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Sample records for model toxicants electronic

  1. 78 FR 52860 - Electronic Reporting of Toxics Release Inventory Data

    Science.gov (United States)

    2013-08-27

    ... to report non- trade-secret Toxics Release Inventory (TRI) forms to EPA using electronic software... AGENCY 40 CFR Part 372 RIN 2025-AA30 Electronic Reporting of Toxics Release Inventory Data AGENCY..., Toxics Release Inventory Program Division, Mailcode 2844T, OEI, Environmental Protection Agency,...

  2. 77 FR 13061 - Electronic Reporting of Toxics Release Inventory Data

    Science.gov (United States)

    2012-03-05

    ... the online reporting software application known as the Toxics Release Inventory-Made Easy Web or... Software TRI-MEweb--Toxics Release Inventory-Made Easy Internet-based Software Application U.S.C.--United... AGENCY 40 CFR Part 372 Electronic Reporting of Toxics Release Inventory Data AGENCY:...

  3. Salicylate toxicity model of tinnitus

    Directory of Open Access Journals (Sweden)

    Daniel eStolzberg

    2012-04-01

    Full Text Available Salicylate, the active component of the common drug aspirin, has mild analgesic, antipyretic, and anti-inflammatory effects at moderate doses. At higher doses, however, salicylate temporarily induces moderate hearing loss and the perception of a high-pitch ringing in humans and animals. This phantom perception of sound known as tinnitus is qualitatively similar to the persistent subjective tinnitus induced by high-level noise exposure, ototoxic drugs or aging which affects ~14% of the general population. For over a quarter century, auditory scientists have used the salicylate toxicity model to investigate candidate biochemical and neurophysiological mechanisms underlying phantom sound perception. In this review, we summarize some of the intriguing biochemical and physiological effects associated with salicylate-induced tinnitus, some of which occur in the periphery and others in the central nervous system. The relevance and general utility of the salicylate toxicity model in understanding phantom sound perception in general are discussed.

  4. Predictive Modeling of Developmental Toxicity

    Science.gov (United States)

    The use of alternative methods in conjunction with traditional in vivo developmental toxicity testing has the potential to (1) reduce cost and increase throughput of testing the chemical universe, (2) prioritize chemicals for further targeted toxicity testing and risk assessment,...

  5. Emissions of Toxic Carbonyls in an Electronic Cigarette

    Directory of Open Access Journals (Sweden)

    Guthery William

    2016-01-01

    Full Text Available Electronic cigarettes (e-cigs provide a smoke-free alternative for inhalation of nicotine without the vast array of toxic and carcinogenic combustion products produced by tobacco smoke. Elevated levels of toxic carbonyls may be generated during vaporisation; however, it is unclear whether that is indicative of a fault with the device or is due to the applied conditions of the test. A device, designed and built at this facility, was tested to determine the levels of selected toxic carbonyls. The reservoir was filled with approximately 960 mg of an e-liquid formulation containing 1.8% (w/v nicotine. Devices were puffed 200 times in blocks of 40 using a standardised regime consisting of a 55 mL puff volume; 3 s puff duration; 30 s puff interval; square wave puff profile. Confirmatory testing for nicotine and total aerosol delivery resulted in mean (n = 8 values of 10 mg (RSD 12.3% and 716 mg (RSD 11.2%, respectively. Emissions of toxic carbonyls were highly variable yet were between < 0.1% and 22.9% of expected levels from a Kentucky Reference Cigarette (K3R4F puffed 200 times under Health Canada Intense smoking conditions. It has been shown that a device built to a high specification with relatively consistent nicotine and aerosol delivery emits inconsistent levels of carbonyls. The exposure is greatly reduced when compared with lit tobacco products. However, it was observed that as the reservoirs neared depletion then emission levels were significantly higher

  6. In vitro models of lung toxicity.

    Science.gov (United States)

    Fisher, G L; Placke, M E

    1987-12-01

    In vitro assays that emphasize cellular components critical to the host defense system have been developed to evaluate pulmonary toxicity and define deleterious changes in parenchymal cell populations. Assays that employ pulmonary alveolar macrophages (PAM) have demonstrated good correlation between macrophage toxicity and pulmonary fibrogenicity for many inorganic compounds. The PAM assays provide simple and inexpensive screens of potential respiratory tract toxicity. Many investigators screen chemicals for their ability to alter the mucosal epithelial cell conducting airways by performing tracheal organ cultures. The tracheal assays have also provided useful screens for Vitamin A analogues required for epithelial cell differentiation. Most recently, in vitro respiratory tract models have been extended to include whole-lung explants, an approach that allows for development of fibrosis and epithelial cell toxicity after in vitro exposure to inorganic and organic fibrogens. The whole-lung explant system appears to duplicate the in vivo response to a variety of lung toxins, including bleomycin, silica, and crocidolite asbestos. Together, these assays provide a description of potential toxicity to key components of the lung, emphasizing the pulmonary macrophage, conducting airways, and alveolar septae. It is expected that continued research in these models will enhance their predictive abilities and utility in risk assessment.

  7. Toxicity Assessment of Refill Liquids for Electronic Cigarettes

    Directory of Open Access Journals (Sweden)

    Vincent Varlet

    2015-04-01

    Full Text Available We analyzed 42 models from 14 brands of refill liquids for e-cigarettes for the presence of micro-organisms, diethylene glycol, ethylene glycol, hydrocarbons, ethanol, aldehydes, tobacco-specific nitrosamines, and solvents. All the liquids under scrutiny complied with norms for the absence of yeast, mold, aerobic microbes, Staphylococcus aureus, and Pseudomonas aeruginosa. Diethylene glycol, ethylene glycol and ethanol were detected, but remained within limits authorized for food and pharmaceutical products. Terpenic compounds and aldehydes were found in the products, in particular formaldehyde and acrolein. No sample contained nitrosamines at levels above the limit of detection (1 μg/g. Residual solvents such as 1,3-butadiene, cyclohexane and acetone, to name a few, were found in some products. None of the products under scrutiny were totally exempt of potentially toxic compounds. However, for products other than nicotine, the oral acute toxicity of the e-liquids tested seems to be of minor concern. However, a minority of liquids, especially those with flavorings, showed particularly high ranges of chemicals, causing concerns about their potential toxicity in case of chronic oral exposure.

  8. Toxicity assessment of refill liquids for electronic cigarettes.

    Science.gov (United States)

    Varlet, Vincent; Farsalinos, Konstantinos; Augsburger, Marc; Thomas, Aurélien; Etter, Jean-François

    2015-04-30

    We analyzed 42 models from 14 brands of refill liquids for e-cigarettes for the presence of micro-organisms, diethylene glycol, ethylene glycol, hydrocarbons, ethanol, aldehydes, tobacco-specific nitrosamines, and solvents. All the liquids under scrutiny complied with norms for the absence of yeast, mold, aerobic microbes, Staphylococcus aureus, and Pseudomonas aeruginosa. Diethylene glycol, ethylene glycol and ethanol were detected, but remained within limits authorized for food and pharmaceutical products. Terpenic compounds and aldehydes were found in the products, in particular formaldehyde and acrolein. No sample contained nitrosamines at levels above the limit of detection (1 μg/g). Residual solvents such as 1,3-butadiene, cyclohexane and acetone, to name a few, were found in some products. None of the products under scrutiny were totally exempt of potentially toxic compounds. However, for products other than nicotine, the oral acute toxicity of the e-liquids tested seems to be of minor concern. However, a minority of liquids, especially those with flavorings, showed particularly high ranges of chemicals, causing concerns about their potential toxicity in case of chronic oral exposure.

  9. Modeling Respiratory Toxicity of Authentic Lunar Dust

    Science.gov (United States)

    Santana, Patricia A.; James, John T.; Lam, Chiu-Wing

    2010-01-01

    The lunar expeditions of the Apollo operations from the 60 s and early 70 s have generated awareness about lunar dust exposures and their implication towards future lunar explorations. Critical analyses on the reports from the Apollo crew members suggest that lunar dust is a mild respiratory and ocular irritant. Currently, NASA s space toxicology group is functioning with the Lunar Airborne Dust Toxicity Assessment Group (LADTAG) and the National Institute for Occupational Safety and Health (NIOSH) to investigate and examine toxic effects to the respiratory system of rats in order to establish permissible exposure levels (PELs) for human exposure to lunar dust. In collaboration with the space toxicology group, LADTAG and NIOSH the goal of the present research is to analyze dose-response curves from rat exposures seven and twenty-eight days after intrapharyngeal instillations, and model the response using BenchMark Dose Software (BMDS) from the Environmental Protection Agency (EPA). Via this analysis, the relative toxicities of three types of Apollo 14 lunar dust samples and two control dust samples, titanium dioxide (TiO2) and quartz will be determined. This will be executed for several toxicity endpoints such as cell counts and biochemical markers in bronchoaveolar lavage fluid (BALF) harvested from the rats.

  10. A Bayesian network model for predicting aquatic toxicity mode ...

    Science.gov (United States)

    The mode of toxic action (MoA) has been recognized as a key determinant of chemical toxicity but MoA classification in aquatic toxicology has been limited. We developed a Bayesian network model to classify aquatic toxicity mode of action using a recently published dataset containing over one thousand chemicals with MoA assignments for aquatic animal toxicity. Two dimensional theoretical chemical descriptors were generated for each chemical using the Toxicity Estimation Software Tool. The model was developed through augmented Markov blanket discovery from the data set with the MoA broad classifications as a target node. From cross validation, the overall precision for the model was 80.2% with a R2 of 0.959. The best precision was for the AChEI MoA (93.5%) where 257 chemicals out of 275 were correctly classified. Model precision was poorest for the reactivity MoA (48.5%) where 48 out of 99 reactive chemicals were correctly classified. Narcosis represented the largest class within the MoA dataset and had a precision and reliability of 80.0%, reflecting the global precision across all of the MoAs. False negatives for narcosis most often fell into electron transport inhibition, neurotoxicity or reactivity MoAs. False negatives for all other MoAs were most often narcosis. A probabilistic sensitivity analysis was undertaken for each MoA to examine the sensitivity to individual and multiple descriptor findings. The results show that the Markov blanket of a structurally

  11. Modelling toxicity induced Neurological disorders in Zebrafish

    Directory of Open Access Journals (Sweden)

    Benin Joseph

    2012-03-01

    Full Text Available Neurological disorders have become more common and prevalent. Cellular pathology and behavioural symptoms in neurodegenerative diseases although connected are still a mystery to solve with no complete cure available yet. Central pathways in neurodegeneration involves impaired ubiquitin-proteasome machinery, autophagy and mitochondrial oxidative stress. In the case of neurodevlopmental disorders, environmental toxins and genetic factors are main causative agents. We aim to create a toxicity induced zebrafish model of neurological disease focussing on cognition, movement and hyperactivity disorders. Zebra fish embryos at 48 hr post fertilization were treated with different doses of lead, cholesterol and acetyl choline and by 7 days post fertilization pectoral fin movement, swimming behaviour and touch response were compromised in parallel with apoptosis identified in the brain by acridine orange fluorescent staining. A marked window is observed, therefore promising for a drug screening platform. Further characterization of pathology associated protein expression and specific behavioural studies could render this as a simple promising toxic model for preclinical drug screening.

  12. COMPUTER-BASED PREDICTION OF TOXICITY USING THE ELECTRON-CONFORMATIONAL METHOD. APPLICATION TO FRAGRANCE ALLERGENS AND OTHER ENVIRONMENTAL POLLUTANTS

    Directory of Open Access Journals (Sweden)

    Natalia N. Gorinchoy

    2012-06-01

    Full Text Available The electron-conformational (EC method is employed for the toxicophore (Tph identification and quantitative prediction of toxicity using the training set of 24 compounds that are considered as fragrance allergens. The values of a=LD50 in oral exposure of rats were chosen as a measure of toxicity. EC parameters are evaluated on the base of conformational analysis and ab initio electronic structure calculations (including solvent influence. The Tph consists of four sites which in this series of compounds are represented by three carbon and one oxygen atoms, but may be any other atoms that have the same electronic and geometric features within the tolerance limits. The regression model taking into consideration the Tph flexibility, anti-Tph shielding, and influence of out-of-Tph functional groups predicts well the experimental values of toxicity (R2 = 0.93 with a reasonable leaveone- out cross-validation.

  13. Predictive QSAR modelling of algal toxicity of ionic liquids and its interspecies correlation with Daphnia toxicity.

    Science.gov (United States)

    Roy, Kunal; Das, Rudra Narayan; Popelier, Paul L A

    2015-05-01

    Predictive toxicology using chemometric tools can be very useful in order to fill the data gaps for ionic liquids (ILs) with limited available experimental toxicity information, in view of their growing industrial uses. Though originally promoted as green chemicals, ILs have now been shown to possess considerable toxicity against different ecological endpoints. Against this background, quantitative structure-activity relationship (QSAR) models have been developed here for the toxicity of ILs against the green algae Scenedesmus vacuolatus using computed descriptors with definite physicochemical meaning. The final models emerged from E-state indices, extended topochemical atom (ETA) indices and quantum topological molecular similarity (QTMS) indices. The developed partial least squares models support the established mechanism of toxicity of ionic liquids in terms of a surfactant action of cations and chaotropic action of anions. The models have been developed within the guidelines of the Organization of Economic Co-operation and Development (OECD) for regulatory QSAR models, and they have been validated both internally and externally using multiple strategies and also tested for applicability domain. A preliminary attempt has also been made, for the first time, to develop interspecies quantitative toxicity-toxicity relationship (QTTR) models for the algal toxicity of ILs with Daphnia toxicity, which should be interesting while predicting toxicity of ILs for an endpoint when the data for the other are available.

  14. [Development of human embryonic stem cell model for toxicity evaluation].

    Science.gov (United States)

    Yu, Guang-yan; Cao, Tong; Ouyang, Hong-wei; Peng, Shuang-qing; Deng, Xu-liang; Li, Sheng-lin; Liu, He; Zou, Xiao-hui; Fu, Xin; Peng, Hui; Wang, Xiao-ying; Zhan, Yuan

    2013-02-18

    The current international standard for toxicity screening of biomedical devices and materials recommend the use of immortalized cell lines because of their homogeneous morphologies and infinite proliferation which provide good reproducibility for in vitro cytotoxicity screening. However, most of the widely used immortalized cell lines are derived from animals and may not be representative of normal human cell behavior in vivo, in particular in terms of the cytotoxic and genotoxic response. Therefore, It is vital to develop a model for toxicity evaluation. In our studies, two Chinese human embryonic stem cell (hESC) lines as toxicity model were established. hESC derived tissue/organ cell model for tissue/organ specific toxicity evaluation were developed. The efficiency and accuracy of using hESC model for cytoxicity, embryotoxicity and genotoxicity evaluation were confirmed. The results indicated that hESCs might be good tools for toxicity testing and biosafety evaluation in vitro.

  15. Evolution of electronic waste toxicity: Trends in innovation and regulation.

    Science.gov (United States)

    Chen, Mengjun; Ogunseitan, Oladele A; Wang, Jianbo; Chen, Haiyan; Wang, Bin; Chen, Shu

    2016-01-01

    Rapid innovation in printed circuit board, and the uncertainties surrounding quantification of the human and environmental health impacts of e-waste disposal have made it difficult to confirm the influence of evolving e-waste management strategies and regulatory policies on materials. To assess these influences, we analyzed hazardous chemicals in a market-representative set of Waste printed circuit boards (WPCBs, 1996-2010). We used standard leaching tests to characterize hazard potential and USEtox® to project impacts on human health and ecosystem. The results demonstrate that command-and-control regulations have had minimal impacts on WPCBs composition and toxicity risks; whereas technological innovation may have been influenced more by resource conservation, including a declining trend in the use of precious metals such as gold. WPCBs remain classified as hazardous under U.S. and California laws because of excessive toxic metals. Lead poses the most significant risk for cancers; zinc for non-cancer diseases; copper had the largest potential impact on ecosystem quality. Among organics, acenaphthylene, the largest risk for cancers; naphthalene for non-cancer diseases; pyrene has the highest potential for ecotoxicological impacts. These findings support the need for stronger enforcement of international policies and technology innovation to implement the strategy of design-for-the-environment and to encourage recovery, recycling, and reuse of WPCBs.

  16. AIR TOXICS MODELING RESEARCH PROGRAM: AN OVERVIEW

    Science.gov (United States)

    This product is a Microsoft Powerpoint slide presentation which was given at the joint EPA Region 3 - Mid-Atlantic Regional Air Management Association (MARAMA) Air Toxic Summit in Philadelphia, Pennsylvania held from October 18, 2005 through October 20, 2005. The slide presentat...

  17. Exploring BSEP Inhibition-Mediated Toxicity with a Mechanistic Model of Drug-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Jeffrey L Woodhead

    2014-11-01

    Full Text Available Inhibition of the bile salt export pump (BSEP has been linked to incidence of drug-induced liver injury (DILI, presumably by the accumulation of toxic bile acids in the liver. We have previously constructed and validated a model of bile acid disposition within DILIsym®, a mechanistic model of DILI. In this paper, we use DILIsym® to simulate the DILI response of the hepatotoxic BSEP inhibitors bosentan and CP-724,714 and the non-hepatotoxic BSEP inhibitor telmisartan in humans in order to explore whether we can predict that hepatotoxic BSEP inhibitors can cause bile acid accumulation to reach toxic levels. We also simulate bosentan in rats in order to illuminate potential reasons behind the lack of toxicity in rats compared to the toxicity observed in humans. DILIsym® predicts that bosentan, but not telmisartan, will cause mild hepatocellular ATP decline and serum ALT elevation in a simulated population of humans. The difference in hepatotoxic potential between bosentan and telmisartan is consistent with clinical observations. However, DILIsym® underpredicts the incidence of bosentan toxicity. DILIsym® also predicts that bosentan will not cause toxicity in a simulated population of rats, and that the difference between the response to bosentan in rats and in humans is primarily due to the less toxic bile acid pool in rats. Our simulations also suggest a potential synergistic role for bile acid accumulation and mitochondrial electron transport chain inhibition in producing the observed toxicity in CP-724,714, and suggest that CP-724,714 metabolites may also play a role in the observed toxicity. Our work also compares the impact of competitive and noncompetitive BSEP inhibition for CP-724,714 and demonstrates that noncompetitive inhibition leads to much greater bile acid accumulation and potential toxicity. Our research demonstrates the potential for mechanistic modeling to contribute to the understanding of how bile acid transport inhibitors

  18. Characterization of a developmental toxicity dose-response model.

    OpenAIRE

    Faustman, E M; Wellington, D G; Smith, W P; Kimmel, C A

    1989-01-01

    The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included ...

  19. Potential resource and toxicity impacts from metals in waste electronic devices.

    Science.gov (United States)

    Woo, Seung H; Lee, Dae Sung; Lim, Seong-Rin

    2016-04-01

    As a result of the continuous release of new electronic devices, existing electronic devices are quickly made obsolete and rapidly become electronic waste (e-waste). Because e-waste contains a variety of metals, information about those metals with the potential for substantial environmental impact should be provided to manufacturers, recyclers, and disposers to proactively reduce this impact. This study assesses the resource and toxicity (i.e., cancer, noncancer, and ecotoxicity) potentials of various heavy metals commonly found in e-waste from laptop computers, liquid-crystal display (LCD) monitors, LCD TVs, plasma TVs, color cathode ray tube (CRT) TVs, and cell phones and then evaluates such potentials using life cycle impact-based methods. Resource potentials derive primarily from Cu, Sb, Ag, and Pb. Toxicity potentials derive primarily from Pb, Ni, and Hg for cancer toxicity; from Pb, Hg, Zn, and As for noncancer toxicity; and from Cu, Pb, Hg, and Zn for ecotoxicity. Therefore, managing these heavy metals should be a high priority in the design, recycling, and disposal stages of electronic devices.

  20. Characterization of Airborne Particles in an Electronic Waste Recycling Facility and Their Toxicity Assessment

    Science.gov (United States)

    Improper disposal of electronic waste (e-waste) can lead to release of toxic chemicals into the environment and also may pose health risks. Thus, recycling e-waste, instead of landfilling, is considered to be an effective way to reduce pollutant release and exposure. However, lit...

  1. Ranking of aquatic toxicity of esters modelled by QSAR.

    Science.gov (United States)

    Papa, Ester; Battaini, Francesca; Gramatica, Paola

    2005-02-01

    Alternative methods like predictions based on Quantitative Structure-Activity Relationships (QSARs) are now accepted to fill data gaps and define priority lists for more expensive and time consuming assessments. A heterogeneous data set of 74 esters was studied for their aquatic toxicity, and available experimental toxicity data on algae, Daphnia and fish were used to develop statistically validated QSAR models, obtained using multiple linear regression (MLR) by the OLS (Ordinary Least Squares) method and GA-VSS (Variable Subset Selection by Genetic Algorithms) to predict missing values. An ESter Aquatic Toxicity INdex (ESATIN) was then obtained by combining, by PCA, experimental and predicted toxicity data, from which model outliers and esters highly influential due to their structure had been eliminated. Finally this integrated aquatic toxicity index, defined by the PC1 score, was modelled using only a few theoretical molecular descriptors. This last QSAR model, statistically validated for its predictive power, could be proposed as a preliminary evaluative method for screening/prioritising esters according to their integrated aquatic toxicity, just starting from their molecular structure.

  2. QSAR Models for Reproductive Toxicity and Endocrine Disruption Activity

    Directory of Open Access Journals (Sweden)

    Marjan Vračko

    2010-03-01

    Full Text Available Reproductive toxicity is an important regulatory endpoint, which is required in registration procedures of chemicals used for different purposes (for example pesticides. The in vivo tests are expensive, time consuming and require large numbers of animals, which must be sacrificed. Therefore an effort is ongoing to develop alternative In vitro and in silico methods to evaluate reproductive toxicity. In this review we describe some modeling approaches. In the first example we describe the CAESAR model for prediction of reproductive toxicity; the second example shows a classification model for endocrine disruption potential based on counter propagation artificial neural networks; the third example shows a modeling of relative binding affinity to rat estrogen receptor, and the fourth one shows a receptor dependent modeling experiment.

  3. Assaying environmental nickel toxicity using model nematodes.

    Science.gov (United States)

    Rudel, David; Douglas, Chandler D; Huffnagle, Ian M; Besser, John M; Ingersoll, Christopher G

    2013-01-01

    Although nickel exposure results in allergic reactions, respiratory conditions, and cancer in humans and rodents, the ramifications of excess nickel in the environment for animal and human health remain largely undescribed. Nickel and other cationic metals travel through waterways and bind to soils and sediments. To evaluate the potential toxic effects of nickel at environmental contaminant levels (8.9-7,600 µg Ni/g dry weight of sediment and 50-800 µg NiCl2/L of water), we conducted assays using two cosmopolitan nematodes, Caenorhabditis elegans and Pristionchus pacificus. We assayed the effects of both sediment-bound and aqueous nickel upon animal growth, developmental survival, lifespan, and fecundity. Uncontaminated sediments were collected from sites in the Midwestern United States and spiked with a range of nickel concentrations. We found that nickel-spiked sediment substantially impairs both survival from larval to adult stages and adult longevity in a concentration-dependent manner. Further, while aqueous nickel showed no adverse effects on either survivorship or longevity, we observed a significant decrease in fecundity, indicating that aqueous nickel could have a negative impact on nematode physiology. Intriguingly, C. elegans and P. pacificus exhibit similar, but not identical, responses to nickel exposure. Moreover, P. pacificus could be tested successfully in sediments inhospitable to C. elegans. Our results add to a growing body of literature documenting the impact of nickel on animal physiology, and suggest that environmental toxicological studies could gain an advantage by widening their repertoire of nematode species.

  4. Assaying environmental nickel toxicity using model nematodes.

    Directory of Open Access Journals (Sweden)

    David Rudel

    Full Text Available Although nickel exposure results in allergic reactions, respiratory conditions, and cancer in humans and rodents, the ramifications of excess nickel in the environment for animal and human health remain largely undescribed. Nickel and other cationic metals travel through waterways and bind to soils and sediments. To evaluate the potential toxic effects of nickel at environmental contaminant levels (8.9-7,600 µg Ni/g dry weight of sediment and 50-800 µg NiCl2/L of water, we conducted assays using two cosmopolitan nematodes, Caenorhabditis elegans and Pristionchus pacificus. We assayed the effects of both sediment-bound and aqueous nickel upon animal growth, developmental survival, lifespan, and fecundity. Uncontaminated sediments were collected from sites in the Midwestern United States and spiked with a range of nickel concentrations. We found that nickel-spiked sediment substantially impairs both survival from larval to adult stages and adult longevity in a concentration-dependent manner. Further, while aqueous nickel showed no adverse effects on either survivorship or longevity, we observed a significant decrease in fecundity, indicating that aqueous nickel could have a negative impact on nematode physiology. Intriguingly, C. elegans and P. pacificus exhibit similar, but not identical, responses to nickel exposure. Moreover, P. pacificus could be tested successfully in sediments inhospitable to C. elegans. Our results add to a growing body of literature documenting the impact of nickel on animal physiology, and suggest that environmental toxicological studies could gain an advantage by widening their repertoire of nematode species.

  5. Assaying environmental nickel toxicity using model nematodes

    Science.gov (United States)

    Rudel, David; Douglas, Chandler; Huffnagle, Ian; Besser, John M.; Ingersoll, Christopher G.

    2013-01-01

    Although nickel exposure results in allergic reactions, respiratory conditions, and cancer in humans and rodents, the ramifications of excess nickel in the environment for animal and human health remain largely undescribed. Nickel and other cationic metals travel through waterways and bind to soils and sediments. To evaluate the potential toxic effects of nickel at environmental contaminant levels (8.9-7,600 µg Ni/g dry weight of sediment and 50-800 µg NiCl2/L of water), we conducted assays using two cosmopolitan nematodes, Caenorhabditis elegans and Pristionchus pacificus. We assayed the effects of both sediment-bound and aqueous nickel upon animal growth, developmental survival, lifespan, and fecundity. Uncontaminated sediments were collected from sites in the Midwestern United States and spiked with a range of nickel concentrations. We found that nickel-spiked sediment substantially impairs both survival from larval to adult stages and adult longevity in a concentration-dependent manner. Further, while aqueous nickel showed no adverse effects on either survivorship or longevity, we observed a significant decrease in fecundity, indicating that aqueous nickel could have a negative impact on nematode physiology. Intriguingly, C. elegansand P. pacificus exhibit similar, but not identical, responses to nickel exposure. Moreover, P. pacificus could be tested successfully in sediments inhospitable to C. elegans. Our results add to a growing body of literature documenting the impact of nickel on animal physiology, and suggest that environmental toxicological studies could gain an advantage by widening their repertoire of nematode species.

  6. Assessment of toxicity potential of metallic elements in discarded electronics:A case study of mobile phones in China

    Institute of Scientific and Technical Information of China (English)

    B. Y. Wu; Y. C. Chan; A. Middendorf; X. Gu; H. W. Zhong

    2008-01-01

    The electronic waste (e-waste) is increasingly flooding Asia, especially China. E-waste could precipitate a growing volume of toxic input to the local environment if it was not handed properly. This makes the evaluation of environmental impact from electronics an essentially important task for the life cycle assessment (LCA) and the end-of-life management of electronic products. This study presented a quantitative investigation on the environmental performance of typical electronics. Two types of disposed mobile phones (MPs), as a representative of consumer electronics, were evaluated in terms of toxicity potential indicator (TPI) with an assumption of worst-case scenario. It is found that the composition and the percentages of constituents in MPs are similar. More than 20 metallic elements make up 35 wt.%-40 wt.% of the total weight, of which 12 elements are identified to be highly hazardous and 12 are less harmful. With the TPI technique, the environmental performance of Pb is attributed to be 20.8 mg-1. The total TPIs of metallic elements in the old and new type MP is 255,403 and 127,639 units, respectively, which is equivalent to the effect of releasing 6.14 and 12.28g Pb into the environment. The average TPI of the old and new type MP is 4.1 and 4.5 mg-1, respectively, which suggests a similar eco-efficiency per unit mass. The new model of MP is more eco-effective than the old one, which is not due to a reduction in the type of hazardous elements, but rather due to a significant miniaturization of the package with less weight. A single MP can have a considerable toxicity to the environment as referred to Pb, which suggests a major concern for the environmental impact of the total e-waste with a huge quantity and a heavy mass in China.

  7. Assessment of toxicity potential of metallic elements in discarded electronics: a case study of mobile phones in China.

    Science.gov (United States)

    Wu, B Y; Chan, Y C; Middendorf, A; Gu, X; Zhong, H W

    2008-01-01

    The electronic waste (e-waste) is increasingly flooding Asia, especially China. E-waste could precipitate a growing volume of toxic input to the local environment if it was not handed properly. This makes the evaluation of environmental impact from electronics an essentially important task for the life cycle assessment (LCA) and the end-of-life management of electronic products. This study presented a quantitative investigation on the environmental performance of typical electronics. Two types of disposed mobile phones (MPs), as a representative of consumer electronics, were evaluated in terms of toxicity potential indicator (TPI) with an assumption of worst-case scenario. It is found that the composition and the percentages of constituents in MPs are similar. More than 20 metallic elements make up 35 wt.%-40 wt.% of the total weight, of which 12 elements are identified to be highly hazardous and 12 are less harmful. With the TPI technique, the environmental performance of Pb is attributed to be 20.8 mg(-1). The total TPIs of metallic elements in the old and new type MP is 255,403 and 127,639 units, respectively, which is equivalent to the effect of releasing 6.14 and 12.28 g Pb into the environment. The average TPI of the old and new type MP is 4.1 and 4.5 mg(-1), respectively, which suggests a similar eco-efficiency per unit mass. The new model of MP is more eco-effective than the old one, which is not due to a reduction in the type of hazardous elements, but rather due to a significant miniaturization of the package with less weight. A single MP can have a considerable toxicity to the environment as referred to Pb, which suggests a major concern for the environmental impact of the total e-waste with a huge quantity and a heavy mass in China.

  8. Literature Review of (Q)SAR Modelling of Nanomaterial Toxicity.

    Science.gov (United States)

    Oksel, Ceyda; Ma, Cai Y; Liu, Jing J; Wilkins, Terry; Wang, Xue Z

    2017-01-01

    Despite the clear benefits that nanotechnology can bring to various sectors of industry, there are serious concerns about the potential health risks associated with engineered nanomaterials (ENMs), intensified by the limited understanding of what makes ENMs toxic and how to make them safe. As the use of ENMs for commercial purposes and the number of workers/end-users being exposed to these materials on a daily basis increases, the need for assessing the potential adverse effects of multifarious ENMs in a time- and cost-effective manner becomes more apparent. One strategy to alleviate the problem of testing a large number and variety of ENMs in terms of their toxicological properties is through the development of computational models that decode the relationships between the physicochemical features of ENMs and their toxicity. Such data-driven models can be used for hazard screening, early identification of potentially harmful ENMs and the toxicity-governing physicochemical properties, and accelerating the decision-making process by maximising the use of existing data. Moreover, these models can also support industrial, regulatory and public needs for designing inherently safer ENMs. This chapter is mainly concerned with the investigation of the applicability of (quantitative) structure-activity relationship ((Q)SAR) methods to modelling of ENMs' toxicity. It summarizes the key components required for successful application of data-driven toxicity prediction techniques to ENMs, the published studies in this field and the current limitations of this approach.

  9. Electron-plasmon model in the electron liquid theory

    Directory of Open Access Journals (Sweden)

    M.V.Vavrukh

    2005-01-01

    Full Text Available Here we propose an accurate approach to the description of the electron liquid model in the electron and plasmon terms. Our ideas in the present paper are close to the conception of the collective variables which was developed in the papers of Bohm and Pines. However we use another body of mathematics in the transition to the expanded space of variable particles and plasmons realized by the transition operator. It is evident that in the Random Phase Approximation (RPA, the model which consists of two interactive subsystems of electrons and plasmons is equivalent to the electron liquid model with Coulomb interaction.

  10. Whole acute toxicity removal from industrial and domestic effluents treated by electron beam radiation: emphasis on anionic surfactants

    Science.gov (United States)

    Moraes, M. C. F.; Romanelli, M. F.; Sena, H. C.; Pasqualini da Silva, G.; Sampa, M. H. O.; Borrely, S. I.

    2004-09-01

    Electron beam radiation has been applied to improve real industrial and domestic effluents received by Suzano wastewater treatment plant. Radiation efficacy has been evaluated as toxicity reduction, using two biological assays. Three sites were sampled and submitted for toxicity assays, anionic surfactant determination and electron beam irradiation. This paper shows the reduction of acute toxicity for both test-organisms, the marine bacteria Vibrio fischeri and the crustacean Daphnia similis. The raw toxic effluents exibitted from 0.6 ppm up to 11.67 ppm for anionic surfactant before being treated by the electron beam. Radiation processing resulted in reduction of the acute toxicity as well as surfactant removal. The final biological effluent was in general less toxic than other sites but the presence of anionic surfactants was evidenced.

  11. Cadmium toxicity to the cornea of pregnant rats: Electron microscopy and x-ray microanalysis

    Energy Technology Data Exchange (ETDEWEB)

    Yoshizuka, M.; McCarthy, K.J.; Kaye, G.I.; Fujimoto, S. (Univ. of Occupational and Environmental Health, School of Medicine, Kitakyushu (Japan))

    1990-05-01

    Cadmium toxicity to the cornea of pregnant rats was studied using the electron microscope and x-ray microanalyzer. In in-vivo experiments, severe corneal edema occurred in pregnant dams that received intraperitoneal injections of cadmium sulphate for 4 days during gestation, but not in nonpregnant rats. Prominent swelling of mitochondria and the occurrence of intra- and intercellular vacuoles in the corneal endothelium were observed only in pregnant dams. In in-vitro experiments, electron-dense deposits consisting of cadmium-oxine complexes were preferentially found in swollen mitochondria of the endothelial cells. Cadmium peaks were obtained from these deposits with x-ray microanalysis. These data suggest that the corneal edema observed after administration of cadmium may imply the disturbance of pump function and barrier function of the corneal endothelium due to the primary toxic effects of this metal on mitochondria.

  12. Mechanism of Anesthetic Toxicity: Metabolism, Reactive Oxygen Species, Oxidative Stress, and Electron Transfer

    OpenAIRE

    2011-01-01

    There is much literature on the toxic effects of anesthetics. This paper deals with both the volatiles and locals. Adverse effects appear to be multifaceted, with the focus on radicals, oxidative stress (OS), and electron transfer (ET). ET functionalities involved are quinone, iminoquinone, conjugated iminium, and nitrone. The non-ET routes involving radicals and OS apparently pertain to haloalkanes and ethers. Beneficial effects of antioxidants, evidently countering OS, are reported. Knowled...

  13. Degradation and toxicity assessment of sulfamethoxazole and chlortetracycline using electron beam, ozone and UV.

    Science.gov (United States)

    Kim, Tae-Hun; Kim, Sang Don; Kim, Hyun Young; Lim, Seung Joo; Lee, Myunjoo; Yu, Seungho

    2012-08-15

    Recently, the occurrence of antibiotics in sewage treatment plant effluent, as well as drinking water, has raised concern about their potential impacts on the environment and public health. Antibiotics are found in surface and ground waters, which indicate their ineffective removal by conventional wastewater treatment processes. Therefore, advanced oxidation processes (AOPs) have received considerable attention for the removal of antibiotics. This study was conducted to evaluate the degradation and mineralization of antibiotics (sulfamethoxazole and chlortetracycline) using an electron beam, ozone and UV, and the change of toxicity. Also, the electrical energy consumption based on the EE/O parameter (the electrical energy required per order of pollutants removal in 1 m(3) wastewater) was used to quantify the energy cost associated with the different AOPs (electron beam, ozone and UV) for the degradation of antibiotics. The results showed that an electron beam effective for the removals of both sulfamethoxazole and chlortetracycline in aqueous solutions. However, degradation of the target compounds by ozone and UV showed different trends. The oxidation efficiency of each organic compound was very dependent upon the AOP used. Algal toxicity was significantly reduced after each treatment. However, based on the electrical energy, the electron beam was more efficient than ozone and UV. Electron beam treatment could be an effective and safe method for the removal of antibiotic compounds.

  14. Combinatorial QSAR modeling of chemical toxicants tested against Tetrahymena pyriformis.

    Science.gov (United States)

    Zhu, Hao; Tropsha, Alexander; Fourches, Denis; Varnek, Alexandre; Papa, Ester; Gramatica, Paola; Oberg, Tomas; Dao, Phuong; Cherkasov, Artem; Tetko, Igor V

    2008-04-01

    Selecting most rigorous quantitative structure-activity relationship (QSAR) approaches is of great importance in the development of robust and predictive models of chemical toxicity. To address this issue in a systematic way, we have formed an international virtual collaboratory consisting of six independent groups with shared interests in computational chemical toxicology. We have compiled an aqueous toxicity data set containing 983 unique compounds tested in the same laboratory over a decade against Tetrahymena pyriformis. A modeling set including 644 compounds was selected randomly from the original set and distributed to all groups that used their own QSAR tools for model development. The remaining 339 compounds in the original set (external set I) as well as 110 additional compounds (external set II) published recently by the same laboratory (after this computational study was already in progress) were used as two independent validation sets to assess the external predictive power of individual models. In total, our virtual collaboratory has developed 15 different types of QSAR models of aquatic toxicity for the training set. The internal prediction accuracy for the modeling set ranged from 0.76 to 0.93 as measured by the leave-one-out cross-validation correlation coefficient ( Q abs2). The prediction accuracy for the external validation sets I and II ranged from 0.71 to 0.85 (linear regression coefficient R absI2) and from 0.38 to 0.83 (linear regression coefficient R absII2), respectively. The use of an applicability domain threshold implemented in most models generally improved the external prediction accuracy but at the same time led to a decrease in chemical space coverage. Finally, several consensus models were developed by averaging the predicted aquatic toxicity for every compound using all 15 models, with or without taking into account their respective applicability domains. We find that consensus models afford higher prediction accuracy for the

  15. Interspecies quantitative structure-toxicity-toxicity (QSTTR) relationship modeling of ionic liquids. Toxicity of ionic liquids to V. fischeri, D. magna and S. vacuolatus.

    Science.gov (United States)

    Das, Rudra Narayan; Roy, Kunal; Popelier, Paul L A

    2015-12-01

    Considering the increasing uses of ionic liquids (ILs) in various industrial processes and chemical engineering operations, a complete assessment of their hazardous profile is essential. In the absence of adequate experimental data, in silico modeling might be helpful in filling data gaps for the toxicity of ILs towards various ecological indicator organisms. Using the rationale of taxonomic relatedness, the development of predictive quantitative structure-toxicity-toxicity relationship (QSTTR) models allows predicting the toxicity of ILs to a particular species using available experimental toxicity data towards a different species. Such studies may employ, along with the available experimental toxicity data to a species, molecular structure features and physicochemical properties of chemicals as independent variables for prediction of the toxicity profile against another closely related species. A few such interspecies toxicity correlation models have been reported in the literature for diverse chemicals in general, but this approach has been rarely applied to the class of ionic liquids. The present study involves the use of IL toxicity data towards the bacteria Vibrio fischeri along with molecular structure derived information or computational descriptors like extended topochemical atom (ETA) indices, quantum topological molecular similarity (QTMS) descriptors and computed lipophilicity measure (logk0) for the interspecies exploration of the toxicity data towards green algae S. vacuolatus and crustacea Daphnia magna, separately. This modeling study has been performed in accordance with the OECD guidelines. Finally, predictions for a true external set have been performed to fill the data gap of toxicity towards daphnids and algae using the Vibrio toxicity data and molecular structure attributes.

  16. Modeling toxic compounds from nitric oxide emission measurements

    Science.gov (United States)

    Vallero, Daniel A.; Peirce, Jeffrey; Cho, Ki Don

    Determining the amount and rate of degradation of toxic pollutants in soil and groundwater is difficult and often requires invasive techniques, such as deploying extensive monitoring well networks. Even with these networks, degradation rates across entire systems cannot readily be extrapolated from the samples. When organic compounds are degraded by microbes, especially nitrifying bacteria, oxides or nitrogen (NO x) are released to the atmosphere. Thus, the flux of nitric oxide (NO) from the soil to the lower troposphere can be used to predict the rate at which organic compounds are degraded. By characterizing and applying biogenic and anthropogenic processes in soils the rates of degradation of organic compounds. Toluene was selected as a representative of toxic aromatic compounds, since it is inherently toxic, it is a substituted benzene compound and is listed as a hazardous air pollutant under Section 12 of the Clean Air Act Amendments of 1990. Measured toluene concentrations in soil, microbial population growth and NO fluxes in chamber studies were used to develop and parameterize a numerical model based on carbon and nitrogen cycling. These measurements, in turn, were used as indicators of bioremediation of air toxic (i.e. toluene) concentrations. The model found that chemical concentration, soil microbial abundance, and NO production can be directly related to the experimental results (significant at P hydrocarbons and oxides of nitrogen. As such, the model may be a tool for decision makers in ozone non-attainment areas.

  17. Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis

    Energy Technology Data Exchange (ETDEWEB)

    Feussner, J.R.; Shelburne, J.D.; Bredehoeft, S.; Cohen, H.J.

    1979-05-01

    A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-proble analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements.

  18. The chemical exposure toxicity space (CETS) model: Displaying exposure time, aqueous and organic concentration, activity, and onset of toxicity

    Science.gov (United States)

    Mackay, Donald; Parnis, J. Mark; McCarty, Lynn S.; Arnot, Jon A.; Powell, David E.

    2016-01-01

    Abstract A 1‐compartment toxicokinetic model is used to characterize the chemical exposure toxicity space (CETS), providing a novel graphic tool that can aid in the design of aquatic toxicity tests for fish and for interpreting their results. The graph depicts the solution to the differential equation describing the uptake kinetics of a chemical by a modeled fish under conventional bioassay conditions. The model relates the exposure concentration in the water to a dimensionless time and the onset of toxicity as determined by an estimated or assumed critical body residue or incipient lethal aqueous concentration. These concentration graphs are specific to each chemical and exposure and organism parameters and clearly demonstrate differences in toxicity between chemicals and how factors such as hydrophobicity influence the toxic endpoint. The CETS plots can also be used to assess bioconcentration test conditions to ensure that concentrations are well below toxic levels. Illustrative applications are presented using a recent set of high‐quality toxicity data. Conversion of concentrations to chemical activities in the plots enables results for different baseline toxicants to be superimposed. For chemicals that have different modes of toxic action, the increased toxicity then becomes apparent. Implications for design and interpretation of aquatic toxicity tests are discussed. The model, and pictorial visualization of the time‐course of aquatic toxicity tests, may contribute to improvements in test design, implementation, and interpretation, and to reduced animal usage. Environ Toxicol Chem 2017;36:1389–1396. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC. PMID:27801500

  19. Modeling of power electronic systems with EMTP

    Science.gov (United States)

    Tam, Kwa-Sur; Dravid, Narayan V.

    1989-01-01

    In view of the potential impact of power electronics on power systems, there is need for a computer modeling/analysis tool to perform simulation studies on power systems with power electronic components as well as to educate engineering students about such systems. The modeling of the major power electronic components of the NASA Space Station Freedom Electric Power System is described along with ElectroMagnetic Transients Program (EMTP) and it is demonstrated that EMTP can serve as a very useful tool for teaching, design, analysis, and research in the area of power systems with power electronic components. EMTP modeling of power electronic circuits is described and simulation results are presented.

  20. Genetic variance of tolerance and the toxicant threshold model.

    Science.gov (United States)

    Tanaka, Yoshinari; Mano, Hiroyuki; Tatsuta, Haruki

    2012-04-01

    A statistical genetics method is presented for estimating the genetic variance (heritability) of tolerance to pollutants on the basis of a standard acute toxicity test conducted on several isofemale lines of cladoceran species. To analyze the genetic variance of tolerance in the case when the response is measured as a few discrete states (quantal endpoints), the authors attempted to apply the threshold character model in quantitative genetics to the threshold model separately developed in ecotoxicology. The integrated threshold model (toxicant threshold model) assumes that the response of a particular individual occurs at a threshold toxicant concentration and that the individual tolerance characterized by the individual's threshold value is determined by genetic and environmental factors. As a case study, the heritability of tolerance to p-nonylphenol in the cladoceran species Daphnia galeata was estimated by using the maximum likelihood method and nested analysis of variance (ANOVA). Broad-sense heritability was estimated to be 0.199 ± 0.112 by the maximum likelihood method and 0.184 ± 0.089 by ANOVA; both results implied that the species examined had the potential to acquire tolerance to this substance by evolutionary change.

  1. Reactor modeling in heterogeneous photocatalysis: toxicity and biodegradability assessment.

    Science.gov (United States)

    Satuf, M L; José, S; Paggi, J C; Brandi, R J; Cassano, A E; Alfano, O M

    2010-01-01

    Photocatalysis employing titanium dioxide is a useful method to degrade a wide variety of organic and inorganic pollutants from water and air. However, the application of this advanced oxidation process at industrial scale requires the development of mathematical models to design and scale-up photocatalytic reactors. In the present work, intrinsic kinetic expressions previously obtained in a laboratory reactor are employed to predict the performance of a bench scale reactor of different configuration and operating conditions. 4-Chlorophenol was chosen as the model pollutant. The toxicity and biodegradability of the irradiated mixture in the bench photoreactor was also assessed. Good agreement was found between simulation and experimental data. The root mean square error of the estimations was 9.9%. The photocatalytic process clearly enhances the biodegradability of the reacting mixture, and the initial toxicity of the pollutant was significantly reduced by the treatment.

