme (NFCP being in place for lymphatic filariasis (LF elimination, several important issues need to be addressed. There is uncertainty about the coverage and compliance to treatment in order to achieve elimination. Method A community based cross-sectional study was conducted as per the National Vector Borne Disease Control Programme (NVBDCP directions. The study included survey of 200 households of Dakshina Kannada District, South India where the Mass drug administration (MDA program was conducted. The main objective of the study was to assess the coverage and compliance to MDA. ResultsOut of the total 1050 eligible people, 876 (83% received the DEC tablets; so, the coverage was 83%. Among those who received the tablets, only 777 (88.7% received the adequate dose and only 670 (76.8% people actually consumed the tablets. Hence, compliance rate was only 76.8%.ConclusionThe planning and implementation of MDA programme needs to be strengthened by efficient micro planning, inter sectoral co-ordination and motivating the community to participate in the MDA programme.

  1. The Geometry of Ideal-specific Elimination-Orders and Improvements to Elimination

    Bosse, Hartwig

    2012-01-01

    This paper shows that Gr\\"obner walks aiming for the elimination of variables from a polynomial ideal can be terminated much earlier than previously known. To this end we provide an improved stopping criterion for a known Gr\\"obner walk algorithm for the elemination of variables. This results from two new geometric insights on Gr\\"obner fans: We show that for any given ideal I \\subset K[x_1, ..., x_n] the collection of Gr\\"obner cones corresponding to I-specific elimination orders may contain Gr\\"obner cones in the relative interior of the positive orthant. Moreover we prove that the corresponding Gr\\"obner cones form a star-shaped region (the center being the set of all universal elimination vectors) which contrary to first intuition in general is not convex.

  2. Accounting for peak shifting in traditional cost-benefit analysis

    Snarr, Hal W.; Axelsen, Dan

    2007-01-01

    When cost-benefit analysis fails to account for peak-shifting the benefits of road improvement options are miscalculated. Using theory from transportation economics, we derive a simple model that disaggregates the average daily equilibrium into peak, counter-peak, and off-peak equilibria. This paper demonstrates how accounting for peak-shifting improves the performance of cost-benefit analysis.

  3. A sticky situation: the unexpected stability of malaria elimination.

    Smith, David L; Cohen, Justin M; Chiyaka, Christinah; Johnston, Geoffrey; Gething, Peter W; Gosling, Roly; Buckee, Caroline O; Laxminarayan, Ramanan; Hay, Simon I; Tatem, Andrew J

    2013-08-01

    Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination's 'stickiness' must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system's increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination's stickiness at moderate

  4. Particle creation by peak electric field

    Adorno, T C; Gitman, D M

    2016-01-01

    The particle creation by the so-called peak electric field is considered. The latter field is a combination of two exponential parts, one exponentially-increasing and another exponentially-decreasing. We find exact solutions of the Dirac equation with the field under consideration with appropriate asymptotic conditions and calculate all the characteristics of particle creation effect, in particular, differential mean numbers of created particle, total number of created particles, and the probability for a vacuum to remain a vacuum. Characteristic asymptotic regimes are discussed in detail and a comparison with the pure asymptotically decaying field is considered.

  5. Probable Values of Current Solar Cycle Peak

    V. M. Silbergleit

    2012-01-01

    Full Text Available An analysis of multiple linear regression method applied to solar cycles 4 to 23 using lagged values of smoothed monthly mean sunspot numbers as independent variables is presented. According to that, the amplitude of current solar cycle 24 is estimated providing a quantitative prediction result. Our adjustment shows that the current cycle would have a sunspot peak less than the biggest one observed during the cycle 19 giving an additional support to the declination in solar activity which is currently happening.

  6. Peak oil, economic growth, and wildlife conservation

    Gates, J Edward; Czech, Brian

    2014-01-01

    The proposed book focuses on one of the most important issues affecting humankind in this century - Peak Oil or the declining availability of abundant, cheap energy-and its effects on our industrialized economy and wildlife conservation. Energy will be one of the defining issues of the 21st Century directly affecting wildlife conservation wherever energy extraction is a primary economic activity and indirectly through deepening economic recessions. Since cheap, abundant energy has been at the core of our industrial society, and has resulted in the technological advancements we enjoy today, the

  7. Derivative polynomials and permutations by numbers of interior peaks and left peaks

    Ma, Shi-Mei

    2011-01-01

    Derivative polynomials in two variables are defined by repeated differentiation of the tangent and secant functions. We establish the connections between the coefficients of these derivative polynomials and the numbers of interior and left peaks over the symmetric group. Properties of the generating functions for the numbers of interior and left peaks over the symmetric group, including recurrence relations, generating functions and real-rootedness, are studied.

