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Search Results: 1 - 10 of 135785 matches for " Mary V. Gamble "
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Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity
Megan N. Hall,Mary V. Gamble
Journal of Toxicology , 2012, DOI: 10.1155/2012/595307
Abstract: Exposure to arsenic (As) through drinking water is a substantial problem worldwide. The methylation of As, a reactive metalloid, generates monomethyl- (MMA) and dimethyl-arsenical (DMA) species. The biochemical pathway that catalyzes these reactions, one-carbon metabolism, is regulated by folate and other micronutrients. Arsenic methylation exerts a critical influence on both its urinary elimination and chemical reactivity. Mice having the As methyltransferase null genotype show reduced urinary As excretion, increased As retention, and severe systemic toxicity. The most toxic As metabolite in vitro is M M A I I I , an intermediate in the generation of D M A V , a much less toxic metabolite. These findings have raised the question of whether As methylation is a detoxification or bioactivation pathway. Results of population-based studies suggest that complete methylation of inorganic As to DMA is associated with reduced risk for As-induced health outcomes, and that nutrients involved in one-carbon metabolism, such as folate, can facilitate As methylation and elimination. 1. Introduction Arsenic (As) is a naturally occurring element commonly present in environmental sources such as air, water, and soil [1]. Through processes that are incompletely understood, As in soil can be mobilized leading to enrichment of As in groundwater. While drinking water is the most common source of exposure, other sources include As from mining and smelting, wood preservatives, pesticides, and foods irrigated and/or prepared with As-contaminated water. Current estimates suggest that roughly 140 million people in Bangladesh, India, Vietnam, Nepal, and Cambodia are drinking water with As concentrations up to 100 times the World Health Organization (WHO) and USA Environmental Protection Agency (EPA) guideline of 10?μg/L [2, 3]. Chile, Mexico, China, and Taiwan also have As in groundwater that is used for drinking. In comparison to the situation in South and East Asia, the magnitude of the problem in the USA is relatively small. Nevertheless, the US Geological Survey estimates that 42 million Americans obtain their drinking water from household wells, and roughly 15% of these wells exceed the WHO guideline, indicating that a large number of USA residents are exposed to excess As from household wells [4]. In addition, not all municipalities are yet in compliance with the EPA requirements, with up to 8% of all public water supplies exceeding 10?μg As/L. Individuals chronically exposed to As are at increased risk for various cancers, including cancers of the skin (Bowen’s disease,
Vitamin A deficiency and inflammatory markers among preschool children in the Republic of the Marshall Islands
Maria Maqsood, Barbara Dancheck, Mary V Gamble, Neal A Palafox, Michelle O Ricks, Kennar Briand, Richard D Semba
Nutrition Journal , 2004, DOI: 10.1186/1475-2891-3-21
Abstract: In a survey in the Republic of the Marshall Islands involving 281 children, aged 1–5 years, serum retinol, C-reactive protein (CRP), and α1-acid glycoprotein (AGP) were measured.Of 281 children, 24 (8.5%) had night blindness and 165 (58.7%) had serum retinol <0.70 μmol/L. Of 248 children with AGP and CRP measurements, 123 (49.6%) had elevated acute phase proteins (CRP >5 mg/L and/or AGP >1000 mg/L). Among children with and without night blindness, the proportion with serum retinol <0.70 μmol/L was 79.2% and 56.8% (P = 0.03) and with anemia was 58.3% and 35.7% (P = 0.029), respectively. The proportion of children with serum retinol <0.70 μmol/L was 52.0% after excluding children with elevated acute phase proteins. Among children with and without elevated acute phase proteins, mean age was 2.8 vs 3.2 years (P = 0.016), the proportion of boys was 43.1% vs. 54.3% (P = 0.075), with no hospitalizations in the last year was 11.0% vs 23.6% (P = 0.024), and with anemia was 43.8% vs 31.7% (P = 0.05), respectively.Exclusion of children with inflammation in this survey of vitamin A deficiency does not improve prevalence estimates for vitamin A deficiency and instead leads to sampling bias for variables such as age, gender, anemia, and hospitalization history.Vitamin A deficiency is a major cause of morbidity and mortality among preschool children in developing countries [1]. Vitamin A, or all-trans retinol, is available as preformed vitamin A in foods such as eggs and dairy products and as provitamin A carotenoids in foods such as dark green leafy vegetables, pumpkin, and papaya. Vitamin A is essential for normal immune function, hematopoiesis, growth, and vision [1]. Among preschool children, risk factors for vitamin A deficiency include age, such as the period that follows weaning when vitamin A intake is low and risk of precipitating infections is high [2,3], recent infections such as diarrheal disease [4], and low socioeconomic status [5]. The syndrome of vitamin A deficien
Mathematical model insights into arsenic detoxification
Sean D Lawley, Molly Cinderella, Megan N Hall, Mary V Gamble, H Frederik Nijhout, Michael C Reed
Theoretical Biology and Medical Modelling , 2011, DOI: 10.1186/1742-4682-8-31