  2. A Structural Modelling Study on Marine Sediments Toxicity

    Directory of Open Access Journals (Sweden)

    Sorana D. Bolboacă

    2008-06-01

    Full Text Available Quantitative structure-activity relationship models were obtained by applying the Molecular Descriptor Family approach to eight ordnance compounds with different toxicity on five marine species (arbacia punctulata, dinophilus gyrociliatus, sciaenops ocellatus, opossum shrimp, and ulva fasciata. The selection of the best among molecular descriptors generated and calculated from the ordnance compounds structures lead to accurate monovariate models. The resulting models obtained for six endpoints proved to be accurate in estimation (the squared correlation coefficient varied from 0.8186 to 0.9997 and prediction (the correlation coefficient obtained in leave-one-out analysis varied from 0.7263 to 0.9984.

  3. Adaptive modelling of structured molecular representations for toxicity prediction

    Science.gov (United States)

    Bertinetto, Carlo; Duce, Celia; Micheli, Alessio; Solaro, Roberto; Tiné, Maria Rosaria

    2012-12-01

    We investigated the possibility of modelling structure-toxicity relationships by direct treatment of the molecular structure (without using descriptors) through an adaptive model able to retain the appropriate structural information. With respect to traditional descriptor-based approaches, this provides a more general and flexible way to tackle prediction problems that is particularly suitable when little or no background knowledge is available. Our method employs a tree-structured molecular representation, which is processed by a recursive neural network (RNN). To explore the realization of RNN modelling in toxicological problems, we employed a data set containing growth impairment concentrations (IGC50) for Tetrahymena pyriformis.

  4. Characterization of Size-Fractionated Airborne Particles Inside an Electronic Waste Recycling Facility and Acute Toxicity Testing in Mice.

    Science.gov (United States)

    Kim, Yong Ho; Wyrzykowska-Ceradini, Barbara; Touati, Abderrahmane; Krantz, Q Todd; Dye, Janice A; Linak, William P; Gullett, Brian; Gilmour, M Ian

    2015-10-06

    Disposal of electronic waste (e-waste) in landfills, incinerators, or at rudimentary recycling sites can lead to the release of toxic chemicals into the environment and increased health risks. Developing e-waste recycling technologies at commercial facilities can reduce the release of toxic chemicals and efficiently recover valuable materials. While these e-waste operations represent a vast improvement over previous approaches, little is known about environmental releases, workplace exposures, and potential health impacts. In this study, airborne particulate matter (PM) was measured at various locations within a modern U.S.-based e-waste recycling facility that utilized mechanical processing. In addition, composite size fractionated PM (coarse, fine and ultrafine) samples were collected, extracted, chemically analyzed, and given by oropharyngeal aspiration to mice or cultured with lung slices for lung toxicity tests. Indoor total PM concentrations measured during the study ranged from 220 to 1200 μg/m(3). In general, the coarse PM (2.5-10 μm) was 3-4 times more abundant than fine/ultrafine PM (10 times) observed for Zn and Sb, modest enrichments (>5 times) for Cu and Sr, and minor enrichments (>2 times) for Cr, Cd, Mn, Ca, Fe, and Ba. Negligible enrichment (<2 times) or depletion (<1 time) were observed for Al, Mg, Ti, Si, and V. The coarse PM fraction elicited significant pro-inflammatory responses in the mouse lung at 24 h postexposure compared to the fine and ultrafine PM, and similar toxicity outcomes were observed in the lung slice model. We conclude that exposure to coarse PM from the facility caused substantial inflammation in the mouse lung and enrichment of these metals compared to levels normally present in the ambient PM could be of potential health concern.

  5. Boltzmann-Electron Model in Aleph.

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, Thomas Patrick; Hooper, Russell

    2014-11-01

    We apply the Boltzmann-electron model in the electrostatic, particle-in-cell, finite- element code Aleph to a plasma sheath. By assuming a Boltzmann energy distribution for the electrons, the model eliminates the need to resolve the electron plasma fre- quency, and avoids the numerical "grid instability" that can cause unphysical heating of electrons. This allows much larger timesteps to be used than with kinetic electrons. Ions are treated with the standard PIC algorithm. The Boltzmann-electron model re- quires solution of a nonlinear Poisson equation, for which we use an iterative Newton solver (NOX) from the Trilinos Project. Results for the spatial variation of density and voltage in the plasma sheath agree well with an analytic model

  6. Toxicity of food-relevant nanoparticles in intestinal epithelial models

    Science.gov (United States)

    McCracken, Christie

    Nanoparticles are increasingly being incorporated into common consumer products, including in foods and food packaging, for their unique properties at the nanoscale. Food-grade silica and titania are used as anti-caking and whitening agents, respectively, and these particle size distributions are composed of approximately one-third nanoparticles. Zinc oxide and silver nanoparticles can be used for their antimicrobial properties. However, little is known about the interactions of nanoparticles in the body upon ingestion. This study was performed to investigate the role of nanoparticle characteristics including surface chemistry, dissolution, and material type on toxicity to the intestinal epithelium. Only mild acute toxicity of zinc oxide nanoparticles was observed after 24-hour treatment of intestinal epithelial C2BBe1 cells based on the results of toxicity assays measuring necrosis, apoptosis, membrane damage, and mitochondrial activity. Silica and titanium dioxide nanoparticles were not observed to be toxic although all nanoparticles were internalized by cells. In vitro digestion of nanoparticles in solutions representing the stomach and intestines prior to treatment of cells did not alter nanoparticle toxicity. Long-term repeated treatment of cells weekly for 24 hours with nanoparticles did not change nanoparticle cytotoxicity or the growth rate of the treated cell populations. Thus, silica, titanium dioxide, and zinc oxide nanoparticles were found to induce little toxicity in intestinal epithelial cells. Fluorescent silica nanoparticles were synthesized as a model for silica used in foods that could be tracked in vitro and in vivo. To maintain an exterior of pure silica, a silica shell was hydrolyzed around a core particle of quantum dots or a fluorescent dye electrostatically associated with a commercial silica particle. The quantum dots used were optimized from a previously reported microwave quantum dot synthesis to a quantum yield of 40%. Characterization

  7. Rotational nuclear models and electron scattering

    Energy Technology Data Exchange (ETDEWEB)

    Moya de Guerra, E.

    1986-05-01

    A review is made of the basic formalism involved in the application of nuclear rotational models to the problem of electron scattering from axially symmetric deformed nuclei. Emphasis is made on the use of electron scattering to extract information on the nature of the collective rotational model. In this respect, the interest of using polarized beam and target is discussed with the help of illustrative examples. Concerning the nuclear structure four rotational models are considered: Two microscopic models, namely the Projected Hartree-Fock (PHF) and cranking models; and two collective models, the rigid rotor and the irrotational flow models. The problem of current conservation within the different models is also discussed.

  8. Baseline toxicity and ion-trapping models to describe the pH-dependence of bacterial toxicity of pharmaceuticals.

    Science.gov (United States)

    Baumer, Andreas; Bittermann, Kai; Klüver, Nils; Escher, Beate I

    2017-07-19

    In numerous studies on the toxicity of ionisable organic chemicals, it has been shown that the toxicity was typically higher, when larger fractions of the neutral species were present. This observation was explained in some cases by slower uptake of charged species. In other cases it was suggested that the neutral species has intrinsically higher toxicity than the charged species or is alone responsible for the toxicity. However, even permanently charged and organic chemicals with multiple acid and base functional groups and zwitterions are toxic. We set out to reconcile the divergent views and to compare the various existing models for describing the pH-dependence of toxicity with the goal to derive one model that is valid independent of the type and number of charges on the molecule. To achieve this goal we measured the cytotoxicity of 18 acidic, 15 basic and 9 multiprotic/zwitterionic pharmaceuticals at pH 5.5 to pH 9 with the bioluminescence inhibition test using Aliivibrio fischeri (Microtox assay). This assay is useful for an evaluation of various models to describe pH-dependent toxicity because the majority of chemicals act as baseline toxicants in this 30 min cytotoxicity assay. Therefore baseline toxicity with constant membrane concentrations of the sum of all chemical species of approximately 200 mmol kglip(-1) served for the validation of the suitability of the various tested models. We confirmed that most tested pharmaceuticals acted as baseline toxicants in this assay at all examined pH values, when toxicity was modeled with a mixture model of concentration addition between the neutral species and all charged species. An ion trapping model, that assumes that the membrane permeability of charged species is kinetically limited, improved model predictions for some pharmaceuticals and pH values. However, neither unhindered uptake nor no uptake of the charged species were ideal models; the reality lies presumably between the two limiting cases with a slower

  9. Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs

    Science.gov (United States)

    Gupta, Himanshu R; Patil, Yogesh; Singh, Dipty

    2016-01-01

    Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used

  10. High content analysis of an in vitro model for metabolic toxicity: results with the model toxicants 4-aminophenol and cyclophosphamide.

    Science.gov (United States)

    Cole, Stephanie D; Madren-Whalley, Janna S; Li, Albert P; Dorsey, Russell; Salem, Harry

    2014-12-01

    In vitro models that accurately and rapidly assess hepatotoxicity and the effects of hepatic metabolism on nonliver cell types are needed by the U.S. Department of Defense and the pharmaceutical industry to screen compound libraries. Here, we report the first use of high content analysis on the Integrated Discrete Multiple Organ Co-Culture (IdMOC) system, a high-throughput method for such studies. We cultured 3T3-L1 cells in the presence and absence of primary human hepatocytes, and exposed the cultures to 4-aminophenol and cyclophosphamide, model toxicants that are respectively detoxified and activated by the liver. Following staining with calcein-AM, ethidium homodimer-1, and Hoechst 33342, high content analysis of the cultures revealed four cytotoxic endpoints: fluorescence intensities of calcein-AM and ethidium homodimer-1, nuclear area, and cell density. Using these endpoints, we observed that the cytotoxicity of 4-aminophenol in 3T3-L1 cells in co-culture was less than that observed for 3T3-L1 monocultures, consistent with the known detoxification of 4-aminophenol by hepatocytes. Conversely, cyclophosphamide cytotoxicity for 3T3-L1 cells was enhanced by co-culturing with hepatocytes, consistent with the known metabolic activation of this toxicant. The use of IdMOC plates combined with high content analysis is therefore a multi-endpoint, high-throughput capability for measuring the effects of metabolism on toxicity.

  11. PABPN1 suppresses TDP-43 toxicity in ALS disease models

    Science.gov (United States)

    Chou, Ching-Chieh; Alexeeva, Olga M.; Yamada, Shizuka; Pribadi, Amy; Zhang, Yi; Mo, Bi; Williams, Kathryn R.; Zarnescu, Daniela C.; Rossoll, Wilfried

    2015-01-01

    TAR DNA-binding protein 43 (TDP-43) is a major disease protein in amyotrophic lateral sclerosis (ALS) and related neurodegenerative diseases. Both the cytoplasmic accumulation of toxic ubiquitinated and hyperphosphorylated TDP-43 fragments and the loss of normal TDP-43 from the nucleus may contribute to the disease progression by impairing normal RNA and protein homeostasis. Therefore, both the removal of pathological protein and the rescue of TDP-43 mislocalization may be critical for halting or reversing TDP-43 proteinopathies. Here, we report poly(A)-binding protein nuclear 1 (PABPN1) as a novel TDP-43 interaction partner that acts as a potent suppressor of TDP-43 toxicity. Overexpression of full-length PABPN1 but not a truncated version lacking the nuclear localization signal protects from pathogenic TDP-43-mediated toxicity, promotes the degradation of pathological TDP-43 and restores normal solubility and nuclear localization of endogenous TDP-43. Reduced levels of PABPN1 enhances the phenotypes in several cell culture and Drosophila models of ALS and results in the cytoplasmic mislocalization of TDP-43. Moreover, PABPN1 rescues the dysregulated stress granule (SG) dynamics and facilitates the removal of persistent SGs in TDP-43-mediated disease conditions. These findings demonstrate a role for PABPN1 in rescuing several cytopathological features of TDP-43 proteinopathy by increasing the turnover of pathologic proteins. PMID:26130692

  12. Electronic Education System Model-2

    Science.gov (United States)

    Güllü, Fatih; Kuusik, Rein; Laanpere, Mart

    2015-01-01

    In this study we presented new EES Model-2 extended from EES model for more productive implementation in e-learning process design and modelling in higher education. The most updates were related to uppermost instructional layer. We updated learning processes object of the layer for adaptation of educational process for young and old people,…

  13. POPULATION EXPOSURE AND DOSE MODEL FOR AIR TOXICS: A BENZENE CASE STUDY

    Science.gov (United States)

    The EPA's National Exposure Research Laboratory (NERL) is developing a human exposure and dose model called the Stochastic Human Exposure and Dose Simulation model for Air Toxics (SHEDS-AirToxics) to characterize population exposure to air toxics in support of the National Air ...

  14. MOAtox: A Comprehensive Mode of Action and Acute Aquatic Toxicity Database for Predictive Model Development

    Science.gov (United States)

    tThe mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity andas an alternative to chemical class-based predictive toxicity modeling. However, the development ofquantitative structure activity relationship (QSAR) and other models has been limite...

  15. 40 CFR Table 4 to Subpart Dddd of... - Model Rule-Toxic Equivalency Factors

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Model Rule-Toxic Equivalency Factors 4... or Before November 30, 1999 Pt. 60, Subpt. DDDD, Table 4 Table 4 to Subpart DDDD of Part 60—Model Rule—Toxic Equivalency Factors Dioxin/furan congener Toxic equivalency factor 2,3,7,8-tetrachlorinated...

  16. Electronic noise modeling in statistical iterative reconstruction.

    Science.gov (United States)

    Xu, Jingyan; Tsui, Benjamin M W

    2009-06-01

    We consider electronic noise modeling in tomographic image reconstruction when the measured signal is the sum of a Gaussian distributed electronic noise component and another random variable whose log-likelihood function satisfies a certain linearity condition. Examples of such likelihood functions include the Poisson distribution and an exponential dispersion (ED) model that can approximate the signal statistics in integration mode X-ray detectors. We formulate the image reconstruction problem as a maximum-likelihood estimation problem. Using an expectation-maximization approach, we demonstrate that a reconstruction algorithm can be obtained following a simple substitution rule from the one previously derived without electronic noise considerations. To illustrate the applicability of the substitution rule, we present examples of a fully iterative reconstruction algorithm and a sinogram smoothing algorithm both in transmission CT reconstruction when the measured signal contains additive electronic noise. Our simulation studies show the potential usefulness of accurate electronic noise modeling in low-dose CT applications.

  17. Toxicity reduction for pharmaceuticals mixture in water by electron beam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Boiani, Nathalia Fonseca; Tominaga, Flavio Kiyoshi; Borrely, Sueli Ivone, E-mail: flavio_tominaga@hotmail.com, E-mail: sborrely@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    The incorrect disposal of products is committing the environment quality once the aquatic environment is the main vehicle for dispersion of pollutants. Among the highlighted contaminants there are the pharmaceuticals, which are also released to the aquatic environment through the domestic sewage, hospitals and effluents. The monitoring of these pharmaceuticals in the environment has grown, showing many of them as persistent pollutants. Pharmaceuticals from different therapeutic classes have been detected in domestic sewage, surface water and groundwater around the world. Several studies evidenced Fluoxetine Hydrochloride residues in waters. Another important product is the Propranolol, used for heart disease treatments as far as fluoxetine is applied for treating mental diseases. The objective of this study was to apply the radiation processing for the abatement of pollutant in waters. Electron beam accelerator was used during irradiation of the mixture (Propranolol + Fluoxetine Hydrochloride) in aqueous solution. Acute toxicity assays were carried out for Vibrio fischeri marine bacterium, 15 minutes exposure. The results showed that irradiation (2.5kGy and 5.0kGy) enhanced the average effective concentration of the mixture, which means reduction of toxicity (56.34%, 55.70% respectively). Inverse effect was obtained with 7.5 kGy and 10 kGy. (author)

  18. Identification of toxicants in cinnamon-flavored electronic cigarette refill fluids.

    Science.gov (United States)

    Behar, R Z; Davis, B; Wang, Y; Bahl, V; Lin, S; Talbot, P

    2014-03-01

    In a prior study on electronic cigarette (EC) refill fluids, Cinnamon Ceylon was the most cytotoxic of 36 products tested. The purpose of the current study was to determine if high cytotoxicity is a general feature of cinnamon-flavored EC refill fluids and to identify the toxicant(s) in Cinnamon Ceylon. Eight cinnamon-flavored refill fluids, which were screened using the MTT assay, varied in their cytotoxicity with most being cytotoxic. Human embryonic stem cells were generally more sensitive than human adult pulmonary fibroblasts. Most products were highly volatile and produced vapors that impaired survival of cells in adjacent wells. Cinnamaldehyde (CAD), 2-methoxycinnamaldehyde (2MOCA), dipropylene glycol, and vanillin were identified in the cinnamon-flavored refill fluids using gas chromatography–mass spectrometry and high-pressure liquid chromatography (HPLC). When authentic standards of each chemical were tested using the MTT assay, only CAD and 2MOCA were highly cytotoxic. The amount of each chemical in the refill fluids was quantified using HPLC, and cytotoxicity correlated with the amount of CAD/product. Duplicate bottles of the same product were similar, but varied in their concentrations of 2MOCA. These data show that the cinnamon flavorings in refill fluids are linked to cytotoxicity, which could adversely affect EC users.

  19. Status of Galileo interim radiation electron model

    Science.gov (United States)

    Garrett, H. B.; Jun, I.; Ratliff, J. M.; Evans, R. W.; Clough, G. A.; McEntire, R. W.

    2003-01-01

    Measurements of the high energy, omni-directional electron environment by the Galileo spacecraft Energetic Particle Detector (EDP) were used to develop a new model of Jupiter's trapped electron radiation in the jovian equatorial plane for the range 8 to 16 Jupiter radii.

  20. Modeling microwave/electron-cloud interaction

    CERN Document Server

    Mattes, M; Zimmermann, F

    2013-01-01

    Starting from the separate codes BI-RME and ECLOUD or PyECLOUD, we are developing a novel joint simulation tool, which models the combined effect of a charged particle beam and of microwaves on an electron cloud. Possible applications include the degradation of microwave transmission in tele-communication satellites by electron clouds; the microwave-transmission tecchniques being used in particle accelerators for the purpose of electroncloud diagnostics; the microwave emission by the electron cloud itself in the presence of a magnetic field; and the possible suppression of electron-cloud formation in an accelerator by injecting microwaves of suitable amplitude and frequency. A few early simulation results are presented.

  1. From basic physics to mechanisms of toxicity: the ``liquid drop'' approach applied to develop predictive classification models for toxicity of metal oxide nanoparticles

    Science.gov (United States)

    Sizochenko, Natalia; Rasulev, Bakhtiyor; Gajewicz, Agnieszka; Kuz'min, Victor; Puzyn, Tomasz; Leszczynski, Jerzy

    2014-10-01

    established. A new approach for representation of nanoparticles' structure is presented. For description of the supramolecular structure of nanoparticles the ``liquid drop'' model was applied. It is expected that a novel, proposed approach could be of general use for predictions related to nanomaterials. In addition, in our study fragmental simplex descriptors and several ligand-metal binding characteristics were calculated. The developed nano-QSAR models were validated and reliably predict the toxicity of all studied metal oxide nanoparticles. Based on the comparative analysis of contributed properties in both models the LDM-based descriptors were revealed to have an almost similar level of contribution to toxicity in both cases, while other parameters (van der Waals interactions, electronegativity and metal-ligand binding characteristics) have unequal contribution levels. In addition, the models developed here suggest different mechanisms of nanotoxicity for these two types of cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03487b

  2. Calvin cycle mutants of photoheterotrophic purple nonsulfur bacteria fail to grow due to an electron imbalance rather than toxic metabolite accumulation.

    Science.gov (United States)

    Gordon, Gina C; McKinlay, James B

    2014-03-01

    Purple nonsulfur bacteria grow photoheterotrophically by using light for energy and organic compounds for carbon and electrons. Disrupting the activity of the CO2-fixing Calvin cycle enzyme, ribulose 1,5-bisphosphate carboxylase (RubisCO), prevents photoheterotrophic growth unless an electron acceptor is provided or if cells can dispose of electrons as H2. Such observations led to the long-standing model wherein the Calvin cycle is necessary during photoheterotrophic growth to maintain a pool of oxidized electron carriers. This model was recently challenged with an alternative model wherein disrupting RubisCO activity prevents photoheterotrophic growth due to the accumulation of toxic ribulose-1,5-bisphosphate (RuBP) (D. Wang, Y. Zhang, E. L. Pohlmann, J. Li, and G. P. Roberts, J. Bacteriol. 193:3293-3303, 2011, http://dx.doi.org/10.1128/JB.00265-11). Here, we confirm that RuBP accumulation can impede the growth of Rhodospirillum rubrum (Rs. rubrum) and Rhodopseudomonas palustris (Rp. palustris) RubisCO-deficient (ΔRubisCO) mutants under conditions where electron carrier oxidation is coupled to H2 production. However, we also demonstrate that Rs. rubrum and Rp. palustris Calvin cycle phosphoribulokinase mutants that cannot produce RuBP cannot grow photoheterotrophically on succinate unless an electron acceptor is provided or H2 production is permitted. Thus, the Calvin cycle is still needed to oxidize electron carriers even in the absence of toxic RuBP. Surprisingly, Calvin cycle mutants of Rs. rubrum, but not of Rp. palustris, grew photoheterotrophically on malate without electron acceptors or H2 production. The mechanism by which Rs. rubrum grows under these conditions remains to be elucidated.

  3. Animal models of peripheral neuropathy due to environmental toxicants.

    Science.gov (United States)

    Rao, Deepa B; Jortner, Bernard S; Sills, Robert C

    2014-01-01

    Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy--namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves.

  4. Multidisciplinary Modelling Tools for Power Electronic Circuits

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad

    This thesis presents multidisciplinary modelling techniques in a Design For Reliability (DFR) approach for power electronic circuits. With increasing penetration of renewable energy systems, the demand for reliable power conversion systems is becoming critical. Since a large part of electricity...... in reliability assessment of power modules, a three-dimensional lumped thermal network is proposed to be used for fast, accurate and detailed temperature estimation of power module in dynamic operation and different boundary conditions. Since an important issue in the reliability of power electronics...... are generic and valid to be used in circuit simulators or any programing software. These models are important building blocks for the reliable design process or performance assessment of power electronic circuits. The models can save time and cost in power electronics packaging and power converter to evaluate...

  5. Toxicity of imine-iminium dyes and pigments: electron transfer, radicals, oxidative stress and other physiological effects.

    Science.gov (United States)

    Kovacic, Peter; Somanathan, Ratnasamy

    2014-08-01

    Although conjugation is well known as an important contributor to color, there is scant recognition concerning involvement of imine and iminium functions in the physiological effects of this class of dyes and pigments. The group includes the dyes methylene blue, rhodamine, malachite green, fuchsin, crystal violet, auramine and cyanins, in addition to the pigments consisting of pyocyanine, phthalocyanine and pheophytin. The physiological effects consist of both toxicity and beneficial aspects. The unifying theme of electron transfer-reactive oxygen species-oxidative stress is used as the rationale in both cases. Toxicity is frequently prevented or alleviated by antioxidants. The apparent dichotomy of methylene blue action as both oxidant and antioxidant is rationalized based on similar previous cases. This mechanistic approach may have practical benefit. This review is important in conveying, for the first time, a unifying mechanism for toxicity based on electron transfer-reactive oxygen species-oxidative stress arising from imine-iminium.

  6. Evaluation of Common Use Brominated Flame Retardant (BFR Toxicity Using a Zebrafish Embryo Model

    Directory of Open Access Journals (Sweden)

    Crystal Y. Usenko

    2016-09-01

    Full Text Available Brominated flame retardants (BFRs are used to reduce the flammability of plastics, textiles, and electronics. BFRs vary in their chemical properties and structures, and it is expected that these differences alter their biological interactions and toxicity. Zebrafish were used as the model organism for assessing the toxicity of nine structurally-diverse BFRs. In addition to monitoring for overt toxicity, the rate of spontaneous movement, and acetylcholinesterase and glutathione-S-transferase (GST activities were assessed following exposure. The toxicities of BFRs tested can be ranked by LC50 as tetrabromobisphenol A (TBBPA < 4,4′-isopropylidenebis[2-(2,6-dibromophenoxylethanol] (TBBPA-OHEE < Pentabromochlorocyclohexane (PBCH < 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB < hexabromocyclododecane (HBCD < hexabromobenzene (HBB < Tetrabromophthalic anhydride (PHT4. No adverse effect was observed in di(2-ethylhexyl tetrabromophthalate (TBPH or dibromoneopentyl glycol (DBNPG-treated embryos. The rate of spontaneous movement was decreased in a concentration-dependent manner following exposure to four of the nine compounds. GST activity was elevated following treatment with PBCH, TBBPA, HBCD, and HBB. The results indicate that exposure to several BFRs may activate an antioxidant response and alter behavior during early development. Some of the BFRs, such as TBBPA and TBBPA-OHEE, induced adverse effects at concentrations lower than chemicals that are currently banned. These results suggest that zebrafish are sensitive to exposure to BFRs and can be used as a comparative screening model, as well as to determine alterations in behavior following exposure and probe mechanisms of action.

  7. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

    Directory of Open Access Journals (Sweden)

    Rahim Dad Brohi

    2017-09-01

    Full Text Available In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

  8. Toxicity of copper and cadmium in combinations to Duckweed analyzed by the biotic ligand model.

    Science.gov (United States)

    Hatano, Ayumi; Shoji, Ryo

    2008-06-01

    The biotic ligand model (BLM) of acute toxicity to aquatic organisms is based on the concept that metals binding onto biotic ligand may cause toxic effect on the organism. The BLM can take into incorporation between metal speciation and the protective effects of competing cations account. The demonstrated BLM can provide a good estimation of the amount of single metal effect under various conditions such as pH, coexistence of other non toxic cations. However, toxic metals are often found as mixture in nature. This study estimated combined toxicity of Cu and Cd examined by growth inhibition of Duckweed (Lemna paucicostata) by using single toxicity data as toxic unit (TU) derived by three types of model, BLM and two conventional models, free ion activity model (FIAM), and total metal concentration model. According to our results, single toxicity data derived by the BLM can estimate combined toxicity described as a function of TU. Particularly under the high level of heavy metals stress, BLM clearly predicted toxicity of heavy metals compared with other two models. According to numeric correlation (R(2), root mean square error), the order is BLM (R=0.83, RMSE=13.5)> total metal concentration model (R=0.41, RMSE=24.9)> FIAM (R=0.36, RMSE=26.1).

  9. QSAR models for reproductive toxicity and endocrine disruption in regulatory use - a preliminary investigation

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Niemela, J.R.; Wedebye, Eva Bay

    2008-01-01

    the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data...... for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption....

  10. Teaching Chemistry with Electron Density Models

    Science.gov (United States)

    Shusterman, Gwendolyn P.; Shusterman, Alan J.

    1997-07-01

    Linus Pauling once said that a topic must satisfy two criteria before it can be taught to students. First, students must be able to assimilate the topic within a reasonable amount of time. Second, the topic must be relevant to the educational needs and interests of the students. Unfortunately, the standard general chemistry textbook presentation of "electronic structure theory", set as it is in the language of molecular orbitals, has a difficult time satisfying either criterion. Many of the quantum mechanical aspects of molecular orbitals are too difficult for most beginning students to appreciate, much less master, and the few applications that are presented in the typical textbook are too limited in scope to excite much student interest. This article describes a powerful new method for teaching students about electronic structure and its relevance to chemical phenomena. This method, which we have developed and used for several years in general chemistry (G.P.S.) and organic chemistry (A.J.S.) courses, relies on computer-generated three-dimensional models of electron density distributions, and largely satisfies Pauling's two criteria. Students find electron density models easy to understand and use, and because these models are easily applied to a broad range of topics, they successfully convey to students the importance of electronic structure. In addition, when students finally learn about orbital concepts they are better prepared because they already have a well-developed three-dimensional picture of electronic structure to fall back on. We note in this regard that the types of models we use have found widespread, rigorous application in chemical research (1, 2), so students who understand and use electron density models do not need to "unlearn" anything before progressing to more advanced theories.

  11. QSAR modeling of toxicity of diverse organic chemicals to Daphnia magna using 2D and 3D descriptors

    Energy Technology Data Exchange (ETDEWEB)

    Kar, Supratik [Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032 (India); Roy, Kunal, E-mail: kunalroy_in@yahoo.com [Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032 (India)

    2010-05-15

    One of the major economic alternatives to experimental toxicity testing is the use of quantitative structure-activity relationships (QSARs) which are used in formulating regulatory decisions of environmental protection agencies. In this background, we have modeled a large diverse group of 297 chemicals for their toxicity to Daphnia magna using mechanistically interpretable descriptors. Three-dimensional (3D) (electronic and spatial) and two-dimensional (2D) (topological and information content indices) descriptors along with physicochemical parameter log K{sub o/w} (n-octanol/water partition coefficient) and structural descriptors were used as predictor variables. The QSAR models were developed by stepwise multiple linear regression (MLR), partial least squares (PLS), genetic function approximation (GFA), and genetic PLS (G/PLS). All the models were validated internally and externally. Among several models developed using different chemometric tools, the best model based on both internal and external validation characteristics was a PLS equation with 7 descriptors and three latent variables explaining 67.8% leave-one-out predicted variance and 74.1% external predicted variance. The PLS model suggests that higher lipophilicity and electrophilicity, less negative charge surface area and presence of ether linkage, hydrogen bond donor groups and acetylenic carbons are responsible for greater toxicity of chemicals. The developed model may be used for prediction of toxicity, safety and risk assessment of chemicals to achieve better ecotoxicological management and prevent adverse health consequences.

  12. Estimation of exposure to toxic releases using spatial interaction modeling

    Directory of Open Access Journals (Sweden)

    Conley Jamison F

    2011-03-01

    Full Text Available Abstract Background The United States Environmental Protection Agency's Toxic Release Inventory (TRI data are frequently used to estimate a community's exposure to pollution. However, this estimation process often uses underdeveloped geographic theory. Spatial interaction modeling provides a more realistic approach to this estimation process. This paper uses four sets of data: lung cancer age-adjusted mortality rates from the years 1990 through 2006 inclusive from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER database, TRI releases of carcinogens from 1987 to 1996, covariates associated with lung cancer, and the EPA's Risk-Screening Environmental Indicators (RSEI model. Results The impact of the volume of carcinogenic TRI releases on each county's lung cancer mortality rates was calculated using six spatial interaction functions (containment, buffer, power decay, exponential decay, quadratic decay, and RSEI estimates and evaluated with four multivariate regression methods (linear, generalized linear, spatial lag, and spatial error. Akaike Information Criterion values and P values of spatial interaction terms were computed. The impacts calculated from the interaction models were also mapped. Buffer and quadratic interaction functions had the lowest AIC values (22298 and 22525 respectively, although the gains from including the spatial interaction terms were diminished with spatial error and spatial lag regression. Conclusions The use of different methods for estimating the spatial risk posed by pollution from TRI sites can give different results about the impact of those sites on health outcomes. The most reliable estimates did not always come from the most complex methods.

  13. Three dimensional quantitative structure-toxicity relationship modeling and prediction of acute toxicity for organic contaminants to algae.

    Science.gov (United States)

    Jin, Xiangqin; Jin, Minghao; Sheng, Lianxi

    2014-08-01

    Although numerous chemicals have been identified to have significant toxicological effect on aquatic organisms, there is still lack of a reliable, high-throughput approach to evaluate, screen and monitor the presence of organic contaminants in aquatic system. In the current study, we proposed a synthetic pipeline to automatically model and predict the acute toxicity of chemicals to algae. In the procedure, a new alignment-free three dimensional (3D) structure characterization method was described and, with this method, several 3D-quantitative structure-toxicity relationship (3D-QSTR) models were developed, from which two were found to exhibit strong internal fitting ability and high external predictive power. The best model was established by Gaussian process (GP), which was further employed to perform extrapolation on a random compound library consisting of 1014 virtually generated substituted benzenes. It was found that (i) substitution number can only exert slight influence on chemical׳s toxicity, but low-substituted benzenes seem to have higher toxicity than those of high-substituted entities, and (ii) benzenes substituted by nitro group and halogens exhibit high acute toxicity as compared to other substituents such as methyl and carboxyl groups. Subsequently, several promising candidates suggested by computational prediction were assayed by using a standard algal growth inhibition test. Consequently, four substituted benzenes, namely 2,3-dinitrophenol, 2-chloro-4-nitroaniline, 1,2,3-trinitrobenzene and 3-bromophenol, were determined to have high acute toxicity to Scenedesmus obliquus, with their EC50 values of 2.5±0.8, 10.5±2.1, 1.4±0.2 and 42.7±5.4μmol/L, respectively.

  14. Modelling acute oral mammalian toxicity. 1. Definition of a quantifiable baseline effect.

    Science.gov (United States)

    Koleva, Yana K; Cronin, Mark T D; Madden, Judith C; Schwöbel, Johannes A H

    2011-10-01

    Quantitative structure-activity relationships (QSARs) provide a useful tool to define a relationship between chemical structure and toxicity and allow for the prediction of the toxicity of untested chemicals. QSAR models based upon an anaesthetic or narcosis mechanism represent a baseline, or minimum, toxicity, i.e. unless a chemical acts by another, more specific, mechanism, its toxicity will be predicted by such models. The aim of this investigation was to develop baseline models for the acute toxicity of chemicals to mammals (rat and mouse) following the oral route of administration. The availability of such baseline toxicity models for mammalian species can provide a probe for testing new chemicals with respect to their molecular mechanism of toxicity. Multiple-regression type structure-toxicity relationships were derived . (i.e., from oral log LD(50)(-1) data for mammalian species (rat and mouse) and the 1-octanol/water partition coefficient (log P) of classic non-polar narcotics). Subsequently, these models were used to distinguish between reactive chemicals of different mechanistic domains and baseline toxic chemicals. Comparison of measured toxicity data for oral rat and mouse LD(50) with predictions from baseline QSAR provides a means of identifying mechanistic categories and for categorising more specific acute mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Itinerant electron model and conductance of DNA

    Institute of Scientific and Technical Information of China (English)

    Zhen QU; Da-wei KANG; Xu-tuan GAO; Shi-jie XIE

    2008-01-01

    DNA (Deoxyribonucleic acid) has recently caught the attention of chemists and physicists.A major reason for this interest is DNA's potential use in nanoelectronie devices,both as a template for assembling nanocireuits and as an element of such circuits.However,the electronic properties of the DNA molecule remain very controversial. Charge-transfer reactions and conductivity measurements show a large variety of possible electronic behavior,ranging from Anderson and bandgap insulators to effective molecular wires and induced superconductors.In this review article,we summarize the wide-ranging experimental and theoretical results of charge transport in DNA.An itinerant electron model is suggested and the effect of the density of itinerant electrons on the conductivity of DNA is studied.Calculations show that a DNA molecule may show conductivity from insulating to metallic,which explains the controversial and profuse electric characteristics of DNA to some extent.

  16. Radiation Belt Electron Dynamics: Modeling Atmospheric Losses

    Science.gov (United States)

    Selesnick, R. S.

    2003-01-01

    The first year of work on this project has been completed. This report provides a summary of the progress made and the plan for the coming year. Also included with this report is a preprint of an article that was accepted for publication in Journal of Geophysical Research and describes in detail most of the results from the first year of effort. The goal for the first year was to develop a radiation belt electron model for fitting to data from the SAMPEX and Polar satellites that would provide an empirical description of the electron losses into the upper atmosphere. This was largely accomplished according to the original plan (with one exception being that, for reasons described below, the inclusion of the loss cone electrons in the model was deferred). The main concerns at the start were to accurately represent the balance between pitch angle diffusion and eastward drift that determines the dominant features of the low altitude data, and then to accurately convert the model into simulated data based on the characteristics of the particular electron detectors. Considerable effort was devoted to achieving these ends. Once the model was providing accurate results it was applied to data sets selected from appropriate periods in 1997, 1998, and 1999. For each interval of -30 to 60 days, the model parameters were calculated daily, thus providing good short and long term temporal resolution, and for a range of radial locations from L = 2.7 to 3.9. .

  17. Electron Correlation Models for Optical Activity

    DEFF Research Database (Denmark)

    Höhn, E. G.; O. E. Weigang, Jr.

    1968-01-01

    A two-system no-overlap model for rotatory strength is developed for electric-dipole forbidden as well as allowed transitions. General equations which allow for full utilization of symmetry in the chromophore and in the environment are obtained. The electron correlation terms are developed in full...

  18. Trapped Electron Model 2 (TEM-2)

    Science.gov (United States)

    2010-04-25

    Ginet (AFRL and MIT/Lincoln Lab). We made extensive use of the IRBEM (formerly ONERA ) library of magnetic field models and field line tracing...several others. We are aware of other efforts to develop reanalysis models of the electron radiation belts. One effort, at ONERA (Office National...sensors on GPS and geosynchronous (GEO) satellites, the ONERA group has obtained promising results, including a first physics-based data

  19. Mathematical model I. Electron and quantum mechanics

    Science.gov (United States)

    Gadre, Nitin Ramchandra

    2011-03-01

    The basic particle electron obeys various theories like electrodynamics, quantum mechanics and special relativity. Particle under different experimental conditions behaves differently, allowing us to observe different characteristics which become basis for these theories. In this paper, we have made an attempt to suggest a classical picture by studying the requirements of these three modern theories. The basic presumption is: There must be certain structural characteristics in a particle like electron which make it obey postulates of modern theories. As it is `difficult' to find structure of electron experimentally, we make a mathematical attempt. For a classical approach, we require well defined systems and we have studied a system with two charged particles, proton and electron in a hydrogen atom. An attempt has been made to give a model to describe electron as seen by the proton. We then discuss how the model can satisfy the requirements of the three modern theories in a classical manner. The paper discusses basic aspects of relativity and electrodynamics. However the focus of the paper is on quantum mechanics.

  20. Mathematical model I. Electron and quantum mechanics

    Directory of Open Access Journals (Sweden)

    Nitin Ramchandra Gadre

    2011-03-01

    Full Text Available The basic particle electron obeys various theories like electrodynamics, quantum mechanics and special relativity. Particle under different experimental conditions behaves differently, allowing us to observe different characteristics which become basis for these theories. In this paper, we have made an attempt to suggest a classical picture by studying the requirements of these three modern theories. The basic presumption is: There must be certain structural characteristics in a particle like electron which make it obey postulates of modern theories. As it is ‘difficult’ to find structure of electron experimentally, we make a mathematical attempt. For a classical approach, we require well defined systems and we have studied a system with two charged particles, proton and electron in a hydrogen atom. An attempt has been made to give a model to describe electron as seen by the proton. We then discuss how the model can satisfy the requirements of the three modern theories in a classical manner. The paper discusses basic aspects of relativity and electrodynamics. However the focus of the paper is on quantum mechanics.

  1. Model Order Reduction for Electronic Circuits:

    DEFF Research Database (Denmark)

    Hjorth, Poul G.; Shontz, Suzanne

    Electronic circuits are ubiquitous; they are used in numerous industries including: the semiconductor, communication, robotics, auto, and music industries (among many others). As products become more and more complicated, their electronic circuits also grow in size and complexity. This increased ...... in the semiconductor industry. Circuit simulation proceeds by using Maxwell’s equations to create a mathematical model of the circuit. The boundary element method is then used to discretize the equations, and the variational form of the equations are then solved on the graph network....

  2. Exactly solvable models of strongly correlated electrons

    CERN Document Server

    Korepin, Vladimir E

    1994-01-01

    Systems of strongly correlated electrons are at the heart of recent developments in condensed matter theory. They have applications to phenomena like high-T c superconductivity and the fractional quantum hall effect. Analytical solutions to such models, though mainly limited to one spatial dimension, provide a complete and unambiguous picture of the dynamics involved. This volume is devoted to such solutions obtained using the Bethe Ansatz, and concentrates on the most important of such models, the Hubbard model. The reprints are complemented by reviews at the start of each chapter and an exte

  3. Modeling of high-speed electronic devices

    Directory of Open Access Journals (Sweden)

    V. G. Kudrya

    2013-09-01

    Full Text Available Introduction. The theme of this publication is the modeling of electronic tools that operate in the frequency range from zero to terahertz and higher. Application of new concepts and technologies, including biotechnology and nanotechnology in the development of monolithic integrated circuits led to a backlog of technologies of projecting from technologies and experimental research and manufacturing. The aim of this work is to develop algorithms for analysis, reflecting not only topological as well as morphological properties of the object, that is designing within the framework of accounting EMI communicational  transmission of energy and information in the volume of the monolithic integrated circuit. Basic steps for constructing the algorithm. The object of design is presented in the form of basic elements, which can be combined with a communication structure. The object of design is presented in the form of basic elements, which can be combined with a communication structure. There are three types of matrix equations: component; component - communication structure; communication structure. Systems of equations are reduced to standardized descriptors of mathematical model by which to understand current of poles and voltage arcs whole set of basic elements. In this way obtained mathematical model that can be implemented in CAD nano and micro technology electronics. Conclusions. Mathematical models of analysis of high-speed digital and analog electronic means. The algorithm allows morphological optimization is to minimize the adverse effects outside the system of electromagnetic interaction between the components and communicator.

  4. Electronic circuits modeling using artificial neural networks

    Directory of Open Access Journals (Sweden)

    Andrejević Miona V.

    2003-01-01

    Full Text Available In this paper artificial neural networks (ANN are applied to modeling of electronic circuits. ANNs are used for application of the black-box modeling concept in the time domain. Modeling process is described, so the topology of the ANN, the testing signal used for excitation, together with the complexity of ANN are considered. The procedure is first exemplified in modeling of resistive circuits. MOS transistor, as a four-terminal device, is modeled. Then nonlinear negative resistive characteristic is modeled in order to be used as a piece-wise linear resistor in Chua's circuit. Examples of modeling nonlinear dynamic circuits are given encompassing a variety of modeling problems. A nonlinear circuit containing quartz oscillator is considered for modeling. Verification of the concept is performed by verifying the ability of the model to generalize i.e. to create acceptable responses to excitations not used during training. Implementation of these models within a behavioral simulator is exemplified. Every model is implemented in realistic surrounding in order to show its interaction, and of course, its usage and purpose.

  5. Neurochemical and Behavioral Characteristics of Toxic Milk Mice: An Animal Model of Wilson’s Disease

    OpenAIRE

    2013-01-01

    Toxic milk mice have an inherited defect of copper metabolism. Hepatic phenotype of the toxic milk mice is similar to clinical findings in humans suffering from Wilson’s disease (WND). In the present study, neurotransmitter system and locomotor performance in toxic milk mice was examined to verify the feasibility of this animal model for studying neuropathology of WND. Mice aged 2 and 12 months were used in the experiment. The mice were tested according to rotarod and footprint protocols. Mon...

  6. Power electronics system modeling and simulation

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Jih-Sheng

    1994-12-31

    This paper introduces control system design based softwares, SIMNON and MATLAB/SIMULINK, for power electronics system simulation. A complete power electronics system typically consists of a rectifier bridge along with its smoothing capacitor, an inverter, and a motor. The system components, featuring discrete or continuous, linear or nonlinear, are modeled in mathematical equations. Inverter control methods,such as pulse-width-modulation and hysteresis current control, are expressed in either computer algorithms or digital circuits. After describing component models and control methods, computer programs are then developed for complete systems simulation. Simulation results are mainly used for studying system performances, such as input and output current harmonics, torque ripples, and speed responses. Key computer programs and simulation results are demonstrated for educational purposes.

  7. Modelling the inelastic scattering of fast electrons

    Energy Technology Data Exchange (ETDEWEB)

    Allen, L.J., E-mail: lja@unimelb.edu.au [School of Physics, University of Melbourne, Parkville, Victoria 3010 (Australia); D' Alfonso, A.J., E-mail: a.j@dalfonso.com.au [School of Physics, University of Melbourne, Parkville, Victoria 3010 (Australia); Findlay, S.D. [School of Physics, Monash University, Clayton, Victoria 3800 (Australia)

    2015-04-15

    Imaging at atomic resolution based on the inelastic scattering of electrons has become firmly established in the last three decades. Harald Rose pioneered much of the early theoretical work on this topic, in particular emphasising the role of phase and the importance of a mixed dynamic form factor. In this paper we review how the modelling of inelastic scattering has subsequently developed and how numerical implementation has been achieved. A software package μSTEM is introduced, capable of simulating various imaging modes based on inelastic scattering in both scanning and conventional transmission electron microscopy. - Highlights: • Harald Rose was a pioneer of important work on atomic resolution imaging using inelastic scattering. • We review how the modelling of inelastic scattering has subsequently developed and been applied. • A software package μSTEM is introduced, capable of simulating various inelastic imaging modes.

  8. A Conceptual Framework for Predicting the Toxicity of Reactive Chemicals: Modeling Soft Electrophilicity

    Science.gov (United States)

    Although the literature is replete with QSAR models developed for many toxic effects caused by reversible chemical interactions, the development of QSARs for the toxic effects of reactive chemicals lacks a consistent approach. While limitations exit, an appropriate starting-point...