  8. Effect of acetylator genotype on the levels of carcinogen-DNA adducts in inbred hamsters treated with 2-aminofluorene

    A genetic polymorphism in N-acetyltransferase has been described previously in humans and in animal models that is known to affect an individual's susceptibility to certain drug toxicities and diseases including bladder cancer. In hamsters, the polymorphism is known to regulate the conversion of carcinogenic 2-aminofluorene to its amide and of N-hydroxy-2-aminofluorene to a reactive electrophile that forms a covalently-bound adduct with DNA; an event thought to initiate the tumorigenic process. A single dose of 2-aminofluorene (60 mg/kg body wt., i.p) was administered to homozygous rapid- (rr) and homozygous slow-acetylator (ss) hamsters, and the levels of aminofluorene-DNA adducts in bladder and liver were evaluated by a 32P-postlabeling assay. Only a non-acetylated aminofluorene-DNA adduct was detected in the DNA samples. In this study, no differences were detected between the levels of hepatic 2-aminofluorene-DNA adducts in males or females or between the rr or ss hamsters. In contrast, the levels of 2-amino-fluorene-adducts in bladder DNA were 5-fold higher in the male rr than in the ss hamsters, and were 2-fold higher in the male rr than in the female rr animals

  9. Formation and persistence of DNA adducts from the carcinogen N-hydroxy-2-acetylaminofluorene in rat mammary gland in vivo

    The rat mammary carcinogen, N-hydroxy-2-acetylaminofluorene (N-hydroxy-2-AAF), has been proposed to be metabolically activated by mammary cytosolic N,O-acetyltransferase to a DNA binding species. To test this hypothesis, adult female Sprague-Dawley derived CD rats were treated, i.p., with 4.0 mg/kg [ring-3H]N-hydroxy-2-AAF. After 4 h, 1, 3, 14, and 28 days, the animals were killed, the mammary epithelium DNA was isolated and the carcinogen-deoxyribonucleoside adducts present were analyzed by high pressure liquid chromatography. At each time, only one adduct was detected and it was chromatographically identical to N-(deoxyguanosin-8-yl)-2-aminofluorene. The level of the adduct was maximal at 4 h (1.5 adducts/10(6) nucleotides) and then decreased, following first order kinetics with a t1/2 of 14.2 days. The detection of a single non-acetylated aminofluorene adduct is consistent with N,O-acyltransferase being involved in the metabolic activation of N-hydroxy-2-AAF in the rat mammary gland

  10. Determining protein adducts of fipexide: mass spectrometry based assay for confirming the involvement of its reactive metabolite in covalent binding.

    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

  11. Cysteine amide adduct formation from carboxylic acid drugs via UGT-mediated bioactivation in human liver microsomes.

    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

  12. RESULTS of the "ELIMINATING NOISE" campaign

    SC Unit

    2008-01-01

    From 4 to 6 August, CERN’s nurses conducted a screening campaign entitled "Eliminating noise". This campaign was especially aimed at young people exposed to noise during their leisure hours (playing in a band, listening to MP3 players, attending concerts, etc.). In all, 166 people attended the Infirmary, where they were able to receive personalised advice, documentation and, above all, a hearing test (audiogram). While the high attendance of people in the younger age category (18-30) was a success, their audiogram data were a cause for concern, with 24.5% showing abnormal results, hearing deficiencies which, we should remind you, are irreversible. It should be noted that such conditions are almost exclusively caused by noise exposure in a non-professional environment (leisure activities, music, etc.). This latest campaign confirms the harmful effects of noise on people’s hearing due to the absence or insufficiency of protective equipment during music-related activities; this further unde...

  13. RESULTS of the "ELIMINATING NOISE" campaign

    SC Unit

    2008-01-01

    From 4 to 6 August, CERN’s nurses conducted a screening campaign entitled "Eliminating noise". This campaign was especially aimed at young people exposed to noise during their leisure hours (playing in a band, listening to MP3 players, attending concerts, etc.). In all, 166 people attended the infirmary, where they were able to receive personalised advice, documentation and, above all, a hearing test (audiogram). While the high attendance of people in the younger age category (18-30) was a success, their audiogram data were a cause for concern, with 24.5% showing abnormal results, hearing deficiencies which, we should remind you, are irreversible. It should be noted that such conditions are almost exclusively caused by noise exposure in a non-professional environment (leisure activities, music, etc.). This latest campaign confirms the harmful effects of noise on people’s hearing due to the absence or insufficiency of protective equipment during music-related activities; this further unde...

  14. Lean for Government: Eliminating the Seven Wastes

    Shepherd, Christena C.

    2012-01-01

    With shrinking budgets and a slow economy, it is becoming increasingly important for all government agencies to become more efficient. Citizens expect and deserve efficient and effective services from federal, state and local government agencies. One of the best methods to improve efficiency and eliminate waste is to institute the business process improvement methodologies known collectively as Lean; however, with reduced budgets, it may not be possible to train everyone in Lean or to engage the services of a trained consultant. It is possible, however, to raise awareness of the "Seven Wastes" of Lean in each employee, and encourage them to identify areas for improvement. Management commitment is vital to the success of these initiatives, and it is also important to develop the right metrics that will track the success of these changes.

