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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

    Energy Technology Data Exchange (ETDEWEB)

    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. Effect of real-time biofeedback on peak knee adduction moment in patients with medial knee osteoarthritis: Is direct feedback effective?

    Science.gov (United States)

    Richards, Rosie E; van den Noort, Josien C; van der Esch, Martin; Booij, Marjolein J; Harlaar, Jaap

    2017-07-13

    Gait modifications can reduce the knee adduction moment, a representation of knee loading. Reduced loading may help to slow progression of medial knee osteoarthritis. We aimed to investigate the response of patients with medial knee osteoarthritis to direct feedback on the knee adduction moment as a method for modifying the gait pattern, before and after training with specific gait modifications. Forty patients with medial knee osteoarthritis underwent 3D gait analysis on an instrumented-treadmill, while receiving real-time feedback on the peak knee adduction moment. Patients were trained with three different modifications; toe-in, wider steps and medial thrust gait. The response to real-time feedback on the knee adduction moment was measured before and after training. To evaluate the short term retention effect, we measured the changes without feedback. We also evaluated the effects on the knee flexion moment and at the hip and ankle joints. With direct feedback on the knee adduction moment, patients were initially unable to reduce the knee adduction moment. After training with specific modifications, peak knee adduction moment was reduced by 14% in response to direct feedback. Without feedback a 9% reduction in peak knee adduction moment was maintained. Hip moments were not increased with modified gait, but small increases in ankle adduction moment and knee flexion moment were observed. Real-time biofeedback directly on the knee adduction moment is a promising option for encouraging gait modifications to reduce knee loading, however only when combined with specific instructions on how to modify the gait. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Elimination of noise peak for signal processing in Johnson noise thermometry development

    International Nuclear Information System (INIS)

    Hwang, I. G.; Moon, B. S.; Jeong, J. E.; Jeo, Y. H.; Kisner, Roger A.

    2003-01-01

    The internal and external noise is the most considering obstacle in development of Johnson Noise Thermometry system. This paper addresses an external noise elimination issue of the Johnson Noise Thermometry system which is underway of development in collaboration between KAERI and ORNL. Although internal random noise is canceled by Cross Power Spectral Density function, a continuous wave penetrating into the electronic circuit is eliminated by the difference of peaks between Johnson signal and external noise. The elimination logic using standard deviation of CPSD and energy leakage problem in discrete CPSD function are discussed in this paper

  4. A New Acquisition Algorithm with Elimination Side Peak for All BOC Signals

    Directory of Open Access Journals (Sweden)

    Fang Liu

    2015-01-01

    Full Text Available A new inhibition side peak acquisition (ISPA algorithm is proposed for binary offset carrier (BOC modulated signals, which will be utilized in global navigation satellite systems (GNSS. We eliminate all side peaks of the BOC correlation function (CF by structuring special sequences composed of PRN code and cycle rectangular sequences. The new algorithm can be applied to both generic sine- and cosine-phased BOC signals, as well as to all modulation orders. Theoretical and simulation results demonstrate that the new algorithm can completely eliminate the ambiguity threat in the acquisition process, and it can adapt to lower SNR. In addition, this algorithm is better than the traditional algorithms in acquisition performance and inhibition side peak ability.

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

    KAUST Repository

    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

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

    KAUST Repository

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Immediate and short-term effects of real-time knee adduction moment feedback on the peak and cumulative knee load during walking.

    Science.gov (United States)

    Jackson, Brennan; Gordon, Keith E; Chang, Alison H

    2018-01-01

    The peak external knee adduction moment (pKAM), KAM impulse, and peak knee flexion moment (pKFM) during gait are important loading variables in medial tibiofemoral osteoarthritis. We evaluated the effects of gait modification, using real-time pKAM visual feedback, on pKAM, KAM impulse, and pKFM; and whether participants could maintain the KAM-reducing gait after feedback removal. Eleven healthy individuals performed a series of walking trials on a split-belt instrumented treadmill under four conditions of Baseline, Feedback, No Feedback Early, and No Feedback Late. Guided by real-time feedback of pKAM, they modified their gait patterns to lower pKAM by 20%. Three-dimensional joint kinematics/kinetics during each walking condition were recorded by a 12-camera motion capture system and the instrumented treadmill. Change in each knee loading parameter from baseline across conditions was assessed using one-way repeated-measures analysis-of-variances. In the feedback limb, successful 20% reductions from baseline in pKAM and KAM impulse were achieved across all three conditions. There was a trend for concomitant pKFM increases, partially attenuating the beneficial effects of pKAM reduction. A carry-over effect of KAM reduction in the non-feedback limb was noted. The altered gait patterns were participant-specific and multi-modal; each participant reported a combination of two to three gait modification strategies used for pKAM reduction. Toe-in and medial foot contact were the most reported strategies. The findings support the real-time pKAM visual feedback as a tool for individualized gait modification to reduce knee load. Future studies to evaluate its effectiveness in persons with or at risk for medial knee osteoarthritis is warranted. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:397-404, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  9. Nontargeted Identification of Reactive Metabolite Protein Adducts.

    Science.gov (United States)

    Leeming, Michael G; Donald, William A; O'Hair, Richard A J

    2017-06-06

    Metabolic bioactivation of many different chemicals results in the formation of highly reactive compounds (chemically reactive metabolites, CRMs) that can lead to toxicity via binding to macromolecular targets (e.g., proteins or DNA). There is a need to develop robust, rapid, and nontargeted analytical techniques to determine the identity of the protein targets of CRMs and their sites of modification. Here, we introduce a nontargeted methodology capable of determining both the identity of a CRM formed from an administered compound as well as the protein targets modified by the reactive metabolite in a single experiment without prior information. Acetaminophen (N-acetyl-p-aminophenol, APAP) and 13 C 6 -APAP were incubated with rat liver microsomes, which are known to bioactivate APAP to the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). Global tryptic digestion followed by liquid chromatographic/mass spectrometric (LC/MS) analysis was used to locate "twin" ion peaks of peptides adducted by NAPQI and for shotgun proteomics via tandem mass spectrometry (MS/MS). By the development of blended data analytics software called Xenophile, the identity of the amino acid residue that was adducted can be established, which eliminates the need for specific parametrization of protein database search algorithms. This combination of experimental design and data analysis software allows the identity of a CRM, the protein target, and the amino acid residues that are modified to be rapidly established directly from experimental data. Xenophile is freely available from https://github.com/mgleeming/Xenophile .

  10. Effect of Nanoemitters on Suppressing the Formation of Metal Adduct Ions in Electrospray Ionization Mass Spectrometry.

    Science.gov (United States)

    Hu, Jun; Guan, Qi-Yuan; Wang, Jiang; Jiang, Xiao-Xiao; Wu, Zeng-Qiang; Xia, Xing-Hua; Xu, Jing-Juan; Chen, Hong-Yuan

    2017-02-07

    In the work, we showed that the use of nanoemitters (tip dimension metal adduction to peptide or protein ions as well as improve the matrix tolerance of electrospray ionization mass spectrometry (ESI-MS). The proton-enriched smaller initial droplets are supposed to have played a significant role in suppressing the formation of metal adduct ions in nanoemitters. The proton-enrichment effect in the nanoemitters is related to both the exclusion-enrichment effect (EEE) and the ion concentration polarization effect (ICP effect), which permit the molecular ions to be regulated to protonated ones. Smaller initial charged droplets generated from nanoemitters need less fission steps to release the gas-phase ions; thus, the enrichment effect of salt was not as significant as that of microemitters (tip dimension >1 μm), resulting in the disappearing of salt cluster peaks in high mass-to-charge (m/z) region. The use of nanoemitters demonstrates a novel method for tuning the distribution of the metal-adducted ions to be in a controlled manner. This method is also characterized by ease of use and high efficiency in eliminating the formation of adduct ions, and no pretreatment such as desalting is needed even in the presence of salt at millimole concentration.

  11. NITRO MUSK ADDUCTS OF RAINBOW TROUT ...

    Science.gov (United States)

    Rainbow trout and other fish species can serve as 'sentinel' species for the assessment of ecological status and the presence of certain environmental contaminants. As such they act as bioindicators of exposure. Here we present seminal data regarding dose-response and toxicokinetics of trout hemoglobin adduct formation from exposure to nitro musks that are frequently used as fragrance ingredients in formulations of personal care products. Hemoglobin adducts serve as biomarkers of exposure of the sentinel species as we have shown in previous studies of hemoglobin adducts formed in trout and environmental carp exposed to musk xylene (MX) and musk ketone (MK). Gas chromatography-electron capture negative ion chemical ionization-mass spectrometry (GC-NICI-MS) employing selected ion monitoring is used to measure 4-amino-MX (4-AMX), 2-amino-MX (2-AMX), and 2-amino-MK (2-AMK) released by alkaline hydrolysis from the sulfinamide adducts of hemoglobin. Dose-response and toxicokinetics were investigated using this sensitive method for analysis of these metabolites. In the dose-response investigation, the concentrations of 4-AMX and 2-2AMX are observed to pass through a maximum at 0.10 mg/g. In the case of 2-AMK, the adduct concentration is almost the same at dosages in the range of 0.030 to 0.10 mg/g. For toxicokinetics, the concentration of the metabolites in the Hb reaches a maximum in the 3-day sample after administration of MX or MK. Further elimination of the metabo

  12. DNA adducts as molecular dosimeters

    International Nuclear Information System (INIS)

    Lucier, G.W.

    1990-01-01

    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 32 P-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

  13. Isolevuglandin adducts in disease.

    Science.gov (United States)

    Salomon, Robert G; Bi, Wenzhao

    2015-06-20

    A diverse family of lipid-derived levulinaldehydes, isolevuglandins (isoLGs), is produced by rearrangement of endoperoxide intermediates generated through both cyclooxygenase (COX) and free radical-induced cyclooxygenation of polyunsaturated fatty acids and their phospholipid esters. The formation and reactions of isoLGs with other biomolecules has been linked to alcoholic liver disease, Alzheimer's disease, age-related macular degeneration, atherosclerosis, cardiac arythmias, cancer, end-stage renal disease, glaucoma, inflammation of allergies and infection, mitochondrial dysfunction, multiple sclerosis, and thrombosis. This review chronicles progress in understanding the chemistry of isoLGs, detecting their production in vivo and understanding their biological consequences. IsoLGs have never been isolated from biological sources, because they form adducts with primary amino groups of other biomolecules within seconds. Chemical synthesis enabled investigation of isoLG chemistry and detection of isoLG adducts present in vivo. The first peptide mapping and sequencing of an isoLG-modified protein present in human retina identified the modification of a specific lysyl residue of the sterol C27-hydroxylase Cyp27A1. This residue is preferentially modified by iso[4]LGE2 in vitro, causing loss of function. Adduction of less than one equivalent of isoLG can induce COX-associated oligomerization of the amyloid peptide Aβ1-42. Adduction of isoLGE2 to phosphatidylethanolamines causes gain of function, converting them into proinflammatory isoLGE2-PE agonists that foster monocyte adhesion to endothelial cells. Among the remaining questions on the biochemistry of isoLGs are the dependence of biological activity on isoLG isomer structure, the structures and mechanism of isoLG-derived protein-protein and DNA-protein cross-link formation, and its biological consequences.

  14. Regiochemically Controlled Synthesis of a β-4-β' [70]Fullerene Bis-Adduct.

    Science.gov (United States)

    Cerón, Maira R; Castro, Edison; Neti, Venkata S Pavan K; Dunk, Paul W; Echegoyen, Luis A

    2017-01-20

    A β-4-β' C 70 bis-adduct regioisomer and an uncommon mono-adduct β-malonate C 70 derivative were synthesized by using a Diels-Alder cycloaddition followed by an addition-elimination of bromo-ethylmalonate and a retro-Diels-Alder cycloaddition reaction. We also report the regioselective synthesis and spectroscopic characterization of C s -symmetric tris- and C 2v -symmetric tetra-adducts of C 70 , which are the precursors of the mono- and bis-adduct final products.

  15. Alcohol, Aldehydes, Adducts and Airways

    Directory of Open Access Journals (Sweden)

    Muna Sapkota

    2015-11-01

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

  16. Eliminating armaments

    International Nuclear Information System (INIS)

    Adams, R.

    1998-01-01

    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

  17. EMG evaluation of hip adduction exercises for soccer players

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Satoshi Yamaguchi

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

  19. Elimination of chromatographic and mass spectrometric problems in GC-MS analysis of Lavender essential oil by multivariate curve resolution techniques: Improving the peak purity assessment by variable size moving window-evolving factor analysis.

    Science.gov (United States)

    Jalali-Heravi, Mehdi; Moazeni-Pourasil, Roudabeh Sadat; Sereshti, Hassan

    2015-03-01

    In analysis of complex natural matrices by gas chromatography-mass spectrometry (GC-MS), many disturbing factors such as baseline drift, spectral background, homoscedastic and heteroscedastic noise, peak shape deformation (non-Gaussian peaks), low S/N ratio and co-elution (overlapped and/or embedded peaks) lead the researchers to handle them to serve time, money and experimental efforts. This study aimed to improve the GC-MS analysis of complex natural matrices utilizing multivariate curve resolution (MCR) methods. In addition, to assess the peak purity of the two-dimensional data, a method called variable size moving window-evolving factor analysis (VSMW-EFA) is introduced and examined. The proposed methodology was applied to the GC-MS analysis of Iranian Lavender essential oil, which resulted in extending the number of identified constituents from 56 to 143 components. It was found that the most abundant constituents of the Iranian Lavender essential oil are α-pinene (16.51%), camphor (10.20%), 1,8-cineole (9.50%), bornyl acetate (8.11%) and camphene (6.50%). This indicates that the Iranian type Lavender contains a relatively high percentage of α-pinene. Comparison of different types of Lavender essential oils showed the composition similarity between Iranian and Italian (Sardinia Island) Lavenders. Published by Elsevier B.V.

  20. Twin Peaks

    Science.gov (United States)

    1997-01-01

    The two hills in the distance, approximately one to two kilometers away, have been dubbed the 'Twin Peaks' and are of great interest to Pathfinder scientists as objects of future study. The white areas on the left hill, called the 'Ski Run' by scientists, may have been formed by hydrologic processes.The image was taken by the Imager for Mars Pathfinder (IMP) after its deployment on Sol 3. Mars Pathfinder was developed and managed by the Jet Propulsion Laboratory (JPL) for the National Aeronautics and Space Administration. The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

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

    DEFF Research Database (Denmark)

    Olesen, Solveig Gaarn; Hammerum, Steen

    2009-01-01

    changes and the redshift favor the Z OH group, matching the results of NBO and AIM calculations. This reflects that the thermochemistry of adduct formation is not a good measure of the hydrogen bond strength in charged adducts, and that the ionic interactions in the E and Z adducts of protonated...

  2. Acetaminophen protein adducts: a review.

    Science.gov (United States)

    Bond, G Randall

    2009-01-01

    Significant controversy surrounds the clinical and legal implications of 3-para cysteinyl acetaminophen, the protein degradation product of acetaminophen protein adducts. Versions of this test have been used for several years in animal research to help understand acetaminophen toxicity. As human research papers have appeared, the allegation has been made that the presence of 3-para cysteinyl acetaminophen in a patient with hepatic injury proves causal association of acetaminophen with the injury. It has also been suggested that quantitative adduct assays can guide the management of acute overdose or repeated supra-therapeutic use of acetaminophen by determining the need for initiating therapy and the timing of the end of therapy. The purpose of this review is to discuss the nature of this molecule and the detection assay, the animal research linking it with injury, and to evaluate the human research--specifically the evidence regarding causality and clinical utility. At the current time there is inadequate evidence for the test alone to prove causal association between acetaminophen and hepatic injury. Also, since quantitative 3-para cysteinyl acetaminophen assays parallel other markers of liver injury, it is not clear that assays alone will guide therapy unless quantitative assay markers can be shown to precede other markers (in elevation or decline) or provide more specificity than the Rumack-Matthew risk categorization nomogram. These advantages have not been demonstrated.

  3. The association between submaximal quadriceps force steadiness and the knee adduction moment during walking in patients with knee osteoarthritis

    DEFF Research Database (Denmark)

    Sørensen, Tina Juul; Langberg, Henning; Aaboe, Jens

    2011-01-01

    , and knee pain was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscale and a visual analog scale. RESULTS: Regression analyses showed that quadriceps force steadiness did not predict the peak knee adduction moment (adjusted R2 = 0.05, P = .41). Inclusion of covariates did......STUDY DESIGN: Cross-sectional study. OBJECTIVES: To investigate the relationship between quadriceps force steadiness and knee adduction moment during walking in patients with knee osteoarthritis (OA). BACKGROUND: Studies have shown that quadriceps force steadiness is impaired in patients with knee...... OA. Furthermore, patients with knee OA, compared to healthy controls, have also demonstrated a significantly higher external knee adduction moment during walking. However, no studies have examined the relationship between quadriceps force steadiness and the peak knee adduction moment during walking...

  4. Monitoring in vivo metabolism and elimination of the endogenous DNA adduct, M1dG (3-(2-deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one), by accelerator mass spectrometry

    Science.gov (United States)

    Knutson, Charles G.; Skipper, Paul L.; Liberman, Rosa G.; Tannenbaum, Steven R.; Marnett, Lawrence J.

    2011-01-01

    Our laboratory is investigating the in vitro and in vivo metabolic processing of endogenously formed DNA adducts as a means of evaluating candidate urinary biomarkers. In particular, we have focused our studies on the metabolism and disposition of the peroxidation-derived pyrimidopurinone deoxyguanosine (dG) adduct, 3-(2-deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) and its principal metabolite, 6-oxo-M1dG. We now report the metabolic processing of M1dG at concentrations 4 to 8 orders of magnitude lower in concentration than previously analyzed, by the use of accelerator mass spectrometry analysis. Administration of 2.0 nCi/kg [14C]M1dG resulted in 49% of the 14C recovered in urine whereas 51% was recovered in feces. In urine samples, approximately 40% of the 14C corresponded to the metabolite, 6-oxo-M1dG. Following iv administration of 0.5 and 54 pCi/kg [14C]M1dG, approximately 25% of the urinary recovery corresponded to the metabolite, 6-oxo-M1dG. Thus, upon administration of trace amounts of M1dG, a significant percentage of 6-oxo-M1dG was produced suggesting that 6-oxo-M1dG maybe a useful urinary marker of exposure to endogenous oxidative damage. PMID:18461974

  5. Monitoring in vivo metabolism and elimination of the endogenous DNA adduct, M1dG {3-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one}, by accelerator mass spectrometry.

    Science.gov (United States)

    Knutson, Charles G; Skipper, Paul L; Liberman, Rosa G; Tannenbaum, Steven R; Marnett, Lawrence J

    2008-06-01

    Our laboratory is investigating the in vitro and in vivo metabolic processing of endogenously formed DNA adducts as a means of evaluating candidate urinary biomarkers. In particular, we have focused our studies on the metabolism and disposition of the peroxidation-derived pyrimidopurinone deoxyguanosine (dG) adduct, 3-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-R]purin-10(3H)-one (M1dG), and its principal metabolite, 6-oxo-M1dG. We now report the metabolic processing of M1dG at concentrations 4-8 orders of magnitude lower in concentration than previously analyzed, by the use of accelerator mass spectrometry analysis. Administration of 2.0 nCi/kg [14C]M1dG resulted in 49% of the 14C recovered in urine, whereas 51% was recovered in feces. In urine samples, approximately 40% of the 14C corresponded to the metabolite, 6-oxo-M1dG. Following iv administration of 0.5 and 54 pCi/kg [14C]M1dG, approximately 25% of the urinary recovery corresponded to the metabolite, 6-oxo-M1dG. Thus, upon administration of trace amounts of M1dG, a significant percentage of 6-oxo-M1dG was produced, suggesting that 6-oxo-M1dG maybe a useful urinary marker of exposure to endogenous oxidative damage.

  6. Hemoglobin adducts in workers exposed to 1,6-hexamethylene diisocyanate

    Science.gov (United States)

    Flack, Sheila L.; Fent, Kenneth W.; Gaines, Linda G. T.; Thomasen, Jennifer M.; Whittaker, Stephen G.; Ball, Louise M.; Nylander-French, Leena A.

    2014-01-01

    We investigated the utility of 1,6-hexamethylene diamine (HDA) hemoglobin adducts as biomarkers of exposure to 1,6-hexamethylene diisocyanate (HDI) monomer. Blood samples from 15 spray painters applying HDI-containing paint were analyzed for hemoglobin HDA (HDA-Hb) and N-acetyl-1,6-hexamethylene diamine (monoacetyl-HDA-Hb) by GC-MS. HDA-Hb was detected in the majority of workers (≤1.2–37 ng/g Hb), whereas monoacetyl-HDA-Hb was detected in one worker (0.06 ng/g Hb). The stronger, positive association between HDA-Hb and cumulative HDI exposure (r2 = 0.3, p < 0.06) than same day exposure (p ≥ 0.13) indicates long-term elimination kinetics for HDA-Hb adducts. This association demonstrates the suitability of HDA-Hb adducts for further validation as a biomarker of HDI exposure. PMID:21506697

  7. Imidazolidinone adducts of peptides and hemoglobin

    International Nuclear Information System (INIS)

    San George, R.C.; Hoberman, H.D.

    1986-01-01

    Acetaldehyde reacts selectively with the terminal amino groups of the α and β chains of hemoglobin to form stable adducts, the structures of which, based on 13 C NMR studies, are proposed to be diastereomeric 2-methyl imidazolidin-4-ones. In this scheme, acetaldelhyde forms a reversible Schiff base with the α-amino groups of the polypeptide chains which cyclize with the amide nitrogen of the first peptide bond to form the stable imidazolidinone adducts. In support of this mechanism, the authors found that in following the reaction of the peptide val-gly-gly with [1,2- 13 C] acetaldehyde, 13 C NMR resonances attributed to a Schiff base (δ = 170 ppm) were observed which slowly disappeared prior to appearance of resonances from a pair of stable adducts (δ = 70 and 71 ppm) believed to be the diastereomeric imidazolidinones. Schiff base formation appeared to limit the overall rate. Tetraglycine reacted in a similar manner but with a resonance from a single stable adduct observed representing the enantiomeric imidazolidinone adducts of this peptide. Peptides with proline in position 2 should be incapable of forming imidazolidinones, and the authors found that ala-pro-gly did in fact fail to form a stable adduct with acetaldehyde. The 2-methyl imidazolidin-4-one adducts of hemoglobin may be useful in determining the contribution of the amino terminal groups to the structure and functional properties of hemoglobins

  8. Hydrogen abstraction reactions by amide electron adducts

    International Nuclear Information System (INIS)

    Sevilla, M.D.; Sevilla, C.L.; Swarts, S.

    1982-01-01

    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 - )ND 2 . 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)

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

    International Nuclear Information System (INIS)

    Cheng Yan; Wang Haifang; Sun Hongfang; Li Hongli

    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 b 5 (CYb 5 ) 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 CYb 5 , 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)

  10. o-Toluidine blood protein adducts: HPLC analysis with fluorescence detection after a single dose in the adult male rat

    International Nuclear Information System (INIS)

    Cheever, K.L.; DeBord, G.D.; Swearengin, T.F.

    1991-01-01

    Hemoglobin (Hb) and albumin (Alb) adducts of the suspect human carcinogen o-toluidine (OT) were quantified in blood samples collected from rats after a single i.p. injection. Mild alkaline hydrolysis of Hb-adducted [ 14 C]OT followed by extraction with ethylacetate resulted in recovery of 66% of the bound radioactivity. HPLC analysis revealed a single radiolabeled peak which was identified as OT by GC-MS. In subsequent experiments the Hb and Alb adduct levels were determined by HPLC analysis of this split product using fluorescence detection. 4-Ethylaniline was used as internal standard. The detection limit for OT was approximately 450 pg/injection of 5 pmol. mg Hb. Mean adduct levels for Hb increased rapidly over the first 4 hr with the highest (ng/mg Hb ± SD) 3.7 ± 0.5 detected 24 hr after OT (50 mg/kg body wt). In contrast, adduct levels for pooled Alb samples increased from 0.7 ng/mg Alb at 2 hr to 2.5 ng/mg Alb at 4 hr, but were not detectable 24 hr after OT (50 mg/kg body wt). In contrast, adduct levels for pooled Alb samples increased from 0.7 ng/mg Alb at 2 hr to 2.5 ng/mg Alb at 4 hr, but were not detectable 24 hr after dosing. Hb adducts showed a linear relationship for OT doses of 10, 20, 40, 50, and 100 mg/kg body wt. The Hb adduct t 1/2 (11.2 days) was determined after a single 100 mg/kg OT dose. Hb adduct levels were quantifiable (1.3 ± 0.2 ng/mg Hb) by HPLC/fluorescence 28 days after 100 mg/kg OT

  11. Repair of furocoumarin adducts in mammalian cells

    International Nuclear Information System (INIS)

    Zolan, M.E.; Smith, C.A.; Hanawalt, P.C.

    1984-01-01

    DNA repair was studied in cultured mammalian cells treated with the furocoumarins 8-methoxypsoralen (8-MOP), aminomethyl trioxsalen, or angelicin and irradiated with near UV light. The amount of DNA cross-linked by 8-MOP in normal human cells decreased by about one-half in 24 hours after treatment; no decrease was observed in xeroderma pigmentosum cells, group A. At present, it is not known to what extent this decrease represents complete repair events at the sites of cross-links. Furocoumarin adducts elicited excision repair in normal human and monkey cells but not in xeroderma pigmentosum group A cells. This excision repair resembled in several aspects that elicited by pyrimidine dimers, formed in DNA by irradiation with 254-nm UV light; however, it appeared that for at least 8-MOP and aminomethyl trioxsalen, removal of adducts was not as efficient as was the removal of pyrimidine dimers. A comparison was also made of repair in the 172-base-pair repetitive alpha-DNA component of monkey cells to repair in the bulk of the genome. Although repair elicited by pyrimidine dimers in alpha-DNA was the same as in the bulk DNA, that following treatment of cells with either aminomethyl trioxsalen or angelicin and near UV was markedly deficient in alpha-DNA. This deficiency reflected the removal of fewer adducts from alpha-DNA after the same initial adduct frequencies. These results could mean that each furocoumarin may produce several structurally distinct adducts to DNA in cells and that the capacity of cellular repair systems to remove these various adducts may vary greatly

  12. Formation of a Hydroxymethylfurfural-Cysteine Adduct and Its Absorption and Cytotoxicity in Caco-2 Cells.

    Science.gov (United States)

    Zhao, Qianzhu; Zou, Yueyu; Huang, Caihuan; Lan, Ping; Zheng, Jie; Ou, Shiyi

    2017-11-15

    Adducts of 5-hydroxymethylfurfural (HMF)-amino acids are formed during food processing and digestion; the elimination capacity of in vitro intestinal digests of biscuits, instant noodles, and potato crisps for HMF is 652, 727, and 540 μg/g, respectively. However, the safety of these adducts is unknown. In this study, an HMF-cysteine adduct named 1-dicysteinethioacetal-5-hydroxymehtylfurfural (DCH), which was found to be produced in the gastrointestinal tract after HMF intake, was prepared to test its effect toward Caco-2 cells. Compared with HMF, the adduct displayed lower cytotoxicity against Caco-2 cells with an IC 50 value of 31.26 mM versus 14.95 mM (HMF). The DCH did not induce cell apoptosis, whereas HMF significantly increased the apoptosis rate after incubation at concentrations of 16, 32, and 48 mM for 72 h. DCH showed an absorption rate considerably lower than that of HMF by Caco-2 cells. Lower absorption of DCH may result in lower toxicity compared with HMF against Caco-2 cells. Intracellular transformation of DCH has been observed.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    significant amount within 24 h incubation. The accumulation and cytotoxicity of HSA-Pt was compared to 10 µmol L¿¹ cisplatin for which a larger accumulation and cytotoxicity were observed in EATC compared to Lettré. The experiment was performed with cell medium exchange every fourth hour as HSA......-Pt and cisplatin were not stable in RPMI-1640 with 10% serum. The stability was determined using size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and after 4 h new platinum peaks were observed. These findings indicate that before conducting cell experiments, the stability......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...

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

    DEFF Research Database (Denmark)

    Thorborg, Kristian; Serner, Andreas; Petersen, Jesper

    2011-01-01

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

  15. Detection of human butyrylcholinesterase-nerve gas adducts by liquid chromatography-mass spectrometric analysis after in gel chymotryptic digestion.

    Science.gov (United States)

    Tsuge, Kouichiro; Seto, Yasuo

    2006-06-21

    To verify the exposure to nerve gas, a method for detecting human butyrylcholinesterase (BuChE)-nerve gas adduct was developed using LC-electrospray mass spectrometry (ESI-MS). Purified human serum BuChE was incubated with sarin, soman or VX, and the adduct was purified by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and digested in gel by treatment with chymotrypsin. The resulting peptide mixture was subjected to LC-ESI-MS. From the chymotryptic digest of untreated human BuChE, one peak corresponding to the peptide fragment containing the active center serine residue was detected on the extracted ion chromatogram at m/z 948.5, and the sequence was ascertained to be "GESAGAASVSL" by MS/MS analysis. From the chymotryptic digest of the human BuChE-sarin adduct, a singly charged peptide peak was detected on the extracted ion chromatogram at m/z 1,069.5, and the sequence was ascertained to be "GEXAGAASVSL" by MS/MS analysis (X denotes isopropylmethylphosphonylated serine). The difference in molecular weight (120.0 Da) between the active center peptide fragments corresponding to the untreated BuChE and BuChE-sarin adduct was assumed to be derived from the addition of an isopropyl methylphosphonyl moiety to the serine residue. The formation of human BuChE adducts with soman, VX and an aged soman adduct was confirmed by detecting the respective active center peptide fragments using LC-ESI-MS. To apply the established method to an actual biological sample, human serum was incubated with VX, and the adduct was purified by procainamide affinity chromatography followed by SDS-PAGE. After chymotryptic in gel digestion, the ethylphosphonylated active center peptide fragment could be detected, and the structure of the residue was ascertained by LC-ESI-MS analysis.

  16. Lewis acid adducts of [PCl2N]3.

    Science.gov (United States)

    Heston, Amy J; Panzner, Matthew J; Youngs, Wiley J; Tessier, Claire A

    2005-09-19

    Reaction of aluminum trichloride or gallium trichloride with the extremely weak base hexachlorotriphosphazene gives adducts in which the group 13 element is bound to a phosphazene nitrogen atom. In solution, the adducts exhibit fluxional behavior. The phosphazene ring of the adducts is distorted into a slight chair conformation.

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

    DEFF Research Database (Denmark)

    Thorborg, Kristian; Serner, Andreas; Petersen, Jesper

    2011-01-01

    An ipsilateral hip adduction/abduction strength ratio of more than 90%, and hip adduction strength equal to that of the contralateral side have been suggested to clinically represent adequate strength recovery of hip adduction strength in athletes after groin injury. However, to what extent side...

  18. 129I Moessbauer spectroscopic study of metallocene-iodine adducts

    International Nuclear Information System (INIS)

    Nakashima, Satoru; Sakai, Hiroshi; Watanabe, Masanobu; Maeda, Yutaka

    1994-01-01

    A 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.)

  19. DNA Adducts aand Human Atherosclerotis Lesions

    Czech Academy of Sciences Publication Activity Database

    Strejc, Přemysl; Boubelík, O.; Stávková, Zdena; Chvátalová, Irena; Šrám, Radim

    2001-01-01

    Roč. 42, - (2001), s. 662 ISSN 0008-5472. [Annual Meeting of Proceedings /92./. 24.03.2001-28.03.2001, New Orleans] R&D Projects: GA MZd NM10 Keywords : DNA adducts * LDL cholesterol Subject RIV: DN - Health Impact of the Environment Quality

  20. New adducts of Lapachol with primary amines

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

  1. Low-dose DNA adduct dosimetry by accelerator mass spectrometry (AMS)

    International Nuclear Information System (INIS)

    Turteltaub, K.W.; Felton, J.S.; Vogel, J.S.; Gledhill, B.L.; Davis, J.C.; Snyderwine, E.G.; Thorgeirsson, S.S.; Adamson, R.H.

    1991-01-01

    DNA adduction was measured following exposure to low doses of [2- 14 C]-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) [2- 14 C]-2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and [U- 14 C]-2,3,7,8-tetrachlorodibenzo-p-dioxin by AMS, a technique used in the earth sciences but not previously in toxicological research. The ability to measure low concentrations of rare isotopes suggested that biomedical research was a potentially powerful application for this technology. Sensitivity of the method was found to be one adduct per 10 11 nucleotides. No DNA adduct formation could be detected in TCDD treated rodents. DNA adducts in cynomolgus monkey lymphocytes following exposure to 500 μg/kg IQ peaked between 6 and 18 hrs following exposure. Sensitivity was limited mainly by the abundance of 14 C in contemporary carbon. Hosts depleted in radiocarbon are being developed, potentially increasing sensitivity another 3 orders of magnitude. These results demonstrate the high sensitivity of AMS for tracing molecules following administration of low levels of isotopically-labeled xenobiotics. In addition to 14 C measurement, AMS offers potential to conduct studies with other isotopes, particularly 3 H and 41 Ca

  2. Peak flow meter (image)

    Science.gov (United States)

    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 ...

  3. Acetaldehyde Adducts in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Mashiko Setshedi

    2010-01-01

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

  4. Individuals with varus thrust do not increase knee adduction when running with body borne load.

    Science.gov (United States)

    Brown, Tyler N; Kaplan, Jonathan T; Cameron, Sarah E; Seymore, Kayla D; Ramsay, John W

    2018-03-01

    Osteoarthritis (OA) is a common occupational hazard for service members. This study quantified how body borne load impacts knee biomechanics for participants who do and do not present varus thrust (range of knee adduction motion exhibited from heel strike to mid-stance (0-51%)) during over-ground running. Eighteen (9 varus thrust and 9 control) military personnel had knee biomechanics recorded when running with three load conditions (light, ∼6 kg, medium, 15% BW, and heavy, 30% BW). Subject-based means for knee biomechanics were calculated and submitted to a RM ANOVA to test the main effects and possible interactions between load and varus thrust group. The varus thrust group exhibited greater varus thrust (p = .001) and peak stance (PS, 0-100%) knee adduction (p = .009) posture compared to the control group with the light load, but not for the medium (p = .741 and p = .825) or heavy loads (p = .142 and p = .429). With the heavy load, varus thrust group reduced varus thrust (p = .023), whereas, the control group increased varus thrust (p = .037) compared to the light load, and increased PS knee adduction moment compared to light (p = .006) and medium loads (p = .031). The varus thrust group, however, exhibited no significant difference in knee adduction moment between any load (p = .174). With the addition of body borne load, varus thrust participants exhibited a significant reduction in knee biomechanics related to OA; whereas, control participants adopted knee biomechanics, including greater varus thrust and knee adduction moment, related to the development of OA. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. USCIS Backlog Elimination

    Data.gov (United States)

    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....

  6. Peak Experience Project

    Science.gov (United States)

    Scott, Daniel G.; Evans, Jessica

    2010-01-01

    This paper emerges from the continued analysis of data collected in a series of international studies concerning Childhood Peak Experiences (CPEs) based on developments in understanding peak experiences in Maslow's hierarchy of needs initiated by Dr Edward Hoffman. Bridging from the series of studies, Canadian researchers explore collected…

  7. EMG evaluation of hip adduction exercises for soccer players: implications for exercise selection in prevention and treatment of groin injuries.

    Science.gov (United States)

    Serner, Andreas; Jakobsen, Markus Due; Andersen, Lars Louis; Hölmich, Per; Sundstrup, Emil; Thorborg, Kristian

    2014-07-01

    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. 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. 40 healthy male elite soccer players, training >5 h a week, participated in the study. Muscle activity using surface electromyography (sEMG) was measured bilaterally for the adductor longus during eight hip adduction strengthening exercises and peak EMG was normalised (nEMG) using an isometric maximal voluntary contraction (MVC) as reference. Furthermore, muscle activation of the gluteus medius, rectus abdominis and the external abdominal obliques was analysed during the exercises. There were large differences in peak nEMG of the adductor longus between the exercises, with values ranging from 14% to 108% nEMG (pinjuries. The Copenhagen Adduction and the hip adduction with an elastic band are dynamic high-intensity exercises, which can easily be performed at any training facility and could therefore be relevant to include in future prevention and treatment programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Overview on extraction kinetics of metal adducts

    International Nuclear Information System (INIS)

    Aly, H.F.; Daoud, J.A.

    1995-01-01

    A overview of extraction kinetics solvent extraction of metal adducts is given. A kinetic regime, diffusional regime, and mixed diffusional-kinetic regime are analysed. The practical applications of kinetics of solvent extraction processes in connection with technical processes and counter-current modelling is discussed. Kinetic studies are essential for the development of new processes and the knowledge of factors governing the mass transfer and mechanism of extraction of metal ions is of major importance in the design, operation, control and optimization of reactors in chemical industry. 23 refs

  9. Peak power ratio generator

    Science.gov (United States)

    Moyer, R.D.

    A peak power ratio generator is described for measuring, in combination with a conventional power meter, the peak power level of extremely narrow pulses in the gigahertz radio frequency bands. The present invention in a preferred embodiment utilizes a tunnel diode and a back diode combination in a detector circuit as the only high speed elements. The high speed tunnel diode provides a bistable signal and serves as a memory device of the input pulses for the remaining, slower components. A hybrid digital and analog loop maintains the peak power level of a reference channel at a known amount. Thus, by measuring the average power levels of the reference signal and the source signal, the peak power level of the source signal can be determined.

  10. Peak Oil, Peak Coal and Climate Change

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Møller, Charlotte; Tastesen, Hanne Sørup; Gammelgaard, Bente; Lambert, Ian Henry; Stürup, Stefan

    2010-12-01

    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 significant amount within 24 h incubation. The accumulation and cytotoxicity of HSA-Pt was compared to 10 μmol L⁻¹ cisplatin for which a larger accumulation and cytotoxicity were observed in EATC compared to Lettré. The experiment was performed with cell medium exchange every fourth hour as HSA-Pt and cisplatin were not stable in RPMI-1640 with 10% serum. The stability was determined using size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and after 4 h new platinum peaks were observed. These findings indicate that before conducting cell experiments, the stability of the compound in the cell medium should be investigated especially when long exposure times are applied. Furthermore, HSA-Pt was found to be stable in Hanks Balanced Saline Solution (HBSS) and in Phosphate Buffered Saline (PBS) at pH 5.3, 6.1 and 7.4. Thus, the shift in pH when HSA-cisplatin passes from blood (pH 7.4) to tumor tissue (pH 5-6) is not capable of releasing cisplatin from HSA.

  12. Adduct Formation in ESI/MS by Mobile Phase Additives.

    Science.gov (United States)

    Kruve, Anneli; Kaupmees, Karl

    2017-05-01

    Adduct formation is a common ionization method in electrospray ionization mass spectrometry (ESI/MS). However, this process is poorly understood and complicated to control. We demonstrate possibilities to control adduct formation via mobile phase additives in ESI positive mode for 17 oxygen and nitrogen bases. Mobile phase additives were found to be a very effective measure for manipulating the formation efficiencies of adducts. An appropriate choice of additive may increase sensitivity by up to three orders of magnitude. In general, sodium adduct [M + Na] + and protonated molecule [M + H] + formation efficiencies were found to be in good correlation; however, the former were significantly more influenced by mobile phase properties. Although the highest formation efficiencies for both species were observed in water/acetonitrile mixtures not containing additives, the repeatability of the formation efficiencies was found to be improved by additives. It is concluded that mobile phase additives are powerful, yet not limiting factors, for altering adduct formation. Graphical Abstract ᅟ.

  13. Peak regulation right

    International Nuclear Information System (INIS)

    Gao, Z. |; Ren, Z.; Li, Z.; Zhu, R.

    2005-01-01

    A peak regulation right concept and corresponding transaction mechanism for an electricity market was presented. The market was based on a power pool and independent system operator (ISO) model. Peak regulation right (PRR) was defined as a downward regulation capacity purchase option which allowed PRR owners to buy certain quantities of peak regulation capacity (PRC) at a specific price during a specified period from suppliers. The PRR owner also had the right to decide whether or not they would buy PRC from suppliers. It was the power pool's responsibility to provide competitive and fair peak regulation trading markets to participants. The introduction of PRR allowed for unit capacity regulation. The PRR and PRC were rated by the supplier, and transactions proceeded through a bidding process. PRR suppliers obtained profits by selling PRR and PRC, and obtained downward regulation fees regardless of whether purchases are made. It was concluded that the peak regulation mechanism reduced the total cost of the generating system and increased the social surplus. 6 refs., 1 tab., 3 figs

  14. Including the Copenhagen Adduction Exercise in the FIFA 11+ Provides Missing Eccentric Hip Adduction Strength Effect in Male Soccer Players

    DEFF Research Database (Denmark)

    Harøy, Joar; Thorborg, Kristian; Serner, Andreas

    2017-01-01

    BACKGROUND: The FIFA 11+ was developed as a complete warm-up program to prevent injuries in soccer players. Although reduced hip adduction strength is associated with groin injuries, none of the exercises included in the FIFA 11+ seem to specifically target hip adduction strength. PURPOSE......: To investigate the effect on eccentric hip adduction strength of the FIFA 11+ warm-up program with or without the Copenhagen adduction exercise. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: We recruited 45 eligible players from 2 U19 elite male soccer teams. Players were randomized...... into 2 groups; 1 group carried out the standard FIFA 11+ program, while the other carried out the FIFA 11+ but replaced the Nordic hamstring exercise with the Copenhagen adduction exercise. Both groups performed the intervention 3 times weekly for 8 weeks. Players completed eccentric strength and sprint...

  15. Biocatalytic Reductions of Baylis - Hillman Adducts

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Peak-interviewet

    DEFF Research Database (Denmark)

    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...

  17. Automated asteroseismic peak detections

    Science.gov (United States)

    García Saravia Ortiz de Montellano, Andrés; Hekker, S.; Themeßl, N.

    2018-05-01

    Space observatories such as Kepler have provided data that can potentially revolutionize our understanding of stars. Through detailed asteroseismic analyses we are capable of determining fundamental stellar parameters and reveal the stellar internal structure with unprecedented accuracy. However, such detailed analyses, known as peak bagging, have so far been obtained for only a small percentage of the observed stars while most of the scientific potential of the available data remains unexplored. One of the major challenges in peak bagging is identifying how many solar-like oscillation modes are visible in a power density spectrum. Identification of oscillation modes is usually done by visual inspection that is time-consuming and has a degree of subjectivity. Here, we present a peak-detection algorithm especially suited for the detection of solar-like oscillations. It reliably characterizes the solar-like oscillations in a power density spectrum and estimates their parameters without human intervention. Furthermore, we provide a metric to characterize the false positive and false negative rates to provide further information about the reliability of a detected oscillation mode or the significance of a lack of detected oscillation modes. The algorithm presented here opens the possibility for detailed and automated peak bagging of the thousands of solar-like oscillators observed by Kepler.

  18. Effects of Lateral Heel Wedges and Lateral Forefoot Wedge on the Knee Adduction Moment in Healthy Male Students

    Directory of Open Access Journals (Sweden)

    Fatemeh Shamsi

    2012-01-01

    Full Text Available Objective: Lateral wedged insoles have been designed to decrease the force applied on the medial knee compartment. The aim of this study was to assess the effects of laterally wedged insoles regarding to the placement of the wedge under the sole (under the heel or under the forefoot on the knee adduction moment and the ground reaction forces. Material & Methods: In this pretest-posttest study, three-dimensional gait analysis was performed on 20 healthy men between 18-30 years old. Knee adduction moment and ground reaction forces were compared among following three types of insoles: a flat insole, a 6˚ laterally inclined heel wedged insole and a 6˚ laterally- inclined forefoot wedged insole. Results: there was no difference between three conditions (flat insole (9.72±1.501, lateral heel wedge (9.866±2.141 and lateral forefoot wedge (9.952±1.986 in peak knee adduction moment (P>0.05. Ground reaction forces and spatiotemporal parameters of gait were not affected by any types of these insoles (P>0.05. Conclusion: Based on the current finding, placement of the lateral wedge under the sole, that is, under the heel or under the forefoot has no effect on the efficacy of these insoles on the adduction moment of the knee and ground reaction forces.

  19. Mutagenicity of acrolein and acrolein-induced DNA adducts.

    Science.gov (United States)

    Liu, Xing-yu; Zhu, Mao-xiang; Xie, Jian-ping

    2010-01-01

    Acrolein mutagenicity relies on DNA adduct formation. Reaction of acrolein with deoxyguanosine generates alpha-hydroxy-1, N(2)-propano-2'-deoxyguanosine (alpha-HOPdG) and gamma-hydroxy-1, N(2)-propano-2'-deoxyguanosine (gamma-HOPdG) adducts. These two DNA adducts behave differently in mutagenicity. gamma-HOPdG is the major DNA adduct and it can lead to interstrand DNA-DNA and DNA-peptide/protein cross-links, which may induce strong mutagenicity; however, gamma-HOPdG can be repaired by some DNA polymerases complex and lessen its mutagenic effects. alpha-HOPdG is formed much less than gamma-HOPdG, but difficult to be repaired, which contributes to accumulation in vivo. Results of acrolein mutagenicity studies haven't been confirmed, which is mainly due to the conflicting mutagenicity data of the major acrolein adduct (gamma-HOPdG). The minor alpha-HOPdG is mutagenic in both in vitro and in vivo test systems. The role of alpha-HOPdG in acrolein mutagenicity needs further investigation. The inconsistent result of acrolein mutagenicity can be attributed, at least partially, to a variety of acrolein-DNA adducts formation and their repair in diverse detection systems. Recent results of detection of acrolein-DNA adduct in human lung tissues and analysis of P53 mutation spectra in acrolein-treated cells may shed some light on mechanisms of acrolein mutagenicity. These aspects are covered in this mini review.

  20. Linking the generation of DNA adducts to lung cancer.

    Science.gov (United States)

    Ceppi, Marcello; Munnia, Armelle; Cellai, Filippo; Bruzzone, Marco; Peluso, Marco E M

    2017-09-01

    Worldwide, lung cancer is the leading cause of cancer death. DNA adducts are considered a reliable biomarker that reflects carcinogen exposure to tobacco smoke, but the central question is what is the relationship of DNA adducts and cancer? Therefore, we investigated this relationship by a meta-analysis of twenty-two studies with bronchial adducts for a total of 1091 subjects, 887 lung cancer cases and 204 apparently healthy individuals with no evidence of lung cancer. Our study shows that these adducts are significantly associated to increase lung cancer risk. The value of Mean Ratio lung-cancer (MR) of bronchial adducts resulting from the random effects model was 2.64, 95% C.I. 2.00-3.50, in overall lung cancer cases as compared to controls. The significant difference, with lung cancer patients having significant higher levels of bronchial adducts than controls, persisted after stratification for smoking habits. The MR lung-cancer value between lung cancer patients and controls for smokers was 2.03, 95% C.I. 1.42-2.91, for ex-smokers 3.27, 95% C.I. 1.49-7.18, and for non-smokers was 3.81, 95% C.I. 1.85-7.85. Next, we found that the generation of bronchial adducts is significantly related to inhalation exposure to tobacco smoke carcinogens confirming its association with volatile carcinogens. The MR smoking estimate of bronchial adducts resulting from meta-regression was 2.28, 95% Confidence Interval (C.I.) 1.10-4.73, in overall smokers in respect to non-smokers. The present work provides strengthening of the hypothesis that bronchial adducts are not simply relate to exposure, but are a cause of chemical-induced lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

    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 32 P-postlabelling protocol with nuclease P1 enrichment adapted from Reddy and Randerath [Reddy, M.V., Randerath, K., 1986. Nuclease P1-mediated enhancement of sensitivity of 32 P-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 4.0/10 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 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 1.13/10 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 32 P-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

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

    Energy Technology Data Exchange (ETDEWEB)

    Le Goff, J. [GRECAN, UPRES EA-1772, University of Caen, Caen (France); Gallois, J. [Laboratory F. Duncombe, Conseil General du Calvados, Caen (France); Pelhuet, L. [LPTC, UMR-5472 CNRS, University Bordeaux I, Bordeaux (France); Devier, M.H. [LPTC, UMR-5472 CNRS, University Bordeaux I, Bordeaux (France); Budzinski, H. [LPTC, UMR-5472 CNRS, University Bordeaux I, Bordeaux (France); Pottier, D. [GRECAN, UPRES EA-1772, University of Caen, Caen (France); Andre, V. [GRECAN, UPRES EA-1772, University of Caen, Caen (France); Cachot, J. [LEMA, UPRES EA-3222, IFRMP 23, University of Le Havre, 25 rue Philippe Lebon, B.P. 540, 76058 Le Havre Cedex (France)]. E-mail: jerome.cachot@univ-lehavre.fr

    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 {sup 32}P-postlabelling protocol with nuclease P1 enrichment adapted from Reddy and Randerath [Reddy, M.V., Randerath, K., 1986. Nuclease P1-mediated enhancement of sensitivity of {sup 32}P-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 {mu}g g{sup -1} dry weight) in comparison to individuals from the reference site (0.053 {mu}g g{sup -1} dry weight). The former exhibited elevated levels of DNA adducts (up to 4.0/10{sup 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 {mu}g g{sup -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 {mu}g g{sup -1} dry weight) and a clear induction of DNA adduct formation in the digestive gland of mussels (up to 1.13/10{sup 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 {sup 32}P-postlabelling method for bulky adduct detection in the digestive gland of zebra mussels. DNA adduct measurement in

  3. Modelling knee flexion effects on joint power absorption and adduction moment.

    Science.gov (United States)

    Nagano, Hanatsu; Tatsumi, Ichiroh; Sarashina, Eri; Sparrow, W A; Begg, Rezaul K

    2015-12-01

    Knee osteoarthritis is commonly associated with ageing and long-term walking. In this study the effects of flexing motions on knee kinetics during stance were simulated. Extended knees do not facilitate efficient loading. It was therefore, hypothesised that knee flexion would promote power absorption and negative work, while possibly reducing knee adduction moment. Three-dimensional (3D) position and ground reaction forces were collected from the right lower limb stance phase of one healthy young male subject. 3D position was sampled at 100 Hz using three Optotrak Certus (Northern Digital Inc.) motion analysis camera units, set up around an eight metre walkway. Force plates (AMTI) recorded ground reaction forces for inverse dynamics calculations. The Visual 3D (C-motion) 'Landmark' function was used to change knee joint positions to simulate three knee flexion angles during static standing. Effects of the flexion angles on joint kinetics during the stance phase were then modelled. The static modelling showed that each 2.7° increment in knee flexion angle produced 2.74°-2.76° increments in knee flexion during stance. Increased peak extension moment was 6.61 Nm per 2.7° of increased knee flexion. Knee flexion enhanced peak power absorption and negative work, while decreasing adduction moment. Excessive knee extension impairs quadriceps' power absorption and reduces eccentric muscle activity, potentially leading to knee osteoarthritis. A more flexed knee is accompanied by reduced adduction moment. Research is required to determine the optimum knee flexion to prevent further damage to knee-joint structures affected by osteoarthritis. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Minding Rachlin's Eliminative Materialism

    Science.gov (United States)

    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…

  5. [Hemoglobin adducts as biomarkers of human exposure to selected xenobiotics].

    Science.gov (United States)

    Bukowska, Bożena

    2015-06-12

    In the living and working environments more and more new substances of anthropogenic origin exerting toxic properties appear. Simultaneously, the evaluation of human exposure is assessed. For many years adducts of hemoglobin (Hb) have been useful markers of the exposure of humans to various xenobiotics. These adducts are also termed biologically effective dose biomarkers. This paper focuses on a review of literature, mainly from the years 2010-2014, which refers to the hemoglobin adducts of toxic compounds with electrophilic properties. In the interactions of xenobiotics with hemoglobin, groups such as thiol, amino, carboxyl and hydroxyl of this hemoprotein are involved. These combinations occur most often in the reaction of xenobiotics with an N-terminal amino group of valine in Hb, imidazole nitrogen of histidine and cysteine sulfhydryl β93. Hb adducts are characterized by high availability, a long period of occurrence (up to 120 days) in the circulatory system, and high durability, and they have contact with all cells of the body. The measurement of hemoglobin adducts can be potentially used in the assessment of exposure to many xenobiotics such as acrylamide; substances present in tobacco smoke, e.g. benzo(α)pyrene and benzanthracene, ethylene oxide, aryl amines; and substances used on a large scale in industry such as glycidol and naphthalene and its derivatives. Recently the possibility of determination of hemoglobin adducts with estrogen metabolites has been postulated as indicators informing about heightened risk of breast cancer. Protein adducts are used as an alternative to DNA adducts for different classes of electrophilic substances.

  6. Condensed tannin-resorcinol adducts in laminating adhesives

    Science.gov (United States)

    Richard W. Hemingway; Roland E. Kreibich

    1985-01-01

    A condensed tannin-resorcinol adduct made by co-reaction of an extract from southern pine bark with resorcinol at a 2 to 1 weight ratio was used to prepare a laminating resin in which the entire amount of resorcinol normally used was replaced by this adduct. The resin was formulated into a room temperature setting adhesive that meets the basic criteria of product...

  7. Twin Peaks - 3D

    Science.gov (United States)

    1997-01-01

    The two hills in the distance, approximately one to two kilometers away, have been dubbed the 'Twin Peaks' and are of great interest to Pathfinder scientists as objects of future study. 3D glasses are necessary to identify surface detail. The white areas on the left hill, called the 'Ski Run' by scientists, may have been formed by hydrologic processes.The IMP is a stereo imaging system with color capability provided by 24 selectable filters -- twelve filters per 'eye.Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  8. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    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.