  9. EFFECTS OF WATER CHEMISTRY ON COPPER TOXICITY - WHAT'S MISSING FROM CURRENT MODELS?

    Science.gov (United States)

    Current models for the acute toxicity of cationic metals to aquatic organisms focus on the binding of free metal ions to gill surfaces. This binding, and the resultant toxicity, can be reduced by metal-complexing ligands in the exposure water, which lower the activity of the free...

  10. A Conceptual Framework for Predicting the Toxicity of Reactive Chemicals: Modeling Soft Electrophilicity

    Science.gov (United States)

    Although the literature is replete with QSAR models developed for many toxic effects caused by reversible chemical interactions, the development of QSARs for the toxic effects of reactive chemicals lacks a consistent approach. While limitations exit, an appropriate starting-point...

  11. Exposure Space: Integrating Exposure Data and Modeling with Toxicity Information

    Science.gov (United States)

    Recent advances have been made in high-throughput (HTP) toxicity testing, e.g. from ToxCast, which will ultimately be combined with HTP predictions of exposure potential to support next-generation chemical safety assessment. Rapid exposure methods are essential in selecting chemi...

  12. In Silico Model for Developmental Toxicity: How to Use QSAR Models and Interpret Their Results.

    Science.gov (United States)

    Marzo, Marco; Roncaglioni, Alessandra; Kulkarni, Sunil; Barton-Maclaren, Tara S; Benfenati, Emilio

    2016-01-01

    Modeling developmental toxicity has been a challenge for (Q)SAR model developers due to the complexity of the endpoint. Recently, some new in silico methods have been developed introducing the possibility to evaluate the integration of existing methods by taking advantage of various modeling perspectives. It is important that the model user is aware of the underlying basis of the different models in general, as well as the considerations and assumptions relative to the specific predictions that are obtained from these different models for the same chemical. The evaluation on the predictions needs to be done on a case-by-case basis, checking the analogs (possibly using structural, physicochemical, and toxicological information); for this purpose, the assessment of the applicability domain of the models provides further confidence in the model prediction. In this chapter, we present some examples illustrating an approach to combine human-based rules and statistical methods to support the prediction of developmental toxicity; we also discuss assumptions and uncertainties of the methodology.

  13. Cell signaling (mechanism and reproductive toxicity): redox chains, radicals, electrons, relays, conduit, electrochemistry, and other medical implications.

    Science.gov (United States)

    Kovacic, Peter; Pozos, Robert S

    2006-12-01

    This article deals with a novel, simple, integrated approach to cell signaling involving basic biochemical principles, and their relationship to reproductive toxicity. Initially, an overview of the biological aspects is presented. According to the hypothetical approach, cell signaling entails interaction of redox chains, involving initiation, propagation, and termination. The messengers are mainly radicals and electrons that are generated during electron transfer (ET) and hydrogen atom abstraction reactions. Termination and initiation processes in the chain occur at relay sites occupied by redox functionalities, including quinones, metal complexes, and imines, as well as redox amino acids. Conduits for the messengers, comprising species with nonbonding electrons, are omnipresent. Details are provided for the various electron transfer processes. In relation to the varying rates of cell communication, rationale is based on electrons and size of radicals. Another fit is similarly seen in inspection of endogenous precursors of reactive oxygen species (ROS); namely, proteins bearing redox moieties, lipid oxidation products, and carbohydrate radicals. A hypothesis is advanced in which electromagnetic fields associated with mobile radicals and electrons play a role. Although radicals have previously been investigated as messengers, the area occupies a minor part of the research, and it has not attracted broad consensus as an important component. For the first time, an integrated framework is presented composed of radicals, electrons, relays, conduits, and electrical fields. The approach is in keeping with the vast majority of experimental observations. Cell signaling also plays an important role in reproductive toxicity. The main classes that cause birth defects, including ROS, radiation, metal compounds, medicinals, abused drugs, and miscellaneous substances, are known to participate in the signaling process. A unifying basis exists, in that both signaling and

  14. Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study

    Directory of Open Access Journals (Sweden)

    Swapnil Chavan

    2014-10-01

    Full Text Available A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

  15. Modelling elliptically polarised Free Electron Lasers

    CERN Document Server

    Henderson, J R; Freund, H P; McNeil, B W J

    2016-01-01

    A model of a Free Electron Laser operating with an elliptically polarised undulator is presented. The equations describing the FEL interaction, including resonant harmonic radiation fields, are averaged over an undulator period and generate a generalised Bessel function scaling factor, similar to that of planar undulator FEL theory. Comparison between simulations of the averaged model with those of an unaveraged model show very good agreement in the linear regime. Two unexpected results were found. Firstly, an increased coupling to harmonics for elliptical rather than planar polarisarised undulators. Secondly, and thought to be unrelated to the undulator polarisation, a signficantly different evolution between the averaged and unaveraged simulations of the harmonic radiation evolution approaching FEL saturation.

  16. Analysis of operating model of electronic invoice colombian Colombian electronic billing analysis of the operational model

    Directory of Open Access Journals (Sweden)

    Sérgio Roberto da Silva

    2016-06-01

    Full Text Available Colombia has been one of the first countries to introduce electronic billing process on a voluntary basis, from a traditional to a digital version. In this context, the article analyzes the electronic billing process implemented in Colombia and the advantages. Methodological research is applied, qualitative, descriptive and documentary; where the regulatory framework and the conceptualization of the model is identified; the process of adoption of electronic billing is analyzed, and finally the advantages and disadvantages of its implementation is analyzed. The findings indicate that the model applied in Colombia to issue an electronic billing in sending and receiving process, is not complex, but it requires a small adequate infrastructure and trained personnel to reach all sectors, especially the micro and business which is the largest business network in the country.

  17. Quantum Ising model coupled with conducting electrons

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Yasufumi; Yonemitsu, Kenji [Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585 (Japan); Graduate University for Advanced studies, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585 (Japan)

    2005-01-01

    The effect of photo-doping on the quantum paraelectric SrTiO{sub 3} is studied by using the one-dimensional quantum Ising model, where the Ising spin describes the effective lattice polarization of an optical phonon. Two types of electron-phonon couplings are introduced through the modulation of transfer integral via lattice deformations. After the exact diagonalization and the perturbation studies, we find that photo-induced low-density carriers can drastically alter quantum fluctuations when the system locates near the quantum critical point between the quantum para- and ferro-electric phases.

  18. Quantum Ising model coupled with conducting electrons

    Science.gov (United States)

    Yamashita, Yasufumi; Yonemitsu, Kenji

    2005-01-01

    The effect of photo-doping on the quantum paraelectric SrTiO3 is studied by using the one-dimensional quantum Ising model, where the Ising spin describes the effective lattice polarization of an optical phonon. Two types of electron-phonon couplings are introduced through the modulation of transfer integral via lattice deformations. After the exact diagonalization and the perturbation studies, we find that photo-induced low-density carriers can drastically alter quantum fluctuations when the system locates near the quantum critical point between the quantum para- and ferro-electric phases.

  19. Semiconductor quantum dot toxicity in a mouse in vivo model

    Science.gov (United States)

    Bozrova, Svetlana V.; Baryshnikova, Maria A.; Nabiev, Igor; Sukhanova, Alyona

    2017-01-01

    Quantum dots (QDs) are increasingly widely used in clinical medicine. Their most promising potential applications are cancer diagnosis, including in vivo tumour imaging and targeted drug delivery. In this connection, the main questions are whether or not QDs are toxic for humans and, if they are, what concentration is relatively harmless. We have carried out in vivo experiments with CdSe/ZnS fluorescent semiconductor core/shell QDs, which are currently the most widely used in research.

  20. 76 FR 2677 - Request Facilities To Report Toxics Release Inventory Information Electronically or Complete Fill...

    Science.gov (United States)

    2011-01-14

    ... process TRI submissions and make valuable toxic chemical release and other waste management data available... codes other than SIC codes 20 through 39): 212111, 212112, 212113 (correspond to SIC 12, Coal Mining (except 1241)); 212221, 212222, 212231, 212234, 212299 (correspond to SIC 10, Metal Mining (except...

  1. Integration into Big Data: First Steps to Support Reuse of Comprehensive Toxicity Model Modules (SOT)

    Science.gov (United States)

    Data surrounding the needs of human disease and toxicity modeling are largely siloed limiting the ability to extend and reuse modules across knowledge domains. Using an infrastructure that supports integration across knowledge domains (animal toxicology, high-throughput screening...

  2. Periodicity in a "Food-limited" Population Model with Toxicants and Time Delays

    Institute of Scientific and Technical Information of China (English)

    Meng Fan; Ke Wang

    2002-01-01

    With the help of a continuation theorem based on Gaines and Mawhin's coincidence degree, we study the global existence of positive periodic solutions of a "food-limited" population model with toxicants and time delays. Some new results are obtained.

  3. Integration into Big Data: First Steps to Support Reuse of Comprehensive Toxicity Model Modules (SOT)

    Science.gov (United States)

    Data surrounding the needs of human disease and toxicity modeling are largely siloed limiting the ability to extend and reuse modules across knowledge domains. Using an infrastructure that supports integration across knowledge domains (animal toxicology, high-throughput screening...

  4. Modeling the toxicity of aromatic compounds to tetrahymena pyriformis: the response surface methodology with nonlinear methods.

    Science.gov (United States)

    Ren, Shijin

    2003-01-01

    Response surface models based on multiple linear regression had previously been developed for the toxicity of aromatic chemicals to Tetrahymena pyriformis. However, a nonlinear relationship between toxicity and one of the molecular descriptors in the response surface model was observed. In this study, response surface models were established using six nonlinear modeling methods to handle the nonlinearity exhibited in the aromatic chemicals data set. All models were validated using the method of cross-validation, and prediction accuracy was tested on an external data set. Results showed that response surface models based on locally weighted regression scatter plot smoothing (LOESS), multivariate adaptive regression splines (MARS), neural networks (NN), and projection pursuit regression (PPR) provided satisfactory power of model fitting and prediction and had similar applicabilities. The response surface models based on nonlinear methods were difficult to interpret and conservative in discriminating toxicity mechanisms.

  5. Development of a new toxic-unit model for the bioassessment of metals in streams

    Science.gov (United States)

    Schmidt, T.S.; Clements, W.H.; Mitchell, K.A.; Church, S.E.; Wanty, R.B.; Fey, D.L.; Verplanck, P.L.; San, Juan C.A.

    2010-01-01

    Two toxic-unit models that estimate the toxicity of trace-metal mixtures to benthic communities were compared. The chronic criterion accumulation ratio (CCAR), a modification of biotic ligand model (BLM) outputs for use as a toxic-unit model, accounts for the modifying and competitive influences of major cations (Ca2+, Mg2+, Na+, K+, H+), anions (HCO3−, CO32−,SO42−, Cl−, S2−) and dissolved organic carbon (DOC) in determining the free metal ion available for accumulation on the biotic ligand. The cumulative criterion unit (CCU) model, an empirical statistical model of trace-metal toxicity, considers only the ameliorative properties of Ca2+ and Mg2+ (hardness) in determining the toxicity of total dissolved trace metals. Differences in the contribution of a metal (e.g., Cu, Cd, Zn) to toxic units as determined by CCAR or CCU were observed and attributed to how each model incorporates the influences of DOC, pH, and alkalinity. Akaike information criteria demonstrate that CCAR is an improved predictor of benthic macroinvertebrate community metrics as compared with CCU. Piecewise models depict great declines (thresholds) in benthic macroinvertebrate communities at CCAR of 1 or more, while negative changes in benthic communities were detected at a CCAR of less than 1. We observed a 7% reduction in total taxa richness and a 43% decrease in Heptageniid abundance between background (CCAR = 0.1) and the threshold of chronic toxicity on the basis of continuous chronic criteria (CCAR = 1). In this first application of the BLM as a toxic-unit model, we found it superior to CCU.

  6. Model of electron pairs in electron-doped cuprates

    Science.gov (United States)

    Singh, R. J.; Khan, Shakeel

    2016-07-01

    In the order parameter of hole-doped cuprate superconductors in the pseudogap phase, two holes enter the order parameter from opposite sides and pass through various CuO2 cells jumping from one O2- to the other under the influence of magnetic field offered by the Cu2+ ions in that CuO2 cell and thus forming hole pairs. In the pseudogap phase of electron-doped cuprates, two electrons enter the order parameter at Cu2+ sites from opposite ends and pass from one Cu2+ site to the diagonally opposite Cu2+ site. Following this type of path, they are subjected to high magnetic fields from various Cu2+ ions in that cell. They do not travel from one Cu2+ site to the other along straight path but by helical path. As they pass through the diagonal, they face high to low to very high magnetic field. Therefore, frequency of helical motion and pitch goes on changing with the magnetic field. Just before reaching the Cu2+ ions at the exit points of all the cells, the pitch of the helical motion is enormously decreased and thus charge density at these sites is increased. So the velocity of electrons along the diagonal path is decreased. Consequently, transition temperature of electron-doped cuprates becomes less than that of hole-doped cuprates. Symmetry of the order parameter of the electron-doped cuprates has been found to be of 3dx2-y2 + iS type. It has been inferred that internal magnetic field inside the order parameter reconstructs the Fermi surface, which is requisite for superconductivity to take place. Electron pairs formed in the pseudogap phase are the precursors of superconducting order parameter when cooled below Tc.

  7. Modeling ion sensing in molecular electronics

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Caroline J.; Smeu, Manuel, E-mail: manuel.smeu@northwestern.edu; Ratner, Mark A., E-mail: ratner@northwestern.edu [Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208 (United States)

    2014-02-07

    We examine the ability of molecules to sense ions by measuring the change in molecular conductance in the presence of such charged species. The detection of protons (H{sup +}), alkali metal cations (M{sup +}), calcium ions (Ca{sup 2+}), and hydronium ions (H{sub 3}O{sup +}) is considered. Density functional theory (DFT) is used within the Keldysh non-equilibrium Green's function framework (NEGF) to model electron transport properties of quinolinedithiol (QDT, C{sub 9}H{sub 7}NS{sub 2}), bridging Al electrodes. The geometry of the transport region is relaxed with DFT. The transport properties of the device are modeled with NEGF-DFT to determine if this device can distinguish among the M{sup +} + QDT species containing monovalent cations, where M{sup +} = H{sup +}, Li{sup +}, Na{sup +}, or K{sup +}. Because of the asymmetry of QDT in between the two electrodes, both positive and negative biases are considered. The electron transmission function and conductance properties are simulated for electrode biases in the range from −0.5 V to 0.5 V at increments of 0.1 V. Scattering state analysis is used to determine the molecular orbitals that are the main contributors to the peaks in the transmission function near the Fermi level of the electrodes, and current-voltage relationships are obtained. The results show that QDT can be used as a proton detector by measuring transport through it and can conceivably act as a pH sensor in solutions. In addition, QDT may be able to distinguish among different monovalent species. This work suggests an approach to design modern molecular electronic conductance sensors with high sensitivity and specificity using well-established quantum chemistry.

  8. Human health and ecological toxicity potentials due to heavy metal content in waste electronic devices with flat panel displays.

    Science.gov (United States)

    Lim, Seong-Rin; Schoenung, Julie M

    2010-05-15

    Display devices such as cathode-ray tube (CRT) televisions and computer monitors are known to contain toxic substances and have consequently been banned from disposal in landfills in the State of California and elsewhere. New types of flat panel display (FPD) devices, millions of which are now purchased each year, also contain toxic substances, but have not previously been systematically studied and compared to assess the potential impact that could result from their ultimate disposal. In the current work, the focus is on the evaluation of end-of-life toxicity potential from the heavy metal content in select FPD devices with the intent to inform material selection and design-for-environment (DfE) decisions. Specifically, the metals antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, mercury, molybdenum, nickel, selenium, silver, vanadium, and zinc in plasma TVs, LCD (liquid crystal display) TVs, LCD computer monitors and laptop computers are considered. The human health and ecotoxicity potentials are evaluated through a life cycle assessment perspective by combining data on the respective heavy metal contents, the characterization factors in the U.S. EPA Tool for the Reduction and Assessment of Chemical and other environmental Impacts (TRACI), and a pathway and impact model. Principal contributors to the toxicity potentials are lead, arsenic, copper, and mercury. Although the heavy metal content in newer flat panel display devices creates less human health toxicity potential than that in CRTs, for ecological toxicity, the new devices are worse, especially because of the mercury in LCD TVs and the copper in plasma TVs.

  9. Human health and ecological toxicity potentials due to heavy metal content in waste electronic devices with flat panel displays

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Seong-Rin [Department of Chemical Engineering and Materials Science, University of California, 2017 Kemper Hall, One Shields Avenue, Davis, CA 95616 (United States); Schoenung, Julie M., E-mail: jmschoenung@ucdavis.edu [Department of Chemical Engineering and Materials Science, University of California, 2017 Kemper Hall, One Shields Avenue, Davis, CA 95616 (United States)

    2010-05-15

    Display devices such as cathode-ray tube (CRT) televisions and computer monitors are known to contain toxic substances and have consequently been banned from disposal in landfills in the State of California and elsewhere. New types of flat panel display (FPD) devices, millions of which are now purchased each year, also contain toxic substances, but have not previously been systematically studied and compared to assess the potential impact that could result from their ultimate disposal. In the current work, the focus is on the evaluation of end-of-life toxicity potential from the heavy metal content in select FPD devices with the intent to inform material selection and design-for-environment (DfE) decisions. Specifically, the metals antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, mercury, molybdenum, nickel, selenium, silver, vanadium, and zinc in plasma TVs, LCD (liquid crystal display) TVs, LCD computer monitors and laptop computers are considered. The human health and ecotoxicity potentials are evaluated through a life cycle assessment perspective by combining data on the respective heavy metal contents, the characterization factors in the U.S. EPA Tool for the Reduction and Assessment of Chemical and other environmental Impacts (TRACI), and a pathway and impact model. Principal contributors to the toxicity potentials are lead, arsenic, copper, and mercury. Although the heavy metal content in newer flat panel display devices creates less human health toxicity potential than that in CRTs, for ecological toxicity, the new devices are worse, especially because of the mercury in LCD TVs and the copper in plasma TVs.

  10. Predicting aquatic toxicities of chemical pesticides in multiple test species using nonlinear QSTR modeling approaches.

    Science.gov (United States)

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2015-11-01

    In this study, we established nonlinear quantitative-structure toxicity relationship (QSTR) models for predicting the toxicities of chemical pesticides in multiple aquatic test species following the OECD (Organization for Economic Cooperation and Development) guidelines. The decision tree forest (DTF) and decision tree boost (DTB) based QSTR models were constructed using a pesticides toxicity dataset in Selenastrum capricornutum and a set of six descriptors. Other six toxicity data sets were used for external validation of the constructed QSTRs. Global QSTR models were also constructed using the combined dataset of all the seven species. The diversity in chemical structures and nonlinearity in the data were evaluated. Model validation was performed deriving several statistical coefficients for the test data and the prediction and generalization abilities of the QSTRs were evaluated. Both the QSTR models identified WPSA1 (weighted charged partial positive surface area) as the most influential descriptor. The DTF and DTB QSTRs performed relatively better than the single decision tree (SDT) and support vector machines (SVM) models used as a benchmark here and yielded R(2) of 0.886 and 0.964 between the measured and predicted toxicity values in the complete dataset (S. capricornutum). The QSTR models applied to six other aquatic species toxicity data yielded R(2) of >0.92 (DTF) and >0.97 (DTB), respectively. The prediction accuracies of the global models were comparable with those of the S. capricornutum models. The results suggest for the appropriateness of the developed QSTR models to reliably predict the aquatic toxicity of chemicals and can be used for regulatory purpose.

  11. A zebrafish model for uremic toxicity: role of the complement pathway.

    Science.gov (United States)

    Berman, Nathaniel; Lectura, Melisa; Thurman, Joshua M; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

    2013-01-01

    Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p 50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement.

  12. A Bayesian network model for predicting aquatic toxicity mode of action using two dimensional theoretical molecular descriptors

    Science.gov (United States)

    The mode of toxic action (MoA) has been recognized as a key determinant of chemical toxicity, but development of predictive MoA classification models in aquatic toxicology has been limited. We developed a Bayesian network model to classify aquatic toxicity MoA using a recently pu...

  13. MOAtox: A comprehensive mode of action and acute aquatic toxicity database for predictive model development (SETAC abstract)

    Science.gov (United States)

    The mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity and as an alternative to chemical class-based predictive toxicity modeling. However, the development of quantitative structure activity relationship (QSAR) and other models has been limit...

  14. The antineoplastic antibiotic taurolidine promotes lung and liver metastasis in two syngeneic osteosarcoma mouse models and exhibits severe liver toxicity.

    Science.gov (United States)

    Arlt, Matthias J E; Walters, Denise K; Banke, Ingo J; Steinmann, Patrick; Puskas, Gabor J; Bertz, Josefine; Rentsch, Katharina M; Ehrensperger, Felix; Born, Walter; Fuchs, Bruno

    2012-09-01

    Osteosarcoma (OS) is the most frequent primary bone tumor. Despite multiagent neoadjuvant chemotherapy, patients with metastatic disease have a poor prognosis. Moreover, currently used chemotherapeutics have severe toxic side effects. Thus, novel agents with improved antimetastatic activity and reduced toxicity are needed. Taurolidine, a broad-spectrum antimicrobial, has recently been shown to have antineoplastic properties against a variety of tumors and low systemic toxicity. Consequently, we investigated in our study the antineoplastic potential of taurolidine against OS in two different mouse models. Although both OS cell lines, K7M2 and LM8, were sensitive for the compound in vitro, intraperitoneal application of taurolidine failed to inhibit primary tumor growth. Moreover, it enhanced the metastatic load in both models 1.7- to 20-fold and caused severe liver deformations and up to 40% mortality. Thus, systemic toxicity was further investigated in tumor-free mice histologically, by electron microscopy and by measurements of representative liver enzymes. Taurolidine dose-dependent fibrous thickening of the liver capsule and adhesions and atrophies of the liver lobes were comparable in healthy and tumor-bearing mice. Liver toxicity was further indicated by up to eightfold elevated levels of the liver enzymes alanine transaminase, aspartate transaminase and GLDH in the circulation. Ultrastructural analysis of affected liver tissue showed swollen mitochondria with cristolysis and numerous lipid vacuoles in the cytoplasm of hepatocytes. The findings of our study question the applicability of taurolidine for OS treatment and may suggest the need for caution regarding the widespread clinical use of taurolidine as an antineoplastic agent.

  15. Gene expression patterns in Rainbow Trout, Oncorhynchus mykiss, exposed to a suite of model toxicants

    Energy Technology Data Exchange (ETDEWEB)

    Hook, Sharon E.; Skillman, Ann D.; Small, Jonathan A.; Schultz, Irv R.

    2006-05-25

    The increased availability and use of DNA microarrays has allowed the characterization of gene expression patterns associated with different toxicants. An important question is whether toxicant induced changes in gene expression in fish are sufficiently diverse to allow for identification of specific modes of action and/or specific contaminants. In theory, each class of toxicant may generate a gene expression profile unique to its mode of toxic action. We exposed isogenic (cloned) rainbow trout Oncorhyncus mykiss, to sublethal levels of a series of model toxicants with varying modes of action, including ethynylestradiol (xeno-estrogen), trenbolone (anabolic steroid; model androgen), 2,2,4,4´tetrabromodiphenyl ether (BDE-47, thyroid active), diquat (oxidant stressor), chromium VI, and benzo[a]pyrene (BaP) for a period of 1-3 weeks. Following exposure, fish were euthanized, livers harvested and RNA extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Atlantic Salmon / Trout array (GRASP project, University of Victoria) spotted with 16,000 cDNA’s. The slides were scanned to measure abundance of a given transcript in each sample relative to controls. Data were analyzed via Genespring (Silicon Genetics) to identify a list of up and down regulated genes, as well as to determine gene clustering patterns that can be used as “expression signatures”. Our analysis indicates each toxicant generated specific gene expression profiles. Most genes exhibiting altered expression responded to only one of the toxicants. Relatively few genes are co-expressed in multiple treatments. For example, BaP and Diquat, both of which exert toxicity via oxidative stress, up-regulated 28 of the same genes, of over 100 genes altered by ether treatment. Other genes associated with steroidogenesis, p450 and estrogen responsive genes appear to be useful for selectively identifying toxicant mode of in fish, suggesting a link between gene expression

  16. Use of a (Quantitative) Structure-Activity Relationship [(Q)SAR] model to predict the toxicity of naphthenic acids

    DEFF Research Database (Denmark)

    Frank, Richard; Sanderson, Hans; Kavanagh, Richard

    2010-01-01

    -Activity Relationship ((Q)SAR) model to accurately predict the toxicity of NA-like surrogates was investigated.  The USEPA’s ECOSAR model predicted the toxicity of NA-like surrogates with acceptable accuracy in comparison to observed toxicity values from Vibrio fischeri and Daphnia magna assays, indicating...... that the model has potential to serve as a prioritization tool for identifying NA structures likely to have an increased toxicity.  Investigating NAs of equal MW, the ECOSAR model predicted increased toxic potency for NAs containing fewer carbon rings.  Furthermore, NA structures with a linear grouping of carbon...

  17. Characterization and Modeling of Power Electronics Device

    Directory of Open Access Journals (Sweden)

    Tandjaoui Mohammed Nasser

    2014-10-01

    Full Text Available During the three decades spent, the advances of high voltage/current semiconductor technology directly affect the power electronics converter technology and its progress. The developments of power semiconductors led successively to the appearance of the elements such as the Thyristors, and become commercially available. The various semiconductor devices can be classified into the way they can be controlled, uncontrolled category such as the Diode when it’s on or off state is controlled by the power circuit, and second category is the fully controlled such as the Metal Oxide Semiconductor Field Effect Transistor (MOSFET, and this category can be included a new hybrid devices such as the Insulated Gate Bipolar Transistor (IGBT, and the Gate Turn-off Thyristor (GTO. This paper describes the characteristics and modeling of several types of power semiconductor devices such as MOSFET, IGBT and GTO.

  18. Prediction of organ toxicity endpoints by QSAR modeling based on precise chemical-histopathology annotations.

    Science.gov (United States)

    Myshkin, Eugene; Brennan, Richard; Khasanova, Tatiana; Sitnik, Tatiana; Serebriyskaya, Tatiana; Litvinova, Elena; Guryanov, Alexey; Nikolsky, Yuri; Nikolskaya, Tatiana; Bureeva, Svetlana

    2012-09-01

    The ability to accurately predict the toxicity of drug candidates from their chemical structure is critical for guiding experimental drug discovery toward safer medicines. Under the guidance of the MetaTox consortium (Thomson Reuters, CA, USA), which comprised toxicologists from the pharmaceutical industry and government agencies, we created a comprehensive ontology of toxic pathologies for 19 organs, classifying pathology terms by pathology type and functional organ substructure. By manual annotation of full-text research articles, the ontology was populated with chemical compounds causing specific histopathologies. Annotated compound-toxicity associations defined histologically from rat and mouse experiments were used to build quantitative structure-activity relationship models predicting subcategories of liver and kidney toxicity: liver necrosis, liver relative weight gain, liver lipid accumulation, nephron injury, kidney relative weight gain, and kidney necrosis. All models were validated using two independent test sets and demonstrated overall good performance: initial validation showed 0.80-0.96 sensitivity (correctly predicted toxic compounds) and 0.85-1.00 specificity (correctly predicted non-toxic compounds). Later validation against a test set of compounds newly added to the database in the 2 years following initial model generation showed 75-87% sensitivity and 60-78% specificity. General hepatotoxicity and nephrotoxicity models were less accurate, as expected for more complex endpoints.

  19. Nanoparticle toxicity assessment using an in vitro 3-D kidney organoid culture model.

    Science.gov (United States)

    Astashkina, Anna I; Jones, Clint F; Thiagarajan, Giridhar; Kurtzeborn, Kristen; Ghandehari, Hamid; Brooks, Benjamin D; Grainger, David W

    2014-08-01

    Nanocarriers and nanoparticles remain an intense pharmaceutical and medical imaging technology interest. Their entry into clinical use is hampered by the lack of reliable in vitro models that accurately predict in vivo toxicity. This study evaluates a 3-D kidney organoid proximal tubule culture to assess in vitro toxicity of the hydroxylated generation-5 PAMAM dendrimer (G5-OH) compared to previously published preclinical in vivo rodent nephrotoxicity data. 3-D kidney proximal tubule cultures were created using isolated murine proximal tubule fractions suspended in a biomedical grade hyaluronic acid-based hydrogel. Toxicity in these cultures to neutral G5-OH dendrimer nanoparticles and gold nanoparticles in vitro was assessed using clinical biomarker generation. Neutral PAMAM nanoparticle dendrimers elicit in vivo-relevant kidney biomarkers and cell viability in a 3-D kidney organoid culture that closely reflect toxicity markers reported in vivo in rodent nephrotoxicity models exposed to this same nanoparticle.

  20. Per- and polyfluoro toxicity (LC(50) inhalation) study in rat and mouse using QSAR modeling.

    Science.gov (United States)

    Bhhatarai, Barun; Gramatica, Paola

    2010-03-15

    Fully or partially fluorinated compounds, known as per- and polyfluorinated chemicals are widely distributed in the environment and released because of their use in different household and industrial products. Few of these long chain per- and polyfluorinated chemicals are classified as emerging pollutants, and their environmental and toxicological effects are unveiled in the literature. This has diverted the production of long chain compounds, considered as more toxic, to short chains, but concerns regarding the toxicity of both types of per- and polyfluorinated chemicals are alarming. There are few experimental data available on the environmental behavior and toxicity of these compounds, and moreover, toxicity profiles are found to be different for the types of animals and species used. Quantitative structure-activity relationship (QSAR) is applied to a combination of short and long chain per- and polyfluorinated chemicals, for the first time, to model and predict the toxicity on two species of rodents, rat (Rattus) and mouse (Mus), by modeling inhalation (LC(50)) data. Multiple linear regression (MLR) models using the ordinary-least-squares (OLS) method, based on theoretical molecular descriptors selected by genetic algorithm (GA), were used for QSAR studies. Training and prediction sets were prepared a priori, and these sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the model was verified on a larger set of per- and polyfluorinated chemicals retrieved from different databases and journals. The descriptors involved, the similarities, and the differences observed between models pertaining to the toxicity related to the two species are discussed. Chemometric methods such as principal component analysis (PCA) and multidimensional scaling (MDS) were used to select most toxic compounds from those within the AD of both models, which will be subjected to experimental tests

  1. Multispecies QSAR modeling for predicting the aquatic toxicity of diverse organic chemicals for regulatory toxicology.

    Science.gov (United States)

    Singh, Kunwar P; Gupta, Shikha; Kumar, Anuj; Mohan, Dinesh

    2014-05-19

    The research aims to develop multispecies quantitative structure-activity relationships (QSARs) modeling tools capable of predicting the acute toxicity of diverse chemicals in various Organization for Economic Co-operation and Development (OECD) recommended test species of different trophic levels for regulatory toxicology. Accordingly, the ensemble learning (EL) approach based classification and regression QSAR models, such as decision treeboost (DTB) and decision tree forest (DTF) implementing stochastic gradient boosting and bagging algorithms were developed using the algae (P. subcapitata) experimental toxicity data for chemicals. The EL-QSAR models were successfully applied to predict toxicities of wide groups of chemicals in other test species including algae (S. obliguue), daphnia, fish, and bacteria. Structural diversity of the selected chemicals and those of the end-point toxicity data of five different test species were tested using the Tanimoto similarity index and Kruskal-Wallis (K-W) statistics. Predictive and generalization abilities of the constructed QSAR models were compared using statistical parameters. The developed QSAR models (DTB and DTF) yielded a considerably high classification accuracy in complete data of model building (algae) species (97.82%, 99.01%) and ranged between 92.50%-94.26% and 92.14%-94.12% in four test species, respectively, whereas regression QSAR models (DTB and DTF) rendered high correlation (R(2)) between the measured and model predicted toxicity end-point values and low mean-squared error in model building (algae) species (0.918, 0.15; 0.905, 0.21) and ranged between 0.575 and 0.672, 0.18-0.51 and 0.605-0.689 and 0.20-0.45 in four different test species. The developed QSAR models exhibited good predictive and generalization abilities in different test species of varied trophic levels and can be used for predicting the toxicities of new chemicals for screening and prioritization of chemicals for regulation.

  2. A Predictive Model for Toxicity Effects Assessment of Biotransformed Hepatic Drugs Using Iterative Sampling Method.

    Science.gov (United States)

    Tharwat, Alaa; Moemen, Yasmine S; Hassanien, Aboul Ella

    2016-12-09

    Measuring toxicity is one of the main steps in drug development. Hence, there is a high demand for computational models to predict the toxicity effects of the potential drugs. In this study, we used a dataset, which consists of four toxicity effects:mutagenic, tumorigenic, irritant and reproductive effects. The proposed model consists of three phases. In the first phase, rough set-based methods are used to select the most discriminative features for reducing the classification time and improving the classification performance. Due to the imbalanced class distribution, in the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique are used to solve the problem of imbalanced datasets. ITerative Sampling (ITS) method is proposed to avoid the limitations of those methods. ITS method has two steps. The first step (sampling step) iteratively modifies the prior distribution of the minority and majority classes. In the second step, a data cleaning method is used to remove the overlapping that is produced from the first step. In the third phase, Bagging classifier is used to classify an unknown drug into toxic or non-toxic. The experimental results proved that the proposed model performed well in classifying the unknown samples according to all toxic effects in the imbalanced datasets.

  3. A Model for Teaching Electronic Commerce Students

    Directory of Open Access Journals (Sweden)

    Howard C. Woodard

    2002-10-01

    Full Text Available The teaching of information technology in an ever-changing world at universities presents a challenge. Are courses taught as concepts, while ignoring hands-on courses, leaving the hands-on classes to the technical colleges or trade schools? Does this produce the best employees for industry or give students the knowledge and skills necessary to function in a high-tech world? At GeorgiaCollege & StateUniversity (GC&SU a model was developed that combines both concepts and practical hands-on skill to meet this challenge. Using this model, a program was developed that consists of classroom lecture of concepts as well as practical hands-on exercises for mastering the knowledge and developing the skills necessary to succeed in the high-tech world of electronic commerce. The students become productive day one of a new job assignment. This solves the problem of students having the "book knowledge" but not knowing how to apply what has been learned.

  4. Are Free Ion Activity Models Sufficient Alternatives to Biotic Ligand Models in Evaluating Metal Toxic Impacts in Terrestrial Environments?

    DEFF Research Database (Denmark)

    Owsianiak, Mikolaj; Rosenbaum, Ralph K.; Larsen, Henrik Fred

    Metal partitioning between solid and aqueous phases and speciation in soil pore water control the bioavailability of toxic forms of metals, while protons and base cations can mitigate metal ecotoxicity by competitive interactions with biotic ligands. e employment of BLMs to evaluate toxicity...... potential of metals in soils results in site-specic toxicity scores due to large variability of soil properties and dierences in ionic composition. Unfortunately, terrestrial BMLs are available only for few metals and few organisms, thus their applicability to hazard ranking or toxic impact assessment...... is low and alternatives must be found. In this study, we compared published terrestrial BLMs and their potential alternatives such as free ion activity models (FIAM), for applicability in addressing metal toxic impacts in terrestrial environments. A set of 1300 soils representative for the whole world...

  5. Progress on Analytical Modeling of Coherent Electron Cooling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, G.; Blaskiewicz, M.; Litvinenko, V.; Webb, S.

    2010-05-23

    We report recent progresses on analytical studies of Coherent Electron Cooling. The phase space electron beam distribution obtained from the 1D FEL amplifier is applied to an infinite electron plasma model and the electron density evolution inside the kicker is derived. We also investigate the velocity modulation in the modulator and obtain a closed form solution for the current density evolution for infinite homogeneous electron plasma.

  6. Theory and modeling of electron fishbones

    Science.gov (United States)

    Vlad, G.; Fusco, V.; Briguglio, S.; Fogaccia, G.; Zonca, F.; Wang, X.

    2016-10-01

    Internal kink instabilities exhibiting fishbone like behavior have been observed in a variety of experiments where a high energy electron population, generated by strong auxiliary heating and/or current drive systems, was present. After briefly reviewing the experimental evidences of energetic electrons driven fishbones, and the main results of linear and nonlinear theory of electron fishbones, the results of global, self-consistent, nonlinear hybrid MHD-Gyrokinetic simulations will be presented. To this purpose, the extended/hybrid MHD-Gyrokinetic code XHMGC will be used. Linear dynamics analysis will enlighten the effect of considering kinetic thermal ion compressibility and diamagnetic response, and kinetic thermal electrons compressibility, in addition to the energetic electron contribution. Nonlinear saturation and energetic electron transport will also be addressed, making extensive use of Hamiltonian mapping techniques, discussing both centrally peaked and off-axis peaked energetic electron profiles. It will be shown that centrally peaked energetic electron profiles are characterized by resonant excitation and nonlinear response of deeply trapped energetic electrons. On the other side, off-axis peaked energetic electron profiles are characterized by resonant excitation and nonlinear response of barely circulating energetic electrons which experience toroidal precession reversal of their motion.

  7. Ecotoxicity interspecies QAAR models from Daphnia toxicity of pharmaceuticals and personal care products.

    Science.gov (United States)

    Sangion, A; Gramatica, P

    2016-10-01

    Pharmaceutical and Personal Care Products (PPCPs) became a class of contaminants of emerging concern because are ubiquitously detected in surface water and soil, where they can affect wildlife. Ecotoxicological data are only available for a few PPCPs, thus modelling approaches are essential tools to maximize the information contained in the existing data. In silico methods may be helpful in filling data gaps for the toxicity of PPCPs towards various ecological indicator organisms. The good correlation between toxicity toward Daphnia magna and those on two fish species (Pimephales promelas and Oncorhynchus mykiss), improved by the addition of one theoretical molecular descriptor, allowed us to develop predictive models to investigate the relationship between toxicities in different species. The aim of this work is to propose quantitative activity-activity relationship (QAAR) models, developed in QSARINS and validated for their external predictivity. Such models can be used to predict the toxicity of PPCPs to a particular species using available experimental toxicity data from a different species, thus reducing the tests on organisms of higher trophic level. Similarly, good QAAR models, implemented by molecular descriptors to improve the quality, are proposed here for fish interspecies. We also comment on the relevance of autocorrelation descriptors in improving all studied interspecies correlations.

  8. Toxicоlogical evaluation of the plant products using Brine Shrimp (Artemia salina L. model

    Directory of Open Access Journals (Sweden)

    Меntor R. Hamidi

    2014-04-01

    Full Text Available Many natural products could serve as the starting point in the development of modern medicines because of their numerous biological and pharmacological activities. However, some of them are known to carry toxicological properties as well. In order to achieve a safe treatment with plant products, numerous research studies have recently been focused on both pharmacology and toxicity of medicinal plants. Moreover, these studies employed efforts for alternative biological assays. Brine Shrimp Lethality Assay is the most convenient system for monitoring biological activities of various plant species. This method is very useful for preliminary assessment of toxicity of the plant extracts. Rapidness, simplicity and low requirements are several advantages of this assay. However, several conditions need to be completed, especially in the means of standardized experimental conditions (temperature, pH of the medium, salinity, aeration and light. The toxicity of herbal extracts using this assay has been determined in a concentration range of 10, 100 and 1000 µg/ml of the examined herbal extract. Most toxicity studies which use the Brine Shrimp Lethality Assay determine the toxicity after 24 hours of exposure to the tested sample. The median lethal concentration (LC50 of the test samples is obtained by a plot of percentage of the dead shrimps against the logarithm of the sample concentration. LC50 values are estimated using a probit regression analysis and compared with either Meyer’s or Clarkson’s toxicity criteria. Furthermore, the positive correlation between Meyer’s toxicity scale for Artemia salina and Gosselin, Smith and Hodge’s toxicity scale for higher animal models confirmed that the Brine Shrimp Lethality Assay is an excellent predictive tool for the toxic potential of plant extracts in humans.

  9. 78 FR 72818 - Electronic Reporting Under the Toxic Substances Control Act

    Science.gov (United States)

    2013-12-04

    ... assurance that electronic signatures resist repudiation by the signatory. The Agency is extending the TSCA... disseminating information to the public. III. Description of Changes to Reporting Procedures This unit provides... share a draft submission within their organization, and more easily save a copy for their records or...

  10. Biodistribution and acute toxicity of naked gold nanoparticles in a rabbit hepatic tumor model.

    Science.gov (United States)

    Glazer, Evan S; Zhu, Cihui; Hamir, Amir N; Borne, Agatha; Thompson, Catherine Shea; Curley, Steven A

    2011-12-01

    There is a paucity of data regarding the safety of administering solid gold nanoparticles (AuNPs) in large animal tumor models. We assessed the acute toxicity and biodistribution of 5 nm and 25 nm solid AuNPs in New Zealand White rabbits (n = 6 in each) with implanted liver Vx2 tumors 24 h after intravenous injection. Gold concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP) and imaged with transmission electron microscopy (TEM). There was no clinico-pathologic evidence of renal, hepatic, pulmonary, or other organ dysfunction. After 25 nm AuNP administration, the concentration of white blood cells increased after treatment (p = 0.001). Most other blood studies were unchanged. AuNPs were distributed to the spleen, liver, and Vx2 tumors, but not to other tissues. The urinary excretion of AuNPs was bimodal as measured by ICP. 25 nm AuNPs were more evenly distributed throughout tissues and may be better tools for medical therapy.

  11. Ecotoxicogenomic approaches for understanding molecular mechanisms of environmental chemical toxicity using aquatic invertebrate, Daphnia model organism.

    Science.gov (United States)

    Kim, Hyo Jeong; Koedrith, Preeyaporn; Seo, Young Rok

    2015-05-29

    Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the term "ecotoxicogenomics" has recently emerged to describe integration of omics studies (i.e., transcriptomics, proteomics, metabolomics, and epigenomics) into ecotoxicological fields. Ecotoxicogenomics is defined as study of an entire set of genes or proteins expression in ecological organisms to provide insight on environmental toxicity, offering benefit in ecological risk assessment. Indeed, Daphnia is a model species to study aquatic environmental toxicity designated in the Organization for Economic Co-operation and Development's toxicity test guideline and to investigate expression patterns using ecotoxicology-oriented genomics tools. Our main purpose is to demonstrate the potential utility of gene expression profiling in ecotoxicology by identifying novel biomarkers and relevant modes of toxicity in Daphnia magna. These approaches enable us to address adverse phenotypic outcomes linked to particular gene function(s) and mechanistic understanding of aquatic ecotoxicology as well as exploration of useful biomarkers. Furthermore, key challenges that currently face aquatic ecotoxicology (e.g., predicting toxicant responses among a broad spectrum of phytogenetic groups, predicting impact of temporal exposure on toxicant responses) necessitate the parallel use of other model organisms, both aquatic and terrestrial. By investigating gene expression profiling in an environmentally important organism, this provides viable support for the utility of ecotoxicogenomics.

  12. Ecotoxicogenomic Approaches for Understanding Molecular Mechanisms of Environmental Chemical Toxicity Using Aquatic Invertebrate, Daphnia Model Organism

    Directory of Open Access Journals (Sweden)

    Hyo Jeong Kim

    2015-05-01

    Full Text Available Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the term “ecotoxicogenomics” has recently emerged to describe integration of omics studies (i.e., transcriptomics, proteomics, metabolomics, and epigenomics into ecotoxicological fields. Ecotoxicogenomics is defined as study of an entire set of genes or proteins expression in ecological organisms to provide insight on environmental toxicity, offering benefit in ecological risk assessment. Indeed, Daphnia is a model species to study aquatic environmental toxicity designated in the Organization for Economic Co-operation and Development’s toxicity test guideline and to investigate expression patterns using ecotoxicology-oriented genomics tools. Our main purpose is to demonstrate the potential utility of gene expression profiling in ecotoxicology by identifying novel biomarkers and relevant modes of toxicity in Daphnia magna. These approaches enable us to address adverse phenotypic outcomes linked to particular gene function(s and mechanistic understanding of aquatic ecotoxicology as well as exploration of useful biomarkers. Furthermore, key challenges that currently face aquatic ecotoxicology (e.g., predicting toxicant responses among a broad spectrum of phytogenetic groups, predicting impact of temporal exposure on toxicant responses necessitate the parallel use of other model organisms, both aquatic and terrestrial. By investigating gene expression profiling in an environmentally important organism, this provides viable support for the utility of ecotoxicogenomics.

  13. Ecotoxicogenomic Approaches for Understanding Molecular Mechanisms of Environmental Chemical Toxicity Using Aquatic Invertebrate, Daphnia Model Organism

    Science.gov (United States)

    Kim, Hyo Jeong; Koedrith, Preeyaporn; Seo, Young Rok

    2015-01-01

    Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the term “ecotoxicogenomics” has recently emerged to describe integration of omics studies (i.e., transcriptomics, proteomics, metabolomics, and epigenomics) into ecotoxicological fields. Ecotoxicogenomics is defined as study of an entire set of genes or proteins expression in ecological organisms to provide insight on environmental toxicity, offering benefit in ecological risk assessment. Indeed, Daphnia is a model species to study aquatic environmental toxicity designated in the Organization for Economic Co-operation and Development’s toxicity test guideline and to investigate expression patterns using ecotoxicology-oriented genomics tools. Our main purpose is to demonstrate the potential utility of gene expression profiling in ecotoxicology by identifying novel biomarkers and relevant modes of toxicity in Daphnia magna. These approaches enable us to address adverse phenotypic outcomes linked to particular gene function(s) and mechanistic understanding of aquatic ecotoxicology as well as exploration of useful biomarkers. Furthermore, key challenges that currently face aquatic ecotoxicology (e.g., predicting toxicant responses among a broad spectrum of phytogenetic groups, predicting impact of temporal exposure on toxicant responses) necessitate the parallel use of other model organisms, both aquatic and terrestrial. By investigating gene expression profiling in an environmentally important organism, this provides viable support for the utility of ecotoxicogenomics. PMID:26035755

  14. A Bayesian network model for predicting aquatic toxicity mode of action using two dimensional theoretical molecular descriptors-abstract

    Science.gov (United States)

    The mode of toxic action (MoA) has been recognized as a key determinant of chemical toxicity but MoA classification in aquatic toxicology has been limited. We developed a Bayesian network model to classify aquatic toxicity mode of action using a recently published dataset contain...