Abstract: We develop a whole body mathematical model of arsenic metabolism including arsenic absorption, storage, methylation, and excretion. The parameters for arsenic methylation in the liver were taken from the biochemical literature. The transport parameters between compartments are largely unknown, so we adjust them so that the model accurately predicts the urine excretion rates of time for the iAs, MMAs, and DMAs in single dose experiments on human subjects.We test the model by showing that, with no changes in parameters, it predicts accurately the time courses of urinary excretion in mutiple dose experiments conducted on human subjects. Our main purpose is to use the model to study and interpret the data on the effects of folate supplementation on arsenic methylation and excretion in clinical trials in Bangladesh. Folate supplementation of folate-deficient individuals resulted in a 14% decrease in arsenicals in the blood. This is confirmed by the model and the model predicts that arsenicals in the liver will decrease by 19% and arsenicals in other body stores by 26% in these same individuals. In addition, the model predicts that arsenic methyltransferase has been upregulated by a factor of two in this population. Finally, we also show that a modification of the model gives excellent fits to the data on arsenic metabolism in human cultured hepatocytes.The analysis of the Bangladesh data using the model suggests that folate supplementation may be more effective at reducing whole body arsenic than previously expected. There is almost no data on the upregulation of arsenic methyltransferase in populations chronically exposed to arsenic. Our model predicts upregulation by a factor of two in the Bangladesh population studied. This prediction should be verified since it could have important public health consequences both for treatment strategies and for setting appropriate limits on arsenic in drinking water. Our model has compartments for the binding of arsenicals to protei
Influence of Prenatal Arsenic Exposure and Newborn Sex on Global Methylation of Cord Blood DNA
J. Richard Pilsner, Megan N. Hall, Xinhua Liu, Vesna Ilievski, Vesna Slavkovich, Diane Levy, Pam Factor-Litvak, Mahammad Yunus, Mahfuzar Rahman, Joseph H. Graziano, Mary V. Gamble
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037147
Abstract: Background An emerging body of evidence indicates that early-life arsenic (As) exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. Objective The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. Design Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs), maternal blood As (mbAs) and cord blood As (cbAs). Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. Results In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1) and Q2 vs. Q4; p = 0.06 and 0.04, respectively). Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58) but negative among female newborns (N = 43); tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively) and for the association between maternal uAs and LINE-1 (p = 0.07). Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05). Conclusions These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm these findings and to examine the persistence of DNA methylation marks over time.
Transmission System Reconfiguration to Reduce Losses and Cost Ensuring Voltage Security  [PDF]
Veerapandiyan V., Mary D.
Journal of Power and Energy Engineering (JPEE) , 2016, DOI: 10.4236/jpee.2016.46002
Abstract: The aim of this paper is to reduce the losses, total generation cost by switching of transmission line and to maintain voltage security under N?- 1 contingency conditions. Generation cost is calculated and the priority list is made for switching the line. The problem is solved by ACOPF using Interior Point Method. In order to test the feasibility and effectiveness of the above method, a sample 6-bus system and IEEE 30-bus system have been used. The impact of switching on system parameter includes the generation cost, locational marginal pricing (LMP) and transmission losses, ensuring voltage security of the system.
A Quantitative LC-MS/MS Study of the Partitioning, Transport, and Fate of Pesticide Residues on Soil  [PDF]
Heather A. Gamble, Donald S. Gamble
Journal of Environmental Protection (JEP) , 2016, DOI: 10.4236/jep.2016.73029

Titration of pesticides onto sorption sites can determine sorption capacities on soils. Previous studies have tracked the sorption capacities and detailed kinetics of the uptake of atrazine and its decomposition byproduct hydroxyatrazine on different soils, including measurements made using LC-MS/MS. These studies have now been extended to explore sorption-desorption equilibria for a mixture of pesticides from soil using LC-MS/MS. Desorption of sorbed pesticide residues has environmental regulatory implications for pesticide levels in runoff, or for longer term sequestration, partitioning, and transport. The uptake of pesticides by the soil at equilibrium was measured for a number of different concentrations, and sorption capacities were estimated. Pesticide-soil interaction studies were conducted by exposing standard stock solutions of pesticide mixtures to a characterized Nova Scotia soil. The mixture contained atrazine and dicamba. Initial aqueous mixture concentrations ranging from 5 × 10-9 to 10-5 M or greater were exposed to 25 mg aliquots of soil and allowed to reach equilibrium. The total uptake of each pesticide was measured indirectly, by measuring the concentration remaining in solution using an IONICS 3Q 120 triple quadrupole mass spectrometer. These sorption capacities have been supplemented by studies examining equilibrium recovery rates from soil aliquots with different initial uptakes. This gives insight into the fraction of easily recoverable (reversibly sorbed) pesticides on the soil. Proper quantification of equilibrium constants and kinetic rate coefficients using high performance LC-MS/MS facilitates the construction of accurate, predictive models. Predictive kinetic models can successfully mimic the experimental results for solution concentration, labile sorption, and intra-particle diffusion, and could be used to guide regulatory practices.