  15. Detergent water use eliminates VOC concerns

    Chang, M. [Dexter Electronic Materials Division, Industry, CA (United States)

    1996-01-01

    The article describes an electronics manufacturer`s use of detergent water and mechanical equipment (heated pressure washers and floor scrubbers) to replace volatile organic compounds. The cleaning formula development and detergent recovery system are emphasized. Detailed chemical analyses of the waste detergent water and spent filters are provided. The rationale for using detergent water; a process flow diagram for cleaning, recovery and storage; and cost considerations are summarized. At a cost of $300,000, the system removed a significant source of air emissions and enabled the plant to eliminate 30 tons of liquid hazardous waste, improve cleaning effectiveness, and save $99,000 per year in cleaning-related costs. 2 figs., 2 tabs.

  16. Direct analysis in real time (DART) mass spectrometry of nucleotides and nucleosides: elucidation of a novel fragment [C5H5O]+ and its in-source adducts.

    Curtis, Matthew; Minier, Mikael A; Chitranshi, Priyanka; Sparkman, O David; Jones, Patrick R; Xue, Liang

    2010-08-01

    Direct analysis in real time (DART) mass spectrometry is a recently developed innovative technology, which has shown broad applications for fast and convenient analysis of complex samples. Due to the ease of sample preparation, we have recently initiated an investigation of the feasibility of detecting nucleotides and nucleosides using the DART-AccuTOF instrument, which we will refer to as the DART mass spectrometer. Our experimental results reveal that the ions representing the intact molecules of nucleotides are not detectable in either positive-ion or negative-ion mode. Instead, all four natural nucleotides fragment in the DART ion source, and a common fragment ion, [C(5)H(5)O](+) (1), is observed, which is probably formed via multiple-elimination reactions. Interestingly, 1 can form adducts with nucleobases in different molar ratios in the DART ion source. In contrast to nucleotides, the ions representing the intact molecules of nucleosides are detected in both positive-ion and negative-ion mode using DART mass spectrometry. Surprisingly, the fragmentation pattern of nucleosides is different from that of nucleotides in the DART ion source. In the cases of nucleosides (under positive-ion conditions), the production of 1 is not observed, indicating that the phosphate group plays an important role for the multiple eliminations observed in the spectra of nucleotides. The in-source reactions described in the present work show the complexity of the conditions in the DART ion source, and we hope that our results illustrate a better understanding about DART mass spectrometry. PMID:20451406

  17. STUDY ON ELIMINATING FLUORESCENCE IN COTTON PULP WITH PERACETIC ACID

    Lixin Xu; Baoguo Sun

    2004-01-01

    This paper has studied processing conditions and the influence of every variable to the pulp when the fluorescence in cotton linter pulp is eliminated with peracetic acid. The suitable variables of the elimination of fluorescence. are found.

  18. STUDY ON ELIMINATING FLUORESCENCE IN COTTON PULP WITH PERACETIC ACID

    LixinXu; BaoguoSun

    2004-01-01

    This paper has studied processing conditions and the influence of every variable to the pulp when the fluorescence in cotton linter pulp is eliminated with peracetic acid. The suitable variables of the elimination of fluorescence, are found.

  19. Gaussian elimination in unitary groups with an application to cryptography

    Mahalanobis, Ayan; Singh, Anupam

    2014-01-01

    Gaussian elimination is used in special linear groups to solve the word problem. In this paper, we extend Gaussian elimination to unitary groups. These algorithms have an application in building a public-key cryptosystem, we demonstrate that.

  20. Documented and potential extreme peak discharges and relation between potential extreme peak discharges and probable maximum flood peak discharges in Texas

    Asquith, W.H.; Slade, R.M., Jr.

    1995-01-01

    The U.S. Geological Survey, in cooperation with the Texas Department of Transportation, conducted a study of extreme flood potential for Texas. Potential extreme peak discharges, derived from the relation between documented extreme peak discharges and their contributing drainage areas, can provide valuable information concerning the maximum expected peak discharge that could occur at a stream site. Documented extreme peak discharges and associated data were aggregated for 832 sites with and without streamflow-gaging stations in natural basins in Texas. A potential extreme peak discharge curve was developed for each of 11 hydrologic regions in Texas and for the State as a whole, based on documented extreme peak discharges and associated contributing drainage areas. The curve envelops, for a large range of drainage areas, the largest documented extreme peak discharges. Potential extreme peak discharges estimated from the curves were compared to probable maximum flood peak discharges estimated from various simulation models.

  1. Tracking matrix effects in the analysis of DNA adducts of polycyclic aromatic hydrocarbons.

    Klaene, Joshua J; Flarakos, Caroline; Glick, James; Barret, Jennifer T; Zarbl, Helmut; Vouros, Paul