  15. Two state electron model for geminate recombination of electron-ion pairs in liquid isooctane

    Energy Technology Data Exchange (ETDEWEB)

    Lukin, L.V., E-mail: lukin@binep.ac.ru [Institute of Energy Problems of Chemical Physics (Branch), Russian Academy of Sciences, Chernogolovka, P.O. Box 56, Moscow oblast 142432 (Russian Federation); Yakovlev, B.S. [Institute of Energy Problems of Chemical Physics (Branch), Russian Academy of Sciences, Chernogolovka, P.O. Box 56, Moscow oblast 142432 (Russian Federation)

    2011-04-28

    Graphical abstract: M + n . h{nu} {yields} mobile electron {yields} trapped electron {yields} free charges. Research highlights: {yields} Electrons produced by ionization of liquid alkanes are trapped near positive ions. {yields} The recombination kinetics was expressed in terms of a trapped electron life time. {yields} Transient absorption after the ionizing pulse was analyzed for liquid isooctane. {yields} The life time of trapped electrons was found. - Abstract: Recombination kinetics of geminate electron-ion pairs is considered in the framework of the two state model for electron transport in liquid hydrocarbons. It is shown that the model well reproduces recent experimental data on the subpicosecond geminate recombination obtained in liquid isooctane. The life time of electrons in a localized state in isooctane is estimated to lie in the range between 0.14 ps and 0.57 ps at room temperature.

  16. Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity

    Directory of Open Access Journals (Sweden)

    William Dott

    2014-01-01

    Full Text Available Mitochondrial toxicity is increasingly being implicated as a contributing factor to many xenobiotic-induced organ toxicities, including skeletal muscle toxicity. This has necessitated the need for predictive in vitro models that are able to sensitively detect mitochondrial toxicity of chemical entities early in the research and development process. One such cell model involves substituting galactose for glucose in the culture media. Since cells cultured in galactose are unable to generate sufficient ATP from glycolysis they are forced to rely on mitochondrial oxidative phosphorylation for ATP generation and consequently are more sensitive to mitochondrial perturbation than cells grown in glucose. The aim of this study was to characterise cellular growth, bioenergetics and mitochondrial toxicity of the L6 rat skeletal muscle cell line cultured in either high glucose or galactose media. L6 myoblasts proliferated more slowly when cultured in galactose media, although they maintained similar levels of ATP. Galactose cultured L6 cells were significantly more sensitive to classical mitochondrial toxicants than glucose-cultured cells, confirming the cells had adapted to galactose media. Analysis of bioenergetic function with the XF Seahorse extracellular flux analyser demonstrated that oxygen consumption rate (OCR was significantly increased whereas extracellular acidification rate (ECAR, a measure of glycolysis, was decreased in cells grown in galactose. Mitochondria operated closer to state 3 respiration and had a lower mitochondrial membrane potential and basal mitochondrial O2·– level compared to cells in the glucose model. An antimycin A (AA dose response revealed that there was no difference in the sensitivity of OCR to AA inhibition between glucose and galactose cells. Importantly, cells in glucose were able to up-regulate glycolysis, while galactose cells were not. These results confirm that L6 cells are able to adapt to growth in a

  17. Modeling Electronic Properties of Complex Oxides

    Science.gov (United States)

    Krishnaswamy, Karthik

    Complex oxides are a class of materials that have recently emerged as potential candidates for electronic applications owing to their interesting electronic properties. The goal of this dissertation is to develop a fundamental understanding of these electronic properties using a combination of first-principles approaches based on density functional theory (DFT), and Schr odinger-Poisson (SP) simulation (Abstract shortened by ProQuest.

  18. Establishment of a new dynamic RRC model in smoke toxicity evaluation and engineering application

    Institute of Scientific and Technical Information of China (English)

    YANG Lizhong; FANG Tingyong; ZHOU Xiaodong; FENG Wenxing; HUANG Rui; ZHAI Guanglong; FAN Weicheng

    2005-01-01

    It is by now a well established fact that the overwhelming hazard from fire is smoke as far as the death of people in the fire is concerned. There are many methodologies for addressing the smoke toxicity component of fire hazard such as CO stochastic model,FED (fractional effective dose) model, FEC (fractional effective concentration) model, N-gas model and so on. None of these models can reflect spatio-temporal variation of the smoke concentration. A new dynamic smoke toxicity evaluation model, RRC (respiration, route and concentration) model, is proposed in this paper concerning the three decisive factors in real fire such as the respiration, movement route of people and the distribution of smoke concentration in the building. Furthermore, an example of the model is presented.

  19. Electron microscopy and theoretical modeling of cochleates.

    Science.gov (United States)

    Nagarsekar, Kalpa; Ashtikar, Mukul; Thamm, Jana; Steiniger, Frank; Schacher, Felix; Fahr, Alfred; May, Sylvio

    2014-11-11

    Cochleates are self-assembled cylindrical condensates that consist of large rolled-up lipid bilayer sheets and represent a novel platform for oral and systemic delivery of therapeutically active medicinal agents. With few preceding investigations, the physical basis of cochleate formation has remained largely unexplored. We address the structure and stability of cochleates in a combined experimental/theoretical approach. Employing different electron microscopy methods, we provide evidence for cochleates consisting of phosphatidylserine and calcium to be hollow tubelike structures with a well-defined constant lamellar repeat distance and statistically varying inner and outer radii. To rationalize the relation between inner and outer radii, we propose a theoretical model. Based on the minimization of a phenomenological free energy expression containing a bending, adhesion, and frustration contribution, we predict the optimal tube dimensions of a cochleate and estimate ratios of material constants for cochleates consisting of phosphatidylserines with varied hydrocarbon chain structures. Knowing and understanding these ratios will ultimately benefit the successful formulation of cochleates for drug delivery applications.

  20. Sorption of toxic organic compounds on wastewater solids: Mechanism and modeling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, L.; Govind, R.; Dobbs, R.A.

    1992-01-01

    Sorption of toxic organic compounds on wastewater solids is an important process in conventional biological wastewater treatment systems. The extent of accumulation of toxic organic compounds by sorption onto wastewater solids not only affects the efficiency of the treatment system, but also impacts the management of wastewater solids. The study is an attempt to propose a mechanism for understanding the sorption phenomenon and to develop a model for sorption on wastewater solids based on the proposed mechanism. It was postulated that sorption was a combination of two processes: adsorption and partitioning. A sorption model was developed for both single component and multicomponent systems. The model was tested using single component experimental isotherm data of eight toxic organic compounds.

  1. Geometry Modeling of an Electronic Expansion Valve Head

    Institute of Scientific and Technical Information of China (English)

    张川; 马善伟; 陈江平; 陈芝久; 陈文勇; 王健

    2004-01-01

    This paper proposed that the flow characteristic of electronic expansion valve should be adapted to the evaporator superheat gain to refrigerant flow rate under different working conditions. Two native methods of geometry modeling of electronic expansion valve head were introduced. By analysis of them, some shortcoming was detected and a universal modeling method of electronic expansion valve head was put forward. Through this model, the flow characteristic of EEV and the influence factors can be investigated more deeply.

  2. QSTR modeling for qualitative and quantitative toxicity predictions of diverse chemical pesticides in honey bee for regulatory purposes.

    Science.gov (United States)

    Singh, Kunwar P; Gupta, Shikha; Basant, Nikita; Mohan, Dinesh

    2014-09-15

    Pesticides are designed toxic chemicals for specific purposes and can harm nontarget species as well. The honey bee is considered a nontarget test species for toxicity evaluation of chemicals. Global QSTR (quantitative structure-toxicity relationship) models were established for qualitative and quantitative toxicity prediction of pesticides in honey bee (Apis mellifera) based on the experimental toxicity data of 237 structurally diverse pesticides. Structural diversity of the chemical pesticides and nonlinear dependence in the toxicity data were evaluated using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) QSTR models were constructed for classification (two and four categories) and function optimization problems using the toxicity end point in honey bees. The predictive power of the QSTR models was tested through rigorous validation performed using the internal and external procedures employing a wide series of statistical checks. In complete data, the PNN-QSTR model rendered a classification accuracy of 96.62% (two-category) and 95.57% (four-category), while the GRNN-QSTR model yielded a correlation (R(2)) of 0.841 between the measured and predicted toxicity values with a mean squared error (MSE) of 0.22. The results suggest the appropriateness of the developed QSTR models for reliably predicting qualitative and quantitative toxicities of pesticides in honey bee. Both the PNN and GRNN based QSTR models constructed here can be useful tools in predicting the qualitative and quantitative toxicities of the new chemical pesticides for regulatory purposes.

  3. Using Online Tool (iPrior) for Modeling ToxCast™ Assays Towards Prioritization of Animal Toxicity Testing.

    Science.gov (United States)

    Abdelaziz, Ahmed; Sushko, Yurii; Novotarskyi, Sergii; Körner, Robert; Brandmaier, Stefan; Tetko, Igor V

    2015-01-01

    The use of long-term animal studies for human and environmental toxicity estimation is more discouraged than ever before. Alternative models for toxicity prediction, including QSAR studies, are gaining more ground. A recent approach is to combine in vitro chemical profiling and in silico chemical descriptors with the knowledge about toxicity pathways to derive a unique signature for toxicity endpoints. In this study we investigate the ToxCast™ Phase I data regarding their ability to predict long-term animal toxicity. We investigated thousands of models constructed in an effort to predict 61 toxicity endpoints using multiple descriptor packages and hundreds of in vitro assays. We investigated the use of in vitro assays and biochemical pathways on model performance. We identified 10 toxicity endpoints where biologically derived descriptors from in vitro assays or pathway perturbations improved the model prediction ability. In vivo toxicity endpoints proved generally challenging to model. Few models were possible to readily model with a balanced accuracy (BA) above 0.7. We also constructed in silico models to predict the outcome of 144 in vitro assays. This showed better statistical metrics with 79 out of 144 assays having median balanced accuracy above 0.7. This suggests that the in vitro datasets have a better modelability than in vivo animal toxicities for the given datasets. Moreover, we published an online platform (http://iprior.ochem.eu) that automates large-scale model building and analysis.

  4. Modelling the Tox21 10 K chemical profiles for in vivo toxicity prediction and mechanism characterization.

    Science.gov (United States)

    Huang, Ruili; Xia, Menghang; Sakamuru, Srilatha; Zhao, Jinghua; Shahane, Sampada A; Attene-Ramos, Matias; Zhao, Tongan; Austin, Christopher P; Simeonov, Anton

    2016-01-26

    Target-specific, mechanism-oriented in vitro assays post a promising alternative to traditional animal toxicology studies. Here we report the first comprehensive analysis of the Tox21 effort, a large-scale in vitro toxicity screening of chemicals. We test ∼ 10,000 chemicals in triplicates at 15 concentrations against a panel of nuclear receptor and stress response pathway assays, producing more than 50 million data points. Compound clustering by structure similarity and activity profile similarity across the assays reveals structure-activity relationships that are useful for the generation of mechanistic hypotheses. We apply structural information and activity data to build predictive models for 72 in vivo toxicity end points using a cluster-based approach. Models based on in vitro assay data perform better in predicting human toxicity end points than animal toxicity, while a combination of structural and activity data results in better models than using structure or activity data alone. Our results suggest that in vitro activity profiles can be applied as signatures of compound mechanism of toxicity and used in prioritization for more in-depth toxicological testing.

  5. Electron impact ionization of tungsten ions in a statistical model

    Science.gov (United States)

    Demura, A. V.; Kadomtsev, M. B.; Lisitsa, V. S.; Shurygin, V. A.

    2015-01-01

    The statistical model for calculations of the electron impact ionization cross sections of multielectron ions is developed for the first time. The model is based on the idea of collective excitations of atomic electrons with the local plasma frequency, while the Thomas-Fermi model is used for atomic electrons density distribution. The electron impact ionization cross sections and related ionization rates of tungsten ions from W+ up to W63+ are calculated and then compared with the vast collection of modern experimental and modeling results. The reasonable correspondence between experimental and theoretical data demonstrates the universal nature of statistical approach to the description of atomic processes in multielectron systems.

  6. The electronic-commerce-oriented virtual merchandise model

    Science.gov (United States)

    Fang, Xiaocui; Lu, Dongming

    2004-03-01

    Electronic commerce has been the trend of commerce activities. Providing with Virtual Reality interface, electronic commerce has better expressing capacity and interaction means. But most of the applications of virtual reality technology in EC, 3D model is only the appearance description of merchandises. There is almost no information concerned with commerce information and interaction information. This resulted in disjunction of virtual model and commerce information. So we present Electronic Commerce oriented Virtual Merchandise Model (ECVMM), which combined a model with commerce information, interaction information and figure information of virtual merchandise. ECVMM with abundant information provides better support to information obtainment and communication in electronic commerce.

  7. Two state electron model for geminate recombination of electron-ion pairs in liquid isooctane

    Science.gov (United States)

    Lukin, L. V.; Yakovlev, B. S.

    2011-04-01

    Recombination kinetics of geminate electron-ion pairs is considered in the framework of the two state model for electron transport in liquid hydrocarbons. It is shown that the model well reproduces recent experimental data on the subpicosecond geminate recombination obtained in liquid isooctane. The life time of electrons in a localized state in isooctane is estimated to lie in the range between 0.14 ps and 0.57 ps at room temperature.

  8. Development and application of a multimetal multibiotic ligand model for assessing aquatic toxicity of metal mixtures.

    Science.gov (United States)

    Santore, Robert C; Ryan, Adam C

    2015-04-01

    A multimetal, multiple binding site version of the biotic ligand model (mBLM) has been developed for predicting and explaining the bioavailability and toxicity of mixtures of metals to aquatic organisms. The mBLM was constructed by combining information from single-metal BLMs to preserve compatibility between the single-metal and multiple-metal approaches. The toxicities from individual metals were predicted by assuming additivity of the individual responses. Mixture toxicity was predicted based on both dissolved metal and mBLM-normalized bioavailable metal. Comparison of the 2 prediction methods indicates that metal mixtures frequently appear to have greater toxicity than an additive estimation of individual effects on a dissolved metal basis. However, on an mBLM-normalized basis, mixtures of metals appear to be additive or less than additive. This difference results from interactions between metals and ligands in solutions including natural organic matter, processes that are accounted for in the mBLM. As part of the mBLM approach, a technique for considering variability was developed to calculate confidence bounds (called response envelopes) around the central concentration-response relationship. Predictions using the mBLM and response envelope were compared with observed toxicity for a number of invertebrate and fish species. The results show that the mBLM is a useful tool for considering bioavailability when assessing the toxicity of metal mixtures.

  9. Phlorizin pretreatment reduces acute renal toxicity in a mouse model for diabetic nephropathy.

    Science.gov (United States)

    Brouwers, Bas; Pruniau, Vincent P E G; Cauwelier, Elisa J G; Schuit, Frans; Lerut, Evelyne; Ectors, Nadine; Declercq, Jeroen; Creemers, John W M

    2013-09-20

    Streptozotocin (STZ) is widely used as diabetogenic agent in animal models for diabetic nephropathy (DN). However, it is also directly cytotoxic to kidneys, making it difficult to distinguish between DN-related and STZ-induced nephropathy. Therefore, an improved protocol to generate mice for DN studies, with a quick and robust achievement of the diabetic state, without direct kidney toxicity is required. To investigate the mechanism leading to STZ-induced nephropathy, kidney damage was induced with a high dose of STZ. This resulted in delayed gastric emptying, at least partially caused by impaired desacyl ghrelin clearance. STZ uptake in the kidneys is to a large extent mediated by the sodium/glucose cotransporters (Sglts) because the Sglt inhibitor phlorizin could reduce STZ uptake in the kidneys. Consequently, the direct toxic effects in the kidney and the gastric dilatation were resolved without interfering with the β-cell toxicity. Furthermore, pancreatic STZ uptake was increased, hereby decreasing the threshold for β-cell toxicity, allowing for single low non-nephrotoxic STZ doses (70 mg/kg). In conclusion, this study provides novel insights into the mechanism of STZ toxicity in kidneys and suggests a more efficient regime to induce DN with little or no toxic side effects.

  10. Teaching Behavioral Modeling and Simulation Techniques for Power Electronics Courses

    Science.gov (United States)

    Abramovitz, A.

    2011-01-01

    This paper suggests a pedagogical approach to teaching the subject of behavioral modeling of switch-mode power electronics systems through simulation by general-purpose electronic circuit simulators. The methodology is oriented toward electrical engineering (EE) students at the undergraduate level, enrolled in courses such as "Power Electronics,"…

  11. Accountability Analysis of Electronic Commerce Protocols by Finite Automaton Model

    Institute of Scientific and Technical Information of China (English)

    Xie Xiao-yao; Zhang Huan-guo

    2004-01-01

    The accountability of electronic commerce protocols is an important aspect to insures security of electronic transaction. This paper proposes to use Finite Automaton (FA) model as a new kind of framework to analyze the trans action protocols in the application of electronic commerce.

  12. Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals on rat and mouse.

    Science.gov (United States)

    Bhhatarai, Barun; Gramatica, Paola

    2011-05-01

    Quantitative structure-activity relationship (QSAR) analyses were performed using the LD(50) oral toxicity data of per- and polyfluorinated chemicals (PFCs) on rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses the available experimental data for prediction and prioritization of toxic chemicals for risk assessment by using the in silico tools. The methodology presented here applies chemometrical analysis on the existing experimental data and predicts the toxicity of new compounds. QSAR analyses were performed on the available 58 mouse and 50 rat LD(50) oral data using multiple linear regression (MLR) based on theoretical molecular descriptors selected by genetic algorithm (GA). Training and prediction sets were prepared a priori from available experimental datasets in terms of structure and response. These sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the models were verified on 376 per- and polyfluorinated chemicals including those in REACH preregistration list. The rat and mouse endpoints were predicted by each model for the studied compounds, and finally 30 compounds, all perfluorinated, were prioritized as most important for experimental toxicity analysis under the project. In addition, cumulative study on compounds within the AD of all four models, including two earlier published models on LC(50) rodent analysis was studied and the cumulative toxicity trend was observed using principal component analysis (PCA). The similarities and the differences observed in terms of descriptors and chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic compounds are highlighted.

  13. Monoenergetic electron parameters in a spheroid bubble model

    Institute of Scientific and Technical Information of China (English)

    H.Sattarian; Sh.Rahmatallahpur; T.Tohidi

    2013-01-01

    A reliable analytical expression for the potential of plasma waves with phase velocities near the speed of light is derived.The presented spheroid cavity model is more consistent than the previous spherical and ellipsoidal models and it explains the mono-energetic electron trajectory more accurately,especially at the relativistic region.The maximum energy of electrons is calculated and it is shown that the maximum energy of the spheroid model is less than that of the spherical model.The electron energy spectrum is also calculated and it is found that the energy distribution ratio of electrons △E/E for the spheroid model under the conditions reported here is half that of the spherical model and it is in good agreement with the experimental value in the same conditions.As a result,the quasi-mono-energetic electron output beam interacting with the laser plasma can be more appropriately described with this model.

  14. Modeling of TCE and Toluene Toxicity to Pseudomonas putida F1

    Science.gov (United States)

    Singh, R.; Olson, M. S.

    2009-12-01

    Prediction of viable bacterial distribution with respect to contaminants is important for efficient bioremediation of contaminated ground-water aquifers, particularly those contaminated with residual NAPLs. While bacterial motility and chemotaxis may help situate bacteria close to high concentrations of contaminant thereby enhancing bioremediation, prolonged exposure to high concentrations of contaminates is toxic to contaminant-degrading bacteria. The purpose of this work is to model the toxicity of trichloroethylene and toluene to Pseudomonas putida F1. The Live/Dead® bacterial viability assay was used to determine the toxic effect of chemical contaminants on the viability of P. putida F1 in a sealed zero head-space experimental environment. Samples of bacterial suspensions were exposed to common ground-water pollutants, TCE and toluene, for different durations. Changes in live and dead cell populations were monitored over the course of experiments using fluorescence microscopy. Data obtained from these toxicity experiments were fit to simple linear and exponential bacterial decay models using non-linear regression to describe loss of bacterial viability. TCE toxicity to P. putida F1 was best described with an exponential decay model (Figure 1a), with a decay constant kTCE = 0.025 h-4.95 (r2 = 0.956). Toluene toxicity showed a marginally better fit to the linear decay model (Figure 1b) (r2 = 0.971), with a decay constant ktoluene = 0.204 h-1. Best-fit model parameters obtained for both TCE and toluene were used to predict bacterial viability in toxicity experiments with higher contaminant concentrations and matched well with experimental data. Results from this study can be used to predict bacterial accumulation and viability near NAPL sources, and thus may be helpful in improving bioremediation performance assessment of contaminated sites. Figure 1: Survival ratios (S = N/No) of P. putida F1 in TCE- (a) and toluene- (b) stressed samples (observed (

  15. Production of no carrier added 80mBr for investigation of Auger electron toxicity.

    Science.gov (United States)

    Mease, R C; DeJesus, O T; Gatley, S J; Harper, P V; Desombre, E R; Friedman, A M

    1991-01-01

    80mBr (half-life = 4.43 h) is an Auger electron emitting nuclide with convenient properties for investigating Auger electron cytotoxicity and with potential for labeling in vivo radiotherapeutic agents. We have investigated three cyclotron target systems capable of generating 80mBr of sufficiently high specific radioactivity (no carrier added) for biomedical experiments. A 83Kr gas target irradiated with 21.5 MeV deuterons made 80mBr at a production yield of 1.6 +/- 0.2 mCi/muAh at saturation. A five-fold increase in 80mBr yield was obtained from 15 MeV proton irradiation of thin elemental Se enriched in 80Se targets although technical improvements are expected to further raise this production yield. This route is therefore superior for current medical cyclotrons. Irradiation of a reusable 80Se copper selenide target also yielded multi-millicurie amounts of 80mBr, and recovery of radiobromine by dry distillation is faster and more convenient than in the elemental Se target, but an optimum copper selenide target for 80mBr production has not yet been built.

  16. Copper Toxicity Affects Photosystem II Electron Transport at the Secondary Quinone Acceptor, QB1

    Science.gov (United States)

    Mohanty, Narendranath; Vass, Imre; Demeter, Sándor

    1989-01-01

    The nature of Cu2+ inhibition of photosystem II (PSII) photochemistry in pea (Pisum sativum L.) thylakoids was investigated monitoring Hill activity and light emission properties of photosystem II. In Cu2+-inhibited thylakoids, diphenyl carbazide addition does not relieve the loss of Hill activity. The maximum yield of fluorescence induction restored by hydroxylamine in Tris-inactivated thylakoids is markedly reduced by Cu2+. This suggests that Cu2+ does not act on the donor side of PSII but on the reaction center of PSII or on components beyond. Thermoluminescence and delayed luminescence studies show that charge recombination between the positively charged intermediate in water oxidation cycle (S2) and negatively charged primary quinone acceptor of pSII (QA−) is largely unaffected by Cu2+. The S2QB− charge recombination, however, is drastically inhibited which parallels the loss of Hill activity. This indicates that Cu2+ inhibits photosystem II photochemistry primarily affecting the function of the secondary quinone electron acceptor, QB. We suggest that Cu2+ does not block electron flow between the primary and secondary quinone acceptor but modifies the QB site in such a way that it becomes unsuitable for further photosystem II photochemistry. PMID:16666731

  17. Cadmium toxicity in perinatal rat hepatocytes: Electron microscopy, X-ray microanalysis, and morphometric analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kawahara, A.; Yoshizuka, M.; Hirano, T.; Ohsato, K.; Fujimoto, S. (Univ. of Occupational and Environmental Health, Kitakyushu (Japan))

    1990-10-01

    Effects of cadmium on the fetal and postnatal rat hepatocytes were studied with an electron microscope and an X-ray microanalyzer. Pregnant and lactating Wistar rat dams at 15 and 21 days of pregnancy and at 3 days after delivery received intraperitoneal injections of cadmium sulfate (1 mg/kg body weight) for 3 days. On the day following the last injection, the livers were isolated from the fetal and suckling rats and provided for electron microscopy. The livers from the untreated fetal and newborn rats served as control. Large bile canaliculi, which were formed by five or more hepatocytes, were frequently observed in the cadmium-treated perinatal rat livers. The intercellular space between each adjacent hepatocyte was widened. By X-ray microanalysis, cadmium peaks were preferentially detected out from intramitochondrial granules of the cadmium-treated hepatocytes. By morphometric analysis, the increase both in the mitochondria volume and in the number of intramitochondrial granules was evident in the cadmium-treated hepatocytes when compared to those of control. These data suggest the preferential accumulation of cadmium in mitochondria of the hepatocytes interferes with the morphogenesis of the perinatal rat liver.

  18. Utilization of toxic and vapors as alternate electron acceptors in biofilters

    Energy Technology Data Exchange (ETDEWEB)

    Lee, B.D.; Apel, W.A.; Walton, M.R.

    1997-08-01

    Conceptually, biofilters are vapor phase bioreactors that rely on microorganisms in the bed medium to oxidize contaminants in off-gases flowing through the bed to less hazardous compounds. In the most studied and utilized systems reduced compounds such as fuel hydrocarbons are enzymatically oxidized to compounds such as carbon dioxide and water. In these types of reactions the microorganisms in the bed oxidize the contaminant and transfer the electrons to oxygen which is the terminal electron acceptor in the process. In essence the contaminant is the carbon and energy source for the microorganisms in the bed medium and through this catabolic process oxygen is reduced to water. An example of this oxidation process can be seen during the degradation of benzene and similar aromatic compounds. Aromatics are initially attacked by a dioxygenase enzyme which oxidizes the compounds to a labile dihydrodiole which is spontaneously converted to a catechol. The dihydroxylated aromatic rings is then opened by oxidative {open_quotes}ortho{close_quotes} or {open_quotes}meta{close_quotes} cleavage yielding cis, cis-muconic acid or 2-hydroxy-cis, cis-muconic semialdehyde, respectively. These organic compounds are further oxidized to carbon dioxide or are assimilated for cellular material. This paper describes the conversion of carbon tetrachloride using methanol as the primary carbon and energy source.

  19. Modelling of electron beam absorption in complex geometries

    Science.gov (United States)

    Klassen, Alexander; Bauereiß, Andreas; Körner, Carolin

    2014-02-01

    Computational modelling of processes that involve highly energetic electrons like electron beam melting, welding, drilling or electron beam lithography, to name but a few, requires information about the attenuation of the electron beam as it passes through the sample. Depth-dose curves as a function of electron energy, target material as well as local surface obliquity have to be provided in situ during the calculation. The most efficient way to address this issue is by employing mathematical expressions. Therefore, we propose an electron beam model based on a set of semi-empirical equations available from different published literature and on theoretical considerations. Particular stress is thereby put on accuracy and the range of validity of the theoretical approach by comparison with experimental data. Finally, we apply our model to powder-bed based additive manufacturing. The numerical results demonstrate that electron beam absorption and depth of penetration have a strong influence on the quality of the fabricated product.

  20. VHDL Model of Electronic-Lock System

    Directory of Open Access Journals (Sweden)

    J. Noga

    2000-04-01

    Full Text Available The paper describes the design of an electronic-lock system which wascompleted as part of the Basic VHDL course in the Department of Controland Measurement Faculty of Electrical Engineering and Informatics,Technical University of Ostrava, Czech Republic in co-operation withthe Department if Electronic Engineering, University of Hull, GreatBritain in the frame of TEMPUS project no. S_JEP/09468-95.

  1. From basic physics to mechanisms of toxicity: the "liquid drop" approach applied to develop predictive classification models for toxicity of metal oxide nanoparticles.

    Science.gov (United States)

    Sizochenko, Natalia; Rasulev, Bakhtiyor; Gajewicz, Agnieszka; Kuz'min, Victor; Puzyn, Tomasz; Leszczynski, Jerzy

    2014-11-21

    Many metal oxide nanoparticles are able to cause persistent stress to live organisms, including humans, when discharged to the environment. To understand the mechanism of metal oxide nanoparticles' toxicity and reduce the number of experiments, the development of predictive toxicity models is important. In this study, performed on a series of nanoparticles, the comparative quantitative-structure activity relationship (nano-QSAR) analyses of their toxicity towards E. coli and HaCaT cells were established. A new approach for representation of nanoparticles' structure is presented. For description of the supramolecular structure of nanoparticles the "liquid drop" model was applied. It is expected that a novel, proposed approach could be of general use for predictions related to nanomaterials. In addition, in our study fragmental simplex descriptors and several ligand-metal binding characteristics were calculated. The developed nano-QSAR models were validated and reliably predict the toxicity of all studied metal oxide nanoparticles. Based on the comparative analysis of contributed properties in both models the LDM-based descriptors were revealed to have an almost similar level of contribution to toxicity in both cases, while other parameters (van der Waals interactions, electronegativity and metal-ligand binding characteristics) have unequal contribution levels. In addition, the models developed here suggest different mechanisms of nanotoxicity for these two types of cells.

  2. Acute toxicity of metals and reference toxicants to a freshwater ostracod, Cypris subglobosa Sowerby, 1840 and correlation to EC{sub 50} values of other test models

    Energy Technology Data Exchange (ETDEWEB)

    Khangarot, B.S., E-mail: bkhangarot@hotmail.com [Ecotoxicology Division, Indian Institute of Toxicology Research (Formerly: Industrial Toxicology Research Centre), Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001 (India); Das, Sangita [Ecotoxicology Division, Indian Institute of Toxicology Research (Formerly: Industrial Toxicology Research Centre), Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001 (India)

    2009-12-30

    The ostracod Cypris subglobosa Sowerby, 1840 static bioassay test on the basis of a 48 h of 50% of immobilization (EC{sub 50}) has been used to measure the toxicity of 36 metals and metalloids and 12 reference toxicants. Among the 36 metals and metalloids, osmium (Os) was found to be the most toxic in the test while boron (B), the least toxic. The EC{sub 50} values of this study revealed positive linear relationship with the established test models of cladoceran (Daphnia magna), sludge worm (Tubifex tubifex), chironomid larvae (Chironomus tentans), protozoan (Tetrahymena pyriformis), fathead minnow (Pimephales promelas), bluegill sunfish (Lepomis macrochirus), and aquatic macrophyte duckweed (Lemna minor). Correlation coefficients (r{sup 2}) for 17 physicochemical properties of metals or metal ions and EC{sub 50}s (as pM) were examined by linear regression analysis. The electronegativity, ionization potential, melting point, solubility product of metal sulfides (pK{sub sp}), softness parameter and some other physicochemical characteristics were significantly correlated with EC{sub 50}s of metals to C. subglobosa. The reproducibility of toxicity test was determined using 12 reference toxicants. The coefficient of variability of the EC{sub 50}s ranged from 6.95% to 55.37% and variability was comparable to that noticed for D. magna and other aquatic test models. The study demonstrated the need to include crustacean ostracods in a battery of biotests to detect the presence of hazardous chemicals in soils, sewage sludges, sediments and aquatic systems.

  3. A kinetic model for runaway electrons in the ionosphere

    Directory of Open Access Journals (Sweden)

    G. Garcia

    2006-09-01

    Full Text Available Electrodynamic models and measurements with satellites and incoherent scatter radars predict large field aligned current densities on one side of the auroral arcs. Different authors and different kinds of studies (experimental or modeling agree that the current density can reach up to hundreds of µA/m2. This large current density could be the cause of many phenomena such as tall red rays or triggering of unstable ion acoustic waves. In the present paper, we consider the issue of electrons moving through an ionospheric gas of positive ions and neutrals under the influence of a static electric field. We develop a kinetic model of collisions including electrons/electrons, electrons/ions and electrons/neutrals collisions. We use a Fokker-Planck approach to describe binary collisions between charged particles with a long-range interaction. We present the essential elements of this collision operator: the Langevin equation for electrons/ions and electrons/electrons collisions and the Monte-Carlo and null collision methods for electrons/neutrals collisions. A computational example is given illustrating the approach to equilibrium and the impact of the different terms (electrons/electrons and electrons/ions collisions on the one hand and electrons/neutrals collisions on the other hand. Then, a parallel electric field is applied in a new sample run. In this run, the electrons move in the z direction parallel to the electric field. The first results show that all the electron distribution functions are non-Maxwellian. Furthermore, runaway electrons can carry a significant part of the total current density, up to 20% of the total current density.

  4. QSAR models for predicting in vivo aquatic toxicity of chlorinated alkanes to fish

    NARCIS (Netherlands)

    Zvinavashe, E.; Berg, H. van den; Soffers, A.E.M.F.; Vervoort, J.; Freidig, A.; Murk, A.J.; Rietjens, I.M.C.M.

    2008-01-01

    Quantitative structure-activity relationship (QSAR) models are expected to play a crucial role in reducing the number of animals to be used for toxicity testing resulting from the adoption of the new European Union chemical control system called Registration, Evaluation, and Authorization of Chemica

  5. Köln-Timişoara Molecular Activity Combined Models toward Interspecies Toxicity Assessment

    Science.gov (United States)

    Chicu, Sergiu A.; Putz, Mihai V.

    2009-01-01

    Aiming to provide a unified picture of computed activity – quantitative structure activity relationships, the so called Köln (ESIP-ElementSpecificInfluenceParameter) model for activity and Timisoara (Spectral-SAR) formulation of QSAR were pooled in order to assess the toxicity modeling and inter-toxicity correlation maps for aquatic organisms against paradigmatic organic compounds. The Köln ESIP model for estimation of a compound toxicity is based on the experimental measurement expressing the direct action of chemicals on the organism Hydractinia echinata so that the structural influence parameters are reflected by the metamorphosis degree itself. As such, the calculation of the structural parameters is absolutely necessary for correct evaluation and interpretation of the evolution of M(easured) and the C(computed) values. On the other hand, the Timişoara Spectral-SAR analysis offers correlation models and paths for H.e. species as well as for four other different organisms with which the toxicity may be inter-changed by means of the same mechanism of action induced by certain common chemicals. PMID:20057956

  6. In silico prediction of toxicity of non-congeneric industrial chemicals using ensemble learning based modeling approaches

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Kunwar P., E-mail: kpsingh_52@yahoo.com; Gupta, Shikha

    2014-03-15

    Ensemble learning approach based decision treeboost (DTB) and decision tree forest (DTF) models are introduced in order to establish quantitative structure–toxicity relationship (QSTR) for the prediction of toxicity of 1450 diverse chemicals. Eight non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals was evaluated using Tanimoto similarity index. Stochastic gradient boosting and bagging algorithms supplemented DTB and DTF models were constructed for classification and function optimization problems using the toxicity end-point in T. pyriformis. Special attention was drawn to prediction ability and robustness of the models, investigated both in external and 10-fold cross validation processes. In complete data, optimal DTB and DTF models rendered accuracies of 98.90%, 98.83% in two-category and 98.14%, 98.14% in four-category toxicity classifications. Both the models further yielded classification accuracies of 100% in external toxicity data of T. pyriformis. The constructed regression models (DTB and DTF) using five descriptors yielded correlation coefficients (R{sup 2}) of 0.945, 0.944 between the measured and predicted toxicities with mean squared errors (MSEs) of 0.059, and 0.064 in complete T. pyriformis data. The T. pyriformis regression models (DTB and DTF) applied to the external toxicity data sets yielded R{sup 2} and MSE values of 0.637, 0.655; 0.534, 0.507 (marine bacteria) and 0.741, 0.691; 0.155, 0.173 (algae). The results suggest for wide applicability of the inter-species models in predicting toxicity of new chemicals for regulatory purposes. These approaches provide useful strategy and robust tools in the screening of ecotoxicological risk or environmental hazard potential of chemicals. - Graphical abstract: Importance of input variables in DTB and DTF classification models for (a) two-category, and (b) four-category toxicity intervals in T. pyriformis data. Generalization and predictive abilities of the

  7. Model Order Reduction for Electronic Circuits:

    DEFF Research Database (Denmark)

    Hjorth, Poul G.; Shontz, Suzanne

    Electronic circuits are ubiquitous; they are used in numerous industries including: the semiconductor, communication, robotics, auto, and music industries (among many others). As products become more and more complicated, their electronic circuits also grow in size and complexity. This increased...... the need for circuit simulators to evaluate potential designs before fabrication, as integrated circuit prototypes are expensive to build, and troubleshooting is difficult. In this report, we focus on the simulation of printed circuit boards (PCB’s) and interconnects both of which are of great importance...

  8. Occurrence and Concentrations of Toxic VOCs in the Ambient Air of Gumi, an Electronics-Industrial City in Korea

    Directory of Open Access Journals (Sweden)

    Sung-Ok Baek

    2015-08-01

    Full Text Available This study was carried out to characterize the occurrence and concentrations of a variety of volatile organic compounds (VOCs including aliphatic, aromatic, halogenated, nitrogenous, and carbonyl compounds, in the ambient air of Gumi City, where a large number of electronics industries are found. Two field monitoring campaigns were conducted for a one year period in 2003/2004 and 2010/2011 at several sampling sites in the city, representing industrial, residential and commercial areas. More than 80 individual compounds were determined in this study, and important compounds were then identified according to their abundance, ubiquity and toxicity. The monitoring data revealed toluene, trichloroethylene and acetaldehyde to be the most significant air toxics in the city, and their major sources were mainly industrial activities. On the other hand, there was no clear evidence of an industrial impact on the concentrations of benzene and formaldehyde in the ambient air of the city. Overall, seasonal variations were not as distinct as locational variations in the VOCs concentrations, whereas the within-day variations showed a typical pattern of urban air pollution, i.e., increase in the morning, decrease in the afternoon, and an increase again in the evening. Considerable decreases in the concentrations of VOCs from 2003 to 2011 were observed. The reductions in the ambient concentrations were confirmed further by the Korean PRTR data in industrial emissions within the city. Significant decreases in the concentrations of benzene and acetaldehyde were also noted, whereas formaldehyde appeared to be almost constant between the both campaigns. The decreased trends in the ambient levels were attributed not only to the stricter regulations for VOCs in Korea, but also to the voluntary agreement of major companies to reduce the use of organic solvents. In addition, a site planning project for an eco-friendly industrial complex is believed to play a contributory

  9. Molecular modeling and multiscaling issues for electronic material applications

    CERN Document Server

    Iwamoto, Nancy; Yuen, Matthew; Fan, Haibo

    Volume 1 : Molecular Modeling and Multiscaling Issues for Electronic Material Applications provides a snapshot on the progression of molecular modeling in the electronics industry and how molecular modeling is currently being used to understand material performance to solve relevant issues in this field. This book is intended to introduce the reader to the evolving role of molecular modeling, especially seen through the eyes of the IEEE community involved in material modeling for electronic applications.  Part I presents  the role that quantum mechanics can play in performance prediction, such as properties dependent upon electronic structure, but also shows examples how molecular models may be used in performance diagnostics, especially when chemistry is part of the performance issue.  Part II gives examples of large-scale atomistic methods in material failure and shows several examples of transitioning between grain boundary simulations (on the atomistic level)and large-scale models including an example ...

  10. TEARHS - Modelling toxic impacts on the airway system from exposure to fluctuating concentrations

    DEFF Research Database (Denmark)

    Duijm, N.J.; Markert, Frank; Ott, Søren

    2000-01-01

    information on toxic effects and the relevant time scale for exposure. Concentration-time-fatality relations areobtained from experiments with rats down to 5 minutes of exposure. If the information from these relations is extrapolated down to 5 to 10 seconds using different assumptions, the predicted...... to be small, in the order of a few seconds. Considering the aspiration pattern, it is concluded that relevant time scale for absorption in the airways is 5 to 10seconds. In real atmospheric, toxic gas clouds, fluctuations at this time scale are large. There is still a large gap between the empirical...... mortality is quite different. This study indicates thatatmospheric dispersion models for acutely toxic substances need to provide information about concentration fluctuations of time scales of 5 to 10 sec. Final conclusions can only be drawn when it becomes clear how the gap betweenconcentration...

  11. A New In Vivo Model System to Assess the Toxicity of Semiconductor Nanocrystals

    Directory of Open Access Journals (Sweden)

    Angela Tino

    2011-01-01

    Full Text Available In the emerging area of nanotechnology, a key issue is related to the potential impacts of the novel nanomaterials on the environment and human health, so that this technology can be used with minimal risk. Specifically designed to combine on a single structure multipurpose tags and properties, smart nanomaterials need a comprehensive characterization of both chemicophysical properties and adequate toxicological evaluation, which is a challenging endeavour; the in vitro toxicity assays that are often employed for nanotoxicity assessments do not accurately predict in vivo response. To overcome these limitations and to evaluate toxicity characteristics of cadmium telluride quantum dots in relation to surface coatings, we have employed the freshwater polyp Hydra vulgaris as a model system. We assessed in vivo acute and sublethal toxicity by scoring for alteration of morphological traits, population growth rates, and influence on the regenerative capabilities providing new investigation clues for nanotoxicology purposes.

  12. Using biotic ligand models to predict metal toxicity in mineralized systems

    Science.gov (United States)

    Smith, Kathleen S.; Balistrieri, Laurie S.; Todd, Andrew S.

    2015-01-01

    The biotic ligand model (BLM) is a numerical approach that couples chemical speciation calculations with toxicological information to predict the toxicity of aquatic metals. This approach was proposed as an alternative to expensive toxicological testing, and the U.S. Environmental Protection Agency incorporated the BLM into the 2007 revised aquatic life ambient freshwater quality criteria for Cu. Research BLMs for Ag, Ni, Pb, and Zn are also available, and many other BLMs are under development. Current BLMs are limited to ‘one metal, one organism’ considerations. Although the BLM generally is an improvement over previous approaches to determining water quality criteria, there are several challenges in implementing the BLM, particularly at mined and mineralized sites. These challenges include: (1) historically incomplete datasets for BLM input parameters, especially dissolved organic carbon (DOC), (2) several concerns about DOC, such as DOC fractionation in Fe- and Al-rich systems and differences in DOC quality that result in variations in metal-binding affinities, (3) water-quality parameters and resulting metal-toxicity predictions that are temporally and spatially dependent, (4) additional influences on metal bioavailability, such as multiple metal toxicity, dietary metal toxicity, and competition among organisms or metals, (5) potential importance of metal interactions with solid or gas phases and/or kinetically controlled reactions, and (6) tolerance to metal toxicity observed for aquatic organisms living in areas with elevated metal concentrations.

  13. A simple and low-toxic method of preparing small specimens of bacteria, flagellates and their likes for Scanning Electron Microscopy

    DEFF Research Database (Denmark)

    Møller, O. S.; Buchman, K.; Dalsgaard, Inger

    2013-01-01

    The preparation of samples of bacteria and other very small organisms (Scanning Electron Microscopy is often complex and intricate, which typically involve the use of specialized filter systems, complex handling and toxic chemicals. Based on the methods described in the literature...

  14. Orbital Models and Electronic Structure Theory

    DEFF Research Database (Denmark)

    Linderberg, Jan

    2012-01-01

    This tribute to the work by Carl Johan Ballhausen focuses on the emergence of quantitative means for the study of the electronic properties of complexes and molecules. Development, refinement and application of the orbital picture elucidated electric and magnetic features of ranges of molecules...

  15. On the applicability of one- and many-electron quantum chemistry models for hydrated electron clusters.

    Science.gov (United States)

    Turi, László

    2016-04-21

    We evaluate the applicability of a hierarchy of quantum models in characterizing the binding energy of excess electrons to water clusters. In particular, we calculate the vertical detachment energy of an excess electron from water cluster anions with methods that include one-electron pseudopotential calculations, density functional theory(DFT) based calculations, and ab initio quantum chemistry using MP2 and eom-EA-CCSD levels of theory. The examined clusters range from the smallest cluster size (n = 2) up to nearly nanosize clusters with n = 1000 molecules. The examined cluster configurations are extracted from mixed quantum-classical molecular dynamics trajectories of cluster anions with n = 1000 water molecules using two different one-electron pseudopotenial models. We find that while MP2 calculations with large diffuse basis set provide a reasonable description for the hydrated electron system, DFT methods should be used with precaution and only after careful benchmarking. Strictly tested one-electron psudopotentials can still be considered as reasonable alternatives to DFT methods, especially in large systems. The results of quantum chemistry calculations performed on configurations, that represent possible excess electron binding motifs in the clusters, appear to be consistent with the results using a cavitystructure preferring one-electron pseudopotential for the hydrated electron, while they are in sharp disagreement with the structural predictions of a non-cavity model.