Genome-Wide Association Study Identifies Chromosome 10q24.32 Variants Associated with Arsenic Metabolism and Toxicity Phenotypes in Bangladesh
Brandon L. Pierce,Muhammad G. Kibriya,Lin Tong,Farzana Jasmine,Maria Argos,Shantanu Roy,Rachelle Paul-Brutus,Ronald Rahaman,Muhammad Rakibuz-Zaman,Faruque Parvez,Alauddin Ahmed,Iftekhar Quasem,Samar K. Hore,Shafiul Alam,Tariqul Islam,Vesna Slavkovich,Mary V. Gamble,Md Yunus,Mahfuzar Rahman,John A. Baron,Joseph H. Graziano,Habibul Ahsan
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002522
Abstract: Arsenic contamination of drinking water is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer. There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however, the basis of this variation is not well understood. Here, we have performed the first genome-wide association study (GWAS) of arsenic-related metabolism and toxicity phenotypes to improve our understanding of the mechanisms by which arsenic affects health. Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs) for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P<5×10?8) for percentages of both monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) near the AS3MT gene (arsenite methyltransferase; 10q24.32), with five genetic variants showing independent associations. In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity) and 1,794 controls, we show that one of these five variants (rs9527) is also associated with skin lesion risk (P = 0.0005). Using a subset of individuals with prospectively measured arsenic (n = 769), we show that rs9527 interacts with arsenic to influence incident skin lesion risk (P = 0.01). Expression quantitative trait locus (eQTL) analyses of genome-wide expression data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs represent cis-eQTLs for AS3MT (P = 10?12) and neighboring gene C10orf32 (P = 10?44), which are involved in C10orf32-AS3MT read-through transcription. This is the largest and most comprehensive genomic investigation of arsenic metabolism and toxicity to date, the only GWAS of any arsenic-related trait, and the first study to implicate 10q24.32 variants in both arsenic metabolism and arsenical skin lesion risk. The observed patterns of associations suggest that MMA% and DMA% have distinct genetic determinants and support the hypothesis that DMA is the less toxic of these two methylated arsenic species. These results have potential translational implications for the prevention and treatment of arsenic-associated toxicities worldwide.
Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model
Lena J Gamble,Hideyo Ugai,Minghui Wang,Anton V Borovjagin
Journal of Molecular Biochemistry , 2012,
Abstract: Ovarian cancer is the leading cause of gynecological disease death despite advances in medicine. Therefore, novel strategies are required for ovarian cancer therapy. Conditionally replicative adenoviruses (CRAds), genetically modified as anti-cancer therapeutics, are one of the most attractive candidate agents for cancer therapy. However, a paucity of coxsackie B virus and adenovirus receptor (CAR) expression on the surface of ovarian cancer cells has impeded treatment of ovarian cancer using this approach. This study sought to engineer a CRAd with enhanced oncolytic ability in ovarian cancer cells, “Δ24DoubleRGD.” Δ24DoubleRGD carries an arginine-glycine-aspartate (RGD) motif incorporated into both fiber and capsid protein IX (pIX) and its oncolytic efficacy was evaluated in ovarian cancer. In vitro analysis of cell viability showed that infection of ovarian cancer cells with Δ24DoubleRGD leads to increased cell killing relative to the control CRAds. Data from this study suggested that not only an increase in number of RGD motifs on the CRAd capsid, but also a change in the repertoir of targeted integrins could lead to enhanced oncolytic potency of Δ24DoubleRGD in ovarian cancer cells in vitro. In an intraperitoneal model of ovarian cancer, mice injected with Δ24DoubleRGD showed, however, a similar survival rate as mice treated with control CRAds.
Jos Gamble
Asian Academy of Management Journal , 2006,
Abstract: The management of host country employees is often portrayed as a particularly fraught dimension for multinational firms. The problems involved are considered exponentially greater when there are substantial institutional differences and 'cultural distance' between the host country and a firm's parent country, as is assumed to be the case for Western firms operating in China. Based upon detailed case study research conducted at a UK-invested firm in China between 1999 and 2003 and a comparative study of a Chinese state-owned firm, this paper explores the veracity of such assumptions. The findings indicate that Western human resource management practices can be transplanted successfully and questions the degree to which foreign-invested enterprises need to adopt 'the Chinese way of doing things'. Indeed, such practices can be innovative in the Chinese context and provide a competitive source of differentiation for multinationals as employees.
Foundations of Quantum Decoherence
John Gamble
Physics , 2008,
Abstract: The conventional interpretation of quantum mechanics, though it permits a correspondence to classical physics, leaves the exact mechanism of transition unclear. Though this was only of philosophical importance throughout the twentieth century, over the past decade new technological developments, such as quantum computing, require a more thorough understanding of not just the result of quantum emergence, but also its mechanism. Quantum decoherence theory is the model that developed out of necessity to deal with the quantum-classical transition explicitly, and without external observers. In this thesis, we present a self-contained and rigorously argued full derivation of the master equation for quantum Brownian motion, one of the key results in quantum decoherence theory. We accomplish this from a foundational perspective, only assuming a few basic axioms of quantum mechanics and deriving their consequences. We then consider a physical example of the master equation and show that quantum decoherence successfully represents the transition from a quantum to classical system.
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