  9. Mass spectrometric analysis of sulfur mustard-induced biomolecular adducts: Are DNA adducts suitable biomarkers of exposure?

    Science.gov (United States)

    Zubel, Tabea; Bürkle, Alexander; Mangerich, Aswin

    2017-12-23

    The bi-functional chemical warfare agent sulfur mustard (SM), whose release in asymmetric conflicts or terrorist attacks represents a realistic threat, induces several kinds of biomolecular adducts, including highly toxic DNA adducts. Isotope dilution liquid chromatographic tandem mass spectrometry (ID-LC-MS/MS) is considered the gold standard for highly accurate, precise, specific and sensitive quantification of DNA adducts in general. Recently, a number of LC-MS/MS approaches have been established to analyze SM-induced protein and DNA adducts in cell culture and rodent animal models. As DNA adducts are mechanism-based biomarkers for SM exposure, results from such studies provide a deeper understanding of the etiology of SM-induced pathologies, especially of long-term effects such as cancer formation. As a result, medical treatment of SM-exposed individuals might be improved. Yet, despite the progress that has been made during the last years, there is still a need for advanced methods of ID-LC-MS/MS for the detection and quantitation of SM adducts. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Adouni, M; Shirazi-Adl, A

    2014-05-07

    Medial knee osteoarthritis is a debilitating disease. Surgical and conservative interventions are performed to manage its progression via reduction of load on the medial compartment or equivalently its surrogate measure, the external adduction moment. However, some studies have questioned a correlation between the medial load and adduction moment. Using a musculoskeletal model of the lower extremity driven by kinematics-kinetics of asymptomatic subjects at gait midstance, we aim here to quantify the relative effects of changes in the knee adduction angle versus changes in the adduction moment on the joint response and medial/lateral load partitioning. The reference adduction rotation of 1.6° is altered by ±1.5° to 3.1° and 0.1° or the knee reference adduction moment of 17Nm is varied by ±50% to 25.5Nm and 8.5Nm. Quadriceps, hamstrings and tibiofemoral contact forces substantially increased as adduction angle dropped and diminished as it increased. The medial/lateral ratio of contact forces slightly altered by changes in the adduction moment but a larger adduction rotation hugely increased this ratio from 8.8 to a 90 while in contrast a smaller adduction rotation yielded a more uniform distribution. If the aim in an intervention is to diminish the medial contact force and medial/lateral load ratio, a drop of 1.5° in adduction angle is much more effective (causing respectively 12% and 80% decreases) than a reduction of 50% in the adduction moment (causing respectively 4% and 13% decreases). Substantial role of changes in adduction angle is due to the associated alterations in joint nonlinear passive resistance. These findings explain the poor correlation between knee adduction moment and tibiofemoral compartment loading during gait suggesting that the internal load partitioning is dictated by the joint adduction angle. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Sunset over Twin Peaks

    Science.gov (United States)

    1997-01-01

    This image was taken by the Imager for Mars Pathfinder (IMP) about one minute after sunset on Mars on Sol 21. The prominent hills dubbed 'Twin Peaks' form a dark silhouette at the horizon, while the setting sun casts a pink glow over the darkening sky. The image was taken as part of a twilight study which indicates how the brightness of the sky fades with time after sunset. Scientists found that the sky stays bright for up to two hours after sunset, indicating that Martian dust extends very high into the atmosphere.Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  12. Risks: diagnosing and eliminating

    Directory of Open Access Journals (Sweden)

    Yuriy A. Tikhomirov

    2016-01-01

    Full Text Available Objective to develop conceptual theoretical and legal provisions and scientific recommendations on the identification analysis and elimination of risk. Methods universal dialectic method of cognition as well as scientific and private research methods based on it. Results the system was researched of risks diagnostics in the legal sphere and mechanism of influencing the quotrisk situationsquot and their consequences damage to the environment and harm to society. The concept of risk in the legal sphere was formulated the author39s classification of risks in the legal sphere is presented. The rules of analysis evaluation and prevention of risks and the model risk management framework are elaborated. Scientific novelty the mechanism for the identification analysis and elimination of risk has been developed and introduced into scientific circulation the author has proposed the classification and types of risks the reasons and the conditions promoting the risk occurrence. Practical significance the provisions and conclusions of the article can be used in the scientific lawmaking and lawenforcement activity as well as in the educational process of higher educational establishments. nbsp

  13. Adduct ion-targeted qualitative and quantitative analysis of polyoxypregnanes by ultra-high pressure liquid chromatography coupled with triple quadrupole mass spectrometry.

    Science.gov (United States)

    Wu, Xu; Zhu, Lin; Ma, Jiang; Ye, Yang; Lin, Ge

    2017-10-25

    Polyoxypregnane and its glycosides (POPs) are frequently present in plants of Asclepiadaceae family, and have a variety of biological activities. There is a great need to comprehensively profile these phytochemicals and to quantify them for monitoring their contents in the herbs and the biological samples. However, POPs undergo extensive adduct ion formation in ESI-MS, which has posed a challenge for qualitative and quantitative analysis of POPs. In the present study, we took the advantage of such extensive adduct ion formation to investigate the suitability of adduct ion-targeted analysis of POPs. For the qualitative analysis, we firstly demonstrated that the sodium and ammonium adduct ion-targeted product ion scans (PIS) provided adequate MS/MS fragmentations for structural characterization of POPs. Aided with precursor ion (PI) scans, which showed high selectivity and sensitivity and improved peak assignment confidence in conjunction with full scan (FS), the informative adduct ion-targeted PIS enabled rapid POPs profiling. For the quantification, we used formic acid rather than ammonium acetate as an additive in the mobile phase to avoid simultaneous formation of sodium and ammonium adduct ions, and greatly improved reproducibility of MS response of POPs. By monitoring the solely formed sodium adduct ions [M+Na] + , a method for simultaneous quantification of 25 POPs in the dynamic multiple reaction monitoring mode was then developed and validated. Finally, the aforementioned methods were applied to qualitative and quantitative analysis of POPs in the extract of a traditional Chinses medicinal herb, Marsdenia tenacissima (Roxb.) Wight et Arn., and in the plasma obtained from the rats treated with this herb. The results demonstrated that adduct ion formation could be optimized for the qualitative and quantitative analysis of POPs, and our developed PI/FS-PIS scanning and sole [M+Na] + ion monitoring significantly improved the analysis of POPs in both herbal and

  14. Characterization of hemoglobin-benzo[a]pyrene adducts

    International Nuclear Information System (INIS)

    Haugen, D.A.; Myers, S.R.

    1987-01-01

    Cultures of Syrian hamster embryo (SHE) cells were supplemented with human Hb (0.2 mM heme) and [ 3 H]BP (1 μM). After a 24-h incubation, the medium was removed and subjected to cation-exchange liquid chromatography (CM-Sepharose) to resolve hemoglobins from serum proteins in the medium. The BP-treated Hb was subjected to analysis in each of three column chromatographic systems established for isolation and characterization of human hemoglobin and its genetic and post-translationally modified variants. Results demonstrate that hemoglobin-carcinogen adducts can be resolved from native hemoglobin by established conventional and high-performance liquid chromatographic procedures, suggesting the basis for development of general approaches for isolating and characterizing hemoglobin-carcinogen adducts. The results also suggest the basis for a model system in which adducts between carcinogens and human hemoglobin are formed in cultures of mammalian cells or tissues

  15. DNA adducts: Mass spectrometry methods and future prospects

    International Nuclear Information System (INIS)

    Farmer, P.B.; Brown, K.; Tompkins, E.; Emms, V.L.; Jones, D.J.L.; Singh, R.; Phillips, D.H.

    2005-01-01

    Detection of DNA adducts is widely used for the monitoring of exposure to genotoxic carcinogens. Knowledge of the nature and amounts of DNA adducts formed in vivo also gives valuable information regarding the mutational effects that may result from particular exposures. The power of mass spectrometry (MS) to achieve qualitative and quantitative analyses of human DNA adducts has increased greatly in recent years with the development of improved chromatographic interfaces and ionisation sources. Adducts have been detected on nucleic acid bases, 2'-deoxynucleosides or 2'-deoxynucleotides, with LC-MS/MS being the favoured technique for many of these analyses. Our current applications of this technique include the determination of N7-(2-carbamoyl-2-hydroxyethyl)-guanine, which was postulated to be found as a DNA repair product in urine following exposure to acrylamide, and of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydro-2'-deoxyadenosine, as markers of oxidative damage in human lymphocyte DNA. Higher sensitivity (with a detection limit of 1-10 adducts/10 12 nucleotides) may be achieved by the use of accelerator mass spectrometry (AMS), although this requires the presence of certain isotopes, such as [ 14 C], in the material being analysed. In order to make this technique more amenable for studies of human exposure to environmental carcinogens, new postlabelling techniques, incorporating [ 14 C] into specific DNA adducts after formation, are being developed. It is expected that combining the use of advanced MS techniques with existing 32 P-postlabelling and immunochemical methodologies will contribute greatly to the understanding of the burden of human exposure to environmental carcinogens

  16. Possible rare congenital dysinnervation disorder: congenital ptosis associated with adduction.

    Science.gov (United States)

    Mendes, Sílvia; Beselga, Diana; Campos, Sónia; Neves, Arminda; Campos, Joana; Carvalho, Sílvia; Silva, Eduardo; Castro Sousa, João Paulo

    2015-01-01

    Ptosis is defined as an abnormally low position of the upper eyelid margin. It can be congenital or acquired, uni or bilateral, and isolated or associated with other ocular and nonocular defects. We report a case of a female child, aged 8 years, with congenital right ptosis increased on right adduction and with left ptosis on left adduction. There was no horizontal ocular movement limitation. Apparent underaction of the right inferior oblique muscle was also present. We believe that within the possible mechanisms it is more likely that it is a congenital innervation dysgenesis syndrome (CID)/congenital cranial dysinnervation disorder (CCDD).

  17. Chemistry and Biology of Aflatoxin-DNA Adducts

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-27

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

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

    Science.gov (United States)

    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.

  19. O⁶-carboxymethylguanine DNA adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem-rich meat.

    Science.gov (United States)

    Vanden Bussche, Julie; Hemeryck, Lieselot Y; Van Hecke, Thomas; Kuhnle, Gunter G C; Pasmans, Frank; Moore, Sharon A; Van de Wiele, Tom; De Smet, Stefaan; Vanhaecke, Lynn

    2014-09-01

    Epidemiological and clinical studies have demonstrated that the consumption of red haem-rich meat may contribute to the risk of colorectal cancer. Two hypotheses have been put forward to explain this causal relationship, i.e. N-nitroso compound (NOC) formation and lipid peroxidation (LPO). In this study, the NOC-derived DNA adduct O(6)-carboxymethylguanine (O(6)-CMG) and the LPO product malondialdehyde (MDA) were measured in individual in vitro gastrointestinal digestions of meat types varying in haem content (beef, pork, chicken). While MDA formation peaked during the in vitro small intestinal digestion, alkylation and concomitant DNA adduct formation was observed in seven (out of 15) individual colonic digestions using separate faecal inocula. From those, two haem-rich meat digestions demonstrated a significantly higher O(6)-CMG formation (p meat. The addition of myoglobin, a haem-containing protein, to the digestive simulation showed a dose-response association with O(6)-CMG (p = 0.004) and MDA (p = 0.008) formation. The results suggest the haem-iron involvement for both the LPO and NOC pathway during meat digestion. Moreover, results unambiguously demonstrate that DNA adduct formation is very prone to inter-individual variation, suggesting a person-dependent susceptibility to colorectal cancer development following haem-rich meat consumption. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Peak flow meter use - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100202.htm Peak flow meter use - Series—Peak flow meter use - part one To use the sharing ... slide 7 out of 7 Overview A peak flow meter helps you check how well your asthma ...

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

    Directory of Open Access Journals (Sweden)

    Judge Bryan S

    2011-03-01

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

  2. Knee joint moments during high flexion movements: Timing of peak moments and the effect of safety footwear.

    Science.gov (United States)

    Chong, Helen C; Tennant, Liana M; Kingston, David C; Acker, Stacey M

    2017-03-01

    (1) Characterize knee joint moments and peak knee flexion moment timing during kneeling transitions, with the intent of identifying high-risk postures. (2) Determine whether safety footwear worn by kneeling workers (construction workers, tile setters, masons, roofers) alters high flexion kneeling mechanics. Fifteen males performed high flexion kneeling transitions. Kinetics and kinematics were analyzed for differences in ascent and descent in the lead and trail legs. Mean±standard deviation peak external knee adduction and flexion moments during transitions ranged from 1.01±0.31 to 2.04±0.66% body weight times height (BW∗Ht) and from 3.33 to 12.6% BW∗Ht respectively. The lead leg experienced significantly higher adduction moments compared to the trail leg during descent, when work boots were worn (interaction, p=0.005). There was a main effect of leg (higher lead vs. trail) on the internal rotation moment in both descent (p=0.0119) and ascent (p=0.0129) phases. Peak external knee adduction moments during transitions did not exceed those exhibited during level walking, thus increased knee adduction moment magnitude is likely not a main factor in the development of knee OA in occupational kneelers. Additionally, work boots only significantly increased the adduction moment in the lead leg during descent. In cases where one knee is painful, diseased, or injured, the unaffected knee should be used as the lead leg during asymmetric bilateral kneeling. Peak flexion moments occurred at flexion angles above the maximum flexion angle exhibited during walking (approximately 60°), supporting the theory that the loading of atypical surfaces may aid disease development or progression. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. DNA bulky adducts in a Mediterranean population correlate with environmental ozone concentration, an indicator of photochemical smog.

    Science.gov (United States)

    Palli, Domenico; Saieva, Calogero; Grechi, Daniele; Masala, Giovanna; Zanna, Ines; Barbaro, Antongiulio; Decarli, Adriano; Munnia, Armelle; Peluso, Marco

    2004-03-01

    Ozone (O(3)), the major oxidant component in photochemical smog, mostly derives from photolysis of nitrogen dioxide. O(3) may have biologic effects directly and/or via free radicals reacting with other primary pollutants and has been reported to influence daily mortality and to increase lung cancer risk. Although DNA damage may be caused by ozone itself, only other photochemical reaction products (as oxidised polycyclic aromatic hydrocarbons) may form bulky DNA adducts, a reliable biomarker of genotoxic damage and cancer risk, showing a seasonal trend. In a large series consisting of 320 residents in the metropolitan area of Florence, Italy, enrolled in a prospective study for the period 1993-1998 (206 randomly sampled volunteers, 114 traffic-exposed workers), we investigated the correlation between individual levels of DNA bulky adducts and a cumulative O(3) exposure score. The average O(3) concentrations were calculated for different time windows (0-5 to 0-90 days) prior to blood drawing for each participant, based on daily measurements provided by the local monitoring system. Significant correlations between DNA adduct levels and O3 cumulative exposure scores in the last 2-8 weeks before enrollment emerged in never smokers. Correlations were highest in the subgroup of never smokers residing in the urban area and not occupationally exposed to vehicle traffic pollution, with peak values for average concentrations 4-6 weeks before enrollment (r = 0.34). Our current findings indicate that DNA adduct formation may be modulated by individual characteristics and by the cumulative exposure to environmental levels of ozone in the last 4-6 weeks, possibly through ozone-associated reactive pollutants. Copyright 2003 Wiley-Liss, Inc.

  4. Elimination of aluminum adjuvants.

    Science.gov (United States)

    Hem, Stanley L

    2002-05-31

    In vitro dissolution experiments although perhaps not at typical body concentrations and temperatures demonstrated that the alpha-hydroxycarboxylic acids present in interstitial fluid (citric acid, lactic acid, and malic acid) are capable of dissolving aluminum-containing adjuvants. Amorphous aluminum phosphate adjuvant dissolved more rapidly than crystalline aluminum hydroxide adjuvant. Intramuscular administration in New Zealand White rabbits of aluminum phosphate and aluminum hydroxide adjuvants, which were labelled with 26Al, revealed that 26Al was present in the first blood sample (1 h) for both adjuvants. The area under the blood level curve for 28 days indicated that three times more aluminum was absorbed from aluminum phosphate adjuvant than aluminum hydroxide adjuvant. In vivo studies using 26Al-labelled adjuvants are relatively safe because accelerator mass spectrometry (AMS) can quantify quantities of 26Al as small as 10(-17) g. A similar study in humans would require a whole-body exposure of 0.7 microSv per year compared to the natural background exposure of 3000 microSv per year. The in vitro dissolution and in vivo absorption studies indicate that aluminum-containing adjuvants which are administered intramuscularly are dissolved by alpha-hydroxycarboxylic acids in interstitial fluid, absorbed into the blood, distributed to tissues, and eliminated in the urine.

  5. 78 FR 46260 - Sorbitan Monooleate Ethylene Oxide Adduct; Exemption From the Requirement of a Tolerance

    Science.gov (United States)

    2013-07-31

    ... Monooleate Ethylene Oxide Adduct; Exemption From the Requirement of a Tolerance AGENCY: Environmental...-ethanediyl) derivs., (Z)- (CAS Reg. No 9005-65-6) (also known as ``sorbitan monooleate ethylene oxide adduct... residues of sorbitan monooleate ethylene oxide adduct. DATES: This regulation is effective July 31, 2013...

  6. 40 CFR 721.3680 - Ethylene oxide adduct of fatty acid ester with pentaerythritol.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Ethylene oxide adduct of fatty acid... New Uses for Specific Chemical Substances § 721.3680 Ethylene oxide adduct of fatty acid ester with... identified generically as ethylene oxide adduct of fatty acid ester with pentaerythritol (PMN P-91-442) is...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-05-01

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

  8. Comparison of estimated dietary intake of acrylamide with hemoglobin adducts of acrylamide and glycidamide

    DEFF Research Database (Denmark)

    Bjellaas, Thomas; Olesen, Pelle Thonning; Frandsen, Henrik Lauritz

    2007-01-01

    , a significant positive correlation was found between the AA-Hb adduct concentration and the intake of chips/snacks and crisp bread. GA-Hb adduct did not correlate with consumption of any of the main food groups. Neither AA-Hb nor GA-Hb adduct concentration correlated with total dietary intake of AA...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  10. Formation of BH 3 Adducts with Pyridine-2-Methylaminophosphine ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 128; Issue 1. Formation of BH3 Adducts with Pyridine-2-Methylaminophosphine ligands: An experimental and computational study. Harinath Adimulam Dwijendra P Kukri Bhabani S Mallik Tarun K Panda. Regular Articles Volume 128 Issue 1 January 2016 pp 53-60 ...

  11. Conformations of stereoisomeric base adducts to 4-hydroxyequilenin.

    Science.gov (United States)

    Ding, Shuang; Shapiro, Robert; Geacintov, Nicholas E; Broyde, Suse

    2003-06-01

    Exposure to estrogen through estrogen replacement therapy increases the risk of women developing cancer in hormone sensitive tissues. Premarin (Wyeth), which has been the most frequent choice for estrogen replacement therapy in the United States, contains the equine estrogens equilin and equilenin as major components. 4-Hydroxyequilenin (4-OHEN) is a phase I metabolite of both of these substances. This catechol estrogen autoxidizes to potent cytotoxic quinoids that can react with dG, dA, and dC to form unusual stereoisomeric cyclic adducts (Bolton, J. L., et al. (1998) Chem. Res. Toxicol. 11, 1113-1127). Like other bulky DNA adducts, these lesions may exhibit different susceptibilities to DNA repair and mutagenic potential, if not repaired in a structure-dependent manner. To ultimately gain insights into structure-function relationships, we computed conformations of stereoisomeric guanine, adenine, and cytosine base adducts using density functional theory. We find near mirror image conformations in stereoisomer adduct pairs for each modified base, suggesting opposite orientations with respect to the 5' --> 3' direction of the modified strand when the stereoisomer pairs are incorporated into duplex DNA. Such opposite orientations could cause stereoisomer pairs of lesions to respond differently to DNA replication and repair enzymes.

  12. Theoretical investigations on the formation of nitrobenzanthrone-DNA adducts.

    Science.gov (United States)

    Arlt, Volker M; Phillips, David H; Reynisson, Jóhannes

    2011-09-07

    3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust. The thermochemical formation cascades were calculated for six 3-NBA-derived DNA adducts employing its arylnitrenium ion as precursor using density functional theory (DFT). Clear exothermic pathways were found for four adducts, i.e., 2-(2'-deoxyadenosin-N(6)-yl)-3-aminobenzanthrone, 2-(2'-deoxyguanosin-N(2)-yl)-3-aminobenzanthrone, N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone and 2-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone. All four have been observed to be formed in cell-free experimental systems. The formation of N-(2'-deoxyadenosin-8-yl)-3-aminobenzanthrone is predicted to be not thermochemically viable explaining its absence in either in vitro or in vivo model systems. However, 2-(2'-deoxyadenosin-8-yl)-3-aminobenzanthrone, can be formed, albeit not as a major product, and is a viable candidate for an unknown adenine adduct observed experimentally. 2-nitrobenzanthrone (2-NBA), an isomer of 3-NBA, was also included in the calculations; it has a higher abundance in ambient air than 3-NBA, but a much lower genotoxic potency. Similar thermochemical profiles were obtained for the calculated 2-NBA-derived DNA adducts. This leads to the conclusion that enzymatic activation as well as the stability of its arylnitrenium ion are important determinants of 2-NBA genotoxicity.

  13. Deuteration of triborane(7) adducts with anhydrous deuterium chloride

    International Nuclear Information System (INIS)

    Dodds, A.R.; Kodama, G.

    1977-01-01

    A hydrogen-deuterium exchange reaction between triborane(7) adducts and deuterium chloride is reported which involves all the hydrogen atoms in the B 3 H 7 moiety and proceeds rapidly even at low temperatures. The exchange reaction is reported to proceed much faster in dichloromethane solution than in tetrahydrofuran

  14. The fate of H atom adducts to 3'-uridine monophosphate.

    Science.gov (United States)

    Wang, Ran; Zhang, Ru Bo; Eriksson, Leif A

    2010-07-29

    The stabilities of the adducts deriving from H free radical addition to the O2, O4, and C5 positions of 3'-uridine monophosphate (3'UMP) are studied by the hybrid density functional B3LYP approach. Upon H atom addition at the O2 position, a concerted low-barrier proton-transfer process will initially occur, followed by the potential ruptures of the N-glycosidic or beta-phosphate bonds. The rupture barriers are strongly influenced by the rotational configuration of the phosphate group at the 3' terminal, and are influenced by bulk solvation effects. The O4-H adduct has the highest thermal stability, as the localization of the unpaired electron does not enable cleavage of either the C1'-N1 or the C3'-O(P) bonds. For the most stable adduct, with H atom added to the C5 position, the rate-controlled step is the H2'a abstraction by the C6 radical site, after which the subsequent strand rupture reactions proceed with low barriers. The main unpaired electron densities are presented for the transient species. Combined with previous results, it is concluded that the H atom adducts are more facile to drive the strand scission rather than N-glycosidic bond ruptures within the nucleic acid bases.

  15. Formation of BH3 Adducts with Pyridine-2-Methylaminophosphine ...

    Indian Academy of Sciences (India)

    tional theoretical (DFT) calculations were performed on the BH3 adducts 1a and 2a. The results are consistent with the experimental results. Keywords. Pyridine; Borane; DFT calculation; X-ray analysis; HOMO; LUMO. 1. Introduction. Various P-N ligands are often used in organometallic chemistry to achieve well-defined ...

  16. Effect of external electric field on Cyclodextrin-Alcohol adducts

    Indian Academy of Sciences (India)

    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, ...

  17. Aldehyde and ketone adducts of the gaseous trifluoromethyl cation

    NARCIS (Netherlands)

    Oomens, J.; Morton, T.H.

    2011-01-01

    IR spectra of CF3+ adduct ions are reported for the first time using infrared multiple photon dissociation (IRMPD). Carbonyl stretches of ketone conjugate acids shift less than do those of ions containing C═OCF3+ groups. Carbonyl absorptions shift in proportion to the empirical softness of the

  18. Metal-isonitrile adducts for preparing radionuclide complexes

    International Nuclear Information System (INIS)

    Carpenter, A.P.; Linder, K.E.; Maheu, L.J.; Patz, M.A.; Thompson, J.S.; Tulip, T.H.; Subramanyam, V.

    1988-01-01

    An method for preparing a coordination complex of isonitrile ligand and a radioisotope of Te, Ru, Co, Pt, Re, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Nb and Ta from a non-radioactive metal adduct of the isonitrile

  19. Eliminating Rabies in Estonia

    Science.gov (United States)

    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, 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. PMID:22393461

  20. 2'-Deoxythymidine Adducts from the Anti-HIV Drug Nevirapine

    Directory of Open Access Journals (Sweden)

    M. Matilde Marques

    2013-04-01

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

  1. Analysis of the factors that correlate with increased knee adduction moment during gait in the early postoperative period following total knee arthroplasty.

    Science.gov (United States)

    Nagura, Takeo; Niki, Yasuo; Harato, Kengo; Mochizuki, Takeshi; Kiriyama, Yoshimori

    2017-03-01

    Analysis of dynamic knee loading during gait is essential to prevent mechanical failures following total knee arthroplasty. External knee adduction moment during gait is the primary factor producing medial joint reaction force, and an increase in the moment is directly related to an increase in the medial compartment load on the knee. Knee adduction moment during gait in 39 knees of 32 female patients following a posterior stabilized knee replacement with a single surgeon was evaluated at 1.3months following surgery. A cut-off moment was determined as mean+1 standard deviation (SD) of the moment from 10 healthy subjects, and patients' knees were divided into high- and normal-moment groups. Significant differences in clinical assessments and gait parameters between the two groups were assessed. Based on the cut-off moment, 23 knees were grouped into normal knees and 16 knees were grouped into high-moment knees. High-moment knees showed identical femorotibial angles and knee society scores but had greater toe-out angles and medially directed ground reaction forces compared to normal-moment knees. High-moment knees showed strong correlations between peak moment and knee adduction angle, and frontal plain moment arm. The clinical significance of a high knee adduction moment following total knee arthroplasty remains unclear, but dynamic frontal alignment during gait is one of the key factors for residual high-moment knees following surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yun-bo

    1988-03-01

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

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  4. Formation of DNA adducts in mouse tissues after 1-nitropyrene administration

    International Nuclear Information System (INIS)

    Mitchell, C.E.

    1986-01-01

    DNA adducts were isolated and characterized in mouse lung, liver and kidney after intratracheal instillation of [ 3 H]-1-nitropyrene (1-NP). HPLC analysis of the enzymatically digested DNA indicated the presence of multiple DNA adducts in mouse lung, liver and kidney. These results indicate that DNA adducts of 1-NP are formed in mouse lung, liver and kidney after intratracheal instillation of 1-NP; the HPLC profiles of the multiple adducts suggests that adducts may be formed via metabolic pathways that involve both nitroreduction and ring-oxidation. 6 references, 1 figure

  5. Detection of Adriamycin-DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations.

    Science.gov (United States)

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

    2008-09-01

    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/10(4) 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 have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

  6. PEAK SHAVING CONSIDERING STREAMFLOW UNCERTAINTIES

    African Journals Online (AJOL)

    user

    Abstract. The main thrust of this paper is peak shaving with a Stochastic hydro model. In peak sharing, the amount of hydro energy scheduled may be a minimum but it serves to replace less efficient thermal units. The sample system is die Kainji hydro plant and the thermal units of the National Electric. Power Authority.

  7. Twin and triple peaks papilledema.

    Science.gov (United States)

    Mehta, Jodhbir S; Plant, Gordon T; Acheson, James F

    2005-07-01

    To describe 2 adult patients who presented with papilledema after band atrophy (i.e., twin and triple peaks papilledema). Retrospective small case series. Two outpatients. Observations made on 2 patients whose cases were reviewed in the neuro-ophthalmology clinic. The first patient had a pituitary tumor presenting with papilledema, causing a triple peaks clinical sign. Color photographs, optical coherence tomograms, and magnetic resonance images are shown. The second patient developed twin peaks papilledema due to a chiasmal glioma causing secondary raised intracranial pressure. Twin peaks papilledema is a rare clinical sign that may develop in adults as well as in children. The first report and optical coherence tomography features of triple peaks papilledema illustrate a new clinical sign.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

  9. PHOSPHATO AND PHOSPHONATO ADDUCTS: SYNTHESIS AND SPECTROSCOPIC STUDY

    Directory of Open Access Journals (Sweden)

    Mouhamadou Birame Diop

    2014-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-06-15

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

  11. Dispersant additives derived from lactone modified amido-amine adducts

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez, A.; Lundberg, R.D.

    1990-10-16

    This patent describes a lactone modified dispersant additive. It comprises one adduct of a polyolefin of 300 to 10,000 number average molecular weight substituted with at least 0.8 (e.g., from about 1 to 4) dicarboxylic acid producing moieties (preferably acid or anhydride moieties) per polyolefin molecule, an amido-amine or thioamido-amine characterized by being a reaction product of at least a polyamine and an alpha, beta-unsaturated compound.

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

    OpenAIRE

    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...

  13. Combined effects of a valgus knee brace and lateral wedge foot orthotic on the external knee adduction moment in patients with varus gonarthrosis.

    Science.gov (United States)

    Moyer, Rebecca F; Birmingham, Trevor B; Dombroski, Colin E; Walsh, Robert F; Leitch, Kristyn M; Jenkyn, Thomas R; Giffin, J Robert

    2013-01-01

    To test the hypothesis that a custom-fit valgus knee brace and custom-made lateral wedge foot orthotic will have greatest effects on decreasing the external knee adduction moment during gait when used concurrently. Proof-of-concept, single test session, crossover trial. Biomechanics laboratory within a tertiary care center. Patients (n=16) with varus alignment and knee osteoarthritis (OA) primarily affecting the medial compartment of the tibiofemoral joint (varus gonarthrosis). Custom-fit valgus knee brace and custom-made full-length lateral wedge foot orthotic. Amounts of valgus angulation and wedge height were tailored to each patient to ensure comfort. The external knee adduction moment (% body weight [BW]*height [Ht]), frontal plane lever arm (cm), and ground reaction force (N/kg), determined from 3-dimensional gait analysis completed under 4 randomized conditions: (1) control (no knee brace, no foot orthotic), (2) knee brace, (3) foot orthotic, and (4) knee brace and foot orthotic. The reduction in knee adduction moment was greatest when concurrently using the knee brace and foot orthotic (effect sizes ranged from 0.3 to 0.4). The mean decrease in first peak knee adduction moment compared with control was .36% BW*Ht (95% confidence interval [CI], -.66 to -.07). This was accompanied by a mean decrease in frontal plane lever arm of .59cm (95% CI, -.94 to -.25). These findings suggest that using a custom-fit knee brace and custom-made foot orthotic concurrently can produce a greater overall reduction in the knee adduction moment, through combined effects in decreasing the frontal plane lever arm. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  16. LOBSTAHS: An Adduct-Based Lipidomics Strategy for Discovery and Identification of Oxidative Stress Biomarkers.

    Science.gov (United States)

    Collins, James R; Edwards, Bethanie R; Fredricks, Helen F; Van Mooy, Benjamin A S

    2016-07-19

    Discovery and identification of molecular biomarkers in large LC/MS data sets requires significant automation without loss of accuracy in the compound screening and annotation process. Here, we describe a lipidomics workflow and open-source software package for high-throughput annotation and putative identification of lipid, oxidized lipid, and oxylipin biomarkers in high-mass-accuracy HPLC-MS data. Lipid and oxylipin biomarker screening through adduct hierarchy sequences, or LOBSTAHS, uses orthogonal screening criteria based on adduct ion formation patterns and other properties to identify thousands of compounds while providing the user with a confidence score for each assignment. Assignments are made from one of two customizable databases; the default databases contain 14 068 unique entries. To demonstrate the software's functionality, we screened more than 340 000 mass spectral features from an experiment in which hydrogen peroxide was used to induce oxidative stress in the marine diatom Phaeodactylum tricornutum. LOBSTAHS putatively identified 1969 unique parent compounds in 21 869 features that survived the multistage screening process. While P. tricornutum maintained more than 92% of its core lipidome under oxidative stress, patterns in biomarker distribution and abundance indicated remodeling was both subtle and pervasive. Treatment with 150 μM H2O2 promoted statistically significant carbon-chain elongation across lipid classes, with the strongest elongation accompanying oxidation in moieties of monogalactosyldiacylglycerol, a lipid typically localized to the chloroplast. Oxidative stress also induced a pronounced reallocation of lipidome peak area to triacylglycerols. LOBSTAHS can be used with environmental or experimental data from a variety of systems and is freely available at https://github.com/vanmooylipidomics/LOBSTAHS .

  17. Effect of turmeric and curcumin on BP-DNA adducts.

    Science.gov (United States)

    Mukundan, M A; Chacko, M C; Annapurna, V V; Krishnaswamy, K

    1993-03-01

    Many human cancers that are widely prevalent today can be prevented through modifications in life-styles, of which diet appears to be an important agent. Several dietary constituents modulate the process of carcinogenesis and prevent genotoxicity. Many plant constituents including turmeric appear to be potent antimutagens and antioxidants. Therefore the modulatory effects of turmeric and curcumin on the levels of benzo[a]pyrene induced DNA adducts in the livers of rats were studied by the newly developed 32P-postlabelling assay method. Turmeric when fed at 0.1, 0.5 and 3% and the active principle of turmeric (curcumin) when fed at a level of 0.03% in the diet for 4 weeks significantly reduced the level of BP-DNA adducts including the major adduct dG-N2-BP, formed within 24 h in response to a single i.p. injection of benzo[a]pyrene. The significance of these effects in terms of the potential anticarcinogenic effects of turmeric is discussed. Further, these results strengthen the various other biological effects of turmeric which have direct relevance to anticarcinogenesis and chemoprevention.

  18. Measuring Your Peak Flow Rate

    Science.gov (United States)

    ... your child so they can help monitor your child's asthma symptoms . Why Should I Measure My Flow Rate? ... help parents determine what might be triggering their child's asthma. How Do You Use a Peak Flow Meter? ...

  19. Hip adduction and abduction strength profiles in elite, sub-elite and amateur Australian footballers.

    Science.gov (United States)

    Prendergast, Ned; Hopper, Diana; Finucane, Mark; Grisbrook, Tiffany L

    2016-09-01

    It has been reported that obtaining an adduction-to-abduction strength ratio of 90-100%, and an adduction strength equal to that of the uninjured side, are suitable clinical milestones for return to sport following groin injury. Little is known about hip adduction and abduction strength profiles in Australian footballers. This study aimed to compare isometric hip adduction and abduction strength profiles between preferred and non-preferred kicking legs in elite, sub-elite and amateur Australian footballers. Cross sectional study 36 elite, 19 sub-elite and 18 amateur Australian footballers, with a mean age of 24, 19 and 23 years respectively, were included. Maximal hip isometric adduction and abduction strength were measured using a hand held dynamometer with external belt fixation. There were no significant differences in isometric hip adduction (p=0.262) or abduction (p=0.934) strength, or the adduction-to-abduction ratio (p=0.163), between preferred and non-preferred kicking legs, regardless of playing level. Elite players had significantly greater isometric hip adduction and abduction strength than both sub-elite (mean difference; adduction=46.01N, pamateur players (mean difference; adduction=78.72N, p<0.001, abduction=59.11N, p<0.001). There was no significant difference in the adduction-to-abduction ratio between the playing levels (p=0.165). No significant differences were found between preferred and non-preferred kicking legs across the playing levels for isometric hip adduction, abduction or the adduction-to-abduction ratio. This may have implications for developing groin injury prediction and return to sport criteria in Australian footballers. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  20. Acetaminophen Adducts Detected in Serum of Pediatric Patients With Acute Liver Failure.

    Science.gov (United States)

    Alonso, Estella M; James, Laura P; Zhang, Song; Squires, Robert H

    2015-07-01

    Previous studies in patients with acute liver failure identified acetaminophen (APAP) protein adducts in the serum of 12% and 19% of children and adults, respectively, with acute liver failure of indeterminate etiology. This article details the testing of APAP adducts in a subset (n = 393) of patients with varied diagnoses in the Pediatric Acute Liver Failure Study Group (PALFSG). Serum samples were available from 393 participants included in the PALFSG registry. Adduct measurement was performed using validated methods. Participants were grouped by diagnostic category as known APAP overdose, known other diagnosis, and indeterminate etiology. Demographic and clinical characteristics and participant outcomes were compared by adduct status (positive or negative) within each group. APAP adduct testing was positive in 86% of participants with known APAP overdose, 6% with other known diagnoses, and 11% with an indeterminate cause of liver failure. Adduct-positive participants were noted to have marked elevation of serum alanine aminotransferase and aspartate aminotransferase coupled with total serum bilirubin that was significantly lower than adduct-negative patients. In the indeterminate group, adduct-positive patients had different outcomes than adduct-negative patients (P = 0.03); spontaneous survival was 16 of 21 (76%) in adduct-positive patients versus 75 of 169 (44%) in adduct-negative patients. Prognosis did not vary by adduct status in patients with known diagnoses. Furthermore, study is needed to understand the relation of APAP exposure, as determined by the presence of APAP adducts, to the clinical phenotype and outcomes of children with acute liver failure.

  1. S-(3-Aminobenzanthron-2-yl)cysteine in the globin of rats as a novel type of adduct and possible biomarker of exposure to 3-nitrobenzanthrone, a potent environmental carcinogen.

    Science.gov (United States)

    Linhart, Igor; Hanzlíková, Iveta; Mráz, Jaroslav; Dušková, Šárka

    2017-10-01

    3-Nitrobenzanthrone (3-NBA), a potent environmental mutagen and carcinogen, is known to be activated in vivo to 3-benzanthronylnitrenium ion which forms both NH and C2-bound adducts with DNA and also reacts with glutathione giving rise to urinary 3-aminobenzanthron-2-ylmercapturic acid. In this study, acid hydrolysate of globin from rats dosed intraperitoneally with 3-NBA was analysed by HPLC/MS to identify a novel type of cysteine adduct, 3-aminobenzanthron-2-ylcysteine (3-ABA-Cys), confirmed using a synthesised standard. The 3-ABA-Cys levels in globin peaked after single 3-NBA doses of 1 and 2 mg/kg on day 2 to attain 0.25 and 0.49 nmol/g globin, respectively, thereafter declining slowly to 70-80% of their maximum values during 15 days. After dosing rats for three consecutive days with 1 mg 3-NBA/kg a significant cumulation of 3-ABA-Cys in globin was observed. 3-ABA-Cys was also found in the plasma hydrolysate. Herein, after dosing with 1 and 2 mg 3-NBA/kg the adduct levels peaked on day 1 at 0.15 and 0.51 nmol/ml plasma, respectively, thereafter declining rapidly to undetectable levels on day 15. In addition, sulphinamide adducts were also found in the exposed rats, measured indirectly as 3-aminobenzanthrone (3-ABA) split off from globin by mild acid hydrolysis. Levels of both types of adducts in the globin samples parallelled very well with 3-ABA/3-ABA-Cys ratio being around 1:8. In conclusion, 3-ABA-Cys is the first example of arylnitrenium-cysteine adduct in globin representing a new promising class of biomarkers to assess cumulative exposures to aromatic amines, nitroaromatics and heteroaromatic amines.

  2. Including the Copenhagen Adduction Exercise in the FIFA 11+ Provides Missing Eccentric Hip Adduction Strength Effect in Male Soccer Players: A Randomized Controlled Trial.

    Science.gov (United States)

    Harøy, Joar; Thorborg, Kristian; Serner, Andreas; Bjørkheim, André; Rolstad, Linn E; Hölmich, Per; Bahr, Roald; Andersen, Thor Einar

    2017-11-01

    The FIFA 11+ was developed as a complete warm-up program to prevent injuries in soccer players. Although reduced hip adduction strength is associated with groin injuries, none of the exercises included in the FIFA 11+ seem to specifically target hip adduction strength. To investigate the effect on eccentric hip adduction strength of the FIFA 11+ warm-up program with or without the Copenhagen adduction exercise. Randomized controlled trial; Level of evidence, 1. We recruited 45 eligible players from 2 U19 elite male soccer teams. Players were randomized into 2 groups; 1 group carried out the standard FIFA 11+ program, while the other carried out the FIFA 11+ but replaced the Nordic hamstring exercise with the Copenhagen adduction exercise. Both groups performed the intervention 3 times weekly for 8 weeks. Players completed eccentric strength and sprint testing before and after the intervention. Per-protocol analyses were performed, and 12 players were excluded due to low compliance (<67% of sessions completed). The main outcome was eccentric hip adduction strength (N·m/kg). Between-group analyses revealed a significantly greater increase in eccentric hip adduction strength of 0.29 Nm/kg (8.9%; P = .01) in favor of the group performing the Copenhagen adduction exercise, whereas no within-group change was noted in the group that used the standard FIFA 11+ program (-0.02 N·m/kg [-0.7%]; P = .69). Including the Copenhagen adduction exercise in the FIFA 11+ program increases eccentric hip adduction strength, while the standard FIFA 11+ program does not. Registration: Registration: ISRCTN13731446 (International Standard Randomised Controlled Trial Number registry).

  3. Defense Logistics Agency Revenue Eliminations

    National Research Council Canada - National Science Library

    1996-01-01

    The issue of revenue eliminations was identified during our work on the Defense Logistics Agency portion of the Audit of Revenue Accounts in the FY 1996 Financial Statements of the Defense Business Operations Fund...

  4. Proportional counter end effects eliminator

    International Nuclear Information System (INIS)

    Meekins, J.F.

    1976-01-01

    An improved gas-filled proportional counter which includes a resistor network connected between the anode and cathode at the ends of the counter in order to eliminate ''end effects'' is described. 3 Claims, 2 Drawing Figures

  5. Ultrasonic Transducer Peak-to-Peak Optical Measurement

    Directory of Open Access Journals (Sweden)

    Pavel Skarvada

    2012-01-01

    Full Text Available Possible optical setups for measurement of the peak-to-peak value of an ultrasonic transducer are described in this work. The Michelson interferometer with the calibrated nanopositioner in reference path and laser Doppler vibrometer were used for the basic measurement of vibration displacement. Langevin type of ultrasonic transducer is used for the purposes of Electro-Ultrasonic Nonlinear Spectroscopy (EUNS. Parameters of produced mechanical vibration have to been well known for EUNS. Moreover, a monitoring of mechanical vibration frequency shift with a mass load and sample-transducer coupling is important for EUNS measurement.

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

    Science.gov (United States)

    Brahma, Sanjaya; Shivashankar, S. A.

    2015-12-01

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

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

    International Nuclear Information System (INIS)

    Sun, H.F.; He, L.; Liu, Y.F.; Liu, K.X.; Lu, X.Y.; Wang, J.J.; Ma, H.J.; Li, K.

    2000-01-01

    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

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

    International Nuclear Information System (INIS)

    Yue Jiang; Lin Weizhen; Yao Side; Lin Nianyun; Zhu Dayuan

    1999-01-01

    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=5-30x10 8 dm 3 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

  9. High-Average, High-Peak Current Injector Design

    CERN Document Server

    Biedron, S G; Virgo, M

    2005-01-01

    There is increasing interest in high-average-power (>100 kW), um-range FELs. These machines require high peak current (~1 kA), modest transverse emittance, and beam energies of ~100 MeV. High average currents (~1 A) place additional constraints on the design of the injector. We present a design for an injector intended to produce the required peak currents at the injector, eliminating the need for magnetic compression within the linac. This reduces the potential for beam quality degradation due to CSR and space charge effects within magnetic chicanes.

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

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

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

    International Nuclear Information System (INIS)

    Batal, Mohamed; Boudry, Isabelle; Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Bérard, Izabel; Cléry-Barraud, Cécile

    2013-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Batal, Mohamed [Laboratoire «Lésions des Acides Nucléiques», Université Joseph Fourier – Grenoble 1, CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); Boudry, Isabelle; Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine [Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); Bérard, Izabel [Laboratoire «Lésions des Acides Nucléiques», Université Joseph Fourier – Grenoble 1, CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Cléry-Barraud, Cécile [Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); and others

    2013-12-15

    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.

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

    Directory of Open Access Journals (Sweden)

    Soon-Hyuck Lee

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

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

    Directory of Open Access Journals (Sweden)

    Gurpreet Kour

    2013-01-01

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

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

    Science.gov (United States)

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

    2009-04-01

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

  16. Proton and hydrogen atom adducts to cytosine. An experimental and computational study

    Science.gov (United States)

    Yao, Chunxiang; Turecek, Frantisek; Polce, Michael J.; Wesdemiotis, Chrys

    2007-09-01

    Cytosine cations were generated by chemical ionization and fast-atom bombardment of cytosine, and their dissociations in the gas phase were studied by tandem mass spectrometry and quantum chemistry calculations at levels of theory up to CCSD(T)/aug-cc-pVTZ. Metastable cytosine cations undergo loss of NH3, H2O, and [CHNO] molecules as major dissociations. Mechanisms for these dissociations were established by a combination of MS3, deuterium labeling, and calculations. Several tautomers of protonated cytosine were identified to exist as local energy minima. The tautomers are predicted to undergo facile prototropic isomerizations at internal energies below the lowest ion-dissociation thresholds. The lowest-energy elimination of ammonia proceeds from open-ring structures and is accompanied by exchange of the N-3 and N-7 positions in cytosine, so that either nitrogen atom can be lost in the ammonia molecule. Cytosine radicals corresponding to hydrogen atom adducts are stable when formed by femtosecond electron transfer to the cations. A fraction of the radicals dissociate by loss of hydrogen atom to form cytosine tautomers. Ring-cleavage dissociations leading to the loss of CO and HNCO are less abundant, and are predicted to proceed from excited electronic states accessed by vertical electron transfer.

  17. Varus thrust in women with early medial knee osteoarthritis and its relation with the external knee adduction moment.

    Science.gov (United States)

    Mahmoudian, Armaghan; van Dieen, Jaap H; Bruijn, Sjoerd M; Baert, Isabel Ac; Faber, Gert S; Luyten, Frank P; Verschueren, Sabine Mp

    2016-11-01

    Varus thrust, defined as an abrupt increase of the knee varus angle during weight-bearing in gait, has been shown to be present in patients with moderate to severe knee osteoarthritis and is considered to be one of the risk factors for progression of symptomatic medial knee osteoarthritis. We evaluated the presence and magnitude of varus thrust and its relation with the Knee Adduction Moment in women with early medial knee osteoarthritis, and compared it to that in a group of controls and in a group of subjects with established medial knee osteoarthritis. Twenty-seven women with early medial knee osteoarthritis, 20 women with established medial knee osteoarthritis and 24 asymptomatic controls were evaluated. Varus thrust was estimated as an increase of the knee varus angle during the weight-bearing phase of gait at self-selected speed, assessed by 3D motion analysis. Varus thrust was significantly higher in both early and established osteoarthritis groups compared to the control group (Pvarus thrust was significantly correlated with the second peak knee adduction moment. Higher varus thrust was found both in early and established stages of knee osteoarthritis, suggesting that problems with dynamic stabilization of the knee are present early in the development of knee osteoarthritis. This highlights the necessity of considering dynamic alignment in rehabilitation already in the early stages of the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Metabolic Activation of the Antibacterial Agent Triclocarban by Cytochrome P450 1A1 Yielding Glutathione Adducts

    Science.gov (United States)

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

    2014-01-01

    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 14C-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 14C-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. Aromatic DNA adducts in human white blood cells and skin after dermal application of coal tar

    Energy Technology Data Exchange (ETDEWEB)

    Godschalk, R.W.L.; Ostertag, J.U.; Moonen, E.J.C.; Neumann, H.A.M.; Kleinjans, J.C.S.; Schooten, F.J. van [University of Maastricht, Maastricht (Netherlands). Dept. of Health Risk Analysis and Toxicology

    1998-09-01

    A group of eczema patients topically treated with coal tar (CT) ointments was used as a model population to examine the applicability of DNA adducts in white blood cell (WBC) subpopulations as a measure of dermal exposure to polycyclic aromatic hydrocarbons (PAHs). Aromatic DNA adducts were examined by {sup 32}P-postlabeling in exposed skin and WBC subsets, and urinary excretion of PAH metabolites was determined to assess the whole-body burden. The median urinary excretion of 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene was 0.39 and 0.01 {mu}mol/mol creatinine respectively, before the dermal application of CT ointments. After treatment for 1 week, these levels increased to 139.7 and 1.18 {mu}mol/mol creatinine respectively, indicating that considerable amounts of PAHs were absorbed. Median aromatic DNA adduct levels were significantly increased in skin from 2.9 adduct/10{sup 8} nucleotides before treatment to 63.3 adducts/10{sup 8} nt after treatment with CT, in monocytes from 0.28 to 0.86 adducts/10{sup 8} nt, in lymphocytes from 0.33 to 0.89 adducts/10{sup 8} nt and in granulocytes from 0.28 to 0.54 adducts/10{sup 8} nt. A week after stopping the CT treatment, the DNA adduct levels in monocytes and granulocytes were reduced to 0.38 and 0.38 adducts/10{sup 8} nt respectively, whereas the adduct levels in lymphocytes remained enhanced. Total DNA adduct levels in skin correlated with the adduct levels in monocytes and lymphocytes. Excretion of urinary metabolites during the first week of treatment was correlated with the percentage of the skin surface treated with CT ointment and decreased within a week after the cessation of treatment. 3-Hydroxybenzo(a)pyrene excretion, correlated with the levels of DNA adducts in skin that comigrated with benzo(a)pyrene-diol-epoxide-DNA. This study indicates that the DNA adduct levels in mononuclear WBCs can possibly be used as a surrogate for skin DNA after dermal exposure to PAHs. 34 refs., 4 figs., 1 tab.

  20. Detection of Riddelliine-Derived DNA Adducts in Blood of Rats Fed Riddelliine

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2002-09-01

    Full Text Available Abstract: We have previously shown that riddelliine, a naturally occurring genotoxic pyrrolizidine alkaloid, induces liver tumors in rats and mice through a genotoxic mechanism mediated by the formation of a set of eight 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine ( DHP-derived DNA adducts. In this study we report the formation of these DHP-derived DNA adducts in blood DNA of rats fed riddelliine. In an adduct formation and removal experiment, male and female F344 rats (8 weeks of age were administered riddelliine by gavage at a single dose of 10.0 mg/kg body weight in 0.1 M phosphate buffer. At 8, 24, 48, and 168 hrs after dosing, the levels of DHP-derived DNA adduct in blood and liver were determined by 32P-postlabeling/HPLC. Maximum DNA adduct formation occurred at 48 hr after treatment. From 48 to 168 hours, the adduct levels in female rat blood were 4-fold greater than those in male rats. In a dose response experiment, female rats were gavaged 0.1 and 1.0 mg/kg doses of riddelliine for three consecutive days and the DHPderived DNA adducts in blood DNA were assayed. The levels of the DHP-derived DNA adducts in blood of rats receiving 0.1 and 1.0 mg/kg doses were 12.9 and 51.8 adducts/107 nucleotides. These results suggest that: (i leucocyte DNA can bind with DHP to form a set of DHP-derived DNA adducts generated in liver; (ii DHP-derived DNA adducts in blood can serve as a potential non-invasive biomarkers for assessing the exposure to riddelliine.

  1. Measles elimination: progress and challenges.

    Science.gov (United States)

    Cutts, F T; Henao-Restrepo, A; Olivé, J M

    1999-10-29

    The accelerating progress in reducing measles incidence and mortality in many parts of the world has led to calls for its global eradication during the next 10-15 years. Three regions have established goals of elimination of indigenous transmission of measles. The strategy used in the Americas of a mass 'catchup' campaign of children 9 months to 15 years of age, high coverage through routine vaccination of infants, intensive surveillance and follow-up campaigns to prevent excessive build-up of susceptibles has had great success in reducing measles transmission close to zero. However, while these developments are impressive, much remains to be done to reduce measles-associated mortality in western and central Africa, where less than half of children are currently receiving measles vaccine and half a million children die from measles each year. The obstacles to global measles eradication are perceived to be predominantly political and financial. There are also technical questions, however. These include the refinement of measles elimination strategies in the light of recent outbreaks in the Americas; the implications of the HIV epidemic for measles elimination, issues around injection safety, and concerns about the possibility that secondary vaccine failures will contribute in sustaining transmission in highly vaccinated populations. The global priorities are to improve measles control in low income countries, increase awareness among industrialized countries of the importance of measles, and conduct studies to answer the technical questions about measles elimination strategies.

  2. Neurofeedback training for peak performance

    OpenAIRE

    Marek Graczyk; Maria Pąchalska; Artur Ziółkowski; Grzegorz Mańko; Beata Łukaszewska; Kazimierz Kochanowicz; Andrzej Mirski; Iurii D. Kropotov

    2014-01-01

    [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 spontaneou...