  16. A new ONERA-CNES Slot Electron Model.

    OpenAIRE

    Sicart-Piet, A.; Boscher, D.; Lazaro, D.; Bourdarie, S.; G. Rolland

    2013-01-01

    A new model of electron flux in the Slot Region has been developed at ONERA. This model is based on several data sets, low altitudes data as POES or SAC-C measurements, but also data at higher altitudes as HEO1, HEO3, ICO and CRRES measurements. This model provides mean electron flux between L=2 and L=4 for energies between 0.1 MeV and 3 MeV. This model includes a confidence level which takes into account the dynamics of electron flux in the slot region.

  17. Human intake fraction of toxic pollutants: a model comparison between caltox and uses-lca

    OpenAIRE

    Huijbregts, Mark A J; Geelen, Loes M.J.; Edgar G. Hertwich; McKone, Thomas E.; Meent, Dik van de

    2004-01-01

    In Life Cycle Assessment and Comparative Risk Assessment potential human exposure to toxic pollutants can be expressed as the human intake fraction (iF), representing the fraction of the quantity emitted that enters the human population. To assess model uncertainty in the human intake fraction, ingestion and inhalation iFs of 367 substances emitted to air and freshwater were calculated with two commonly applied multi-media fate and exposure models, CalTOX and USES-LCA. Comparison of the ...

  18. Unifying mechanism for toxicity and addiction by abused drugs: electron transfer and reactive oxygen species.

    Science.gov (United States)

    Kovacic, Peter; Cooksy, Andrew L

    2005-01-01

    Abused drugs are of grave concern throughout the world for a variety of reasons. Although impressive advances have been made, there are many unknown mechanistic aspects. This report presents a novel hypothesis based on a unifying theme for action of the major classes of abused drugs, in addition to commonly abused therapeutic drugs. The approach is based on electron transfer (ET), reactive oxygen species (ROS), and oxidative stress (OS). It is significant that physiologically active substances generally incorporate ET functionalities, either per se, or more usually in their metabolites. In order to achieve ET in vivo, the reduction potential must be more positive than -0.5 V, which is the case for metabolites of abused drugs, except for special cases. Since the ET process is catalytic, only small quantities of agent are needed for generation of large amounts of ROS during redox cycyling. Bioaction with cellular materials could entail ET alone or participation of ROS. In the abused category, among the main classes of ET functionalities are quinones and iminiums, with alpha-dicarbonyl and nitroxyl radical being rarer. Nicotine yields nicotine iminium, myosmine iminium, and DNA base iminium via alkylation by a metabolic nitrosamine. In the case of alcohol, diacetyl (an alpha-dicarbonyl) is formed, which can lead to conjugated imine (or iminium) by condensation with pri-amine of protein. Phencyclidine is unusual since the iminium product is non-conjugated. However, data indicate that the conformation present at the binding site can accommodate delocalization of the derived radical. For cocaine, various metabolites may play a role: iminium, nitroxyl radical, nitrosonium and formaldehyde. Dealkylation of the ether moiety of ecstasy provides a catechol function capable of redox cycling with the o-quinone partner. Amphetamine and methamphetamine also appear to function by way of the catechol route, as well as morphine and heroin. Tetrahydrocannabinol produces an epoxide, a

  19. Insights on in vitro models for safety and toxicity assessment of cosmetic ingredients.

    Science.gov (United States)

    Almeida, Andreia; Sarmento, Bruno; Rodrigues, Francisca

    2017-03-15

    According to the current European legislation, the safety assessment of each individual cosmetic ingredient of any formulation is the basis for the safety evaluation of a cosmetic product. Also, animal testing in the European Union is prohibited for cosmetic ingredients and products since 2004 and 2009, respectively. Additionally, the commercialization of any cosmetic products containing ingredients tested on animal models was forbidden in 2009. In consequence of these boundaries, the European Centre for the Validation of Alternative Methods (ECVAM) proposes a list of validated cell-based in vitro models for predicting the safety and toxicity of cosmetic ingredients. These models have been demonstrated as valuable and effective tools to overcome the limitations of animal in vivo studies. Although the use of in vitro cell-based models for the evaluation of absorption and permeability of cosmetic ingredients is widespread, a detailed study on the properties of these platforms and the in vitro-in vivo correlation compared with human data are required. Moreover, additional efforts must be taken to develop in vitro models to predict carcinogenicity, repeat dose toxicity and reproductive toxicity, for which no alternative in vitro methods are currently available. This review paper summarizes and characterizes the most relevant in vitro models validated by ECVAM employed to predict the safety and toxicology of cosmetic ingredients. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Modeling Kleinian cosmology with electronic metamaterials

    CERN Document Server

    Figueiredo, David; Fumeron, Sébastien; Berche, Betrand; Moraes, Fernando

    2016-01-01

    This paper deals with the propagation of Klein-Gordon particles in flat background spacetime exhibiting discontinuous metric changes from a Lorentzian signature (-,+,+,+) to a Kleinian signature (-,+,+,-). A formal analogy with the propagation of electrons at a junction between an anisotropic semiconductor and an electronic metamaterial is presented. From that analogy, we study the dynamics of these particles falling onto planar boundary interfaces between these two families of media and show a mirror-like behavior for the particle flux. Finally, the case of a double junction of finite thickness is examined and the possibility of tunneling through it is discussed. A physical link between the metamaterial and the Kleinian slabs is found by calculating the time of flight of the respective traversing particles.

  1. Modeling Kleinian cosmology with electronic metamaterials

    Science.gov (United States)

    Figueiredo, David; Gomes, Felipe A.; Fumeron, Sébastien; Berche, Bertrand; Moraes, Fernando

    2016-08-01

    This paper deals with the propagation of Klein-Gordon particles in flat background spacetime exhibiting discontinuous metric changes from a Lorentzian signature (-,+,+,+) to a Kleinian signature (-,+,+,-) . A formal analogy with the propagation of electrons at a junction between an anisotropic semiconductor and an electronic metamaterial is presented. From that analogy, we study the dynamics of these particles falling onto planar boundary interfaces between these two families of media and show a mirror-like behavior for the particle flux. Finally, the case of a double junction of finite thickness is examined and the possibility of tunneling through it is discussed. A physical link between the metamaterial and the Kleinian slabs is found by calculating the time of flight of the respective traversing particles.

  2. USEtox - The UNEP-SETAC toxicity model: recommended characterisation factors for human toxicity and freshwater ecotoxicity in Life Cycle Impact Assessment

    DEFF Research Database (Denmark)

    Rosenbaum, Ralph K.; Bachmann, Till M; Gold, Lois S.

    2008-01-01

    Background, Aim and Scope. In 2005 a comprehensive comparison of LCIA toxicity characterisation models was initiated by the UNEP-SETAC Life Cycle Initiative, directly involving the model developers of CalTOX, IMPACT 2002, USES-LCA, BETR, EDIP, WATSON, and EcoSense. In this paper we describe......, it has now been used to calculate CFs for several thousand substances and forms the basis of the recommendations from UNEP-SETAC’s Life Cycle Initiative regarding characterization of toxic impacts in Life Cycle Assessment. Recommendations and Perspectives. We provide both recommended and interim (not...... this model-comparison process and its results—in particular the scientific consensus model developed by the model developers. The main objectives of this effort were (i) to identify specific sources of differences between the models’ results and structure, (ii) to detect the indispensable model components...

  3. Diminution of toxic copper accumulation in toxic milk mice modeling Wilson disease by embryonic hepatocyte intrasplenic transplantation

    Institute of Scientific and Technical Information of China (English)

    Zhu Shi; Xiu-Ling Liang; Bing-Xun Lu; Su-Yue Pan; Xi Chen; Qi-Qiang Tang; Ying Wang; Fan Huang

    2005-01-01

    AIM: To observe the therapeutic effect of intrasplenic transplantation with embryonic hepatocytes on amelioration of hereditary copper accumulation in toxic milk (TX) mouse modeling Wilson disease. METHODS: Donor hepatocytes were harvested from 14-d fetal liver of a pregnant homogeneous DL mouse. These cells were successively cultured, labeled with fluorescein dye Hoechst 33342 for 24 h, and sequentially infused into the spleen parenchyma of the recipient TX mice. No host immunosuppression measures were taken. Two and four weeks after transplantation, the recipients were killed for routine histologic investigation and immunohistochemistry study up to 4 wk after transplantation. The serum copper and ceruloplasmin concentrations of the recipient mice were determined by graphite furnace atomic absorption spectroscopy.RESULTS: In the following 2nd and 4th wk after transplantation, the donor hepatocytes could be visualized in the livers of 47.3% recipients. The serum ceruloplasmin and copper concentrations increased by 1.6-fold after 2 wk and 2.0-fold times after 4 wk respectively, which ultimately rose from about 30% of the normal level to nearly 60%(P<0.01). The hepatic copper concentration decreased 7.2%, 4 wk after transplantation. Pathologic examination showed that there were many actively proliferative hepatocyte precursor cells with specific embryonic hepatocyte marker AFP migrated into hepatic sinusoidsof the recipients. A large number of cells carrying hepatocytes marker and albumin were observed in the recipient spleen tissues.CONCLUSION: Embryonic hepatocytes are capable of differentiating into mature hepatocytes in vivo. After transplantation, the hereditary abnormalities of copper metabolism in TX mice could be corrected partially by intrasplenic transplantation of homogeneous embryonic hepatocytes.

  4. Reproductive toxicity and gender differences induced by cadmium telluride quantum dots in an invertebrate model organism

    Science.gov (United States)

    Yan, Si-Qi; Xing, Rui; Zhou, Yan-Feng; Li, Kai-Le; Su, Yuan-Yuan; Qiu, Jian-Feng; Zhang, Yun-Hu; Zhang, Ke-Qin; He, Yao; Lu, Xiao-Ping; Xu, Shi-Qing

    2016-09-01

    Sexual glands are key sites affected by nanotoxicity, but there is no sensitive assay for measuring reproductive toxicity in animals. The aim of this study was to investigate the toxic effects of cadmium telluride quantum dots (CdTe-QDs) on gonads in a model organism, Bombyx mori. After dorsal vein injection of 0.32 nmol of CdTe-QDs per individual, the QDs passed through the outer membranes of gonads via the generation of ROS in the membranes of spermatocysts and ovarioles, as well as internal germ cells, thereby inducing early germ cell death or malformations via complex mechanisms related to apoptosis and autophagy through mitochondrial and lysosomal pathways. Histological observations of the gonads and quantitative analyses of germ cell development showed that the reproductive toxicity was characterized by obvious male sensitivity. Exposure to QDs in the early stage of males had severe adverse effects on the quantity and quality of sperm, which was the main reason for the occurrence of unfertilized eggs. Ala- or Gly-conjugated QDs could reduce the nanotoxicity of CdTe-QDs during germ cell development and fertilization of their offspring. The results demonstrate that males are preferable models for evaluating the reproductive toxicity of QDs in combined in vivo/in vitro investigations.

  5. Reproductive toxicity and gender differences induced by cadmium telluride quantum dots in an invertebrate model organism

    Science.gov (United States)

    Yan, Si-Qi; Xing, Rui; Zhou, Yan-Feng; Li, Kai-Le; Su, Yuan-Yuan; Qiu, Jian-Feng; Zhang, Yun-Hu; Zhang, Ke-Qin; He, Yao; Lu, Xiao-Ping; Xu, Shi-Qing

    2016-01-01

    Sexual glands are key sites affected by nanotoxicity, but there is no sensitive assay for measuring reproductive toxicity in animals. The aim of this study was to investigate the toxic effects of cadmium telluride quantum dots (CdTe-QDs) on gonads in a model organism, Bombyx mori. After dorsal vein injection of 0.32 nmol of CdTe-QDs per individual, the QDs passed through the outer membranes of gonads via the generation of ROS in the membranes of spermatocysts and ovarioles, as well as internal germ cells, thereby inducing early germ cell death or malformations via complex mechanisms related to apoptosis and autophagy through mitochondrial and lysosomal pathways. Histological observations of the gonads and quantitative analyses of germ cell development showed that the reproductive toxicity was characterized by obvious male sensitivity. Exposure to QDs in the early stage of males had severe adverse effects on the quantity and quality of sperm, which was the main reason for the occurrence of unfertilized eggs. Ala- or Gly-conjugated QDs could reduce the nanotoxicity of CdTe-QDs during germ cell development and fertilization of their offspring. The results demonstrate that males are preferable models for evaluating the reproductive toxicity of QDs in combined in vivo/in vitro investigations. PMID:27669995

  6. Electronic learning and constructivism: a model for nursing education.

    Science.gov (United States)

    Kala, Sasikarn; Isaramalai, Sang-Arun; Pohthong, Amnart

    2010-01-01

    Nurse educators are challenged to teach nursing students to become competent professionals, who have both in-depth knowledge and decision-making skills. The use of electronic learning methods has been found to facilitate the teaching-learning process in nursing education. Although learning theories are acknowledged as useful guides to design strategies and activities of learning, integration of these theories into technology-based courses appears limited. Constructivism is a theoretical paradigm that could prove to be effective in guiding the design of electronic learning experiences for the purpose of providing positive outcomes, such as the acquisition of knowledge and decision-making skills. Therefore, the purposes of this paper are to: describe electronic learning, present a brief overview of what is known about the outcomes of electronic learning, discuss constructivism theory, present a model for electronic learning using constructivism, and describe educators' roles emphasizing the utilization of the model in developing electronic learning experiences in nursing education.

  7. Power Electronic Packaging Design, Assembly Process, Reliability and Modeling

    CERN Document Server

    Liu, Yong

    2012-01-01

    Power Electronic Packaging presents an in-depth overview of power electronic packaging design, assembly,reliability and modeling. Since there is a drastic difference between IC fabrication and power electronic packaging, the book systematically introduces typical power electronic packaging design, assembly, reliability and failure analysis and material selection so readers can clearly understand each task's unique characteristics. Power electronic packaging is one of the fastest growing segments in the power electronic industry, due to the rapid growth of power integrated circuit (IC) fabrication, especially for applications like portable, consumer, home, computing and automotive electronics. This book also covers how advances in both semiconductor content and power advanced package design have helped cause advances in power device capability in recent years. The author extrapolates the most recent trends in the book's areas of focus to highlight where further improvement in materials and techniques can d...

  8. Mathematical model of the growth of a mollusk affected by a toxicant and by temperature fluctuations

    Energy Technology Data Exchange (ETDEWEB)

    Kurchenko, T.S.; Burtnaya, I.L.

    1979-01-01

    An attempt is made to model the effect of a gamma isomer of hexachloran (lindane) and of temperature fluctuations on the growth of bivalves. The model is based on an experimental study of the effect of the toxicant on Radix ovata and Viviparus viviparus, and also on the Putter-Bertalanffy-Vinberg models and the model of Zotin. Quite good agreements has been obtained between calculated and experimental data, and growth curves have been constructed for the weight increase of the animals when exposed to lindane concentrations not tested in the experiment.

  9. Dechlorination kinetics of TCE at toxic TCE concentrations: Assessment of different models.

    Science.gov (United States)

    Haest, P J; Springael, D; Smolders, E

    2010-01-01

    The reductive dechlorination of trichloroethene (TCE) in a TCE source zone can be self-inhibited by TCE toxicity. A study was set up to examine the toxicity of TCE in terms of species specific degradation kinetics and microbial growth and to evaluate models that describe this self-inhibition. A batch experiment was performed using the TCE dechlorinating KB-1 culture at initial TCE concentrations ranging from 0.04mM to saturation (8.4mM). Biodegradation activity was highest at 0.3mM TCE and no activity was found at concentrations from 4 to 8mM. Species specific TCE and cis-DCE (cis-dichloroethene) degradation rates and Dehalococcoides numbers were modeled with Monod kinetics combined with either Haldane inhibition or a log-logistic dose-response inhibition on these rates. The log-logistic toxicity model appeared the most appropriate model and predicts that the species specific degradation activities are reduced by a factor 2 at about 1mM TCE, respectively cis-DCE. However, the model showed that the inhibitive effects on the time for TCE to ethene degradation are a complex function of degradation kinetics and the initial cell densities of the dechlorinating species. Our analysis suggests that the self-inhibition on biodegradation cannot be predicted by a single concentration threshold without information on the cell densities.

  10. Web-Based Toxic Gas Dispersion Model for Shuttle Launch Operations

    Science.gov (United States)

    Bardina, Jorge; Thirumalainambi, Rajkumar

    2004-01-01

    During the launch of the Space Shuttle vehicle, the burning of liquid hydrogen fuel with liquid oxygen at extreme high temperatures inside the three space shuttle main engines, and the burning of the solid propellant mixture of ammonium perchlorate oxidizer, aluminum fuel, iron oxide catalyst, polymer binder, and epoxy curing agent in the two solid rocket boosters result in the formation of a large cloud of hot, buoyant toxic exhaust gases near the ground level which subsequently rises and entrains into ambient air until the temperature and density of the cloud reaches an approximate equilibrium with ambient conditions. In this paper, toxic gas dispersion for various gases are simulated over the web for varying environmental conditions which is provided by rawinsonde data. The model simulates chemical concentration at ground level up to 10 miles (1 KM grids) in downrange up to an hour after launch. The ambient concentration of the gas dispersion and the deposition of toxic particles are used as inputs for a human health risk assessment model. The advantage of the present model is the accessibility and dissemination of model results to other NASA centers over the web. The model can be remotely operated and various scenarios can be analyzed.

  11. alpha-Synuclein budding yeast model: toxicity enhanced by impaired proteasome and oxidative stress.

    Science.gov (United States)

    Sharma, Nijee; Brandis, Katrina A; Herrera, Sara K; Johnson, Brandon E; Vaidya, Tulaza; Shrestha, Ruja; Debburman, Shubhik K

    2006-01-01

    Parkinson's disease (PD) is a common neurodegenerative disorder that results from the selective loss of midbrain dopaminergic neurons. Misfolding and aggregation of the protein alpha-synuclein, oxidative damage, and proteasomal impairment are all hypotheses for the molecular cause of this selective neurotoxicity. Here, we describe a Saccharomyces cerevisiae model to evaluate the misfolding, aggregation, and toxicity-inducing ability of wild-type alpha-synuclein and three mutants (A30P, A53T, and A30P/A53T), and we compare regulation of these properties by dysfunctional proteasomes and by oxidative stress. We found prominent localization of wild-type and A53T alpha-synuclein near the plasma membrane, supporting known in vitro lipid-binding ability. In contrast, A30P was mostly cytoplasmic, whereas A30P/A53T displayed both types of fluorescence. Surprisingly, alpha-synuclein was not toxic to several yeast strains tested. When yeast mutants for the proteasomal barrel (doa3-1) were evaluated, delayed alpha-synuclein synthesis and membrane association were observed; yeast mutant for the proteasomal cap (sen3-1) exhibited increased accumulation and aggregation of alpha-synuclein. Both sen3-1and doa3-1 mutants exhibited synthetic lethality with alpha-synuclein. When yeasts were challenged with an oxidant (hydrogen peroxide), alpha-synuclein was extremely lethal to cells that lacked manganese superoxide dismutase Mn-SOD (sod2Delta) but not to cells that lacked copper, zinc superoxide dismutase Cu,Zn-SOD (sod1Delta). Despite the toxicity, sod2Delta cells never displayed intracellular aggregates of alpha-synuclein. We suggest that the toxic alpha-synuclein species in yeast are smaller than the visible aggregates, and toxicity might involve alpha-synuclein membrane association. Thus, yeasts have emerged effective organisms for characterizing factors and mechanisms that regulate alpha-synuclein toxicity.

  12. Real-Time Cell-Electronic Sensing of Coal Fly Ash Particulate Matter for Toxicity-Based Air Quality Monitoring.

    Science.gov (United States)

    Moe, Birget; Yuan, Chungang; Li, Jinhua; Du, Haiying; Gabos, Stephan; Le, X Chris; Li, Xing-Fang

    2016-06-20

    The development of a unique bioassay for cytotoxicity analysis of coal fly ash (CFA) particulate matter (PM) and its potential application for air quality monitoring is described. Using human cell lines, A549 and SK-MES-1, as live probes on microelectrode-embedded 96-well sensors, impedance changes over time are measured as cells are treated with varying concentrations (1 μg/mL-20 mg/mL) of CFA samples. A dose-dependent impedance change is determined for each CFA sample, from which an IC50 histogram is obtained. The assay was successfully applied to examine CFA samples collected from three coal-fired power plants (CFPs) in China. The samples were separated into three size fractions: PM2.5 (10 μm). Dynamic cell-response profiles and temporal IC50 histograms of all samples show that CFA cytotoxicity depends on concentration, exposure time (0-60 h), and cell-type (SK-MES-1 > A549). The IC50 values differentiate the cytotoxicity of CFA samples based on size fraction (PM2.5 ≈ PM10-2.5 ≫ PM10) and the sampling location (CFP2 > CFP1 ≈ CFP3). Differential cytotoxicity measurements of particulates in human cell lines using cell-electronic sensing provide a useful tool for toxicity-based air quality monitoring and risk assessment.

  13. Forecasting relativistic electron flux using dynamic multiple regression models

    Directory of Open Access Journals (Sweden)

    H.-L. Wei

    2011-02-01

    Full Text Available The forecast of high energy electron fluxes in the radiation belts is important because the exposure of modern spacecraft to high energy particles can result in significant damage to onboard systems. A comprehensive physical model of processes related to electron energisation that can be used for such a forecast has not yet been developed. In the present paper a systems identification approach is exploited to deduce a dynamic multiple regression model that can be used to predict the daily maximum of high energy electron fluxes at geosynchronous orbit from data. It is shown that the model developed provides reliable predictions.

  14. Peculiarities of designing Holistic Electronic Government Services Integration Model

    Directory of Open Access Journals (Sweden)

    Tadas Limba

    2011-12-01

    Full Text Available Purpos– the aim ok this paper is to develop a Holistic Electronic Government Services Integration Model which could ensure the efficient integration of electronic government services in the local self-government level.Methodolog– the following analyses have been carried out in thirkpaper: theoretical-systematic; normative and conceptual comparative analysis of the researcha A method of modeling has also been applied.Finding– the scientific work analyzes the improvement opportunities of the models of electronic government services and their application alternatives in Lithuanian municipalities. The newly developed model of electronic government services that has been designed basng on the principle of integrating online expert consultation is primarily targeted at improvement of inside processes’ changes of an organization. Practicing the application of that model in the local self-government level starting with improvement of inside processes of an organization should help adapt more accurately and efficiently to the changing needs of the society while providing electronic government services, thus establishing a higher public value.Practical implication– the practical novelty of work is reflected not only through the integration opportunities’ assessment of the principle of online expert consultation services into the theoretical models of electronic government services that have already been developed by the scientists, but also on the basis of this principle there has been created a “Holistic Electronic Government Services Integration Model” in accordance with “E-Diamond” model basis and its practical application realization with the design of “The project of implementing the principle of online expert consultation on the model of electronic government services” for the future investigations.Originalit– the systematic, comparative analysis of the models of electronic government services carried out in the scientific

  15. A polaron model for electron transfer in globular proteins.

    Science.gov (United States)

    Chuev, G N; Lakhno, V D

    1993-07-07

    Polaron models have been considered for the electron states in protein globules existing in a solvent. These models account for two fundamental effects, viz, polarization interaction of an electron with the conformational vibrations and the heterogeneity of the medium. Equations have been derived to determine the electron state in a protein globule. The parameters of this state show that it is an extended state with an energy of 2 eV. The electron transfer rate for cyt C self-exchange reaction has been calculated in the polaron model. Reorganization energy, tunneling matrix element and the rate constant have also been estimated. The results are compared with experimental data. The influence of model parameters on the significance of the data obtained has been studied. The potentialities of the model are discussed.

  16. Dynamic pricing models for electronic business

    Indian Academy of Sciences (India)

    Y Narahari; C V L Raju; K Ravikumar; Sourabh Shah

    2005-04-01

    Dynamic pricing is the dynamic adjustment of prices to consumers depending upon the value these customers attribute to a product or service. Today’s digital economy is ready for dynamic pricing; however recent research has shown that the prices will have to be adjusted in fairly sophisticated ways, based on sound mathematical models, to derive the benefits of dynamic pricing. This article attempts to survey different models that have been used in dynamic pricing. We first motivate dynamic pricing and present underlying concepts, with several examples, and explain conditions under which dynamic pricing is likely to succeed. We then bring out the role of models in computing dynamic prices. The models surveyed include inventory-based models, data-driven models, auctions, and machine learning. We present a detailed example of an e-business market to show the use of reinforcement learning in dynamic pricing.

  17. Lattice Boltzmann Model for Electronic Structure Simulations

    CERN Document Server

    Mendoza, M; Succi, S

    2015-01-01

    Recently, a new connection between density functional theory and kinetic theory has been proposed. In particular, it was shown that the Kohn-Sham (KS) equations can be reformulated as a macroscopic limit of the steady-state solution of a suitable single-particle kinetic equation. By using a discrete version of this new formalism, the exchange and correlation energies of simple atoms and the geometrical configuration of the methane molecule were calculated accurately. Here, we discuss the main ideas behind the lattice kinetic approach to electronic structure computations, offer some considerations for prospective extensions, and also show additional numerical results, namely the geometrical configuration of the water molecule.

  18. Teaching Behavioral Modeling and Simulation Techniques for Power Electronics Courses

    Science.gov (United States)

    Abramovitz, A.

    2011-01-01

    This paper suggests a pedagogical approach to teaching the subject of behavioral modeling of switch-mode power electronics systems through simulation by general-purpose electronic circuit simulators. The methodology is oriented toward electrical engineering (EE) students at the undergraduate level, enrolled in courses such as "Power…

  19. Electron thermal transport barriers in RTP: experiment and modelling

    NARCIS (Netherlands)

    Schilham, A.M.R.; Hogeweij, G. M. D.; Cardozo, N. J. L.

    2001-01-01

    Experiments in which very localized electron cyclotron heating (ECH) is scanned through the RTP plasma show sharp transitions, in which the electron temperature profile abruptly changes shape. The phenomenology-the profiles shapes, the sharp transitions-can be reproduced with a transport model which

  20. Temperature dependence of electronic heat capacity in Holstein model

    CERN Document Server

    Fialko, N S; Lakhno, V D

    2015-01-01

    The dynamics of charge migration was modeled to calculate temperature dependencies of its thermodynamic equilibrium values such as energy and electronic heat capacity in homogeneous adenine fragments. The energy varies from nearly polaron one at T~0 to midpoint of the conductivity band at high temperatures. The peak on the graph of electronic heat capacity is observed at the polaron decay temperature.

  1. Teaching Behavioral Modeling and Simulation Techniques for Power Electronics Courses

    Science.gov (United States)

    Abramovitz, A.

    2011-01-01

    This paper suggests a pedagogical approach to teaching the subject of behavioral modeling of switch-mode power electronics systems through simulation by general-purpose electronic circuit simulators. The methodology is oriented toward electrical engineering (EE) students at the undergraduate level, enrolled in courses such as "Power…

  2. Problem Resolution through Electronic Mail: A Five-Step Model.

    Science.gov (United States)

    Grandgenett, Neal; Grandgenett, Don

    2001-01-01

    Discusses the use of electronic mail within the general resolution and management of administrative problems and emphasizes the need for careful attention to problem definition and clarity of language. Presents a research-based five-step model for the effective use of electronic mail based on experiences at the University of Nebraska at Omaha.…

  3. GLOBOX: A spatially differentiated global fate, intake and effect model for toxicity assessment in LCA.

    Science.gov (United States)

    Wegener Sleeswijk, Anneke; Heijungs, Reinout

    2010-06-15

    GLOBOX is a model for the calculation of spatially differentiated LCA toxicity characterisation factors on a global scale. It can also be used for human and environmental risk assessment. The GLOBOX model contains equations for the calculation of fate, intake and effect factors, and equations for the calculation of LCA characterisation factors for human toxicity and ecotoxicity. The model is differentiated on the level of 239 countries/territories and 50 seas/oceans. Each region has its own set of homogeneous compartments, and the regions are interconnected by atmospheric and aquatic flows. Multimedia transport and degradation calculations are largely based on the EUSES 2.0 multimedia model, and are supplemented by specific equations to account for the advective air and water transport between different countries and/or seas. Metal-specific equations are added to account for speciation in fresh and marine surface water. Distribution parameters for multimedia transport equations are differentiated per country or sea with respect to geographic features, hydrology, and climate. The model has been tested with nitrobenzene as a test chemical, for emissions to all countries in the world. Spatially differentiated characterisation factors turn out to show wide ranges of variation between countries, especially for releases to inland water and soil compartments. Geographic position, distribution of lakes and rivers and variations in environmental temperature and rain rate are decisive parameters for a number of different characterisation factors. Population density and dietary intake play central roles in the variation of characterisation factors for human toxicity. Among the countries that show substantial deviations from average values of the characterisation factors are not only small and remote islands, but also countries with a significant economic production rate, as indicated by their GDPs. It is concluded that spatial differentiation between countries is an important

  4. Polaron Model of the Formation of Hydrated Electron States

    OpenAIRE

    2015-01-01

    A computer simulation of the formation of photoexcited electrons in water is performed within the framework of a dynamic model. The obtained results are discussed in comparison with experimental data and theoretical estimates.

  5. Blocking layer modeling for temperature analysis of electron transfer ...

    African Journals Online (AJOL)

    Blocking layer modeling for temperature analysis of electron transfer rate in quantum dot sensitized solar cells. ... Journal of Fundamental and Applied Sciences ... of the quantum dots and free energy of system and finally the Marcus equation.

  6. Electronic Modeling and Design for Extreme Temperatures Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We are developing CAD tools, models and methodologies for electronics design for circuit operation in extreme environments with focus on very low temperatures...

  7. A QICAR Model for Metal Ion Toxicity Established via PLS Method

    Institute of Scientific and Technical Information of China (English)

    LI Yu; JIANG Long; LI Xiao-li; HU Yan; WEN Jing-ya

    2013-01-01

    The partial least squares(PLS) method was employed to establish a quantitative ion characteristics-activity relationship(QICAR) model for metal ion toxicity(EC50 of 15 metal ions).The ion characteristics included AN(the atomic number),AIP(the change in ionization potential,eV),Xm(the electronegativity,eV),AW(the atomic weight),Xm2r(the covalent index),△E0(the absolute difference between electrochemical potential of the ion and that of its first stable reduced state,eV),│lgKoH│(the absolute value of the lg of the first hydrolysis constant),AR(the atomic radius,nm),AR/AW(the ratio between atomic radius and atomic weight) and σp(the softness index) selected based on relative correlation analysis.The simulated and tested(with the other four metals) efficiency coefficients of the model are 0.88 and 0.96,respectively.The information revealed from the QICAR model indicates that the value of the metal ion toxicity was positively correlated with variables AN,△IP,Xm,AW and Xm2r; negatively correlated with variables △E0,│lgKoH│,AR/AW,AR and σp,and ion characteristics AE0,Xm,σp and Xm2r were found to contribute more to the toxicity of metal ions via the accurate analysis method provided by PLS.The model could be used to predict the toxicity of the target metals and preliminary to assess combined pollution and environmental risk for heavy metals in the environments.

  8. Toxicity Mechanisms of the Food Contaminant Citrinin: Application of a Quantitative Yeast Model

    OpenAIRE

    Amparo Pascual-Ahuir; Elena Vanacloig-Pedros; Markus Proft

    2014-01-01

    Mycotoxins are important food contaminants and a serious threat for human nutrition. However, in many cases the mechanisms of toxicity for this diverse group of metabolites are poorly understood. Here we apply live cell gene expression reporters in yeast as a quantitative model to unravel the cellular defense mechanisms in response to the mycotoxin citrinin. We find that citrinin triggers a fast and dose dependent activation of stress responsive promoters such as GRE2 or SOD2. More specifical...

  9. Modelling and implementing electronic health records in Denmark

    DEFF Research Database (Denmark)

    Bernstein, Knut; Rasmussen, Morten Bruun; Vingtoft, Søren;

    2003-01-01

    The Danish Health IT strategy points out that integration between electronic health records (EHR) systems has a high priority. This paper reporst reports new tendencies in modelling and integration platforms globally and how this is reflected in the natinal development.......The Danish Health IT strategy points out that integration between electronic health records (EHR) systems has a high priority. This paper reporst reports new tendencies in modelling and integration platforms globally and how this is reflected in the natinal development....

  10. Modelling and implementing electronic health records in Denmark

    DEFF Research Database (Denmark)

    Bernstein, Knut; Rasmussen, Morten Bruun; Vingtoft, Søren

    2003-01-01

    The Danish Health IT strategy points out that integration between electronic health records (EHR) systems has a high priority. This paper reporst reports new tendencies in modelling and integration platforms globally and how this is reflected in the natinal development.......The Danish Health IT strategy points out that integration between electronic health records (EHR) systems has a high priority. This paper reporst reports new tendencies in modelling and integration platforms globally and how this is reflected in the natinal development....

  11. Peculiarities of designing Holistic Electronic Government Services Integration Model

    OpenAIRE

    Tadas Limba

    2011-01-01

    Purpose – the aim ok this paper is to develop a Holistic Electronic Government Services Integration Model which could ensure the efficient integration of electronic government services in the local self-government level. Methodology - the following analyses have been carried out in thirkpaper: theoretical-systematic; normative and conceptual comparative analysis of the researcha A method of modeling has also been applied. Finding – the scientific work analyzes the improvement opportunities of...

  12. Modeling Electronic Circular Dichroism within the Polarizable Embedding Approach

    DEFF Research Database (Denmark)

    Nørby, Morten S; Olsen, Jógvan Magnus Haugaard; Steinmann, Casper

    2017-01-01

    We present a systematic investigation of the key components needed to model single chromophore electronic circular dichroism (ECD) within the polarizable embedding (PE) approach. By relying on accurate forms of the embedding potential, where especially the inclusion of local field effects...... sampling. We show that a significant number of snapshots are needed to avoid artifacts in the calculated electronic circular dichroism parameters due to insufficient configurational sampling, thus highlighting the efficiency of the PE model....

  13. Comprehensive toxicity study of safrole using a medium-term animal model with gpt delta rats.

    Science.gov (United States)

    Jin, M; Kijima, A; Suzuki, Y; Hibi, D; Inoue, T; Ishii, Y; Nohmi, T; Nishikawa, A; Ogawa, K; Umemura, T

    2011-12-18

    In order to investigate a medium-term animal model using reporter gene transgenic rodents in which general toxicity, genotoxicity and carcinogenicity are evaluated, F344 gpt delta rats were given a diet containing 0.1% and 0.5% (a carcinogenic dose) safrole for 13 weeks. Serum biochemistry and histopathological examinations revealed overt hepatotoxicity of safrole, in line with previous reports. In the current study, safrole treatment possibly resulted in renal toxicity in male rats. In the in vivo mutation assays, an increase or a tendency to increase of the gpt mutant frequencies (MFs) was observed in both sexes at the carcinogenic dose. The number and area of foci of glutathione S-transferase placental form (GST-P) positive hepatocytes, ratio of proliferating cell nuclear antigen (PCNA)-positive hepatocytes and 8-hydroxydeoxyguanosine (8-OHdG) levels in liver DNA were significantly increased in both sexes of the 0.5% group. The overall data suggested that the present model might be a promising candidate for investigating comprehensive toxicities of the agents. In addition, data demonstrating the base modification and cell proliferation due to exposure to safrole could contribute to understanding safrole-induced hepatocarcinogenesis, which imply expanding in application of this model.

  14. Evaluation of Toxicity Ranking for Metal Oxide Nanoparticles via an in Vitro Dosimetry Model.

    Science.gov (United States)

    Liu, Rong; Liu, Haoyang Haven; Ji, Zhaoxia; Chang, Chong Hyun; Xia, Tian; Nel, Andre E; Cohen, Yoram

    2015-09-22

    It has been argued that in vitro toxicity testing of engineered nanoparticles (NPs) should consider delivered dose (i.e., NP mass settled per suspension volume) rather than relying exclusively on administered dose (initial NP mass concentration). Delivered dose calculations require quantification of NP sedimentation in tissue cell culture media, taking into consideration fundamental suspension properties. In this article, we calculate delivered dose using a first-principles "particles in a box" sedimentation model, which accounts for the particle size distribution, fractal dimension, and permeability of agglomerated NPs. The sedimentation model was evaluated against external and our own experimental sedimentation data for metal oxide NPs. We then utilized the model to construct delivered dose-response analysis for a library of metal oxide NPs (previously used for hazard ranking and prediction making) in different cell culture media. Hierarchical hazard ranking of the seven (out of 24) toxic metal oxide NPs in our library, using EC50 calculated on the basis of delivered dose, did not measurably differ from our ranking based on administered dose. In contrast, simplified sedimentation calculations based on the assumption of impermeable NP agglomerates of a single average size significantly underestimated the settled NPs' mass, resulting in misinterpretation of toxicity ranking. It is acknowledged that in vitro dose-response outcomes are likely to be shaped by complex toxicodynamics, which include NP/cellular association, triggering of dynamic cell response pathways involved in NP uptake, and multiple physicochemical parameters that influence NP sedimentation and internalization.

  15. Off-site toxic consequence assessment: a simplified modeling procedure and case study.

    Science.gov (United States)

    Guarnaccia, Joe; Hoppe, Tom

    2008-11-15

    An assessment of off-site exposure from spills/releases of toxic chemicals can be conducted by compiling site-specific operational, geographic, demographic, and meteorological data and by using screening-level public-domain modeling tools (e.g., RMP Comp, ALOHA and DEGADIS). In general, the analysis is confined to the following: event-based simulations (allow for the use of known, constant, atmospheric conditions), known receptor distances (on the order of miles or less), short time scale for the distances considered (order of 10's of minutes or less), gently sloping rough terrain, dense and neutrally buoyant gas dispersion, known chemical inventory and infrastructure (used to define source-term), and known toxic endpoint (defines significance). While screening-level models are relatively simple to use, care must be taken to ensure that the results are meaningful. This approach allows one to assess risk from catastrophic release (e.g., via terrorism), or plausible release scenarios (related to standard operating procedures and industry standards). In addition, given receptor distance and toxic endpoint, the model can be used to predict the critical spill volume to realize significant off-site risk. This information can then be used to assess site storage and operation parameters and to determine the most economical and effective risk reduction measures to be applied.

  16. The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-response curves for in vivo developmental toxicity of glycol ethers in rat and man.

    NARCIS (Netherlands)

    Louisse, J.; de Jong, E.; van de Sandt, J.J.M.; Blaauboer, B.J.; Woutersen, R.A.; Piersma, A.H.; Rietjens, I.M.C.M.; Verwei, M.

    2010-01-01

    At present, regulatory assessment of systemic toxicity is almost solely performed using animal models. The EU REACH legislation stimulates the use of animal-free approaches to obtain information on the toxicity of chemicals. In vitro toxicity tests provide in vitro concentration-response curves for

  17. The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-response curves for in vivo developmental toxicity of glycol ethers in rat and man

    NARCIS (Netherlands)

    Louisse, J.; Jong, E. de; Sandt, J.J.M. van de; Blaauboer, B.J.; Woutersen, R.A.; Piersma, A.H.; Rietjens, I.M.C.M.; Verwei, M.

    2010-01-01

    At present, regulatory assessment of systemic toxicity is almost solely carried out using animal models. The European Commission's REACH legislation stimulates the use of animal-free approaches to obtain information on the toxicity of chemicals. In vitro toxicity tests provide in vitro concentration

  18. The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-respomse curves for in vivo developmental toxicity of glycol ethers in rat and man

    NARCIS (Netherlands)

    Louisse, J.; Jong, de E.; Sandt, van de J.J.M.; Blaauboer, B.J.; Woutersen, R.A.; Piersma, A.H.; Rietjens, I.; Verwei, M.

    2010-01-01

    At present, regulatory assessment of systemic toxicity is almost solely performed using animal models. The EU REACH legislation stimulates the use of animal-free approaches to obtain information on the toxicity of chemicals. In vitro toxicity tests provide in vitro concentration-response curves for

  19. Modelling low energy electron interactions for biomedical uses of radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fuss, M; Garcia, G [Instituto de Fisica Fundamental, Consejo Superior de Investigaciones CientIficas (CSIC), Serrano 113-bis, 28006 Madrid (Spain); Munoz, A; Oller, J C [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT), Avenida Complutense 22, 28040 Madrid (Spain); Blanco, F [Departamento de Fisica Atomica, Molecular y Nuclear, Universidad Complutense de Madrid, Avenida Complutense s.n., 28040 Madrid (Spain); Limao-Vieira, P [Departamento de Fisica, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Huerga, C; Tellez, M [Hospital Universitario La Paz, paseo de la Castellana 261, 28046 Madrid (Spain); Hubin-Fraskin, M J [Department of Chemistry, University of Liege, 4000 Liege 1 (Belgium); Nixon, K; Brunger, M, E-mail: g.garcia@imaff.cfmac.csic.e [School of Chemistry, Physics and Earth Sciences, Flinders University, GPO Box 2100, Adelaide, SA 5001 (Australia)

    2009-11-15

    Current radiation based medical applications in the field of radiotherapy, radio-diagnostic and radiation protection require modelling single particle interactions at the molecular level. Due to their relevance in radiation damage to biological systems, special attention should be paid to include the effect of low energy secondary electrons. In this study we present a single track simulation procedure for photons and electrons which is based on reliable experimental and theoretical cross section data and the energy loss distribution functions derived from our experiments. The effect of including secondary electron interactions in this model will be discussed.

  20. Toxic effects of nucleoside reverse transcriptase inhibitors on the liver. Value of electron microscopy analysis for the diagnosis of mitochondrial cytopathy.

    Science.gov (United States)

    Duong Van Huyen, Jean-Paul; Landau, Alain; Piketty, Christophe; Bélair, Marie-France; Batisse, Dominique; Gonzalez-Canali, Gustavo; Weiss, Laurence; Jian, Raymond; Kazatchkine, Michel D; Bruneval, Patrick

    2003-04-01

    Nucleoside reverse transcriptase inhibitors (NRTIs) induce mitochondrial toxic effects resulting in multiple organ disorders. Liver involvement has been associated mainly with severe lactic acidosis and massive steatosis. However, patients with HIV infection who are receiving antiretroviral treatment frequently have mildly abnormal liver test results that, to date, have not been linked unambiguously to the toxic effects of NRTIs. Thirteen patients with HIV infection treated with NRTI-based regimens had low-grade abnormal liver test results associated with digestive and nonspecific general symptoms. Histologic examination of liver samples showed diffuse steatosis in only 6 cases and mild steatosis in the remaining cases, associated with megamitochondria, mild lobular inflammation and necrosis, Mallory bodies, and perisinusoidal fibrosis. In all cases, ultrastructural study disclosed mitochondrial abnormalities. Our work demonstrates that NRTI-induced toxic effects in the liver may occur as indolent nonspecific disease with variable histologic features and emphasizes the diagnostic value of electron microscopy, particularly when diffuse steatosis is absent.

  1. Effects of pesticides on soil invertebrates in model ecosystem and field studies: a review and comparison with laboratory toxicity data

    NARCIS (Netherlands)

    Jänsch, S.; Frampton, G.K.; Römbke, J.; Brink, van den P.J.; Scott-Fordsmand, J.J.

    2006-01-01

    A systematic review was carried out to investigate the extent to which higher-tier (terrestrial model ecosystem [TME] and field) data regarding pesticide effects can be compared with laboratory toxicity data for soil invertebrates. Data in the public domain yielded 970 toxicity endpoint data sets, r

  2. Modeling Deterministic Chaos Using Electronic Circuits

    Directory of Open Access Journals (Sweden)

    T. Gotthans

    2011-06-01

    Full Text Available This paper brings a note on systematic circuit synthesis methods for modeling the dynamical systems given by mathematical model. Both classical synthesis and integrator based method is demonstrated via the relatively complicated real physical systems with possible chaotic solution. A variety of the different active building blocks are utilized to make the final circuits as simple as possible while preserving easily measurable voltage-mode state variables. Brief experimental verification, i.e. oscilloscope screenshots, is presented. The observed attractors have some structural stability and good relationship to their numerically integrated counterparts.

  3. Development of a biotic ligand model to predict the acute toxicity of cadmium to Daphnia pulex.

    Science.gov (United States)

    Clifford, Matthew; McGeer, James C

    2010-06-01

    The goal of this study was to develop a biotic ligand model (BLM) to predict the acute toxicity of cadmium to Daphnia pulex. Organisms were cultured in moderately soft water and standard 48h acute toxicity tests were used to determine EC50s in various water chemistries where the effects of Ca(2+), Na(+), Mg(2+), Cl(-), K(+), pH, and two sources of natural organic matter (Suwannee River and Nordic Reservoir) were evaluated. Overall, toxicity responses were consistent with the free-ion activity model and the principles inherent in the BLM. Increases in Ca(2+) resulted in higher EC50s, indicating that Cd(2+) competes with Ca(2+) for uptake at the biotic ligand. Similar cation competition effects were observed when Mg(2+) was varied but with a less pronounced protective effect relative to Ca(2+). Changes in Na(+) and K(+) concentrations had no significant effect on Cd toxicity. EC50 values did not change significantly when pH was adjusted over a range from 8.0 to 6.1. Additions of natural organic matter resulted in elevated dissolved organic carbon (DOC) concentrations that significantly reduced Cd bioavailability via complexation of Cd(2+). An existing biotic ligand model (HydroQual BLM ver 2.2.3) was tested for its ability to predict acute Cd toxicity to D. pulex. Once the BLM was adjusted for the relatively sensitivity of D. pulex the protective effects of Ca and DOC could be predicted reasonably well but other test chemistries did not match with measured EC50s. Binding constants derived from the test results (logK(CaBL) of 4.1, logK(MgBL) of 3.7, logK(HBL) of 6.1 and logK(CdBL) of 7.0) were used to develop a modified BLM for the effects of Cd on D. pulex that accounted for the moderating effect of Ca and Mg on acute toxicity but overestimated the protective effect of DOC. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  4. Dispersion modeling of accidental releases of toxic gases - Sensitivity study and optimization of the meteorological input

    Science.gov (United States)

    Baumann-Stanzer, K.; Stenzel, S.