    2016-03-25

    LC-MS using electrospray ionization is currently the method of choice in bio-organic analysis covering a wide range of applications in a broad spectrum of biological media. The technique is noted for its high sensitivity but one major limitation that hinders achievement of its optimal sensitivity is the signal suppression due to matrix inferences introduced by the presence of co-extracted compounds during the sample preparation procedure. The analysis of DNA adducts of common environmental carcinogens is particularly sensitive to such matrix effects as sample preparation is a multistep process which involves "contamination" of the sample due to the addition of enzymes and other reagents for digestion of the DNA in order to isolate the analyte(s). This problem is further exacerbated by the need to reach low levels of quantitation (LOQ in the ppb level) while also working with limited (2-5μg) quantities of sample. We report here on the systematic investigation of ion signal suppression contributed by each individual step involved in the sample preparation associated with the analysis of DNA adducts of polycyclic aromatic hydrocarbon (PAH) using as model analyte BaP-dG, the deoxyguanosine (dG) adduct of benzo[a]pyrene (BaP). The individual matrix contribution of each one of these sources to analyte signal was systematically addressed as were any interactive effects. The information was used to develop a validated analytical protocol for the target biomarker at levels typically encountered in vivo using as little as 2μg of DNA and applied to a dose response study using a metabolically competent cell line. PMID:26607319

  2. Characterization of quinone derived protein adducts and their selective identification using redox cycling based chemiluminescence assay.

    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

  3. Eliminating paediatric infections and keeping mothers alive

    Gray G

    2012-11-01

    Full Text Available The global plan of reducing the number of new child HIV infections and a reduction in the number of HIV-related maternal deaths by 2015 will require inordinate political commitment and strengthening of health systems in Sub-Saharan Africa where the burden of HIV infections in pregnant women is the highest. Preventing HIV infection in women of child-bearing age and unwanted pregnancies in HIV-positive women forms the cornerstone of long-term control of paediatric HIV infections. To achieve the goal of eliminating paediatric HIV infection by 2015, health systems strengthening to address prevention of mother-to-child HIV transmission cascade attrition and focusing on the elimination of breastmilk transmission is critical. Understanding the pathogenesis of breastmilk transmission and the mechanisms by which antiretroviral therapy impacts on transmission through this compartment will drive future interventions. Identifying and retaining HIV-positive pregnant women in care and committed to long-term antiretroviral therapy will improve maternal outcomes and concomitant reductions in maternal mortality. Research assessing the natural history of HIV infection and long-term outcomes in women who interrupt antiretroviral therapy post-weaning is urgently required. Data on the outcome of women who opt to continue the long-term use of antiretroviral therapy after initiating therapy during pregnancy will determine future policy in countries considering option B+. The prevalence of antiretroviral resistance and impact on survival in infants who sero-convert whilst receiving neonatal prophylaxis, or are exposed to maternal HAART through breastmilk at a population level, are currently unknown. In addition to the provision of biomedical interventions, healthcare workers and policy makers must address the structural, cultural and community issues that impact on treatment uptake, adherence to medication and retention in care.

  4. Comparing three feedback internal multiple elimination methods

    Song, Jiawen; Verschuur, Eric; Chen, Xiaohong

    2013-08-01

    Multiple reflections have posed a great challenge for current seismic imaging and inversion methods. Compared to surface multiples, internal multiples are more difficult to remove due to poorer move-out discrimination with primaries and we are left with wave equation-based prediction and subtraction methods. In this paper, we focus on the comparison of three data-driven internal multiple elimination (IME) methods based on the feedback model, where two are well established prediction-and-subtraction methods using back-propagated data and surface data, referred to as CFP-based method and surface-based method, respectively, and the third one, an inversion-based method, has been recently extended from estimation of primaries by sparse inversion (EPSI). All these three methods are based on the separation of events from above and below a certain level, after which internal multiples are predicted by convolutions and correlations. We begin with theory review of layer-related feedback IME methods, where implementation steps for each method are discussed, and involved event separation are further analyzed. Then, recursive application of the three IME methods is demonstrated on synthetic data and field data. It shows that the two well established prediction-and-subtraction methods provide similar primary estimation results, with most of the internal multiples being removed while multiple leakage and primary distortion have been observed where primaries and internal multiples interfere. In contrast, generalized EPSI provides reduced multiple leakage and better primary restoration which is of great value for current seismic amplitude-preserved processing. As a main conclusion, with adaptive subtraction avoided, the inversion-based method is more effective than the prediction-and-subtraction methods for internal multiple elimination when primaries and internal multiples overlap. However, the inversion-based method is quite computationally intensive, and more researches on

  5. Peak Load Electricity Production with Cryogenic Fuels

    Gaetano Zumbo

    2009-09-01

    Full Text Available

    Natural Gas is often liquefied (LNG for its transport by ships over long distances. In order to prepare it for further transport by pipelines it has to be reduced again to a gaseous state, normally by heating it with sea water. A similar technology is envisaged for long-distance transport of Hydrogen as an energy carrier. The scope of this article is the thermodynamic investigation of two power plants for peak load energy production. These two power plants use as fuel the fluids obtained by the re-gasification of the cryogenic fluids. The first proposal is a Hydrogen-fired steam power plant, while the second considers the use of LNG in an oxy-combustion arrangement with subsequent CO2 separation, which is obtained by a three-stage intercooled compression train. The power cycle performance was verified in both cases by exergy analysis. Since the size of these power plants is relatively small (10 MWe, they can be easily built inside the area of LNG gasifiers, or inside the area of the plant producing liquid Hydrogen; the cryogenic fuel and oxidizer are thus considered available, and the purpose of the power plant is peak load energy production rather than obtaining high values of conversion efficiency.