  3. Twin Peaks (B/W)

    Science.gov (United States)

    1997-01-01

    The Twin Peaks are modest-size hills to the southwest of the Mars Pathfinder landing site. They were discovered on the first panoramas taken by the IMP camera on the 4th of July, 1997, and subsequently identified in Viking Orbiter images taken over 20 years ago. The peaks are approximately 30-35 meters (-100 feet) tall. North Twin is approximately 860 meters (2800 feet) from the lander, and South Twin is about a kilometer away (3300 feet). The scene includes bouldery ridges and swales or 'hummocks' of flood debris that range from a few tens of meters away from the lander to the distance of the South Twin Peak. The large rock at the right edge of the scene is nicknamed 'Hippo'. This rock is about a meter (3 feet) across and 25 meters (80 feet) distant.Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech). The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  4. Proteomic profiling of acrolein adducts in human lung epithelial cells

    Science.gov (United States)

    Spiess, Page C.; Deng, Bin; Hondal, Robert J.; Matthews, Dwight E.; van der Vliet, Albert

    2011-01-01

    Acrolein (2,3-propenal) is a major indoor and outdoor air pollutant originating largely from tobacco smoke or organic combustion. Given its high reactivity, the adverse effects of inhaled acrolein are likely due to direct interactions with the airway epithelium, resulting in altered epithelial function, but only limited information exists to date regarding the primary direct cellular targets for acrolein. Here, we describe a global proteomics approach to characterize the spectrum of airway epithelial protein targets for Michael adduction in acrolein-exposed bronchial epithelial (HBE1) cells, based on biotin hydrazide labeling and avidin purification of biotinylated proteins or peptides for analysis by LC-MS/MS. Identified protein targets included a number of stress proteins, cytoskeletal proteins, and several key proteins involved in redox signaling, including thioredoxin reductase, thioredoxin, peroxiredoxins, and glutathione S-transferase π. Because of the central role of thioredoxin reductase in cellular redox regulation, additional LC-MS/MS characterization was performed on purified mitochondrial thioredoxin reductase to identify the specific site of acrolein adduction, revealing the catalytic selenocysteine residue as the target responsible for enzyme inactivation. Our findings indicate that these approaches are useful in characterizing major protein targets for acrolein, and will enhance mechanistic understanding of the impact of acrolein on cell biology. PMID:21704744

  5. Fullerene–Carbene Lewis Acid–Base Adducts

    KAUST Repository

    Li, Huaping

    2011-08-17

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

  6. Kinetics, mechanism and thermodynamics of bisulfite-aldehyde adduct formation

    Energy Technology Data Exchange (ETDEWEB)

    Olson, T.M.; Boyce, S.D.; Hoffmann, M.R.

    1986-04-01

    The kinetics and mechanism of bisulfite addition to benzaldehyde were studied at low pH in order to assess the importance of this reaction in stabilizing S(IV) in fog-, cloud-, and rainwater. Previously, the authors established that appreciable concentrations of the formaldehyde-bisulfite adduct (HMSA) are often present in fogwater. Measured HMSA concentrations in fogwater often do not fully account for observed excess S(IV) concentrations, however, so that other S(IV)-aldehyde adducts may be present. Reaction rates were determined by monitoring the disappearance of benzaldehyde by U.V. spectrophotometry under pseudo-first order conditions, (S(IV))/sub T/ >>(phi-CHO)/sub T/, in the pH range 0 - 4.4 at 25/sup 0/C. The equilibrium constant was determined by dissolving the sodium salt of the addition compound in a solution adjusted to pH 3.9, and measuring the absorbance of the equilibrated solution at 250 nm. A literature value of the extinction coefficient for benzaldehyde was used to calculate the concentration of free benzaldehyde. All solutions were prepared under an N/sub 2/ atmosphere using deoxygenated, deionized water and ionic strength was maintained at 1.0 M with sodium chloride.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    The lymphocyte bulky PAH-DNA adduct levels have been studied in persons occupationally exposed to ambient air pollution. The exposure group consisted of 90 healthy, nonsmoking bus drivers from the Copenhagen area, divided into three exposure groups according to driving area, and 60 rural controls...... (smokers and non-smokers). PAH-DNA adducts were determined by 32P-postlabelling with the butanol enrichment procedure. The bus drivers answered a comprehensive questionnaire on passive smoking, residential area, diet and other potential confounding variables. A significantly higher adduct level...... was observed in bus drivers working in central Copenhagen (1.214 fmol/microg DNA, n = 49) compared with both those driving in the dormitory (median: 0.507 fmol/microg DNA, P = 0.046, n = 16) and suburban (median: 0.585 fmol/microg DNA, P = 0.041, n = 25) areas. All three groups had higher adduct levels than...

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

    Science.gov (United States)

    2010-07-01

    ... phenol, ethylene oxide adduct. 721.3700 Section 721.3700 Protection of Environment ENVIRONMENTAL..., ethylene oxide adduct. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid, ester with styrenated phenol, ethylene oxide...

  9. Distribution of DNA adducts in the respiratory tract of rats exposed to diesel exhaust

    International Nuclear Information System (INIS)

    Bond, J.A.; Wolff, R.K.; Harkema, J.R.; Mauderly, J.L.; Henderson, R.F.; Griffith, W.C.; McClellan, R.O.

    1988-01-01

    Diesel exhaust, Inhaled chronically at high concentrations, induced tumors that were located exclusively In the peripheral lung of rats. The purpose of this study was to determine if differences in the level of DNA adducts among the regions of the respiratory tract paralleled the site of tumors. Groups of male F344/N rats were exposed 7 h/day, 5 day/wk for 12 wk to diesel engine exhaust at a soot concentration of 10 mg/m 3 or were sham-exposed to air. Respiratory tract tissues were dissected and DNA was isolated from the dissected samples and analyzed for the presence of adducts using the 32 P-postlabeling assay. The highest level of total DNA adducts occurred In peripheral lung tissue (∼ 18 adducts per 10 9 bases). About 1/4 to 1/5 the level of DNA adducts was detected in the nasal tissues as in peripheral lung. There were less than 3 adducts per 10 9 bases n each of the regions of the major conducting airways (.e., trachea, bronchi, axial airway). The data from this study indicate that higher levels of total DNA adducts were present In tissues where exhaust-induced tumors were located. These data suggest that DNA adduct levels in discrete locations of the respiratory tract may be good measures of the 'effective dose' of carcinogenic compounds. (author)

  10. Inert Reassessment Document for Poly(oxyethylene) adducts of mixed phytosterols

    Science.gov (United States)

    Poly(oxyethy1ene) adducts of mixed phytosterols is uncategorized as to list classification status. Based upon the reasonable certainty of no harm safety finding, the List 4B classification for poly(oxyethy1ene) adducts of mixed phytosterols is affirmed.

  11. Abundance of DNA adducts of 4-oxo-2-alkenals, lipid peroxidation-derived highly reactive genotoxins.

    Science.gov (United States)

    Kawai, Yoshichika; Nuka, Erika

    2018-01-01

    Reactive oxygen species and their reaction products can damage DNA to form mutagenic lesions. Among the reactive species, lipid peroxidation-derived aldehydes react with nucleobases and form bulky exocyclic adducts. Many types of aldehyde-derived DNA adducts have been characterized, identified and detected in vitro and in vivo , whereas relative quantitative and pathophysiological contributions of each adduct still remain unclear. In recent years, an abundant class of DNA adducts derived from 4-oxo-2-alkenals have been identified, in addition to classic aldehyde-derived adducts. The presence of 4-oxo-2-alkenal-derived DNA adducts associated with age-related diseases has been revealed in rodents and humans. In vitro studies have demonstrated that 4-oxo-2-alkenals, as compared with other classes of lipid peroxidation-derived aldehydes, are highly reactive with nucleobases. It has been generally recognized that 4-oxo-2-alkenals are generated through oxidative degradation of the corresponding 4-hydroperoxy-2-alkenals, homolytic degradation products of polyunsaturated fatty acid hydroperoxides. Our recent results have also shown an alternative pathway for the formation of 4-oxo-2-alkenals, in which 2-alkenals could undergo the metal-catalyzed autoxidation resulting in the formation of the corresponding 4-oxo-2-alkenals. This review summarizes the basis of the formation of lipid peroxidation-derived genotoxic aldehydes and their covalent adduction to nucleobases, especially focusing on the abundance of 4-oxo-2-alkenal-derived DNA adducts.

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  13. γIrradiation induced formation of PCB-solvent adducts in aliphatic solvents

    International Nuclear Information System (INIS)

    Lepine, F.; Milot, S.; Gagne, N.

    1990-01-01

    γIrradiation induced formation of PCB-solvent adducts was investigated as a model for PCB residues in irradiated food. Formation of cyclohexyl adducts of PCBs was found to be significant when pure PCB congeners and Aroclor mixture were irradiated in cyclohexane and cyclohexene. Reaction pathways were investigated, and the effects of oxygen and electron scavenger were studied

  14. Condensed tannin-resorcinol adducts and their use in wood-laminating adhesives: An exploratory study

    Science.gov (United States)

    Richard W. Hemingway; R.E. Kreibich

    1984-01-01

    The reaction of a tannin extract (containing about 30% carbohydrate) from loblolly pine (Pinus taeda L.) bark (two parts) and resorcinol (one part) at 120°C for 24 h with acetic acid catalyst gave a product containing predominantly oligomeric procyanidin-4-resorcinol adducts (39%), unreacted resorcinol (22%), carbohydrate (20%). the resorcinol adduct...

  15. Drivers of peak sales for pharmaceutical brands

    NARCIS (Netherlands)

    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.

  16. Genetic polymorphisms in catalase and CYP1B1 determine DNA adduct formation by bento(a)pyrene ex vivo

    NARCIS (Netherlands)

    Schults, Marten A.; Chiu, Roland K.; Nagle, Peter; Kleinjans, J C; van Schooten, Frederik Jan; Godschalk, Roger W.

    Genetic polymorphisms can partially explain the large inter-individual variation in DNA adduct levels following exposure to polycyclic aromatic hydrocarbons. Effects of genetic polymorphisms on DNA adduct formation are difficult to assess in human studies because exposure misclassification

  17. Comparison of EMG activity on abdominal muscles during plank exercise with unilateral and bilateral additional isometric hip adduction.

    Science.gov (United States)

    Kim, Soo-Yong; Kang, Min-Hyeok; Kim, Eui-Ryong; Jung, In-Gui; Seo, Eun-Young; Oh, Jae-Seop

    2016-10-01

    The aim of this study was to investigate the effects of additional isometric hip adduction during the plank exercise on the abdominal muscles. Twenty healthy young men participated in this study. Surface electromyography (EMG) was used to monitor the activity of the bilateral rectus abdominis (RA), the internal oblique (IO), and the external oblique (EO) muscles. The participants performed three types of plank exercise; the standard plank exercise, the plank exercise with bilateral isometric hip adduction, and the plank exercise with unilateral isometric hip adduction. All abdominal muscle activity was significantly increased during the plank exercise combined with the bilateral and unilateral isometric hip adduction compared with the standard plank exercise (pmuscle activity was significantly increased during the unilateral isometric hip adduction compared with the bilateral isometric hip adduction (pabdominal muscle activity. In particular, the unilateral isometric hip adduction is a more beneficial exercise than the bilateral isometric hip adduction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Quantitation of 4,4′-methylene diphenyl diisocyanate human serum albumin adducts

    Directory of Open Access Journals (Sweden)

    Leah G. Luna

    2014-01-01

    Full Text Available 4,4′-Methylene diphenyl diisocyanate (herein 4,4′-MDI is used in the production of polyurethane foams, elastomers, coatings, adhesives and the like for a wide range of commercial products. Occupational exposure to MDI levels above current airborne exposure limits can elicit immune mediated hypersensitivity reactions such as occupational asthma in sensitive individuals. To accurately determine exposure, there has been increasing interest in developing analytical methods to measure internal biomarkers of exposure to MDI. Previous investigators have reported methodologies for measuring MDI diamine metabolites and MDI-Lysine (4,4′-MDI-Lys adducts. The purpose of this study was to develop and validate an ultra performance liquid chromatography isotope dilution tandem mass spectrometry (UPLC-ID/MS/MS quantitation method via a signature peptide approach to enable biomonitoring of 4,4′-MDI adducted to human serum albumin (HSA in plasma. A murine, anti-4,4′-MDI monoclonal IgM antibody was bound to magnetic beads and utilized for enrichment of the MDI adducted HSA. Following enrichment, trypsin digestion was performed to generate the expected 414 site (primary site of adduction 4,4′-MDI-adducted HSA signature peptide that was quantified by UPLC-ID/MS/MS. An Agilent 6530 UPLC/quadrupole time of flight MS (QTOF system was utilized for intact adducted protein analysis and an Agilent 6490 UPLC/MS/MS system operated in multiple reaction monitoring (MRM mode was utilized for quantification of the adducted signature peptide biomarker both for in chemico and worker serum samples. Worker serum samples were initially screened utilizing the previously developed 4,4′-MDI-Lys amino acid method and results showed that 12 samples were identified as quantifiable for 4,4′-MDI-Lys adducts. The signature peptide adduct approach was applied to the 12 worker samples identified as quantifiable for 4,4′-MDI-Lys adducts. Results indicated no positive results

  19. Bracken (Pteridium aquilinum)-induced DNA adducts in mouse tissues are different from the adduct induced by the activated form of the Bracken carcinogen ptaquiloside.

    Science.gov (United States)

    Freitas, R N; O'Connor, P J; Prakash, A S; Shahin, M; Povey, A C

    2001-02-23

    Following treatment with bracken fern (Pteridium aquilinum) extract and bracken spores a number of DNA adducts were detected by (32)P-postlabeling. Three of these adducts have been described previously (Povey et al., Br. J. Cancer (1996) 74, 1342-1348) and in this study, using a slightly different protocol, four new adducts, with higher chromatographic mobility, were detected at levels ranging from 50 to 230% of those previously described. When DNA was treated in vitro with activated ptaquiloside (APT) and analysed by butanol extraction or nuclease P1 treatment, only one adduct was detected by (32)P-postlabeling. This adduct was not present in the DNA from mice treated with bracken fern or spores, suggesting either that bracken contains genotoxins other than ptaquiloside or that the metabolism of ptaquiloside produces genotoxins not reflected by activated ptaquiloside. However, as the ATP-derived adduct has been detected previously in ileal DNA of bracken-fed calves, species-specific differences in the metabolism of bracken genotoxins may exist, thereby leading to differences in their biological outcomes. Copyright 2001 Academic Press.

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

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Myungkoo [Iowa State Univ., Ames, IA (United States)

    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 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.

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

    International Nuclear Information System (INIS)

    Suh, Myungkoo.

    1995-01-01

    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 G 2 or G 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 2 -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-N 2 -dG

  2. Cancer risks: Strategies for elimination

    International Nuclear Information System (INIS)

    Bannasch, P.

    1987-01-01

    This book deals with the possibilities for identifying and eliminating cancer risk factors. The current state of knowledge on the detection, assessment and elimination of chemical, physical (radiation), and biological (viruses) risk factors are comprehensively presented in 15 contributions. Chemical risk factors resulting from smoking and environmental contamination are given special attention. The coverage of cancer risks by radiation includes some of the consequences of the Chernobyl disaster. Finally, the discussion of the possible risks that certain viruses hold for cancer in man is intended to further the development of vaccinations against these viral infections. The information is directed not only at specialists, but also at a wider interested audience. Its primary aim is to convey established findings that are already being used for cancer prevention. Furthermore, the book aims to promote more intense research in the field of primary cancer prevention. Contents: General aspects; chemical carcinogens: Risk assessment; chemical carcinogens: Primary prevention; physical carcinogens - Oncogenic viruses and subject index

  3. Retrospective detection of sulfur mustard exposure by mass spectrometric analysis of adducts to albumin and hemoglobin: An in vivo study

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Degenhardt-Langelaan, C.E.A.M.; Hulst, A.G.

    2008-01-01

    The persistence in rats of sulfur mustard adducts to albumin and hemoglobin was studied in vivo after exposure (intravenously; 0.3 mg/kg; approximately 0.1 LD50) of rats to sulfur mustard. The albumin adduct (S-HETE)Cys-Pro-Tyr was detectable up to 7 days after the exposure, while the adduct to the

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

    Science.gov (United States)

    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.

  5. Non Covalent Interactions and Internal Dynamics in Adducts of Freons

    Science.gov (United States)

    Caminati, Walther; Gou, Qian; Evangelisti, Luca; Feng, Gang; Spada, Lorenzo; Vallejo-López, Montserrat; Lesarri, Alberto; Cocinero, Emilio J.

    2014-06-01

    The complexation of chlorofluorocarbons (CFCs) with atmospheric water and pollutants of the atmosphere affects their reactivity and it seems to accelerate, for example, the decomposition rate of freons in the atmosphere [1]. For this reason we characterized shapes, stabilities, nature of the non-covalent interactions, structures and internal dynamics of a number of complexes of CFCs with water and of their dimers or oligomers by rotational spectroscopy. It has been found that hydrogenated CFCs form adducts with other molecules through weak hydrogen bonds (WHBs). Their C-H groups can act as proton donors, enhanced by the electron withdrawing of the halogen atoms, interacting with the electron rich regions of the partner molecules [2]. Also in adducts or oligomers of hydrogenated CFCs the monomer units are held together by nets of WHBs [3]. When CFCs are perhalogenated, the positive electrostatic region ("σ-hole") can interact electrostatically with negative sites of another, or of the same molecular entity, giving rise, according to IUPAC, to the so called halogen bond (HaB). However, it has been observed that when the perhalogenated CFCs has a Π electron system, a lone pair•••Π interaction (Bürgi-Dunitz) is favoured [4]. We describe here the HaBs that CF4 and CF3Cl form with a variety of partner molecules such as water, ammonia, dimethyl ether, etc. Important spectroscopic features outline strong dynamics effects taking place in this kind of complex. References [1] V. Vaida, H. G. Kjaergaard, K. J. Feierabend, Int. Rev. Phys. Chem. 22 (2003) 203. [2] See, for example: W. Caminati, S. Melandri, A. Maris, P. Ottaviani, Angew. Chem. Int. Ed. 45 (2006) 2438. [3] G. Feng, L. Evangelisti, I. Cacelli, L. Carbonaro, G. Prampolini, W. Caminati, Chem. Commun. 50 (2014) 171. [4] Q. Gou, G. Feng, L. Evangelisti, W. Caminati, Angew. Chem. Int. Ed. 52 (2013) 52 11888.

  6. Measuring DNA nucleobase adducts using neutral hydrolysis and liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Tarun, Maricar; Rusling, James F

    2005-01-01

    The detection and identification of DNA adducts is important for predicting human cancer risk posed by chemicals and for uncovering potential genotoxicity of new drug and agricultural chemical candidates. For compounds that react with DNA to form N7-guanine and/or N3-adenine adducts, neutral thermal hydrolysis provides a simple procedure for sample preparation. The N7-guanine and N3-adenine adducts are selectively ejected from the DNA chain, resulting in a clean sample matrix enriched in nucleobase adducts. Coupling neutral thermal hydrolysis with liquid chromatography-mass spectrometry (LC-MS) provides sensitive methods to detect and quantitate DNA adducts, and structural information is provided by MS. Combining these technologies with capillary liquid chromatography sample preconcentration systems can provide exquisitely sensitive detection. In this review, we first summarize the chemistry of nucleobase adduct formation, briefly summarize modern methods to detect DNA adducts, and then describe neutral thermal hydrolysis coupled to LC-MS/MS and some of its applications to DNA damage studies. Finally, we review recent applications of neutral thermal hydrolysis and LC-MS to toxicity screening of chemicals.

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

    International Nuclear Information System (INIS)

    Sagiv, Sharon K.; Gaudet, Mia M.; Eng, Sybil M.; Abrahamson, Page E.; Shantakumar, Sumitra; Teitelbaum, Susan L.; Bell, Paula; Thomas, Joyce A.; Neugut, Alfred I.; Santella, Regina M.; Gammon, Marilie D.

    2009-01-01

    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

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

    International Nuclear Information System (INIS)

    Hou Qin; Sun Hongfang; Shi Jingyuan; Liu Yuanfang; Wang Jianjun; Lu Xiangyang; Li Kun; Zhao Qiang

    1997-01-01

    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 10 3 -10 4 adducts/10 12 nucleotides, and the adducts increased linearly with increasing dose of nicotine; the adducts number of liver DNA reached to 10 4 -10 5 adducts/10 12 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

  9. Replication of acetylaminofluorene-adducted plasmids in human cells: Spectrum of base substitutions and evidence of excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Mah, M.C.; Boldt, J.; Maher, V.M.; McCormick, J.J. (Michigan State Univ., East Lansing (United States)); Culp, S.J. (National Center for Toxicological Research, Jefferson, AR (United States))

    1991-11-15

    In rats fed the liver carcinogen 2-acetylaminofluorene (AAF), the two most abundant types of DNA adduct are N-(deoxyguanosin-8-yl)-2-acetylaminofluorene and its deacetylated derivative. When plasmids carrying AAF adducts replicate in bacteria, the predominant mutations are frameshifts, whereas with deacetylated (AF) adducts, they are mainly base substitutions, just as the authors found when plasmids carrying AF adducts replicated in human cells. The authors have investigated the frequency and spectrum of mutations induced when a shuttle vector carrying AAF adducts (85% bound to the C8 position of guanine, 15% to the N{sup 2} position) replicated in human cells. The frequency induced per initial AAF adduct was higher than with AF adducts, but the kinds of mutations were similar - i.e., 85% base substitutions, principally G {center dot} C {yields} T {center dot} A transversions. There was good correlation between the hot spots for mutations and hot spots for AAF adduct formation, suggesting that mutational hot spots reflect preferential binding of the carcinogen to DNA. {sup 32}P-postlabeling analysis of the adducts before and after the DNA was transfected of AAF adducts and that 85% of both types of adducts were removed within 3.5 hours, most probably by excision repair.

  10. Pulse radiolysis studies of the interaction of tea polyphenol derivatives with oxidizing OH adduct of thymine

    International Nuclear Information System (INIS)

    Jiang Yue; Li Hucheng; Yao Side; Zuo Zhihua; Wang Zailan; Zhang Jiashan; Lin Nianyun

    1996-01-01

    The electron transfer reactions between oxidizing OH adduct of thymine with tea polyphenol derivatives has been investigated by pulse radiolysis. The tea polyphenol derivatives are identified as good antioxidants for reduction of oxidizing OH adducts of thymine. From buildup kinetic analysis of radical phenoxyl product, the rate constants for reactions of the N 3 radical with tea polyphenol derivatives have been determined to be (8-9) x 10 9 dm 3 /mol s, while the rate constants of electron transfer from tea polyphenol derivatives to oxidizing OH adducts of thymine was obtained to be around 10 9 dm 3 /mol s. Copyright direct C 1996 Elsevier Science Ltd

  11. Mutagenic replication in human cell extracts of DNA containing site-specific N-2-acetylaminofluorene adducts.

    OpenAIRE

    Thomas, D C; Veaute, X; Kunkel, T A; Fuchs, R P

    1994-01-01

    We have analyzed the effects of site-specific N-2-acetylaminofluorene (AAF) adducts on the efficiency and frameshift fidelity of bidirectional replication of double-stranded DNA in a human cell extract. Plasmid vectors were constructed containing the simian virus 40 origin of replication and single AAF adducts at one of three guanines in the Nar I sequence GGCGCC in a lacZ reporter gene. The presence of an AAF adduct diminishes replication efficiency in HeLa cell extracts by 70-80%. Replicati...

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

    Science.gov (United States)

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

    2015-12-21

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    for analysis of Hb adducts by liquid chromatography-mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide......, and ethylene oxide, were increased in tobacco smokers. Highly significant correlations were found between cord and maternal blood with regard to measured adduct levels of the three compounds. The mean cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27-0.86) for acrylamide, 0.38 (range 0.......20-0.73) for glycidamide, and 0.43 (range 0.17-1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38-0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together...

  14. Neurofeedback training for peak performance.

    Science.gov (United States)

    Graczyk, Marek; Pąchalska, Maria; Ziółkowski, Artur; Mańko, Grzegorz; Łukaszewska, Beata; Kochanowicz, Kazimierz; Mirski, Andrzej; Kropotov, Iurii D

    2014-01-01

    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). 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. 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.

  15. Neurofeedback training for peak performance

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    Autrup, Herman; Essigmann, John M.; Croy, Robert G.

    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...... compared to aflatoxin B1, the binding level of benzo(a)pyrene to both bronchial and colonic DNA was generally higher. The major adducts formed in both tissues by the interaction of aflatoxin B1 and DNA were chromatographically identical to 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1 (Structure 1...... 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...

  17. Elimination Problems in Infants and Children

    Science.gov (United States)

    ... Infants and Children Chest Pain, Acute Chest Pain, Chronic Cold and Flu Cough Diarrhea Ear Problems Elimination Problems Elimination Problems in Infants and Children Eye Problems Facial Swelling Feeding Problems in Infants ...

  18. Formal algorithmic elimination for PDEs

    CERN Document Server

    Robertz, Daniel

    2014-01-01

    Investigating the correspondence between systems of partial differential equations and their analytic solutions using a formal approach, this monograph presents algorithms to determine the set of analytic solutions of such a system and conversely to find differential equations whose set of solutions coincides with a given parametrized set of analytic functions. After giving a detailed introduction to Janet bases and Thomas decomposition, the problem of finding an implicit description of certain sets of analytic functions in terms of differential equations is addressed. Effective methods of varying generality are developed to solve the differential elimination problems that arise in this context. In particular, it is demonstrated how the symbolic solution of partial differential equations profits from the study of the implicitization problem. For instance, certain families of exact solutions of the Navier-Stokes equations can be computed.

  19. Facility Location with Double-peaked Preferences

    DEFF Research Database (Denmark)

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

    2015-01-01

    We study the problem of locating a single facility on a real line based on the reports of self-interested agents, when agents have double-peaked preferences, with the peaks being on opposite sides of their locations. We observe that double-peaked preferences capture real-life scenarios and thus...... complement the well-studied notion of single-peaked preferences. We mainly focus on the case where peaks are equidistant from the agents’ locations and discuss how our results extend to more general settings. We show that most of the results for single-peaked preferences do not directly apply to this setting...

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

    Directory of Open Access Journals (Sweden)

    HASSAN ALLOUCH

    2013-12-01

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

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

    International Nuclear Information System (INIS)

    Sun, J.D.; McBride, S.M.

    1988-01-01

    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 14 C-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 14 C-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)

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

    Science.gov (United States)

    Hanrahan, Kevin G.

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

  3. Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from a Drug Acyl Glucuronide Metabolite: Multiple Albumin Adductions in Diclofenac Patients

    Science.gov (United States)

    Hammond, Thomas G.; Meng, Xiaoli; Jenkins, Rosalind E.; Maggs, James L.; Castelazo, Anahi Santoyo; Regan, Sophie L.; Bennett, Stuart N. L.; Earnshaw, Caroline J.; Aithal, Guruprasad P.; Pande, Ira; Kenna, J. Gerry; Stachulski, Andrew V.; Park, B. Kevin

    2014-01-01

    Covalent protein modifications by electrophilic acyl glucuronide (AG) metabolites are hypothetical causes of hypersensitivity reactions associated with certain carboxylate drugs. The complex rearrangements and reactivities of drug AG have been defined in great detail, and protein adducts of carboxylate drugs, such as diclofenac, have been found in liver and plasma of experimental animals and humans. However, in the absence of definitive molecular characterization, and specifically, identification of signature glycation conjugates retaining the glucuronyl and carboxyl residues, it cannot be assumed any of these adducts is derived uniquely or even fractionally from AG metabolites. We have therefore undertaken targeted mass spectrometric analyses of human serum albumin (HSA) isolated from diclofenac patients to characterize drug-derived structures and, thereby, for the first time, have deconstructed conclusively the pathways of adduct formation from a drug AG and its isomeric rearrangement products in vivo. These analyses were informed by a thorough understanding of the reactions of HSA with diclofenac AG in vitro. HSA from six patients without drug-related hypersensitivities had either a single drug-derived adduct or one of five combinations of 2–8 adducts from among seven diclofenac N-acylations and three AG glycations on seven of the protein’s 59 lysines. Only acylations were found in every patient. We present evidence that HSA modifications by diclofenac in vivo are complicated and variable, that at least a fraction of these modifications are derived from the drug’s AG metabolite, and that albumin adduction is not inevitably a causation of hypersensitivity to carboxylate drugs or a coincidental association. PMID:24902585

  4. Test Bias and the Elimination of Racism

    Science.gov (United States)

    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)

  5. Synthesis and structural studies of flavin and alloxazine adducts with O-nucleophiles

    Czech Academy of Sciences Publication Activity Database

    Ménová, P.; Eigner, V.; Čejka, J.; Dvořáková, H.; Šanda, Miloslav; Cibulka, R.

    2011-01-01

    Roč. 1004, 1/3 (2011), s. 178-187 ISSN 0022-2860 R&D Projects: GA ČR(CZ) GA203/07/1246 Institutional research plan: CEZ:AV0Z40550506 Keywords : alloxazine adducts * flavin adducts * flavoenzymes * X-ray structural analysis * NMR spectroscopy * UV-VIS spectroscopy Subject RIV: CC - Organic Chemistry Impact factor: 1.634, year: 2011

  6. Translesion Synthesis Past Acrolein-derived DNA Adducts by Human Mitochondrial DNA Polymerase γ*

    Science.gov (United States)

    Kasiviswanathan, Rajesh; Minko, Irina G.; Lloyd, R. Stephen; Copeland, William C.

    2013-01-01

    Acrolein, a mutagenic aldehyde, is produced endogenously by lipid peroxidation and exogenously by combustion of organic materials, including tobacco products. Acrolein reacts with DNA bases forming exocyclic DNA adducts, such as γ-hydroxy-1,N2-propano-2′-deoxyguanosine (γ-HOPdG) and γ-hydroxy-1,N6-propano-2′-deoxyadenosine (γ-HOPdA). The bulky γ-HOPdG adduct blocks DNA synthesis by replicative polymerases but can be bypassed by translesion synthesis polymerases in the nucleus. Although acrolein-induced adducts are likely to be formed and persist in mitochondrial DNA, animal cell mitochondria lack specialized translesion DNA synthesis polymerases to tolerate these lesions. Thus, it is important to understand how pol γ, the sole mitochondrial DNA polymerase in human cells, acts on acrolein-adducted DNA. To address this question, we investigated the ability of pol γ to bypass the minor groove γ-HOPdG and major groove γ-HOPdA adducts using single nucleotide incorporation and primer extension analyses. The efficiency of pol γ-catalyzed bypass of γ-HOPdG was low, and surprisingly, pol γ preferred to incorporate purine nucleotides opposite the adduct. Pol γ also exhibited ∼2-fold lower rates of excision of the misincorporated purine nucleotides opposite γ-HOPdG compared with the corresponding nucleotides opposite dG. Extension of primers from the termini opposite γ-HOPdG was accomplished only following error-prone purine nucleotide incorporation. However, pol γ preferentially incorporated dT opposite the γ-HOPdA adduct and efficiently extended primers from the correctly paired terminus, indicating that γ-HOPdA is probably nonmutagenic. In summary, our data suggest that acrolein-induced exocyclic DNA lesions can be bypassed by mitochondrial DNA polymerase but, in the case of the minor groove γ-HOPdG adduct, at the cost of unprecedented high mutation rates. PMID:23543747

  7. Structure and Oxidation of Pyrrole Adducts Formed between Aflatoxin B2aand Biological Amines.

    Science.gov (United States)

    Rushing, Blake R; Selim, Mustafa I

    2017-06-19

    Aflatoxin B 2a has been shown to bind to proteins through a dialdehyde intermediate under physiological conditions. The proposed structure of this adduct has been published showing a Schiff base interaction, but adequate verification using structural elucidation instrumental techniques has not been performed. In this work, we synthesized the aflatoxin B 2a amino acid adduct under alkaline conditions, and the formation of a new product was determined using high performance liquid chromatography-time-of-flight mass spectrometry. The resulting accurate mass was used to generate a novel proposed chemical structure of the adduct in which the dialdehyde forms a pyrrole ring with primary amines rather than the previously proposed Schiff base interaction. The pyrrole structure was confirmed using 1 H, 13 C, correlation spectroscopy, heteronuclear single quantum correlation, and heteronuclear multiple bond correlation NMR and tandem mass spectrometry. Reaction kinetics show that the reaction is overall second order and that the rate increases as pH increases. Additionally, this study shows for the first time that aflatoxin B 2a dialdehyde forms adducts with phosphatidylethanolamines and does so through pyrrole ring formation, which makes it the first aflatoxin-lipid adduct to be structurally identified. Furthermore, oxidation of the pyrrole adduct produced a product that was 16 m/z heavier. When the aflatoxin B 2a -lysine (ε) adduct was oxidized, it gave a product with an accurate mass, mass fragmentation pattern, and 1 H NMR spectrum that match aflatoxin B 1 -lysine, which suggest the transformation of the pyrrole ring to a pyrrolin-2-one ring. These data give new insight into the fate and chemical properties of biological adducts formed from aflatoxin B 2a as well as possible interferences with known aflatoxin B 1 exposure biomarkers.

  8. Base-Resolution Analysis of Cisplatin–DNA Adducts at the Genome Scale

    OpenAIRE

    Shu, Xiaoting; Xiong, Xushen; Song, Jinghui; He, Chuan; Yi, Chengqi

    2016-01-01

    Cisplatin, one of the most widely used anticancer drugs, crosslinks DNA and ultimately induces cell death. However, the genomic pattern of cisplatin–DNA adducts has remained unknown owing to the lack of a reliable and sensitive genome-wide method. Herein we present “cisplatin-seq” to identify genome-wide cisplatin crosslinking sites at base resolution. Cisplatin-seq reveals that mitochondrial DNA is a preferred target of cisplatin. For nuclear genomes, cisplatin–DNA adducts are enriched withi...

  9. Correlation of tumors with DNA adducts from methyl eugenol and tamoxifen in rats.

    Science.gov (United States)

    Waddell, William J; Crooks, Neil H; Carmichael, Paul L

    2004-05-01

    Data on percent tumors in male rats after administration of methyl eugenol, obtained from the National Toxicology Program, or tamoxifen were plotted on a linear scale for percent tumors against the dose on a logarithmic scale. Data on (32)P-postlabelled DNA adducts were plotted on the same graphs for each of these two compounds in order to correlate adduct formation and tumor incidence with dose. The resulting graph for methyl eugenol showed a linear response for both adduct formation and tumor incidence. The threshold dose of administered methyl eugenol for adduct formation (zero adducts) was 10(19.3) molecules of methyl eugenol/kg/day, which compared with a threshold of 10(20.1) molecules of methyl eugenol/kg/day for tumor formation; however, 30 adducts/10(8) nucleotides was the threshold for tumor formation. The dose of tamoxifen for adduct formation fit an exponential plot slightly better than a linear plot, but reached minimal values close to the threshold of 10(18.7) molecules of tamoxifen/kg/day for tumor formation. These data confirm that tumor formation coincides with adduct formation and that both have thresholds, or at least reach minimal values, above levels to which humans are exposed. Although the threshold dose for tumor formation from tamoxifen is only about 10x above the dose received by women at risk for breast cancer, this should be an adequate safety margin. The safety factor for methyl eugenol is several orders of magnitude; therefore, there should be no cause for concern for humans at current levels of exposure.

  10. DNA adduct profiling of in vitro colonic meat digests to map red vs. white meat genotoxicity.

    Science.gov (United States)

    Hemeryck, Lieselot Y; Rombouts, Caroline; De Paepe, Ellen; Vanhaecke, Lynn

    2018-02-16

    The consumption of red meat has been linked to an increased colorectal cancer (CRC) risk. One of the major hypotheses states that heme iron (present in red meat) stimulates the formation of genotoxic N-nitroso compounds (NOCs) and lipid peroxidation products (LPOs). By means of DNA adductomics, chemically induced DNA adduct formation can be mapped in relation to e.g. dietary exposures. In this study, this state-of-the-art methodology was used to investigate alkylation and (lipid per)oxidation induced DNA adduct formation in in vitro red vs. white meat digests. In doing so, 90 alkylation and (lipid per)oxidation induced DNA adduct types could be (tentatively) identified. Overall, 12 NOC- and/or LPO-related DNA adduct types, i.e. dimethyl-T (or ethyl-T), hydroxymethyl-T, tetramethyl-T, methylguanine (MeG), guanidinohydantoin, hydroxybutyl-C, hydroxymethylhydantoin, malondialdehyde-x3-C, O 6 -carboxymethylguanine, hydroxyethyl-T, carboxyethyl-T and 3,N 4 -etheno-C were singled out as potential heme-rich meat digestion markers. The retrieval of these DNA adduct markers is in support of the heme, NOC and LPO hypotheses, suggesting that DNA adduct formation may indeed contribute to red meat related CRC risk. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. DNA adduct quantification in Eisenia fetida after subchronic exposures to creosote contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Charrois, J.W.A.; McGill, W.B. [Alberta Univ., Dept. of Renewable Resources, Edmonton, AB (Canada)

    1999-07-01

    Within soil ecosystems contaminant toxicity can vary from acute and chronic, depending on the time of exposure. Due to the long times involved chronic toxicity is difficult to determine. DNA adducts fall into the category of biochemical markers that act as an early warning system in environmental monitoring. It has been proposed that they could be used as a sensitive method to determine environmental exposures to compounds such as polycyclic aromatic hydrocarbons (PAHs), which can occur, although not exclusively, in creosote. In this connection, Benzo[a]pyrene (BaP) is a PAH that can be transformed into an electrophilic metabolite, which ultimately results in DNA adduct formation. Use was made of a 32P postlabeling method to quantify the number of DNA adducts occurring in the earthworm Eisenia fetida after exposure to weathered creosote contaminated- and biotreated-soils with and without additions of extra BaP. DNA adducts can be measured in earthworms exposed to creosote contaminated- and biotreated-soils. E. fetida exposed to weathered creosote contaminated soils had significantly more DNA adducts than those exposed to a pristine control soil. Exposures to creosote contaminated soils with additional BaP (1000 mg/kg) or biotreatment did not yield statistically significant increases in DNA adducts compared to the pristine control. (Abstract only)

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

    Science.gov (United States)

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

    2015-11-04

    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.

  13. Chemistry and Chemical Equilibrium Dynamics of BMAA and Its Carbamate Adducts.

    Science.gov (United States)

    Diaz-Parga, Pedro; Goto, Joy J; Krishnan, V V

    2018-01-01

    Beta-N-methylamino-L-alanine (BMAA) has been demonstrated to contribute to the onset of the ALS/Parkinsonism-dementia complex (ALS/PDC) and is implicated in the progression of other neurodegenerative diseases. While the role of BMAA in these diseases is still debated, one of the suggested mechanisms involves the activation of excitatory glutamate receptors. In particular, the excitatory effects of BMAA are shown to be dependent on the presence of bicarbonate ions, which in turn forms carbamate adducts in physiological conditions. The formation of carbamate adducts from BMAA and bicarbonate is similar to the formation of carbamate adducts from non-proteinogenic amino acids. Structural, chemical, and biological information related to non-proteinogenic amino acids provide insight into the formation of and possible neurological action of BMAA. This article reviews the carbamate formation of BMAA in the presence of bicarbonate ions, with a particular focus on how the chemical equilibrium of BMAA carbamate adducts may affect the molecular mechanism of its function. Highlights of nuclear magnetic resonance (NMR)-based studies on the equilibrium process between free BMAA and its adducts are presented. The role of divalent metals on the equilibrium process is also explored. The formation and the equilibrium process of carbamate adducts of BMAA may answer questions on their neuroactive potency and provide strong motivation for further investigations into other toxic mechanisms.

  14. Cellulose based hybrid hydroxylated adducts for polyurethane foams

    Science.gov (United States)

    De Pisapia, Laura; Verdolotti, Letizia; Di Mauro, Eduardo; Di Maio, Ernesto; Lavorgna, Marino; Iannace, Salvatore

    2012-07-01

    Hybrid flexible polyurethane foams (HPU) were synthesized by using a hybrid hydroxilated adduct (HHA) based on renewable resources. In particular the HHA was obtained by dispersing cellulose wastes in colloidal silica at room temperature, pressure and humidity. The colloidal silica was selected for its ability of modifying the cellulose structure, by inducing a certain "destructurization" of the crystalline phase, in order to allow cellulose to react with di-isocyanate for the final synthesis of the polyurethane foam. In fact, cellulose-polysilicate complexes are engaged in the reaction with the isocyanate groups. This study provides evidence of the effects of the colloidal silica on the cellulose structure, namely, a reduction of the microfiber cellulose diameter and the formation of hydrogen bonds between the polysilicate functional groups and the hydroxyl groups of the cellulose, as assessed by IR spectroscopy and solid state NMR. The HHA was added to a conventional polyol in different percentages (between 5 and 20%) to synthesize HPU in presence of catalysts, silicone surfactant and diphenylmethane diisocyanate (MDI). The mixture was expanded in a mold and cured for two hours at room temperature. Thermal analysis, optical microscopy and mechanical tests were performed on the foams. The results highlighted an improvement of thermal stability and a decrease of the cell size with respect neat polyurethane foam. Mechanical tests showed an improvement of the elastic modulus and of the damping properties with increasing HHA amount.

  15. Costs and financial feasibility of malaria elimination

    Science.gov (United States)

    Sabot, Oliver; Cohen, Justin M; Hsiang, Michelle S; Kahn, James G; Basu, Suprotik; Tang, Linhua; Zheng, Bin; Gao, Qi; Zou, Linda; Tatarsky, Allison; Aboobakar, Shahina; Usas, Jennifer; Barrett, Scott; Cohen, Jessica L; Jamison, Dean T; Feachem, Richard GA

    2010-01-01

    Summary The marginal costs and benefits of converting malaria programmes from a control to an elimination goal are central to strategic decisions, but empirical evidence is scarce. We present a conceptual framework to assess the economics of elimination and analyse a central component of that framework—potential short-term to medium-term financial savings. After a review that showed a dearth of existing evidence, the net present value of elimination in five sites was calculated and compared with effective control. The probability that elimination would be cost-saving over 50 years ranged from 0% to 42%, with only one site achieving cost-savings in the base case. These findings show that financial savings should not be a primary rationale for elimination, but that elimination might still be a worthy investment if total benefits are sufficient to outweigh marginal costs. Robust research into these elimination benefits is urgently needed. PMID:21035839

  16. Fabrication techniques to eliminate postweld heat treatment

    International Nuclear Information System (INIS)

    Lochhead, J.C.

    1978-01-01

    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)

  17. Effects of thiourea and ammonium bicarbonate on the formation and stability of bifunctional cisplatin-DNA adducts : consequences for the accurate quantification of adducts in (cellular) DNA

    NARCIS (Netherlands)

    Fichtinger-Schepman, A.M.J.; Dijk-Knijnenburg, H.C.M. van; Dijt, F.J.; Velde-Visser, S.D. van der; Berends, F.; Baan, R.A.

    1995-01-01

    Cisplatin reacts with DNA by forming mainly bifunctional adducts via reactive monofunctional intermediates. When freshly platinated DNA was postincubated with thiourea (10 mM, at 23 or 37°C) for periods of up to 24 h, followed by determination of mono- and diadducts, a rapid initial decrease was

  18. Mechanistic aspects of the reaction between Br2 and chalcogenone donors (LE; E=S, Se): competitive formation of 10-E-3, T-shaped 1:1 molecular adducts, charge-transfer adducts, and [ (LE)2]2+ dications.

    Science.gov (United States)

    Aragoni, M C; Arca, M; Demartin, F; Devillanova, F A; Garau, A; Isaia, F; Lelj, F; Lippolis, V; Verani, G

    2001-07-16

    The synthesis and spectroscopic characterisation of the products obtained by treatment of N,N'-dimethylimidazolidine-2-thione (1), N,N'-dimethylimidazolidine-2-selone (2), N,N'-dimethylbenzoimidazole-2-thione (3) and N,N'-dimethylbenzoimidazole-2-selone (4) with Br2 in MeCN are reported, together with the crystal structures of the 10-E-3, T-shaped adducts 2 . Br2 (12), 3 . Br2 (13) and 4 . Br2 (14). A conductometric and spectrophotometric investigation into the reaction between 1-4 and Br2, carried out in MeCN, allows the equilibria involved in the formation of the isolated 10-E-3 (E = S, Se) hypervalent compounds to be hypothesised. In order to understand the reasons why S and Se donors can give different product types on treatment with Br2 and I2, DFT calculations have been carried out on 1-8, 19 and 20, and on their corresponding hypothetical [LEX]+ cations (L = organic framework; E = S, Se; X = Br, I), which are considered to be key intermediates in the formation of the different products. The results obtained in terms of NBO charge distribution on [LEX]+ species explain the different behaviour of 1-8, 19 and 20 in their reactions with Br2 and I2 fairly well. X-ray diffraction studies show 12-14 to have a T-shaped (10-E-3; E = S, Se) hypervalent chalcogen nature. They contain an almost linear Br-E-Br (E = S, Se) system roughly perpendicular to the average plane of the organic molecules. In 12, the Se atom of each adduct molecule has a short interaction with the Br(1) atom of an adjacent unit, such that the Se atom displays a roughly square planar coordination. The Se-Br distances are asymmetric [2.529(1) vs. 2.608(1) A], the shorter distance being that with the Br(1) atom involved in the short intermolecular contact. In contrast, in the molecular adducts 13 and 14, which lie on a two-fold crystallographic axis, the Br-E-Br system is symmetric and no short intermolecular interactions involving chalcogen and bromine atoms are observed. The adducts are arranged in

  19. Detecting and eliminating slippery footwear.

    Science.gov (United States)

    Jones, C; Manning, D P; Bruce, M

    1995-02-01

    A recently developed walking traction test has proved to be a reliable and rapid method of measuring coefficient of friction (c.o.f.) of floor surfaces and footwear, and is a suitable method for ranking the grip of footwear solings on slippery floors. This paper describes four new experiments in which footwear samples were ranked. The first experiment compared mean rank orders on water wet (wet) and oily surfaces of seven flat solings. Spearman's rank correlation coefficient rs was 0·893, P test methods. The test surfaces were oily stainless steel plates cut from the same sheet. Rank orders of the three test methods were significantly similar. Kendall's coefficient of concordance w = 8·68, P < 0·001. In another experiment samples of commercially available footwear were issued to factory workers and recalled for c.o.f. measurements at intervals. Their rank orders on wet and oily surfaces were not statistically similar but when wet surface results obtained at 4 months, were compared with those at 10 months, rank orders were significant; rs = 0·994, P < 0·01. Also on oily surfaces, rank orders of two measurements were significant, rs = 0·982, P <0·01. Although most experiments have revealed significant correlations between footwear samples on wet and oily surfaces there are examples where a soling performs well on wet surfaces but is at the lower end of rank order on oily surfaces. It is concluded that rank orders on wet, oily and icy surfaces should be calculated but also it is necessary to examine rank orders on each surface-lubricant combination, by comparing results obtained at intervals during the useful lives of the solings. In future, samples at the lower end of the rank orders of c.o.f. will be eliminated from the varieties available to workers.

  20. Elimination of Onchocerciasis from Mexico

    Science.gov (United States)

    Rodríguez-Pérez, Mario A.; Fernández-Santos, Nadia A.; Orozco-Algarra, María E.; Rodríguez-Atanacio, José A.; Domínguez-Vázquez, Alfredo; Rodríguez-Morales, Kristel B.; Real-Najarro, Olga; Prado-Velasco, Francisco G.; Cupp, Eddie W.; Richards, Frank O.; Hassan, Hassan K.; González-Roldán, Jesús F.; Kuri-Morales, Pablo A.; Unnasch, Thomas R.

    2015-01-01

    Background 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. Methodology/Principal findings 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. Conclusions/Significance 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. PMID:26161558

  1. Elimination of Onchocerciasis from Mexico.

    Directory of Open Access Journals (Sweden)

    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.

  2. Genetic modifiers of carcinogen DNA adducts in target lung and peripheral blood mononuclear cells.

    Science.gov (United States)

    Lee, Mi-Sun; Su, Li; Mark, Eugene J; Wain, John C; Christiani, David C

    2010-12-01

    Measurement of carcinogen DNA adducts in blood has been used as a surrogate for the target lung tissue. We aimed to examine whether genetic polymorphisms in several metabolic pathway genes modify the relation between DNA adducts in target lung and blood. One hundred and thirty-five early-stage lung cancer patients from the Massachusetts General Hospital were studied. DNA adducts were measured by the (32)P-postlabeling assay in lung and blood mononuclear cells (MNCs) in a subset of 53 who had paired blood samples. Single-nucleotide polymorphisms (SNPs) were assessed in genes involved in phase II (GSTs, NAT2, EPHX and NQO1), DNA repair (ERCC1, ERCC2 and XRCC1) and DNA methylation (MTHFR C677T and A1298C) pathways. There was a significant correlation between DNA adduct levels in lung and blood within the different genotypes, with one exception. Significant modifications in adducts were found by variants in genes for phase II metabolism [NAT2 (1.51 for rapid versus 0.76 for slow, P = 0.022)], DNA repair [ERCC1 C118T (P = 0.014), ERCC2 (P = 0.003) and XRCC1 (P = 0.025)] and MTHFR [C677T (P = 0.005) and A1298C (P = 0.005)]. The relation between DNA adducts in blood MNCs and target lung tissue was significantly modified by the single-nucleotide polymorphisms in the three main pathways. Despite the relatively small sample size, our results suggest that genetic factors may need to be considered when assessing the association of DNA adducts using surrogate tissue in studies of lung cancer. Further studies are needed to better understand their role and the mechanisms.

  3. DNA adduct formation by the ubiquitous environmental pollutant 3-nitrobenzanthrone and its metabolites in rats

    International Nuclear Information System (INIS)

    Arlt, Volker M.; Sorg, Bernd L.; Osborne, Martin; Hewer, Alan; Seidel, Albrecht; Schmeiser, Heinz H.; Phillips, David H.

    2003-01-01

    Diesel exhaust is known to induce tumours in animals and is suspected of being carcinogenic in humans. Of the compounds found in diesel exhaust, 3-nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspected human carcinogen forming multiple DNA adducts in vitro. 3-Aminobenzanthrone (3-ABA), 3-acetylaminobenzanthrone (3-Ac-ABA), and N-acetyl-N-hydroxy-3-aminobenzanthrone (N-Ac-N-OH-ABA) were identified as 3-NBA metabolites. In order to gain insight into the pathways of metabolic activation leading to 3-NBA-derived DNA adducts we treated Wistar rats intraperitoneally with 2 mg/kg body weight of 3-NBA, 3-ABA, 3-Ac-ABA, or N-Ac-N-OH-ABA and compared DNA adducts present in different organs. With each compound either four or five DNA adduct spots were detected by TLC in all tissues examined (lung, liver, kidney, heart, pancreas, and colon) using the nuclease P1 or butanol enrichment version of the 32 P-postlabelling method, respectively. Using HPLC co-chromatographic analysis we showed that all major 3-NBA-DNA adducts produced in vivo in rats are derived from reductive metabolites bound to purine bases and lack an N-acetyl group. Our results indicate that 3-NBA metabolites (3-ABA, 3-Ac-ABA and N-Ac-N-OH-ABA) undergo several biotransformations and that N-hydroxy-3-aminobenzanthrone (N-OH-ABA) appears to be the common intermediate in 3-NBA-derived DNA adduct formation. Therefore, 3-NBA-DNA adducts are useful biomarkers for exposure to 3-NBA and its metabolites and may help to identify enzymes involved in their metabolic activation

  4. Protective effects of selenium against DNA adducts formation in Inuit environmentally exposed to PCBs

    Science.gov (United States)

    Ravoori, Srivani; Srinivasan, Cidambi; Pereg, Daria; Robertson, Larry W; Ayotte, Pierre; Gupta, Ramesh C

    2012-01-01

    Dietary habits that expose populations to potential toxicants as well as protective agents simultaneously is a realistic scenario where a meaningful assessment of the interactions and net benefit or damage can be made. A group of Inuit from Salluit, Northern Canada are exposed to high levels of PCBs and selenium, both present in the Inuit traditional foods such as blubber from sea mammals and fatty fish. Blood samples were collected from 83 Inuit, 22–70 years old. Blood selenium and PCB levels were determined previously and ranged from 227 to 2,069 µg/L and 1.7 to 143 µg/L, respectively. DNA isolated from white blood cells were analyzed by modified 32P-postlabeling adductomics technology that detects a multitude of highly polar to lipophilic adducts. The levels of 8-oxodG adducts ranged from 470 to 7,400 adducts/109 nucleotides. Other as yet unidentified polar adducts showed a 30 to 800–fold inter-individual variability. Adduct levels were negatively associated with PCB and selenium levels. The subjects were classified into high and low ratio groups, with respect to selenium/PCB. In the high ratio group, the coefficient of selenium is significantly negatively correlated with 8-oxodG (r = −0.38, p = 0.014) and total adducts (r = −0.41, p = 0.009) while there was no correlation within the low selenium/PCB group. This study suggests increasing selenium has mitigating effect in reducing DNA adducts and therefore, possible negative effects of PCB were not rendered. A protective effect of selenium is highlighted. PMID:19735942

  5. Protonation reactions of electron adducts of acrylamide derivatives. A pulse radiolytic-kinetic spectrophotometric study

    International Nuclear Information System (INIS)

    Madhavan, V.; Lichtin, N.N.; Hayon, E.