    2009-04-01

    Several air dispersion models are available for prediction and simulation of the hazard areas associated with accidental releases of toxic gases. The most model packages (commercial or free of charge) include a chemical database, an intuitive graphical user interface (GUI) and automated graphical output for effective presentation of results. The models are designed especially for analyzing different accidental toxic release scenarios ("worst-case scenarios"), preparing emergency response plans and optimal countermeasures as well as for real-time risk assessment and management. Uncertainties in the meteorological input together with incorrect estimates of the source play a critical role for the model results. The research project RETOMOD (reference scenarios calculations for toxic gas releases - model systems and their utility for the fire brigade) was conducted by the Central Institute for Meteorology and Geodynamics (ZAMG) in cooperation with the Vienna fire brigade, OMV Refining & Marketing GmbH and Synex Ries & Greßlehner GmbH. RETOMOD was funded by the KIRAS safety research program at the Austrian Ministry of Transport, Innovation and Technology (www.kiras.at). The main tasks of this project were 1. Sensitivity study and optimization of the meteorological input for modeling of the hazard areas (human exposure) during the accidental toxic releases. 2. Comparison of several model packages (based on reference scenarios) in order to estimate the utility for the fire brigades. This presentation gives a short introduction to the project and presents the results of task 1 (meteorological input). The results of task 2 are presented by Stenzel and Baumann-Stanzer in this session. For the aim of this project, the observation-based analysis and forecasting system INCA, developed in the Central Institute for Meteorology and Geodynamics (ZAMG) was used. INCA (Integrated Nowcasting through Comprehensive Analysis) data were calculated with 1 km horizontal resolution and

  5. Template and Model Driven Development of Standardized Electronic Health Records.

    Science.gov (United States)

    Kropf, Stefan; Chalopin, Claire; Denecke, Kerstin

    2015-01-01

    Digital patient modeling targets the integration of distributed patient data into one overarching model. For this integration process, both a theoretical standard-based model and information structures combined with concrete instructions in form of a lightweight development process of single standardized Electronic Health Records (EHRs) are needed. In this paper, we introduce such a process along side a standard-based architecture. It allows the modeling and implementation of EHRs in a lightweight Electronic Health Record System (EHRS) core. The approach is demonstrated and tested by a prototype implementation. The results show that the suggested approach is useful and facilitates the development of standardized EHRSs.

  6. Dispersion modeling of accidental releases of toxic gases - utility for the fire brigades.

    Science.gov (United States)

    Stenzel, S.; Baumann-Stanzer, K.

    2009-09-01

    Several air dispersion models are available for prediction and simulation of the hazard areas associated with accidental releases of toxic gases. The most model packages (commercial or free of charge) include a chemical database, an intuitive graphical user interface (GUI) and automated graphical output for effective presentation of results. The models are designed especially for analyzing different accidental toxic release scenarios ("worst-case scenarios”), preparing emergency response plans and optimal countermeasures as well as for real-time risk assessment and management. The research project RETOMOD (reference scenarios calculations for toxic gas releases - model systems and their utility for the fire brigade) was conducted by the Central Institute for Meteorology and Geodynamics (ZAMG) in cooperation with the Viennese fire brigade, OMV Refining & Marketing GmbH and Synex Ries & Greßlehner GmbH. RETOMOD was funded by the KIRAS safety research program of the Austrian Ministry of Transport, Innovation and Technology (www.kiras.at). The main tasks of this project were 1. Sensitivity study and optimization of the meteorological input for modeling of the hazard areas (human exposure) during the accidental toxic releases. 2. Comparison of several model packages (based on reference scenarios) in order to estimate the utility for the fire brigades. For the purpose of our study the following models were tested and compared: ALOHA (Areal Location of Hazardous atmosphere, EPA), MEMPLEX (Keudel av-Technik GmbH), Trace (Safer System), Breeze (Trinity Consulting), SAM (Engineering office Lohmeyer). A set of reference scenarios for Chlorine, Ammoniac, Butane and Petrol were proceed, with the models above, in order to predict and estimate the human exposure during the event. Furthermore, the application of the observation-based analysis and forecasting system INCA, developed in the Central Institute for Meteorology and Geodynamics (ZAMG) in case of toxic release was

  7. Computer modeling of electron and proton transport in chloroplasts.

    Science.gov (United States)

    Tikhonov, Alexander N; Vershubskii, Alexey V

    2014-07-01

    Photosynthesis is one of the most important biological processes in biosphere, which provides production of organic substances from atmospheric CO2 and water at expense of solar energy. In this review, we contemplate computer models of oxygenic photosynthesis in the context of feedback regulation of photosynthetic electron transport in chloroplasts, the energy-transducing organelles of the plant cell. We start with a brief overview of electron and proton transport processes in chloroplasts coupled to ATP synthesis and consider basic regulatory mechanisms of oxygenic photosynthesis. General approaches to computer simulation of photosynthetic processes are considered, including the random walk models of plastoquinone diffusion in thylakoid membranes and deterministic approach to modeling electron transport in chloroplasts based on the mass action law. Then we focus on a kinetic model of oxygenic photosynthesis that includes key stages of the linear electron transport, alternative pathways of electron transfer around photosystem I (PSI), transmembrane proton transport and ATP synthesis in chloroplasts. This model includes different regulatory processes: pH-dependent control of the intersystem electron transport, down-regulation of photosystem II (PSII) activity (non-photochemical quenching), the light-induced activation of the Bassham-Benson-Calvin (BBC) cycle. The model correctly describes pH-dependent feedback control of electron transport in chloroplasts and adequately reproduces a variety of experimental data on induction events observed under different experimental conditions in intact chloroplasts (variations of CO2 and O2 concentrations in atmosphere), including a complex kinetics of P700 (primary electron donor in PSI) photooxidation, CO2 consumption in the BBC cycle, and photorespiration. Finally, we describe diffusion-controlled photosynthetic processes in chloroplasts within the framework of the model that takes into account complex architecture of

  8. Toxic releases and risk disparity: a spatiotemporal model of industrial ecology and social empowerment.

    Science.gov (United States)

    Aoyagi, Hannah; Ogunseitan, Oladele A

    2015-06-02

    Information-based regulations (IBRs) are founded on the theoretical premise that public participation in accomplishing policy goals is empowered by open access to information. Since its inception in 1988, the Toxics Release Inventory (TRI) has provided the framework and regulatory impetus for the compilation and distribution of data on toxic releases associated with industrial development, following the tenets of IBR. As TRI emissions are reputed to disproportionately affect low-income communities, we investigated how demographic characteristics are related to change in TRI emissions and toxicity risks between 1989 and 2002, and we sought to identify factors that predict these changes. We used local indicators of spatial association (LISA) maps and spatial regression techniques to study risk disparity in the Los Angeles urban area. We also surveyed 203 individuals in eight communities in the same region to measure the levels of awareness of TRI, attitudes towards air pollution, and general environmental risk. We discovered, through spatial lag models, that changes in gross and toxic emissions are related to community ethnic composition, poverty level, home ownership, and base 1989 emissions (R-square=0.034-0.083). We generated a structural equation model to explain the determinants of social empowerment to act on the basis of environmental information. Hierarchical confirmatory factor analysis (HCFA) supports the theoretical model that individual empowerment is predicted by risk perception, worry, and awareness (Chi-square=63.315, p=0.022, df=42). This study provides strong evidence that spatiotemporal changes in regional-scale environmental risks are influenced by individual-scale empowerment mediated by IBRs.

  9. Dispersion modeling of accidental releases of toxic gases - Comparison of the models and their utility for the fire brigades.

    Science.gov (United States)

    Stenzel, S.; Baumann-Stanzer, K.

    2009-04-01

    Dispersion modeling of accidental releases of toxic gases - Comparison of the models and their utility for the fire brigades. Sirma Stenzel, Kathrin Baumann-Stanzer In the case of accidental release of hazardous gases in the atmosphere, the emergency responders need a reliable and fast tool to assess the possible consequences and apply the optimal countermeasures. For hazard prediction and simulation of the hazard zones a number of air dispersion models are available. The most model packages (commercial or free of charge) include a chemical database, an intuitive graphical user interface (GUI) and automated graphical output for display the results, they are easy to use and can operate fast and effective during stress situations. The models are designed especially for analyzing different accidental toxic release scenarios ("worst-case scenarios"), preparing emergency response plans and optimal countermeasures as well as for real-time risk assessment and management. There are also possibilities for model direct coupling to automatic meteorological stations, in order to avoid uncertainties in the model output due to insufficient or incorrect meteorological data. Another key problem in coping with accidental toxic release is the relative width spectrum of regulations and values, like IDLH, ERPG, AEGL, MAK etc. and the different criteria for their application. Since the particulate emergency responders and organizations require for their purposes unequal regulations and values, it is quite difficult to predict the individual hazard areas. There are a quite number of research studies and investigations coping with the problem, anyway the end decision is up to the authorities. The research project RETOMOD (reference scenarios calculations for toxic gas releases - model systems and their utility for the fire brigade) was conducted by the Central Institute for Meteorology and Geodynamics (ZAMG) in cooperation with the Vienna fire brigade, OMV Refining & Marketing GmbH and

  10. STEADY-STATE MODEL OF SOLAR WIND ELECTRONS REVISITED

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Peter H.; Kim, Sunjung; Choe, G. S., E-mail: yoonp@umd.edu [School of Space Research, Kyung Hee University, Yongin, Gyeonggi 446-701 (Korea, Republic of)

    2015-10-20

    In a recent paper, Kim et al. put forth a steady-state model for the solar wind electrons. The model assumed local equilibrium between the halo electrons, characterized by an intermediate energy range, and the whistler-range fluctuations. The basic wave–particle interaction is assumed to be the cyclotron resonance. Similarly, it was assumed that a dynamical steady state is established between the highly energetic superhalo electrons and high-frequency Langmuir fluctuations. Comparisons with the measured solar wind electron velocity distribution function (VDF) during quiet times were also made, and reasonable agreements were obtained. In such a model, however, only the steady-state solution for the Fokker–Planck type of electron particle kinetic equation was considered. The present paper complements the previous analysis by considering both the steady-state particle and wave kinetic equations. It is shown that the model halo and superhalo electron VDFs, as well as the assumed wave intensity spectra for the whistler and Langmuir fluctuations, approximately satisfy the quasi-linear wave kinetic equations in an approximate sense, thus further validating the local equilibrium model constructed in the paper by Kim et al.

  11. The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease

    Energy Technology Data Exchange (ETDEWEB)

    Spincemaille, Pieter [Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium); Pham, Duc-Hung [Laboratory for Molecular Biodiscovery, KU Leuven, Campus Gasthuisberg, Herestraat 49, O and N2, 3000 Leuven (Belgium); Chandhok, Gursimran [Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster (Germany); Verbeek, Jef [Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven (Belgium); Zibert, Andree [Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster (Germany); Libbrecht, Louis [Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven (Belgium); Department of Pathology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent (Belgium); Schmidt, Hartmut [Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster (Germany); Esguerra, Camila V.; Witte, Peter A.M. de [Laboratory for Molecular Biodiscovery, KU Leuven, Campus Gasthuisberg, Herestraat 49, O and N2, 3000 Leuven (Belgium); Cammue, Bruno P.A., E-mail: bruno.cammue@biw.kuleuven.be [Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium); Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Ghent (Belgium); Cassiman, David [Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven (Belgium); Thevissen, Karin [Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium)

    2014-10-15

    Background: Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu-induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD. Methods: The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu-treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae. Results: OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B{sup H1069Q}, but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species. Conclusions: OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD. General significance: All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment. - Highlights: • Wilson disease (WD) is characterized by accumulation of toxic copper (Cu). • OSIP108 increases viability of Cu-treated cellular models applicable to WD. • OSIP108 injections preserve liver morphology of Cu-treated zebrafish larvae. • OSIP108 injections into zebrafish larvae abrogates Cu-induced oxidative stress.

  12. A Model for an Electronic Information Marketplace

    Directory of Open Access Journals (Sweden)

    Wei Ge

    2005-11-01

    Full Text Available As the information content on the Internet increases, the task of locating desired information and assessing its quality becomes increasingly difficult. This development causes users to be more willing to pay for information that is focused on specific issues, verifiable, and available upon request. Thus, the nature of the Internet opens up the opportunity for information trading. In this context, the Internet cannot only be used to close the transaction, but also to deliver the product - desired information - to the user. Early attempts to implement such business models have fallen short of expectations. In this paper, we discuss the limitations of such practices and present a modified business model for information trading, which uses a reverse auction approach together with a multiple-buyer price discovery process

  13. Electronic Warfare in Army Models - A Survey.

    Science.gov (United States)

    1980-08-01

    Improvement Program (AMIP), Joint (Army, AF, Marines) EW Center, and SAGA (Studies, Analysis, and Gaming Agency) of the Joint Chiefs of Staff to identify an...Virginia, January, 1973. 5. Catalog of Wargaming and Military Simulation Models, 7th Edition, SAGA 180-77, Studies, Analysis, and Gaming Agency, Organization...snow/sleet. It can simulate nighttime with full moon and twilight , smoke and dust as they affect the target acquisition capability of an RPV-type device

  14. Toxicity of pristine graphene in experiments in a chicken embryo model

    Directory of Open Access Journals (Sweden)

    Sawosz E

    2014-08-01

    Full Text Available Ewa Sawosz,1 Slawomir Jaworski,1 Marta Kutwin,1 Anna Hotowy,1 Mateusz Wierzbicki,1 Marta Grodzik,1 Natalia Kurantowicz,1 Barbara Strojny,1 Ludwika Lipinska,2 André Chwalibog3 1Division of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, Poland; 2Institute of Electronic Materials Technology, Warsaw, Poland; 3Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark Abstract: Evaluation of the potential cytotoxicity of graphene is a key factor for medical applications, where flakes or a surface of graphene may be used as bioactive molecules, drug carriers, or biosensors. In the present work, effects of pristine graphene (pG on the development of a living organism, with an emphasis on morphological and molecular states of the brain, were investigated using a chicken embryo model. Fertilized chicken eggs were divided into the control group and groups administered with pG suspended in milli-Q water at concentrations of 50 µg/L, 100 µg/L, 500 µg/L, 1,000 µg/L, 5,000 µg/L, and 10,000 µg/L (n=30 per group. The experimental solutions were injected in ovo into the albumin and then the eggs were incubated. After 19 days of incubation, the survival, weight of the body and organs, and blood serum biochemical indices were measured. The brain samples were collected for microscopic examination of brain ultrastructure and measurements of gene and protein expression. Survival of embryos was significantly decreased after treatment with pG, but the body and organ weights as well as biochemical indices were not affected. In all treatment groups, some atypical ultrastructures of the brain were observed, but they were not enhanced by the increasing concentrations of pG. Expression of proliferating cell nuclear antigen at the messenger ribonucleic acid level was downregulated, and the number of proliferating cell nuclear antigen-positive nuclei was significantly reduced in the 500–10,000 µg

  15. Zebrafish Embryo Toxicity Microscale Model for Ichthyotoxicity Evaluation of Marine Natural Products.

    Science.gov (United States)

    Bai, Hong; Kong, Wen-Wen; Shao, Chang-Lun; Li, Yun; Liu, Yun-Zhang; Liu, Min; Guan, Fei-Fei; Wang, Chang-Yun

    2016-04-01

    Marine organisms often protect themselves against their predators by chemical defensive strategy. The second metabolites isolated from marine organisms and their symbiotic microbes have been proven to play a vital role in marine chemical ecology, such as ichthyotoxicity, allelopathy, and antifouling. It is well known that the microscale models for marine chemoecology assessment are urgently needed for trace quantity of marine natural products. Zebrafish model has been widely used as a microscale model in the fields of environment ecological evaluation and drug safety evaluation, but seldom reported for marine chemoecology assessment. In this work, zebrafish embryo toxicity microscale model was established for ichthyotoxicity evaluation of marine natural products by using 24-well microplate based on zebrafish embryo. Ichthyotoxicity was evaluated by observation of multiple toxicological endpoints, including coagulation egg, death, abnormal heartbeat, no spontaneous movement, delayed hatch, and malformation of the different organs during zebrafish embryogenesis periods at 24, 48, and 72 h post-fertilization (hpf). 3,4-Dichloroaniline was used as the positive control for method validation. Subsequently, the established model was applied to test the ichthyotoxic activity of the compounds isolated from corals and their symbiotic microbes and to isolate the bioactive secondary metabolites from the gorgonian Subergorgia mollis under bioassay guidance. It was suggested that zebrafish embryo toxicity microscale model is suitable for bioassay-guided isolation and preliminary bioactivity screening of marine natural products.

  16. Simple in vitro models can predict pulmonary toxicity of silver nanoparticles.

    Science.gov (United States)

    Braakhuis, Hedwig M; Giannakou, Christina; Peijnenburg, Willie J G M; Vermeulen, Jolanda; van Loveren, Henk; Park, Margriet V D Z

    2016-08-01

    To study the effects of nanomaterials after inhalation, a large number of in vitro lung models have been reported in literature. Although the in vitro models contribute to the reduction of animal studies, insufficient data exists to determine the predictive value of these in vitro models for the in vivo situation. The aim of this study was to determine the correlation between in vitro and in vivo data by comparing the dose metrics of silver nanoparticles in an in vitro lung model of increasing complexity to our previously published in vivo inhalation study. In vivo, the previously published study showed that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation. The results of the present study show that particle surface area is a suitable dose metric to describe the effects of silver nanoparticles when using a simple monolayer of lung epithelial cells. The dose metric shifted from particle surface area to particle mass when adding an increasing number of macrophages. In addition, a co-culture of endothelial cells, epithelial cells and macrophages on a Transwell® insert correlated less well to the in vivo results compared to the epithelial monolayer. We conclude that for studying the acute pulmonary toxicity of nanoparticles simple in vitro models using an epithelial monolayer better predict the in vivo response compared to complex co-culture models.

  17. Metal Oxide Nanomaterial QNAR Models: Available Structural Descriptors and Understanding of Toxicity Mechanisms

    Directory of Open Access Journals (Sweden)

    Jiali Ying

    2015-10-01

    Full Text Available Metal oxide nanomaterials are widely used in various areas; however, the divergent published toxicology data makes it difficult to determine whether there is a risk associated with exposure to metal oxide nanomaterials. The application of quantitative structure activity relationship (QSAR modeling in metal oxide nanomaterials toxicity studies can reduce the need for time-consuming and resource-intensive nanotoxicity tests. The nanostructure and inorganic composition of metal oxide nanomaterials makes this approach different from classical QSAR study; this review lists and classifies some structural descriptors, such as size, cation charge, and band gap energy, in recent metal oxide nanomaterials quantitative nanostructure activity relationship (QNAR studies and discusses the mechanism of metal oxide nanomaterials toxicity based on these descriptors and traditional nanotoxicity tests.

  18. Caenorhabditis elegans as a Model System for Studying Drug Induced Mitochondrial Toxicity.

    Directory of Open Access Journals (Sweden)

    Richard de Boer

    Full Text Available Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the mitochondrial DNA polymerase. For detailed investigation of the yet partially understood underlying mechanisms, the availability of a versatile model system is crucial. We therefore set out to develop the use of Caenorhabditis elegans to study drug induced mitochondrial toxicity. Using a combination of molecular-biological and functional assays, combined with a quantitative analysis of mitochondrial network morphology, we conclude that anti-retroviral drugs with similar working mechanisms can be classified into distinct groups based on their effects on mitochondrial morphology and biochemistry. Additionally we show that mitochondrial toxicity of antiretroviral drugs cannot be exclusively attributed to interference with the mitochondrial DNA polymerase.

  19. Ferromagnetism in Electronic Models for Manganites

    OpenAIRE

    Riera, Jose; Hallberg, Karen; Dagotto, Elbio

    1996-01-01

    Ground state properties of the Kondo model for manganese oxides in one dimension are studied using numerical techniques. The large Hund coupling ($J_{H}$) limit is specially analyzed. A robust region of fully saturated ferromagnetism (FM) is identified at all densities. For open boundary conditions it is shown exactly that the ground state is FM at $J_{H} = \\infty$. Hole-spin phase separation competing with FM was also observed when a large exchange $J$ between the $Mn^{3+}$ ions is used. As ...

  20. A simple and low-toxic method of preparing small specimens of bacteria, flagellates and their likes for Scanning Electron Microscopy

    OpenAIRE

    Møller, O. S.; Buchman, K.; Dalsgaard, Inger

    2013-01-01

    The preparation of samples of bacteria and other very small organisms (<50 μm) for Scanning Electron Microscopy is often complex and intricate, which typically involve the use of specialized filter systems, complex handling and toxic chemicals. Based on the methods described in the literature and our own tests, we have distilled a simpler (although slightly crude) method to prepare bacterial samples in a fast way. We only employ readily available chemicals requiring no more than a fume hoo...

  1. Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.

    Science.gov (United States)

    Peterson, Mark E

    2014-11-01

    Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission.

  2. Modeling and simulation of electronic structure, material interface and random doping in nano electronic devices

    Science.gov (United States)

    Chen, Duan; Wei, Guo-Wei

    2010-01-01

    The miniaturization of nano-scale electronic devices, such as metal oxide semiconductor field effect transistors (MOSFETs), has given rise to a pressing demand in the new theoretical understanding and practical tactic for dealing with quantum mechanical effects in integrated circuits. Modeling and simulation of this class of problems have emerged as an important topic in applied and computational mathematics. This work presents mathematical models and computational algorithms for the simulation of nano-scale MOSFETs. We introduce a unified two-scale energy functional to describe the electrons and the continuum electrostatic potential of the nano-electronic device. This framework enables us to put microscopic and macroscopic descriptions in an equal footing at nano scale. By optimization of the energy functional, we derive consistently-coupled Poisson-Kohn-Sham equations. Additionally, layered structures are crucial to the electrostatic and transport properties of nano transistors. A material interface model is proposed for more accurate description of the electrostatics governed by the Poisson equation. Finally, a new individual dopant model that utilizes the Dirac delta function is proposed to understand the random doping effect in nano electronic devices. Two mathematical algorithms, the matched interface and boundary (MIB) method and the Dirichlet-to-Neumann mapping (DNM) technique, are introduced to improve the computational efficiency of nano-device simulations. Electronic structures are computed via subband decomposition and the transport properties, such as the I-V curves and electron density, are evaluated via the non-equilibrium Green's functions (NEGF) formalism. Two distinct device configurations, a double-gate MOSFET and a four-gate MOSFET, are considered in our three-dimensional numerical simulations. For these devices, the current fluctuation and voltage threshold lowering effect induced by the discrete dopant model are explored. Numerical convergence

  3. Modeling and simulation of electronic structure, material interface and random doping in nano-electronic devices

    Science.gov (United States)

    Chen, Duan; Wei, Guo-Wei

    2010-06-01

    The miniaturization of nano-scale electronic devices, such as metal oxide semiconductor field effect transistors (MOSFETs), has given rise to a pressing demand in the new theoretical understanding and practical tactic for dealing with quantum mechanical effects in integrated circuits. Modeling and simulation of this class of problems have emerged as an important topic in applied and computational mathematics. This work presents mathematical models and computational algorithms for the simulation of nano-scale MOSFETs. We introduce a unified two-scale energy functional to describe the electrons and the continuum electrostatic potential of the nano-electronic device. This framework enables us to put microscopic and macroscopic descriptions in an equal footing at nano-scale. By optimization of the energy functional, we derive consistently coupled Poisson-Kohn-Sham equations. Additionally, layered structures are crucial to the electrostatic and transport properties of nano-transistors. A material interface model is proposed for more accurate description of the electrostatics governed by the Poisson equation. Finally, a new individual dopant model that utilizes the Dirac delta function is proposed to understand the random doping effect in nano-electronic devices. Two mathematical algorithms, the matched interface and boundary (MIB) method and the Dirichlet-to-Neumann mapping (DNM) technique, are introduced to improve the computational efficiency of nano-device simulations. Electronic structures are computed via subband decomposition and the transport properties, such as the I- V curves and electron density, are evaluated via the non-equilibrium Green's functions (NEGF) formalism. Two distinct device configurations, a double-gate MOSFET and a four-gate MOSFET, are considered in our three-dimensional numerical simulations. For these devices, the current fluctuation and voltage threshold lowering effect induced by the discrete dopant model are explored. Numerical

  4. Modelling of accidental released toxic gases for emergency responders in Austria, Kosovo and Bulgaria.

    Science.gov (United States)

    Stenzel, Sirma; Baumann-Stanzer, Kathrin; Gashi, Salih; Thaci, Bashkim; Batchvarova, Ekaterina; Spassova, Tatiana

    2010-05-01

    In the case of accidental release of hazardous gases in the atmosphere, the emergency responders need a reliable and fast tool to assess the possible consequences and apply the optimal countermeasures. A number of models for the prediction and simulation of hazard areas affected by accidental releases of toxic gases are available worldwide. Modelling accidental releases may be required for a variety of reasons: for analyzing different accidental toxic release scenarios ("worst-case scenarios"), for preparing emergency response plans and optimal countermeasures as well as for real-time risk assessment and management (e.g. in the frame of the SEVESO directive). Depending on the demand and the particular purposes, the choice of the appropriate model is up to the authorities. The one year project was funded by the Austrian Science and research liaison Office (ASO, www.aso.zsi.at) as a part of the program: Research Cooperation and Networking between Austria, the public higher education institutions in Kosovo and South Eastern Europe. The project was conducted by the Central Institute for Meteorology and Geodynamics (ZAMG, http://www.zamg.ac.at) in cooperation with the University of Prishtina (Kosovo, www.uni-pr.edu and the National Institute of meteorology and Hydrology (NIHM Bulgaria, www.meteo.bg). One of the main purposes of the project was to provide the both partners with basic knowledge in modelling with accidental release of toxic gases, based on the practical experience of the meteorologists from the ZAMG in the area. This knowledge can be used as scientific response to society driven current or upcoming problems especially in Kosovo. The activities involved know-how transfer on European standards and practice among the project partners, as well as joint efforts to adapt and disseminate the scientific methods and results in Kosovo. Within the project, the partners from Kosovo and Bulgaria were introduced to the atmospheric dispersion model (ALOHA - Areal

  5. Modeling the customer in electronic commerce.

    Science.gov (United States)

    Helander, M G; Khalid, H M

    2000-12-01

    This paper reviews interface design of web pages for e-commerce. Different tasks in e-commerce are contrasted. A systems model is used to illustrate the information flow between three subsystems in e-commerce: store environment, customer, and web technology. A customer makes several decisions: to enter the store, to navigate, to purchase, to pay, and to keep the merchandize. This artificial environment must be designed so that it can support customer decision-making. To retain customers it must be pleasing and fun, and create a task with natural flow. Customers have different needs, competence and motivation, which affect decision-making. It may therefore be important to customize the design of the e-store environment. Future ergonomics research will have to investigate perceptual aspects, such as presentation of merchandize, and cognitive issues, such as product search and navigation, as well as decision making while considering various economic parameters. Five theories on e-commerce research are presented.

  6. Predicting toxic effects of copper on aquatic biota in mineralized areas by using the Biotic Ligand Model

    Science.gov (United States)

    Smith, Kathleen S.; Ranville, James F.; Adams, M.; Choate, LaDonna M.; Church, Stan E.; Fey, David L.; Wanty, Richard B.; Crock, James G.

    2006-01-01

    The chemical speciation of metals influences their biological effects. The Biotic Ligand Model (BLM) is a computational approach to predict chemical speciation and acute toxicological effects of metals on aquatic biota. Recently, the U.S. Environmental Protection Agency incorporated the BLM into their regulatory water-quality criteria for copper. Results from three different laboratory copper toxicity tests were compared with BLM predictions for simulated test-waters. This was done to evaluate the ability of the BLM to accurately predict the effects of hardness and concentrations of dissolved organic carbon (DOC) and iron on aquatic toxicity. In addition, we evaluated whether the BLM and the three toxicity tests provide consistent results. Comparison of BLM predictions with two types of Ceriodaphnia dubia toxicity tests shows that there is fairly good agreement between predicted LC50 values computed by the BLM and LC50 values determined from the two toxicity tests. Specifically, the effect of increasing calcium concentration (and hardness) on copper toxicity appears to be minimal. Also, there is fairly good agreement between the BLM and the two toxicity tests for test solutions containing elevated DOC, for which the LC50 is 3-to-5 times greater (less toxic) than the LC50 for the lower-DOC test water. This illustrates the protective effects of DOC on copper toxicity and demonstrates the ability of the BLM to predict these protective effects. In contrast, for test solutions with added iron there is a decrease in LC50 values (increase in toxicity) in results from the two C. dubia toxicity tests, and the agreement between BLM LC50 predictions and results from these toxicity tests is poor. The inability of the BLM to account for competitive iron binding to DOC or DOC fractionation may be a significant shortcoming of the BLM for predicting site- specific water-quality criteria in streams affected by iron-rich acidic drainage in mined and mineralized areas.

  7. Numerical modeling of electron-beam welding of dissimilar metals

    Science.gov (United States)

    Krektuleva, R. A.; Cherepanov, O. I.; Cherepanov, R. O.

    2016-11-01

    This paper is devoted to numerical modeling of heat transfer processes and estimation of thermal stresses in weld seams created by electron beam welding of heterogeneous metals. The mathematical model is based on a system of equations that includes the Lagrange's variational equation of theory of plasticity and variational equation of M. Biot's principle to simulate the heat transfer processes. The two-dimensional problems (plane strain and plane stress) are considered for estimation of thermal stresses in welds considering differences of mechanical properties of welded materials. The model is developed for simulation of temperature fields and stresses during electron beam welding.

  8. The influence of toxicity constraints in models of chemotherapeutic protocol escalation

    KAUST Repository

    Boston, E. A. J.

    2011-04-06

    The prospect of exploiting mathematical and computational models to gain insight into the influence of scheduling on cancer chemotherapeutic effectiveness is increasingly being considered. However, the question of whether such models are robust to the inclusion of additional tumour biology is relatively unexplored. In this paper, we consider a common strategy for improving protocol scheduling that has foundations in mathematical modelling, namely the concept of dose densification, whereby rest phases between drug administrations are reduced. To maintain a manageable scope in our studies, we focus on a single cell cycle phase-specific agent with uncomplicated pharmacokinetics, as motivated by 5-Fluorouracil-based adjuvant treatments of liver micrometastases. In particular, we explore predictions of the effectiveness of dose densification and other escalations of the protocol scheduling when the influence of toxicity constraints, cell cycle phase specificity and the evolution of drug resistance are all represented within the modelling. For our specific focus, we observe that the cell cycle and toxicity should not simply be neglected in modelling studies. Our explorations also reveal the prediction that dose densification is often, but not universally, effective. Furthermore, adjustments in the duration of drug administrations are predicted to be important, especially when dose densification in isolation does not yield improvements in protocol outcomes. © The author 2011. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  9. Modified binary encounter Bethe model for electron-impact ionization

    CERN Document Server

    Guerra, M; Indelicato, P; Santos, J P

    2013-01-01

    Theoretical expressions for ionization cross sections by electron impact based on the binary encounter Bethe (BEB) model, valid from ionization threshold up to relativistic energies, are proposed. The new modified BEB (MBEB) and its relativistic counterpart (MRBEB) expressions are simpler than the BEB (nonrelativistic and relativistic) expressions because they require only one atomic parameter, namely the binding energy of the electrons to be ionized, and use only one scaling term for the ionization of all sub-shells. The new models are used to calculate the K-, L- and M-shell ionization cross sections by electron impact for several atoms with Z from 6 to 83. Comparisons with all, to the best of our knowledge, available experimental data show that this model is as good or better than other models, with less complexity.

  10. Relativistic models for quasielastic electron and neutrino-nucleus scattering

    Directory of Open Access Journals (Sweden)

    Meucci Andrea

    2012-12-01

    Full Text Available Relativistic models developed within the framework of the impulse approximation for quasielastic (QE electron scattering and successfully tested in comparison with electron-scattering data have been extended to neutrino-nucleus scattering. Different descriptions of final-state interactions (FSI in the inclusive scattering are compared. In the relativistic Green’s function (RGF model FSI are described consistently with the exclusive scattering using a complex optical potential. In the relativistic mean field (RMF model FSI are described by the same RMF potential which gives the bound states. The results of the models are compared for electron and neutrino scattering and, for neutrino scattering, with the recently measured charged-current QE (CCQE MiniBooNE cross sections.

  11. A conceptual model for assessing the impact of electronic procurement

    NARCIS (Netherlands)

    Boer, de Luitzen; Harink, Jeroen; Heijboer, Govert

    2002-01-01

    This paper aims to contribute to the development of a conceptual model for studying the direct and indirect impact of various forms of electronic procurement (EP) on a firm's integral purchasing (-related) costs. The model builds on existing classifications of purchasing-related costs and benefits a

  12. Modeling paraxial wave propagation in free-electron laser oscillators

    NARCIS (Netherlands)

    Karssenberg, J.G.; van der Slot, Petrus J.M.; Volokhine, I.; Verschuur, Jeroen W.J.; Boller, Klaus J.

    2006-01-01

    Modeling free-electron laser (FEL) oscillators requires calculation of both the light-beam interaction within the undulator and the light propagation outside the undulator. We have developed a paraxial optical propagation code that can be combined with various existing models of gain media, for

  13. Modeling paraxial wave propagation in free-electron laser oscillators

    NARCIS (Netherlands)

    Karssenberg, J.G.; Slot, van der P.J.M.; Volokhine, I.V.; Verschuur, J.W.J.; Boller, K.J.

    2006-01-01

    Modeling free-electron laser (FEL) oscillators requires calculation of both the light-beam interaction within the undulator and the light propagation outside the undulator. We have developed a paraxial optical propagation code that can be combined with various existing models of gain media, for exam

  14. Density-dependent electron transport and precise modeling of GaN high electron mobility transistors

    Energy Technology Data Exchange (ETDEWEB)

    Bajaj, Sanyam, E-mail: bajaj.10@osu.edu; Shoron, Omor F.; Park, Pil Sung; Krishnamoorthy, Sriram; Akyol, Fatih; Hung, Ting-Hsiang [Department of Electrical and Computer Engineering, The Ohio State University, Columbus, Ohio 43210 (United States); Reza, Shahed; Chumbes, Eduardo M. [Raytheon Integrated Defense Systems, Andover, Massachusetts 01810 (United States); Khurgin, Jacob [Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Rajan, Siddharth [Department of Electrical and Computer Engineering, The Ohio State University, Columbus, Ohio 43210 (United States); Department of Material Science and Engineering, The Ohio State University, Columbus, Ohio 43210 (United States)

    2015-10-12

    We report on the direct measurement of two-dimensional sheet charge density dependence of electron transport in AlGaN/GaN high electron mobility transistors (HEMTs). Pulsed IV measurements established increasing electron velocities with decreasing sheet charge densities, resulting in saturation velocity of 1.9 × 10{sup 7 }cm/s at a low sheet charge density of 7.8 × 10{sup 11 }cm{sup −2}. An optical phonon emission-based electron velocity model for GaN is also presented. It accommodates stimulated longitudinal optical (LO) phonon emission which clamps the electron velocity with strong electron-phonon interaction and long LO phonon lifetime in GaN. A comparison with the measured density-dependent saturation velocity shows that it captures the dependence rather well. Finally, the experimental result is applied in TCAD-based device simulator to predict DC and small signal characteristics of a reported GaN HEMT. Good agreement between the simulated and reported experimental results validated the measurement presented in this report and established accurate modeling of GaN HEMTs.

  15. Kinetic modelling of runaway electrons in dynamic scenarios

    CERN Document Server

    Stahl, A; Papp, G; Landreman, M; Fülöp, T

    2016-01-01

    Improved understanding of runaway-electron formation and decay processes are of prime interest for the safe operation of large tokamaks, and the dynamics of the runaway electrons during dynamical scenarios such as disruptions are of particular concern. In this paper, we present kinetic modelling of scenarios with time-dependent plasma parameters; in particular, we investigate hot-tail runaway generation during a rapid drop in plasma temperature. With the goal of studying runaway-electron generation with a self-consistent electric-field evolution, we also discuss the implementation of a conservative collision operator and demonstrate its properties. An operator for avalanche runaway-electron generation, which takes the energy dependence of the scattering cross section and the runaway distribution into account, is investigated. We show that the simpler avalanche model of Rosenbluth & Putvinskii [Nucl. Fusion 37, 1355 (1997)] can give very inaccurate results for the avalanche growth rate (either lower or hig...

  16. Modeling electron fractionalization with unconventional Fock spaces

    Science.gov (United States)

    Cobanera, Emilio

    2017-08-01

    It is shown that certain fractionally-charged quasiparticles can be modeled on D-dimensional lattices in terms of unconventional yet simple Fock algebras of creation and annihilation operators. These unconventional Fock algebras are derived from the usual fermionic algebra by taking roots (the square root, cubic root, etc) of the usual fermionic creation and annihilation operators. If the fermions carry non-Abelian charges, then this approach fractionalizes the Abelian charges only. In particular, the mth-root of a spinful fermion carries charge e/m and spin 1/2. Just like taking a root of a complex number, taking a root of a fermion yields a mildly non-unique result. As a consequence, there are several possible choices of quantum exchange statistics for fermion-root quasiparticles. These choices are tied to the dimensionality D=1,2,3,\\ldots of the lattice by basic physical considerations. One particular family of fermion-root quasiparticles is directly connected to the parafermion zero-energy modes expected to emerge in certain mesoscopic devices involving fractional quantum Hall states. Hence, as an application of potential mesoscopic interest, I investigate numerically the hybridization of Majorana and parafermion zero-energy edge modes caused by fractionalizing but charge-conserving tunneling.

  17. USign--a security enhanced electronic consent model.

    Science.gov (United States)

    Li, Yanyan; Xie, Mengjun; Bian, Jiang

    2014-01-01

    Electronic consent becomes increasingly popular in the healthcare sector given the many benefits it provides. However, security concerns, e.g., how to verify the identity of a person who is remotely accessing the electronic consent system in a secure and user-friendly manner, also arise along with the popularity of electronic consent. Unfortunately, existing electronic consent systems do not pay sufficient attention to those issues. They mainly rely on conventional password based authentication to verify the identity of an electronic consent user, which is far from being sufficient given that identity theft threat is real and significant in reality. In this paper, we present a security enhanced electronic consent model called USign. USign enhances the identity protection and authentication for electronic consent systems by leveraging handwritten signatures everyone is familiar with and mobile computing technologies that are becoming ubiquitous. We developed a prototype of USign and conducted preliminary evaluation on accuracy and usability of signature verification. Our experimental results show the feasibility of the proposed model.

  18. Molecular modeling of inelastic electron transport in molecular junctions

    Science.gov (United States)

    Jiang, Jun; Kula, Mathias; Luo, Yi

    2008-09-01

    A quantum chemical approach for the modeling of inelastic electron tunneling spectroscopy of molecular junctions based on scattering theory is presented. Within a harmonic approximation, the proposed method allows us to calculate the electron-vibration coupling strength analytically, which makes it applicable to many different systems. The calculated inelastic electron transport spectra are often in very good agreement with their experimental counterparts, allowing the revelation of detailed information about molecular conformations inside the junction, molecule-metal contact structures, and intermolecular interaction that is largely inaccessible experimentally.

  19. Molecular modeling of inelastic electron transport in molecular junctions

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Jun; Kula, Mathias; Luo Yi [Department of Theoretical Chemistry, School of Biotechnology, Royal Institute of Technology, S-106 91 Stockholm (Sweden)], E-mail: luo@kth.se

    2008-09-17

    A quantum chemical approach for the modeling of inelastic electron tunneling spectroscopy of molecular junctions based on scattering theory is presented. Within a harmonic approximation, the proposed method allows us to calculate the electron-vibration coupling strength analytically, which makes it applicable to many different systems. The calculated inelastic electron transport spectra are often in very good agreement with their experimental counterparts, allowing the revelation of detailed information about molecular conformations inside the junction, molecule-metal contact structures, and intermolecular interaction that is largely inaccessible experimentally.

  20. alpha-Synuclein fission yeast model: concentration-dependent aggregation without plasma membrane localization or toxicity.

    Science.gov (United States)

    Brandis, Katrina A; Holmes, Isaac F; England, Samantha J; Sharma, Nijee; Kukreja, Lokesh; DebBurman, Shubhik K

    2006-01-01

    Despite fission yeast's history of modeling salient cellular processes, it has not yet been used to model human neurodegeneration-linked protein misfolding. Because alpha-synuclein misfolding and aggregation are linked to Parkinson's disease (PD), here, we report a fission yeast (Schizosaccharomyces pombe) model that evaluates alpha-synuclein misfolding, aggregation, and toxicity and compare these properties with those recently characterized in budding yeast (Saccharomyces cerevisiae). Wild-type alpha-synuclein and three mutants (A30P, A53T, and A30P/A53T) were expressed with thiamine-repressible promoters (using vectors of increasing promoter strength: pNMT81, pNMT41, and pNMT1) to test directly in living cells the nucleation polymerization hypothesis for alpha-synuclein misfolding and aggregation. In support of the hypothesis, wild-type and A53T alpha-synuclein formed prominent intracellular cytoplasmic inclusions within fission yeast cells in a concentration- and time-dependent manner, whereas A30P and A30P/A53T remained diffuse throughout the cytoplasm. A53T alpha-synuclein formed aggregates faster than wild-type alpha-synuclein and at a lower alpha-synuclein concentration. Unexpectedly, unlike in budding yeast, wild-type and A53T alpha-synuclein did not target to the plasma membrane in fission yeast, not even at low alpha-synuclein concentrations or as a precursor step to forming aggregates. Despite alpha-synuclein's extensive aggregation, it was surprisingly nontoxic to fission yeast. Future genetic dissection might yield molecular insight into this protection against toxicity. We speculate that alpha-synuclein toxicity might be linked to its membrane binding capacity. To conclude, S. pombe and S. cerevisiae model similar yet distinct aspects of alpha-synuclein biology, and both organisms shed insight into alpha-synuclein's role in PD pathogenesis.

  1. Towards elucidation of the toxic mechanism of copper on the model green alga Chlamydomonas reinhardtii.

    Science.gov (United States)

    Jiang, Yongguang; Zhu, Yanli; Hu, Zhangli; Lei, Anping; Wang, Jiangxin

    2016-09-01

    Toxic effects of copper on aquatic organisms in polluted water bodies have garnered particular attention in recent years. Microalgae play an important role in aquatic ecosystems, and they are sensitive to heavy metal pollution. Thus, it is important to clarify the mechanism of copper toxicity first for ecotoxicology studies. In this study, the physiological, biochemical and gene expression characteristics of a model green microalga, Chlamydomonas reinhardtii, with 0, 50, 150 and 250 μM copper treatments were investigated. The response of C. reinhardtii to copper stress was significantly shown at a dose dependent manner. Inhibition of cell growth and variation of total chlorophyll content were observed with copper treatments. The maximum photochemical efficiency of PSII, actual photochemical efficiency of PSII and photochemical quenching value decreased in the 250 μM copper treatment with minimum values equal to 28, 24 and 60 % of the control values respectively. The content of lipid peroxidation biomarker malondialdehyde with copper treatments increased with a maximum value sevenfold higher than the control value. Inhibition of cell growth and photosynthesis was ascribed to peroxidation of membrane lipids. The glutathione content and activities of antioxidant enzymes, glutathione S-transferase, glutathione peroxidase, superoxide dismutase and peroxidase were induced by copper. Interestingly, the expression of antioxidant genes and the photosynthetic gene decreased in most copper treatments. In conclusion, oxidative stress caused by production of excess reactive oxidative species might be the major mechanism of copper toxicity on C. reinhardtii.

  2. Cadmium Handling, Toxicity and Molecular Targets Involved during Pregnancy: Lessons from Experimental Models

    Science.gov (United States)

    Santoyo-Sánchez, Mitzi; Thévenod, Frank; Barbier, Olivier

    2017-01-01

    Even decades after the discovery of Cadmium (Cd) toxicity, research on this heavy metal is still a hot topic in scientific literature: as we wrote this review, more than 1440 scientific articles had been published and listed by the PubMed.gov website during 2017. Cadmium is one of the most common and harmful heavy metals present in our environment. Since pregnancy is a very particular physiological condition that could impact and modify essential pathways involved in the handling of Cd, the prenatal life is a critical stage for exposure to this non-essential element. To give the reader an overview of the possible mechanisms involved in the multiple organ toxic effects in fetuses after the exposure to Cd during pregnancy, we decided to compile some of the most relevant experimental studies performed in experimental models and to summarize the advances in this field such as the Cd distribution and the factors that could alter it (diet, binding-proteins and membrane transporters), the Cd-induced toxicity in dams (preeclampsia, fertility, kidney injury, alteration in essential element homeostasis and bone mineralization), in placenta and in fetus (teratogenicity, central nervous system, liver and kidney). PMID:28737682

  3. Toxicity assessment and modelling of Moringa oleifera seeds in water purification by whole cell bioreporter.

    Science.gov (United States)

    Al-Anizi, Ali Adnan; Hellyer, Maria Theresa; Zhang, Dayi

    2014-06-01

    Moringa oleifera has been used as a coagulation reagent for drinking water purification, especially in developing countries such as Malawi. This research revealed the cytoxicity and genotoxicity of M. oleifera by Acinetobacter bioreporter. The results indicated that significant cytoxicity effects were observed when the powdered M. oleifera seeds concentration is from 1 to 50 mg/L. Through direct contact, ethanolic-water extraction and hexane extraction, the toxic effects of hydrophobic and hydrophilic components in M. oleifera seeds were distinguished. It suggested that the hydrophobic lipids contributed to the dominant cytoxicity, consequently resulting in the dominant genotoxicity in the water-soluble fraction due to limited dissolution when the M. oleifera seeds granule concentration was from 10 to 1000 mg/L. Based on cytoxicity and genotoxicity model, the LC50 and LC90 of M. oleifera seeds were 8.5 mg/L and 300 mg/L respectively and their genotoxicity was equivalent to 8.3 mg mitomycin C per 1.0 g dry M. oleifera seed. The toxicity of M. oleifera has also remarkable synergistic effects, suggesting whole cell bioreporter as an appropriate and complementary tool to chemical analysis for environmental toxicity assessment.