    • This paper is an updated version of a paper published in the ECOS'08 proceedings. 

  6. Peak heart rates at extreme altitudes

    Lundby, C; Van Hall, Gerrit

    2001-01-01

    We have measured maximal heart rate during a graded maximal bicycle exercise test to exhaustion in five healthy climbers before and during an expedition to Mt. Everest. Maximal heart rates at sea level were 186 (177-204) beats/min(-1) at sea level and 170 (169-182) beats/min(-1) with acute hypoxia....... After 1, 4 and 6 weeks of acclimatization to 5400 m, maximal heart rates were 155 (135-182), 158 (144-182), and 155 (140-183) beats/min(-1), respectively. Heart rates of two of the climbers were measured during their attempt to reach the summit of Mt. Everest without the use of supplemental oxygen. The...... peak heart rates at 8,750 m for the two climbers were 142 and 144 beats/min(-1), which were similar to their maximal heart rates during exhaustive bicycle exercise at 5,400 m, the values being 144 and 148 beats/min(-1), respectively. The peak heart rates at 8,750 m are in agreement with other field...

  7. Outreach Plans for Storm Peak Laboratory

    Hallar, A. G.; McCubbin, I. B.

    2006-12-01

    The Desert Research Institute (DRI) operates a high elevation facility, Storm Peak Laboratory (SPL), located on the west summit of Mt. Werner in the Park Range near Steamboat Springs, Colorado at an elevation 10,500 ft. SPL provides an ideal location for long-term research on the interactions of atmospheric aerosol and gas- phase chemistry with cloud and natural radiation environments. SPL includes an office-type laboratory room for computer and instrumentation setup with outside air ports and cable access to the roof deck, a full kitchen and two bunk rooms with sleeping space for nine persons. We plan to create a unique summer undergraduate education experiences for students of diversity at Storm Peak Laboratory. As stressed by the College Pathways to Science Education Standards [Siebert and McIntosh, 2001], to support changes in K-12 science education transformations must first be made at the college level, including inquiry-oriented opportunities to engage in meaningful research. These workshops will be designed to allow students to experience the excitement of science, increasing their likelihood of pursing careers within the fields of scientific education or research.

  8. A mini-review on Biginelli adducts with notable pharmacological properties

    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.

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

    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...

  10. Cisplatin–DNA adducts inhibit translocation of the Ku subunits of DNA-PK

    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...

  11. STM/STS observation of ferrocene derivative adduct to C60 on HOPG

    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

  12. Shape of the Adduct Formic Acid-Dimethyl Ether: A Rotational Study.

    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

  13. TRANSPLATIN-CONJUGATED TRIPLEX-FORMING OLIGONUCLEOTIDES FORM ADDUCTS WITH BOTH STRANDS OF DNA

    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...

  14. Electron transfer from nucleobase electron adducts to 5-bromouracil: a radiation chemical study

    Electron transfer to 5-bromouracil from their nucleobase electron adducts and their protonated forms has been studied by product analysis. When an electron is transferred to 5-bromouracil, the ensuing 5-bromouracil radical anion rapidly loses a bromide ion. The uracilyl radical thus formed reacts with added t-butanol, yielding uracil. From the uracil yields measured as a function of (N)/(5-BrU) after γ-radiolysis of Ar-saturated solutions it is concluded that the hetero atom protonated forms transfer electron quantitatively to 5-bromouracil. (author). 3 refs., 1 fig

  15. Preparation of SRN1-Type Coupling Adducts from Aliphatic gem-Dinitro Compounds in Ionic Liquids

    Seiichi Toyoshima

    2012-04-01

    Full Text Available SRN1-type coupling adducts are readily prepared by the reaction between a-sulfonylesters or a-cyanosulfones and gem-dinitro compounds in ionic liquids. The reactions progress smoothly and recovered ionic liquids can be used for several iterations, as long as they are washed with water to remove alkali metallic salts. The reaction rate is slower than the corresponding SRN1 reaction in DMSO, but no acceleration on irradiation or no inhibition in the presence of m-DNB are observed.

  16. Lead tetraacetate oxidation of the Diels-Alder adduct of 7-dehydrocholestryl acetate with maleic anhydride

    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.

  17. Hitting Hotspots: Spatial Targeting of Malaria for Control and Elimination

    Bousema, Jan Teun; Griffin, J.T.; Sauerwein, R.W.; Smith, D. L.; Churcher, T.S.; Takken, W.; Ghani, A.; Drakeley, C.; Gosling, R.

    2012-01-01

    Current malaria elimination guidelines are based on the concept that malaria transmission becomes heterogeneous in the later phases of malaria elimination [1]. In the pre-elimination and elimination phases, interventions have to be targeted to entire villages or towns with higher malaria incidence until only individual episodes of malaria remain and become the centre of attention [1]. With increasing evidence of clustering of malaria episodes within villages, we argue that there is an interme...