    1974-01-01

    The absorption spectra of electron adducts of a number of α,β-unsaturated carboxamides and of methyl methacrylate, as well as of two isomeric types of protonated electron adducts, have been characterized by means of the technique of pulse radiolysis-kinetic absorption spectrophotometry. Spectra of the electron adducts are characterized by bands in the uv (epsilon/sub max/ approximately 10 4 M -1 cm -1 ) and in the visible (epsilon/sub max/ approximately 10 3 M -1 cm -1 ). The position of the uv band shifts 10--30 nm to shorter wavelength upon reversible protonation. Fast reversible protonation of electron adducts takes place at the carbonyl oxygen. The pK/sub a/ values of the electron adducts vary linearly with the pK/sub a/ values of the corresponding carboxylic acids: for acrylamide, 7.9; methacrylamide, 8.0; trans-crotonamide, 8.5; β,β-dimethylacrylamide, 9.5; N,N-dimethylacrylamide, 8.5; trans-cinnamamide, 7.2; methyl methacrylate, approximately7. Slower irreversible protonation of the electron adducts takes place at the β-carbon atom and is subject to general acid catalysis which obeys the Bronsted catalysis law. Uncatalyzed specific rates of β protonation of anion radicals (in units of 10 5 sec -1 ) are: for acrylamide, 1.4; for methacrylamide, 13; for trans-crotonamide, 0.22; for β,β-dimethylacrylamide, 0.21; for N,N-dimethylacrylamide, 3.7; for trans-cinnamamide, less than or equal to approximately .01; for methyl methacrylate, 4.5. The second-order decay of reversibly protonated electron adducts competes with irreversible β protonation. (U.S.)

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

    DEFF Research Database (Denmark)

    Andreassen, Åshild; Kure, Elin H.; Nielsen, Per Sabro

    1996-01-01

    )-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......Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were studied in human lung from 39 lung cancer patients by synchronous fluorescence spectrophotometric (SFS) and 32P-postlabeling assays. Regression analysis of the samples failed to detect any correlation between benzo[a]pyrene-diolepoxide (BPDE...... and the adduct level ranged from 6.81 to 108.50 adducts/10(8) nucleotide. Thirty-three of 39 (85%) had detectable levels of BPDE-DNA adducts (> 1 adduct/10(9) nucleotide). Current heavy smokers (> 20 cigarettes/day) have significantly higher DRZ adduct levels compared to individuals smoking less than 20...

  7. Reaction of aryne with aza-Morita–Baylis–Hillman adducts: Synthesis of 4-quinolones and N-arylation products

    Directory of Open Access Journals (Sweden)

    Li-Li Liu

    2017-05-01

    Full Text Available The reaction of aryne with aza-Morita–Baylis–Hillman (aza-MBH adducts has been studied. Aryne reacts with aza-MBH adducts through a cascade insertion–cyclization–ene reaction to produce 4-quinolones in 18–44% yields; meanwhile, aza-MBH adducts undergo N-insertion reaction with aryne to afford N-arylation products in 27–77% yields.

  8. Outcomes of medialization laryngoplasty with and without arytenoid adduction.

    Science.gov (United States)

    Chang, Joseph; Schneider, Sarah L; Curtis, James; Langenstein, Jonelyn; Courey, Mark S; Yung, Katherine C

    2017-11-01

    To evaluate the effect of medialization laryngoplasty (ML) performed alone compared to ML with arytenoid adduction (AA) on glottic gap and voice quality in unilateral vocal fold paralysis (UVFP) patients. Retrospective case series. UVFP patients treated with ML alone and ML with AA at the University of California San Francisco Voice and Swallowing Center were identified. Demographic information and history of laryngeal procedures were collected. Preoperative and postoperative examinations were digitally analyzed using ImageJ for normalized anterior and posterior glottic gap and voice samples graded with CAPE-V scores. Forty-seven patients underwent ML and 27 patients underwent ML with AA. Normalized anterior gap (AG) improved in both ML (preop: 4.4 pixel units (u), postop: 0.8 u; P < 0.001) and ML with AA groups (preop: 3.3 u, postop 0.6 u; P < 0.001). There was no statistically significant difference in normalized AG values between treatment groups. Postoperative normalized posterior gap (PG) improved in the ML with AA group only (preop: 1.8 u, postop: 0.5 u; P = 0.01). Overall severity, roughness, and strain voice parameters had acceptable reliability for analysis. Overall severity improved in ML (preop: 54, postop: 27; P < 0.001) and ML with AA (preop: 44, postop: 24; P = 0.005). There was no statistically significant difference in any voice parameter between treatment groups. UVFP patients undergoing ML may benefit from addition of AA when a large posterior glottic gap is present. In this study, ML with AA but not ML alone resulted in statistically significant improvement in PG. 4. Laryngoscope, 127:2591-2595, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  9. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

    International Nuclear Information System (INIS)

    Mei, Nan; Arlt, Volker M.; Phillips, David H.; Heflich, Robert H.; Chen, Tao

    2006-01-01

    Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by 32 P-postlabeling and mutant frequency (MF) was determined using the λ Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N 6 -yl]-aristolactam I, 7-[deoxyadenosin-N 6 -yl]-aristolactam II and 7-[deoxyguanosin-N 2 -yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10 8 nucleotides in liver and 95-4598 adducts/10 8 nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10 -6 in liver compared with the MFs of 78-1319 x 10 -6 that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T → T:A transversion was the predominant mutation in AA-treated rats; whereas G:C → A:T transition was the main type of mutation in control rats. These results indicate that the AA treatment that eventually

  10. Passive radio frequency peak power multiplier

    Science.gov (United States)

    Farkas, Zoltan D.; Wilson, Perry B.

    1977-01-01

    Peak power multiplication of a radio frequency source by simultaneous charging of two high-Q resonant microwave cavities by applying the source output through a directional coupler to the cavities and then reversing the phase of the source power to the coupler, thereby permitting the power in the cavities to simultaneously discharge through the coupler to the load in combination with power from the source to apply a peak power to the load that is a multiplication of the source peak power.

  11. Modifications to the organophosphorus nerve agent-protein adduct refluoridation method for retrospective analysis of nerve agent exposures.

    Science.gov (United States)

    Holland, Kerry E; Solano, Maria I; Johnson, Rudolph C; Maggio, Vincent L; Barr, John R

    2008-01-01

    Organophosphorus nerve agents (OPNAs) continue to pose a threat to military personnel and the general public because of their toxicity and their potential use as weapons of mass destruction. An effective method for the detection of human exposure to OPNAs involves the refluoridation of nerve agents adducted to the serum protein butyrylcholinesterase. The regenerated agents are then enriched by solid-phase extraction and quantified by isotope-dilution gas chromatography-mass spectrometry. We have previously reported improvements that resulted in a 10-fold increase in sensitivity. We have now made further changes to the method that include the addition of confirmation ions, the addition of soman (GD) to the assay, the expansion of the linear range, and the elimination of high-volume injection to decrease background noise and run time while improving sensitivity. This report includes the standard operating procedures for this method for tabun, sarin, soman, cyclohexylsarin, and VX and validation studies. The method's limits of detection ranged from 5.5 to 16.5 pg/mL for the G analogue of VX and GD, respectively. Characterization of quality control (QC) materials resulted in an average coefficient of variation of 15.1% for the five analytes in low QC pools and 11.7% in high QC pools.

  12. Abdominal Hollowing Reduces Lateral Trunk Displacement During Single-Leg Squats in Healthy Females But Does Not Affect Peak Hip Abduction Angle or Knee Abductio Angle/Moment.

    Science.gov (United States)

    Linde, Lukas D; Archibald, Jessica; Lampert, Eve C; Srbely, John Z

    2017-07-17

    Females suffer 4-6 times more non-contact anterior cruciate ligament (ACL) injuries than males due to neuromuscular control deficits of the hip musculature leading to increases in hip adduction angle, knee abduction angle, and knee abduction moment during dynamic tasks such as single-leg squats. Lateral trunk displacement has been further related to ACL injury risk in females, leading to the incorporation of core strength/stability exercises in ACL preventative training programs. However, the direct mechanism relating lateral trunk displacement and lower limb ACL risk factors is not well established. To assess the relationship between lateral trunk displacement and lower limb measures of ACL injury risk by altering trunk control through abdominal activation techniques during single-leg squats in healthy females. Interventional Study Setting: Movement and Posture Laboratory Participants: 13 healthy females (21.3±0.88y, 1.68±0.07m, 58.27±5.46kg) Intervention: Trunk position and lower limb kinematics were recorded using an optoelectric motion capture system during single-leg squats under differing conditions of abdominal muscle activation (abdominal hollowing, abdominal bracing, control), confirmed via surface electromyography. Lateral trunk displacement, peak hip adduction angle, peak knee abduction angle/moment, and average muscle activity from bilateral internal oblique, external oblique, and erector spinae muscles. No differences were observed for peak lateral trunk displacement, peak hip adduction angle or peak knee abduction angle/moment. Abdominal hollowing and bracing elicited greater muscle activation than the control condition, and bracing was greater than hollowing in four of six muscles recorded. The lack of reduction in trunk, hip, and knee measures of ACL injury risk during abdominal hollowing and bracing suggests that these techniques alone may provide minimal benefit in ACL injury prevention training.

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

    Energy Technology Data Exchange (ETDEWEB)

    Moryia, M.; Takeshita, M.; Johnson, F.; Peden, K.; Will, S.; Grollman, A.P.

    1988-03-01

    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 /sup 32/P-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.

  14. Formation, Repair, and Genotoxic Properties of Bulky DNA Adducts Formed from Tobacco-Specific Nitrosamines

    Directory of Open Access Journals (Sweden)

    Lisa A. Peterson

    2010-01-01

    Full Text Available 4-(Methylnitrosamino-1-(3-pyridyl-1-butanone (NNK and N′-nitrosonornicotine (NNN are tobacco-specific nitrosamines present in tobacco products and smoke. Both compounds are carcinogenic in laboratory animals, generating tumors at sites comparable to those observed in smokers. These Group 1 human carcinogens are metabolized to reactive intermediates that alkylate DNA. This paper focuses on the DNA pyridyloxobutylation pathway which is common to both compounds. This DNA route generates 7-[4-(3-pyridyl-4-oxobut-1-yl]-2′-deoxyguanosine, O2-[4-(3-pyridyl-4-oxobut-1-yl]-2′-deoxycytosine, O2-[4-(3-pyridyl-4-oxobut-1-yl]-2′-deoxythymidine, and O6-[4-(3-pyridyl-4-oxobut-1-yl]-2′-deoxyguanosine as well as unstable adducts which dealkylate to release 4-hydroxy-1-{3-pyridyl-1-butanone or depyriminidate/depurinate to generate abasic sites. There are multiple repair pathways responsible for protecting against the genotoxic effects of these adducts, including adduct reversal as well as base and nucleotide excision repair pathways. Data indicate that several DNA adducts contribute to the overall mutagenic properties of pyridyloxobutylating agents. Which adducts contribute to the carcinogenic properties of this pathway are likely to depend on the biochemistry of the target tissue.

  15. Novel approach of medialization thyroplasty with arytenoid adduction performed under general anesthesia with a laryngeal mask.

    Science.gov (United States)

    Stow, Nicholas W; Lee, Jennifer W; Cole, Ian E

    2012-02-01

    To objectively assess the voice outcomes of patients with unilateral vocal fold paralysis treated with medialization thyroplasty and arytenoid adduction suture. Case series of patients who underwent medialization thyroplasty and arytenoid adduction suture. Preoperative and postoperative voice testing was performed and the data were compared by statistical analysis. Tertiary referral teaching hospital in Sydney, Australia. All patients had a unilateral vocal fold paralysis, with a large posterior glottic gap and vocal symptoms affecting their quality of life. Thirteen patients with a diagnosis of a unilateral vocal fold paralysis with a large posterior glottic gap, vocal symptoms, and total denervation of the vocal fold underwent medialization thyroplasty and arytenoid adduction suture. The surgery was performed in a novel method under a general anesthetic using a laryngeal mask and with direct intraoperative endoscopic feedback. Preoperative and postoperative measures of voice performance were compared, including acoustic analysis (fundamental frequency, speech intensity against quiet and loud background noise, speech rate) and aerodynamic assessment (airflow, maximum phonation time). Medialization thyroplasty with arytenoid adduction suture significantly improved aerodynamic assessment and phonation duration for both male and female subjects overall. There were 2 of 13 treatment failures. Median follow-up time was 6 months. Preliminary results indicate that in selected patients with vocal fold paralysis, medialization thyroplasty with arytenoid adduction suture leads to significant improvements in objective voice measures. Longer follow-up data are required to further quantify the voice outcomes after this procedure.

  16. Repair capacity for platinum-DNA adducts determines the severity of cisplatin-induced peripheral neuropathy.

    Science.gov (United States)

    Dzagnidze, Anna; Katsarava, Zaza; Makhalova, Julia; Liedert, Bernd; Yoon, Min-Suk; Kaube, Holger; Limmroth, Volker; Thomale, Juergen

    2007-08-29

    The pronounced neurotoxicity of the potent antitumor drug cisplatin frequently results in the onset of peripheral polyneuropathy (PNP), which is assumed to be initially triggered by platination products in the nuclear DNA of affected tissues. To further elucidate the molecular mechanisms, we analyzed in a mouse model the formation and processing of the main cisplatin-induced DNA adduct (guanine-guanine intrastrand cross-link) in distinct neuronal cell types by adduct-specific monoclonal antibodies. Comparison of the adduct kinetics in cisplatin-injected mice either proficient or deficient for nucleotide excision repair (NER) functions revealed the essential role of this DNA repair pathway in protecting differentiated cells of the nervous system from excessive formation of such lesions. Hence, chronic exposure to cisplatin resulted in an accelerated accumulation of unrepaired intrastrand cross-links in neuronal cells of mice with dysfunctional NER. The augmented adduct levels in dorsal root ganglion (DRG) cells of those animals coincided with an earlier onset of PNP-like functional disturbance of their sensory nervous system. Independently from the respective repair phenotype, the amount of persisting DNA cross-links in DRG neurons at a given cumulative dose was significantly correlated to the degree of sensory impairment as measured by electroneurography. Collectively, these findings suggest a new model for the processing of cisplatin adducts in primary neuronal cells and accentuate the crucial role of effectual DNA repair capacity in the target cells for the individual risk of therapy-induced PNP.

  17. Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N-oxides.

    Science.gov (United States)

    He, Xiaobo; Xia, Qingsu; Woodling, Kellie; Lin, Ge; Fu, Peter P

    2017-10-01

    There are 660 pyrrolizidine alkaloids (PAs) and PA N-oxides present in the plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine) and their corresponding PA N-oxides produced the same set of DNA adducts. Among these compounds, lasiocarpine N-oxide, retrorsine N-oxide, monocrotaline N-oxide, and heliotrine N-oxide are for first time shown to be able to produce these DNA adducts. These results further support the role of these DNA adducts as potential common biomarkers of PA-induced liver tumor initiation. Copyright © 2017. Published by Elsevier B.V.

  18. Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N-oxides

    Directory of Open Access Journals (Sweden)

    Xiaobo He

    2017-10-01

    Full Text Available There are 660 pyrrolizidine alkaloids (PAs and PA N-oxides present in the plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine and their corresponding PA N-oxides produced the same set of DNA adducts. Among these compounds, lasiocarpine N-oxide, retrorsine N-oxide, monocrotaline N-oxide, and heliotrine N-oxide are for first time shown to be able to produce these DNA adducts. These results further support the role of these DNA adducts as potential common biomarkers of PA-induced liver tumor initiation.

  19. Differential protein adduction by seven organophosphorus pesticides in both brain and thymus.

    Science.gov (United States)

    Carter, Wayne G; Tarhoni, Mabruka; Rathbone, Alexandra J; Ray, David E

    2007-04-01

    There is a need for mechanistic understanding of the lasting ill health reported in several studies of workers exposed to organophosphorus (OP) pesticide. Although the acute toxicity is largely explicable by acetylcholinesterase inhibition and the lasting effects of frank poisoning by direct excitotoxicity or indirect consequences of the cholinergic syndrome, effects at lower levels of exposure would not be predicted from these mechanisms. Similarly, reversible interactions with nicotinic and muscarinic receptors in adults would not predict continuing ill health. Many OP pesticides produce protein adduction, and the lasting nature of this makes it a candidate mechanism for the production of continuing ill health. We found significant adduction of partially characterized protein targets in both rat brain and thymus by azamethiphos, chlorfenvinphos, chlorpyrifos-oxon, diazinon-oxon, dichlorvos and malaoxon, in vitro and pirimiphos-methyl in vivo. The diversity in the adduction pattern seen across these agents at low dose levels means that any longer term effects of adduction would be specific to specific organophosphates, rather than generic. This presents a challenge to epidemiology, as most exposures are to different agents over time. However, some adducted proteins are also expressed in blood, notably albumin, and so may provide exposure measures to increase the power of future epidemiological studies.

  20. Aflatoxin B1-lysine adduct in dried blood spot samples of animals and humans.

    Science.gov (United States)

    Xue, Kathy S; Cai, Wenjie; Tang, Lili; Wang, Jia-Sheng

    2016-12-01

    Dried blood spots (DBS) were proposed as potentially viable method for exposure assessment of environmental toxicants in infant and young children. For this study, we validated an experimental protocol to quantify AFB 1 -lysine adduct in DBS samples of AFB 1 -treated F344 rats, as well as samples from human field study. Significant dose-response relationships in AFB 1 -lysine adduct formation were found in DBS samples of rats treated with single- and repeated-dose AFB 1 . AFB 1 -lysine levels in DBS samples were highly correlated with corresponding serum sample levels. The Person coefficients were 0.997 for the single-dose exposure, and 0.996 for the repeated-dose exposure. Levels of AFB 1 -lysine adduct had also good agreement between DBS and serum samples as shown by Bland-Altman plot analysis. For human field study samples (n = 36), a Pearson correlation coefficient of 0.784 was found between AFB 1 -lysine adduct levels of DBS and corresponding serum samples. Bland-Altman plots showed the distribution of the log differences between DBS and serum AFB 1 -lysine levels are within 95% confidence intervals. These results showed AFB 1 -lysine adduct levels in DBS cards and serum samples from animals and human samples are comparable, and the DBS technique and analytical protocol is a good means to assess AFB 1 exposure in infant and children populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Nathalie T Pham

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

  2. The geomorphic structure of the runoff peak

    Directory of Open Access Journals (Sweden)

    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.

  3. Toxicokinetics of mercury elimination by succimer in twin toddlers.

    Science.gov (United States)

    Fayez, Ibrahim; Paiva, Michelle; Thompson, Margaret; Verjee, Zulfukarali; Koren, Gideon

    2005-01-01

    We describe the toxicokinetics of mercury in two twin toddlers poisoned by an East Indian remedy for teething. Succimer (dimercaprosuccinic acid, DMSA) decreased the plasma elimination half-life of mercury by 3-fold in the patient with high exposure; a more modest effect was observed in the other twin. Succimer is a chelation agent used in the treatment of heavy metal intoxication. A water-soluble agent, it increases the urinary excretion of lead and mercury. The drug is rapidly but variably absorbed through the gastrointestinal tract, with peak levels occurring at 1-2 hours. After its absorption, peak mercury excretion through the urine occurs within 2-4 hours. In the poisoned twin sisters, succimer administration led to a mercury plasma elimination half-life of 6 weeks. Although succimer has been used in mercury poisoning in adults and children, the toxicokinetics of mercury have not previously been characterized in either age group. We believe this is the first such description. More studies on the toxicokinetics and dynamics of mercury chelation with succimer in young children are needed to ensure the optimal use of the drug in this population.

  4. Hypothesis elimination on a quantum computer

    OpenAIRE

    Soklakov, Andrei N.; Schack, Ruediger

    2004-01-01

    Hypothesis elimination is a special case of Bayesian updating, where each piece of new data rules out a set of prior hypotheses. We describe how to use Grover's algorithm to perform hypothesis elimination for a class of probability distributions encoded on a register of qubits, and establish a lower bound on the required computational resources.

  5. The influence of antagonist muscle electrical stimulation on maximal hip adduction force.

    Science.gov (United States)

    Nakano, Sota; Wada, Chikamune

    2016-01-01

    [Purpose] The aim of this study was to determine whether electrical stimulation of the tensor fascia lata muscle decreases voluntary maximum resistance to passive abduction motion in participants without disease of the central nervous system. [Subjects] The participants were 16 healthy men. [Methods] The hip joint was moved from 10° adduction to 0° adduction with an angular velocity of 7°/s. During the passive leg motion, the subject was asked to resist the motion with maximum force. Two experimental conditions were prepared: (1) electrical stimulation provided to the tensor fascia lata muscle during the passive motion; and (2) no electrical stimulation provided. [Results] The force was 10.2 ± 3.5 kgf with electrical stimulation and 12.2 ± 3.8 kgf without electrical stimulation. [Conclusion] The results suggested that the maximum hip adduction force decreased in participants because of electrical stimulation of the tensor fascia lata muscle.

  6. Activation of dihaloalkanes by glutathione conjugation and formation of DNA adducts.

    Science.gov (United States)

    Guengerich, F P; Peterson, L A; Cmarik, J L; Koga, N; Inskeep, P B

    1987-01-01

    Ethylene dibromide (1,2-dibromoethane, EDB) can be activated to electrophilic species by either oxidative metabolism or conjugation with glutathione. Although conjugation is generally a route of detoxication, in this case it leads to genetic damage. The major DNA adduct has been identified as S-[2-(N7-guanyl)ethyl]glutathione, which is believed to arise via half-mustard and episulfonium ion intermediates. The adduct has a half-life of about 70 to 100 hr and does not appear to migrate to other DNA sites. Glutathione-dependent DNA damage by EDB was also demonstrated in human hepatocyte preparations. The possible relevance of this DNA adduct to genetic damage is discussed. Images FIGURE 3. PMID:3329096

  7. Activation of dihaloalkanes by glutathione conjugation and formation of DNA adducts

    International Nuclear Information System (INIS)

    Guengerich, F.P.; Peterson, L.A.; Cmarik, J.L.; Koga, N.; Inskeep, P.B.

    1987-01-01

    Ethylene dibromide (1,2-dibromoethane, EDB) can be activated to electrophilic species by either oxidative metabolism or conjugation with glutathione. Although conjugation is generally a route of detoxication, in this case it leads to genetic damage. The major DNA adduct has been identified as S-[2-(N 7 -guanyl)ethyl]glutathione, which is believed to arise via half-mustard and episulfonium ion intermediates. The adduct has a half-life of about 70 to 100 hr and does not appear to migrate to other DNA sites. Glutathione-dependent DNA damage by EDB was also demonstrated in human hepatocyte preparations. The possible relevance of this DNA adduct to genetic damage is discussed

  8. Quantitative measurement of DNA adducts using neutral hydrolysis and LC-MS. Validation of genotoxicity sensors.

    Science.gov (United States)

    Tarun, Maricar; Rusling, James F

    2005-04-01

    Neutral hydrolysis and LC-MS/MS analysis of 6-nm-thick DNA-polyion films used in voltammetric genotoxicity screening sensors showed that concentrations of N7-guanine DNA adducts with methyl methanesulfonate and styrene oxide increased with incubation time with the same trends as found for sensor response. Results show that the genotoxicity sensors can be used to estimate relative DNA damage rates for chemical toxicity screening. Neutral thermal hydrolysis provided a relatively clean sample matrix allowing quantitative estimates of nucleobase adducts after several minutes of incubation with damage agents. In addition, an approximate standardization procedure for neutral thermal hydrolysis was developed and validated that avoids need for a pure standard and should be useful in cases where nucleobase adduct standards are unavailable or where their identities are unknown.

  9. Synthesis of Cyclopropane Derivatives Starting from the Baylis-Hillman Adducts Using Sulfur Ylide Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ka Young; Kim, Seung Chan; Kim, Jae Nyoung [Chonnam National University, Gwangju (Korea, Republic of)

    2006-02-15

    During the extensive studies on the chemical transformations of Baylis-Hillman adducts, we examined the introduction of cyclopropane moiety at the primary position of Baylis-Hillman adducts to form vinyl cyclopropane derivatives. Such vinyl cyclopropane backbone is an important entity in many naturally occurring and synthetic pyrethroidal insectides, and could be used for further chemical transformations. Our synthetic rationale is shown in Scheme 1. The starting cinnamyl bromide was prepared from the Baylis-Hillman adduct and HBr according to the reported method. The reaction of and dimethyl sulfide in CH{sub 3}CN generated the sulfonium salt, which was converted into the corresponding sulfur ylide by treatment with NaOH.

  10. Peak Shaving Considering Streamflow Uncertainties | Iwuagwu ...

    African Journals Online (AJOL)

    The main thrust of this paper is peak shaving with a Stochastic hydro model. In peak sharing, the amount of hydro energy scheduled may be a minimum but it serves to replace less efficient thermal units. The sample system is die Kainji hydro plant and the thermal units of the National Electric Power Authority. The random ...

  11. MTHFR polymorphisms, folate intake and carcinogen DNA adducts in the lung.

    Science.gov (United States)

    Lee, Mi-Sun; Asomaning, Kofi; Su, Li; Wain, John C; Mark, Eugene J; Christiani, David C

    2012-09-01

    The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was completed for MTHFR C677T (rs1801133) and A1298C (rs1801131). Information on dietary intake for one-carbon related micronutrients, folate and other B vitamin was derived from a validated food frequency questionnaire. DNA adducts in lung were measured by (32) P-postlabeling. After adjusting for potential confounders, DNA adduct levels in lung significantly increased by 69.2% [95% confidence interval (CI), 5.5% to 171.5%] for the MTHFR 1298AC+CC genotype. The high risk group, combining the A1298C (AC+CC) plus C677T (CT+TT) genotypes, had significantly enhanced levels of lung adducts by 210.7% (95% CI, 21.4% to 695.2%) in contrast to the A1298C (AA) plus C677T (CC) genotypes. Elevation of DNA adduct was pronounced-111.3% (95% CI, -3.0 to 360.5%) among 1298AC+CC patients, who consumed the lowest level of folate intake as compared to 1298AA individuals with highest tertile of intake. These results indicate that DNA adducts levels are influenced by MTHFR polymorphisms and low folate consumption, suggesting an important role of genetic and nutritional factors in protecting DNA damage from lung carcinogen in at-risk populations. Copyright © 2011 UICC.

  12. Mutagenic replication in human cell extracts of DNA containing site-specific N-2-acetylaminofluorene adducts.

    Science.gov (United States)

    Thomas, D C; Veaute, X; Kunkel, T A; Fuchs, R P

    1994-08-02

    We have analyzed the effects of site-specific N-2-acetylaminofluorene (AAF) adducts on the efficiency and frameshift fidelity of bidirectional replication of double-stranded DNA in a human cell extract. Plasmid vectors were constructed containing the simian virus 40 origin of replication and single AAF adducts at one of three guanines in the Nar I sequence GGCGCC in a lacZ reporter gene. The presence of an AAF adduct diminishes replication efficiency in HeLa cell extracts by 70-80%. Replication product analyses reveal unique termination sites with each damaged vector, suggesting that when the replication fork encounters an AAF adduct, it often stops before incorporation opposite the adduct. We also observed a higher proportion of products representing replication of the undamaged strand compared to the damaged strand. This suggests that the undamaged strand is replicated more readily, either by uncoupling the first fork to encounter the lesion or by replication using the fork arriving from the other direction. Also included among replication products are covalently closed monomer-length molecules resistant to cleavage at the AAF-modified Nar I site. This resistance is characteristic of substrates containing the AAF adduct, suggesting that translesion bypass had occurred. Transformation of Escherichia coli cells with the replicated damaged DNA yielded lacZ alpha revertant frequencies significantly above values obtained with undamaged DNA or with damaged DNA not replicated in vitro. This increase was only seen with the substrate modified at the third guanine position. Analysis of mutant DNA demonstrated the loss of a GC dinucleotide at the Nar I sequence. Generation of this position-dependent AAF-induced frameshift error in a human replication system is consistent with previous observations in E. coli suggesting that, after incorporation of dCMP opposite modified guanine in the third position, realignment of the template-primer occurs to form an intermediate with two

  13. VIDEO-ANALYSIS OF THE EFFECT OF DIFFERENT TYPES OF ADAPTED SHOES ON KNEE ADDUCTION MOMENT

    Directory of Open Access Journals (Sweden)

    Andrey Yu. Aksenov

    2017-03-01

    Full Text Available Background. The effect of different footwear profiles on knee adduction moment have not been fully studied. Methods. Fifteen healthy volunteer subjects, age 25.3 (±2.73, undertook a series of gait laboratory trials with adapted shoes. Kinematic and kinetic data were collect using 16 Oqus 3+ cameras and the walking speed was controlled using timing gates. High street shoes were adapted to include five different heel heights (varying from a 1.5 cm to 5.5 cm heels, two heel profile conditions (curved and semi-curved heels, three varying apex angles (10, 15, and 20 degrees, and barefoot and 3CR footwear conditions. The baseline shoe had no heel curve, a heel height of 3.5cm, an apex position of 62.5% of the shoe length, an apex angle of 15 deg, and a rigid forepart of the shoe. Results. The shoe with 5.5 cm heel height significantly increased the mean knee adduction moment during 50%–100% of the stance phase compared to the 1.5 cm heel (p = 0.008. The high heel shoe also significantly increased knee adduction impulse (area under the curve versus the 1.5, 2.5, and 3.5 cm heels, and the 10° toe angle and barefoot condition. Ten degrees of toe angle reduced mean knee adduction moment during 0%–50% of the stance phase versus 20° and significantly reduced mean knee adduction moment during the late stance phase versus 15° and 20° toe angle footwear conditions. Walking with the curved heel for the healthy subjects increased mean knee adduction moment during 0%–50% of the stance phase compared to the heel without curvature (p < 0.0009. Conclusion. Further study is required to investigate those changes in patients with high risk of knee osteoarthritis.

  14. Proteomic analysis of acrylamide-protein adduct formation in rat brain synaptosomes

    International Nuclear Information System (INIS)

    Barber, David S.; LoPachin, Richard M.

    2004-01-01

    Evidence suggests that the neurological defects (gait abnormalities, foot splay, and skeletal muscle weakness) associated with acrylamide (ACR) intoxication are mediated by impaired neurotransmission at central and peripheral synapses. ACR can form adducts with nucleophilic residues on proteins and thereby alter corresponding structure and function. To evaluate protein adduction in nerve terminals as a possible mechanism of action, recombinant N-ethylmaleimide sensitive factor (NSF) was exposed in vitro to ACR (10 μmol) and mass spectrometry (MS) was used to identify adduct sites. MS analyses demonstrated that ACR formed adducts with sulfhydryl groups on cysteine residues (carbamoylethylcysteine, or CEC) of NSF. Ex vivo incubation of whole brain synaptosomes with ACR (0.001-1.0 M) produced concentration-dependent increases in CEC that were inversely correlated to reductions in neurotransmitter release that occurred over the same neurotoxicant concentration range. In synaptosomes isolated from rats intoxicated at a higher (50 mg/kg per day x 3, 5, 8, or 11 days) or a lower (21 mg/kg per day x 14, 21, or 28 day) ACR dose rate, CEC levels increased progressively up to a moderate level of neurotoxicity. To identify protein adducts, synaptosomal proteins labeled by ex vivo 14 C-ACR exposure were separated by gel electrophoresis and probed by immunoblot analysis. Results showed that NSF and the SNARE protein, SNAP-25, were tentative ACR targets. Subsequent experiments indicated that ACR exposure increased synaptosomal levels of the 7S SNARE core complex, which is consistent with inhibition of NSF, SNAP-25 function, or both. These data suggest that adduction of cysteine residues on NSF and certain SNARE proteins might be causally involved in the nerve terminal dysfunction induced by ACR

  15. Synthesis, characterisation and optical studies of new tetraethyl- rubyrin-graphene oxide covalent adducts

    Science.gov (United States)

    Garg, Kavita; Shanmugam, Ramakrishanan; Ramamurthy, Praveen C.

    2018-02-01

    Tetrathia-rubyrin and graphene oxide (GO) covalent adduct was synthesized, characterised and optical properties were studied. GO-Rubyrin adducts showed fluorescence quenching of rubyrin due to electron or energy transfer from rubyrin to graphene oxide, which also reflected in UV-vis absorbance spectroscopy. The non-linear optical responses were measured through Z scan technique in nano-second regime. The enhanced optical non-linearity was observed after attachment of GO with rubyrin, can be ascribed to the photo-induced electron or energy transfer from the electron rich rubyrin moiety to the electron deficient GO.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Hip adductor injuries are frequent in football, and players with low adductor strength appear to be at increased risk of injury. High adductor muscle activity has been shown in the Copenhagen Adduction exercise (CA); however, an associated strength gain has not been investigated. This study aims...... to examine the eccentric hip adduction strength (EHAD) gain using the CA in-season. Two U-19 sub-elite football teams, including 24 football players, were randomized to either an 8-week supervised progressive training program in addition to the usual training (intervention) or to continue training as usual...

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

    Science.gov (United States)

    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.

  18. Mechanisms of formation of adducts from reactions of glycidaldehyde with 2'-deoxyguanosine and/or guanosine.

    Science.gov (United States)

    Golding, B T; Slaich, P K; Kennedy, G; Bleasdale, C; Watson, W P

    1996-01-01

    Convenient synthesis of rac-glycidaldehyde from rac-but-3-ene-1,2-diol and (R)-glycidaldehyde from D-mannitol are described. (R)-Glycidaldehyde (1) reacts with guanosine in water (pH 4-11, faster reaction at higher pH) to give initially 6(S)-hydroxy-7(S)-(hydroxymethyl)-3-(beta-D-ribofuranosyl)-5,6,7- trihydroimidazo[1,2-alpha]purin-9(3H)-one (7a) and 6(S),7(R)-dihydroxy-3-(beta-D-ribofuranosyl)-5,6,7,8- tetrahydropyrimido[1,2- alpha]purin-10(3H)-one (8a). The former decomposes to 7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo[1,2- alpha]purine (3a), 5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo[1,2-alpha]purine (5a, 1,N2-ethenoguanosine), and formaldehyde, while the latter adduct is relatively stable. The position of the hydroxymethyl group on the imidazo ring of 7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo-[1,2 - alpha]purine was proved by 13C NMR analysis of adducts derived from [1-15N]guanosine and [amino-15N]guanosine. At longer reaction times, the adduct 7,7'-methylenebis[5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo[1,2- alpha]purine (4a) is formed from guanosine and glycidaldehyde. The structure analysis of this adduct was also aided by 13C NMR analysis of the 15N-labeled adduct derived from [1-15N]guanosine. Analogous adducts were obtained from the reaction between glycidaldehyde and deoxyguanosine. Mechanisms of formation of the adducts from glycidaldehyde and guanosine/deoxyguanosine are proposed and supported by model studies with simple amines. The formaldehyde produced in the reactions described reacts with guanosine to give the known adduct N2-(hydroxymethyl)guanosine (9).

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

    DEFF Research Database (Denmark)

    Veglia, Fabrizio; Loft, Steffen; Matullo, Giuseppe

    2008-01-01

    . 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 association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association...

  20. Identification and quantification of drug-albumin adducts in serum samples from a drug exposure study in mice

    NARCIS (Netherlands)

    Switzar, L.; Kwast, L.M.; Lingeman, H.; Giera, M.; Pieters, R.H.H.; Niessen, W.M.A.

    2013-01-01

    The formation of drug-protein adducts following the bioactivation of drugs to reactive metabolites has been linked to adverse drug reactions (ADRs) and is a major complication in drug discovery and development. Identification and quantification of drug-protein adducts in vivo may lead to a better

  1. Boron Difluoride Adducts of a Flexidentate Pyridine-Substituted Formazanate Ligand: Property Modulation via Protonation and Coordination Chemistry.

    Science.gov (United States)

    Barbon, Stephanie M; Buddingh, Jasmine V; Maar, Ryan R; Gilroy, Joe B

    2017-10-02

    The synthesis and characterization of a flexidentate pyridine-substituted formazanate ligand and its boron difluoride adducts, formed via two different coordination modes of the title ligand, are described. The first adduct adopted a structure that was typical of other boron difluoride adducts of triarylformazanate ligands and contained a free pyridine subsituent, while the second was formed via the chelation of nitrogen atoms from the formazanate backbone and the pyridine substituent. Stepwise protonation of the pydridine-functionalized adduct, which is essentially nonemissive, resulted in a significant increase in the fluorescence quantum yield up to a maximum of 18%, prompting the study of this adduct as a pH sensor. The coordination chemistry of each adduct was explored through reactions with nickel(II) bromide [NiBr 2 (CH 3 CN) 2 ], triflate [Ni(OTf) 2 ], and 1,1,1,4,4,4-hexafluoroacetylacetonate [Ni(hfac) 2 (H 2 O) 2 ] salts. Coordination to nickel(II) ions altered the physical properties of the boron difluoride formazanate adducts, including red-shifted absorption maxima and less negative reduction potentials. Together, these studies have demonstrated that the physical and electronic properties of boron difluoride adducts of formazanate ligands can be readily modulated through protonation and coordination chemistry.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sabro Nielsen, P.

    1996-12-31

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

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

    International Nuclear Information System (INIS)

    Sabro Nielsen, P.

    1996-01-01

    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 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)

  4. Cut elimination in multifocused linear logic

    DEFF Research Database (Denmark)

    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....

  5. Automated Peak Picking and Peak Integration in Macromolecular NMR Spectra Using AUTOPSY

    Science.gov (United States)

    Koradi, Reto; Billeter, Martin; Engeli, Max; Güntert, Peter; Wüthrich, Kurt

    1998-12-01

    A new approach for automated peak picking of multidimensional protein NMR spectra with strong overlap is introduced, which makes use of the program AUTOPSY (automatedpeak picking for NMRspectroscopy). The main elements of this program are a novel function for local noise level calculation, the use of symmetry considerations, and the use of lineshapes extracted from well-separated peaks for resolving groups of strongly overlapping peaks. The algorithm generates peak lists with precise chemical shift and integral intensities, and a reliability measure for the recognition of each peak. The results of automated peak picking of NOESY spectra with AUTOPSY were tested in combination with the combined automated NOESY cross peak assignment and structure calculation routine NOAH implemented in the program DYANA. The quality of the resulting structures was found to be comparable with those from corresponding data obtained with manual peak picking.

  6. Bayesian Peak Picking for NMR Spectra

    KAUST Repository

    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.

  7. Global Earthquake Hazard Distribution - Peak Ground Acceleration

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Earthquake Hazard Distribution-Peak Ground Acceleration is a 2.5 by 2.5 minute grid of global earthquake hazards developed using Global Seismic Hazard Program...

  8. Helping System Engineers Bridge the Peaks

    Science.gov (United States)

    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.

  9. Bayesian Peak Picking for NMR Spectra

    Directory of Open Access Journals (Sweden)

    Yichen Cheng

    2014-02-01

    Full Text Available 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.

  10. How to use your peak flow meter

    Science.gov (United States)

    ... attack . This can tell you how bad your asthma attack is and if your medicine is working. Any ... Make peak flow a habit! Signs of an asthma attack Stay away from asthma triggers Review Date 2/ ...

  11. Global Earthquake Hazard Distribution - Peak Ground Acceleration

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Earthquake Hazard Distribution-peak ground acceleration is a 2.5 minute grid of global earthquake hazards developed using Global Seismic Hazard Program...

  12. Peak-Seeking Control for Trim Optimization

    Data.gov (United States)

    National Aeronautics and Space Administration — Innovators have developed a peak-seeking algorithm that can reduce drag and improve performance and fuel efficiency by optimizing aircraft trim in real time. The...

  13. How do rocker-soled shoes influence the knee adduction moment in people with knee osteoarthritis? An analysis of biomechanical mechanisms.

    Science.gov (United States)

    Madden, Elizabeth G; Kean, Crystal O; Wrigley, Tim V; Bennell, Kim L; Hinman, Rana S

    2017-05-24

    The primary objective was to examine mechanisms behind previously observed changes in the knee adduction moment (KAM) with rocker-soled shoes, in participants sub-grouped according to whether they experienced an immediate decrease, or increase, in peak KAM. In subgroups where frontal plane knee ground reaction force (GRF) lever-arm emerged as a significant predictor, a secondary aim was to examine biomechanical factors that contributed to change in this parameter. Thirty individuals with symptomatic, radiographic knee osteoarthritis (OA) underwent 3D gait analysis in unstable rocker-soled shoes and non-rocker-soled shoes. Multiple regression analyses, within each subgroup, examined relationships between changes in frontal plane knee-GRF lever arm and frontal plane resultant GRF magnitude and changes in peak KAM and KAM impulse between shoe conditions. In the subgroup that decreased peak KAM with rocker-soled shoes (n=23), change in knee-GRF lever arm and frontal plane GRF magnitude at peak KAM together were significant predictors of change in peak KAM; however, only change in mean knee-GRF lever arm significantly predicted change in KAM impulse. Decreased medial GRF magnitude, increased lateral trunk lean towards the stance limb and reduced varus/increased valgus hip-knee-ankle angle were associated with a lower knee-GRF lever arm in this group, with rocker-soled shoes. In contrast, none of the independent variables predicted changes in KAM in the subgroup who increased peak KAM with rocker-soled shoes (n=7). Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  15. Improved peak shape fitting in alpha spectra

    OpenAIRE

    POMME Stefaan; CARO MARROYO BELEN

    2014-01-01

    Peak overlap is a recurrent issue ina lpha-particle spectrometry, not only in routine analyses but also in the high-resolution spectra from which reference values for alpha emission probabilities are derived. In this work, improved peak shape formulae are presented for the deconvolution of alpha-particle spectra. They have been implemented as fit functions in a spreadsheet application and optimum fit parameters were searched with built-in optimisation routines. Deconvolution results are shown...

  16. Elimination of variables in simple laser equations

    Energy Technology Data Exchange (ETDEWEB)

    Ning, C.Z.; Haken, H. (Stuttgart Univ. (Germany). Inst. fuer Theoretische Physik)

    1992-08-01

    The usual way of obtaining rate equations (RE) and a single equation for the field amplitude (EFA) from the semiclassical laser equations (Lorentz-Haken model) is reexamined by undertaking a systematic elimination procedure developed in synergetics. The RE and EFA are justified in the case 1 ({gamma}{sub perpendicular} {sub to}>> {gamma}{sub parallel}, {kappa}) and case 2 ({gamma}{sub perpendicular} {sub to}, {gamma}{sub parallel}>>{kappa}), respectively. We show that, because the eliminated variable happens to contain a considerable contribution from an unstable mode, the usual elimination technique in the case 3 ({gamma}{sub perpendicular} {sub to}, {kappa}>>{gamma}{sub parallel}) leads to an inconsistency. As important by-products we obtain the RE and EFA for arbitrary cavity relaxation constant ({kappa}). Some remarks are given on the direct elimination technique in the non-diagonal representation in the study of instabilities. (orig.).

  17. Instream flow needs below peaking hydroelectric projects

    International Nuclear Information System (INIS)

    Milhous, R.T.

    1991-01-01

    This paper reports on a method developed to assist in the determination of instream flow needs below hydroelectric projects operated in a peaking mode. Peaking hydroelectric projects significantly change streamflow over a short period of time; consequently, any instream flow methodology must consider the dual flows associated with peaking projects. The dual flows are the lowest flow and the maximum generation flow of a peaking cycle. The methodology is based on elements of the Physical Habitat Simulation System of the U.S. Fish and Wildlife Service and uses habitat, rather than fish numbers or biomas, as at basic response variable. All aquatic animals are subject to the rapid changes in streamflow which cause rapid swings in habitat quality. Some aquatic organisms are relatively fixed in location in the stream while others can move when flows change. The habitat available from a project operated in peaking mode is considered to be the minimum habitat occurring during a cycle of habitat change. The methodology takes in to consideration that some aquatic animals can move and others cannot move during a peaking cycle

  18. Role of CYP1B1 in PAH-DNA Adduct Formation and Breast Cancer Risk

    National Research Council Canada - National Science Library

    Goth-Goldstein, Regine

    2002-01-01

    ...) to reactive intermediates appears to be the cytochrome P45O enzyme CYPlB1. High CYPlB1 enzyme levels may result in increased formation of PAH-DNA adducts in breast tissue and lead to subsequent development of breast cancer...

  19. In vitro adduct formation of phosgene with albumin and hemoglobin in human blood

    NARCIS (Netherlands)

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

    2000-01-01

    The development of procedures for retrospective detection and quantitation of exposure to phosgene, based on adducts to hemoglobin and albumin, is described. Upon incubation of human blood with [14C]phosgene (0-750 μM), a significant part of radioactivity (0-13%) became associated with globin and

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

    DEFF Research Database (Denmark)

    Thorborg, Kristian; Couppé, C; Petersen, J

    2011-01-01

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

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

    Science.gov (United States)

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

  2. Hemoglobin adducts in 1,3-butadiene exposed Czech workers: Female–male comparisons

    Czech Academy of Sciences Publication Activity Database

    Vacek, P. M.; Albertini, R. J.; Šrám, Radim; Upton, P.; Swenberg, J. A.

    2010-01-01

    Roč. 188, č. 3 (2010), s. 668-676 ISSN 0009-2797 Institutional research plan: CEZ:AV0Z50390512 Keywords : 3-Butadiene * metabolism * THB-Val hemoglobin adducts Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.832, year: 2010

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  4. Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kousuke Ishino

    2015-02-01

    Full Text Available Nanosized-magnetite (MGT is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC, revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice.

  5. Immunomagnetic separation and quantification of butyrylcholinesterase nerve agent adducts in human serum

    NARCIS (Netherlands)

    Sporty, J.L.S.; Lemire, S.W.; Jakubowski, E.M.; Renner, J.A.; Evans, R.A.; Williams, R.F.; Schmidt, J.G.; Schans, M.J. van der; Noort, D.; Johnson, R.C.

    2010-01-01

    A novel method for extracting butyrylcholinesterase (BuChE) from serum as a means of identifying and measuring nerve agent adducts to human BuChE is presented here. Antibutyrylcholinesterase monoclonal antibodies were conjugated to protein-G ferromagnetic particles and mixed with 500 μL serum

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

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 127; Issue 6. Effect of external electric field on Cyclodextrin-Alcohol adducts: A DFT study. Kundan Baruah Pradip Kr Bhattacharyya. Regular Articles Volume 127 Issue 6 June 2015 pp 1109-1117 ... Keywords. Membrane; electric field; DFT; reactivity descriptor; MHP.

  7. ANTIMONY HALIDES AND HgX2 (X = Cl, Br AMINE ADDUCTS: SYNTHESIS AND INFRARED STUDY

    Directory of Open Access Journals (Sweden)

    NDONGO GUEYE

    2013-12-01

    Full Text Available Eight new SbF3, SbCl5 and HgX2 (X = Cl, Br amine adducts have been synthesized and their infrared study carried out. Discrete structures have been suggested on the basis of elemental analysis and infrared data, the coordination number of antimony varying from five to nine, while the environment around Hg is tetrahedral.

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

    DEFF Research Database (Denmark)

    Thorborg, K; 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...

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

    Indian Academy of Sciences (India)

    Keywords. Membrane; electric field; DFT; reactivity descriptor; MHP. 1. Introduction. Cyclodextrins (CDs) are natural ... for membrane preparations, which are used extensively in separation science offering a good choice .... culated BSSE corrected gas phase interaction energies in adducts (figure 1) are found to be −33.737, ...

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

    Czech Academy of Sciences Publication Activity Database

    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 - others: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

  11. 32P-Postlabelling/HPLC analysis of various styrene-induced DNA adducts in mice

    Czech Academy of Sciences Publication Activity Database

    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 - others:GA-(EU) QLK4-1999-01368 Institutional research plan: CEZ:AV0Z5039906 Keywords : DNA adducts Subject RIV: EA - Cell Biology Impact factor: 1.118, year: 2001

  12. Facile Synthesis of 5-Hydroxy-3-pyrrolin-2-ones from Morita-Baylis-Hillman Adducts

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Cheol Hee; Kim, Sung Hwan; Kim, Jae Nyoung [Chonnam National University, Gwangju (Korea, Republic of)

    2012-05-15

    An efficient synthetic method of various 5-hydroxy-3-pyrrolin-2-one derivatives has been developed starting from the MBH adducts. In addition, some synthetic applicability of the prepared 5-hydroxy-3-pyrrolin-2-ones was demonstrated including the synthesis of lactam-fused tetrahydroisoquinolines.

  13. Crystal structure of the pyridine-diiodine (1/1) adduct.

    Science.gov (United States)

    Tuikka, Matti; Haukka, Matti

    2015-07-01

    In the title adduct, C5H5N·I2, the N-I distance [2.424 (8) Å] is remarkably shorter than the sum of the van der Waals radii. The line through the I atoms forms an angle of 78.39 (16)° with the normal to the pyridine ring.

  14. Crystal structure of the pyridine–diiodine (1/1 adduct

    Directory of Open Access Journals (Sweden)

    Matti Tuikka

    2015-07-01

    Full Text Available In the title adduct, C5H5N·I2, the N—I distance [2.424 (8 Å] is remarkably shorter than the sum of the van der Waals radii. The line through the I atoms forms an angle of 78.39 (16° with the normal to the pyridine ring.

  15. Poly(acrylic acid)/poly(ethylene glycol) adduct for attaining multifunctional cellulosic fabrics.

    Science.gov (United States)

    Ibrahim, N A; Amr, A; Eid, B M; Mohamed, Z E; Fahmy, H M

    2012-06-20

    Aqueous polymerization of partially neutralized acrylic acid (AA) along with polyethylene glycol (PEG-600) at AA/PEG-600 mass ratio 3/1 using ammonium persulfate as initiator under proper conditions results in formation of PAA/PEG-600 adduct. The structure of the adduct was confirmed by FT-IR spectra. The potential applications of the prepared adduct in: sizing, durable hand building of cotton cellulose, as well as in functional finishing of cellulose containing fabrics, i.e. cotton, viscose and cotton/polyester, with Ag- or TiO2-nanoparticles were investigated. The modified substrates using the prepared adduct showed a remarkable improvement in their sizing, hand building and/or functional properties, i.e. antibacterial, anti-UV, and self cleaning, in addition to durability to wash. TEM images of the prepared nano-particles, SEM images of the untreated and treated substrates, as well as EDX spectra to analyze the surface elemental compositions were examined. The tentative mechanisms were also suggested. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Silva, M. das G. da.

    1983-01-01

    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.) [pt

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

    Czech Academy of Sciences Publication Activity Database

    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 - others: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

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

    Czech Academy of Sciences Publication Activity Database

    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

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

    Czech Academy of Sciences Publication Activity Database

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

    2001-01-01

    Roč. 74, - (2001), s. 680-687 ISSN 0340-5761 Grant - others: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. Bypass of Aflatoxin B[subscript 1] Adducts by the Sulfolobus solfataricus DNA Polymerase IV

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-18

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

  1. Predicting Peak Flows following Forest Fires

    Science.gov (United States)

    Elliot, William J.; Miller, Mary Ellen; Dobre, Mariana

    2016-04-01

    Following forest fires, peak flows in perennial and ephemeral streams often increase by a factor of 10 or more. This increase in peak flow rate may overwhelm existing downstream structures, such as road culverts, causing serious damage to road fills at stream crossings. In order to predict peak flow rates following wildfires, we have applied two different tools. One is based on the U.S.D.A Natural Resource Conservation Service Curve Number Method (CN), and the other is by applying the Water Erosion Prediction Project (WEPP) to the watershed. In our presentation, we will describe the science behind the two methods, and present the main variables for each model. We will then provide an example of a comparison of the two methods to a fire-prone watershed upstream of the City of Flagstaff, Arizona, USA, where a fire spread model was applied for current fuel loads, and for likely fuel loads following a fuel reduction treatment. When applying the curve number method, determining the time to peak flow can be problematic for low severity fires because the runoff flow paths are both surface and through shallow lateral flow. The WEPP watershed version incorporates shallow lateral flow into stream channels. However, the version of the WEPP model that was used for this study did not have channel routing capabilities, but rather relied on regression relationships to estimate peak flows from individual hillslope polygon peak runoff rates. We found that the two methods gave similar results if applied correctly, with the WEPP predictions somewhat greater than the CN predictions. Later releases of the WEPP model have incorporated alternative methods for routing peak flows that need to be evaluated.

  2. O6-pyridyloxobutylguanine adducts contribute to the mutagenic properties of pyridyloxobutylating agents.

    Science.gov (United States)

    Mijal, Renée S; Loktionova, Natalia A; Vu, Choua C; Pegg, Anthony E; Peterson, Lisa A

    2005-10-01

    The tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are potent carcinogens in animal models and likely human carcinogens. Both NNK and NNN can be activated to a pyridyloxobutylating agent. This alkylating agent contributes to the carcinogenic effects of NNK and NNN via the formation of miscoding DNA adducts. One of these adducts, O6-[4-oxo-4-(3-pyridyl)butyl]guanine (O6-pobG) has been characterized as a mutagenic adduct which is a substrate for the repair protein O6-alkylguanine-DNA alkyltransferase (AGT). Repair of O6-alkylguanine adducts by AGT protects cells from the mutagenic and carcinogenic effects of alkylating agents and is likely to play a similar role in shielding cells from the adverse effects of pyridyloxobutylating agents. Therefore, we examined the mutagenicity of the model pyridyloxobutylating agent, 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc), in Salmonella typhimurium YG7108 expressing hAGT. Expression of hAGT protected cells from NNKOAc-induced mutagenicity. Interestingly, hAGT did not shield cells from the toxicity of this agent. To confirm that the repair of O6-pobG was increased in the bacteria expressing hAGT, we measured levels of this adduct in NNKOAc-treated cultures. The levels of O6-pobG were lower in DNA from bacteria expressing hAGT. This work establishes an important role for O6-pobG in mediating the mutagenic, and possibly carcinogenic, effects of pyridyloxobutylating compounds.