  4. An alternative antidote therapy in amitriptyline-induced rat toxicity model: theophylline.

    Science.gov (United States)

    Oransay, Kubilay; Kalkan, Sule; Hocaoglu, Nil; Arici, Aylin; Tuncok, Yesim

    2011-01-01

    We planned this study in order to investigate the effects of theophylline on cardiovascular parameters in an anaesthetized rat model of amitriptyline toxicity. In the preliminary study, we tested theophylline as 1 mg/kg of bolus, followed by a 0.5-mg/kg infusion. Toxicity was induced by the infusion of 0.94 mg/kg/min of amitriptyline up to the point of a 40-45% inhibition of mean arterial pressure (MAP). The rats were randomized to two groups: a group of 5% dextrose bolus followed by 5% dextrose infusion, and another group with theophylline bolus followed by infusion. Amitriptyline caused a significant decrease in MAP and prolongation in QRS; however, it did not alter heart rate (HR). When compared to the dextrose group, theophylline administration increased MAP, shortened prolonged QRS duration, and increased HR (P  0.05). Bolus doses followed by a continuous infusion of theophylline were found to be effective in reversing the hypotension and QRS prolongation seen in amitriptyline toxicity. One of the possible explanations of this beneficial effect is nonselective adenosine antagonism of theophylline. Further studies are needed to reveal the exact mechanism of the observed effect.

  5. Linking in Vitro Effects and Detected Organic Micropollutants in Surface Water Using Mixture-Toxicity Modeling.

    Science.gov (United States)

    Neale, Peta A; Ait-Aissa, Selim; Brack, Werner; Creusot, Nicolas; Denison, Michael S; Deutschmann, Björn; Hilscherová, Klára; Hollert, Henner; Krauss, Martin; Novák, Jiří; Schulze, Tobias; Seiler, Thomas-Benjamin; Serra, Helene; Shao, Ying; Escher, Beate I

    2015-12-15

    Surface water can contain countless organic micropollutants, and targeted chemical analysis alone may only detect a small fraction of the chemicals present. Consequently, bioanalytical tools can be applied complementary to chemical analysis to detect the effects of complex chemical mixtures. In this study, bioassays indicative of activation of the aryl hydrocarbon receptor (AhR), activation of the pregnane X receptor (PXR), activation of the estrogen receptor (ER), adaptive stress responses to oxidative stress (Nrf2), genotoxicity (p53) and inflammation (NF-κB) and the fish embryo toxicity test were applied along with chemical analysis to water extracts from the Danube River. Mixture-toxicity modeling was applied to determine the contribution of detected chemicals to the biological effect. Effect concentrations for between 0 to 13 detected chemicals could be found in the literature for the different bioassays. Detected chemicals explained less than 0.2% of the biological effect in the PXR activation, adaptive stress response, and fish embryo toxicity assays, while five chemicals explained up to 80% of ER activation, and three chemicals explained up to 71% of AhR activation. This study highlights the importance of fingerprinting the effects of detected chemicals.

  6. Ionospheric topside models compared with experimental electron density profiles

    Directory of Open Access Journals (Sweden)

    S. M. Radicella

    2005-06-01

    Full Text Available Recently an increasing number of topside electron density profiles has been made available to the scientific community on the Internet. These data are important for ionospheric modeling purposes, since the experimental information on the electron density above the ionosphere maximum of ionization is very scarce. The present work compares NeQuick and IRI models with the topside electron density profiles available in the databases of the ISIS2, IK19 and Cosmos 1809 satellites. Experimental electron content from the F2 peak up to satellite height and electron densities at fixed heights above the peak have been compared under a wide range of different conditions. The analysis performed points out the behavior of the models and the improvements needed to be assessed to have a better reproduction of the experimental results. NeQuick topside is a modified Epstein layer, with thickness parameter determined by an empirical relation. It appears that its performance is strongly affected by this parameter, indicating the need for improvements of its formulation. IRI topside is based on Booker's approach to consider two parts with constant height gradients. It appears that this formulation leads to an overestimation of the electron density in the upper part of the profiles, and overestimation of TEC.

  7. Modeling physiological processes that relate toxicant exposure and bacterial population dynamics.

    Directory of Open Access Journals (Sweden)

    Tin Klanjscek

    Full Text Available Quantifying effects of toxicant exposure on metabolic processes is crucial to predicting microbial growth patterns in different environments. Mechanistic models, such as those based on Dynamic Energy Budget (DEB theory, can link physiological processes to microbial growth.Here we expand the DEB framework to include explicit consideration of the role of reactive oxygen species (ROS. Extensions considered are: (i additional terms in the equation for the "hazard rate" that quantifies mortality risk; (ii a variable representing environmental degradation; (iii a mechanistic description of toxic effects linked to increase in ROS production and aging acceleration, and to non-competitive inhibition of transport channels; (iv a new representation of the "lag time" based on energy required for acclimation. We estimate model parameters using calibrated Pseudomonas aeruginosa optical density growth data for seven levels of cadmium exposure. The model reproduces growth patterns for all treatments with a single common parameter set, and bacterial growth for treatments of up to 150 mg(Cd/L can be predicted reasonably well using parameters estimated from cadmium treatments of 20 mg(Cd/L and lower. Our approach is an important step towards connecting levels of biological organization in ecotoxicology. The presented model reveals possible connections between processes that are not obvious from purely empirical considerations, enables validation and hypothesis testing by creating testable predictions, and identifies research required to further develop the theory.

  8. Human Umbilical Cord Blood-Derived Neural Stem Cell Line as a Screening Model for Toxicity.

    Science.gov (United States)

    Patnaik, Rajashree; Padhy, Rabindra Nath

    2017-04-01

    The aim was to investigate whether a human neural stem cell (NSC) line derived from human umbilical cord blood (hUCB) can be used for toxicity study. Toxicity of both neurotoxic environmental xenobiotics, methyl mercury chloride (CH3HgCl), lead acetate (CH3COOPb), and chlorpyrifos (CP), and non-neurotoxic insecticide, dichlorvos, as well as non-neurotoxic drugs, theophylline and acetaminophen were assessed. Additionally, differentiation of neuronal and glial cell lines derived from hUCB was elucidated. It was observed that CH3HgCl was more toxic to human NSCs in comparison to CH3COOPb and CP. The minimum inhibitory concentration (MIC) value against NSCs was 3, 10, and 300 mg/L, in each staining process, acridine orange/ethidium bromide (AO/EB) staining, 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay, and Hoechst staining, for CH3HgCl, CP, and CH3COOPb, respectively. CH3HgCl had the LC25 value as 10.0, 14.4, and 12.7 mg/L, by staining method mentioned in succession. CP had the LC25 value as 21.9, 23.7, and 18.4 mg/L; similarly, CH3COOPb had LC25 values, successively as 616.9, 719.2, and 890.3 mg/L. LC50 values ranged from 18.2 to 21.7 mg/L for CH3HgCl, 56.4 to 60.2 mg/L for CP, and 1000 to 1460.1 for CH3COOPb. Theophylline, acetaminophen, and dichlorvos had no impact on the viability of NSCs. This work justified that hUCB-NSC model can be used for toxicity study.

  9. A Physical Model of Electron Radiation Belts of Saturn

    Science.gov (United States)

    Lorenzato, L.; Sicard-Piet, A.; Bourdarie, S.

    2012-04-01

    Radiation belts causes irreversible damages on on-board instruments materials. That's why for two decades, ONERA proposes studies about radiation belts of magnetized planets. First, in the 90's, the development of a physical model, named Salammbô, carried out a model of the radiation belts of the Earth. Then, for few years, analysis of the magnetosphere of Jupiter and in-situ data (Pioneer, Voyager, Galileo) allow to build a physical model of the radiation belts of Jupiter. Enrolling on the Cassini age and thanks to all information collected, this study permits to adapt Salammbô jovian radiation belts model to the case of Saturn environment. Indeed, some physical processes present in the kronian magnetosphere are similar to those present in the magnetosphere of Jupiter (radial diffusion; interaction of energetic electrons with rings, moons, atmosphere; synchrotron emission). However, some physical processes have to be added to the kronian model (compared to the jovian model) because of the particularity of the magnetosphere of Saturn: interaction of energetic electrons with neutral particles from Enceladus, and wave-particle interaction. This last physical process has been studied in details with the analysis of CASSINI/RPWS (Radio and Plasma Waves Science) data. The major importance of the wave particles interaction is now well known in the case of the radiation belts of the Earth but it is important to investigate on its role in the case of Saturn. So, importance of each physical process has been studied and analysis of Cassini MIMI-LEMMS and CAPS data allows to build a model boundary condition (at L = 6). Finally, results of this study lead to a kronian electrons radiation belts model including radial diffusion, interactions of energetic electrons with rings, moons and neutrals particles and wave-particle interaction (interactions of electrons with atmosphere particles and synchrotron emission are too weak to be taken into account in this model). Then, to

  10. USEtox - The UNEP-SETAC toxicity model: recommended characterisation factors for human toxicity and freshwater ecotoxicity in Life Cycle Impact Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Rosenbaum, Ralph K.; Bachmann, Till M.; Swirsky Gold, Lois; Huijbregts, Mark A.J.; Jolliet, Olivier; Juraske, Ronnie; Koehler, Annette; Larsen, Henrik F.; MacLeod, Matthew; Margni, Manuele; McKone, Thomas E.; Payet, Jerome; Schuhmacher, Marta; van de Meent, Dik; Hauschild, Michael Z.

    2008-02-03

    Background, Aim and Scope. In 2005 a comprehensive comparison of LCIA toxicity characterisation models was initiated by the UNEP-SETAC Life Cycle Initiative, directly involving the model developers of CalTOX, IMPACT 2002, USES-LCA, BETR, EDIP, WATSON, and EcoSense. In this paper we describe this model-comparison process and its results--in particular the scientific consensus model developed by the model developers. The main objectives of this effort were (i) to identify specific sources of differences between the models' results and structure, (ii) to detect the indispensable model components, and (iii) to build a scientific consensus model from them, representing recommended practice. Methods. A chemical test set of 45 organics covering a wide range of property combinations was selected for this purpose. All models used this set. In three workshops, the model comparison participants identified key fate, exposure and effect issues via comparison of the final characterisation factors and selected intermediate outputs for fate, human exposure and toxic effects for the test set applied to all models. Results. Through this process, we were able to reduce inter-model variation from an initial range of up to 13 orders of magnitude down to no more than 2 orders of magnitude for any substance. This led to the development of USEtox, a scientific consensus model that contains only the most influential model elements. These were, for example, process formulations accounting for intermittent rain, defining a closed or open system environment, or nesting an urban box in a continental box. Discussion. The precision of the new characterisation factors (CFs) is within a factor of 100-1000 for human health and 10-100 for freshwater ecotoxicity of all other models compared to 12 orders of magnitude variation between the CFs of each model respectively. The achieved reduction of inter-model variability by up to 11 orders of magnitude is a significant improvement

  11. Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants

    Directory of Open Access Journals (Sweden)

    Ntie-Kang F

    2016-07-01

    Full Text Available Fidele Ntie-Kang,1,2,* Conrad Veranso Simoben,1,2,* Berin Karaman,1 Valery Fuh Ngwa,3 Philip Neville Judson,4 Wolfgang Sippl,1 Luc Meva’a Mbaze5 1Department of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Halle (Saale, Germany; 2Department of Chemistry, University of Buea, Buea, Cameroon; 3Interuniversity Institute For Biostatistics and Statistical Bioinformatics (I-BioStat, University of Hasselt, Hasselt, Belgium; 4Chemical Bioactivity Information Centre, Harrogate, UK; 5Department of Chemistry, Faculty of Science, University of Douala, Douala, Cameroon *These authors contributed equally to this work Abstract: Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B β, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and Güner–Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (~400 compounds from African medicinal plants, along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising ~1,500 published naturally occurring plant-based compounds from around the world. Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa’s expert knowledge-based system (Derek, showing that only an insignificant proportion of the promising

  12. QSTR with extended topochemical atom (ETA) indices. 14. QSAR modeling of toxicity of aromatic aldehydes to Tetrahymena pyriformis

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Kunal, E-mail: kunalroy_in@yahoo.com [Drug Theoretics and Cheminformatics Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032 (India); Das, Rudra Narayan [Drug Theoretics and Cheminformatics Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032 (India)

    2010-11-15

    Aldehydes are a toxic class of chemicals causing severe health hazards. In this background, quantitative structure-toxicity relationship (QSTR) models have been developed in the present study using Extended Topochemical Atom (ETA) indices for a large group of 77 aromatic aldehydes for their acute toxicity against the protozoan ciliate Tetrahymena pyriformis. The ETA models have been compared with those developed using various non-ETA topological indices. Attempt was also made to include the n-octanol/water partition coefficient (log K{sub o/w}) as an additional descriptor considering the importance of hydrophobicity in toxicity prediction. Thirty different models were developed using different chemometric tools. All the models have been validated using internal validation and external validation techniques. The statistical quality of the ETA models was found to be comparable to that of the non-ETA models. The ETA models have shown the important effects of steric bulk, lipophilicity, presence of electronegative atom containing substituents and functionality of the aldehydic oxygen to the toxicity of the aldehydes. The best ETA model (without using log K{sub o/w}) shows encouraging statistical quality (Q{sub int}{sup 2}=0.709,Q{sub ext}{sup 2}=0.744). It is interesting to note that some of the topological models reported here are better in statistical quality than previously reported models using quantum chemical descriptors.

  13. An extended model for electron spin polarization in photosynthetic bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Morris, A.L.; Norris, J.R. (Argonne National Lab., IL (USA) Chicago Univ., IL (USA). Dept. of Chemistry); Thurnauer, M.C. (Argonne National Lab., IL (USA))

    1990-01-01

    We have developed a general model for electron spin polarization which includes contributions from both CIDEP (chemically induced dynamic electron polarization) and CRP (correlated radical polarization). In this paper, we apply this model to sequential electron transfer in photosynthetic bacteria. Our model calculates the density matrix for the P{sup +}I{sup {minus}} radical pair and transfers the polarization as it develops to the P{sup +}Q{sup {minus}} radical pair. We illustrate several possible cases. One case is equivalent to CIDEP; no interactions are included on the secondary radical pair, P{sup +}Q{sup {minus}}. Another approximates CRPP by either increasing the transfer rate from P{sup +}I{sup {minus}} to P{sup +}Q{sup {minus}} or restricting interactions to the secondary radical pair, P{sup +}Q{sup {minus}}. Others allow interactions on both the primary and secondary radical pairs with various transfer rates. 15 refs., 4 figs.

  14. Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.

    Science.gov (United States)

    Villain, Jonathan; Minguez, Laetitia; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2016-02-01

    The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water).

  15. Integrating (Q)SAR models, expert systems and read-across approaches for the prediction of developmental toxicity.

    Science.gov (United States)

    Hewitt, M; Ellison, C M; Enoch, S J; Madden, J C; Cronin, M T D

    2010-08-01

    It has been estimated that reproductive and developmental toxicity tests will account for a significant proportion of the testing costs associated with REACH compliance. Consequently, the use of alternative methods to predict developmental toxicity is an attractive prospect. The present study evaluates a number of computational models and tools which can be used to aid assessment of developmental toxicity potential. The performance and limitations of traditional (quantitative) structure-activity relationship ((Q)SARs) modelling, structural alert-based expert system prediction and chemical profiling approaches are discussed. In addition, the use of category formation and read-across is also addressed. This study demonstrates the limited success of current modelling methods when used in isolation. However, the study also indicates that when used in combination, in a weight-of-evidence approach, better use may be made of the limited toxicity data available and predictivity improved. Recommendations are provided as to how this area could be further developed in the future.

  16. In vivo toxicity of enoxaparin encapsulated in mucoadhesive nanoparticles: Topical application in a wound healing model

    Science.gov (United States)

    Huber, S. C.; Marcato, P. D.; Barbosa, R. M.; Duran, N.; Annichino-Bizzacchi, J. M.

    2013-04-01

    Wound healing comprises four distinct phases and involves many cell events and biologic markers. The use of nanoparticles for topical application has gaining attention due to its deeper penetration in the skin and the retention capacity of the drug in the site of application. In this study the effect and toxicity of mucoadhesive polymeric nanoparticles loaded with enoxaparin was evaluated in in vivo model of skin ulcer. Our results showed an interesting formulation based on mucoadhesive nanoparticles with enoxaparin that improved wound healing without cytotoxicity in vitro in all endpoint evaluated. Then, this semi-solid formulation is a promising option for skin ulcer treatment.

  17. Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on in vitro toxicity data and in silico physiologically based kinetic modeling.

    Science.gov (United States)

    Louisse, Jochem; Bosgra, Sieto; Blaauboer, Bas J; Rietjens, Ivonne M C M; Verwei, Miriam

    2015-07-01

    The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity data obtained from in vitro assays for risk assessment, in vitro concentration-response data need to be translated into in vivo dose-response data that are needed to obtain points of departure for risk assessment, like a benchmark dose (BMD). In the present study, we translated in vitro concentration-response data of the retinoid all-trans-retinoic acid (ATRA), obtained in the differentiation assay of the embryonic stem cell test, into in vivo dose-response data using a physiologically based kinetic model for rat and human that is mainly based on kinetic model parameter values derived using in vitro techniques. The predicted in vivo dose-response data were used for BMD modeling, and the obtained BMDL10 values [lower limit of the 95 % confidence interval on the BMD at which a benchmark response equivalent to a 10 % effect size (BMR10) is reached (BMD10)] for rat were compared with BMDL10 values derived from in vivo developmental toxicity data in rats reported in the literature. The results show that the BMDL10 values from predicted dose-response data differ about sixfold from the BMDL10 values obtained from in vivo data, pointing at the feasibility of using a combined in vitro-in silico approach for defining a point of departure for toxicological risk assessment.

  18. Model Checking Electronic Commerce Security Protocols Based on CTL

    Institute of Scientific and Technical Information of China (English)

    XIAO De-qin; ZHANG Huan-guo

    2005-01-01

    We present a model based on Computational Temporal Logic (CTL) methods for verifying security requirements of electronic commerce protocols. The model describes formally the authentication, confidentiality integrity,non-repudiation, denial of service and access control of the electronic commerce protocols. We illustrate as case study a variant of the Lu-Smolka protocol proposed by Lu-Smolka.Moreover, we have discovered two attacks that allow a dishonest user to purchase a good debiting the amount to another user. And also, we compared our work with relative research works and found that the formal way of this paper is more general to specify security protocols for E-Commerce.

  19. Protein electron transfer (mechanism and reproductive toxicity): iminium, hydrogen bonding, homoconjugation, amino acid side chains (redox and charged), and cell signaling.

    Science.gov (United States)

    Kovacic, Peter

    2007-03-01

    This contribution presents novel biochemical perspectives of protein electron transfer (ET) with focus on the iminium nature of the peptide link, along with relationships to reproductive toxicity. The favorable influence of hydrogen bonding on protein ET has been widely documented. Hydrogen bonding of the zwitterionic peptide enhances iminium character. A wide array of such bonding agents is available in vivo, with many reports on the peptide link itself. ET proceeds along the backbone, due in part, to homoconjugation. Redox amino acids (AAs), mainly tyrosine (Tyr), tryptophan (Typ), histidine (His), cysteine (Cys), disulfide, and methionine (Met), are involved in the competing processes for radical formation: direct hydrogen atom abstraction versus electron and proton loss. It appears that the radical or radical cation generated during the redox process is capable of interacting with n-electrons of the backbone. Beneficial effects of cationic AAs impact the conduction process. A relationship apparently exists involving cell signaling, protein conduction, and radicals or electrons. In addition, the link between protein ET and reproductive toxicity is examined. A key element is the role of reactive oxygen species (ROS) generated by protein ET. There is extensive evidence for involvement of ROS in generation of birth defects. The radical species arise in protein mainly by ET transformations by enzymes, as illustrated in the case of alcoholism. (c) 2007 Wiley-Liss, Inc.

  20. Trophic State and Toxic Cyanobacteria Density in Optimization Modeling of Multi-Reservoir Water Resource Systems

    Directory of Open Access Journals (Sweden)

    Andrea Sulis

    2014-04-01

    Full Text Available The definition of a synthetic index for classifying the quality of water bodies is a key aspect in integrated planning and management of water resource systems. In previous works [1,2], a water system optimization modeling approach that requires a single quality index for stored water in reservoirs has been applied to a complex multi-reservoir system. Considering the same modeling field, this paper presents an improved quality index estimated both on the basis of the overall trophic state of the water body and on the basis of the density values of the most potentially toxic Cyanobacteria. The implementation of the index into the optimization model makes it possible to reproduce the conditions limiting water use due to excessive nutrient enrichment in the water body and to the health hazard linked to toxic blooms. The analysis of an extended limnological database (1996–2012 in four reservoirs of the Flumendosa-Campidano system (Sardinia, Italy provides useful insights into the strengths and limitations of the proposed synthetic index.

  1. Electron-scale reduced fluid models with gyroviscous effects

    Science.gov (United States)

    Passot, T.; Sulem, P. L.; Tassi, E.

    2017-08-01

    Reduced fluid models for collisionless plasmas including electron inertia and finite Larmor radius corrections are derived for scales ranging from the ion to the electron gyroradii. Based either on pressure balance or on the incompressibility of the electron fluid, they respectively capture kinetic Alfvén waves (KAWs) or whistler waves (WWs), and can provide suitable tools for reconnection and turbulence studies. Both isothermal regimes and Landau fluid closures permitting anisotropic pressure fluctuations are considered. For small values of the electron beta parameter e$ , a perturbative computation of the gyroviscous force valid at scales comparable to the electron inertial length is performed at order e)$ , which requires second-order contributions in a scale expansion. Comparisons with kinetic theory are performed in the linear regime. The spectrum of transverse magnetic fluctuations for strong and weak turbulence energy cascades is also phenomenologically predicted for both types of waves. In the case of moderate ion to electron temperature ratio, a new regime of KAW turbulence at scales smaller than the electron inertial length is obtained, where the magnetic energy spectrum decays like \\bot -13/3$ , thus faster than the \\bot -11/3$ spectrum of WW turbulence.

  2. Neutrino-Electron Scattering and the Little Higgs Models

    Institute of Scientific and Technical Information of China (English)

    LI Na; YUE Chong-Xing; LI Xu-Xin

    2011-01-01

    The neutrino-electron scattering process is sensitive to the standard model (SM) and the new physics beyond the SM.We calculate the corrections of the littlest Higgs model and the SU(3) simple group model to the vee scattering cross section.Using the LSND experimental measured values,we obtain the bounds on the relevant free parameters,which might be compatible with those from the electroweak precision data.Neutrino-electron scattering is a simple and purely leptonic weak interaction process that can play an important role to perform precision tests of the standard model (SM) and probe various kinds of new physics models beyond the SM.[1-3] Thus,this process provides an ideal tool for electroweak studies.%The neutrino-electron scattering process is sensitive to the standard model (SM) and the new physics beyond the SM. We calculate the corrections of the littlest Higgs model and the SU(3) simple group model to the vee scattering cross section. Using the LSND experimental measured values, we obtain the bounds on the relevant free parameters, which might be compatible with those from the electroweak precision data.

  3. NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction

    Energy Technology Data Exchange (ETDEWEB)

    Wennberg, Berit M.; Baumann, Pia; Gagliardi, Giovanna (Dept. of Medical Physics, Karolinska Univ. Hospital and the Karolinska Inst., Stockholm (Sweden)), e-mail: berit.wennberg@karolinska.se (and others)

    2011-05-15

    Background. In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. Material and methods. Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman- Kutcher-Burman (LKB) model. In the LQ-correction alpha/beta = 3 Gy was used and the USC parameters used were: alpha/beta = 3 Gy, D{sub 0} = 1.0 Gy, n = 10, alpha 0.206 Gy-1 and d{sub T} = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether 'high doses to small volumes' or 'low doses to large volumes' are most important for lung toxicity. Results and Discussion. NTCP analysis with the LKB-model using parameters m = 0.4, D50 = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D{sub 50} = 20 Gy n = 0.93 with LQ correction and n 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ,USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling

  4. A predictive standard model for heavy electron systems

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yifeng [Los Alamos National Laboratory; Curro, N J [UC DAVIS; Fisk, Z [UC DAVIS; Pines, D [UC DAVIS

    2010-01-01

    We propose a predictive standard model for heavy electron systems based on a detailed phenomenological two-fluid description of existing experimental data. It leads to a new phase diagram that replaces the Doniach picture, describes the emergent anomalous scaling behavior of the heavy electron (Kondo) liquid measured below the lattice coherence temperature, T*, seen by many different experimental probes, that marks the onset of collective hybridization, and enables one to obtain important information on quantum criticality and the superconducting/antiferromagnetic states at low temperatures. Because T* is {approx} J{sup 2} {rho}/2, the nearest neighbor RKKY interaction, a knowledge of the single-ion Kondo coupling, J, to the background conduction electron density of states, {rho}, makes it possible to predict Kondo liquid behavior, and to estimate its maximum superconducting transition temperature in both existing and newly discovered heavy electron families.

  5. Two-Temperature Model of Nonequilibrium Electron Relaxation:. a Review

    Science.gov (United States)

    Singh, Navinder

    The present paper is a review of the phenomena related to nonequilibrium electron relaxation in bulk and nano-scale metallic samples. The workable Two-Temperature Model (TTM) based on Boltzmann-Bloch-Peierls kinetic equation has been applied to study the ultra-fast (femto-second) electronic relaxation in various metallic systems. The advent of new ultra-fast (femto-second) laser technology and pump-probe spectroscopy has produced wealth of new results for micro- and nano-scale electronic technology. The aim of this paper is to clarify the TTM, conditions of its validity and nonvalidity, its modifications for nano-systems, to sum-up the progress, and to point out open problems in this field. We also give a phenomenological integro-differential equation for the kinetics of nondegenerate electrons that goes beyond the TTM.

  6. Rigorous selection of random forest models for identifying compounds that activate toxicity-related pathways

    Directory of Open Access Journals (Sweden)

    Yoshihiro eUesawa

    2016-02-01

    Full Text Available Random forest (RF is a machine-learning ensemble method with high predictive performance. Majority voting in RF uses the discrimination results in numerous decision trees produced from bootstrapping data. For the same dataset, the bootstrapping process yields different predictive capacities in each generation. As participants in the Toxicology in the 21st Century (Tox21 DATA Challenge 2014, we produced numerous RF models for predicting the structures of compounds that can activate each toxicity-related pathway, and then selected the model with the highest predictive ability. Half of the compounds in the training dataset supplied by the competition organizer were allocated to the validation dataset. The remaining compounds were used in model construction. The charged and uncharged forms of each molecule were calculated using the molecular operating environment (MOE software. Subsequently, the descriptors were computed using MOE, MarvinView, and Dragon. These combined methods yielded over 4,071 descriptors for model construction. Using these descriptors, pattern recognition analyses were performed by RF implemented in JMP Pro (a statistical software package. A hundred to two hundred RF models were generated for each pathway. The predictive performance of each model was tested against the validation dataset, and the best-performing model was selected. In the competition, the latter model selected a best-performing model from the 50% test set that best predicted the structures of compounds that activate the estrogen receptor ligand-binding domain (ER-LBD.

  7. Kinetic modelling of runaway electrons in dynamic scenarios

    Science.gov (United States)

    Stahl, A.; Embréus, O.; Papp, G.; Landreman, M.; Fülöp, T.

    2016-11-01

    Improved understanding of runaway-electron formation and decay processes are of prime interest for the safe operation of large tokamaks, and the dynamics of the runaway electrons during dynamical scenarios such as disruptions are of particular concern. In this paper, we present kinetic modelling of scenarios with time-dependent plasma parameters; in particular, we investigate hot-tail runaway generation during a rapid drop in plasma temperature. With the goal of studying runaway-electron generation with a self-consistent electric-field evolution, we also discuss the implementation of a collision operator that conserves momentum and energy and demonstrate its properties. An operator for avalanche runaway-electron generation, which takes the energy dependence of the scattering cross section and the runaway distribution into account, is investigated. We show that the simplified avalanche model of Rosenbluth and Putvinskii (1997 Nucl. Fusion 37 1355) can give inaccurate results for the avalanche growth rate (either lower or higher) for many parameters, especially when the average runaway energy is modest, such as during the initial phase of the avalanche multiplication. The developments presented pave the way for improved modelling of runaway-electron dynamics during disruptions or other dynamic events.

  8. Identification of Chemical Vascular Disruptors During Development Using An Integrative Predictive Toxicity Model and Zebrafish and in Vitro Functional Angiogenesis Assays.

    Science.gov (United States)

    Identification of chemical vascular disruptors during development using an integrative predictive toxicity model and zebrafish and in vitro functional angiogenesis assays Chemically-induced vascular toxicity during embryonic development can result in a wide range of adverse pre...

  9. Identification of Chemical Vascular Disruptors During Development Using An Integrative Predictive Toxicity Model and Zebrafish and in Vitro Functional Angiogenesis Assays.

    Science.gov (United States)

    Identification of chemical vascular disruptors during development using an integrative predictive toxicity model and zebrafish and in vitro functional angiogenesis assays Chemically-induced vascular toxicity during embryonic development can result in a wide range of adverse pre...

  10. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

    Directory of Open Access Journals (Sweden)

    Plengsuriyakarn Tullayakorn

    2012-03-01

    Full Text Available Abstract Background Chemotherapy of cholangiocarcinoma (CCA, a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. Methods/Design The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR, the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL, fruits of Piper chaba Hunt. (De-Plee: PC, and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Results Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively. PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL, analgesic (CUR and

  11. Modeling dispersion from toxic gas released after a train collision in Graniteville, SC.

    Science.gov (United States)

    Buckley, Robert L; Hunter, Charles H; Addis, Robert P; Parker, Matthew J

    2007-03-01

    The Savannah River National Laboratory (SRNL) Weather Information and Display System was used to provide meteorological and atmospheric modeling/consequence assessment support to state and local agencies after the collision of two Norfolk Southern freight trains on the morning of January 6, 2005. This collision resulted in the release of several toxic chemicals to the environment, including chlorine. The dense and highly toxic cloud of chlorine gas that formed in the vicinity of the accident was responsible for 9 fatalities and caused injuries to more than 500 others. Transport model results depicting the forecast path of the ongoing release were made available to emergency managers in the county's Unified Command Center shortly after SRNL received a request for assistance. Support continued over the ensuing 2 days of the active response. The SRNL also provided weather briefings and transport/consequence assessment model results to responders from the South Carolina Department of Health and Environmental Control, the Savannah River Site (SRS) Emergency Operations Center, Department of Energy headquarters, and hazard material teams dispatched from the SRS. Operational model-generated forecast winds used in consequence assessments conducted during the incident were provided at 2-km horizontal grid spacing during the accident response. High-resolution Regional Atmospheric Modeling System (RAMS, version 4.3.0) simulation was later performed to examine potential influences of local topography on plume migration in greater detail. The detailed RAMS simulation was used to determine meteorology using multiple grids with an innermost grid spacing of 125 m. Results from the two simulations are shown to generally agree with meteorological observations at the time; consequently, local topography did not significantly affect wind in the area. Use of a dense gas dispersion model to simulate localized plume behavior using the higher-resolution winds indicated agreement with

  12. Modeling the interaction of light intensity, nutrient concentration and uranium toxicity in Lemna minor

    Energy Technology Data Exchange (ETDEWEB)

    Zimmer, E.; Horemans, N.; Vandenhove, H. [Belgian Nuclear Research Centre SCK-CEN (Belgium); Cedergreen, N. [University of Copenhagen (Denmark); Jager, T. [Vrije Universiteit Amsterdam (Netherlands)

    2014-07-01

    Radioecology aims at assessing the effect of radionuclides and radiation on the environment. Since we cannot test every possible environmental situation in the laboratory, we need modeling approaches to extrapolate the results of toxicity assays to environmentally relevant scenarios. Therefore, it is of crucial importance to understand the effect of relevant environmental factors, such as nutrients, temperature and light on the toxicity of the test. Radionuclides are often found to induce the production of reactive oxygen species (ROS). In plants, an overload of ROS can lead to disturbances of the photosynthetic system. Since the light intensity determines the efficiency of the photo-systems in plants, it can be expected to interact with the effect of radionuclides. The nutrient concentration of the test medium determines the physiological state of the plant, affecting in turn the plant's capability of dealing with stress and hence influences the toxicity of the contaminant. To study the interaction of stressors with environmental conditions, mechanistic effect modeling is promoted widely in ecotoxicology. In principle, the modelling aims at a mechanistic understanding of the different processes causing the stress individually, and integrating them in one framework to study their joint effect and possible interaction. We here present a mechanistic effect model for Lemna minor (common duckweed), which is based on Dynamic Energy Budget (DEB) theory. Models based on DEB have been used widely to study the effects of compounds on animals. Due to its general applicability to all types of organisms, it holds potential to be used for comparison of species and compounds in a broad context. Energy uptake from the environment is modeled explicitly, and metabolic rates are set to depend on temperature in DEB models. Therefore, they can be used to extrapolate effects to a wide range of environmentally relevant scenarios. Until now, the DEB research in ecotoxicology has

  13. The embryonic stem cell test combined with toxicogenomics as an alternative testing model for the assessment of developmental toxicity.

    Science.gov (United States)

    van Dartel, Dorien A M; Piersma, Aldert H

    2011-09-01

    One of the most studied in vitro alternative testing methods for identification of developmental toxicity is the embryonic stem cell test (EST). Although the EST has been formally validated, the applicability domain as well as the predictability of the model needs further study to allow successful implementation of the EST as an alternative testing method in regulatory toxicity testing. Genomics technologies have already provided a proof of principle of their value in identification of toxicants such as carcinogenic compounds. Also within the EST, gene expression profiling has shown its value in the identification of developmental toxicity and in the evaluation of factors critical for risk assessment, such as dose and time responses. It is expected that the implementation of genomics into the EST will provide a more detailed end point evaluation as compared to the classical morphological scoring of differentiation cultures. Therefore, genomics may contribute to improvement of the EST, both in terms of definition of its applicability domain as well as its predictive capacity. In the present review, we present the progress that has been made with regard to the prediction of developmental toxicity using the EST combined with transcriptomics. Furthermore, we discuss the developments of additional aspects required for further optimization of the EST, including kinetics, the use of human embryonic stem cells (ESC) and computational toxicology. Finally, the current and future use of the EST model for prediction of developmental toxicity in testing strategies and in regulatory toxicity evaluations is discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Electron-gas clusters: the ultimate jellium model

    Science.gov (United States)

    Koskinen, M.; Lipas, P. O.; Manninen, M.

    1995-12-01

    The local spin-density approximation is used to calculate ground- and isomeric-state geometries of jellium clusters with 2 to 22 electrons. The positive background charge of the model is completely deformable, both in shape and in density. The model has no input parameters. The resulting shapes of the clusters exhibit breaking of axial and inversion symmetries; in general the shapes are far from ellipsoidal. Those clusters which lack inversion symmetry are extremely soft against odd-multipole deformations. Some clusters can be interpreted as molecules built from magic clusters. The deformation produces a gap at the Fermi level. This results in a regular odd-even staggering of the total energy per electron and of the HOMO level. The strongly deformed 14-electron cluster is semimagic. Stable isomers are predicted. The splitting of the plasmon resonance due to deformation is estimated on a classical argument.

  15. Electronic market models for decision support systems on the Web

    Institute of Scientific and Technical Information of China (English)

    谢勇; 王红卫; 费奇

    2004-01-01

    With the prevalence of the Web, most decision-makers are likely to use the Web to support their decision-making. Web-based technologies are leading a major stream of researching decision support systems (DSS). We propose a formal definition and a conceptual framework for Web-based open DSS (WODSS). The formal definition gives an overall view of WODSS, and the conceptual framework based on browser/broker/server computing mode employs the electronic market to mediate decision-makers and providers, and facilitate sharing and reusing of decision resources. We also develop an admitting model, a trading model and a competing model of electronic market in WODSS based on market theory in economics. These models reveal the key mechanisms that drive WODSS operate efficiently.

  16. Insulin versus Lipid Emulsion in a Rabbit Model of Severe Propranolol Toxicity: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Martyn Harvey

    2011-01-01

    Full Text Available Background and objective. Beta-blocker overdose may result in intractable cardiovascular collapse despite conventional antidotal treatments. High dose insulin/glucose (ING, and more recently intravenous lipid emulsion (ILE, have been proposed as potentially beneficial therapies in beta blocker intoxication. We compare efficacy of the novel antidotes ING, with ILE, in a rabbit model of combined enteric/intravenous propranolol toxicity. Methods. Sedated, mechanically ventilated and invasively monitored New Zealand White rabbits underwent mini-laparotomy and enterostomy formation with 40 mg/kg propranolol instilled into the proximal small bowel. At 30 minutes propranolol infusion was commenced at 4 mg/kg/hr and continued to a target mean arterial pressure (MAP of 50% baseline MAP. Animals were resuscitated with insulin at 3 U/kg plus 0.5 g/kg glucose (ING group, or 10 mL/kg 20% Intralipid (ILE group. Results. Rate pressure product (RPP; RPP = heart rate × mean arterial pressure was greatest in the ING group at 60 minutes (P<.05. A trend toward greater heart rate was observed in the ING group (P=.06. No difference was observed in survival between groups (4/5 ING versus 2/5 ILE; P=.524. Conclusions. High dose insulin resulted in greater rate pressure product compared with lipid emulsion in this rabbit model of severe enteric/intravenous propranolol toxicity.

  17. The galactose-induced decrease in phosphate levels leads to toxicity in yeast models of galactosemia.

    Science.gov (United States)

    Machado, Caio M; De-Souza, Evandro A; De-Queiroz, Ana Luiza F V; Pimentel, Felipe S A; Silva, Guilherme F S; Gomes, Fabio M; Montero-Lomelí, Mónica; Masuda, Claudio A

    2017-02-14

    Classic galactosemia is an inborn error of metabolism caused by deleterious mutations in the GALT gene. A number of evidences indicate that the galactose-1-phosphate accumulation observed in patient cells is a cause of toxicity in this disease. Nevertheless, the consequent molecular events caused by the galactose-1-phosphate accumulation remain elusive. Here we show that intracellular inorganic phosphate levels decreased when yeast models of classic galactosemia were exposed to galactose. The decrease in phosphate levels is probably due to the trapping of phosphate in the accumulated galactose-1-phosphate since the deletion of the galactokinase encoding gene GAL1 suppressed this phenotype. Galactose-induced phosphate depletion caused an increase in glycogen content, an expected result since glycogen breakdown by the enzyme glycogen phosphorylase is dependent on inorganic phosphate. Accordingly, an increase in intracellular phosphate levels suppressed the galactose effect on glycogen content and conferred galactose tolerance to yeast models of galactosemia. These results support the hypothesis that the galactose-induced decrease in phosphate levels leads to toxicity in galactosemia and opens new possibilities for the development of better treatments for this disease.

  18. Toxicity of different forms of graphene in a chicken embryo model.

    Science.gov (United States)

    Szmidt, Maciej; Sawosz, Ewa; Urbańska, Kaja; Jaworski, Sławomir; Kutwin, Marta; Hotowy, Anna; Wierzbicki, Mateusz; Grodzik, Marta; Lipińska, Ludwika; Chwalibog, André

    2016-10-01

    In the present work, the toxicity of three forms of graphene: pristine graphene (pG), graphene oxide (GO), and reduced graphene oxide (rGO) was investigated using a chicken embryo model. Fertilized chicken eggs were divided into the control group and groups administered with pG, GO, and rGO, in concentrations of 50, 500, and 5000 μg/ml. The experimental solutions were injected in ovo into the eggs, and at day 18 of incubation, the embryo survival, body and organ weights, the ultrastructure of liver samples, and the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the livers were measured. Survival of embryos decreased significantly after treatment with all types of graphene, but not in a dose-dependent manner. The body weights were only slightly affected by the highest doses of graphene, while the organ weights were not different among treatment groups. In all experimental groups, atypical hepatocyte ultrastructure and mitochondrial damage were observed. The concentration of the marker of DNA damage 8-OHdG in the liver significantly decreased after pG and rGO treatments. Further in vivo studies with different animal models are necessary to clarify the level of toxicity of different types of graphene and to estimate the concentrations appropriate to evaluate their biomedical applications and environmental hazard.

  19. Chronic behavioral and cognitive deficits in a rat survival model of paraoxon toxicity.

    Science.gov (United States)

    Deshpande, Laxmikant S; Phillips, Kristin; Huang, Beverly; DeLorenzo, Robert J

    2014-09-01

    Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure produced overt signs of cholinergic toxicity. Rats were rescued using an optimized atropine, 2-PAM and diazepam therapy. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-months after POX exposure. In the forced swim test, POX rats exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX rats consumed significantly less sucrose water indicating anhedonia-like condition. POX rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Further, when tested with a novel object recognition paradigm, POX rats exhibited a negative discrimination ratio indicative of impaired recognition memory. The results indicate that this model of survival from severe POX exposure can be employed to study some of the molecular bases for OP-induced chronic behavioral and cognitive comorbidities and develop therapies for their treatment.

  20. Progranulin protects against amyloid β deposition and toxicity in Alzheimer's disease mouse models.

    Science.gov (United States)

    Minami, S Sakura; Min, Sang-Won; Krabbe, Grietje; Wang, Chao; Zhou, Yungui; Asgarov, Rustam; Li, Yaqiao; Martens, Lauren H; Elia, Lisa P; Ward, Michael E; Mucke, Lennart; Farese, Robert V; Gan, Li

    2014-10-01

    Haploinsufficiency of the progranulin (PGRN) gene (GRN) causes familial frontotemporal lobar degeneration (FTLD) and modulates an innate immune response in humans and in mouse models. GRN polymorphism may be linked to late-onset Alzheimer's disease (AD). However, the role of PGRN in AD pathogenesis is unknown. Here we show that PGRN inhibits amyloid β (Aβ) deposition. Selectively reducing microglial expression of PGRN in AD mouse models impaired phagocytosis, increased plaque load threefold and exacerbated cognitive deficits. Lentivirus-mediated PGRN overexpression lowered plaque load in AD mice with aggressive amyloid plaque pathology. Aβ plaque load correlated negatively with levels of hippocampal PGRN, showing the dose-dependent inhibitory effects of PGRN on plaque deposition. PGRN also protected against Aβ toxicity. Lentivirus-mediated PGRN overexpression prevented spatial memory deficits and hippocampal neuronal loss in AD mice. The protective effects of PGRN against Aβ deposition and toxicity have important therapeutic implications. We propose enhancing PGRN as a potential treatment for PGRN-deficient FTLD and AD.

  1. Re-evaluation of metal bioaccumulation and chronic toxicity in Hyalella azteca using saturation curves and the biotic ligand model

    Energy Technology Data Exchange (ETDEWEB)

    Borgmann, U.; Norwood, W.P.; Dixon, D.G

    2004-10-01

    Bioaccumulation by Hyalella of all metals studied so far in our laboratory was re-evaluated to determine if the data could be explained satisfactorily using saturation models. Saturation kinetics are predicted by the biotic ligand model (BLM), now widely used in modelling acute toxicity, and are a pre-requisite if the BLM is to be applied to chronic toxicity. Saturation models provided a good fit to all the data. Since these are mechanistically based, they provide additional insights into metal accumulation mechanisms not immediately apparent when using allometric models. For example, maximum Cd accumulation is dependent on the hardness of the water to which Hyalella are acclimated. The BLM may need to be modified when applied to chronic toxicity. Use of saturation models for bioaccumulation, however, also necessitates the need for using saturation models for dose-response relationships in order to produce unambiguous estimates of LC50 values based on water and body concentrations. This affects predictions of toxicity at very low metal concentrations and results in lower predicted toxicity of mixtures when many metals are present at low concentrations.

  2. Fuse Modeling for Reliability Study of Power Electronics Circuits

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad; Iannuzzo, Francesco; Blaabjerg, Frede

    2017-01-01

    This paper describes a comprehensive modeling approach on reliability of fuses used in power electronic circuits. When fuses are subjected to current pulses, cyclic temperature stress is introduced to the fuse element and will wear out the component. Furthermore, the fuse may be used in a large...