  18. EXPERIMENTAL DEVICE OF THE HIGH HUMIDITY AIR ELECTROSTATIC ELIMINATOR

    吴筱青; 何尉岚

    1990-01-01

    As for electrostatic elimination there are many means.But the high humidity air electrostatic eliminator has simple,efficient, lightproof and fireproof etc. advantages. Thus it is often used in some industrial enterprises. The aim of this paper is to introduce an experimental device of high humidity air electrostatic eliminator and its principle and experimental data.

  19. Formation and persistence of sterigmatocystin-DNA adducts in rat liver determined via 32P-postlabeling analysis

    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.)

  20. Myeloperoxidase - 463A variant reduces benzo(a)pyrene diol epoxide DNA adducts in skin of coal tar treated patients

    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.

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

    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+.

  2. BUFFALO PEAKS WILDERNESS STUDY AREA, COLORADO.

    Hedlund, D.C.; Wood, R.H.

    1984-01-01

    Field investigations were conducted to evaluate the mineral-resource potential of the Buffalo Peaks Wilderness Study Area, Colorado. On the basis of this study there is a probable mineral-resource potential for silver vein and bedding replacement deposits along the Weston Pass fault zone, for hydrothermal vein-type uranium deposits in the vicinity of the Parkdale iron pit, and for gold vein deposits in the parts of the Granite and Four Mile districts that are within the wilderness study area. A probable barite resource potential occurs at Rough and Tumbling Creek and near Spring Creek on the east side of the study area. There is little promise for the occurrence of energy resources.

  3. Power peakings in mixed TRIGA cores

    Snoj, Luka; Ravnik, Matjaz [Jozef Stefan Institute, Reactor Physics Division F-8, Jamova 39, SI-1000 Ljubljana (Slovenia)], E-mail: luka.snoj@ijs.si

    2006-07-01

    Power distribution in the reactor core is normally calculated by the diffusion codes (e.g. TRIGLAV package) in 2-D approximation. Diffusion codes normally treat the fuel rods and surrounding water as homogeneous regions called unit cells. Modern Monte-Carlo codes (e.g. MCNP) allow calculation of the power density distribution in 3-D geometry assuming detailed geometry without unit-cell homogenization. The power density distribution (and its maximum value - the peaking) can be calculated 'point-wise' with the resolution of approximately 1 mm. Results of the detailed power density distribution calculated by MCNP are presented for 250 kW TRIGA Mark II reactor, assuming various realistic and hypothetical core loading patterns with focus on the mixed cores. Combinations of 8.5 w/o, 12 w/o and 20 w/o low enriched (20 %) TRIGA fuel elements are systematically treated in the mixed cores. (author)

  4. Deuterium treatment of low water peak fiber

    Xinwei QIAN; Deming LIU; Feng TU

    2009-01-01

    The deuterium (D2) treatment of low water peak single-mode fiber (LWP-SMF) after drawing has been investigated. The D2 treatment time and concentra-tion have important effect on fiber's properties after D2 treatment. The insufficient treatment of D2 cannot ensure fiber resistant to hydrogen aging, whereas excessive treatment of D2 will result in excess loss on fiber at 13 83 nm. The optimization on viscosity match between the core and the cladding is helpful on problem solving of excess loss after the D2 treatment. However, by designing proper time and D2 concentration in the D2 treatment process, it can produce fiber with good hydrogen aging resistance and low excess loss and lower the cost of the D2 treatment process.

  5. Association between plasma BPDE‐Alb adduct concentrations and DNA damage of peripheral blood lymphocytes among coke oven workers

    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

  6. Accumulation of miscoding etheno-DNA adducts and highly expressed DNA repair during liver fluke-induced cholangiocarcinogenesis in hamsters.

    Dechakhamphu, Somkid; Pinlaor, Somchai; Sitthithaworn, Paiboon; Bartsch, Helmut; Yongvanit, Puangrat

    2010-09-10

    Infection by Opisthorchis viverrini, a risk factor for cholangiocarcinoma (CCA) may act through chronic inflammation, oxidative stress and lipid peroxidation (LPO)-related damage and growth stimuli. 1,N6-etheno-2'-deoxyadenosine (epsilondA), and 3,N4-etheno-2'-deoxycytidine (epsilondC), markers for LPO-derived DNA damage were highly increased in white blood cell and urine of O. viverrini-infected Thai patients. In order to investigate tissue specificity etheno adducts were measured in a cholangiocarcinogenesis model, in O. viverrini-infected hamsters that had received N-nitrosodimethylamine (NDMA, 12.5 ppm in dw) for 2 months. epsilondA- and epsilondC-levels were analyzed in paraffin-embedded liver sections by a novel immunohistochemical method, from 21 up to 180 days post-O. viverrini-infection. In inflamed areas of the liver, etheno adducts were localized in the nuclei of inflammatory cells and in the epithelial lining of the bile duct. Semi-quantitative image analysis showed higher adduct levels in the liver of O. viverrini-infected hamsters, treated with or w/o NDMA when compared with untreated controls. Levels were found highest in the liver of O. viverrini-infected plus NDMA-treated hamsters. Adducts increased in an age-dependent manner from O. viverrini-infection until CCA development. Increased adduct formation paralleled histopathological changes in plasma alkaline phosphatase (ALP) activity, bile duct hyperplasia, dysplasia, precancerous lesions, and CCA appearance. Also elevated expression of alkyladenine DNA glycosylase (AAG), which excises 1,N6-ethenoadenine (epsilonA) was linked to higher adduct formation, suggesting imbalanced repair. Our results implicate accumulation of inflammation-related, promutagenic DNA damage in target tissue and possibly imbalanced repair in the onset of cholangiocarcinogenesis. PMID:20541562

  7. Benzene-derived N2-(4-hydroxyphenyl)-deoxyguanosine adduct: UvrABC incision and its conformation in DNA

    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.