  3. Base Excision Repair of N6-Deoxyadenosine Adducts of 1,3-Butadiene.

    Science.gov (United States)

    Wickramaratne, Susith; Banda, Douglas M; Ji, Shaofei; Manlove, Amelia H; Malayappan, Bhaskar; Nuñez, Nicole N; Samson, Leona; Campbell, Colin; David, Sheila S; Tretyakova, Natalia

    2016-11-01

    The important industrial and environmental carcinogen 1,3-butadiene (BD) forms a range of adenine adducts in DNA, including N 6 -(2-hydroxy-3-buten-1-yl)-2'-deoxyadenosine (N 6 -HB-dA), 1,N 6 -(2-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyadenosine (1,N 6 -HMHP-dA), and N 6 ,N 6 -(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (N 6 ,N 6 -DHB-dA). If not removed prior to DNA replication, these lesions can contribute to A → T and A → G mutations commonly observed following exposure to BD and its metabolites. In this study, base excision repair of BD-induced 2'-deoxyadenosine (BD-dA) lesions was investigated. Synthetic DNA duplexes containing site-specific and stereospecific (S)-N 6 -HB-dA, (R,S)-1,N 6 -HMHP-dA, and (R,R)-N 6 ,N 6 -DHB-dA adducts were prepared by a postoligomerization strategy. Incision assays with nuclear extracts from human fibrosarcoma (HT1080) cells have revealed that BD-dA adducts were recognized and cleaved by a BER mechanism, with the relative excision efficiency decreasing in the following order: (S)-N 6 -HB-dA > (R,R)-N 6 ,N 6 -DHB-dA > (R,S)-1,N 6 -HMHP-dA. The extent of strand cleavage at the adduct site was decreased in the presence of BER inhibitor methoxyamine and by competitor duplexes containing known BER substrates. Similar strand cleavage assays conducted using several eukaryotic DNA glycosylases/lyases (AAG, Mutyh, hNEIL1, and hOGG1) have failed to observe correct incision products at the BD-dA lesion sites, suggesting that a different BER enzyme may be involved in the removal of BD-dA adducts in human cells.

  4. Differences in micronucleus frequency and acrylamide adduct levels with hemoglobin between vegetarians and non-vegetarians.

    Science.gov (United States)

    Kotova, Natalia; Frostne, Cecilia; Abramsson-Zetterberg, Lilianne; Tareke, Eden; Bergman, Rolf; Haghdoost, Siamak; Paulsson, Birgit; Törnqvist, Margareta; Segerbäck, Dan; Jenssen, Dag; Grawé, Jan

    2015-10-01

    Nutrients and food constituents can prevent or contribute to genotoxicity. In this study, the possible influence of a vegetarian/non-vegetarian diet on genotoxic effects was investigated in 58 non-smoking healthy vegetarians (V) and non-vegetarians (NV), age 21-37 years from the Stockholm area in Sweden. Physical activity and dietary habits were similar in both groups, with the exception of the intake of meat and fish. Using flow cytometry, we determined the formation of micronuclei (MN) in transferrin-positive immature peripheral blood reticulocytes (Trf-Ret) (Total: n = 53; V: n = 27; NV: n = 26). Dietary exposure to acrylamide was measured through hemoglobin (Hb) adducts in peripheral erythrocytes (Total: n = 53; V: n = 29; NV: n = 24). Hb adducts of both acrylamide and its genotoxic metabolite glycidamide were monitored as a measure of the corresponding in vivo doses. Our data demonstrated that compared with the non-vegetarians, the vegetarians exhibited lower frequencies of MN (fMN) in the Trf-Ret (p vegetarians and non-vegetarians. Furthermore, there were no significant relationships between the adduct levels and fMN in the individuals. The ratio of the Hb adduct levels from glycidamide and acrylamide, however, showed a significant difference (p vegetarian diet might be beneficial in lowering genomic instability in healthy individuals. The measured Hb adduct levels indicate that the total intake of acrylamide does not differ between the two studied groups and does not contribute to the observed difference in fMN, although an influence of the diet on the metabolic rates of acrylamide was indicated. In addition, the observed significant difference in the background fMN in the two groups demonstrated that the MN analysis method has a sensitivity applicable to the biomonitoring of human lifestyle factors.

  5. Formation of Hydroxymethyl DNA Adducts in Rats Orally Exposed to Stable Isotope Labeled Methanol

    Science.gov (United States)

    Lu, Kun; Gul, Husamettin; Upton, Patricia B.; Moeller, Benjamin C.; Swenberg, James A.

    2012-01-01

    Methanol is a large volume industrial chemical and widely used solvent and fuel additive. Methanol’s well known toxicity and use in a wide spectrum of applications has raised long-standing environmental issues over its safety, including its carcinogenicity. Methanol has not been listed as a carcinogen by any regulatory agency; however, there are debates about its carcinogenic potential. Formaldehyde, a metabolite of methanol, has been proposed to be responsible for the carcinogenesis of methanol. Formaldehyde is a known carcinogen and actively targets DNA and protein, causing diverse DNA and protein damage. However, formaldehyde-induced DNA adducts arising from the metabolism of methanol have not been reported previously, largely due to the absence of suitable DNA biomarkers and the inability to differentiate what was due to methanol compared with the substantial background of endogenous formaldehyde. Recently, we developed a unique approach combining highly sensitive liquid chromatography-mass spectrometry methods and exposure to stable isotope labeled chemicals to simultaneously quantify formaldehyde-specific endogenous and exogenous DNA adducts. In this study, rats were exposed daily to 500 or 2000 mg/kg [13CD4]-methanol by gavage for 5 days. Our data demonstrate that labeled formaldehyde arising from [13CD4]-methanol induced hydroxymethyl DNA adducts in multiple tissues in a dose-dependent manner. The results also demonstrated that the number of exogenous DNA adducts was lower than the number of endogenous hydroxymethyl DNA adducts in all tissues of rats administered 500 mg/kg per day for 5 days, a lethal dose to humans, even after incorporating an average factor of 4 for reduced metabolism due to isotope effects of deuterium-labeled methanol into account. PMID:22157354

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

    Directory of Open Access Journals (Sweden)

    Laura James

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

  7. PAH-DNA adducts in cord blood and fetal and child development in a Chinese cohort

    Energy Technology Data Exchange (ETDEWEB)

    Tang, D.L.; Li, T.Y.; Liu, J.J.; Chen, Y.H.; Qu, L.R.; Perera, F. [Columbia University, New York, NY (United States). Dept. for Environmental Health Science

    2006-08-15

    Polycyclic aromatic hydrocarbons (PAHs) are an important class of toxic pollutants released by fossil fuel combustion. Other pollutants include metals and particulate matter. PAH-DNA adducts, or benzo(a)pyrene (BaP) adducts as their proxy, provide a chemical-specific measure of individual biologically effective doses that have been associated with increased risk of cancer and adverse birth outcomes. In the present study we examined the relationship between prenatal PAH exposure and fetal and child growth and development in Tongliang, China, where a seasonally operated coal-fired power plant was the major pollution source. In a cohort of 150 nonsmoking women and their newborns enrolled between 4 March 2002 and 19 June 2002, BaP-DNA adducts were measured in maternal and umbilical cord blood obtained at delivery. High PAH-DNA adduct levels (above the median of detectable adduct level) were associated with decreased birth head circumference (p = 0.057) and reduced children's weight at 18 months, 24 months, and 30 months of age (p {lt} 0.05), after controlling for potential confounders. In addition, in separate models, longer duration of prenatal exposure was associated with reduced birth length (p = 0.033) and reduced children's height at 18 (p = 0.001), 24 (p {lt} 0.001), and 30 months of age (p {lt} 0.001). The findings suggest that exposure to elevated levels of PAHS, with the Tongliang power plant being a significant source, is associated with reduced fetal and child growth in this population.

  8. Detection of Pyrrolizidine Alkaloid DNA Adducts in Livers of Cattle Poisoned with Heliotropium europaeum.

    Science.gov (United States)

    Fu, Peter P; Xia, Qingsu; He, Xiaobo; Barel, Shimon; Edery, Nir; Beland, Frederick A; Shimshoni, Jakob A

    2017-03-20

    Pyrrolizidine alkaloids are among the most common poisonous plants affecting livestock, wildlife, and humans. Exposure of humans and livestock to toxic pyrrolizidine alkaloids through the intake of contaminated food and feed may result in poisoning, leading to devastating epidemics. During February 2014, 73 mixed breed female beef cows from the Galilee region of Israel were accidently fed pyrrolizidine alkaloid contaminated hay for 42 days, resulting in the sudden death of 24 cows over a period of 63 days. The remaining cows were slaughtered 2.5 months after the last ingestion of the contaminated hay. In this study, we report the histopathological analysis of the livers from five of the slaughtered cows and quantitation of pyrrolizidine alkaloid-derived DNA adducts from their livers and three livers of control cows fed with feed free of weeds producing pyrrolizidine alkaloids. Histopathological examination revealed that the five cows suffered from varying degrees of bile duct proliferation, fibrosis, and megalocytosis. Selected reaction monitoring HPLC-ES-MS/MS analysis indicated that (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts were formed in all five livers. The livers from the three control cows did not have any liver damage nor any indication of DHP-DNA adduct formed. These results confirm that the toxicity observed in these cattle was caused by pyrrolizidine alkaloid poisoning and that pyrrolizidine alkaloid-derived DNA adducts could still be detected and quantified in the livers of the chronically poisoned cows 2.5 months after their last exposure to the contaminated feed, suggesting that DHP-derived DNA adducts can serve as biomarkers for pyrrolizidine alkaloid exposure and poisoning.

  9. Full structure assignments of pyrrolizidine alkaloid DNA adducts and mechanism of tumor initiation.

    Science.gov (United States)

    Zhao, Yuewei; Xia, Qingsu; Gamboa da Costa, Gonçalo; Yu, Hongtao; Cai, Lining; Fu, Peter P

    2012-09-17

    Pyrrolizidine alkaloid-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids are among the first chemical carcinogens identified in plants. Previously, we determined that metabolism of pyrrolizidine alkaloids in vivo and in vitro generated a common set of DNA adducts that are responsible for tumor induction. Using LC-ESI/MS/MS analysis, we previously determined that four DNA adducts (DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4) were formed in rats dosed with riddelliine, a tumorigenic pyrrolizidine alkaloid. Because of the lack of an adequate amount of authentic standards, the structures of DHP-dA-3 and DHP-dA-4 were not elucidated, and the structural assignment for DHP-dG-4 warranted further validation. In this study, we developed an improved synthetic methodology for these DNA adducts, enabling their full structural elucidation by mass spectrometry and NMR spectroscopy. We determined that DHP-dA-3 and DHP-dA-4 are a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl) dehydrosupinidine, while DHP-dG-4 is 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine, an epimer of DHP-dG-3. With the structures of these DNA adducts unequivocally elucidated, we conclude that cellular DNA preferentially binds dehydropyrrolizidine alkaloid, for example, dehydroriddelliine, at the C9 position of the necine base, rather than at the C7 position. We also determined that DHP-dA-3 and DHP-dA-4, as well as DHP-dG-3 and DHP-dG-4, are interconvertible. This study represents the first report with detailed structural assignments of the DNA adducts that are responsible for pyrrolizidine alkaloid tumor induction on the molecular level. A mechanism of tumor initiation by pyrrolizidine alkaloids is consequently fully determined.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-01

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

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

    KAUST Repository

    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.

  12. Noise Elimination Study for a Single Station Magnetotelluric Data

    Science.gov (United States)

    Şengül, Ebru; Uǧur Ulugergerli, Emin; Göktaş, Hilal

    2010-05-01

    Five components of the natural electromagnetic field relating to underground conductivity distribution on Earth are measured as a time series in the Magnetotelluric (MT) method. E (Ex, Ey) and H (Hx, Hy, Hz) components of the electromagnetic field suffers from noise contamination. The noise, in general, can be classified as random and systematic noise. Random noise disrupts the pattern of data such as sudden signal peaks and/or step structures called impulsive effect. This type of noise usually is dominant in some parts of the time series. The sources of random noise vary; some of the sources are instrumental problems and atmospheric events. On the other hand, systematic noise occurs at certain frequencies and is added to the data. Industrial activities cause such type of the noise and can corrupt all the data set. The estimation of the impedance tensor from single-station MT data is subject to this study. The proposed method uses statistical approaches focused on the noise elimination techniques. Noise elimination from MT time series is very important particularly to achieve repeatable impedance values using single station MT data. The conventional impedance estimation technique requires solution of a linear equation system (E = ZH) based on Gaussian statistical model which requires the noise of electric channels should obey Gaussian distribution and magnetic channels should be noise free. In fact, measured data never provides this ideal condition. Therefore, noise elimination techniques are very important step in data processing works in MT method. Random noise such as spikes makes deviations in impedance values, resistivity and phase curves. Random noise should be eliminated to correct of these deviations in the data. For this purpose firstly, all data are divided into time windows. Each window consists of 512 values. After that, spikes are removed and missing data are regenerated by using interpolation technique for each window in time domain. Then, data are

  13. The accumulation and elimination of 89Sr in tea leaves

    International Nuclear Information System (INIS)

    Zhang Yongxi; Wang Shouxiang; Chen Chuanqun; Sun Zhiming; Hu Bingmin; Huang Dan

    1995-01-01

    The 89 Sr was added to the tea tree-soil system by different ways. The 89 Sr in the system through the over-ground part of tea tree, was much more than that through soil. The 89 Sr concentration in older leaves was higher than in shoot for a definite treatment. The accumulation elimination law of 89 Sr in leaves varied with the treatments. For the treatment through the over-ground part, the 89 Sr concentration in older leaves and shoot was monotonously decreased with time increasing. But for the treatment through soil the 89 Sr concentration in shoot was increased to reach a peak value, and then decreased slowly; while the 89 Sr concentration in older leaves increased quickly in a period, then increased slowly to attain a saturated value. In addition, the concentration factor of 89 Sr in older leaves and shoot were determined

  14. DNA adduct formation in B6C3F1 mice and Fischer-344 rats exposed to 1,2,3-trichloropropane.

    Science.gov (United States)

    La, D K; Lilly, P D; Anderegg, R J; Swenberg, J A

    1995-06-01

    1,2,3-Trichloropropane (TCP) is a multispecies, multisite carcinogen which has been found to be an environmental contaminant. In this study, we have characterized and measured DNA adducts formed in vivo following exposure to TCP. [14C]TCP was administered to male B6C3F1 mice and Fischer-344 rats by gavage at doses used in the NTP carcinogenesis bioassay. Both target and nontarget organs were examined for the formation of DNA adducts. Adducts were hydrolyzed from DNA by neutral thermal or mild acid hydrolysis, isolated by HPLC, and detected and quantitated by measurement of radioactivity. The HPLC elution profile of radioactivity suggested that one major DNA adduct was formed. To characterize this adduct, larger yields were induced in rats by intraperitoneal administration of TCP (300 mg/kg). The DNA adduct was isolated by HPLC based on coelution with the radiolabeled adduct, and compared to previously identified adducts. The isolated adduct coeluted with S-[1-(hydroxymethyl)-2-(N7-guanyl)-ethyl]glutathione, an adduct derived from the structurally related carcinogen 1,2-dibromo-3-chloropropane (DBCP). Analysis by electrospray mass spectrometry suggested that the TCP-induced adduct and the DBCP-derived adduct were identical. The 14C-labeled DNA adduct was distributed widely among the organs examined. Adduct levels varied depending on species, organ, and dose. In rat organs, adduct concentrations for the low dose ranged from 0.8 to 6.6 mumol per mol guanine and from 7.1 to 47.6 mumol per mol guanine for the high dose. In the mouse, adduct yields ranged from 0.32 to 28.1 mumol per mol guanine for the low dose and from 12.2 to 208.1 mumol per mol guanine for the high dose. The relationship between DNA adduct formation and organ-specific tumorigenesis was unclear. Although relatively high concentrations of DNA adducts were detected in target organs, several nontarget sites also contained high adduct levels. Our data suggest that factors in addition to adduct formation

  15. Analysis of fuel end-temperature peaking

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Z.; Jiang, Q.; Lai, L.; Shams, M. [CANDU Energy Inc., Fuel Engineering Dept., Mississauga, Ontario (Canada)

    2013-07-01

    During normal operation and refuelling of CANDU® fuel, fuel temperatures near bundle ends will increase due to a phenomenon called end flux peaking. Similar phenomenon would also be expected to occur during a postulated large break LOCA event. The end flux peaking in a CANDU fuel element is due to the fact that neutron flux is higher near a bundle end, in contact with a neighbouring bundle or close to heavy water coolant, than in the bundle mid-plane, because of less absorption of thermal neutrons by Zircaloy or heavy water than by the UO{sub 2} material. This paper describes Candu Energy experience in analysing behaviour of bundle due to end flux peaking using fuel codes FEAT, ELESTRES and ELOCA. (author)

  16. Body elimination attitude family resemblance in Kuwait.

    Science.gov (United States)

    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.

  17. Martian Atmospheric Pressure Static Charge Elimination Tool

    Science.gov (United States)

    Johansen, Michael R.

    2014-01-01

    A Martian pressure static charge elimination tool is currently in development in the Electrostatics and Surface Physics Laboratory (ESPL) at NASA's Kennedy Space Center. In standard Earth atmosphere conditions, static charge can be neutralized from an insulating surface using air ionizers. These air ionizers generate ions through corona breakdown. The Martian atmosphere is 7 Torr of mostly carbon dioxide, which makes it inherently difficult to use similar methods as those used for standard atmosphere static elimination tools. An initial prototype has been developed to show feasibility of static charge elimination at low pressure, using corona discharge. A needle point and thin wire loop are used as the corona generating electrodes. A photo of the test apparatus is shown below. Positive and negative high voltage pulses are sent to the needle point. This creates positive and negative ions that can be used for static charge neutralization. In a preliminary test, a floating metal plate was charged to approximately 600 volts under Martian atmospheric conditions. The static elimination tool was enabled and the voltage on the metal plate dropped rapidly to -100 volts. This test data is displayed below. Optimization is necessary to improve the electrostatic balance of the static elimination tool.

  18. Effects of footwear on the knee adduction moment in medial knee osteoarthritis: classification criteria for flat flexible vs stable supportive shoes.

    Science.gov (United States)

    Paterson, K L; Bennell, K L; Wrigley, T V; Metcalf, B R; Kasza, J; Hinman, R S

    2017-02-01

    To validate simple criteria that distinguish flat flexible from stable supportive walking shoes by comparing their effects on the knee adduction moment (KAM) in people with medial knee osteoarthritis (OA). This was a cross-sectional biomechanical study. We proposed five criteria to differentiate flat flexible from stable supportive shoes, and selected three pairs of shoes representing each class for biomechanical testing. 28 participants aged ≥50 years with symptomatic medial knee OA underwent gait analysis barefoot and wearing each of the six selected shoes, in random order. Differences in the peak KAM, KAM impulse and peak knee flexion moment (KFM) across test conditions were evaluated with a two-way repeated measures analysis of variance (ANOVA). Immediate changes in walking pain between conditions were also compared. Increases in KAM from barefoot were lower with each of the three flat flexible shoe styles (peak KAM: 6.1-8.9%; KAM impulse: 2.4-5.1%) compared to their stable supportive counterparts (peak KAM: 11.6-15.1%; KAM impulse 10.5-13.2%). There was a significant main effect for footwear class on peak KAM and KAM impulse, whereby stable supportive shoes increased the KAM significantly more than flat flexible shoes (P shoes for people with medial knee OA to minimise knee loading. Future research should evaluate whether wearing shoes based on these criteria translates to improvements in knee OA symptoms and/or slows structural disease progression. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

    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 N2-dG-ABA adduct reported by de los Santos and co-workers, which oriented in the minor groove towards 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-dG-ABA and

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

    Science.gov (United States)

    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. Elimination of Ideas and Professional Socialisation

    DEFF Research Database (Denmark)

    Gravengaard, Gitte; Rimestad, Lene

    2012-01-01

    . 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......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...... for 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...

  2. Ten years left to eliminate blinding trachoma

    Directory of Open Access Journals (Sweden)

    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.

  3. Norfolk Schools Talked to Astronaut Tim Peake

    Science.gov (United States)

    Grant, Stephanie

    2016-01-01

    Tim Peake's mission to the International Space Station captured the imagination of the UK and this article describes a live radio link with him, to help him to reach out to pupils across the country and inspire them in STEM subjects. It describes the project, from bidding for the opportunity to host it, to the planning and realisation of the…

  4. Generalized Eck peak in inhomogeneous Josephson junctions

    Science.gov (United States)

    Fistul, Mikhail V.; Giuliani, Gabriele F.

    1997-02-01

    In inhomogeneous Josephson junctions the Eck peak characterizing the current-voltage characteristics is predicted to be replaced by a rather different yet prominent feature whose location and shape strongly depend on the strength of the applied magnetic field and the spatial correlations of the associated distorted Abrikosov flux lattice.

  5. Biomonitoring DNA Adducts of Cooked Meat Carcinogens in Human Prostate by Nano Liquid Chromatography-High Resolution Tandem Mass Spectrometry: Identification of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine DNA Adduct.

    Science.gov (United States)

    Xiao, Shun; Guo, Jingshu; Yun, Byeong Hwa; Villalta, Peter W; Krishna, Suprita; Tejpaul, Resha; Murugan, Paari; Weight, Christopher J; Turesky, Robert J

    2016-12-20

    Epidemiologic studies have reported an association between frequent consumption of well-done cooked meats and prostate cancer risk. However, unambiguous physiochemical markers of DNA damage from carcinogens derived from cooked meats, such as DNA adducts, have not been identified in human samples to support this paradigm. We have developed a highly sensitive nano-LC-Orbitrap MS n method to measure DNA adducts of several carcinogens originating from well-done cooked meats, tobacco smoke, and environmental pollution, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-9H-pyrido[2,3-b]indole (AαC), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), benzo[a]pyrene (B[a]P), and 4-aminobiphenyl (4-ABP). The limit of quantification (LOQ) of the major deoxyguanosine (dG) adducts of these carcinogens ranged between 1.3 and 2.2 adducts per 10 9 nucleotides per 2.5 μg of DNA assayed. The DNA adduct of PhIP, N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP) was identified in 11 out of 35 patients, at levels ranging from 2 to 120 adducts per 10 9 nucleotides. The dG-C8 adducts of AαC and MeIQx, and the B[a]P adduct, 10-(deoxyguanosin-N 2 -yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N 2 -B[a]PDE) were not detected in any specimen, whereas N-(deoxyguanosin-8-yl)-4-ABP (dG-C8-4-ABP) was identified in one subject (30 adducts per 10 9 nucleotides). PhIP-DNA adducts also were recovered quantitatively from formalin fixed paraffin embedded (FFPE) tissues, signifying FFPE tissues can serve as biospecimens for carcinogen DNA adduct biomarker research. Our biomarker data provide support to the epidemiological observations implicating PhIP, one of the most mass-abundant heterocyclic aromatic amines formed in well-done cooked meats, as a DNA-damaging agent that may contribute to the etiology of prostate cancer.

  6. Nuclear magnetic resonance studies of an N2-guanine adduct derived from the tumorigen dibenzo[a,l]pyrene in DNA: impact of adduct stereochemistry, size, and local DNA sequence on solution conformations.

    Science.gov (United States)

    Rodríguez, Fabián A; Liu, Zhi; Lin, Chin H; Ding, Shuang; Cai, Yuqin; Kolbanovskiy, Alexander; Kolbanovskiy, Marina; Amin, Shantu; Broyde, Suse; Geacintov, Nicholas E

    2014-03-25

    The dimensions and arrangements of aromatic rings (topology) in adducts derived from the reactions of polycyclic aromatic hydrocarbon (PAH) diol epoxide metabolites with DNA influence the distortions and stabilities of double-stranded DNA, and hence their recognition and processing by the human nucleotide excision repair (NER) system. Dibenzo[a,l]pyrene (DB[a,l]P) is a highly tumorigenic six-ring PAH, which contains a nonplanar and aromatic fjord region that is absent in the structurally related bay region five-ring PAH benzo[a]pyrene (B[a]P). The PAH diol epoxide-DNA adducts formed include the stereoisomeric 14S and 14R trans-anti-DB[a,l]P-N(2)-dG and the stereochemically analogous 10S- and 10R-B[a]P-N(2)-dG (B[a]P-dG) guanine adducts. However, nuclear magnetic resonance (NMR) solution studies of the 14S-DB[a,l]P-N(2)-dG adduct in DNA have not yet been presented. Here we have investigated the 14S-DB[a,l]P-N(2)-dG adduct in two different sequence contexts using NMR methods with distance-restrained molecular dynamics simulations. In duplexes with dC opposite the adduct deleted, a well-resolved base-displaced intercalative adduct conformation can be observed. In full duplexes, in contrast to the intercalated 14R stereoisomeric adduct, the bulky DB[a,l]P residue in the 14S adduct is positioned in a greatly widened and distorted minor groove, with significant disruptions and distortions of base pairing at the lesion site and two 5'-side adjacent base pairs. These unique structural features are significantly different from those of the stereochemically analogous but smaller B[a]P-dG adduct. The greater size and different topology of the DB[a,l]P aromatic ring system lead to greater structurally destabilizing DNA distortions that are partially compensated by stabilizing DB[a,l]P-DNA van der Waals interactions, whose combined effects impact the NER response to the adduct. These structural results broaden our understanding of the structure-function relationship in NER.

  7. Prediction of peak overlap in NMR spectra

    International Nuclear Information System (INIS)

    Hefke, Frederik; Schmucki, Roland; Güntert, Peter

    2013-01-01

    Peak overlap is one of the major factors complicating the analysis of biomolecular NMR spectra. We present a general method for predicting the extent of peak overlap in multidimensional NMR spectra and its validation using both, experimental data sets and Monte Carlo simulation. The method is based on knowledge of the magnetization transfer pathways of the NMR experiments and chemical shift statistics from the Biological Magnetic Resonance Data Bank. Assuming a normal distribution with characteristic mean value and standard deviation for the chemical shift of each observable atom, an analytic expression was derived for the expected overlap probability of the cross peaks. The analytical approach was verified to agree with the average peak overlap in a large number of individual peak lists simulated using the same chemical shift statistics. The method was applied to eight proteins, including an intrinsically disordered one, for which the prediction results could be compared with the actual overlap based on the experimentally measured chemical shifts. The extent of overlap predicted using only statistical chemical shift information was in good agreement with the overlap that was observed when the measured shifts were used in the virtual spectrum, except for the intrinsically disordered protein. Since the spectral complexity of a protein NMR spectrum is a crucial factor for protein structure determination, analytical overlap prediction can be used to identify potentially difficult proteins before conducting NMR experiments. Overlap predictions can be tailored to particular classes of proteins by preparing statistics from corresponding protein databases. The method is also suitable for optimizing recording parameters and labeling schemes for NMR experiments and improving the reliability of automated spectra analysis and protein structure determination.

  8. Determination of Catechol Estrogen Adducts by High-Performance Liquid Chromatography: Establishing Biomarkers for the Early Detection of Breast Cancer

    National Research Council Canada - National Science Library

    Stack, Douglas

    2002-01-01

    In order to better understand the role of estrogen metabolism as it relates to breast cancer etiology, a new analytical technique that can measure CE and CE-DNA adducts at low endogenous levels is being developed...

  9. Determination of Catechol Estrogen Adducts by High-Performance Liquid Chromatography: Establishing Biomarkers for the Early Detection of Breast Cancer

    National Research Council Canada - National Science Library

    Stack, Douglas

    2001-01-01

    In order to better understand the role of estrogen metabolism as it relates to breast cancer etiology, a new analytical technique that can measure CE and CE-DNA adducts at low endogenous levels is being developed...

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

    Directory of Open Access Journals (Sweden)

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Danish cohort. At enrollment, blood samples were collected and information on lifestyle, including dietary and smoking habits, obtained. Previously, bulky DNA adducts were measured in 245 individuals who developed lung cancer and 255 control members of the cohort. Of these 500 individuals, data on 375...... individuals were included in this study, excluding 125 cases, which developed lung cancer within the first 3 yr after blood sampling. Bulky DNA adduct levels were measured by 32P-postlabeling technique and polymorphisms in carcinogen metabolism and DNA repair genes were determined. Potential predictors...... found between dietary factors or smoking and DNA adduct levels. Further, the results showed no prominent associations between any of 12 genetic polymorphisms and adduct levels. Overall, our study showed only few associations between dietary, environmental, and genetic factors and levels of bulky DNA...

  12. Diagnosis and Dosimetry of Exposure to Sulfur Mustard: Development of Standard Operating Procedures; Further Exploratory Research on Protein Adducts

    National Research Council Canada - National Science Library

    Benschop, H

    1999-01-01

    .... Both procedures could be substantially shortened, while their sensitivities were improved. Furthermore, exploratory research is performed aiming at the development of a fieldable immunochemical assay for sulfur mustard adducts with proteins, i.e...

  13. Strategy elimination in games with interaction structures

    NARCIS (Netherlands)

    Witzel, A.; Apt, K.R.; Zvesper, J.A.

    2009-01-01

    We study games in the presence of an interaction structure, which allows players to communicate their preferences, assuming that each player initially only knows his own preferences. We study the outcomes of iterated elimination of strictly dominated strategies (IESDS) that can be obtained in any

  14. Elimination of Constraints from Feature Trees

    NARCIS (Netherlands)

    van den Broek, P.M.; Galvao, I.; Noppen, J.A.R.

    2008-01-01

    We present an algorithm which eliminates constraints from a feature model whose feature diagram is a tree and whose constraints are "requires" or "excludes" constraints. The algorithm constructs a feature tree which has the same semantics as the original feature model. The computational complexity

  15. Eliminating transducer distortion in acoustic measurements

    DEFF Research Database (Denmark)

    Agerkvist, Finn T.; Torras Rosell, Antoni; McWalter, Richard Ian

    2014-01-01

    This paper investigates the in uence of nonlinear components that contaminate the linear response of acoustic transducer, and presents a method for eliminating the in uence of nonlinearities in acoustic measurements. The method is evaluated on simulated as well as experimental data, and is shown ...

  16. Gram-Schmidt Orthogonalization by Gauss Elimination.

    Science.gov (United States)

    Pursell, Lyle; Trimble, S. Y.

    1991-01-01

    Described is the hand-calculation method for the orthogonalization of a given set of vectors through the integration of Gaussian elimination with existing algorithms. Although not numerically preferable, this method adds increased precision as well as organization to the solution process. (JJK)

  17. A kinetic and spectroscopic study of the CH3I-Cl and ICH2I-Cl adducts.

    Science.gov (United States)

    Gravestock, T J; Blitz, M A; Heard, D E

    2008-10-02

    Laser-induced fluorescence from the CH3I-Cl and ICH2I-Cl adducts formed in association reactions between chlorine atoms and CH3I and CH2I2 has been observed for the first time. The LIF excitation and dispersed fluorescence spectra have been measured in the range 345-375 nm and 380-480 nm, respectively, at 204 and 296 K. The excitation spectra exhibit vibrational fine structure, and a semiquantitative analysis of the spectra yields a similar binding energy for both adducts of approximately 60 kJ mol(-1). The adduct fluorescence is efficiently quenched by N2 and exhibits a zero-pressure lifetime of approximately 25-30 ns. Using LIF excited from the CH3I-Cl and ICH2I-Cl adducts, the kinetics of the reactions of atomic chlorine with methyl iodide and diiodomethane have been investigated, the results showing that both reactions proceed via two independent channels, an association reaction to form the adduct and a bimolecular abstraction reaction. At T approximately 200 K, the association reaction is predominant, and CH3I-Cl formation is irreversible, with rate coefficients for adduct formation found to be pressure-dependent and in reasonable agreement with the literature. At approximately 200 K, removal of the adduct is dominated by reaction with radical species (CH3 and ClSO) and by self-reaction, which proceed at close to the gas kinetic limit. At 296 K, CH3I-Cl formation is reversible, and the equilibrium constant, K(p) = (70.9 +/- 27.4) x 10(3) atm(-1), was determined, which is in excellent agreement with the literature, and the adduct does not significantly react with CH3I. The uncertainty is at the 95% confidence level (2sigma) and includes systematic errors. At approximately 200 K, the ICH2I-Cl adduct is again stabilized, with pressure-dependent rate coefficients reaching the high pressure limit at lower pressures than for the Cl + CH3I reaction. At room temperature, the ICH2I-Cl adduct is removed via an additional unimolecular decomposition channel, which

  18. Pyrrolizidine alkaloid-derived DNA adducts as a common biological biomarker of pyrrolizidine alkaloid-induced tumorigenicity.

    Science.gov (United States)

    Xia, Qingsu; Zhao, Yuewei; Von Tungeln, Linda S; Doerge, Daniel R; Lin, Ge; Cai, Lining; Fu, Peter P

    2013-09-16

    Pyrrolizidine alkaloid-containing plants are the most common poisonous plants affecting livestock, wildlife, and humans. The U.S. National Toxicology Program (NTP) classified riddelliine, a tumorigenic pyrrolizidine alkaloid, as "reasonably anticipated to be a human carcinogen" in the NTP 12th Report on Carcinogens in 2011. We previously determined that four DNA adducts were formed in rats dosed with riddelliine. The structures of the four DNA adducts were elucidated as (i) a pair of epimers of 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine adducts (termed as DHP-dG-3 and DHP-dG-4) as the predominant adducts; and (ii) a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl)dehydrosupinidine adducts (termed as DHP-dA-3 and DHP-dA-4 adducts). In this study, we selected a nontumorigenic pyrrolizidine alkaloid, platyphylliine, a pyrrolizidine alkaloid N-oxide, riddelliine N-oxide, and nine tumorigenic pyrrolizidine alkaloids (riddelliine, retrorsine, monocrotaline, lycopsamine, retronecine, lasiocarpine, heliotrine, clivorine, and senkirkine) for study in animals. Seven of the nine tumorigenic pyrrolizidine alkaloids, with the exception of lycopsamine and retronecine, are liver carcinogens. At 8-10 weeks of age, female F344 rats were orally gavaged for 3 consecutive days with 4.5 and 24 μmol/kg body weight test article in 0.5 mL of 10% DMSO in water. Twenty-four hours after the last dose, the rats were sacrificed, livers were removed, and liver DNA was isolated for DNA adduct analysis. DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts were formed in the liver of rats treated with the individual seven hepatocarcinogenic pyrrolizidine alkaloids and riddelliine N-oxide. These DNA adducts were not formed in the liver of rats administered retronecine, the nontumorigenic pyrrolizidine alkaloid, platyphylliine, or vehicle control. These results indicate that this set of DNA adducts, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, is a common biological biomarker of

  19. The relationship between prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAHs) and PAH-DNA adducts in cord blood.

    Science.gov (United States)

    Jedrychowski, Wieslaw A; Perera, Frederica P; Tang, Deliang; Rauh, Virginia; Majewska, Renata; Mroz, Elzbieta; Flak, Elzbieta; Stigter, Laura; Spengler, John; Camann, David; Jacek, Ryszard

    2013-07-01

    In a birth cohort study, we have assessed the dose-response relationship between individual measurements of prenatal airborne polycyclic aromatic hydrocarbon (PAH) exposure and specific PAH-DNA adducts in cord blood adjusted for maternal blood adducts and season of birth. The study uses data from an earlier established birth cohort of children in Krakow. The final analysis included 362 pregnant women who gave birth to term babies and had complete data on personal exposure in the second trimester of pregnancy to eight airborne PAHs including benzo[a]pyrene (B[a]P), as well as DNA adducts, both in maternal and cord blood. The relation between cord blood PAH-DNA adducts and airborne prenatal PAH exposure was non-linear. Although cord blood PAH-DNA adducts were significantly associated with the B[a]P exposure categorized by tertiles (non-parametric trend z=3.50, P<0.001), the relationship between B[a]P and maternal blood adducts was insignificant (z=1.63, P=0.103). Based on the multivariable linear regression model, we estimated the effect of the prenatal airborne B[a]P on the level of cord blood adducts. In total, 14.8% of cord blood adducts variance was attributed to the level of maternal adducts and 3% to a higher prenatal B[a] exposure above 5.70 ng/m(3). The calculated fetal/maternal blood adduct ratio (FMR) linearly increased with B[a]P exposure (z=1.99, P=0.047) and was highest at B[a]P concentrations exceeding 5.70 ng/m(3). In conclusion, the results support other findings that transplacental exposure to B[a]P from maternal inhalation produces DNA damage in the developing fetus. It also confirms the heightened fetal susceptibility to prenatal PAH exposure that should be a matter of public health concern, particularly in the highly polluted areas, because DNA adducts represent a pro-carcinogenic alteration in DNA. The continuation of this birth cohort study will assess the possible health effects of fetal DNA damage on the health of children and help in

  20. THE RELATIONSHIP BETWEEN PRENATAL EXPOSURE TO AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS (PAH) AND PAH-DNA ADDUCTS IN CORD BLOOD

    Science.gov (United States)

    Jedrychowski, Wieslaw; Perera, Frederica P.; Tang, Deliang; Rauh, Virginia; Majewska, Renata; Mroz, Elzbieta; Flak, Elzbieta; Stigter, Laura; Spengler, John; Camann, David; Jacek, Ryszard

    2013-01-01

    In a birth cohort study, we have assessed the dose-response relationship between individual measurements of prenatal airborne PAH exposure and specific PAH-DNA adducts in cord blood adjusted for maternal blood adducts and season of birth. The study uses data from an earlier established birth cohort of children in Krakow. The final analysis included 362 pregnant women who gave birth to term babies and had complete data on personal exposure in the second trimester of pregnancy to eight airborne polycyclic aromatic hydrocarbons (PAH) including benzo[a]pyrene (B[a]P), as well as DNA adducts, both in maternal and cord blood. The relation between cord blood PAH-DNA adducts and airborne prenatal PAH exposure was non-linear. While cord blood PAH-DNA adducts were significantly associated with the B[a]P exposure categorized by tertiles (nonparametric trend z = 3.50, p < 0.001), the relationship between B[a]P and maternal blood adducts was insignificant (z = 1.63, p = 0.103). Based on the multivariable linear regression model we estimated the effect of the prenatal airborne B[a]P on the level of cord blood adducts. In total, 14.8% of cord blood adducts variance was attributed to the level of maternal adducts and 3% to a higher prenatal B[a] exposure above 5.70 ng/m3. The calculated fetal/maternal blood adducts ratio (FMR) linearly increased with the B[a]P exposure (z = 1.99, p = 0.047) and was highest at B[a]P concentrations exceeding 5.70 ng/m3. In conclusion, the results support other findings that transplacental exposure to B[a[P from maternal inhalation produces DNA damage in the developing fetus. It also confirms the heightened fetal susceptibility to prenatal PAH exposure that should be a matter of public health concern particularly in the highly polluted areas because DNA adducts represent a pro-carcinogenic alteration in DNA The continuation of this birth cohort study will assess the possible health effects of fetal DNA damage on health of children and help in

  1. Monitoring of environmental cancer initiators through hemoglobin adducts by a modified Edman degradation method

    International Nuclear Information System (INIS)

    Toernqvist, M.M.; Mowrer, J.; Jensen, S.; Ehrenberg, L.

    1986-01-01

    Tissue doses of cancer initiators/mutagens are suitably monitored through hemoglobin adducts formed in vivo, but the use of this method has been hampered by a lack of sufficiently simple and fast procedures. It was previously observed that when the N-terminal amino acid in hemoglobin, valine, is alkylated it is cleaved off by the Edman sequencing reagent, phenyl isothiocyanate, in the neutral-alkaline coupling medium, as opposed to the acidic medium required by normal amino acids. Based on this principle, conditions for a functioning procedure for gas chromatography/mass spectrometry (GC/MS) determination of N-terminal alkylvalines in hemoglobin were worked out. Derivatizing the protein in formamide solution with pentafluorophenyl isothiocyanate, using a 2 H-alkylated protein as internal standard, and applying on-column injection during analysis, permit reproducible determination of hydroxyethylvaline and other adducts down into the dose range where cancer risks may be considered acceptably low

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

    DEFF Research Database (Denmark)

    Pedersen, Marie; Halldorsson, Thorhallur I; Autrup, Herman

    2012-01-01

    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......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...

  3. Activation of Reactive MALDI Adduct Ions Enables Differentiation of Dihydroxylated Vitamin D Isomers

    Science.gov (United States)

    Qi, Yulin; Müller, Miriam J.; Volmer, Dietrich A.

    2017-12-01

    Vitamin D compounds are secosteroids, which are best known for their role in bone health. More recent studies have shown that vitamin D metabolites and catabolites such as dihydroxylated species (e.g., 1,25- and 24,25-dihydroxyvitamin D3) play key roles in the pathologies of various diseases. Identification of these isomers by mass spectrometry is challenging and currently relies on liquid chromatography, as the isomers exhibit virtually identical product ion spectra under collision induced dissociation conditions. Here, we developed a simple MALDI-CID method that utilizes ion activation of reactive analyte/matrix adducts to distinguish isomeric dihydroxyvitamin D3 species, without the need for chromatography separation or chemical derivatization techniques. Specifically, reactive 1,5-diaminonaphthalene adducts of dihydroxyvitamin D3 compounds formed during MADI were activated and specific cleavages in the secosteroid's backbone structure were achieved that produced isomer-diagnostic fragment ions. [Figure not available: see fulltext.

  4. Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents.

    Science.gov (United States)

    Beranek, D T

    1990-07-01

    Alkylating agents, because of their ability to react directly with DNA either in vitro or in vivo, or following metabolic activation as in the case of the dialkylnitrosamines, have been used extensively in studying the mechanisms of mutagenicity and carcinogenicity. Their occurrence is widespread in the environment and human exposure from natural and pollutant sources is universal. Since most of these chemicals show varying degrees of both carcinogenicity and mutagenicity, and exhibit compound-specific binding patterns, they provide an excellent model for studying molecular dosimetry. Molecular dosimetry defines dose as the number of adducts bound per macromolecule and relates the binding of these adducts to the human mutagenic or carcinogenic response. This review complies DNA alkylation data for both methylating and ethylating agents in a variety of systems and discusses the role these alkylation products plays in molecular mutagenesis.

  5. Lactone modified mono-or dicarboxylic acid based adduct dispersant compositions

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez, A.; Lundberg, R.D.

    1990-03-06

    This patent describes a C{sub 5}-C{sub 9} lactone adduct material useful as an oil additive formed by reacting an aliphatic hydrocarbyl saturated or unsaturated, natural or synthetic, straight chain or branched chain monocarboxylic or dicarboxylic acylating agent heaving from about 1 to about 165 total carbon atoms with the reaction product of a C{sub 5}-C{sub 9} lactone with a member selected from the group consisting of a polyamine having from bout 2 to 60 total carbon atoms and from about 2 to about 12 nitrogen atoms, an amino alcohol containing up to about 50 total carbon atoms, from 1 to about 5 nitrogen atoms and from 1 to about 15 hydroxyl groups, and mixtures thereof. The aliphatic acylating agent having at least about twelve carbon atoms in said straight or branched chain to produce lactone adduct material that is hydrocarbon soluble.

  6. Morphological changes of calcite single crystals induced by graphene-biomolecule adducts

    Science.gov (United States)

    Calvaresi, Matteo; Di Giosia, Matteo; Ianiro, Alessandro; Valle, Francesco; Fermani, Simona; Polishchuk, Iryna; Pokroy, Boaz; Falini, Giuseppe

    2017-01-01

    Calcite has the capability to interact with a wide variety of molecules. This usually induces changes in shape and morphology of crystals. Here, this process was investigated using sheets of graphene-biomolecule adducts. They were prepared and made dispersible in water through the exfoliation of graphite by tip sonication in the presence tryptophan or N-acetyl-D-glucosamine. The crystallization of calcium carbonate in the presence of these additives was obtained by the vapor diffusion method and only calcite formed. The analysis of the microscopic observations showed that the graphene-biomolecule adducts affected shape and morphology of rhombohedral {10.4} faced calcite crystals, due to their stabilization of additional {hk.0} faces. The only presence of the biomolecule affected minimally shape and morphology of calcite crystals, highlighting the key role of the graphene sheets as 2D support for the adsorption of the biomolecules.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-01

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

  8. TLC surface integrity affects the detection of alkali adduct ions in TLC-MALDI analysis.

    Science.gov (United States)

    Dong, Yonghui; Ferrazza, Ruggero; Anesi, Andrea; Guella, Graziano; Franceschi, Pietro

    2017-09-01

    Direct coupling of thin-layer chromatography (TLC) with matrix-assisted laser desorption ionization (MALDI) mass spectrometry allows fast and detailed characterization of a large variety of analytes. The use of this technique, however, presents great challenges in semiquantitative applications because of the complex phenomena occurring at the TLC surface. In our laboratory, we recently observed that the ion intensities of several alkali adduct ions were significantly different between the top and interior layer of the TLC plate. This indicates that the integrity of the TLC surface can have an important effect on the reproducibility of TLC- MALDI analyses. Graphical Abstract MALDI imaging reveals that surface integrity affects the detection of alkali adductions in TLC-MALDI.

  9. 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.

    Science.gov (United States)

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

    2016-04-01

    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). Females with greater hip abduction and extension RTD would exhibit lesser frontal plane hip and knee motion during a single-leg jump-cutting task. Descriptive laboratory study. 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. 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. 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. 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 control during high-risk maneuvers such as cutting.

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

    International Nuclear Information System (INIS)

    Pribush, A.G.

    1986-01-01

    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

  11. An alternative approach to aminodiols from Baylis-Hillman adducts. Stereoselective synthesis of chloramphenicol, fluoramphenicol and thiamphenicol

    Energy Technology Data Exchange (ETDEWEB)

    Mateus, Cristiano R.; Coelho, Fernando [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica]. E-mail: coelho@iqm.unicamp.br

    2005-05-15

    We describe herein a new approach for the stereoselective synthesis of broad spectrum antibiotics from Baylis-Hillman adducts. The strategy is based on the preparation of an ene-carbamate directly from a Baylis-Hillman adduct using a Curtius rearrangement reaction. Stereoselective hydroboration furnished a mixture of diastereoisomeric aminoalcohols (syn and anti). After chromatographic separation, the syn diastereoisomer was directly transformed into the antibiotics. (author)

  12. Effect of gear ratio on peak power and time to peak power in BMX cyclists.

    Science.gov (United States)

    Rylands, Lee P; Roberts, Simon J; Hurst, Howard T

    2017-03-01

    The aim of this study was to ascertain if gear ratio selection would have an effect on peak power and time to peak power production in elite Bicycle Motocross (BMX) cyclists. Eight male elite BMX riders volunteered for the study. Each rider performed three, 10-s maximal sprints on an Olympic standard indoor BMX track. The riders' bicycles were fitted with a portable SRM power meter. Each rider performed the three sprints using gear ratios of 41/16, 43/16 and 45/16 tooth. The results from the 41/16 and 45/16 gear ratios were compared to the current standard 43/16 gear ratio. Statistically, significant differences were found between the gear ratios for peak power (F(2,14) = 6.448; p = .010) and peak torque (F(2,14) = 4.777; p = .026), but no significant difference was found for time to peak power (F(2,14) = 0.200; p = .821). When comparing gear ratios, the results showed a 45/16 gear ratio elicited the highest peak power,1658 ± 221 W, compared to 1436 ± 129 W and 1380 ± 56 W, for the 43/16 and 41/16 ratios, respectively. The time to peak power showed a 41/16 tooth gear ratio attained peak power in -0.01 s and a 45/16 in 0.22 s compared to the 43/16. The findings of this study suggest that gear ratio choice has a significant effect on peak power production, though time to peak power output is not significantly affected. Therefore, selecting a higher gear ratio results in riders attaining higher power outputs without reducing their start time.

  13. MTHFR Polymorphisms, Folate Intake, and Carcinogen DNA Adducts in the Lung

    OpenAIRE

    Lee, Mi-Sun; Asomaning, Kofi; Su, Li; Wain, John C.; Mark, Eugene J.; Christiani, David C.

    2012-01-01

    The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was complet...

  14. Analytical determination of specific 4,4'-methylene diphenyl diisocyanate hemoglobin adducts in human blood.

    Science.gov (United States)

    Gries, Wolfgang; Leng, Gabriele

    2013-09-01

    4,4'-Methylene diphenyl diisocyanate (MDI) is one of the most important isocyanates in the industrial production of polyurethane and other MDI-based synthetics. Because of its high reactivity, it is known as a sensitizing agent, caused by protein adducts. Analysis of MDI is routinely done by determination of the nonspecific 4,4'-methylenedianiline as a marker for MDI exposure in urine and blood. Since several publications have reported specific adducts of MDI and albumin or hemoglobin, more information about their existence in humans is necessary. Specific adducts of MDI and hemoglobin were only reported in rats after high-dose MDI inhalation. The aim of this investigation was to detect the hemoglobin adduct 5-isopropyl-3-[4-(4-aminobenzyl)phenyl]hydantoin (ABP-Val-Hyd) in human blood for the first time. We found values up to 5.2 ng ABP-Val-Hyd/g globin (16 pmol/g) in blood samples of workers exposed to MDI. Because there was no information available about possible amounts of this specific MDI marker, the analytical method focused on optimal sensitivity and selectivity. Using gas chromatography-high-resolution mass spectrometry with negative chemical ionization, we achieved a detection limit of 0.02 ng ABP-Val-Hyd/g globin (0.062 pmol/g). The robustness of the method was confirmed by relative standard deviations between 3.0 and 9.8 %. Combined with a linear detection range up to 10 ng ABP-Val-Hyd/g globin (31 pmol/g), the enhanced precision parameter demonstrates that the method described is optimized for screening studies of the human population.

  15. Free flow electrophoresis separation and AMS quantitation of 14C-naphthalene-protein adducts

    Science.gov (United States)

    Buchholz, Bruce A.; Haack, Kurt W.; Sporty, Jennifer L.; Buckpitt, Alan R.; Morin, Dexter

    2010-04-01

    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 μCi) of 14C 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 14C-AMS. We describe the processing techniques required to couple FFE to AMS for quantitation of protein adducts.

  16. Genotoxicity induced by xenobiotics:the role of DNA adducts, individual susceptibility and DNA repair

    Czech Academy of Sciences Publication Activity Database

    Vodička, Pavel; Koskinen, M.; Štětina, R.; Vodičková, L.; Kuricová, M.; Hemminki, K.

    2002-01-01

    Roč. 10, č. 1 (2002), s. 322 ISSN 1107-3756. [World Congress on Advances in Oncology /7./ and International Symposium on Molecular Medicine /5./. Hersonissos, 10.10.2002-12.10.2002] R&D Projects: GA ČR GA310/01/0802 Institutional research plan: CEZ:AV0Z5039906 Keywords : DNA adducts Subject RIV: FM - Hygiene Impact factor: 2.063, year: 2002

  17. Quantitation of acrolein-protein adducts: potential biomarker of acrolein exposure.

    Science.gov (United States)

    Li, Hui; Wang, Jianling; Kaphalia, Bhupendra; Ansari, G A S; Khan, M Firoze

    2004-03-26

    Acrolein, an alpha,beta-unsaturated aldehyde, is a ubiquitous environmental toxic pollutant. Because of potential human exposure, there is a need for a sensitive, reliable, and specific method to monitor acrolein exposure. Acrolein is a potent electrophile and reacts with proteins mainly through Michael addition reaction, leading to acrolein-protein adducts (APA). The present study aimed to develop a competitive enzyme-linked immunosorbent assay (ELISA) method for the quantitation of APA in biological samples. Antibody to acrolein-keyhole limpet hemocyanin adduct was raised in rabbits, and the specificity of the antibody was determined by ELISA using acrolein-albumin adduct (AAA) or native albumin. A dose-dependent response was observed with AAA, but no immunoreactivity with native albumin. Further, lack of cross-reactivity of anti-acrolein antibody with formaldehyde-, malondialdehyde-, or 4-hydroxynonenal-albumin adducts indicates its specificity for acrolein. For the competitive ELISA, 1:16,000 diluted antisera was used with varying concentrations of AAA, which provided a linear detection range between 250 and 10,000 pg. To test the efficacy of the method for possible use as a biomarker of acrolein exposure, SD rats were orally administered 1 or 7 doses of 9.2 mg/kg/d acrolein. APA levels, quantitated in the serum, showed significantly greater formation (32% and 58% after 1 and 7 doses, respectively) in acrolein-treated rats as compared to the controls. Western blot analyses of APA in the sera from acrolein-treated rats showed APA bands (especially 29, 31, and 100 kD) with greater intensity in comparison to controls, further supporting our ELISA results. These results suggest that quantitation of APA has potential to be used as biomarker of acrolein exposure and eventually for molecular dosimetry and risk assessment.

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

    Directory of Open Access Journals (Sweden)

    Moazzam H. Bhatti

    2011-09-01

    Full Text Available In the crystal structure of the title adduct [systematic name: 2-(1,3-dioxoisoindolin-2-ylacetic acid–1,3,7-trimethyl-1,2,3,6-tetrahydro-7H-purine-2,6-dione (1/1], C8H10N4O2·C10H7NO4, the components are linked by an O—H...N hydrogen-bond and no proton transfer occurs.

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

    International Nuclear Information System (INIS)

    Castro e Silva, E. de.

    1983-01-01

    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.) [pt

  20. Fe(III)-Catalyzed Hydroallylation of Unactivated Alkenes with Morita-Baylis-Hillman Adducts.

    Science.gov (United States)

    Qi, Jifeng; Zheng, Jing; Cui, Sunliang

    2018-03-02

    An Fe(III)-catalyzed hydroallylation of unactivated alkenes with Morita-Baylis-Hillman adducts via an Fe-catalyzed process is described. A variety of alkenes, including mono-, di-, and trisubstituted alkenes, could all smoothly convert to structural diversified cinnamates in this protocol. Interestingly, when the hydroxyl-containing alkenes were used, various lactones could be rapidly assembled. Moreover, this protocol could be applied to late-stage functionalization of natural products.