  8. Comparison of five portable peak flow meters

    Glaucia Nency Takara

    2010-01-01

    Full Text Available OBJECTIVE: To compare the measurements of spirometric peak expiratory flow (PEF from five different PEF meters and to determine if their values are in agreement. Inaccurate equipment may result in incorrect diagnoses of asthma and inappropriate treatments. METHODS: Sixty-eight healthy, sedentary and insufficiently active subjects, aged from 19 to 40 years, performed PEF measurements using Air Zone®, Assess®, Galemed®, Personal Best® and Vitalograph® peak flow meters. The highest value recorded for each subject for each device was compared to the corresponding spirometric values using Friedman's test with Dunn's post-hoc (p<0.05, Spearman's correlation test and Bland-Altman's agreement test. RESULTS: The median and interquartile ranges for the spirometric values and the Air Zone®, Assess®, Galemed®, Personal Best® and Vitalograph® meters were 428 (263-688 L/min, 450 (350-800 L/min, 420 (310-720 L/min, 380 (300-735 L/min, 400 (310-685 L/min and 415 (335-610 L/min, respectively. Significant differences were found when the spirometric values were compared to those recorded by the Air Zone® (p<0.001 and Galemed ® (p<0.01 meters. There was no agreement between the spirometric values and the five PEF meters. CONCLUSIONS: The results suggest that the values recorded from Galemed® meters may underestimate the actual value, which could lead to unnecessary interventions, and that Air Zone® meters overestimate spirometric values, which could obfuscate the need for intervention. These findings must be taken into account when interpreting both devices' results in younger people. These differences should also be considered when directly comparing values from different types of PEF meters.

  9. Polio elimination in Nigeria: A review.

    Nasir, Usman Nakakana; Bandyopadhyay, Ananda Sankar; Montagnani, Francesca; Akite, Jacqueline Elaine; Mungu, Etaluka Blanche; Uche, Ifeanyi Valentine; Ismaila, Ahmed Mohammed

    2016-03-01

    Nigeria has made tremendous strides towards eliminating polio and has been free of wild polio virus (WPV) for more than a year as of August 2015. However, sustained focus towards getting rid of all types of poliovirus by improving population immunity and enhancing disease surveillance will be needed to ensure it sustains the polio-free status. We reviewed the pertinent literature including published and unpublished, official reports and working documents of the Global Polio Eradication Initiative (GPEI) partners as well as other concerned organizations. The literature were selected based on the following criteria: published in English Language, published after year 2000, relevant content and conformance to the theme of the review and these were sorted accordingly. The challenges facing the Polio Eradication Initiative (PEI) in Nigeria were found to fall into 3 broad categories viz failure to vaccinate, failure of the Oral Polio Vaccine (OPV) and epidemiology of the virus. Failure to vaccinate resulted from insecurity, heterogeneous political support, programmatic limitation in implementation of vaccination campaigns, poor performance of vaccination teams in persistently poor performing Local Government areas and sporadic vaccine refusals in Northern Nigeria. Sub optimal effectiveness of OPV in some settings as well as the rare occurrence of VDPVs associated with OPV type 2 in areas of low immunization coverage were also found to be key issues. Some of the innovations which helped to manage the threats to the PEI include a strong government accountability frame work, change from type 2 containing OPV to bi valent OPVs for supplementary immunization activities (SIA), enhancing environmental surveillance in key states (Sokoto, Kano and Borno) along with an overall improvement in SIA quality. There has been an improvement in coverage of routine immunization and vaccination campaigns, which has resulted in Nigeria being removed from the list of endemic countries

  10. On the Importance of Elimination Heuristics in Lazy Propagation

    Madsen, Anders Læsø; Butz, Cory J.

    2012-01-01

    elimination orders on-line. This paper considers the importance of elimination heuristics in LP when using Variable Elimination (VE) as the message and single marginal computation algorithm. It considers well-known cost measures for selecting the next variable to eliminate and a new cost measure. The...... empirical evaluation examines dierent heuristics as well as sequences of cost measures, and was conducted on real-world and randomly generated Bayesian networks. The results show that for most cases performance is robust relative to the cost measure used and in some cases the elimination heuristic can have...