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

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, Bruce A., E-mail: bbuchholz@llnl.go [Center for AMS, LLNL, 7000 East Avenue, Livermore, CA 94551 (United States); Haack, Kurt W.; Sporty, Jennifer L. [Center for AMS, LLNL, 7000 East Avenue, Livermore, CA 94551 (United States); Buckpitt, Alan R.; Morin, Dexter [Department of Molecular Biosciences, School of Veterinary Medicine, UC Davis, Davis, CA 95616 (United States)

    2010-04-15

    Naphthalene is a volatile aromatic hydrocarbon to which humans are exposed from a variety of sources including mobile air sources and cigarette smoke. Naphthalene produces dose-(concentration)dependent injury to airway epithelial cells of murine lung which is observed at concentrations well below the current occupational exposure standard. Toxicity is dependent upon the cytochrome P450 mediated metabolic activation of the parent substrate to unstable metabolites which become bound covalently to tissue proteins. Nearly 70 proteins have been identified as forming adducts with reactive naphthalene metabolites using in vitro systems but very little work has been conducted in vivo because reasonably large amounts (100 muCi) of {sup 14}C labeled parent compound must be administered to generate detectable adduct levels on storage phosphor screens following separation of labeled proteins by 2D gel electrophoresis. The work described here was done to provide proof of concept that protein separation by free flow electrophoresis followed by AMS detection of protein fractions containing protein bound reactive metabolites would provide adducted protein profiles in animals dosed with trace quantities of labeled naphthalene. Mice were administered 200 mg/kg naphthalene intraperitoneally at a calculated specific activity of 2 DPM/nmol (1 pCi/nmol) and respiratory epithelial tissue was obtained by lysis lavage 4 h post injection. Free flow electrophoresis (FFE) separates proteins in the liquid phase over a large pH range (2.5-11.5) using low molecular weight acids and bases to modify the pH. The apparatus separates fractions into standard 96-well plates that can be used in other protein analysis techniques. The buffers of the fractions have very high carbon content, however, and need to be dialyzed to yield buffers compatible with {sup 14}C-AMS. We describe the processing techniques required to couple FFE to AMS for quantitation of protein adducts.

  2. Mass-spectrometric investigation of rare earth acetylacetonates dipivaloylmethanates and their adducts

    International Nuclear Information System (INIS)

    Gavrishzhuk, E.M.; Dzyubenko, N.G.; Martynenko, L.I.

    1985-01-01

    Peculiarities of fragmentation of molecular ions of rare earth acetylacetonates and dipivaloylmethanates under mass-spectrometric investigation of these compounds as well as their adducts with o-phenanthroline, α,α'-dipyridyl, triphenylphosphine oxide are considered in the given review. Similar data for identical derivants of some transitions metals are presented. Data on potentials of appearance and dissociation energy of basic ions in mass-spectra of the studied β-diketonates are analyzed

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

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, Marie, E-mail: mpedersen@creal.cat [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark); Halldorsson, Thorhallur I., E-mail: lur@ssi.dk [Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland Reykjavik (Iceland); Center for Fetal Programming, Department of Epidemiology, Statens Serum Institute, Copenhagen (Denmark); Autrup, Herman, E-mail: ha@mil.au.dk [School of Public Health, Department of Environmental and Occupational Medicine, Aarhus University, Aarhus (Denmark); Brouwer, Abraham, E-mail: Bram.Brouwer@bds.nl [BioDetection Systems B.V., Amsterdam (Netherlands); Besselink, Harrie, E-mail: Harrie.Besselink@bds.nl [BioDetection Systems B.V., Amsterdam (Netherlands); Loft, Steffen, E-mail: stl@sund.ku.dk [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark); Knudsen, Lisbeth E., E-mail: liek@sund.ku.dk [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark)

    2012-06-01

    Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006-2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX){sup Registered-Sign} bioassay, {sup 32}P-postlabelling technique and cytokinesis-block MN assay. Maternal preference for meats with dark surface were significantly associated with higher bulky DNA adducts in both maternal ({beta} 95%CI; 0.46 (0.08, 0.84)) and cord blood ({beta} 95%CI; 0.46 (0.05, 0.86)) before and after adjustment for potential confounders. No other significant associations between the 18 dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA adducts appear to be captured by a FFQ while potential associations for other biomarkers might be more complex or need larger sample size.

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

    International Nuclear Information System (INIS)

    Pedersen, Marie; Halldorsson, Thorhallur I.; Autrup, Herman; Brouwer, Abraham; Besselink, Harrie; Loft, Steffen; Knudsen, Lisbeth E.

    2012-01-01

    Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006–2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX) ® bioassay, 32 P-postlabelling technique and cytokinesis-block MN assay. 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.

  5. Electrochemical oxidation and protein adduct formation of aniline: a liquid chromatography/mass spectrometry study.

    Science.gov (United States)

    Melles, Daniel; Vielhaber, Torsten; Baumann, Anne; Zazzeroni, Raniero; Karst, Uwe

    2012-04-01

    Historically, skin sensitization tests are typically based on in vivo animal tests. However, for substances used in cosmetic products, these tests have to be replaced according to the European Commission regulation no. 1223/2009. Modification of skin proteins by electrophilic chemicals is a key process associated with the induction of skin sensitization. The present study investigates the capabilities of a purely instrumental setup to determine the potential of commonly used non-electrophilic chemicals to cause skin sensitization by the generation of electrophilic species from the parent compound. In this work, the electrophiles were generated by the electrochemical oxidation of aniline, a basic industrial chemical which may also be released from azo dyes in cosmetics. The compound is a known sensitizer and was oxidized in an electrochemical thin-layer cell which was coupled online to electrospray ionization-mass spectrometry. The electrochemical oxidation was performed on a boron-doped diamond working electrode, which is able to generate hydroxyl radicals in aqueous solutions at high potentials. Without any pretreatment, the oxidation products were identified by electrospray ionization/time-of-flight mass spectrometry (ESI-ToF-MS) using their exact masses. A mass voltammogram was generated by plotting the obtained mass spectra against the applied potential. Oligomerization states with up to six monomeric units in different redox states of aniline were observed using this setup. This approach was extended to generate adducts between the oxidation products of aniline and the tripeptide glutathione. Two adducts were identified with this trapping experiment. Protein modification was carried out subsequently: Aniline was oxidized at a constant potential and was allowed to react with β-lactoglobulin A (β-LGA) or human serum albumin (HSA), respectively. The generated adducts were analyzed by liquid chromatography coupled to ESI-ToF-MS. For both β-LGA and HSA, aniline

  6. Improved peak shape fitting in alpha spectra.

    Science.gov (United States)

    Pommé, S; Caro Marroyo, B

    2015-02-01

    Peak overlap is a recurrent issue in alpha-particle spectrometry, not only in routine analyses but also in the high-resolution spectra from which reference values for alpha emission probabilities are derived. In this work, improved peak shape formulae are presented for the deconvolution of alpha-particle spectra. They have been implemented as fit functions in a spreadsheet application and optimum fit parameters were searched with built-in optimisation routines. Deconvolution results are shown for a few challenging spectra with high statistical precision. The algorithm outperforms the best available routines for high-resolution spectrometry, which may facilitate a more reliable determination of alpha emission probabilities in the future. It is also applicable to alpha spectra with inferior energy resolution. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Peak Oil, Food Systems, and Public Health

    Science.gov (United States)

    Parker, Cindy L.; Kirschenmann, Frederick L.; Tinch, Jennifer; Lawrence, Robert S.

    2011-01-01

    Peak oil is the phenomenon whereby global oil supplies will peak, then decline, with extraction growing increasingly costly. Today's globalized industrial food system depends on oil for fueling farm machinery, producing pesticides, and transporting goods. Biofuels production links oil prices to food prices. We examined food system vulnerability to rising oil prices and the public health consequences. In the short term, high food prices harm food security and equity. Over time, high prices will force the entire food system to adapt. Strong preparation and advance investment may mitigate the extent of dislocation and hunger. Certain social and policy changes could smooth adaptation; public health has an essential role in promoting a proactive, smart, and equitable transition that increases resilience and enables adequate food for all. PMID:21778492

  8. First diffraction peak in alkali metaphosphate glasses

    Science.gov (United States)

    Beaufils, S.; Bionducci, M.; Ecolivet, C.; Marchand, R.; Le Sauze, A.

    2000-11-01

    The structure factor of the alkali metaphosphate glasses LiPO 3 and Na 0.5Li 0.5PO 3 has been measured at 300 K for both systems and up to 800 K for the latter. The first diffraction peak of alkali metaphosphate glasses merges at lower Q (around 1.1 Å -1) than in other covalent glasses, with the highest intensity for Li-containing glasses. These points are discussed following the hypothesis of voids ordering in the structure and contrasts effects due to the negative neutron Li scattering length. The intensity of the prepeak is significantly growing with temperature, in case of Na 0.5Li 0.5PO 3, in contrast to the other peaks of the structure factor. This point is discussed in relation with literature data from flow birefringence indicating structural changes in these glassy systems.

  9. Differences in knee adduction moment between healthy subjects and patients with osteoarthritis depend on the knee axis definition.

    Science.gov (United States)

    Meireles, S; De Groote, F; Van Rossom, S; Verschueren, S; Jonkers, I

    2017-03-01

    This study, firstly, investigates the effect of using an anatomical versus a functional axis of rotation (FAR) on knee adduction moment (KAM) in healthy subjects and patients with knee osteoarthritis (KOA). Secondly, this study reports KAM for models with FAR calculated using weight-bearing and non-weight-bearing motion. Three musculoskeletal models were created using OpenSim with different knee axis of rotation (AR): transepicondylar axis (TEA); FAR calculated based on SARA algorithm using a weight-bearing motion (wFAR) and a non-weight-bearing motion (nwFAR). KAM were calculated during gait in fifty-nine subjects (n=20 healthy, n=16 early OA, n=23 established OA) for all models and groups. Significant differences between the three groups in the first peak KAM were found when TEA was used (p=0.038). However, these differences were no longer present when using FAR. In subjects with established OA, KAMs were significantly reduced when using nwFAR compared to TEA models but also compared to wFAR models. The presence of excessive KAM in subjects with established KOA showed to be dependent on the definition of the AR: anatomical versus functional. Therefore, caution should be accounted when comparing KAM in different studies on KOA patients. In patients with end-stage knee OA where increased passive knee laxity is likely to exist, the use of weight-bearing motions should be considered to avoid increased variability in the location and orientation of a FAR obtained from activities with only limited joint loading. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    International Nuclear Information System (INIS)

    Kim, Hyun-Suk; Guo, Chunlu; Thompson, Eric L.; Jiang, Yanlin; Kelley, Mark R.; Vasko, Michael R.; Lee, Suk-Hee

    2015-01-01

    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

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

    International Nuclear Information System (INIS)

    Bedford, P.; Fichtinger-Schepman, A.M.; Shellard, S.A.; Walker, M.C.; Masters, J.R.; Hill, B.T.

    1988-01-01

    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

  13. Activation of proinflammatory signaling by 4-hydroxynonenal-Src adducts in aged kidneys.

    Science.gov (United States)

    Jang, Eun Ji; Kim, Dae Hyun; Lee, Bonggi; Lee, Eun Kyeong; Chung, Ki Wung; Moon, Kyoung Mi; Kim, Min Jo; An, Hye Jin; Jeong, Ji Won; Kim, Ye Ra; Yu, Byung Pal; Chung, Hae Young

    2016-08-09

    In our previous study, reactive 4-hydroxy-2-nonenal (4-HNE) was shown to activate Src (a non-receptor tyrosine kinase) by forming an adduct on binding with a specific residue of Src, leading to the activation of proinflammatory signaling pathways in cultured cells. However, to date, the deleterious roles of 4-HNE in inflammatory signaling activation in kidneys during aging have not been explored. The purpose of the present study was to document the mechanisms by which 4-HNE induces inflammation in the kidney during aging. Initial experiments revealed that activated nuclear factor-κB (NF-κB) expression was caused by 4-HNE activation, which suppressed transcriptional activity in the aged kidney. Treatment of human umbilical vein endothelial cells with 4-HNE revealed that Src caused senescence via NF-κB activation. Furthermore, our immunohistochemistry data showed that 4-HNE-adducted Src significantly increased in aged kidney tissues. The data showed age-related upregulation of downstream signaling molecules such as mitogen activated protein kinases (MAPKs), activator protein-1 (AP-1), NF-κB, and COX-2 in a cell culture cell system.Taken together, the results of this study show that the formation of adducts between 4-HNE and Src activates inflammatory signaling pathways in the aged kidney, contributing to age-related nephropathy.

  14. Thermochemistry of adducts of some bivalent transition metal bromides with aniline

    International Nuclear Information System (INIS)

    Dunstan, Pedro Oliver

    2006-01-01

    The compounds [MBr 2 (an) 2 ] (where M is Mn(II), Fe(II), Co(II), Ni(II), Cu(II) or Zn(II); an=aniline) were synthesized and characterized by melting points, elemental analysis, thermal studies, and electronic and IR spectroscopy. The enthalpies of dissolution of the adducts, metal(II) bromides and aniline in methanol, aqueous 1.2M HCl or 25% (v/v) aqueous 1.2M HCl in methanol were measured. The following thermochemical parameters for the adducts have been determined by thermochemical cycles: the standard enthalpies for the Lewis acid/base reactions (Δ r H o ), the standard enthalpies of formation (Δ f H o ), the standard enthalpies of decomposition (Δ D H o ), the lattice standard enthalpies (Δ M H o ) and the standard enthalpies of the Lewis acid/base reactions in the gaseous phase (Δ r H o (g)). The mean bond dissociation enthalpies of the M(II)-nitrogen bonds (D-bar (M?N) ) and the enthalpies of formation of the adducts from the ions in the gaseous phase: M 2+ (g) +Br - (g) +an (g) ->[MBr 2 (an) 2 ] (g) (Δ fi H o ) have been estimated

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

    International Nuclear Information System (INIS)

    Roa, W.H.Y.; Chapman, J.D.

    1987-01-01

    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 25 0 C for up to 96 hr to accumulate radioactive decays and transferred at various times to 37 0 C 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

  16. Characterization and reactivity of a terminal nickel(III)-oxygen adduct.

    Science.gov (United States)

    Pirovano, Paolo; Farquhar, Erik R; Swart, Marcel; Fitzpatrick, Anthony J; Morgan, Grace G; McDonald, Aidan R

    2015-02-23

    High-valent terminal metal-oxygen adducts are hypothesized to be the potent oxidizing reactants in late transition metal oxidation catalysis. In particular, examples of high-valent terminal nickel-oxygen adducts are scarce, meaning there is a dearth in the understanding of such oxidants. A monoanionic Ni(II)-bicarbonate complex has been found to react in a 1:1 ratio with the one-electron oxidant tris(4-bromophenyl)ammoniumyl hexachloroantimonate, yielding a thermally unstable intermediate in high yield (ca. 95%). Electronic absorption, electronic paramagnetic resonance, and X-ray absorption spectroscopies and density functional theory calculations confirm its description as a low-spin (S = 1/2), square planar Ni(III)-oxygen adduct. This rare example of a high-valent terminal nickel-oxygen complex performs oxidations of organic substrates, including 2,6-di-tert-butylphenol and triphenylphosphine, which are indicative of hydrogen atom abstraction and oxygen atom transfer reactivity, respectively. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Unprecedented solvent induced inter-conversion between monomeric and dimeric silylene-zinc iodide adducts.

    Science.gov (United States)

    Yadav, Sandeep; Sangtani, Ekta; Dhawan, Diksha; Gonnade, Rajesh G; Ghosh, Debashree; Sen, Sakya S

    2017-08-29

    Usually, when a silylene reacts with a transition metal Lewis acid, it forms an adduct which could be either monomeric or dimeric. However, we present here that a silylene, [PhC(NtBu) 2 SiN(SiMe 3 ) 2 ] can form both monomeric [PhC(NtBu) 2 Si{N(SiMe 3 ) 2 } → ZnI 2 ]·THF (1) and dimeric [{PhC(NtBu) 2 }(N(SiMe 3 ) 2 )SiZnI,(μ-I)] 2 (2) adducts upon reaction with ZnI 2 . The formation of 1 and 2 relies upon the solvent used for the reaction or crystallization. When the crystallization is carried out in THF complex 1 is formed, however, when the reaction and crystallization are performed in acetonitrile complex 2 is obtained. Both 1 and 2 were structurally authenticated and the nature of the Si-Zn bond in these complexes was determined by quantum chemical calculations. In addition, a spontaneous inter-conversion between 1 and 2 just by changing the solvents has been also observed; a feature presently not known for silylene-transition metal Lewis adducts.

  18. RecBCD (Exonuclease V) is inhibited by DNA adducts produced by cisplatin and ultraviolet light.

    Science.gov (United States)

    Leung, Wai Y; Chung, Long H; Kava, Hieronimus W; Murray, Vincent

    2018-01-01

    The presence of adducts on the DNA double-helix can have major consequences for the efficient functioning of DNA repair enzymes. E. coli RecBCD (exonuclease V) is involved in recombinational repair of double-strand breaks that are caused by defective DNA replication, DNA damaging agents and other factors. The holoenzyme possesses a bipolar helicase activity which helps unwind DNA from both 3'- and 5'-directions and is coupled with a potent exonuclease activity that is also capable of digesting DNA from both 3'- and 5'-ends. In this study, DNA sequences were damaged with cisplatin or UV followed by RecBCD treatment. DNA damaging agents such as cisplatin and UV induce the formation of intrastrand adducts in the DNA template. It was demonstrated that RecBCD degradation was inhibited by either cisplatin-damaged or UV-damaged DNA sequences. This is the first occasion that RecBCD has been demonstrated to be inhibited by DNA adducts induced by cisplatin or UV. In addition, we quantified the amounts of DNA remaining after RecBCD treatment and observed that the level of inhibition was concentration and dose dependent. A DNA-targeted 9-aminoacridinecarboxamide cisplatin analogue was also found to inhibit RecBCD activity. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  19. Detection of benzo[a]pyrene-guanine adducts in single-stranded DNA using the α-hemolysin nanopore

    Science.gov (United States)

    Perera, Rukshan T.; Fleming, Aaron M.; Johnson, Robert P.; Burrows, Cynthia J.; White, Henry S.

    2015-02-01

    The carcinogenic precursor benzo[a]pyrene (BP), a polycyclic aromatic hydrocarbon, is released into the environment through the incomplete combustion of hydrocarbons. Metabolism of BP in the human body yields a potent alkylating agent (benzo[a]pyrene diol epoxide, BPDE) that reacts with guanine (G) in DNA to form an adduct implicated in cancer initiation. We report that the α-hemolysin (αHL) nanopore platform can be used to detect a BPDE adduct to G in synthetic oligodeoxynucleotides. Translocation of a 41-mer poly-2‧-deoxycytidine strand with a centrally located BPDE adduct to G through αHL in 1 M KCl produces a unique multi-level current signature allowing the adduct to be detected. This readily distinguishable current modulation was observed when the BPDE-adducted DNA strand translocated from either the 5‧ or 3‧ directions. This study suggests that BPDE adducts and other large aromatic biomarkers can be detected with αHL, presenting opportunities for the monitoring, quantification, and sequencing of mutagenic compounds from cellular DNA samples.

  20. Tumors and DNA adducts in mice exposed to benzo(a)pyrene and coal tars: implications for risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, L.S.; Weyand, E.H.; Safe, S.; Steinberg, M.; Culp, S.J.; Gaylor, D.W.; Beland, F.A.; Rodriguez, L.V. [Electric Power Research Institute, Palo Alto, CA (United States)

    1998-12-01

    Current methods to estimate the quantitative cancer risk of complex mixtures of polycyclic aromatic hydrocarbons (PAH) such as coal tar assume that overall potency can be derived from knowledge of the concentration of a few carcinogenic components such as benzo(a)pyrene (B(a)P). Genotoxic damage, such as DNA adducts, is thought to be an essential aspect of PAH-induced tumorigenesis and could be a biomarker for exposure useful for estimating risk. However, the role of B(a)P and the relationship of adduct formation in tumorigenesis have not been tested rigorously in models appropriate for human health risk assessment. This paper compares tumor induction and adduct formation by B(a)P and coal tars in several experimental protocols, including one broadly accepted and used by regulators. It was found that B(a)P content did not account for tumor incidences after exposure to coal tars. DNA adducts were found in both tumors and tumor-free tissue and tumor outcomes were not predicted by either quantitation of total DNA adducts or by the DNA adduct formed by B(a)P. These data suggest that risk assessments based on B(a)P content may not predict accurately risk to human health posed by environmental PAH.

  1. The presence of aflatoxin B₁-FAPY adduct and human papilloma virus in cervical smears from cancer patients in Mexico.

    Science.gov (United States)

    Carvajal, Magda; Berumen, Jaime; Guardado-Estrada, Mariano

    2012-01-01

    The carcinogenic biomarker aflatoxin B(1)-formamidopyrimidine 2,3-dihydro-2-(N-formyl)-2',5',6'-triamino-4'-4'-oxy-N-pyrimidyl-3-hydroxy-AFB(1) called AFB(1)-FAPY adduct, and Human Papilloma Virus (HPV) types 16 and 18 were quantified from DNA cervical scrapes from 40 women with cervical cancer (CC) and 14 healthy women as controls. The relationship between the AFB(1)-FAPY adduct and HPV types 16 and 18 was determined. Competitive inhibitory indirect ELISA was validated with 94% inhibition to quantify the AFB(1)-FAPY adducts in picograms per milligram of DNA (limit of detection = 0.1 pg/mg, and limit of quantification = 10 pg/mg), polymerase chain reaction and DNA sequencing to identify HPV types. The average concentration of AFB(1)-FAPY adducts/mg DNA in the CC cases was 1025 pg, 1420 pg with HPV16 and 630 pg sharing HPV18 (p = 0.03). In comparison, healthy controls had ≤ 2.6 pg/mg DNA, a statistically significant difference (p = 0.00006). The presence of AFB(1)-FAPY adduct increased six-fold the risk for CC between cases and controls, the odds ratio was 6.1 (95% CI = 1.4-25.4). There was a close relationship between the AFB(1)-FAPY adducts and HPV16 in CC samples.

  2. Reducing Peak Power in Automated Weapon Laying

    Science.gov (United States)

    2016-02-01

    LAYING Joshua Stapp Matthew Tomik February 2016 Approved for public release; distribution is unlimited...PEAK POWER IN AUTOMATED WEAPON LAYING 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHORS Joshua Stapp and...aiming a weapon is referred to as gun laying . This report describes a method to calculate motion profiles that reach a given lay within the least

  3. Structural and chemical characterization of S-[2-(N7-guanyl)-ethyl]glutathione, the major DNA adduct formed from 1,2-dibromoethane

    International Nuclear Information System (INIS)

    Inskeep, P.B.; Koga, N.; Cmarik, J.L.; Peterson, L.A.; Guengerich, F.P.

    1986-01-01

    Glutathione (GSH) S-transferase catalyzes the reaction of the carcinogen 1,2-dibromoethane (DBE) with DNA, resulting in the formation of a major DNA adduct which can be released by thermal hydrolysis at neutral pH and purified by octadecylsilyl- and propylamino high performance liquid chromatography. This adduct was also the only major liver and kidney DNA adduct isolated from rats treated with [1,2- 14 C]-DBE. Administration of 1,2-dichloroethane to rats also led to the production of this and other DNA adducts. The DNA adduct was assigned the structure S-[2-(N'-guanyl)ethyl]GSH as determined by positive and negative ion mass spectrometry and two-dimensional NMR correlated spectroscopy (COSY). Consistently, the chromatographic characteristics of the adduct could be altered upon treatment with γ-glutamic transpeptidase or pronase. No evidence for in vitro or in vivo guanyl imidazole ring opening was observed under these experimental conditions. Additionally, S-[2-(N 7 -guanyl)ethyl]GSH was found to be stable to further reaction with DNA to generate new DNA adducts. The structure of the isolated adduct is consistent with a proposed bioactivation pathway of DBE which involves enzyme catalyzed conjugation of DBE with GSH followed by attack of the N 7 -position of DNA guanine residues to generate this major adduct. The chemical stability of the adduct suggests that it may be important to the carcinogenicity of this compound

  4. METing SUSY on the Z peak

    International Nuclear Information System (INIS)

    Barenboim, G.; Bernabeu, J.; Vives, O.; Mitsou, V.A.; Romero, E.

    2016-01-01

    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 T 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 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.)

  5. Ten Reasons to Take Peak Oil Seriously

    Directory of Open Access Journals (Sweden)

    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.

  6. METing SUSY on the Z peak

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  7. Peak and ceiling effects in final-product analysis of mastoidectomy performance

    DEFF Research Database (Denmark)

    West, N; Konge, L; Cayé-Thomasen, P

    2015-01-01

    BACKGROUND: Virtual reality surgical simulation of mastoidectomy is a promising training tool for novices. Final-product analysis for assessing novice mastoidectomy performance could be limited by a peak or ceiling effect. These may be countered by simulator-integrated tutoring. METHODS: Twenty......-two participants completed a single session of self-directed practice of the mastoidectomy procedure in a virtual reality simulator. Participants were randomised for additional simulator-integrated tutoring. Performances were assessed at 10-minute intervals using final-product analysis. RESULTS: In all, 45.5 per...... cent of participants peaked before the 60-minute time limit. None of the participants achieved the maximum score, suggesting a ceiling effect. The tutored group performed better than the non-tutored group but tutoring did not eliminate the peak or ceiling effects. CONCLUSION: Timing and adequate...

  8. Chinese emissions peak: Not when, but how

    International Nuclear Information System (INIS)

    Spencer, Thomas; Colombier, Michel; Wang, Xin; Sartor, Oliver; Waisman, Henri

    2016-07-01

    It seems highly likely that China will overachieve its 2020 and 2030 targets, and peak its emissions before 2030 and possibly at a lower level than often assumed. This paper argues that the debate on the timing of the peak is misplaced: what matters is not when by why. For the peak to be seen as a harbinger of deep transformation, it needs to be based on significant macro-economic reform and restructuring, with attendant improvement in energy intensity. The Chinese economic model has been extraordinarily investment and resource intensive, and has driven the growth in GHG emissions. That model is no longer economically or environmentally sustainable. Therefore Chinese policy-makers are faced with a trade-off between slower short-term growth and economic reform, versus supporting short-term growth but slowing economic reform. The outcome will be crucial for the transition to a low-carbon economy. Overall, the 13. FYP (2016-2020) gives the impression of a cautious reflection of the new normal paradigm on the economic front, and a somewhat conservative translation of this shift into the energy and climate targets. Nonetheless, the 13. FYP targets set China well on the way to overachieving its 2020 pledge undertaken at COP15 in Copenhagen, and to potentially overachieving its INDC. It thus seems likely that China will achieve its emissions peak before 2030. However, the crucial question is not when China peaks, but whether the underlying transformation of the Chinese economy and energy system lays the basis for deep decarbonization thereafter. Thorough assessments of the implications of the 'new normal' for Chinese emissions and energy system trajectories, taking into account the link with the Chinese macro-economy, are needed. Scenarios provide a useful framework and should focus on a number of short-term uncertainties. Most energy system and emissions scenarios published today assume a continuity of trends between 2010-2015 and 2015-2020, which is at odds

  9. Differential repair of etheno-DNA adducts by bacterial and human AlkB proteins.

    Science.gov (United States)

    Zdżalik, Daria; Domańska, Anna; Prorok, Paulina; Kosicki, Konrad; van den Born, Erwin; Falnes, Pål Ø; Rizzo, Carmelo J; Guengerich, F Peter; Tudek, Barbara

    2015-06-01

    AlkB proteins are evolutionary conserved Fe(II)/2-oxoglutarate-dependent dioxygenases, which remove alkyl and highly promutagenic etheno(ɛ)-DNA adducts, but their substrate specificity has not been fully determined. We developed a novel assay for the repair of ɛ-adducts by AlkB enzymes using oligodeoxynucleotides with a single lesion and specific DNA glycosylases and AP-endonuclease for identification of the repair products. We compared the repair of three ɛ-adducts, 1,N(6)-ethenoadenine (ɛA), 3,N(4)-ethenocytosine (ɛC) and 1,N(2)-ethenoguanine (1,N(2)-ɛG) by nine bacterial and two human AlkBs, representing four different structural groups defined on the basis of conserved amino acids in the nucleotide recognition lid, engaged in the enzyme binding to the substrate. Two bacterial AlkB proteins, MT-2B (from Mycobacterium tuberculosis) and SC-2B (Streptomyces coelicolor) did not repair these lesions in either double-stranded (ds) or single-stranded (ss) DNA. Three proteins, RE-2A (Rhizobium etli), SA-2B (Streptomyces avermitilis), and XC-2B (Xanthomonas campestris) efficiently removed all three lesions from the DNA substrates. Interestingly, XC-2B and RE-2A are the first AlkB proteins shown to be specialized for ɛ-adducts, since they do not repair methylated bases. Three other proteins, EcAlkB (Escherichia coli), SA-1A, and XC-1B removed ɛA and ɛC from ds and ssDNA but were inactive toward 1,N(2)-ɛG. SC-1A repaired only ɛA with the preference for dsDNA. The human enzyme ALKBH2 repaired all three ɛ-adducts in dsDNA, while only ɛA and ɛC in ssDNA and repair was less efficient in ssDNA. ALKBH3 repaired only ɛC in ssDNA. Altogether, we have shown for the first time that some AlkB proteins, namely ALKBH2, RE-2A, SA-2B and XC-2B can repair 1,N(2)-ɛG and that ALKBH3 removes only ɛC from ssDNA. Our results also suggest that the nucleotide recognition lid is not the sole determinant of the substrate specificity of AlkB proteins. Copyright © 2015 Elsevier B

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

    International Nuclear Information System (INIS)

    Nair, Jagadeesan; De Flora, Silvio; Izzotti, Alberto; Bartsch, Helmut

    2007-01-01

    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 6 -ethenodeoxyadenine (εdA) and 3,N 4 -ethenodeoxycytosine (εdC). By applying an ultrasensitive 32 P-postlabeling-immunoaffinity method, εdA and εdC 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 εdA from 2.3 to 39.6/10 8 dA and for εdC from 10.7 to 157.7/10 8 dC, with a high correlation between εdA and εdC (r = 0.84, P = 0.0001). Etheno-adduct levels were higher in atherosclerotic smokers than in ex-smokers for both εdA (means 15.2 versus 7.3, P = 0.06) and εdC (71.9 versus 51.6, not significant). εdC 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 εdA or εdC 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 generation of reactive oxygen species, LPO-products and increasing DNA-damage, as documented by the presence of high levels of

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

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2005-04-01

    Full Text Available Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. The high toxicity of many pyrrolizidine alkaloids has caused considerable loss of free-ranging livestock due to liver and pulmonary lesions. Chronic exposure of toxic pyrrolizidine alkaloids to laboratory animals induces cancer. This investigation studies the metabolic activation of retrorsine, a representative naturally occurring tumorigenic pyrrolizidine alkaloid, and shows that a genotoxic mechanism is correlated to the tumorigenicity of retrorsine. Metabolism of retrorsine by liver microsomes of F344 female rats produced two metabolites, 6, 7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, at a rate of 4.8 ± 0.1 nmol/mg/min, and retrorsine-N-oxide, at a rate of 17.6±0.5 nmol/mg/min. Metabolism was enhanced 1.7-fold by using liver microsomes prepared from dexamethasone-treated rats. DHP formation was inhibited 77% and retrorsine N-oxide formation was inhibited 29% by troleandomycin, a P450 3A enzyme inhibitor. Metabolism of retrorsine with lung, kidney, and spleen microsomes from dexamethasone-treated rats also generated DHP and the N-oxide derivative. When rat liver microsomal metabolism of retrorsine occurred in the presence of calf thymus DNA, a set of DHP-derived DNA adducts was formed; these adducts were detected and quantified by using a previously developed 32P-postlabeling/HPLC method. These same DNA adducts were also found in liver DNA of rats gavaged with retrorsine. Since DHP-derived DNA adducts are suggested to be potential biomarkers of riddelliine-induced tumorigenicity, our results indicate that (i similar to the metabolic activation of riddelliine, the mechanism of retrorsine-induced carcinogenicity in rats is also through a genotoxic mechanism involving DHP; and (ii the set of DHP-derived DNA adducts found in liver DNA of rats gavaged with retrorsine or riddelliine can serve as biomarkers for the

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

    Science.gov (United States)

    Wang, Yu-Ping; Fu, Peter P.; Chou, Ming W.

    2005-01-01

    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 tumorigenicity induced by

  13. Eliminative behaviour of dairy cows at pasture

    DEFF Research Database (Denmark)

    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

  14. Elimination of salmonella from animal glandular products.

    Science.gov (United States)

    De Fiebre, C W; Burck, K T; Feldman, D

    1969-03-01

    Methods for the elimination of salmonellae from selected powdered pharmaceuticals of animal glandular origin were studied. Terminal heat treatment under carefully controlled conditions was effective for pancreatin-a powder containing proteolytic, amylolytic, and lipolytic enzymes prepared from hog pancreas glands. Use of this method resulted in a significant reduction in the number of salmonella-positive batches and also reduced the testing procedures required to confirm the absence of viable salmonellae among the majority of samples tested. Powders such as stomach substance and thyroid, in which the biological activity is not enzyme in nature, were treated successfully with acidified organic solvents. Other methods were investigated but were not suitable because of a deleterious effect on the biological activity or physical properties of the product or an inability to effect salmonella elimination.

  15. Elimination of Salmonellae from Animal Glandular Products

    Science.gov (United States)

    De Fiebre, Conrad W.; Burck, Kenneth T.; Feldman, David

    1969-01-01

    Methods for the elimination of salmonellae from selected powdered pharmaceuticals of animal glandular origin were studied. Terminal heat treatment under carefully controlled conditions was effective for pancreatin—a powder containing proteolytic, amylolytic, and lipolytic enzymes prepared from hog pancreas glands. Use of this method resulted in a significant reduction in the number of salmonella-positive batches and also reduced the testing procedures required to confirm the absence of viable salmonellae among the majority of samples tested. Powders such as stomach substance and thyroid, in which the biological activity is not enzyme in nature, were treated successfully with acidified organic solvents. Other methods were investigated but were not suitable because of a deleterious effect on the biological activity or physical properties of the product or an inability to effect salmonella elimination. PMID:5780395

  16. Practical load management - Peak shaving using photovoltaics; Peak Shaving mit der Fotovoltaik. Praktisches Lastmanagement

    Energy Technology Data Exchange (ETDEWEB)

    Berger, W.

    2009-07-01

    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.

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

    NARCIS (Netherlands)

    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

  18. New View of Twin Peaks Region

    Science.gov (United States)

    1997-01-01

    This image taken on Sol 74 ( September 17) from the Sojourner rover's right front camera shows areas of the Pathfinder landing site never before seen. The shadow of the rover and its antenna is visible in the foreground. On the horizon at right are the Twin Peaks, about 1 kilometer away.Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech).

  19. Recent considerations of the GSI positron peaks

    International Nuclear Information System (INIS)

    Soff, G.; Reinhardt, J.; Reus, J. de; Ionescu, D.; Schramm, S.; Mueller, B.; Greiner, W.

    1987-08-01

    In this report we examine various attempts to explain the GSI positron peaks. After the presentation of recent experimental data we briefly sketch theoretical investigations concerning the new particle hypothesis. The failure of standard models employing a linear coupling led to more exotic scenarios for particle production. One exciting recent idea is outlined. After that we treat the possible formation of a resonance in ordinary Bhabha scattering which could represent a time-reversed channel to the observations in heavy-ion collisions. Finally we discuss the poly-positronium model and a purely atomic physics model to interprete the GSI positron events. (orig./HSI)

  20. Engineering training-success at Comanche Peak

    International Nuclear Information System (INIS)

    Oliver, M.G.; Preston, W.D.; McMahon, J.F.

    1993-01-01

    The engineering training program at Comanche Peak steam electric station (CPSES) has received favorable industry recognition. The Institute of Nuclear Power Operations has recommended the CPSES program as a source of information for plants trying to build their own successful programs and has featured the program in an article in the spring 1993 issue of The Nuclear Professional. The U.S. Nuclear Regulatory Commission described the program as superior in a preoperational review and assessment team inspection report and in the most recent systematic assessment of licensee performance. This industry recognition is an important measure of the program's success

  1. Electromechanical Peak Devices of Distributed Power Generation

    Directory of Open Access Journals (Sweden)

    S. V. Konstantinova

    2011-01-01

    Full Text Available The power world crises (1973, 1979 have demonstrated that mankind entered the expensive energy epoch. More and more attitude is given to power saving problem by including renewable power sources in energy balance of the countries. The paper analyzes a power system inBelarusand a typical chart of the active load is cited in the paper. Equalization of load chart is considered as one of measures directed on provision of higher operational efficiency of power system and power saving.  This purpose can be obtained while including electromechanical peak devices of the distributed generation in the energy balance.

  2. Particle creation by peak electric field

    Energy Technology Data Exchange (ETDEWEB)

    Adorno, T.C. [Tomsk State University, Department of Physics, Tomsk (Russian Federation); Gavrilov, S.P. [Tomsk State University, Department of Physics, Tomsk (Russian Federation); Herzen State Pedagogical University of Russia, Department of General and Experimental Physics, St. Petersburg (Russian Federation); Gitman, D.M. [Tomsk State University, Department of Physics, Tomsk (Russian Federation); P. N. Lebedev Physical Institute, Moscow (Russian Federation); University of Sao Paulo, Institute of Physics, CP 66318, Sao Paulo, SP (Brazil)

    2016-08-15

    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. (orig.)

  3. Probable Values of Current Solar Cycle Peak

    Directory of Open Access Journals (Sweden)

    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.

  4. PeakVizor: Visual Analytics of Peaks in Video Clickstreams from Massive Open Online Courses.

    Science.gov (United States)

    Chen, Qing; Chen, Yuanzhe; Liu, Dongyu; Shi, Conglei; Wu, Yingcai; Qu, Huamin

    2016-10-01

    Massive open online courses (MOOCs) aim to facilitate open-access and massive-participation education. These courses have attracted millions of learners recently. At present, most MOOC platforms record the web log data of learner interactions with course videos. Such large amounts of multivariate data pose a new challenge in terms of analyzing online learning behaviors. Previous studies have mainly focused on the aggregate behaviors of learners from a summative view; however, few attempts have been made to conduct a detailed analysis of such behaviors. To determine complex learning patterns in MOOC video interactions, this paper introduces a comprehensive visualization system called PeakVizor. This system enables course instructors and education experts to analyze the "peaks" or the video segments that generate numerous clickstreams. The system features three views at different levels: the overview with glyphs to display valuable statistics regarding the peaks detected; the flow view to present spatio-temporal information regarding the peaks; and the correlation view to show the correlation between different learner groups and the peaks. Case studies and interviews conducted with domain experts have demonstrated the usefulness and effectiveness of PeakVizor, and new findings about learning behaviors in MOOC platforms have been reported.

  5. Probenecid, an inhibitor of transmembrane organic anion transporters, alters tissue distribution of DNA adducts in 1-hydroxymethylpyrene-treated rats.

    Science.gov (United States)

    Monien, Bernhard H; Müller, Carolin; Bakhiya, Nadiya; Donath, Claudia; Frank, Heinz; Seidel, Albrecht; Glatt, Hansruedi

    2009-07-28

    1-Methylpyrene (1-MP), an abundant alkylated polycyclic aromatic hydrocarbon, is activated by side-chain hydroxylation to 1-hydroxymethylpyrene (1-HMP) and subsequent sulfo-conjugation to electrophilic 1-sulfooxymethylpyrene (1-SMP). In rats, this activation mainly occurs in liver. 1-SMP may react with hepatic DNA or be exported into the blood circulation to reach other tissues, in particular kidneys. Findings with recombinant cell lines suggest that renal 1-SMP uptake proceeds via organic anion transporters (OATs). Here, we tested the hypothesis that probenecid, a characteristic OAT inhibitor, interferes with kidney damage brought about by 1-SMP formed in rats. 1-HMP was administered intraperitoneally to 30 rats, half of which were co-treated with probenecid. The tissue distribution of DNA adducts was analyzed using (32)P-postlabeling and isotope dilution LC-MS/MS for the detection of the adducts N(2)-(1-methylpyrenyl)-2'-deoxyguanosine and N(6)-(1-methylpyrenyl)-2'-deoxyadenosine. In rats treated solely with 1-HMP, adduct levels in kidney tissue were about 3-fold and 8-fold higher than those in liver and lung, respectively. After co-treatment with probenecid, hepatic and pulmonary adduct levels were 12-fold and 4-fold elevated, respectively, whereas renal adduct levels were slightly lower compared to those of rats receiving 1-HMP alone. Moreover, serum levels of 1-SMP were increased 23-fold in animals pre-treated with probenecid. The differential effects on hepatic and pulmonary adduct levels suggest that not only renal OATs, but also additional anion transporters, e.g. those mediating the hepatic export of 1-SMP into the bile, were inhibited. Thus, transmembrane transport proteins play a crucial role in the distribution of reactive phase II metabolites, and thereby in tissue allocation of DNA adducts.

  6. Exposure to meat-derived carcinogens and bulky DNA adduct levels in normal-appearing colon mucosa.

    Science.gov (United States)

    Ho, Vikki; Brunetti, Vanessa; Peacock, Sarah; Massey, Thomas E; Godschalk, Roger W L; van Schooten, Frederik J; Ashbury, Janet E; Vanner, Stephen J; King, Will D

    2017-09-01

    Meat consumption is a risk factor for colorectal cancer. This research investigated the relationship between meat-derived carcinogen exposure and bulky DNA adduct levels, a biomarker of DNA damage, in colon mucosa. Least squares regression was used to examine the relationship between meat-derived carcinogen exposure (PhIP and meat mutagenicity) and bulky DNA adduct levels in normal-appearing colon tissue measured using 32 P-postlabelling among 202 patients undergoing a screening colonoscopy. Gene-diet interactions between carcinogen exposure and genetic factors relevant to biotransformation and DNA repair were also examined. Genotyping was conducting using the MassARRAY ® iPLEX ® Gold SNP Genotyping assay. PhIP and higher meat mutagenicity exposures were not associated with levels of bulky DNA adducts in colon mucosa. The XPC polymorphism (rs2228001) was found to associate with bulky DNA adduct levels, whereby genotypes conferring lower DNA repair activity were associated with higher DNA adduct levels than the normal activity genotype. Among individuals with genotypes associated with lower DNA repair (XPD, rs13181 and rs1799179) or detoxification activity (GSTP1, rs1695), higher PhIP or meat mutagenicity exposures were associated with higher DNA adduct levels. Significant interactions between the XPC polymorphism (rs2228000) and both dietary PhIP and meat mutagenicity on DNA adduct levels was observed, but associations were inconsistent with the a priori hypothesized direction of effect. Exposure to meat-derived carcinogens may be associated with increased DNA damage occurring directly in the colon among genetically susceptible individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2015-02-01

    Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6 μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response. - Highlights: • PM forms ovarian DNA adducts. • DNA damage marker γH2AX increased by PM exposure. • PM induces ovarian DNA double strand break repair.

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

    Directory of Open Access Journals (Sweden)

    Peter P. Fu

    2005-04-01

    Full Text Available DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.

  9. Outreach Plans for Storm Peak Laboratory

    Science.gov (United States)

    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.

  10. Peak heart rates at extreme altitudes

    DEFF Research Database (Denmark)

    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...

  11. Monitoring device for local power peaking coefficient

    International Nuclear Information System (INIS)

    Mitsuhashi, Ishi

    1987-01-01

    Purpose: To monitor the local power peaking coefficients obtained by the method not depending on the combination of fuel types. Method: A plurality of representative values for the local power distribution determined by the nuclear constant calculation for one fuel assembly are memorized regarding each of the burn-up degree and the void coefficient on every positions and fuel types in fuel rod assemblies. While on the other hand, the representative values for the local power distribution as described above are compensated by a compensation coefficient considering the effect of adjacent segments and a control rod compensation coefficient considering the effect due to the control rod insertion relative to the just-mentioned compensation coefficient. Then, the maximum value among them is selected to determine the local power peaking coefficient at each of the times and each of the segments, which is monitored. According to this system, the calculation and the working required for the fitting work depending on the combination of fuel types are no more required at all to facilitate the maintenance as well. (Horiuchi, T.)

  12. Peak capacity and peak capacity per unit time in capillary and microchip zone electrophoresis.

    Science.gov (United States)

    Foley, Joe P; Blackney, Donna M; Ennis, Erin J

    2017-11-10

    The origins of the peak capacity concept are described and the important contributions to the development of that concept in chromatography and electrophoresis are reviewed. Whereas numerous quantitative expressions have been reported for one- and two-dimensional separations, most are focused on chromatographic separations and few, if any, quantitative unbiased expressions have been developed for capillary or microchip zone electrophoresis. Making the common assumption that longitudinal diffusion is the predominant source of zone broadening in capillary electrophoresis, analytical expressions for the peak capacity are derived, first in terms of migration time, diffusion coefficient, migration distance, and desired resolution, and then in terms of the remaining underlying fundamental parameters (electric field, electroosmotic and electrophoretic mobilities) that determine the migration time. The latter expressions clearly illustrate the direct square root dependence of peak capacity on electric field and migration distance and the inverse square root dependence on solute diffusion coefficient. Conditions that result in a high peak capacity will result in a low peak capacity per unit time and vice-versa. For a given symmetrical range of relative electrophoretic mobilities for co- and counter-electroosmotic species (cations and anions), the peak capacity increases with the square root of the electric field even as the temporal window narrows considerably, resulting in a significant reduction in analysis time. Over a broad relative electrophoretic mobility interval [-0.9, 0.9], an approximately two-fold greater amount of peak capacity can be generated for counter-electroosmotic species although it takes about five-fold longer to do so, consistent with the well-known bias in migration time and resolving power for co- and counter-electroosmotic species. The optimum lower bound of the relative electrophoretic mobility interval [μ r,Z , μ r,A ] that provides the maximum

  13. Synthesis and Characterization of the Adducts of Morpholinedithioccarbamate Complexes of Oxovanadium (IV, Nickel(II, and Copper(II with Piperidine and Morpholine

    Directory of Open Access Journals (Sweden)

    Mousami Sharma

    2012-01-01

    Full Text Available A series of 1:1 adducts of bis(morpholinedithiocarbamato complex of VO(IV, 1:1 and 1:2 adducts of bis(morpholinedithiocarbamato complexes of Ni(II and Cu(II with piperidine and morpholine have been synthesized and characterized by elemental analysis, molar conductance, magnetic susceptibility, IR, UV-Vis, and TGA/DTA techniques. Analytical data reveals that VO(IV complex forms only 1:1 adducts with the formula [VO(morphdtc2L].H2O while Ni(II and Cu(II complexes form both 1:1 and 1:2 adducts with 1:1 adducts having general formula Ni(morphdtc2.L and Cu(morphdtc2.L and 1:2 adducts having general formula Ni(morphdtc2.L2 and Cu(morphdtc2.L2 (morphdtc = morpholinedithiocarbamate, L = morpholine and piperidine. Antifungal activity of some complexes has been carried out against the fungal strain Fusarium oxysporium. Thermal studies indicate a continuous weight loss. A square pyramidal geometry has been proposed for the 1:1 adducts of Ni(II and Cu(II complexes while an octahedral geometry has been proposed for the 1:1 adducts of VO(IV and for the 1:2 adducts of Ni(II and Cu(II complexes.

  14. Formation of 7-hydroxymethyl-12-methylbenz(a)anthracene-DNA adducts from 7,12-dimethylbenz(a)anthracene in mouse epidermis

    International Nuclear Information System (INIS)

    DiGiovanni, J.; Nebzydoski, A.P.; Decina, P.C.

    1983-01-01

    The formation of DNA adducts from [ 3 H]-7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA) and [ 3 H]-7,12-dimethylbenz(a)anthracene (DMBA) in the epidermis of Sencar mice was analyzed. Comparison of Sephadex LH-20 chromatographic profiles of DNA samples isolated from mice treated with DMBA or 7-OHM-12-MBA suggested that the DMBA-treated animals contained DNA adduct(s) derived from the further metabolism of 7-OHM-12-MBA. Further analysis of DNA samples from DMBA-treated mice by high-pressure liquid chromatography demonstrated the presence of 5 DNA adducts which were chromatographically indistinguishable from the DNA adducts formed in 7-OHM-12-MBA-treated mice. Epidermal homogenates were utilized to catalyze the covalent binding of [ 3 H]DMBA and [ 3 H]-7-OHM-12-MBA to calf thymus DNA in vitro. Under conditions of limiting concentrations of [ 3 H]DMBA, the majority of the DNA adducts formed chromatographed in regions where 7-OHM-12-MBA-DNA adducts eluted. A major DMBA-DNA adduct formed in this in vitro system eluted with the same retention time as did the major 7-OHM-12-MBA-DNA adduct formed in mouse skin in vivo. These results when coupled with the in vivo data suggest that 7-OHM-12-MBA is an intermediate for at least some of the binding of DMBA to epidermal DNA in Sencar mice

  15. Peak Wind Tool for General Forecasting

    Science.gov (United States)

    Barrett, Joe H., III

    2010-01-01

    The expected peak wind speed of the day is an important forecast element in the 45th Weather Squadron's (45 WS) daily 24-Hour and Weekly Planning Forecasts. The forecasts are used for ground and space launch operations at the Kennedy Space Center (KSC) and Cape Canaveral Air Force Station (CCAFS). The 45 WS also issues wind advisories for KSC/CCAFS when they expect wind gusts to meet or exceed 25 kt, 35 kt and 50 kt thresholds at any level from the surface to 300 ft. The 45 WS forecasters have indicated peak wind speeds are challenging to forecast, particularly in the cool season months of October - April. In Phase I of this task, the Applied Meteorology Unit (AMU) developed a tool to help the 45 WS forecast non-convective winds at KSC/CCAFS for the 24-hour period of 0800 to 0800 local time. The tool was delivered as a Microsoft Excel graphical user interface (GUI). The GUI displayed the forecast of peak wind speed, 5-minute average wind speed at the time of the peak wind, timing of the peak wind and probability the peak speed would meet or exceed 25 kt, 35 kt and 50 kt. For the current task (Phase II ), the 45 WS requested additional observations be used for the creation of the forecast equations by expanding the period of record (POR). Additional parameters were evaluated as predictors, including wind speeds between 500 ft and 3000 ft, static stability classification, Bulk Richardson Number, mixing depth, vertical wind shear, temperature inversion strength and depth and wind direction. Using a verification data set, the AMU compared the performance of the Phase I and II prediction methods. Just as in Phase I, the tool was delivered as a Microsoft Excel GUI. The 45 WS requested the tool also be available in the Meteorological Interactive Data Display System (MIDDS). The AMU first expanded the POR by two years by adding tower observations, surface observations and CCAFS (XMR) soundings for the cool season months of March 2007 to April 2009. The POR was expanded

  16. Reducing allergic symptoms through eliminating subgingival plaque

    Directory of Open Access Journals (Sweden)

    Haryono Utomo

    2008-12-01

    Full Text Available Background: Elimination of subgingival plaque for prevention and treatment of periodontal diseases through scaling is a routine procedure. It is also well-known that periodontal disease is related to systemic diseases. Nevertheless, the idea how scaling procedures also able to reduce allergic symptoms i.e. eczema and asthma, is not easily accepted, because it is contradictory to the “hygiene hypothesis”. However, since allergic symptoms also depend on variable factors such as genetic, environmental and infection factors; every possible effort to eliminate or avoid from these factors had to be considered. Subgingival plaque is a source of infection, especially the Gram-negative bacteria that produced endotoxin (lipopolysaccharides, LPS, a potential stimulator of immunocompetent cells, which may also related to allergy, such as mast cells and basophils. In addition, it also triggers the “neurogenic switching” mechanism which may be initiated from chronic gingivitis. Objective: This case report may explain the possible connection between subgingival plaque and allergy based on evidence-based cases. Case: Two adult siblings who suffered from chronic gingivitis also showed different manifestations of allergy that were allergic dermatitis and asthma for years. They were also undergone unsuccessful medical treatment for years. Oral and topical corticosteroids were taken for dermatitis and inhalation for asthma. Case Management: Patients were conducted deep scaling procedures, allergic symptoms gradually diminished in days even though without usual medications. Conclusion: Concerning to the effectiveness of scaling procedures which concomitantly eliminate subgingival plaque in allergic patients, it concluded that this concept is logical. Nevertheless, further verification and collaborated study with allergic expert should be done.

  17. The global cost of eliminating avoidable blindness

    Directory of Open Access Journals (Sweden)

    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.