  11. OPEN-LOOP FOG SIGNAL TESTING AND WAVELET ELIMINATING NOISE

    ZHUYun-zhao; WANGShun-ring; MIAOLing-juan; WANGBo

    2005-01-01

    An open-loop fiber optic gyro (FOG) testing system is designed. The noise characteristic of open-loop fiber optic gyro signals is analyzed. The wavelet eliminating noise method is discussed and compared with other methods, such as smoothing and low-pass filter methods. Results indicate that the wavelet eliminating noise method can satisfy the measuring demand of the FOG weak output signal with noise disturbing. The wavelet analysis method can efficiently eliminate the noise and reserve the information of the signal. The eliminating noise effect of using different wavelet base functions is compared. The effectiveness of multiresolution wavelet analyses of eliminating noise is proved by experimental results.

  12. A Method of Eliminating Information Disclosure in View Publishing

    LIU Guohua; GAO Shihong

    2006-01-01

    Although it is convenient to exchange data by publishing view, but it may disclose sensitive information. The problem of how to eliminate information disclosure becomes a core problem in the view publishing process. In order to eliminate information disclosure, deciding view security algorithm and eliminating information disclosure algorithm are proposed, and the validity of the algorithms are proved by experiment. The experimental results showing, deciding view security algorithm can decide the safety of a set of views under prior knowledge, and eliminating information disclosure algorithm can eliminate disclosure efficiently.

  13. Etheno-DNA adduct formation in rats gavaged with linoleic acid, oleic acid and coconut oil is organ- and gender specific

    Fang Qingming [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280 69120 Heidelberg (Germany); Nair, Jagadeesan [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280 69120 Heidelberg (Germany)], E-mail: j.nair@dkfz.de; Sun Xin [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280 69120 Heidelberg (Germany); Hadjiolov, Dimiter [National Oncological Centre, Sofia (Bulgaria); Bartsch, Helmut [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280 69120 Heidelberg (Germany)

    2007-11-01

    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 {omega}-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, N{sup 6}-ethenodeoxyadenosine ({epsilon}dA) and 3, N{sup 4}-ethenodeoxycytidine ({epsilon}dC) by immunoaffinity/{sup 32}P-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 {omega}-6 PUFA induced colon carcinogenesis.

  14. Eccentric and Isometric Hip Adduction Strength in Male Soccer Players With and Without Adductor-Related Groin Pain An Assessor-Blinded Comparison

    Thorborg, Kristian; Branci, Sonia; Nielsen, Peter Martin;

    2014-01-01

    .5 ± 2.5 years, and the mean age of the asymptomatic controls was 22.9 ± 2.4 years. Isometric hip strength (adduction, abduction, and flexion) and eccentric hip strength (adduction) were assessed with a handheld dynamometer using reliable test procedures and a blinded assessor. RESULTS: Eccentric hip...

  15. STABILITY OF HEMOGLOBIN AND ALBUMIN ADDUCTS OF BENZENE OXIDE AND 1,4-BENZOQUINONE AFTER ADMINISTRATION OF BENZENE TO F344 RATS

    The stability of cysteinyl adducts of benzene oxide (BO) and mono-S-substituted cysteinyl adducts of 1,4-benzoquinone (1,4-BQ) was investigated in both hemoglobin (Hb) and albumin (Alb) following administration of a single oral dose of 400 mg [U-14C/13C6]benzene/kg body weight ...

  16. Pulse radiolysis investigation of the reaction of the electronic adduct of bovine serum albumin with oxygen. Polychromatic kinetics of the reaction with adsorbed oxygen

    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

  17. DIFFERENCES IN DETECTION OF DNA ADDUCTS IN THE 32P-POSTLABELING ASSAY AFTER EITHER 1-BUTANOL EXTRACTION OR NUCLEASE P1 TREATMENT

    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...

  18. Acute and sub-acute effects of repetitive kicking on hip adduction torque in injury-free elite youth soccer players

    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...

  19. Fast repair of oxidizing OH radical adducts of dGMP, dAMP and DNA by hydroxycinnamic acid derivatives. A pulse radiolytic study

    Using a pulse radiolytic technique, it has been demonstrated that the interaction of oxidizing OH adducts of DNA with hydroxycinnamic acid derivatives proceeds via an electron transfer process with rate constant of (5-7) x 108dm3mol-1s-1. Besides, the rate for fast repair of OH adducts of dAMP and DNA (ssDNA and dsDNA) are slower than the corresponding rate for the rest OH adducts of DNA constituents, such as dGMP (2-3*109 dm1mol-1s-1). The slower rate for oxidizing OH adduct of dAMP and DNA has indicated that repair of oxidizing OH adduct of dAMP may be the rate determining process during the interaction of hydroxycinnamic acid derivatives with OH adduct of DNA containing the varieties of OH adducts of DNA components. On other hand, the yields for oxidizing OH radical adduct with dGMP and dAMP were determined to be 50% and 30% respectively

  20. Molar ratios of therapeutic water-soluble phenothiazine⋅water-insoluble phospholipid adducts reveal a Fibonacci correlation and a putative link for structure–activity relationships

    Keyzer, Hendrik; Fey, S. J.; Thornton, Barry;

    2015-01-01

    larger than that of the self-associated pure PTH. In summary, the reproducibility and similarity of the measurements using different PTH derivatives and PL suggests that similar adducts are formed in all the cases. We propose that the PTH$PL adduct has a “helical shape” showing Fibonacci properties...