  18. Neuromuscular NMDA Receptors Modulate Developmental Synapse Elimination.

    Science.gov (United States)

    Personius, Kirkwood E; Slusher, Barbara S; Udin, Susan B

    2016-08-24

    At birth, each mammalian skeletal muscle fiber is innervated by multiple motor neurons, but in a few weeks, all but one of those axons retracts (Redfern, 1970) and differential activity between inputs controls this phenomenon (Personius and Balice-Gordon, 2001; Sanes and Lichtman, 2001; Personius et al., 2007; Favero et al., 2012). Acetylcholine, the primary neuromuscular transmitter, has long been presumed to mediate this activity-dependent process (O'Brien et al., 1978), but glutamatergic transmission also occurs at the neuromuscular junction (Berger et al., 1995; Grozdanovic and Gossrau, 1998; Mays et al., 2009). To test the role of neuromuscular NMDA receptors, we assessed their contribution to muscle calcium fluxes in mice and tested whether they influence removal of excess innervation at the end plate. Developmental synapse pruning was slowed by reduction of NMDA receptor activation or expression and by reduction of glutamate production. Conversely, pruning is accelerated by application of exogenous NMDA. We also found that NMDA induced increased muscle calcium only during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play previously unsuspected roles in neuromuscular activity and synaptic pruning during development. In normal adult muscle, each muscle fiber is innervated by a single axon, but at birth, fibers are multiply innervated. Elimination of excess connections requires neural activity; because the neuromuscular junction (NMJ) is a cholinergic synapse, acetylcholine has been assumed to be the critical mediator of activity. However, glutamate receptors are also expressed at the NMJ. We found that axon removal in mice is slowed by pharmacological and molecular manipulations that decrease signaling through neuromuscular NMDA receptors, whereas application of exogenous NMDA at the NMJ accelerates synapse elimination and increases muscle calcium levels during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play

  19. The global cost of eliminating avoidable blindness

    Science.gov (United States)

    Armstrong, Kirsten L; Jovic, Martin; Vo-Phuoc, Jennifer L; Thorpe, Jeremy G; Doolan, Brian L

    2012-01-01

    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. PMID:22944763

  20. Heuristic Drift Elimination for Personnel Tracking Systems

    Science.gov (United States)

    Borenstein, Johann; Ojeda, Lauro

    This paper pertains to the reduction of the effects of measurement errors in rate gyros used for tracking, recording, or monitoring the position of persons walking indoors. In such applications, bias drift and other gyro errors can degrade accuracy within minutes. To overcome this problem we developed the Heuristic Drift Elimination (HDE) method, that effectively corrects bias drift and other slow-changing errors. HDE works by making assumptions about walking in structured, indoor environments. The paper explains the heuristic assumptions and the HDE method, and shows experimental results. In typical applications, HDE maintains near-zero heading errors in walks of unlimited duration.

  1. Redundancy Elimination in DTN via ACK Mechanism

    Directory of Open Access Journals (Sweden)

    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.

  2. Elimination of Chagas disease transmission: perspectives.

    Science.gov (United States)

    Dias, João Carlos Pinto

    2009-07-01

    One hundred years after its discovery by Carlos Chagas, American trypanosomiasis, or Chagas disease, remains an epidemiologic challenge. Neither a vaccine nor an ideal specific treatment is available for most chronic cases. Therefore, the current strategy for countering Chagas disease consists of preventive actions against the vector and transfusion-transmitted disease. Here, the present challenges, including congenital and oral transmission of Trypanosoma cruzi infections, as well as the future potential for Chagas disease elimination are discussed in light of the current epidemiological picture. Finally, a list of challenging open questions is presented about Chagas disease control, patient management, programme planning and priority definitions faced by researchers and politicians.

  3. Myeloperoxidase (MPO) -463G->A reduces MPO activity and DNA adduct levels in bronchoalveolar lavages of smokers.

    Science.gov (United States)

    Van Schooten, Frederik J; Boots, Agnes W; Knaapen, Ad M; Godschalk, Roger W L; Maas, Lou M; Borm, Paul J A; Drent, Marjolein; Jacobs, Jan A

    2004-05-01

    The myeloperoxidase (MPO) -463G-->A genetic polymorphism is associated with a reduced risk for lung cancer, but the underlying mechanism is not yet elucidated. Therefore, the impact of this polymorphism on MPO activity and lipophilic DNA adducts was studied in respectively bronchoalveolar lavage (BAL) fluid and cells, from 106 smoking Caucasian lung patients. MPO activity was determined spectrophotometrically, aromatic DNA adducts by (32)P-postlabeling and MPO genotypes by RFLP analysis. Frequencies of MPO -463AA (13%), MPO -463AG (36%), and MPO -463GG (51%) were in line with earlier observations. MPO activity/neutrophil was lower in MPO -463AA (median 0.04 pU/cell) than in MPO -463AG (median 0.07 pU/cell) and MPO -463GG (median 0.14 pU/cell; P = 0.059) individuals. DNA adducts in BAL cells were measured in 11 MPO -463AA subjects and equal numbers of MPO -463AG and MPO -463GG subjects matched for smoking, age, gender, and clinical diagnosis. DNA adduct levels in MPO -463AA individuals (median 0.62 adducts/10(8) nucleotides) were lower than in MPO -463AG (median 1.51 adducts/10(8) nucleotides) and MPO -463GG (median 3.26 adducts/10(8) nucleotides; P = 0.003) subjects. Overall, no significant correlation was observed between amount of inhaled tar/day and DNA adduct levels. However, correlations improved considerably on grouping according to the MPO genotype; MPO -463AA subjects were the least responsive (R(2) = 0.73, slope = 0.4, P = 0.01) followed by MPO -463AG subjects (R(2) = 0.70, slope = 1.3, P = 0.01) and MPO -463GG patients (R(2) = 0.67, slope = 2.8, P = 0.02). These data demonstrate that MPO -463AA/AG genotypes are associated with (a) reduced MPO activity in BAL fluid and (b) reduced smoking-related DNA adduct levels in BAL cells in a gene-dose manner. These data provide a plausible biological explanation for the reduced risk for lung cancer as observed in MPO -463AA/AG compared with MPO -463GG subjects.

  4. Quantification of 3-nitrobenzanthrone-DNA adducts using online column-switching HPLC-electrospray tandem mass spectrometry.

    Science.gov (United States)

    Gamboa da Costa, Gonçalo; Singh, Rajinder; Arlt, Volker M; Mirza, Amin; Richards, Meirion; Takamura-Enya, Takeji; Schmeiser, Heinz H; Farmer, Peter B; Phillips, David H

    2009-11-01

    The aromatic nitroketone 3-nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one; 3-NBA) is an extremely potent mutagen and a suspected human carcinogen detected in the exhaust of diesel engines and in airborne particulate matter. 3-NBA is metabolically activated via reduction of the nitro group to the hydroxylamine (N-OH-3-ABA) to form covalent DNA adducts. Thus far, the detection and quantification of covalent 3-NBA-DNA adducts has relied solely on (32)P-postlabeling methodologies. In order to expand the range of available techniques for the detection and improved quantification of 3-NBA-DNA adducts, we have developed a method based upon online column-switching HPLC coupled to electrospray tandem mass spectrometry, with isotopic dilution of (15)N-labeled internal standards. This methodology was applied to the determination of three 3-NBA-derived adducts: 2-(2'-deoxyguanosin-N(2)-yl)-3-aminobenzanthrone (dG-N(2)-3-ABA), N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (dG-C8-N-3-ABA) and 2-(2'-deoxyguanosine-8-yl)-3-aminobenzanthrone (dG-C8-C2-3-ABA). Dose-dependent increases were observed for all three adducts when salmon testis DNA was reacted with N-acetoxy-3-aminobenzanthrone (N-AcO-3-ABA). dG-C8-C2-3-ABA was detected at much lower levels (overall 1%) than the other two adducts. DNA samples isolated from tissues of rats treated either intratracheally with 3-NBA or intraperitoneally with N-OH-3-ABA were analyzed by mass spectrometry, and the results compared to those obtained by (32)P-postlabeling. The method required 50 microg of hydrolyzed animal DNA on column and the limit of detection was 2.0 fmol for each adduct. dG-C8-C2-3-ABA was not observed in any of the samples providing confirmation that it is not formed in vivo. Linear regression analysis of the levels of dG-N(2)-3-ABA and dG-C8-N-3-ABA in the rat DNA showed a reasonable correlation between the two methods (R(2) = 0.88 and 0.93, respectively). In summary, the mass spectrometric method is a faster, more

  5. Posterior Tibial Slope Angle Correlates With Peak Sagittal and Frontal Plane Knee Joint Loading During Robotic Simulations of Athletic Tasks

    Science.gov (United States)

    Bates, Nathaniel A.; Nesbitt, Rebecca J.; Shearn, Jason T.; Myer, Gregory D.; Hewett, Timothy E.

    2017-01-01

    Background Tibial slope angle is a nonmodifiable risk factor for anterior cruciate ligament (ACL) injury. However, the mechanical role of varying tibial slopes during athletic tasks has yet to be clinically quantified. Purpose To examine the influence of posterior tibial slope on knee joint loading during controlled, in vitro simulation of the knee joint articulations during athletic tasks. Study Design Descriptive laboratory study. Methods A 6 degree of freedom robotic manipulator positionally maneuvered cadaveric knee joints from 12 unique specimens with varying tibial slopes (range, −7.7° to 7.7°) through drop vertical jump and sidestep cutting tasks that were derived from 3-dimensional in vivo motion recordings. Internal knee joint torques and forces were recorded throughout simulation and were linearly correlated with tibial slope. Results The mean (6SD) posterior tibial slope angle was 2.2° ± 4.3° in the lateral compartment and 2.3° ± 3.3° in the medial compartment. For simulated drop vertical jumps, lateral compartment tibial slope angle expressed moderate, direct correlations with peak internally generated knee adduction (r = 0.60–0.65), flexion (r = 0.64–0.66), lateral (r = 0.57–0.69), and external rotation torques (r = 0.47–0.72) as well as inverse correlations with peak abduction (r = −0.42 to −0.61) and internal rotation torques (r = −0.39 to −0.79). Only frontal plane torques were correlated during sidestep cutting simulations. For simulated drop vertical jumps, medial compartment tibial slope angle expressed moderate, direct correlations with peak internally generated knee flexion torque (r = 0.64–0.69) and lateral knee force (r = 0.55–0.74) as well as inverse correlations with peak external torque (r = −0.34 to 20.67) and medial knee force (r = −0.58 to −0.59). These moderate correlations were also present during simulated sidestep cutting. Conclusion The investigation supported the theory that increased posterior

  6. Peak Electric Load Relief in Northern Manhattan

    Directory of Open Access Journals (Sweden)

    Hildegaard D. Link

    2014-08-01

    Full Text Available The aphorism “Think globally, act locally,” attributed to René Dubos, reflects the vision that the solution to global environmental problems must begin with efforts within our communities. PlaNYC 2030, the New York City sustainability plan, is the starting point for this study. Results include (a a case study based on the City College of New York (CCNY energy audit, in which we model the impacts of green roofs on campus energy demand and (b a case study of energy use at the neighborhood scale. We find that reducing the urban heat island effect can reduce building cooling requirements, peak electricity loads stress on the local electricity grid and improve urban livability.

  7. Twin Peaks in 360-degree panorama

    Science.gov (United States)

    1997-01-01

    The prominent hills dubbed 'Twin Peaks' approximately 1-2 kilometers away were imaged by the Imager for Mars Pathfinder (IMP) as part of a 360-degree color panorama, taken over sols 8, 9 and 10. A lander petal and deflated airbag are at the bottom of the image.Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  8. Tim Peake and Britain's road to space

    CERN Document Server

    Seedhouse, Erik

    2017-01-01

    This book puts the reader in the flight suit of Britain’s first male astronaut, Tim Peake. It chronicles his life, along with the Principia mission and the down-to-the-last-bolt descriptions of life aboard the ISS, by way of the hurdles placed by the British government and the rigors of training at Russia’s Star City military base. In addition, this book discusses the learning curves required in astronaut and mission training and the complexity of the technologies required to launch an astronaut and keep them alive for months on end. This book underscores the fact that technology and training, unlike space, do not exist in a vacuum; complex technical systems, like the ISS, interact with the variables of human personality, and the cultural background of the astronauts. .

  9. Comparison of five portable peak flow meters

    Directory of Open Access Journals (Sweden)

    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.

  10. Comparison of five portable peak flow meters.

    Science.gov (United States)

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

    2010-05-01

    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. 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. 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(R) (p<0.001) and Galemed (p<0.01) meters. There was no agreement between the spirometric values and the five PEF meters. 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.

  11. Calcium Isotope Analysis with "Peak Cut" Method on Column Chemistry

    Science.gov (United States)

    Zhu, H.; Zhang, Z.; Liu, F.; Li, X.

    2017-12-01

    To eliminate isobaric interferences from elemental and molecular isobars (e.g., 40K+, 48Ti+, 88Sr2+, 24Mg16O+, 27Al16O+) on Ca isotopes during mass determination, samples should be purified through ion-exchange column chemistry before analysis. However, large Ca isotopic fractionation has been observed during column chemistry (Russell and Papanastassiou, 1978; Zhu et al., 2016). Therefore, full recovery during column chemistry is greatly needed, otherwise uncertainties would be caused by poor recovery (Zhu et al., 2016). Generally, matrix effects could be enhanced by full recovery, as other elements might overlap with Ca cut during column chemistry. Matrix effects and full recovery are difficult to balance and both need to be considered for high-precision analysis of stable Ca isotopes. Here, we investigate the influence of poor recovery on δ44/40Ca using TIMS with the double spike technique. The δ44/40Ca values of IAPSO seawater, ML3B-G and BHVO-2 in different Ca subcats (e.g., 0-20, 20-40, 40-60, 60-80, 80-100%) with 20% Ca recovery on column chemistry display limited variation after correction by the 42Ca-43Ca double spike technique with the exponential law. Notably, δ44/40Ca of each Ca subcut is quite consistent with δ44/40Ca of Ca cut with full recovery within error. Our results indicate that the 42Ca-43Ca double spike technique can simultaneously correct both of the Ca isotopic fractionation that occurred during column chemistry and thermal ionization mass spectrometry (TIMS) determination properly, because both of the isotopic fractionation occurred during analysis follow the exponential law well. Therefore, we propose the "peak cut" method on Ca column chemistry for samples with complex matrix effects. Briefly, for samples with low Ca contents, we can add the double spike before column chemistry, and only collect the middle of the Ca eluate and abandon the both sides of Ca eluate that might overlap with other elements (e.g., K, Sr). This method would

  12. Adducts of Oxylipin Electrophiles to Glutathione Reflect a 13 Specificity of the Downstream Lipoxygenase Pathway in the Tobacco Hypersensitive Response

    Science.gov (United States)

    Davoine, Céline; Falletti, Olivier; Douki, Thierry; Iacazio, Gilles; Ennar, Najla; Montillet, Jean-Luc; Triantaphylidès, Christian

    2006-01-01

    The response to reactive electrophile species (RES) is now considered as part of the plant response to pathogen and insect attacks. Thanks to a previously established high-performance liquid chromatography tandem mass spectrometry methodology, we have investigated the production of oxylipin RES adducts to glutathione (GSH) during the hypersensitive response (HR) of plants. We have observed that RES conjugation to GSH in tobacco (Nicotiana tabacum) leaves is facile and nonspecific. In cryptogein-elicited tobacco leaves, we show that the oxylipin RES adducts to GSH are produced in correlation with GSH consumption, increase in glutathione S-transferase activity, and the appearance of the cell death symptoms. In this model, the adducts arise mainly from the downstream 13 lipoxygenase (LOX) metabolism, although the induced 9 LOX pathway leads massively to the accumulation of upstream metabolites. The main adducts were obtained from 2-hexenal and 12-oxo-phytodienoic acid. They accumulate transiently as 1-hexanol-3-GSH, a reduced adduct, and 12-oxo-phytodienoic acid-GSH, respectively. RES conjugation does not initiate cell death but explains part of the GSH depletion that accompanies HR cell death. The nature of these GSH conjugates shows the key role played by the 13 LOX pathway in RES signaling in the tobacco HR. PMID:16500992

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

    International Nuclear Information System (INIS)

    Allaben, W.T.; Weis, C.C.; Fullerton, N.F.; Beland, F.A.

    1983-01-01

    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- 3 H]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

  14. Separation and identification of DNA-carcinogen adduct conformers by polyacrylamide gel electrophoresis with laser-induced fluorescence detection

    Energy Technology Data Exchange (ETDEWEB)

    Marsch, G.A.; Jankowiak, R.; Farhat, J.H.; Small, G.J. (Ames Lab., IA (United States) Iowa State Univ., Ames (United States))

    1992-12-01

    The authors have developed a separation protocol utilizing high-resolution polyacrylamide gel electrophoresis (PAGE) to isolate stable anti-benzo[a]pyrene diol epoxide adducts of oligodeoxynucleotides. Both enantiomers produced multiple adduct species. The distribution of adduct types could be quantitated by densitometry of autoradiograms or Cerenkov counting of eluted oligomers modified by anti-BPDE isomers. Laser-induced fluorescence (LIF) spectra of eluted adducts at 4.2 K (fluorescence line-narrowing spectroscopy) and 77 K revealed that bands corresponded to pure conformers of pyrene chromophore. Carcinogen-modified oligodeoxynucleotides were single-stranded, but there were often considerable stacking interactions between the pyrenyl residues and the oligonucleotide bases, indicating that electrophoresed oligomers were single-stranded but in a native, versus random-coil conformation. The ability to identify and quantitate adducts by PAGE-LIF, coupled with the high resolution and sensitivity of both techniques, makes PAGE and LIF in tandem a potentially powerful tool in the study of chemical carcinogenesis or other ligand-DNA interactions. 43 refs., 7 figs., 1 tab.

  15. Electronic structure and optical properties of Eu(III) tris-β-diketonate adducts with 1,10-phenanthroline

    Science.gov (United States)

    Shurygin, A. V.; Korochentsev, V. V.; Cherednichenko, A. I.; Mirochnik, A. G.; Kalinovskaya, I. V.; Vovna, V. I.

    2018-03-01

    Adducts of tris-β-diketonates of the rare earth metal Eu(III) with 1,10-phenanthroline are studied by photoelectron spectroscopy and quantum chemistry methods. The electronic structure, peculiarities of the nature of chemical bonds, and the geometric structure of the adducts are determined. The interpretation of UV photoelectron spectra of vapors and X-ray photoelectron spectra of solid is carried out with the chosen technique. DFT/TDDFT methods make it possible to study the 1,10-phenanthroline molecule influence on the adduct electronic structure and to analyze the electronic effects of substitution of methyl groups by trifluoromethyl groups in the ligands. At transition from the tris-β-diketonate complexes to the adducts, it is observed an increase of the absorption region and a decrease in the energy gap that contributes to the efficiency growth in electronic excitation energy transfer in the ligand-metal. Moreover, phenanthroline displaces water groups, that are luminescence quenchers, from the first coordination sphere, closes coordination in the adduct, and blocks their further attachment. Both factors contribute to an increase in the luminescence intensity.

  16. Gold Nanoparticles for the Detection of DNA Adducts as Biomarkers of Exposure to Acrylamide

    Science.gov (United States)

    Larguinho, Miguel Angelo Rodrigues

    The main objective of this thesis was the development of a gold nanoparticle-based methodology for detection of DNA adducts as biomarkers, to try and overcome existing drawbacks in currently employed techniques. For this objective to be achieved, the experimental work was divided in three components: sample preparation, method of detection and development of a model for exposure to acrylamide. Different techniques were employed and combined for de-complexation and purification of DNA samples (including ultrasonic energy, nuclease digestion and chromatography), resulting in a complete protocol for sample treatment, prior to detection. The detection of alkylated nucleotides using gold nanoparticles was performed by two distinct methodologies: mass spectrometry and colorimetric detection. In mass spectrometry, gold nanoparticles were employed for laser desorption/ionisation instead of the organic matrix. Identification of nucleotides was possible by fingerprint, however no specific mass signals were denoted when using gold nanoparticles to analyse biological samples. An alternate method using the colorimetric properties of gold nanoparticles was employed for detection. This method inspired in the non-cross-linking assay allowed the identification of glycidamide-guanine adducts and DNA adducts generated in vitro. For the development of a model of exposure, two different aquatic organisms were studies: a goldfish and a mussel. Organisms were exposed to waterborne acrylamide, after which mortality was recorded and effect concentrations were estimated. In goldfish, both genotoxicity and metabolic alterations were assessed and revealed dose-effect relationships of acrylamide. Histopathological alterations were verified primarily in pancreatic cells, but also in hepatocytes. Mussels showed higher effect concentrations than goldfish. Biomarkers of oxidative stress, biotransformation and neurotoxicity were analysed after prolonged exposure, showing mild oxidative stress in

  17. Kinetics of hydroperoxy radical reactions with acetone/HO2 adduct and with acetonylperoxy radical

    Science.gov (United States)

    Grieman, F. J.; VanDerGeest, K.; Newenhouse, E.; Watkins, K.; Noell, A. C.; Hui, A.; Sander, S. P.; Okumura, M.

    2013-12-01

    Reactions of hydroperoxy radical, HO2, with acetone and with acetonylperoxy radical, CH3C(O)CH2OO, may play an important role in the oxidation chemistry of the troposphere. Using a temperature-controlled slow-flow tube cell and laser flash photolysis of Cl2 to produce HO2 and CH3C(O)CH2OO from methanol and acetone, respectively, we studied the chemical kinetics involved over the temperature range of 215 to 298 K at 100 Torr. Rates of chemical reactions were determined by monitoring the HO2 concentration as a function of time by near-IR diode laser wavelength modulation spectroscopy. (See Fig.1.) The primary reactions are rapid (reactions to form the adducts HO2-CH3OH and HO2-CH3C(O)CH3 followed by HO2 reactions with itself, the adducts (chaperone mechanisms), and acetonylperoxy radical. The equilibrium constants for adduct formation were determined in previous work.1,2 In this work, rate coefficients were determined for the acetone chaperone mechanism over the entire temperature range. (E.g., see Fig. 2.) The rate coefficients and energies obtained are very similar to those found for the methanol case.1 Rate coefficients for the CH3C(O)CH2OO/HO2 reaction were also determined over a smaller temperature range, extending the measured value beyond room temperature, and yielding an activation energy. 1. Christensen et al. J. Phys. Chem. A 2006, 110, 6948-6959. 2. Grieman et al. J. Phys. Chem. A 2011, 115, 10527-10538. Fig.1. HO2 decay for HO2/Acetone chemistry at T = 298 K. Fig.2. Determining rate coefficient (k") for HO2/acetone chaperone effect at T = 222.5 K.

  18. Shutdown potential adjustment of modified carbene adducts as additives for lithium ion battery electrolytes

    Science.gov (United States)

    Janssen, Pia; Streipert, Benjamin; Krafft, Roman; Murmann, Patrick; Wagner, Ralf; Lewis-Alleyne, Lesley; Röschenthaler, Gerd-Volker; Winter, Martin; Cekic-Laskovic, Isidora

    2017-11-01

    To improve the intrinsic safety of lithium ion batteries (LIBs) by preventing cells from a thermal runaway, we studied two carbene adduct electrolyte additives. The recently synthesized compounds (1,3-dimethylimidazolidin-2-μm-trifluoroborate (NHC-BF3) and 1,3-dimethylimidazolidin-2-μm-tetrafluorotrifluoromethylphosphate (NHC-PF4CF3)) were investigated on LiNi1/3Co1/3Mn1/3O2 (NMC111) electrodes in Li metal and Li-ion cell setups as overcharge protection shutdown additives in 1M LiPF6 in EC:DEC (3:7, by wt.) electrolyte. By varying the NHC-ligand (-BF3, -PF5, -PF4CF3) in the molecule, the shutdown potential of the investigated carbene adduct electrolyte additives can be tailored for specific applications with different cut-off potentials. NHC-BF3 was identified as a promising candidate for the application with NMC111 electrodes up to 4.4 V vs. Li/Li+, whereas the carbene adduct NHC-PF4CF3 is ideal for the high-voltage application with the NMC-based electrode up to 4.6 V vs. Li/Li+. Next to electrochemical investigations in NMC111/Li and NMC111/graphite cells, Atomic Force Microscopy (AFM) and X-Ray Photoelectron Spectroscopy (XPS) were performed to verify the presence of a decomposition layer on the cathode, responsible for the shutdown effect. Furthermore, it has been proven that the investigated electrolyte additives have no influence on the cell performance under normal conditions in both, Li metal and Li-ion cell setups.

  19. Feasibility of vocal fold abduction and adduction assessment using cine-MRI.

    Science.gov (United States)

    Baki, Marina Mat; Menys, Alex; Atkinson, David; Bassett, Paul; Morley, Simon; Beale, Timothy; Sandhu, Guri; Naduvilethil, Georgekutty; Stevenson, Nicola; Birchall, Martin A; Punwani, Shonit

    2017-02-01

    Determine feasibility of vocal fold (VF) abduction and adduction assessment by cine magnetic resonance imaging (cine-MRI) METHODS: Cine-MRI of the VF was performed on five healthy and nine unilateral VF paralysis (UVFP) participants using an axial gradient echo acquisition with temporal resolution of 0.7 s. VFs were continuously imaged with cine-MRI during a 10-s period of quiet respiration and phonation. Scanning was repeated twice within an individual session and then once again at a 1-week interval. Asymmetry of VF position during phonation (VF phonation asymmetry, VFPa) and respiration (VF respiration asymmetry, VFRa) was determined. Percentage reduction in total glottal area between respiration and phonation (VF abduction potential, VFAP) was derived to measure overall mobility. An un-paired t-test was used to compare differences between groups. Intra-session, inter-session and inter-reader repeatability of the quantitative metrics was evaluated using intraclass correlation coefficient (ICC). VF position asymmetry (VFPa and VFRa) was greater (p=0.012; p=0.001) and overall mobility (VFAP) was lower (p=0.008) in UVFP patients compared with healthy participants. ICC of repeatability of all metrics was good, ranged from 0.82 to 0.95 except for the inter-session VFPa (0.44). Cine-MRI is feasible for assessing VF abduction and adduction. Derived quantitative metrics have good repeatability. • Cine-MRI is used to assess vocal folds (VFs) mobility: abduction and adduction. • New quantitative metrics are derived from VF position and abduction potential. • Cine-MRI able to depict the difference between normal and abnormal VF mobility. • Cine-MRI derived quantitative metrics have good repeatability.

  20. Pneumatic Multi-Pocket Elastomer Actuators for Metacarpophalangeal Joint Flexion and Abduction-Adduction

    Directory of Open Access Journals (Sweden)

    Tapio Veli Juhani Tarvainen

    2017-09-01

    Full Text Available During recent years, interest has been rising towards developing fluidic fiber-reinforced elastomer actuators for wearable soft robotics used in hand rehabilitation and power-assist. However, they do not enable finger abduction-adduction, which plays an important role in activities of daily living, when grasping larger objects. Furthermore, the developed gloves often do not have separate control of joints, which is important for doing various common rehabilitation motions. The main obstacle for the development of a fully-assisting glove is moving a joint with multiple degrees of freedom. If the functions are built into the same structure, they are naturally coupled and affect each other, which makes them more difficult to design and complex to control than a simple flexion-extension actuator. In this study, we explored the key design elements and fabrication of pneumatic multi-pocket elastomer actuators for a soft rehabilitation glove. The goal was to gain more control over the metacarpophalangeal joint’s response by increasing the degree of actuation. Three main functional designs were tested for achieving both flexion and abduction-adduction. Five prototypes, with four different actuator geometries and four different reinforcement types, were designed and fabricated. They were evaluated by recording their free motion with motion capture and measuring their torque output using a dummy finger. Results showed the strengths and weaknesses of each design in separating the control of the two functions. We discuss the different improvements that are needed in order to make each design plausible for developing an actuator that meets the requirements for full assist of the hand’s motions. In conclusion, we show that it is possible to produce multi-pocket actuators for assisting MCP joint motion in both flexion and abduction-adduction, although coupling between the separate functions is still problematic and should be considered further.

  1. Peak expiratory flow rate and Pulse Pressure values during the ...

    African Journals Online (AJOL)

    This study assessed the peak expiratory flow rate and pulse pressure during the luteal and menstruation phases of the menstrual cycle. The peak expiratory flow rate and pulse pressure were measured using the Wright's Peak Flow Meter and Mercury Sphygmomanometer respectively. The peak expiratory flow rate and ...

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

    DEFF Research Database (Denmark)

    Frederiksen, Hanne

    2005-01-01

    or proteins of animal or vegetable origin, furthermore they are found in many cooked foods, such as fish, meat, and chicken. The specific mutagenicity of the amino-a-carbolines are lower in the Ames Salmonella assay than other heterocyclic amines, but in rodent studies the carcinogenicity of the aminoa, alpha......-carbolines are comparable to other heterocyclic amines. The metabolic pathways of the amino-alpha-carbolines have been studied in vitro and in vivo, and the detoxified phase I and phase II metabolites characterized and quantified. The metabolic activation of the amino-a-carbolines and the formation of DNA-adducts have also...

  3. Azoliniums, Adducts, NHCs and Azomethine Ylides: Divergence in Wanzlick Equilibrium and Olefin Metathesis Catalyst Formation.

    Science.gov (United States)

    Jolly, Phillip I; Marczyk, Anna; Małecki, Paweł; Ablialimov, Osman; Trzybiński, Damian; Woźniak, Krzysztof; Osella, Silvio; Trzaskowski, Bartosz; Grela, Karol

    2018-04-03

    The dimerization of a saturated N-heterocyclic carbene (NHC) to tricyclic piperazine in preference to the commonly observed Wanzlick dimerization is presented. Mechanistic investigations revealed that the N-fluorene substituent of the heterocycle is implicated in both ring opening of corresponding carbene dimer and tautomerization of NHC to an azomethine ylide. This has consequences for the fate of the NHC when generated from either an azolinium salt or a pentafluorophenyl adduct. The insights gained permitted the synthesis of a new indenylidene metathesis precatalyst, which exhibits exceptional selectivity and high TONS in self-metathesis of 1-octene. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Polymerase Bypass of N(6)-Deoxyadenosine Adducts Derived from Epoxide Metabolites of 1,3-Butadiene.

    Science.gov (United States)

    Kotapati, Srikanth; Wickramaratne, Susith; Esades, Amanda; Boldry, Emily J; Quirk Dorr, Danae; Pence, Matthew G; Guengerich, F Peter; Tretyakova, Natalia Y

    2015-07-20

    N(6)-(2-Hydroxy-3-buten-1-yl)-2'-deoxyadenosine (N(6)-HB-dA I) and N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (N(6),N(6)-DHB-dA) are exocyclic DNA adducts formed upon alkylation of the N(6) position of adenine in DNA by epoxide metabolites of 1,3-butadiene (BD), a common industrial and environmental chemical classified as a human and animal carcinogen. Since the N(6)-H atom of adenine is required for Watson-Crick hydrogen bonding with thymine, N(6)-alkylation can prevent adenine from normal pairing with thymine, potentially compromising the accuracy of DNA replication. To evaluate the ability of BD-derived N(6)-alkyladenine lesions to induce mutations, synthetic oligodeoxynucleotides containing site-specific (S)-N(6)-HB-dA I and (R,R)-N(6),N(6)-DHB-dA adducts were subjected to in vitro translesion synthesis in the presence of human DNA polymerases β, η, ι, and κ. While (S)-N(6)-HB-dA I was readily bypassed by all four enzymes, only polymerases η and κ were able to carry out DNA synthesis past (R,R)-N(6),N(6)-DHB-dA. Steady-state kinetic analyses indicated that all four DNA polymerases preferentially incorporated the correct base (T) opposite (S)-N(6)-HB-dA I. In contrast, hPol β was completely blocked by (R,R)-N(6),N(6)-DHB-dA, while hPol η and κ inserted A, G, C, or T opposite the adduct with similar frequency. HPLC-ESI-MS/MS analysis of primer extension products confirmed that while translesion synthesis past (S)-N(6)-HB-dA I was mostly error-free, replication of DNA containing (R,R)-N(6),N(6)-DHB-dA induced significant numbers of A, C, and G insertions and small deletions. These results indicate that singly substituted (S)-N(6)-HB-dA I lesions are not miscoding, but that exocyclic (R,R)-N(6),N(6)-DHB-dA adducts are strongly mispairing, probably due to their inability to form stable Watson-Crick pairs with dT.

  5. Polymerase Bypass of N6-Deoxyadenosine Adducts Derived from Epoxide Metabolites of 1,3-Butadiene

    Science.gov (United States)

    Kotapati, Srikanth; Wickramaratne, Susith; Esades, Amanda; Boldry, Emily J.; Dorr, Danae Quirk; Pence, Matthew G.; Guengerich, F. Peter; Tretyakova, Natalia Y.

    2015-01-01

    N 6-(2-Hydroxy-3-buten-1-yl)-2′-deoxyadenosine (N6-HB-dA I) and N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (N6,N6-DHB-dA) are exocyclic DNA adducts formed upon alkylation of the N6 position of adenine in DNA by epoxide metabolites of 1,3-butadiene (BD), a common industrial and environmental chemical classified as a human and animal carcinogen. Since the N6-H atom of adenine is required for Watson-Crick hydrogen bonding with thymine, N6-alkylation can prevent adenine from normal pairing with thymine, potentially compromising the accuracy of DNA replication. To evaluate the ability of BD-derived N6-alkyladenine lesions to induce mutations, synthetic oligodeoxynucleotides containing site-specific (S)-N6-HB-dA I and (R,R)-N6,N6-DHB-dA adducts were subjected to in vitro translesion synthesis in the presence of human DNA polymerases β, η, ι, and κ. While (S)-N6-HB-dA I was readily bypassed by all four enzymes, only polymerases η and κ were able to carry out DNA synthesis past (R,R)-N6,N6-DHB-dA. Steady-state kinetic analyses indicated that all four DNA polymerases preferentially incorporated the correct base (T) opposite (S)-N6-HB-dA I. In contrast, hPol β was completely blocked by (R,R)-N6,N6-DHB-dA, while hPol η and κ inserted A, G, C, or T opposite the adduct with similar frequency. HPLC-ESI-MS/MS analysis of primer extension products confirmed that while translesion synthesis past (S)-N6-HB-dA I was mostly error-free, replication of DNA containing (R,R)-N6,N6-DHB-dA induced significant numbers of A, C, and G insertions and small deletions. These results indicate that singly substituted (S)-N6-HB-dA I lesions are not miscoding, but exocyclic (R,R)-N6,N6-DHB-dA adducts are strongly mispairing, probably due to their inability to form stable Watson-Crick pairs with dT. PMID:26098310

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

    Directory of Open Access Journals (Sweden)

    Ângelo de Fátima

    2015-05-01

    Full Text Available Since the disclosure of Biginelli reaction by the chemist Pietro Biginelli, functionalized 3,4-dihydropyrimidin-2(1H-ones/thiones (DHPMs have emerged as prototypes for the design of compounds with a broad variety of biological activities. This mini-review describes over 100 Biginelli adducts demonstrated to be promising anticancer, inhibitors of calcium channel, anti-inflammatory, antimicrobial and antioxidant agents. Thus, this compilation presents the most notable in vitro and in vivo results for such fascinating class of organic compounds.

  7. Unexpected synthesis of cinnamaldehyde-dimedone adduct using samarium (III) chloride

    Science.gov (United States)

    Cahyana, A. H.; Nadila, A.; Ardiansah, B.

    2017-07-01

    In the present work, 1,8-dioxooctahydroxanthene cannot be obtained from the reaction between cinnamaldehyde and dimedone (ratio 1:2) using samarium(III) chloride as a Lewis acid catalyst. The unexpected product formed is 5,5-dimethyl-2-(3-phenylallylidene)cyclohexane-1,3-dione as a result of 1:1 adduct. The product is obtained in a low to good yield and the optimum protocol can be achieved by running the reaction using 10% mol SmCl3 in water at room temperature for 2 h. This product is preliminary screened for its radical scavenging test with moderate activity.

  8. Mainstream and sidestream cigarette smoke-induced DNA adducts in C7Bl and DBA mice.

    OpenAIRE

    Gairola, C G; Wu, H; Gupta, R C; Diana, J N

    1993-01-01

    Exposure to environmental tobacco smoke (ETS), which is largely composed of the sidestream cigarette smoke, has been implicated in increased incidence of cancer among nonsmokers. The present study was conducted to compare the potential of mainstream and sidestream cigarette smoke to induce DNA adducts in mice. Groups of female C57Bl and DBA mice were exposed twice daily for 65-70 weeks to mainstream or sidestream smoke from the University of Kentucky reference cigarettes (2R1) in a nose-only ...

  9. Peak-valley-peak pattern of histone modifications delineates active regulatory elements and their directionality

    DEFF Research Database (Denmark)

    Pundhir, Sachin; Bagger, Frederik Otzen; Lauridsen, Felicia Kathrine Bratt

    2016-01-01

    Formation of nucleosome free region (NFR) accompanied by specific histone modifications at flanking nucleosomes is an important prerequisite for enhancer and promoter activity. Due to this process, active regulatory elements often exhibit a distinct shape of histone signal in the form of a peak......-valley-peak (PVP) pattern. However, different features of PVP patterns and their robustness in predicting active regulatory elements have never been systematically analyzed. Here, we present PARE, a novel computational method that systematically analyzes the H3K4me1 or H3K4me3 PVP patterns to predict NFRs. We show...

  10. The elimination of Chagas' disease from Brazil.

    Science.gov (United States)

    Massad, E

    2008-09-01

    On 9 June 2006 the Pan American Health Organization (PAHO) presented the Minister of Health of Brazil with the International Elimination of Transmission of Chagas' Disease Certificate. This act was the culmination of an intensive process that began in 1991 with the Southern Cone Initiative, a joint agreement between the governments of Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay and Peru, to control Chagas' disease by the elimination of the main vector, Triatoma infestans. This initiative has been highly successful and the prevalence area of the vector diminished rapidly in the last years. As a consequence, the current seroprevalence in children aged between 0 and 5 years is of the order of 10(-5), a clear indication that transmission, if it is occurring, is only accidental. In this review I calculate the basic reproduction number, R0, for Chagas' disease and demonstrate that its relatively low value (1.25) explains why vectorial transmission was interrupted relatively easily. In addition, I used a mathematical model to forecast how long the remaining cases of the disease, as well as the additional vertically transmitted cases will last.

  11. Elimination of Lymphatic Filariasis in Southern India

    Directory of Open Access Journals (Sweden)

    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.

  12. Molecular Modeling of the Major DNA Adduct Formed from Food Mutagen Ochratoxin A in NarI Two-Base Deletion Duplexes: Impact of Sequence Context and Adduct Ionization on Conformational Preference and Mutagenicity.

    Science.gov (United States)

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

    2017-08-21

    Exposure to ochratoxin A (OTA), a possible human carcinogen, leads to many different DNA mutations. As a first step toward understanding the structural basis of OTA-induced mutagenicity, the present work uses a robust computational approach and a slipped mutagenic intermediate model previously studied for C 8 -dG aromatic amine adducts to analyze the conformational features of postreplication two-base deletion DNA duplexes containing OT-dG, the major OTA lesion at the C 8 position of guanine. Specifically, a total of 960 ns of molecular dynamics simulations (excluding trial simulations) were carried out on four OT-dG ionization states in three sequence contexts within oligomers containing the NarI recognition sequence, a known hotspot for deletion mutations induced by related adducts formed from known carcinogens. Our results indicate that the structural properties and relative stability of the competing "major groove" and "stacked" conformations of OTA adducted two-base deletion duplexes depend on both the OTA ionization state and the sequence context, mainly due to conformation-dependent deviations in discrete local (hydrogen-bonding and stacking) interactions at the lesion site, as well as DNA bending. When the structural characteristics of the OT-dG adducted two-base deletion duplexes are compared to those associated with previously studied C 8 -dG adducts, a greater understanding of the effects of the nucleobase-carcinogen linkage, and size of the carcinogenic moiety on the conformational preferences of damaged DNA is obtained. Most importantly, our work predicts key structural features for OT-dG-adducted deletion DNA duplexes, which in turn allow us to develop hypotheses regarding OT-dG replication outcomes. Thus, our computational results are valuable for the design and interpretation of future biochemical studies on the potentially carcinogenic OT-dG lesion.

  13. Cut Elimination, Identity Elimination, and Interpolation in Super-Belnap Logics

    Czech Academy of Sciences Publication Activity Database

    Přenosil, Adam

    2017-01-01

    Roč. 105, č. 6 (2017), s. 1255-1289 ISSN 0039-3215 R&D Projects: GA ČR GBP202/12/G061 EU Projects: European Commission(XE) 689176 - SYSMICS Institutional support: RVO:67985807 Keywords : Super-Belnap logics * Dunn–Belnap logic * Logic of Paradox * Strong Kleene logic * Exactly True Logic * Gentzen calculus * Cut elimination * Identity elimination * Interpolation Subject RIV: BA - General Mathematics OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.589, year: 2016

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

    Energy Technology Data Exchange (ETDEWEB)

    Rojas, M.; Godschalk, R.; Alexandrov, K.; Cascorbi, I.; Kriek, E.; Ostertag, J.; Van Schooten, F.J.; Bartsch, H. [German Cancer Research Center, Heidelberg (Germany). Div. of Toxicology & Cancer Risk Factors

    2001-07-01

    The skin of atopic dermatitis patients provides an excellent model to study the role of inflammation in benzo(a)pyrene (BaP) activation, since these individuals are often topically treated with ointments containing high concentrations of BaP. The authors determined, by HPLC with fluorescence detection, the BaP diol epoxide (BPDE)-DNA adduct levels in human skin after topical treatment with coal tar and their modulation by the -453G into A myeloperoxidase (MPO) polymorphism, which reduces MPO mRNA expression. The data show for the first time: (i) the in vivo formation of BPDE-DNA adducts in human skin treated with coal tar; (ii) that the MPO-463AA/AG genotype reduced BPDE-DNA adduct levels in human skin.

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

    Directory of Open Access Journals (Sweden)

    Zhen-Zhen Yang

    2014-08-01

    Full Text Available Highly efficient CO2 absorption was realized through formation of zwitterionic adducts, combining synthetic strategies to ionic liquids (ILs and coordination. The essence of our strategy is to make use of multidentate cation coordination between Li+ and an organic base. Also PEG-functionalized organic bases were employed to enhance the CO2-philicity. The ILs were reacted with CO2 to form the zwitterionic adduct. Coordination effects between various lithium salts and neutral ligands, as well as the CO2 capacity of the chelated ILs obtained were investigated. For example, the CO2 capacity of PEG150MeBu2N increased steadily from 0.10 to 0.66 (mol CO2 absorbed per mol of base through the formation of zwitterionic adducts being stabilized by Li+.

  16. Blood Pyrrole-Protein Adducts--A Biomarker of Pyrrolizidine Alkaloid-Induced Liver Injury in Humans.

    Science.gov (United States)

    Ruan, Jianqing; Gao, Hong; Li, Na; Xue, Junyi; Chen, Jie; Ke, Changqiang; Ye, Yang; Fu, Peter Pi-Cheng; Zheng, Jiang; Wang, Jiyao; Lin, Ge

    2015-01-01

    Pyrrolizidine alkaloids (PAs) induce liver injury (PA-ILI) and is very likely to contribute significantly to drug-induced liver injury (DILI). In this study we used a newly developed ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry (UHPLC-MS)-based method to detect and quantitate blood pyrrole-protein adducts in DILI patients. Among the 46 suspected DILI patients, 15 were identified as PA-ILI by the identification of PA-containing herbs exposed. Blood pyrrole-protein adducts were detected in all PA-ILI patients (100%). These results confirm that PA-ILI is one of the major causes of DILI and that blood pyrrole-protein adducts quantitated by the newly developed UHPLC-MS method can serve as a specific biomarker of PA-ILI.

  17. Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2002-09-01

    Full Text Available Abstract: Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine (DHP-derived DNA adduct formation. This mechanism may be general to most carcinogenic pyrrolizidine alkaloids, including the retronecine-, heliotridine-, and otonecinetype pyrrolizidine alkaloids. It is hypothesized that these DHP-derived DNA adducts are potential biomarkers of pyrrolizidine alkaloid tumorigenicity. The mechanisms that involve the formation of DNA cross-linking and endogenous DNA adducts are also discussed.

  18. OccuPeak: ChIP-Seq peak calling based on internal background modelling

    NARCIS (Netherlands)

    de Boer, Bouke A.; van Duijvenboden, Karel; van den Boogaard, Malou; Christoffels, Vincent M.; Barnett, Phil; Ruijter, Jan M.

    2014-01-01

    ChIP-seq has become a major tool for the genome-wide identification of transcription factor binding or histone modification sites. Most peak-calling algorithms require input control datasets to model the occurrence of background reads to account for local sequencing and GC bias. However, the

  19. Can You Hear That Peak? Utilization of Auditory and Visual Feedback at Peak Limb Velocity

    Science.gov (United States)

    Loria, Tristan; de Grosbois, John; Tremblay, Luc

    2016-01-01

    Purpose: At rest, the central nervous system combines and integrates multisensory cues to yield an optimal percept. When engaging in action, the relative weighing of sensory modalities has been shown to be altered. Because the timing of peak velocity is the critical moment in some goal-directed movements (e.g., overarm throwing), the current study…

  20. Lander petal & Twin Peaks - 3D

    Science.gov (United States)

    1997-01-01

    Many prominent rocks near the Sagan Memorial Station are featured in this image, taken in stereo by the Imager for Mars Pathfinder (IMP) on Sol 3. 3D glasses are necessary to identify surface detail. The two hills in the distance, approximately one to two kilometers away, have been dubbed the 'Twin Peaks' and are of great interest to Pathfinder scientists as objects of future study. The white areas on the left hill, called the 'Ski Run' by scientists, may have been formed by hydrologic processes. A lander petal, airbag, and the rear ramp are at the lower area of the image.The image was taken by the Imager for Mars Pathfinder (IMP) after its deployment on Sol 3. Mars Pathfinder was developed and managed by the Jet Propulsion Laboratory (JPL) for the National Aeronautics and Space Administration. The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  1. North Twin Peak in super resolution

    Science.gov (United States)

    1997-01-01

    This pair of images shows the result of taking a sequence of 25 identical exposures from the Imager for Mars Pathfinder (IMP) of the northern Twin Peak, with small camera motions, and processing them with the Super-Resolution algorithm developed at NASA's Ames Research Center.The upper image is a representative input image, scaled up by a factor of five, with the pixel edges smoothed out for a fair comparison. The lower image allows significantly finer detail to be resolved.Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.The super-resolution research was conducted by Peter Cheeseman, Bob Kanefsky, Robin Hanson, and John Stutz of NASA's Ames Research Center, Mountain View, CA. More information on this technology is available on the Ames Super Resolution home page athttp://ic-www.arc.nasa.gov/ic/projects/bayes-group/ group/super-res/

  2. Prediction of iodine activity peak during refuelling

    International Nuclear Information System (INIS)

    Hozer, Z.; Vajda, N.

    2001-01-01

    The increase of fission product activities in the primary circuit of a nuclear power plant indicates the existence of defects in some fuel rods. The power change leads to the cooling down of the fuel and results in the fragmentation of the UO 2 pellets, which facilitates the release of fission products from the intergranular regions. Furthermore the injection of boric acid after shutdown will increase the primary activity, due to the solution of deposited fission products from the surface of the core components. The calculation of these phenomena usually is based on the evaluation of activity measurements and power plant data. The estimation of iodine spiking peak during reactor transients is based on correlation with operating parameters, such as reactor power and primary pressure. The approach used in the present method was applied for CANDU reactors. The VVER-440 specific correlations were determined using the activity measurements of the Paks NPP and the data provided by the Russian fuel supplier. The present method is used for the evaluation of the iodine isotopes, as well as the noble gases. A numerical model has been developed for iodine spiking simulation and has been validated against several shutdown transients, measured at Paks NPP. (R.P.)

  3. Human behavioral complexity peaks at age 25

    Science.gov (United States)

    Brugger, Peter

    2017-01-01

    Random Item Generation tasks (RIG) are commonly used to assess high cognitive abilities such as inhibition or sustained attention. They also draw upon our approximate sense of complexity. A detrimental effect of aging on pseudo-random productions has been demonstrated for some tasks, but little is as yet known about the developmental curve of cognitive complexity over the lifespan. We investigate the complexity trajectory across the lifespan of human responses to five common RIG tasks, using a large sample (n = 3429). Our main finding is that the developmental curve of the estimated algorithmic complexity of responses is similar to what may be expected of a measure of higher cognitive abilities, with a performance peak around 25 and a decline starting around 60, suggesting that RIG tasks yield good estimates of such cognitive abilities. Our study illustrates that very short strings of, i.e., 10 items, are sufficient to have their complexity reliably estimated and to allow the documentation of an age-dependent decline in the approximate sense of complexity. PMID:28406953

  4. Human behavioral complexity peaks at age 25.

    Directory of Open Access Journals (Sweden)

    Nicolas Gauvrit

    2017-04-01

    Full Text Available Random Item Generation tasks (RIG are commonly used to assess high cognitive abilities such as inhibition or sustained attention. They also draw upon our approximate sense of complexity. A detrimental effect of aging on pseudo-random productions has been demonstrated for some tasks, but little is as yet known about the developmental curve of cognitive complexity over the lifespan. We investigate the complexity trajectory across the lifespan of human responses to five common RIG tasks, using a large sample (n = 3429. Our main finding is that the developmental curve of the estimated algorithmic complexity of responses is similar to what may be expected of a measure of higher cognitive abilities, with a performance peak around 25 and a decline starting around 60, suggesting that RIG tasks yield good estimates of such cognitive abilities. Our study illustrates that very short strings of, i.e., 10 items, are sufficient to have their complexity reliably estimated and to allow the documentation of an age-dependent decline in the approximate sense of complexity.

  5. Fast clustering using adaptive density peak detection.

    Science.gov (United States)

    Wang, Xiao-Feng; Xu, Yifan

    2017-12-01

    Common limitations of clustering methods include the slow algorithm convergence, the instability of the pre-specification on a number of intrinsic parameters, and the lack of robustness to outliers. A recent clustering approach proposed a fast search algorithm of cluster centers based on their local densities. However, the selection of the key intrinsic parameters in the algorithm was not systematically investigated. It is relatively difficult to estimate the "optimal" parameters since the original definition of the local density in the algorithm is based on a truncated counting measure. In this paper, we propose a clustering procedure with adaptive density peak detection, where the local density is estimated through the nonparametric multivariate kernel estimation. The model parameter is then able to be calculated from the equations with statistical theoretical justification. We also develop an automatic cluster centroid selection method through maximizing an average silhouette index. The advantage and flexibility of the proposed method are demonstrated through simulation studies and the analysis of a few benchmark gene expression data sets. The method only needs to perform in one single step without any iteration and thus is fast and has a great potential to apply on big data analysis. A user-friendly R package ADPclust is developed for public use.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hang, Bo; Rodriguez, Ben; Yang, Yanu; Guliaev, Anton B.; Chenna, Ahmed

    2010-06-14

    Benzene, a ubiquitous human carcinogen, forms DNA adducts through its metabolites such as p-benzoquinone (p-BQ) and hydroquinone (HQ). N(2)-(4-Hydroxyphenyl)-2'-deoxyguanosine (N(2)-4-HOPh-dG) is the principal adduct identified in vivo by (32)P-postlabeling in cells or animals treated with p-BQ or HQ. To study its effect on repair specificity and replication fidelity, we recently synthesized defined oligonucleotides containing a site-specific adduct using phosphoramidite chemistry. We here report the repair of this adduct by Escherichia coli UvrABC complex, which performs the initial damage recognition and incision steps in the nucleotide excision repair (NER) pathway. We first showed that the p-BQ-treated plasmid was efficiently cleaved by the complex, indicating the formation of DNA lesions that are substrates for NER. Using a 40-mer substrate, we found that UvrABC incises the DNA strand containing N(2)-4-HOPh-dG in a dose- and time-dependent manner. The specificity of such repair was also compared with that of DNA glycosylases and damage-specific endonucleases of E. coli, both of which were found to have no detectable activity toward N(2)-4-HOPh-dG. To understand why this adduct is specifically recognized and processed by UvrABC, molecular modeling studies were performed. Analysis of molecular dynamics trajectories showed that stable G:C-like hydrogen bonding patterns of all three Watson-Crick hydrogen bonds are present within the N(2)-4-HOPh-G:C base pair, with the hydroxyphenyl ring at an almost planar position. In addition, N(2)-4-HOPh-dG has a tendency to form more stable stacking interactions than a normal G in B-type DNA. These conformational properties may be critical in differential recognition of this adduct by specific repair enzymes.

  7. Detection of malondialdehyde DNA adducts in human colorectal mucosa: relationship with diet and the presence of adenomas.

    Science.gov (United States)

    Leuratti, Chiara; Watson, Mark A; Deag, Eliot J; Welch, Ailsa; Singh, Rajinder; Gottschalg, Elke; Marnett, Lawrence J; Atkin, Wendy; Day, Nicholas E; Shuker, David E G; Bingham, Sheila A

    2002-03-01

    Colorectal biopsies from normal mucosa of participants in the United Kingdom Flexible Sigmoidoscopy Trial and European Prospective Investigation on Cancer (EPIC; n = 162) were analyzed for the presence of malondialdehyde-deoxyguanosine (M(1)-dG), a DNA adduct derived from lipid peroxidation. The aim was to investigate whether dietary factors can modulate M(1)-dG levels and whether M(1)-dG in normal mucosa is a risk factor for colorectal adenomas. Samples were analyzed using a sensitive immunoblot blot assay. This study has shown for the first time that M(1)-dG is present in human colorectal tissue. M(1)-dG levels ranged from undetectable (n = 13) to 12.23 per 10(7) total bases. Mean levels were 4.3 +/- 3 and 4.6 +/- 2.9 per 10(7) total bases in men and women, respectively. In men, there were positive associations of adduct levels with height and age, and inverse associations with body mass index. Legumes, fruit, salad, and whole meal bread were inversely associated with M(1)-dG adducts, whereas consumption of offal, white meat, beer, and alcohol were positively associated with elevated levels. In women, there was an inverse association of the adduct with the ratio of polyunsaturated:saturated fatty acids (P = 0.019) and a weak positive correlation with saturated fat (P < 0.061). When levels of adducts were compared in individuals with and without adenomas, there was a trend for higher levels in individuals presenting with adenomas especially in the highest category of M(1)-dG adducts (P < 0.005).

  8. An Analytical Model for Spectral Peak Frequency Prediction of Substrate Noise in CMOS Substrates

    DEFF Research Database (Denmark)

    Shen, Ming; Mikkelsen, Jan H.

    2013-01-01

    This paper proposes an analytical model describing the generation of switching current noise in CMOS substrates. The model eliminates the need for SPICE simulations in existing methods by conducting a transient analysis on a generic CMOS inverter and approximating the switching current waveform us......- ing a Modified Raised Cosine (MORAC) equation. The proposed model is scalable, easy to implement and capable of predicting the spectral peak frequency of the substrate noise. The validation has been done via simulations and measurements. Good agreement has been found between the modeled...

  9. Troglitazone thiol adduct formation in human liver microsomes: enzyme kinetics and reaction phenotyping.

    Science.gov (United States)

    Gan, Jinping; Qu, Qinling; He, Bing; Shyu, Wen C; Rodrigues, A David; He, Kan

    2008-08-01

    Troglitazone (TGZ) induced hepatotoxicity has been linked to cytochrome P450 (CYP)-catalyzed reactive metabolite formation. Therefore, the kinetics and CYP specificity of reactive metabolite formation were studied using dansyl glutathione (dGSH) as a trapping agent after incubation of TGZ with human liver microsomes (HLM) and recombinant human CYP proteins. CYP2C8 exhibited the highest rate of TGZ adduct (TGZ-dGS) formation, followed by CYP3A4, CYP3A5, and CYP2C19. The involvement of CYP2C8 and CYP3A4 was confirmed with CYP form-selective chemical inhibitors. The impact of TGZ concentration on the rate of TGZ-dGS formation was also evaluated. In this instance, two distinctly different profiles were observed with recombinant CYP3A4 and CYP2C8. It is concluded that both CYP3A4/5 and CYP2C8 play a major role in the formation of TGZ adduct in HLM. However, the contribution of these CYPs varies depending on their relative expression and the concentration of TGZ.

  10. Enzymology of repair of DNA adducts produced by N-nitroso compounds

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.; Cao, E.H.; Delihas, N.C.

    1983-01-01

    The biological effects of DNA adducts depend on their nature, and on their half-lives relative to the rates of DNA replication and transcription. Their half-lives are determined by the rates of spontaneous decay, such as depurination, and the rates of enzymatic repair of the adducts or their decay products. The principle modes of repair of methylating and ethylating agents are by glycosylase catalyzed depurination of 7-alkylguanine and 3-alkyladenine and by the dealkalation of O/sup 6/-alkylguanine. Repair by dealkylation cannot be detected by the standard methods used to measure DNA repair, but it is easy to estimate the acceptor activity in cell extracts by measuring the transfer of radioactive O/sup 6/-alkyl groups in an exogenous DNA to protein. In extracts of cells treated with alkylating agents the activity is depressed because the endogenous DNA is rapidly dealkylated, using up the acceptor activity. In many cell types the decrease in activity is followed by an increase to the normal constitutive level. In other cells there is no such adaptive response. Differences in constitutive levels of methyl accepting activity in extracts of human lymphocytes and on the acceptor activity in lung macrophages from smokers (low activity) and non-smokers (high activity) have been observed. 46 references.

  11. High-Confidence Qualitative Identification of Organophosphorus Nerve Agent Adducts to Human Butyrylcholinesterase.

    Science.gov (United States)

    Mathews, Thomas P; Carter, Melissa D; Johnson, Darryl; Isenberg, Samantha L; Graham, Leigh Ann; Thomas, Jerry D; Johnson, Rudolph C

    2017-02-07

    In this study, a data-dependent, high-resolution tandem mass spectrometry (ddHRMS/MS) method capable of detecting all organophosphorus nerve agent (OPNA) adducts to human butyrylcholinesterase (BChE) was developed. After an exposure event, immunoprecipitation from blood with a BChE-specific antibody and digestion with pepsin produces a nine amino acid peptide containing the OPNA adduct. Signature product ions of this peptic BChE nonapeptide (FGES*AGAAS) offer a route to broadly screen for OPNA exposure. Taking this approach on an HRMS instrument identifies biomarkers, including unknowns, with high mass accuracy. Using a set of pooled human sera exposed to OPNAs as quality control (QC) materials, the developed method successfully identified precursor ions with 15 ng/mL. The developed method was applied to a convenience set of 96 unexposed serum samples and a blinded set of 80 samples treated with OPNAs. OPNA biomarkers were not observed in convenience set samples and no false positive or negative identifications were observed in blinded samples. All biomarkers in the blinded serum set >15 ng/mL were correctly identified. For the first time, this study reports a ddHRMS/MS method capable of complementing existing quantitative methodologies and suitable for identifying exposure to unknown organophosphorus agents.

  12. Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.

    Science.gov (United States)

    Head, R J; Fay, M F; Cosgrove, L; Y C Fung, K; Rundle-Thiele, D; Martin, J H

    2017-12-02

    Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O 6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.

  13. Retardation of experimental tumorigenesis and reduction in DNA adducts by turmeric and curcumin.

    Science.gov (United States)

    Krishnaswamy, K; Goud, V K; Sesikeran, B; Mukundan, M A; Krishna, T P

    1998-01-01

    Turmeric and its active principle curcumin have been extensively investigated for their antimutagenic and antioxidant effects in bacterial and animal systems. Because oral cancers are common in India, an experimental model of 7,12-dimethylbenzanthracene-induced buccal pouch tumors in Syrian Golden hamsters was used to evaluate the tumor retardation effects of turmeric and curcumin. Turmeric and/or curcumin was administered in the diet and/or applied locally for 14 weeks along with 7,12-dimethylbenzanthracene. After the experimental period, the animals were sacrificed and oral pouches were examined for tumor number and size. DNA adducts were estimated by 32P postlabel assay in the cheek pouches. Neoplastic changes were graded by histopathology. The results of the study suggest that turmeric or curcumin in the diet and/or applied locally significantly reduced DNA adducts at the target site. Tumor number and tumor burden were significantly lower (p curcumin (p curcumin administered in the diet or applied as paint may have a plausible chemopreventive effect on oral precancerous lesions.

  14. Feasibility of vocal fold abduction and adduction assessment using cine-MRI

    Energy Technology Data Exchange (ETDEWEB)

    Baki, Marina Mat [National University of Malaysia, Faculty of Medicine, Kuala Lumpur (Malaysia); Menys, Alex; Morley, Simon; Beale, Timothy [University College London, Centre for Medical Imaging, London (United Kingdom); Atkinson, David; Punwani, Shonit [University College London, Centre for Medical Imaging, London (United Kingdom); Royal National Throat Nose Ear Hospital, University College London Hospital NHS Trust, London (United Kingdom); Bassett, Paul [University College London, London (United Kingdom); Sandhu, Guri [Charing Cross Hospital, Imperial College Healthcare NHS Trust, London (United Kingdom); Naduvilethil, Georgekutty; Stevenson, Nicola [Royal National Throat Nose Ear Hospital, University College London Hospital NHS Trust, London (United Kingdom); Birchall, Martin A. [Royal National Throat Nose Ear Hospital, University College London Hospital NHS Trust, London (United Kingdom); University of California, Davis, Department of Otolaryngology, Davis, CA (United States); University College London, Ear Institute, London (United Kingdom)

    2017-02-15

    Determine feasibility of vocal fold (VF) abduction and adduction assessment by cine magnetic resonance imaging (cine-MRI) Cine-MRI of the VF was performed on five healthy and nine unilateral VF paralysis (UVFP) participants using an axial gradient echo acquisition with temporal resolution of 0.7 s. VFs were continuously imaged with cine-MRI during a 10-s period of quiet respiration and phonation. Scanning was repeated twice within an individual session and then once again at a 1-week interval. Asymmetry of VF position during phonation (VF phonation asymmetry, VFPa) and respiration (VF respiration asymmetry, VFRa) was determined. Percentage reduction in total glottal area between respiration and phonation (VF abduction potential, VFAP) was derived to measure overall mobility. An un-paired t-test was used to compare differences between groups. Intra-session, inter-session and inter-reader repeatability of the quantitative metrics was evaluated using intraclass correlation coefficient (ICC). VF position asymmetry (VFPa and VFRa) was greater (p=0.012; p=0.001) and overall mobility (VFAP) was lower (p=0.008) in UVFP patients compared with healthy participants. ICC of repeatability of all metrics was good, ranged from 0.82 to 0.95 except for the inter-session VFPa (0.44). Cine-MRI is feasible for assessing VF abduction and adduction. Derived quantitative metrics have good repeatability. (orig.)

  15. Feasibility of vocal fold abduction and adduction assessment using cine-MRI

    International Nuclear Information System (INIS)

    Baki, Marina Mat; Menys, Alex; Morley, Simon; Beale, Timothy; Atkinson, David; Punwani, Shonit; Bassett, Paul; Sandhu, Guri; Naduvilethil, Georgekutty; Stevenson, Nicola; Birchall, Martin A.

    2017-01-01

    Determine feasibility of vocal fold (VF) abduction and adduction assessment by cine magnetic resonance imaging (cine-MRI) Cine-MRI of the VF was performed on five healthy and nine unilateral VF paralysis (UVFP) participants using an axial gradient echo acquisition with temporal resolution of 0.7 s. VFs were continuously imaged with cine-MRI during a 10-s period of quiet respiration and phonation. Scanning was repeated twice within an individual session and then once again at a 1-week interval. Asymmetry of VF position during phonation (VF phonation asymmetry, VFPa) and respiration (VF respiration asymmetry, VFRa) was determined. Percentage reduction in total glottal area between respiration and phonation (VF abduction potential, VFAP) was derived to measure overall mobility. An un-paired t-test was used to compare differences between groups. Intra-session, inter-session and inter-reader repeatability of the quantitative metrics was evaluated using intraclass correlation coefficient (ICC). VF position asymmetry (VFPa and VFRa) was greater (p=0.012; p=0.001) and overall mobility (VFAP) was lower (p=0.008) in UVFP patients compared with healthy participants. ICC of repeatability of all metrics was good, ranged from 0.82 to 0.95 except for the inter-session VFPa (0.44). Cine-MRI is feasible for assessing VF abduction and adduction. Derived quantitative metrics have good repeatability. (orig.)

  16. Synthesis, structure characterization, and anticancer activity of a novel oxygen-bridged tricyclic Biginelli adduct

    Science.gov (United States)

    Ibrahim, Mohamed M.; El-Sheshtawy, Hamdy S.; El-Kemary, Maged; Al-Juaid, Salih; Youssef, Mohamed; El-Azab, Islam H.

    2017-06-01

    Herein, we report the one-pot cyclization of Biginelli Adduct, ethyl 4-(2-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (I) to the oxygen-bridged adduct, ethyl 2-methyl-4-thioxo-3,4,5,6-tetrahydro-2H-2,6-methanobenzo[g] [1,3,5]oxadiazocine-11-carboxylate (II) in a high yield and purity under mild reaction condition using zinc(II) perchlorate hexahydrate as a highly efficient catalyst. The cyclic product (II) was characterized both in the solid state and in solution using FT-IR, 1H NMR, and UV-visible spectroscopy. Theoretical calculations using density functional theory with B3LYP/6-311++G(d,p) level were used to further investigate the structure properties. DFT calculations (gas phase) revealed the stability of cyclic compound II (3.45 kcal/mol) than compound I. In addition, the anticancer activity of II was investigated using MCF-7 human breast cell line. The results revealed a moderate activity with 223.55 μg/ml IC50 value.

  17. Lysine- and cysteine-based protein adductions derived from toxic metabolites of 8-epidiosbulbin E acetate.

    Science.gov (United States)

    Lin, Dongju; Wang, Kai; Guo, Xiucai; Gao, Huiyuan; Peng, Ying; Zheng, Jiang

    2016-12-15

    Furanoid 8-epidiosbulbin E acetate (EEA) is a major constituent of herbal medicine Dioscorea bulbifera L. (DB), a traditional herbal medicine widely used in Asian nations. Our early studies demonstrated that administration of EEA caused acute hepatotoxicity in mice and the observed toxicity required P450-mediated metabolic activation. Protein modification by reactive metabolites of EEA has been suggested to be an important mechanism of EEA-induced hepatotoxicity. The objectives of the present study were to investigate the interaction of the electrophilic reactive metabolites derived from EEA with lysine and cysteine residues of proteins and to define the correlation of protein adductions of EEA and the hepatotoxicity induced by EEA. EEA-derived cis-enedial was found to modify both lysine and cysteine residues of proteins. The observed modifications increased with the increase in doses administered in the animals. The formation of protein adductions derived from the reactive metabolites of EEA were potentiated by buthionine sulfoximine, but were attenuated by ketoconazole. This work facilitated better understanding of the mechanisms of toxic action of EEA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Cysteine-Based Protein Adduction by Epoxide-Derived Metabolite(s) of Benzbromarone.

    Science.gov (United States)

    Wang, Hui; Feng, Yukun; Wang, Qian; Guo, Xiucai; Huang, Wenlin; Peng, Ying; Zheng, Jiang

    2016-12-19

    Benzbromarone (BBR) is a therapeutically useful uricosuric agent but can also cause acute liver injury. The hepatotoxicity of BBR is suggested to be associated with its metabolic activation. Our recent metabolic study demonstrated that BBR was metabolized to epoxide intermediate(s) by cytochrome P450 3A, and the intermediate(s) was reactive to N-acetylcysteine. The objectives of the present study were to determine the chemical identity of the interaction of protein with the epoxide intermediate(s) of BBR and to define the association of the protein modification with hepatotoxicity induced by BBR. Microsomal incubation study showed that the reactive intermediate(s) covalently modified microsomal protein at cysteine residues. Such adduction was also observed in hepatic protein obtained from liver of mice given BBR. The protein covalent binding occurred in time- and dose-dependent manners. Pretreatment with ketoconazole attenuated BBR-induced protein modification and hepatotoxicity, while pretreatment with dexamethasone or buthionine sulfoximine potentiated the protein adduction and hepatotoxicity induced by BBR. A good correlation was observed between BBR-induced hepatotoxicity and the epoxide-derived hepatic protein modification in mice. The present study provided in-depth mechanistic insight into BBR-induced hepatotoxicity.

  19. For a convention for nuclear weapon elimination

    International Nuclear Information System (INIS)

    2008-03-01

    This document contains two texts linked with the project of an international convention for the elimination of nuclear weapons (the text of this project has been sent to the UN General Secretary and is part of an international campaign to abolish nuclear weapons, ICAN). These two texts are contributions presented in London at the Global Summit for a Nuclear Weapon-free World. The first one calls into question the deterrence principle and the idea of a nuclear weapon-based security. It calls for different forms of action to promote a nuclear weapon-free world. The second text stresses the role and the responsibility of states with nuclear weapons in nuclear disarmament and in the reinforcement of the nuclear non proliferation treaty (NPT)

  20. Adaptive elimination of synchronization in coupled oscillator

    International Nuclear Information System (INIS)

    Zhou, Shijie; Lin, Wei; Ji, Peng; Feng, Jianfeng; Zhou, Qing; Kurths, Jürgen

    2017-01-01

    We present here an adaptive control scheme with a feedback delay to achieve elimination of synchronization in a large population of coupled and synchronized oscillators. We validate the feasibility of this scheme not only in the coupled Kuramoto’s oscillators with a unimodal or bimodal distribution of natural frequency, but also in two representative models of neuronal networks, namely, the FitzHugh–Nagumo spiking oscillators and the Hindmarsh–Rose bursting oscillators. More significantly, we analytically illustrate the feasibility of the proposed scheme with a feedback delay and reveal how the exact topological form of the bimodal natural frequency distribution influences the scheme performance. We anticipate that our developed scheme will deepen the understanding and refinement of those controllers, e.g. techniques of deep brain stimulation, which have been implemented in remedying some synchronization-induced mental disorders including Parkinson disease and epilepsy. (paper)

  1. Lean for Government: Eliminating the Seven Wastes

    Science.gov (United States)

    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.

  2. RESULTS of the "ELIMINATING NOISE" campaign

    CERN Multimedia

    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...

  3. RESULTS of the "ELIMINATING NOISE" campaign

    CERN Multimedia

    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...

  4. Cell competition: how to eliminate your neighbours

    Science.gov (United States)

    Amoyel, Marc; Bach, Erika A.

    2014-01-01

    A conventional view of development is that cells cooperate to build an organism. However, based on studies of Drosophila, it has been known for years that viable cells can be eliminated by their neighbours through a process termed cell competition. New studies in mammals have revealed that this process is universal and that many factors and mechanisms are conserved. During cell competition, cells with lower translation rates or those with lower levels of proteins involved in signal transduction, polarity and cellular growth can survive in a homogenous environment but are killed when surrounded by cells of higher fitness. Here, we discuss recent advances in the field as well as the mechanistic steps involved in this phenomenon, which have shed light on how and why cell competition exists in developing and adult organisms. PMID:24550108

  5. Adaptive elimination of synchronization in coupled oscillator

    Science.gov (United States)

    Zhou, Shijie; Ji, Peng; Zhou, Qing; Feng, Jianfeng; Kurths, Jürgen; Lin, Wei

    2017-08-01

    We present here an adaptive control scheme with a feedback delay to achieve elimination of synchronization in a large population of coupled and synchronized oscillators. We validate the feasibility of this scheme not only in the coupled Kuramoto’s oscillators with a unimodal or bimodal distribution of natural frequency, but also in two representative models of neuronal networks, namely, the FitzHugh-Nagumo spiking oscillators and the Hindmarsh-Rose bursting oscillators. More significantly, we analytically illustrate the feasibility of the proposed scheme with a feedback delay and reveal how the exact topological form of the bimodal natural frequency distribution influences the scheme performance. We anticipate that our developed scheme will deepen the understanding and refinement of those controllers, e.g. techniques of deep brain stimulation, which have been implemented in remedying some synchronization-induced mental disorders including Parkinson disease and epilepsy.

  6. Recognition and repair of the CC-1065-(N3-Adenine)-DNA adduct by the UVRABC nuclease

    International Nuclear Information System (INIS)

    Tang, M.; Lee, C.S.; Doisy, R.; Ross, L.; Needham-VanDevanter, D.R.; Hurley, L.H.

    1988-01-01

    The recognition and repair of the helix-stabilizing and relatively nondistortive CC-1065-(N3-adenine)-DNA adduct by UVRABC nuclease has been investigated both in vivo with phi X174RFI DNA by a transfection assay and in vitro by a site-directed adduct in a 117 base pair fragment from M13mp1. CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis which binds within the minor groove of DNA through N3 of adenine. In contrast to the helix-destabilizing and distortive modifications of DNA caused by ultraviolet light or N-acetoxy-2-(acetylamino)fluorene, CC-1065 increases the melting point of DNA and decreases the S1 nuclease activity. Using a viral DNA-Escherichia coli transfection system, the authors have found that the uvrA, uvrB, and uvrC genes, which code for the major excision repair proteins for UV- and NAAAF-induced DNA damage, are also involved in the repair of CC-1065-DNA adducts. In contrast, the uvrD gene product, which has been found to be involved in the repair of UV damage, has no effect in repairing CC-1065-DNA adducts. Purified UVRA, UVRB, and UVRC proteins must work in concert to incise the drug-modified phi X174RFI DNA. Using a site-directed and multiple CC-1065 modified (MspI-BstNI) 117 base pair fragment from M13mp1, they have found that UVRABC nuclease incises at the eight phosphodiester bond on the 5' side of the CC-1065-DNA adduct on the drug-modified strand. The enzymes do not cut the noncovalently modified strand. The DNA sequence and/or helix-stabilizing effect of multiple adducts may determine the recognition and/or incision of the drug-DNA adduct by UVRABC nuclease. These results are discussed in relation to the structure of the CC-1065-DNA adduct and the effect of drug binding on local DNA structure

  7. Using lysine adducts of human serum albumin to investigate the disposition of exogenous formaldehyde in human blood.

    Science.gov (United States)

    Regazzoni, Luca G; Grigoryan, Hasmik; Ji, Zhiying; Chen, Xi; Daniels, Sarah I; Huang, Deyin; Sanchez, Sylvia; Tang, Naijun; Sillé, Fenna C M; Iavarone, Anthony T; Williams, Evan R; Zhang, Luoping; Rappaport, Stephen M

    2017-02-15

    Formaldehyde is a human carcinogen that readily binds to nucleophiles, including proteins and DNA. To investigate whether exogenous formaldehyde produces adducts in extracellular fluids, we characterized modifications to human serum albumin (HSA) following incubation of whole blood, plasma, and saliva with formaldehyde at concentrations of 1, 10 and 100μM. The only HSA locus that showed the presence of formaldehyde modifications was Lys199. A N(6)-Lys adduct with added mass of 12Da, representing a putative intramolecular crosslink, was detected in biological fluids that had been incubated with formaldehyde but not in control fluids. An adduct representing N(6)-Lys formylation was detected in all fluids, but levels did not increase above control values over the tested range of formaldehyde concentrations. An adduct representing N(6)-Lys199 acetylation was also measured in all samples. We then applied the assay to repeated samples of human plasma from 6 nonsmoking volunteer subjects (from Berkeley, CA), and single samples of serum from 15 workers exposed to airborne formaldehyde at about 1.5ppm in a production facility and 15 control workers from Tianjin, China. Although all human plasma/serum samples contained basal levels of the products of N(6)-Lys formylation and acetylation, the putative crosslink product was not detected. Since the putative crosslink was observed in plasma incubated with formaldehyde at 1μM, this suggests that the endogenous concentration of formaldehyde in serum was much lower than reported in the literature. Furthermore, concentrations of the formyl adduct were not higher in workers exposed to formaldehyde at about 1.5ppm than in controls. Follow-up in vitro experiments with gaseous formaldehyde at 1.4ppm detected the putative crosslink in plasma but not whole blood. This combination of results suggests that N(6) formylation occurs within cells with subsequent release of adducted HSA to the systemic circulation. Comparing across human

  8. Renal lactate elimination is maintained during moderate exercise in humans

    DEFF Research Database (Denmark)

    Volianitis, Stefanos; Dawson, Ellen A; Dalsgaard, Mads

    2012-01-01

    Reduced hepatic lactate elimination initiates blood lactate accumulation during incremental exercise. In this study, we wished to determine whether renal lactate elimination contributes to the initiation of blood lactate accumulation. The renal arterial-to-venous (a-v) lactate difference...... ischaemia, and renal lactate elimination is maintained. Thus, kidney lactate elimination is unlikely to contribute to the initial blood lactate accumulation during progressive exercise....

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

    International Nuclear Information System (INIS)

    Fang Qingming; Nair, Jagadeesan; Sun Xin; Hadjiolov, Dimiter; Bartsch, Helmut

    2007-01-01

    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 ω-6 polyunsaturated fatty acids drastically increase the formation of etheno-DNA adducts in white blood cells of female subjects, Cancer Epidemiol. Biomarkers Prev. 6 (1997) 597-601]. Etheno-adducts were measured in rats gavaged with LA, oleic acid (OA) and saturated fatty acid rich coconut oil for 30 days. DNA from organs and total WBC was analyzed for 1, N 6 -ethenodeoxyadenosine (εdA) and 3, N 4 -ethenodeoxycytidine (εdC) by immunoaffinity/ 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 ω-6 PUFA induced colon carcinogenesis

  10. NEW TIN (IV, MX2 AND M’Cl3 (M= Zn, Hg; M’= Pr, Er ADDUCTS AND COMPLEXES OF BIS(AMINOMETHYLBENZENE: SYNTHESIS AND INFRARED STUDY

    Directory of Open Access Journals (Sweden)

    ASSANE TOURE

    2015-10-01

    Full Text Available The new adducts and complexes obtained have discrete or dimeric structures; in these structures the diamine behaves as a monodentate and hydrogen bonds involved or bidentate ligand. In one rare earth halide adduct the high coordination number (7 proposed is common for this family. When extra intermolecular hydrogen bonds are taken into account, supramolecular architectures may be obtained.

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

    International Nuclear Information System (INIS)

    Pribush, A.G.

    1986-01-01

    The method of pulse radiolysis was used to investigate the reaction of the electronic adduct of bovine serum albumin with oxygen. It was suggested that the disappearance of the electronic adduct of the protein occurs in the course of its interaction with oxygen adsorbed on the globular protein molecule

  12. A highly efficient kinetic resolution of Morita-Baylis-Hillman adducts achieved by N-Ar axially chiral Pd-complexes catalyzed asymmetric allylation.

    Science.gov (United States)

    Wang, Feijun; Li, Shengke; Qu, Mingliang; Zhao, Mei-Xin; Liu, Lian-Jun; Shi, Min

    2011-12-28

    Palladium complexes with an axially chiral N-Ar framework have been developed. These complexes showed high stereoselectivities in asymmetric allylic arylation to achieve the kinetic resolution of Morita-Baylis-Hillman adducts, affording up to 99% ee of (E)-allylation products and 92% ee of recovered Morita-Baylis-Hillman adducts. This journal is © The Royal Society of Chemistry 2011

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

    DEFF Research Database (Denmark)

    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...

  14. Selective electrolytic removal of bis(alkoxycarbonyl)methano addends from C60 bis-adducts and electrochemical stability of C70 derivatives

    Science.gov (United States)

    Kessinger; Fender; Echegoyen; Thilgen; Echegoyen; Diederich

    2000-06-16

    The novel mixed bis-adducts of C60, (+/-)-4-(+/-)-8 and 9, with a bis(ethoxycarbonyl)methano addend (Bingel addend) and a second addend ([1,2]benzeno, but[2]eno, methaniminomethano, or diarylmethano) bridging 6,6-closed bonds of the carbon sphere were synthesized in two-step reactions. Each bis-adduct was exhaustively electrolyzed at the potential of the second fullerene-centered reduction step, resulting in the selective removal of the Bingel addend (retro-Bingel reaction) to produce the corresponding mono-adducts, which were isolated in yields of over 60%. These results open up the possibility of using the Bingel addend as a temporary protecting and directing group in the construction of multiple adducts of C60 with unusual addition patterns. The Bingel-type mono-adduct of C70 10 and the constitutionally isomeric bis-adducts 11, (+/-)-12, and (+/-)-13 were also included in this investigation. A large difference in the electrochemical behavior between C70 bis-adducts and the corresponding C60 derivatives was observed. Thus, the intramolecular "walk-on-the-sphere" isomerization which occurs readily with Bingel-type bis-adducts of C60 under the conditions of two-electron controlled potential electrolysis (CPE) is only a minor reaction pathway in the series of C70 derivatives. The latter preferentially undergo retro-Bingel reaction.

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

    Science.gov (United States)

    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. Research Opportunities at Storm Peak Laboratory

    Science.gov (United States)

    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 of 3210 m MSL (Borys and Wetzel, 1997). 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. The ridge-top location produces almost daily transition from free tropospheric to boundary layer air which occurs near midday in both summer and winter seasons. Long-term observations at SPL document the role of orographically induced mixing and convection on vertical pollutant transport and dispersion. During winter, SPL is above cloud base 25% of the time, providing a unique capability for studying aerosol-cloud interactions (Borys and Wetzel, 1997). A comprehensive set of continuous aerosol measurements was initiated at SPL in 2002. SPL includes an office-type laboratory room for computer and instrumentation setup with outside air ports and cable access to the roof deck, a cold room for precipitation and cloud rime ice sample handling and ice crystal microphotography, a 150 m2 roof deck area for outside sampling equipment, a full kitchen and two bunk rooms with sleeping space for nine persons. The laboratory is currently well equipped for aerosol and cloud measurements. Particles are sampled from an insulated, 15 cm diameter manifold within approximately 1 m of its horizontal entry point through an outside wall. The 4 m high vertical section outside the building is capped with an inverted can to exclude large particles.

  17. Facile Synthesis of N-Tosyl Aza-Baylis-Hillman Adducts of Acrylamide via a Pd-Catalyzed Hydration of Nitrile to Amide

    International Nuclear Information System (INIS)

    Kim, Eun Sun; Kim, Yu Mi; Kim, Jae Nyoung

    2010-01-01

    We developed an efficient palladium-catalyzed two-step protocol for the synthesis of N-tosyl aza-Baylis-Hillman adducts of acrylamide. The method involved the preparation of the corresponding Baylis-Hillman adducts of acrylonitrile and the following Pd-catalyzed hydration of nitrile with acetaldoxime. The Baylis-Hillman reaction, which involves the coupling of activated vinyl compounds with electrophiles under the catalytic influence of a tertiary amine, gives rise to adducts, so called Baylis-Hillman adducts, with a new stereocenter and has proven to be a very useful carbon-carbon bond-forming method in the synthesis of highly functionalized molecules. As the activated vinyl compounds, various compounds have been used in the Baylis-Hillman reaction including acrylates, acrylonitrile, vinyl ketones, vinyl sulfones and acrylamides. However, among the activated vinyl compounds acrylamide has not been used much for the synthesis of the corresponding Baylis-Hillman adducts due to its sluggish reactivity

  18. Facile Synthesis of N-Tosyl Aza-Baylis-Hillman Adducts of Acrylamide via a Pd-Catalyzed Hydration of Nitrile to Amide

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Sun; Kim, Yu Mi; Kim, Jae Nyoung [Chonnam National Univ., Gwangju (Korea, Republic of)

    2010-03-15

    We developed an efficient palladium-catalyzed two-step protocol for the synthesis of N-tosyl aza-Baylis-Hillman adducts of acrylamide. The method involved the preparation of the corresponding Baylis-Hillman adducts of acrylonitrile and the following Pd-catalyzed hydration of nitrile with acetaldoxime. The Baylis-Hillman reaction, which involves the coupling of activated vinyl compounds with electrophiles under the catalytic influence of a tertiary amine, gives rise to adducts, so called Baylis-Hillman adducts, with a new stereocenter and has proven to be a very useful carbon-carbon bond-forming method in the synthesis of highly functionalized molecules. As the activated vinyl compounds, various compounds have been used in the Baylis-Hillman reaction including acrylates, acrylonitrile, vinyl ketones, vinyl sulfones and acrylamides. However, among the activated vinyl compounds acrylamide has not been used much for the synthesis of the corresponding Baylis-Hillman adducts due to its sluggish reactivity.

  19. MOCVD Layer growth of ZnSe and ZnS / ZnSe multiple layers using nitrogen containing adducts of dimethylzinc

    Science.gov (United States)

    Wright, P. J.; Cockayne, B.; Parbrook, P. J.; Jones, A. C.; O'Brien, P.; Walsh, J. R.

    1990-08-01

    It is shown that adducts between dimethylzinc and the nitrogen donor ligands triethylamine and triazine can be used successfully as the zinc sources to grow ZnSe and related compounds by MOCVD. High quality single crystal layers of ZnSe have been grown without any significant pre-reaction of the constituent reactants. The high quality character of the layers is demonstrated by the presence of free exciton dominated photoluminescence. Some general points concerning the use of zinc adducts are also reviewed and discussed. In particular, it is shown that one reason for the improved purity of layers grown using adducts compared to dimethylzinc alone is the removal of iodine, an n-type donor in ZnSe, by the adducting process. The relationship between the nature of the adducting species and the control of prereaction is also discussed briefly.

  20. Choquet and Shilov Boundaries, Peak Sets, and Peak Points for Real Banach Function Algebras

    Directory of Open Access Journals (Sweden)

    Davood Alimohammadi

    2013-01-01

    Full Text Available Let be a compact Hausdorff space and let be a topological involution on . In 1988, Kulkarni and Arundhathi studied Choquet and Shilov boundaries for real uniform function algebras on . Then in 2000, Kulkarni and Limaye studied the concept of boundaries and Choquet sets for uniformly closed real subspaces and subalgebras of or . In 1971, Dales obtained some properties of peak sets and p-sets for complex Banach function algebras on . Later in 1990, Arundhathi presented some results on peak sets for real uniform function algebras on . In this paper, while we present a brief account of the work of others, we extend some of their results, either to real subspaces of or to real Banach function algebras on .

  1. Easy peak tracking in CE-UV and CE-UV-ESI-MS by incorporating temperature-correlated mobility scaling

    DEFF Research Database (Denmark)

    Li, Bin; Petersen, Nickolaj Jacob; Andersen, Line Hvass

    2013-01-01

    resistance of the buffer-filled capillary. The temperature-correlated mobility calculation eliminates the peak shifts due to the viscosity changes, improves the precision of peak identification using the observed temperature-correlated mobilities and allows a direct comparison of signals from different......A simple data reconstruction technique in capillary electrophoresis - ultraviolet - electrospray ionization - mass spectrometry (CE-UV-ESI-MS) is presented to overcome the drift in mobilities caused by various factors compromising the reproducibility of such data, e.g. Joule heating effects...

  2. The evaluation of speed skating helmet performance through peak linear and rotational accelerations.

    Science.gov (United States)

    Karton, Clara; Rousseau, Philippe; Vassilyadi, Michael; Hoshizaki, Thomas Blaine

    2014-01-01

    Like many sports involving high speeds and body contact, head injuries are a concern for short track speed skating athletes and coaches. While the mandatory use of helmets has managed to nearly eliminate catastrophic head injuries such as skull fractures and cerebral haemorrhages, they may not be as effective at reducing the risk of a concussion. The purpose of this study was to evaluate the performance characteristics of speed skating helmets with respect to managing peak linear and peak rotational acceleration, and to compare their performance against other types of helmets commonly worn within the speed skating sport. Commercially available speed skating, bicycle and ice hockey helmets were evaluated using a three-impact condition test protocol at an impact velocity of 4 m/s. Two speed skating helmet models yielded mean peak linear accelerations at a low-estimated probability range for sustaining a concussion for all three impact conditions. Conversely, the resulting mean peak rotational acceleration values were all found close to the high end of a probability range for sustaining a concussion. A similar tendency was observed for the bicycle and ice hockey helmets under the same impact conditions. Speed skating helmets may not be as effective at managing rotational acceleration and therefore may not successfully protect the user against risks associated with concussion injuries.

  3. Identification of Bound Nitro Musk-Protein Adduct in Fish Liver By Gas Chromatography-Mass Sectrometry: Biotransformation, Dose-Response and Toxicokinetics of Nitro Musk Metabolites Protein Adducts in Trout Liver as Biomarker of Exposure

    Science.gov (United States)

    Ubiquitous occurrences of synthetic nitro musks are evident in the literature. The In vivo analysis of musk xylene (MX) and musk ketone (MK) - protein adducts in trout liver have been performed by gas chromatography-mass spectrometry using selected ion monitoring (GC-SIM-MS). Bio...

  4. On the Importance of Elimination Heuristics in Lazy Propagation

    DEFF Research Database (Denmark)

    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...

  5. Miscoding properties of 1,N{sup 6}-ethanoadenine, a DNA adduct derived from reaction with antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-03-05

    1,N{sup 6}-Ethanoadenine (EA) is an exocyclic adduct formed from DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). To understand the role of this adduct in the mechanism of mutagenicity or carcinogenicity by BCNU, an oligonucleotide with a site-specific EA was synthesized using phosphoramidite chemistry. We now report the in vitro miscoding properties of EA in translesion DNA synthesis catalyzed by mammalian DNA polymerases (pols) {alpha}, {beta}, {eta} and {iota}. These data were also compared with those obtained for the structurally related exocyclic adduct, 1,N{sup 6}-ethenoadenine ({var_epsilon}A). Using a primer extension assay, both pols {alpha} and {beta} were primarily blocked by EA or {var_epsilon}A with very minor extension. Pol {eta} a member of the Y family of polymerases, was capable of catalyzing a significant amount of bypass across both adducts. Pol {eta} incorporated all four nucleotides opposite EA and {var_epsilon}A, but with differential preferences and mainly in an error-prone manner. Human pol {iota}, a paralog of human pol {eta}, was blocked by both adducts with a very small amount of synthesis past {var_epsilon}A. It incorporated C and, to a much lesser extent, T, opposite either adduct. In addition, the presence of an A adduct, e.g. {var_epsilon}A, could affect the specificity of pol {iota} toward the template T immediately 3 feet to the adduct. In conclusion, the four polymerases assayed on templates containing an EA or {var_epsilon}A showed differential bypass capacity and nucleotide incorporation specificity, with the two adducts not completely identical in influencing these properties. Although there was a measurable extent of error-free nucleotide incorporation, all these polymerases primarily misincorporated opposite EA, indicating that the adduct, similar to {var_epsilon}A, is a miscoding lesion.

  6. The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice.

    Science.gov (United States)

    Zhu, Lin; Xue, Junyi; Xia, Qingsu; Fu, Peter P; Lin, Ge

    2017-02-01

    Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and the most common poisonous plants affecting livestock, wildlife, and humans. Our previous studies demonstrated that PA-derived DNA adducts can potentially be a common biological biomarker of PA-induced liver tumor formation. In order to validate the use of these PA-derived DNA adducts as a biomarker, it is necessary to understand the basic kinetics of the PA-derived DNA adducts formed in vivo. In this study, we studied the dose-dependent response and kinetics of PA-derived DNA adduct formation and removal in male ICR mice orally administered with a single dose (40 mg/kg) or multiple doses (10 mg/kg/day) of retrorsine, a representative carcinogenic PA. In the single-dose exposure, the PA-derived DNA adducts exhibited dose-dependent linearity and persisted for up to 4 weeks. The removal of the adducts following a single-dose exposure to retrorsine was biphasic with half-lives of 9 h (t 1/2α ) and 301 h (~12.5 days, t 1/2β ). In the 8-week multiple exposure study, a marked accumulation of PA-derived DNA adducts without attaining a steady state was observed. The removal of adducts after the multiple exposure also demonstrated a biphasic pattern but with much extended half-lives of 176 h (~7.33 days, t 1/2α ) and 1736 h (~72.3 days, t 1/2β ). The lifetime of PA-derived DNA adducts was more than 8 weeks following the multiple-dose treatment. The significant persistence of PA-derived DNA adducts in vivo supports their role in serving as a biomarker of PA exposure.

  7. Formation of tamoxifen-DNA adducts via O-sulfonation, not O-acetylation, of alpha-hydroxytamoxifen in rat and human livers.

    Science.gov (United States)

    Kim, Sung Yeon; Laxmi, Y R Santosh; Suzuki, Naomi; Ogura, Kenichiro; Watabe, Tadashi; Duffel, Michael W; Shibutani, Shinya

    2005-11-01

    Tamoxifen (TAM) is used as the standard endocrine therapy for breast cancer patients and as a chemopreventive agent for women at high risk for this disease. Unfortunately, treatment of TAM increases the incidence of endometrial cancer; this may be due to the genotoxic damage induced by TAM metabolites. Formation of TAM-DNA adducts in rat liver correlates with the development of hepatocarcinoma. TAM-DNA adducts are proposed to be formed through O-sulfonation and/or O-acetylation of alpha-hydroxylated TAM and its metabolites. However, the role of O-sulfonation and O-acetylation in the formation of TAM-DNA adducts has not been extensively investigated. Rat or human hydroxysteroid sulfotransferases (HST), acetyltransferases, and liver cytosol were incubated with calf thymus DNA, alpha-OHTAM, and either 3'-phosphoadenosine 5'-phosphosulfate (PAPS) or acetyl coenzyme A (acetyl-CoA) as a cofactor and analyzed for TAM-DNA adduct formation, using 32P postlableling/polyacrylamide gel electrophoresis analysis. TAM-DNA adduct was formed when PAPS, not acetyl-CoA, was used. No TAM-DNA adducts were produced using human N-acetyltransferase I and II. HST antibody inhibited approximately 90% of TAM-DNA adduct formation generated by the cytosol or HST, suggesting that HST is primarily involved in the formation of TAM-DNA adducts. The formation of TAM-DNA adducts with rat liver cytosol and HST was much higher than that of human liver cytosol and HST. Our results indicate that TAM-DNA adducts are formed via O-sulfonation, not O-acetylation, of alpha-hydroxylated TAM and its metabolites.

  8. Improving EEG signal peak detection using feature weight learning ...

    Indian Academy of Sciences (India)

    Asrul Adam

    Neural network with random weights (NNRW); feature weight learning (FWL); electroencephalogram (EEG); peak detection algorithm; pattern recognition; particle swarm optimization (PSO). 1. Introduction. The utilization of peak detection algorithms has emerged as a useful tool in several physiological signal applications,.

  9. Malaria vaccine: a step toward elimination.

    Science.gov (United States)

    Jindal, Harashish; Bhatt, Bhumika; Malik, Jagbir S; Sk, Shashikantha; Mehta, Bharti

    2014-01-01

    Malaria has long been recognized as a public health problem. At the community level, vector control, and antimalarial medicines are the main means for reducing incidence, morbidity, and mortality of malaria. A vaccine not only would bring streamlining in the prevention of morbidity and mortality from malaria but also would be more accessible if integrated with Expanded Programme of Immunization (EPI). Globally, an estimated 3.4 billion people are at risk of malaria. Most cases (80%) and deaths (90%) occurred in Africa, and most deaths (77%) are in children under 5 years of age. An effective vaccine has long been envisaged as a valuable addition to the available tools for malaria control. Although research toward the development of malaria vaccines has been pursued since the 1960s, there are no licensed malaria vaccines. The RTS,S/AS01 vaccine, which targets P. falciparum, has reached phase 3 clinical trials and results are promising. Malaria Vaccine Technology Road Map 2013 has envisaged the world aiming for a licensed vaccine by 2030 that would reduce malaria cases by 75% and be capable of eliminating malaria. It will not only fill the gaps of today's interventions but also be a cost-effective method of decreasing morbidity and mortality from malaria.

  10. Method of eliminating radioactive substances in atmosphere

    International Nuclear Information System (INIS)

    Hashimoto, Tadayuki.

    1981-01-01

    Purpose: To eliminate natural radioactive substance (in particular, gases 222 Rn) in the atmosphere. Method: Air removed with dusts of greater than several μ in a filter is introduced into a mixer using a blower. In the blower, super-heated steams at 120 - 200 0 C and the airs are mixed together. Then, the air mixture is introduced into a cooler and cooled to room temperature -50 0 C to condensate water. Subsequently, the cooled air mixture is passed through an activated carbon adsorption device (6 - 12 mesh, air passing speed less than 4 cm/sec. and activated carbon layer thickness 50 - 100 cm) to adsorb 222 Rn. Finally, the air passed through the activated carbon adsorption device is introduced to an ultrafilter for collecting fine particles (asbesto filter, glass filter, etc.) to collect fine particles of activated carbon, lead, bismuth, etc. (decaying products of gaseous 222 Rn). Liquid issued from the mixer and the cooler are discharged by way of drain pipes. (Ikeda, J.)

  11. Seasonal blood shortages can be eliminated.

    Science.gov (United States)

    Gilcher, Ronald O; McCombs, Suzanne

    2005-11-01

    This review is designed to help readers understand seasonal blood shortages and provide solutions through the use of technology that can increase the number of red blood cell units collected and the use of recruitment and marketing initiatives that appeal to the increasingly diverse donor base. Seasonal shortages are, in reality, mostly shortages of group O red blood cells and occur most commonly during midsummer and early winter. The shortages occur primarily from increased use of group O red blood cells at times of decreased donor availability. While reducing the disproportionate use of red cells will help, blood centers can more quickly reduce the seasonal deficits by using automated red cell technology to collect double red blood cell units; targeted marketing programs to provide effective messages; seasonal advertising campaigns; and recognition, benefits, and incentives to enhance the donor motivation donation threshold. A multi-level approach to increasing blood donations at difficult times of the year can ensure that donations are increased at a time when regular donor availability is decreased. Seasonal blood shortages can be eliminated by understanding the nature of the shortages, why and when they occur, and using more sophisticated recruitment and marketing strategies as well as automated collection technologies to enhance the blood supply.

  12. Elimination of excess molybdenum by cattle

    Energy Technology Data Exchange (ETDEWEB)

    Toelgyesi, G.; Elmoty, I.A.

    1967-01-01

    It was found that cattle would ingest spontaneously 5-15 g of molybdenum on one occasion. The uptake of this quantity caused but moderate loss of appetite and mild enteritis, both normalizing in one week. The occurrence of a severe acute molybdenum poisoning can be practically excluded, owing to refusal of the poisoned feed. Spontaneously ingested molybdenum caused on the first day a 30-100 fold rise of ruminal Mo-level, decreasing to the order of the normal value in about one week. But in the urine and faeces, Mo-level was at least 10 fold, in the blood and milk about 4 fold of the normal one, even one or two weeks after ingestion. During this period at least 90% of ingested Mo was eliminated with the faeces, urine and milk. One week after the ingestion of molybdenum, the rumen content showed no evidence on poisoning and no trace of molybdenum. Oral administration of ammonium molybdenate in an amount equivalent to 40 g molybdenum caused no fatality. In fact, cattle would never ingest spontaneously such a large dose.

  13. Minimizing or eliminating refueling of nuclear reactor

    Science.gov (United States)

    Doncals, Richard A.; Paik, Nam-Chin; Andre, Sandra V.; Porter, Charles A.; Rathbun, Roy W.; Schwallie, Ambrose L.; Petras, Diane S.

    1989-01-01

    Demand for refueling of a liquid metal fast nuclear reactor having a life of 30 years is eliminated or reduced to intervals of at least 10 years by operating the reactor at a low linear-power density, typically 2.5 kw/ft of fuel rod, rather than 7.5 or 15 kw/ft, which is the prior art practice. So that power of the same magnitude as for prior art reactors is produced, the volume of the core is increased. In addition, the height of the core and it diameter are dimensioned so that the ratio of the height to the diameter approximates 1 to the extent practicable considering the requirement of control and that the pressure drop in the coolant shall not be excessive. The surface area of a cylinder of given volume is a minimum if the ratio of the height to the diameter is 1. By minimizing the surface area, the leakage of neutrons is reduced. By reducing the linear-power density, increasing core volume, reducing fissile enrichment and optimizing core geometry, internal-core breeding of fissionable fuel is substantially enhanced. As a result, core operational life, limited by control worth requirements and fuel burnup capability, is extended up to 30 years of continuous power operation.

  14. Reward eliminates retrieval-induced forgetting.

    Science.gov (United States)

    Imai, Hisato; Kim, Dongho; Sasaki, Yuka; Watanabe, Takeo

    2014-12-02

    Although it is well known that reward enhances learning and memory, how extensively such enhancement occurs remains unclear. To address this question, we examined how reward influences retrieval-induced forgetting (RIF) in which the retrieval of a nonpracticed item under the same category as a practiced item is worse than the retrieval of a nonpracticed item outside the category. Subjects were asked to try to encode category-exemplar pairs (e.g., FISH-salmon). Then, they were presented with a category name and a two-letter word stem (e.g., FISH-sa) and were asked to complete an encoded word (retrieval practice). For a correct response, apple juice was given as a reward in the reward condition and a beeping sound was presented in the no-reward condition. Finally, subjects were asked to report whether each exemplar had been presented in the first phase. RIF was replicated in the no-reward condition. However, in the reward condition, RIF was eliminated. These results suggest that reward enhances processing of retrieval of unpracticed members by mechanisms such as spreading activation within the same category, irrespective of whether items were practiced or not.

  15. Progress toward measles elimination in kyrgyzstan.

    Science.gov (United States)

    Suvanbekov, Akbar; Kitarova, Gulzhan; Reyer, Joshua A; Hamajima, Nobuyuki

    2015-02-01

    Measles is one of the most severe infectious diseases of childhood, and one of the major causes of mortali-ty, especially in developing countries. Despite rare measles outbreaks in recent years, Kyrgyzstan seeks to show its commitment towards the global anti-measles campaign. The aim of this article is to summarize the scattered information on the recent status of measles, valid surveillance system, and measles elimination strategies in Kyrgyzstan, based on sources that include non-confidential but usually inaccessible governmental data. Infor-mation was extracted from the reports to the Ministry of Health and documents on the national surveillance system, in addition to outbreak cases extracted from the Republican Infectious Diseases Hospital's archive. To tackle the worsening measles situation in Kyrgyzstan, the Ministry of Health established the Republican Center for Immunoprophylaxis in 1994. Measles related death, which was rampant up until 1992, has not been registered since 2000 due to improved routine vaccination coverage, increasing from 88% in 1994 to 97% and over in 1997. The national surveillance system was modernized thanks to the World Health Organization, helping to detect measles cases and prevent major outbreaks. The system identified 222 cases in the outbreak of 2011, and the case cards in the hospital provided the findings of 69 admitted cases (42 infants, 22 children aged 1 to 14 years, and 5 aged 15 years or over), including 32 severe cases. This article provides a whole view on measles in Kyrgyzstan, which would be useful to control measles worldwide.

  16. Mitochondrial reactive oxygen species production and elimination.

    Science.gov (United States)

    Nickel, Alexander; Kohlhaas, Michael; Maack, Christoph

    2014-08-01

    Reactive oxygen species (ROS) play an important role in cardiovascular diseases, and one important source for ROS are mitochondria. Emission of ROS from mitochondria is the net result of ROS production at the electron transport chain (ETC) and their elimination by antioxidative enzymes. Both of these processes are highly dependent on the mitochondrial redox state, which is dynamically altered under different physiological and pathological conditions. The concept of "redox-optimized ROS balance" integrates these aspects and implies that oxidative stress occurs when the optimal equilibrium of an intermediate redox state is disturbed towards either strong oxidation or reduction. Furthermore, mitochondria integrate ROS signals from other cellular sources, presumably through a process termed "ROS-induced ROS release" that involves mitochondrial ion channels. Here, we attempt to integrate these recent advances in our understanding of the control of mitochondrial ROS emission and develop a concept of how in heart failure, defects in ion handling can lead to mitochondrial oxidative stress. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System". Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Tardive dyskinesia: eliminated, forgotten, or overshadowed?

    Science.gov (United States)

    Remington, Gary

    2007-03-01

    The present review focuses on atypical antipsychotics and tardive dyskinesia. We have known for many years that clozapine has a diminished risk of tardive dyskinesia compared with typical antipsychotics. The last decade has seen the introduction of a number of other atypical antipsychotics, allowing us to begin evaluating whether they too share this attribute. In addition, the opportunity to use these drugs as first-line treatment permits a more precise means of establishing risk. While longer-term data are required, the limited evidence available clearly indicates that the atypical antipsychotics have a decreased liability of tardive dyskinesia, approximately 1% compared with 5% for typical agents annually. Like clozapine, the other atypical antipsychotics also demonstrate antidyskinetic properties in individuals with preexisting tardive dyskinesia. The underlying mechanisms remain unclear, and without such information it is not possible to say what clinical conditions, if any, might diminish or even eliminate these advantages. An update is provided regarding the atypical antipsychotics and tardive dyskinesia. This information is critical in our decision-making regarding choice of antipsychotic and optimal use in the clinical setting.

  18. Elimination of mercury in health care facilities.

    Science.gov (United States)

    2000-03-01

    Mercury is a persistent, bioaccumulative toxin that has been linked to numerous health effects in humans and wildlife. It is a potent neurotoxin that may also harm the brain, kidneys, and lungs. Unborn children and young infants are at particular risk for brain damage from mercury exposure. Hospitals' use of mercury in chemical solutions, thermometers, blood pressure gauges, batteries, and fluorescent lamps makes these facilities large contributors to the overall emission of mercury into the environment. Most hospitals recognize the dangers of mercury. In a recent survey, four out of five hospitals stated that they have policies in place to eliminate the use of mercury-containing products. Sixty-two percent of them require vendors to disclose the presence of mercury in chemicals that the hospitals purchase. Only 12 percent distribute mercury-containing thermometers to new parents. Ninety-two percent teach their employees about the health and environmental effects of mercury, and 46 percent teach all employees how to clean up mercury spills. However, the same study showed that many hospitals have not implemented their policies. Forty-two percent were not aware whether they still purchased items containing mercury. In addition, 49 percent still purchase mercury thermometers, 44 percent purchase mercury gastrointestinal diagnostic equipment, and 64 percent still purchase mercury lab thermometers.

  19. The effect of utility time-varying pricing and load control strategies on residential summer peak electricity use. A review

    International Nuclear Information System (INIS)

    Newsham, Guy R.; Bowker, Brent G.

    2010-01-01

    Peak demand for electricity in North America is expected to grow, challenging electrical utilities to supply this demand in a cost-effective, reliable manner. Therefore, there is growing interest in strategies to reduce peak demand by eliminating electricity use, or shifting it to non-peak times. This strategy is commonly called 'demand response'. In households, common strategies are time-varying pricing, which charge more for energy use on peak, or direct load control, which allows utilities to curtail certain loads during high demand periods. We reviewed recent North American studies of these strategies. The data suggest that the most effective strategy is a critical peak price (CPP) program with enabling technology to automatically curtail loads on event days. There is little evidence that this causes substantial hardship for occupants, particularly if they have input into which loads are controlled and how, and have an override option. In such cases, a peak load reduction of at least 30% is a reasonable expectation. It might be possible to attain such load reductions without enabling technology by focusing on household types more likely to respond, and providing them with excellent support. A simple time-of-use (TOU) program can only expect to realise on-peak reductions of 5%. (author)

  20. PEAK TRACKING WITH A NEURAL NETWORK FOR SPECTRAL RECOGNITION

    NARCIS (Netherlands)

    COENEGRACHT, PMJ; METTING, HJ; VANLOO, EM; SNOEIJER, GJ; DOORNBOS, DA

    1993-01-01

    A peak tracking method based on a simulated feed-forward neural network with back-propagation is presented. The network uses the normalized UV spectra and peak areas measured in one chromatogram for peak recognition. It suffices to train the network with only one set of spectra recorded in one