  3. An Emerging Model for Student Feedback: Electronic Distributed Evaluation

    Science.gov (United States)

    Brunk-Chavez, Beth; Arrigucci, Annette

    2012-01-01

    In this article we address several issues and challenges that the evaluation of writing presents individual instructors and composition programs as a whole. We present electronic distributed evaluation, or EDE, as an emerging model for feedback on student writing and describe how it was integrated into our program's course redesign. Because the…

  4. Toward a generic model of trust for electronic commerce

    NARCIS (Netherlands)

    Tan, YH; Thoen, W

    2000-01-01

    The authors present a generic model of trust for electronic commerce consisting of two basic components, party trust and control trust, based on the concept that trust in a transaction with another party combines trust in the other parry and trust in the control mechanisms that ensure the successful

  5. Fuse Modeling for Reliability Study of Power Electronics Circuits

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad; Iannuzzo, Francesco; Blaabjerg, Frede

    2017-01-01

    This paper describes a comprehensive modeling approach on reliability of fuses used in power electronic circuits. When fuses are subjected to current pulses, cyclic temperature stress is introduced to the fuse element and will wear out the component. Furthermore, the fuse may be used in a large...

  6. High power electronics package: from modeling to implementation

    NARCIS (Netherlands)

    Yuan, C.A.; Kregting, R.; Ye, H.; Driel, W. van; Gielen, A.W.J.; Zhang, G.Q.

    2011-01-01

    Power electronics, such as high power RF components and high power LEDs, requires the combination of robust and reliable package structures, materials, and processes to guarantee their functional performance and lifetime. We started with the thermal and thermal-mechanical modeling of such component

  7. Dimers of Azurin as model systems for electron transfer

    NARCIS (Netherlands)

    Jongh, Thyra Estrid de

    2006-01-01

    This thesis describes the investigation of crosslinked complexes of the blue copper protein azurin by means of spectroscopic techniques such as Uv-Vis and NMR as well as by X-ray crystallography. These non-physiological dimers serve as model systems for interprotein electron transfer (ET) and allow

  8. Toward a generic model of trust for electronic commerce

    NARCIS (Netherlands)

    Tan, YH; Thoen, W

    2000-01-01

    The authors present a generic model of trust for electronic commerce consisting of two basic components, party trust and control trust, based on the concept that trust in a transaction with another party combines trust in the other parry and trust in the control mechanisms that ensure the successful

  9. Technical Communicator: A New Model for the Electronic Resources Librarian?

    Science.gov (United States)

    Hulseberg, Anna

    2016-01-01

    This article explores whether technical communicator is a useful model for electronic resources (ER) librarians. The fields of ER librarianship and technical communication (TC) originated and continue to develop in relation to evolving technologies. A review of the literature reveals four common themes for ER librarianship and TC. While the…

  10. Functional models of power electronic components for system studies

    Science.gov (United States)

    Tam, Kwa-Sur; Yang, Lifeng; Dravid, Narayan

    1991-01-01

    A novel approach to model power electronic circuits has been developed to facilitate simulation studies of system-level issues. The underlying concept for this approach is to develop an equivalent circuit, the functional model, that performs the same functions as the actual circuit but whose operation can be simulated by using larger time step size and the reduction in model complexity, the computation time required by a functional model is significantly shorter than that required by alternative approaches. The authors present this novel modeling approach and discuss the functional models of two major power electronic components, the DC/DC converter unit and the load converter, that are being considered by NASA for use in the Space Station Freedom electric power system. The validity of these models is established by comparing the simulation results with available experimental data and other simulation results obtained by using a more established modeling approach. The usefulness of this approach is demonstrated by incorporating these models into a power system model and simulating the system responses and interactions between components under various conditions.

  11. Optimization Model for Environmental Stress Screening of Electronic Components

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Environmental stress screening (ESS) is a technological process to reduce the costly early field failure ofelectronic components. This paper builds an optimization model for ESS of electronic components to obtain the optimalESS duration. The failure phenomena of ESS are modeled by mix ed distribution, and optimal ESS duration is definedby maximizing life-cycle cost savings under the condition of meeting reliability requirement.

  12. Anaerobic microbial transformation of halogenated aromatics and fate prediction using electron density modeling.

    Science.gov (United States)

    Cooper, Myriel; Wagner, Anke; Wondrousch, Dominik; Sonntag, Frank; Sonnabend, Andrei; Brehm, Martin; Schüürmann, Gerrit; Adrian, Lorenz

    2015-05-19

    Halogenated homo- and heterocyclic aromatics including disinfectants, pesticides and pharmaceuticals raise concern as persistent and toxic contaminants with often unknown fate. Remediation strategies and natural attenuation in anaerobic environments often build on microbial reductive dehalogenation. Here we describe the transformation of halogenated anilines, benzonitriles, phenols, methoxylated, or hydroxylated benzoic acids, pyridines, thiophenes, furoic acids, and benzenes by Dehalococcoides mccartyi strain CBDB1 and environmental fate modeling of the dehalogenation pathways. The compounds were chosen based on structural considerations to investigate the influence of functional groups present in a multitude of commercially used halogenated aromatics. Experimentally obtained growth yields were 0.1 to 5 × 10(14) cells mol(-1) of halogen released (corresponding to 0.3-15.3 g protein mol(-1) halogen), and specific enzyme activities ranged from 4.5 to 87.4 nkat mg(-1) protein. Chlorinated electron-poor pyridines were not dechlorinated in contrast to electron-rich thiophenes. Three different partial charge models demonstrated that the regioselective removal of halogens is governed by the least negative partial charge of the halogen. Microbial reaction pathways combined with computational chemistry and pertinent literature findings on Co(I) chemistry suggest that halide expulsion during reductive dehalogenation is initiated through single electron transfer from B12Co(I) to the apical halogen site.

  13. A new parametrizable model of molecular electronic structure

    CERN Document Server

    Laikov, Dimitri N

    2011-01-01

    A new electronic structure model is developed in which the ground state energy of a molecular system is given by a Hartree-Fock-like expression with parametrized one- and two-electron integrals over an extended (minimal + polarization) set of orthogonalized atom-centered basis functions, the variational equations being solved formally within the minimal basis but the effect of polarization functions being included in the spirit of second-order perturbation theory. It is designed to yield good dipole polarizabilities and improved intermolecular potentials with dispersion terms. The molecular integrals include up to three-center one-electron and two-center two-electron terms, all in simple analytical forms. A method to extract the effective one-electron Hamiltonian of nonlocal-exchange Kohn-Sham theory from the coupled-cluster one-electron density matrix is designed and used to get its matrix representation in a molecule-intrinsic minimal basis as an input to the paramtrization procedure -- making a direct link...

  14. ADMET Evaluation in Drug Discovery. Part 17: Development of Quantitative and Qualitative Prediction Models for Chemical-Induced Respiratory Toxicity.

    Science.gov (United States)

    Lei, Tailong; Chen, Fu; Liu, Hui; Sun, Huiyong; Kang, Yu; Li, Dan; Li, Youyong; Hou, Tingjun

    2017-07-03

    As a dangerous end point, respiratory toxicity can cause serious adverse health effects and even death. Meanwhile, it is a common and traditional issue in occupational and environmental protection. Pharmaceutical and chemical industries have a strong urge to develop precise and convenient computational tools to evaluate the respiratory toxicity of compounds as early as possible. Most of the reported theoretical models were developed based on the respiratory toxicity data sets with one single symptom, such as respiratory sensitization, and therefore these models may not afford reliable predictions for toxic compounds with other respiratory symptoms, such as pneumonia or rhinitis. Here, based on a diverse data set of mouse intraperitoneal respiratory toxicity characterized by multiple symptoms, a number of quantitative and qualitative predictions models with high reliability were developed by machine learning approaches. First, a four-tier dimension reduction strategy was employed to find an optimal set of 20 molecular descriptors for model building. Then, six machine learning approaches were used to develop the prediction models, including relevance vector machine (RVM), support vector machine (SVM), regularized random forest (RRF), extreme gradient boosting (XGBoost), naïve Bayes (NB), and linear discriminant analysis (LDA). Among all of the models, the SVM regression model shows the most accurate quantitative predictions for the test set (q(2)ext = 0.707), and the XGBoost classification model achieves the most accurate qualitative predictions for the test set (MCC of 0.644, AUC of 0.893, and global accuracy of 82.62%). The application domains were analyzed, and all of the tested compounds fall within the application domain coverage. We also examined the structural features of the compounds and important fragments with large prediction errors. In conclusion, the SVM regression model and the XGBoost classification model can be employed as accurate prediction tools

  15. Band electron spectrum and thermodynamic properties of the pseudospin-electron model with tunneling splitting of levels

    Directory of Open Access Journals (Sweden)

    O.Ya.Farenyuk

    2006-01-01

    Full Text Available The pseudospin-electron model with tunneling splitting of levels is considered. Generalization of dynamic mean-field method for systems with correlated hopping was applied to the investigation of the model. Electron spectra, electron concentrations, average values of pseudospins and grand canonical potential were calculated within the alloy-analogy approximation. Electron spectrum and dependencies of the electron concentrations on chemical potential were obtained. It was shown that in the alloy-analogy approximation, the model possesses the first order phase transition to ferromagnetic state with the change of chemical potential and the second order phase transition with the change of temperature.

  16. Genetic and chemical modifiers of a CUG toxicity model in Drosophila.

    Directory of Open Access Journals (Sweden)

    Amparo Garcia-Lopez

    Full Text Available Non-coding CUG repeat expansions interfere with the activity of human Muscleblind-like (MBNL proteins contributing to myotonic dystrophy 1 (DM1. To understand this toxic RNA gain-of-function mechanism we developed a Drosophila model expressing 60 pure and 480 interrupted CUG repeats in the context of a non-translatable RNA. These flies reproduced aspects of the DM1 pathology, most notably nuclear accumulation of CUG transcripts, muscle degeneration, splicing misregulation, and diminished Muscleblind function in vivo. Reduced Muscleblind activity was evident from the sensitivity of CUG-induced phenotypes to a decrease in muscleblind genetic dosage and rescue by MBNL1 expression, and further supported by the co-localization of Muscleblind and CUG repeat RNA in ribonuclear foci. Targeted expression of CUG repeats to the developing eye and brain mushroom bodies was toxic leading to rough eyes and semilethality, respectively. These phenotypes were utilized to identify genetic and chemical modifiers of the CUG-induced toxicity. 15 genetic modifiers of the rough eye phenotype were isolated. These genes identify putative cellular processes unknown to be altered by CUG repeat RNA, and they include mRNA export factor Aly, apoptosis inhibitor Thread, chromatin remodelling factor Nurf-38, and extracellular matrix structural component Viking. Ten chemical compounds suppressed the semilethal phenotype. These compounds significantly improved viability of CUG expressing flies and included non-steroidal anti-inflammatory agents (ketoprofen, muscarinic, cholinergic and histamine receptor inhibitors (orphenadrine, and drugs that can affect sodium and calcium metabolism such as clenbuterol and spironolactone. These findings provide new insights into the DM1 phenotype, and suggest novel candidates for DM1 treatments.

  17. Evaluation of toxic effects of several carboxylic acids on bacterial growth by toxicodynamic modelling

    Directory of Open Access Journals (Sweden)

    Vázquez José

    2011-11-01

    Full Text Available Abstract Background Effects of organic acids on microbial fermentation are commonly tested in investigations about metabolic behaviour of bacteria. However, they typically provide only descriptive information without modelling the influence of acid concentrations on bacterial kinetics. Results We developed and applied a mathematical model (secondary model to capture the toxicological effects of those chemicals on kinetic parameters that define the growth of bacteria in batch cultures. Thus, dose-response kinetics were performed with different bacteria (Leuconostoc mesenteroides, Carnobacterium pisicola, Escherichia coli, Bacillus subtilis and Listonella anguillarum exposed at increasing concentrations of individual carboxylic acids (formic, acetic, propionic, butyric and lactic. In all bioassays the acids affected the maximum bacterial load (Xm and the maximum growth rate (vm but only in specific cases the lag phase (λ was modified. Significance of the parameters was always high and in all fermentations the toxicodynamic equation was statistically consistent and had good predictability. The differences between D and L-lactic acid effects were significant for the growth of E. coli, L. mesenteroides and C. piscicola. In addition, a global parameter (EC50,τ was used to compare toxic effects and provided a realistic characterization of antimicrobial agents using a single value. Conclusions The effect of several organic acids on the growth of different bacteria was accurately studied and perfectly characterized by a bivariate equation which combines the basis of dose-response theory with microbial growth kinetics (secondary model. The toxicity of carboxylic acids was lower with the increase of the molecular weight of these chemicals.

  18. Transformer Model in Wide Frequency Bandwidth for Power Electronics Systems

    Directory of Open Access Journals (Sweden)

    Carlos Gonzalez-Garcia

    2013-01-01

    Full Text Available The development of the smart grids leads to new challenges on the power electronics equipment and power transformers. The use of power electronic transformer presents several advantages, but new problems related with the application of high frequency voltage and current components come across. Thus, an accurate knowledge of the transformer behavior in a wide frequency range is mandatory. A novel modeling procedure to relate the transformer physical behavior and its frequency response by means of electrical parameters is presented. Its usability is demonstrated by an example where a power transformer is used as filter and voltage reducer in an AC-DC-AC converter.

  19. Hopping electron model with geometrical frustration: kinetic Monte Carlo simulations

    Science.gov (United States)

    Terao, Takamichi

    2016-09-01

    The hopping electron model on the Kagome lattice was investigated by kinetic Monte Carlo simulations, and the non-equilibrium nature of the system was studied. We have numerically confirmed that aging phenomena are present in the autocorrelation function C ({t,tW )} of the electron system on the Kagome lattice, which is a geometrically frustrated lattice without any disorder. The waiting-time distributions p(τ ) of hopping electrons of the system on Kagome lattice has been also studied. It is confirmed that the profile of p (τ ) obtained at lower temperatures obeys the power-law behavior, which is a characteristic feature of continuous time random walk of electrons. These features were also compared with the characteristics of the Coulomb glass model, used as a model of disordered thin films and doped semiconductors. This work represents an advance in the understanding of the dynamics of geometrically frustrated systems and will serve as a basis for further studies of these physical systems.

  20. What correlation does the electron structure of environmental hormones have with manifestation of their toxicity and biological activity. Application of the hardness conception to biology; Kankyo horumon no denshi kozo wa sono dokusei ya seibutsu kassei no hatsugen ni donoyona sokansei wo motsunode aroka. Hardness gainen no seibutsugaku eno oyo

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, S.; Tanaka, A. [Showa College of Pharmaceutical Sciences, Tokyo (Japan); Sameshima, K. [Fujitsu Ltd., Tokyo (Japan)

    1999-01-01

    This paper indicates that the relationship between toxicity and biological activity of environmental hormones such as dioxin and their chemical structures may be predicted by using parameters (physical quantity) derived from the chemical hardness conception. According to this conception, softness and hardness of molecules are important in addition to electron receptivity and donation properties of molecules. Soft compounds facilitate electrons to migrate. Chlorine displacement of dioxin skeleton to 2nd, 3rd, 7th and 8th orders softens the molecules and displacement to 1st, 4th, 6th and 9th orders hardens them. The toxicity and biological activity of the environmental hormones cannot be explained only with the fit model of key-keyhole with the counterpart they act on (receptor). The softer the chemical hardness, the greater the toxicity and biological activity. Development has been made on an absolute hardness versus absolute electrical negative activity diagram to learn electron structure of molecules. This diagram indicates that the toxicity of dioxin depends more strongly on the chemical hardness than the strength of the electrical negativity, and the softer the hardness, the stronger the toxicity. (NEDO)

  1. Analog electronic model of the lobster pyloric central pattern generator

    Energy Technology Data Exchange (ETDEWEB)

    Volkovskii, A [Institute for Nonlinear Science, University of California San Diego, CA (United States); Brugioni, S [Institute for Nonlinear Science, University of California San Diego, CA (United States); Istituto Nazionale di Ottica Applicata Largo E. Fermi 6 50125 Florence (Italy); Levi, R [Institute for Nonlinear Science, University of California San Diego, CA (United States); Rabinovich, M [Institute for Nonlinear Science, University of California San Diego, CA (United States); Selverston, A [Institute for Nonlinear Science, University of California San Diego, CA (United States); Abarbane, H D I [Institute for Nonlinear Science, University of California San Diego, CA (United States)

    2005-01-01

    An electronic circuit intended to simulate the nonlinear dynamics of a simplified 3-cell model of the pyloric central pattern generator in California spiny lobster stomato gastric ganglion is presented. The model employs the synaptic phase locked loop (SPLL) concept where the frequency of oscillations of a postsynaptic cell is mainly controlled by the synaptic current which depends on the phase shift between the oscillations. The theoretical study showed that the system has a stable steady state with correct phase shifts between the oscillations and that this regime is stable when the frequency of the pacemaker cell is varied over a wide range. The main bifurcations in the system were studied analytically, in computer simulations, and in experiments with the electronic circuit. The experimental measurements are in good agreement with the expectations of the theoretical model.

  2. The Development Model Electronic Commerce of Regional Agriculture

    Science.gov (United States)

    Kang, Jun; Cai, Lecai; Li, Hongchan

    With the developing of the agricultural information, it is inevitable trend of the development of agricultural electronic commercial affairs. On the basis of existing study on the development application model of e-commerce, combined with the character of the agricultural information, compared with the developing model from the theory and reality, a new development model electronic commerce of regional agriculture base on the government is put up, and such key issues as problems of the security applications, payment mode, sharing mechanisms, and legal protection are analyzed, etc. The among coordination mechanism of the region is discussed on, it is significance for regulating the development of agricultural e-commerce and promoting the regional economical development.

  3. Daphnia and fish toxicity of (benzo)triazoles: validated QSAR models, and interspecies quantitative activity-activity modelling.

    Science.gov (United States)

    Cassani, Stefano; Kovarich, Simona; Papa, Ester; Roy, Partha Pratim; van der Wal, Leon; Gramatica, Paola

    2013-08-15

    Due to their chemical properties synthetic triazoles and benzo-triazoles ((B)TAZs) are mainly distributed to the water compartments in the environment, and because of their wide use the potential effects on aquatic organisms are cause of concern. Non testing approaches like those based on quantitative structure-activity relationships (QSARs) are valuable tools to maximize the information contained in existing experimental data and predict missing information while minimizing animal testing. In the present study, externally validated QSAR models for the prediction of acute (B)TAZs toxicity in Daphnia magna and Oncorhynchus mykiss have been developed according to the principles for the validation of QSARs and their acceptability for regulatory purposes, proposed by the Organization for Economic Co-operation and Development (OECD). These models are based on theoretical molecular descriptors, and are statistically robust, externally predictive and characterized by a verifiable structural applicability domain. They have been applied to predict acute toxicity for over 300 (B)TAZs without experimental data, many of which are in the pre-registration list of the REACH regulation. Additionally, a model based on quantitative activity-activity relationships (QAAR) has been developed, which allows for interspecies extrapolation from daphnids to fish. The importance of QSAR/QAAR, especially when dealing with specific chemical classes like (B)TAZs, for screening and prioritization of pollutants under REACH, has been highlighted. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. The Toxic Effects of Pathogenic Ataxin-3 Variants in a Yeast Cellular Model

    Science.gov (United States)

    Bonanomi, Marcella; Visentin, Cristina; Invernizzi, Gaetano; Tortora, Paolo; Regonesi, Maria Elena

    2015-01-01

    Ataxin-3 (AT3) is a deubiquitinating enzyme that triggers an inherited neurodegenerative disorder, spinocerebellar ataxia type 3, when its polyglutamine (polyQ) stretch close to the C-terminus exceeds a critical length. AT3 variants carrying the expanded polyQ are prone to associate with each other into amyloid toxic aggregates, which are responsible for neuronal death with ensuing neurodegeneration. We employed Saccharomyces cerevisiae as a eukaryotic cellular model to better clarify the mechanism by which AT3 triggers the disease. We expressed three variants: one normal (Q26), one expanded (Q85) and one truncated for a region lying from the beginning of its polyQ stretch to the end of the protein (291Δ). We found that the expression of the expanded form caused reduction in viability, accumulation of reactive oxygen species, imbalance of the antioxidant defense system and loss in cell membrane integrity, leading to necrotic death. The truncated variant also exerted a qualitatively similar, albeit milder, effect on cell growth and cytotoxicity, which points to the involvement of also non-polyQ regions in cytotoxicity. Guanidine hydrochloride, a well-known inhibitor of the chaperone Hsp104, almost completely restored wild-type survival rate of both 291Δ- and Q85-expressing strains. This suggests that AT3 aggregation and toxicity is mediated by prion forms of yeast proteins, as this chaperone plays a key role in their propagation. PMID:26052945

  5. The Toxic Effects of Pathogenic Ataxin-3 Variants in a Yeast Cellular Model.

    Directory of Open Access Journals (Sweden)

    Marcella Bonanomi

    Full Text Available Ataxin-3 (AT3 is a deubiquitinating enzyme that triggers an inherited neurodegenerative disorder, spinocerebellar ataxia type 3, when its polyglutamine (polyQ stretch close to the C-terminus exceeds a critical length. AT3 variants carrying the expanded polyQ are prone to associate with each other into amyloid toxic aggregates, which are responsible for neuronal death with ensuing neurodegeneration. We employed Saccharomyces cerevisiae as a eukaryotic cellular model to better clarify the mechanism by which AT3 triggers the disease. We expressed three variants: one normal (Q26, one expanded (Q85 and one truncated for a region lying from the beginning of its polyQ stretch to the end of the protein (291Δ. We found that the expression of the expanded form caused reduction in viability, accumulation of reactive oxygen species, imbalance of the antioxidant defense system and loss in cell membrane integrity, leading to necrotic death. The truncated variant also exerted a qualitatively similar, albeit milder, effect on cell growth and cytotoxicity, which points to the involvement of also non-polyQ regions in cytotoxicity. Guanidine hydrochloride, a well-known inhibitor of the chaperone Hsp104, almost completely restored wild-type survival rate of both 291Δ- and Q85-expressing strains. This suggests that AT3 aggregation and toxicity is mediated by prion forms of yeast proteins, as this chaperone plays a key role in their propagation.

  6. Otophylloside B Protects Against Aβ Toxicity in Caenorhabditis elegans Models of Alzheimer's Disease.

    Science.gov (United States)

    Yang, Jie; Huang, Xiao-Bing; Wan, Qin-Li; Ding, Ai-Jun; Yang, Zhong-Lin; Qiu, Ming-Hua; Sun, Hua-Ying; Qi, Shu-Hua; Luo, Huai-Rong

    2017-02-13

    Alzheimer's disease (AD) is a major public health concern worldwide and the few drugs currently available only treat the symptoms. Hence, there is a strong need to find more effective anti-AD agents. Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy, and otophylloside B (Ot B), isolated from C. otophyllum, is the essential active component. Having previously identified anti-aging effects of Ot B, we evaluated Ot B for AD prevention in C. elegans models of AD and found that Ot B extended lifespan, increased heat stress-resistance, delayed body paralysis, and increased the chemotaxis response. Collectively, these results indicated that Ot B protects against Aβ toxicity. Further mechanistic studies revealed that Ot B decreased Aβ deposition by decreasing the expression of Aβ at the mRNA level. Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor (HSF) by upregulating the expression of hsf-1 and its target genes, hsp-12.6, hsp-16.2 and hsp-70. Ot B also increased the expression of sod-3 by partially activating DAF-16, while SKN-1 was not essential in Ot B-mediated protection against Aβ toxicity.

  7. Hepatoprotective Effect of ψ-Glutathione in a Murine Model of Acetaminophen-Induced Liver Toxicity.

    Science.gov (United States)

    More, Swati S; Nugent, Jaime; Vartak, Ashish P; Nye, Steffan M; Vince, Robert

    2017-03-20

    Ψ-Glutathione (ψ-GSH) is an orally bioavailable and metabolism-resistant glutathione analogue that has been shown previously to substitute glutathione in most of its biochemical roles. Described here in its entirety is the preclinical evaluation of ψ-GSH as a rescue agent for acetaminophen (APAP) overdose: an event where time is of essence. By employing a murine model, four scenarios commonly encountered in emergency medicine are reconstructed. ψ-GSH is juxtaposed against N-acetylcysteine (NAC), the sole clinically available drug, in each of the scenarios. While both agents appear to be equally efficacious when timely administered, ψ-GSH partly retains its efficacy even in the face of substantial delay in administration. Thus, implied is the ability of ψ-GSH to intercept secondary toxicology following APAP insult. Oral availability and complete lack of toxicity as evaluated by liver function tests and survival analysis underscored ψ-GSH as a safer and more efficacious alternative to NAC. Finally, the pharmacodynamic mimicry of GSH by ψ-GSH is illustrated through the isolation and chemical characterization of an entity that can arise only through direct encounter of ψ-GSH with N-acetyl-p-benzoquinoneimine, the primary toxic metabolite of APAP.

  8. Toxicity and metabolism of layered double hydroxide intercalated with levodopa in a Parkinson's disease model.

    Science.gov (United States)

    Kura, Aminu Umar; Ain, Nooraini Mohd; Hussein, Mohd Zobir; Fakurazi, Sharida; Hussein-Al-Ali, Samer Hasan

    2014-04-09

    Layered hydroxide nanoparticles are generally biocompatible, and less toxic than most inorganic nanoparticles, making them an acceptable alternative drug delivery system. Due to growing concern over animal welfare and the expense of in vivo experiments both the public and the government are interested to find alternatives to animal testing. The toxicity potential of zinc aluminum layered hydroxide (ZAL) nanocomposite containing anti-Parkinsonian agent may be determined using a PC 12 cell model. ZAL nanocomposite demonstrated a decreased cytotoxic effect when compared to levodopa on PC12 cells with more than 80% cell viability at 100 µg/mL compared to less than 20% cell viability in a direct levodopa exposure. Neither levodopa-loaded nanocomposite nor the un-intercalated nanocomposite disturbed the cytoskeletal structure of the neurogenic cells at their IC50 concentration. Levodopa metabolite (HVA) released from the nanocomposite demonstrated the slow sustained and controlled release character of layered hydroxide nanoparticles unlike the burst uptake and release system shown with pure levodopa treatment.

  9. Toxicity mechanisms of the food contaminant citrinin: application of a quantitative yeast model.

    Science.gov (United States)

    Pascual-Ahuir, Amparo; Vanacloig-Pedros, Elena; Proft, Markus

    2014-05-22

    Mycotoxins are important food contaminants and a serious threat for human nutrition. However, in many cases the mechanisms of toxicity for this diverse group of metabolites are poorly understood. Here we apply live cell gene expression reporters in yeast as a quantitative model to unravel the cellular defense mechanisms in response to the mycotoxin citrinin. We find that citrinin triggers a fast and dose dependent activation of stress responsive promoters such as GRE2 or SOD2. More specifically, oxidative stress responsive pathways via the transcription factors Yap1 and Skn7 are critically implied in the response to citrinin. Additionally, genes in various multidrug resistance transport systems are functionally involved in the resistance to citrinin. Our study identifies the antioxidant defense as a major physiological response in the case of citrinin. In general, our results show that the use of live cell gene expression reporters in yeast are a powerful tool to identify toxicity targets and detoxification mechanisms of a broad range of food contaminants relevant for human nutrition.

  10. Toxicity Mechanisms of the Food Contaminant Citrinin: Application of a Quantitative Yeast Model

    Directory of Open Access Journals (Sweden)

    Amparo Pascual-Ahuir

    2014-05-01

    Full Text Available Mycotoxins are important food contaminants and a serious threat for human nutrition. However, in many cases the mechanisms of toxicity for this diverse group of metabolites are poorly understood. Here we apply live cell gene expression reporters in yeast as a quantitative model to unravel the cellular defense mechanisms in response to the mycotoxin citrinin. We find that citrinin triggers a fast and dose dependent activation of stress responsive promoters such as GRE2 or SOD2. More specifically, oxidative stress responsive pathways via the transcription factors Yap1 and Skn7 are critically implied in the response to citrinin. Additionally, genes in various multidrug resistance transport systems are functionally involved in the resistance to citrinin. Our study identifies the antioxidant defense as a major physiological response in the case of citrinin. In general, our results show that the use of live cell gene expression reporters in yeast are a powerful tool to identify toxicity targets and detoxification mechanisms of a broad range of food contaminants relevant for human nutrition.

  11. Standardizing acute toxicity data for use in ecotoxicology models: influence of test type, life stage, and concentration reporting.

    Science.gov (United States)

    Raimondo, Sandy; Vivian, Deborah N; Barron, Mace G

    2009-10-01

    Ecotoxicological models generally have large data requirements and are frequently based on existing information from diverse sources. Standardizing data for toxicological models may be necessary to reduce extraneous variation and to ensure models reflect intrinsic relationships. However, the extent to which data standardization is necessary remains unclear, particularly when data transformations are used in model development. An extensive acute toxicity database was compiled for aquatic species to comprehensively assess the variation associated with acute toxicity test type (e.g., flow-through, static), reporting concentrations as nominal or measured, and organism life stage. Three approaches were used to assess the influence of these factors on log-transformed acute toxicity: toxicity ratios, log-linear models of factor groups, and comparison of interspecies correlation estimation (ICE) models developed using either standardized test types or reported concentration type. In general, median ratios were generally less than 2.0, the slopes of log-linear models were approximately one for well-represented comparisons, and ICE models developed using data from standardized test types or reported concentrations did not differ substantially. These results indicate that standardizing test data by acute test type, reported concentration type, or life stage may not be critical for developing ecotoxicological models using large datasets of log-transformed values.

  12. Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments.

    Science.gov (United States)

    Astashkina, Anna; Grainger, David W

    2014-04-01

    Drug failure due to toxicity indicators remains among the primary reasons for staggering drug attrition rates during clinical studies and post-marketing surveillance. Broader validation and use of next-generation 3-D improved cell culture models are expected to improve predictive power and effectiveness of drug toxicological predictions. However, after decades of promising research significant gaps remain in our collective ability to extract quality human toxicity information from in vitro data using 3-D cell and tissue models. Issues, challenges and future directions for the field to improve drug assay predictive power and reliability of 3-D models are reviewed. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Modeling power electronics and interfacing energy conversion systems

    CERN Document Server

    Simões, Marcelo Godoy

    2017-01-01

    Discusses the application of mathematical and engineering tools for modeling, simulation and control oriented for energy systems, power electronics and renewable energy. This book builds on the background knowledge of electrical circuits, control of dc/dc converters and inverters, energy conversion and power electronics. The book shows readers how to apply computational methods for multi-domain simulation of energy systems and power electronics engineering problems. Each chapter has a brief introduction on the theoretical background, a description of the problems to be solved, and objectives to be achieved. Block diagrams, electrical circuits, mathematical analysis or computer code are covered. Each chapter concludes with discussions on what should be learned, suggestions for further studies and even some experimental work.

  14. Improving CASINO performance for models with large number of electrons

    Energy Technology Data Exchange (ETDEWEB)

    Anton, L; Alfe, D; Hood, R Q; Tanqueray, D

    2009-05-13

    Quantum Monte Carlo calculations have at their core algorithms based on statistical ensembles of multidimensional random walkers which are straightforward to use on parallel computers. Nevertheless some computations have reached the limit of the memory resources for models with more than 1000 electrons because of the need to store a large amount of electronic orbitals related data. Besides that, for systems with large number of electrons, it is interesting to study if the evolution of one configuration of random walkers can be done faster in parallel. We present a comparative study of two ways to solve these problems: (1) distributed orbital data done with MPI or Unix inter-process communication tools, (2) second level parallelism for configuration computation.

  15. Human intake fraction of toxic pollutants: a model comparison between caltox and uses-lca

    Energy Technology Data Exchange (ETDEWEB)

    Huijbregts, Mark A.J.; Geelen, Loes M.J.; Hertwich, Edgar G.; McKone, Thomas E.; van de Meent, Dik

    2004-01-06

    In Life Cycle Assessment and Comparative Risk Assessment potential human exposure to toxic pollutants can be expressed as the human intake fraction (iF), representing the fraction of the quantity emitted that enters the human population. To assess model uncertainty in the human intake fraction, ingestion and inhalation iFs of 367 substances emitted to air and freshwater were calculated with two commonly applied multi-media fate and exposure models, CalTOX and USES-LCA. Comparison of the model outcomes reveal that uncertainty in the ingestion iFs was up to a factor of 70. The uncertainty in the inhalation iFs was up to a factor of 865,000. The comparison showed that relatively few model differences account for the uncertainties found. An optimal model structure in the calculation of human intake fractions can be achieved by including (1) rain and no-rain scenarios, (2) a continental sea water compartment, (3) drinking water purification, (4) pH-correction of chemical properties, and (5) aerosol-associated deposition on plants. Finally, vertical stratification of the soil compartment combined with a chemical-dependent soil depth may be considered in future intake fraction calculations.

  16. Modeling marrow damage from response data: Morphallaxis from radiation biology to benzene toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T.D.; Morris, M.D.; Hasan, J.S.

    1995-12-01

    Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between {approximately} 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is ``critical`` to hematopoietic recovery does not resemble stem-like cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD{sub 50} and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in the fitting of model coefficients.

  17. Application of transmission electron tomography for modeling the renal corpuscle.

    Science.gov (United States)

    Cheng, Delfine; Shen, Sylvie; Chen, Xin-Ming; Pollock, Carol; Braet, Filip

    2013-11-01

    Structural alteration to the microanatomical organization of the glomerular filtration barrier results in proteinuria. Conventional transmission electron microscopy is an important diagnostic tool to assess the degree of ultrastructural damage of the corpusclar filtration unit. However, this approach lacks the ability to collect accurate stereological insights in a relative large tissue volume. Transmission electron tomography offers the ability to gather three-dimensional information with relative ease. Therefore, this contribution aims to highlight what electron tomography can bring to the pathologist in this challenging area of diagnostic practice. Kidney tissue was prepared for routine ultrastructural transmission electron microscopy investigation. Three-dimensional data stacks were automatically acquired by tilting semi-thin sections of 270 nm in an angular range of typically -60° to +60° with 1° increment. Subsequently, models of the filtration unit were produced by computer-assisted tracking of structures of interest. This short report illustrates the capability that transmission electron tomography can offer in the fine structure-function assessment of the porous fenestrated glomerular capillary endothelium, the underlying basement membrane and the podocyte filtration slits. Furthermore, this approach allows the generation of morphometric data about size, shape and volume alterations of the kidney's filtration barrier at the nanoscale.

  18. Power electronic converters modeling and control with case studies

    CERN Document Server

    Bacha, Seddik; Bratcu, Antoneta Iuliana

    2014-01-01

    Modern power electronic converters are involved in a very broad spectrum of applications: switched-mode power supplies, electrical-machine-motion-control, active power filters, distributed power generation, flexible AC transmission systems, renewable energy conversion systems and vehicular technology, among them. Power Electronics Converters Modeling and Control teaches the reader how to analyze and model the behavior of converters and so to improve their design and control. Dealing with a set of confirmed algorithms specifically developed for use with power converters, this text is in two parts: models and control methods. The first is a detailed exposition of the most usual power converter models: ·        switched and averaged models; ·        small/large-signal models; and ·        time/frequency models. The second focuses on three groups of control methods: ·        linear control approaches normally associated with power converters; ·        resonant controllers b...

  19. MATHEMATICAL MODELING OF EXTRACELLULAR ELECTRON TRANSFER IN BIOFILMS

    Energy Technology Data Exchange (ETDEWEB)

    Renslow, Ryan S.; Babauta, Jerome T.; Kuprat, Andrew P.; Schenk, Jim; Ivory, Cornelius; Fredrickson, Jim K.; Beyenal, Haluk

    2015-09-12

    Electrochemically active biofilms have a unique form of respiration in which they utilize solid external materials as terminal electron acceptors for their metabolism. Currently, two primary mechanisms have been identified for long-range extracellular electron transfer (EET): a diffusion- and a conduction-based mechanism. Evidence in the literature suggests that some biofilms, particularly Shewanella oneidensis, produce the requisite components for both mechanisms. In this study, a generic model is presented that incorporates the diffusion- and the conduction-based mechanisms and allows electrochemically active biofilms to utilize both simultaneously. The model was applied to S. oneidensis and Geobacter sulfurreducens biofilms using experimentally generated data found in the literature. Our simulation results show that 1) biofilms having both mechanisms available, especially if they can interact, may have a metabolic advantage over biofilms that can use only a single mechanism; 2) the thickness of G. sulfurreducens biofilms is likely not limited by conductivity; 3) accurate intrabiofilm diffusion coefficient values are critical for current generation predictions; and 4) the local biofilm potential and redox potential are two distinct parameters and cannot be assumed to have identical values. Finally, we determined that simulated cyclic and squarewave voltammetry based on our model are currently not capable of determining the specific percentages of extracellular electron transfer mechanisms in a biofilm. The developed model will be a critical tool for designing experiments to explain EET mechanisms.

  20. Modeling biofilms with dual extracellular electron transfer mechanisms

    Science.gov (United States)

    Renslow, Ryan; Babauta, Jerome; Kuprat, Andrew; Schenk, Jim; Ivory, Cornelius; Fredrickson, Jim; Beyenal, Haluk

    2013-01-01

    Electrochemically active biofilms have a unique form of respiration in which they utilize solid external materials as terminal electron acceptors for their metabolism. Currently, two primary mechanisms have been identified for long-range extracellular electron transfer (EET): a diffusion- and a conduction-based mechanism. Evidence in the literature suggests that some biofilms, particularly Shewanella oneidensis, produce the requisite components for both mechanisms. In this study, a generic model is presented that incorporates the diffusion- and the conduction-based mechanisms and allows electrochemically active biofilms to utilize both simultaneously. The model was applied to S. oneidensis and Geobacter sulfurreducens biofilms using experimentally generated data found in the literature. Our simulation results show that 1) biofilms having both mechanisms available, especially if they can interact, may have a metabolic advantage over biofilms that can use only a single mechanism; 2) the thickness of G. sulfurreducens biofilms is likely not limited by conductivity; 3) accurate intrabiofilm diffusion coefficient values are critical for current generation predictions; and 4) the local biofilm potential and redox potential are two distinct parameters and cannot be assumed to have identical values. Finally, we determined that simulated cyclic and squarewave voltammetry based on our model are currently not capable of determining the specific percentages of extracellular electron transfer mechanisms in a biofilm. The developed model will be a critical tool for designing experiments to explain EET mechanisms. PMID:24113651

  1. Preparation and analysis of active rat model of rheumatoid arthritis with features of TCM toxic heat-stasis painful obstruction

    Directory of Open Access Journals (Sweden)

    Yanan Wang

    2015-07-01

    Conclusion: The CIA model established in this study presents both active RA pathologic features and characteristics of the symptoms of toxic heat-stasis painful obstruction 12 weeks after successful establishment of an animal model. In addition, this study may be a valuable reference for development of animal studies with combined Eastern and Western medicines in dialectics and identification of diseases.

  2. Antiandrogen flutamide protects male mice from androgen-dependent toxicity in three models of spinal bulbar muscular atrophy.

    Science.gov (United States)

    Renier, Kayla J; Troxell-Smith, Sandra M; Johansen, Jamie A; Katsuno, Masahisa; Adachi, Hiroaki; Sobue, Gen; Chua, Jason P; Sun Kim, Hong; Lieberman, Andrew P; Breedlove, S Marc; Jordan, Cynthia L

    2014-07-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset, progressive neurodegenerative disease linked to a polyglutamine (polyQ) expansion in the androgen receptor (AR). Men affected by SBMA show marked muscle weakness and atrophy, typically emerging midlife. Given the androgen-dependent nature of this disease, one might expect AR antagonists to have therapeutic value for treating SBMA. However, current work from animal models suggests otherwise, raising questions about whether polyQ-expanded AR exerts androgen-dependent toxicity through mechanisms distinct from normal AR function. In this study, we asked whether the nonsteroidal AR antagonist flutamide, delivered via a time-release pellet, could reverse or prevent androgen-dependent AR toxicity in three different mouse models of SBMA: the AR97Q transgenic (Tg) model, a knock-in (KI) model, and a myogenic Tg model. We find that flutamide protects mice from androgen-dependent AR toxicity in all three SBMA models, preventing or reversing motor dysfunction in the Tg models and significantly extending the life span in KI males. Given that flutamide effectively protects against androgen-dependent disease in three different mouse models of SBMA, our data are proof of principle that AR antagonists have therapeutic potential for treating SBMA in humans and support the notion that toxicity caused by polyQ-expanded AR uses at least some of the same mechanisms as normal AR before diverging to produce disease and muscle atrophy.

  3. Modeling and multidimensional optimization of a tapered free electron laser

    Directory of Open Access Journals (Sweden)

    Y. Jiao

    2012-05-01

    Full Text Available Energy extraction efficiency of a free electron laser (FEL can be greatly increased using a tapered undulator and self-seeding. However, the extraction rate is limited by various effects that eventually lead to saturation of the peak intensity and power. To better understand these effects, we develop a model extending the Kroll-Morton-Rosenbluth, one-dimensional theory to include the physics of diffraction, optical guiding, and radially resolved particle trapping. The predictions of the model agree well with that of the GENESIS single-frequency numerical simulations. In particular, we discuss the evolution of the electron-radiation interaction along the tapered undulator and show that the decreasing of refractive guiding is the major cause of the efficiency reduction, particle detrapping, and then saturation of the radiation power. With this understanding, we develop a multidimensional optimization scheme based on GENESIS simulations to increase the energy extraction efficiency via an improved taper profile and variation in electron beam radius. We present optimization results for hard x-ray tapered FELs, and the dependence of the maximum extractable radiation power on various parameters of the initial electron beam, radiation field, and the undulator system. We also study the effect of the sideband growth in a tapered FEL. Such growth induces increased particle detrapping and thus decreased refractive guiding that together strongly limit the overall energy extraction efficiency.

  4. Comparative in vitro toxicity profile of electronic and tobacco cigarettes, smokeless tobacco and nicotine replacement therapy products: e-liquids, extracts and collected aerosols.

    Science.gov (United States)

    Misra, Manoj; Leverette, Robert D; Cooper, Bethany T; Bennett, Melanee B; Brown, Steven E

    2014-10-30

    The use of electronic cigarettes (e-cigs) continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT) products and a nicotine replacement therapy (NRT) product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.

  5. Comparative In Vitro Toxicity Profile of Electronic and Tobacco Cigarettes, Smokeless Tobacco and Nicotine Replacement Therapy Products: E-Liquids, Extracts and Collected Aerosols

    Directory of Open Access Journals (Sweden)

    Manoj Misra

    2014-10-01

    Full Text Available The use of electronic cigarettes (e-cigs continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT products and a nicotine replacement therapy (NRT product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.

  6. Predicting acute contact toxicity of pesticides in honeybees (Apis mellifera) through a k-nearest neighbor model.

    Science.gov (United States)

    Como, F; Carnesecchi, E; Volani, S; Dorne, J L; Richardson, J; Bassan, A; Pavan, M; Benfenati, E

    2017-01-01

    Ecological risk assessment of plant protection products (PPPs) requires an understanding of both the toxicity and the extent of exposure to assess risks for a range of taxa of ecological importance including target and non-target species. Non-target species such as honey bees (Apis mellifera), solitary bees and bumble bees are of utmost importance because of their vital ecological services as pollinators of wild plants and crops. To improve risk assessment of PPPs in bee species, computational models predicting the acute and chronic toxicity of a range of PPPs and contaminants can play a major role in providing structural and physico-chemical properties for the prioritisation of compounds of concern and future risk assessments. Over the last three decades, scientific advisory bodies and the research community have developed toxicological databases and quantitative structure-activity relationship (QSAR) models that are proving invaluable to predict toxicity using historical data and reduce animal testing. This paper describes the development and validation of a k-Nearest Neighbor (k-NN) model using in-house software for the prediction of acute contact toxicity of pesticides on honey bees. Acute contact toxicity data were collected from different sources for 256 pesticides, which were divided into training and test sets. The k-NN models were validated with good prediction, with an accuracy of 70% for all compounds and of 65% for highly toxic compounds, suggesting that they might reliably predict the toxicity of structurally diverse pesticides and could be used to screen and prioritise new pesticides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Predictive Modelling of Toxicity Resulting from Radiotherapy Treatments of Head and Neck Cancer

    CERN Document Server

    Dean, Jamie A; Harrington, Kevin J; Nutting, Christopher M; Gulliford, Sarah L

    2014-01-01

    In radiotherapy for head and neck cancer, the radiation dose delivered to the pharyngeal mucosa (mucosal lining of the throat) is thought to be a major contributing factor to dysphagia (swallowing dysfunction), the most commonly reported severe toxicity. There is a variation in the severity of dysphagia experienced by patients. Understanding the role of the dose distribution in dysphagia would allow improvements in the radiotherapy technique to be explored. The 3D dose distributions delivered to the pharyngeal mucosa of 249 patients treated as part of clinical trials were reconstructed. Pydicom was used to extract DICOM (digital imaging and communications in medicine) data (the standard file formats for medical imaging and radiotherapy data). NumPy and SciPy were used to manipulate the data to generate 3D maps of the dose distribution delivered to the pharyngeal mucosa and calculate metrics describing the dose distribution. Multivariate predictive modelling of severe dysphagia, including descriptions of the d...

  8. Zebrafish: A Model for the Study of Toxicants Affecting Muscle Development and Function

    Directory of Open Access Journals (Sweden)

    Magda Dubińska-Magiera

    2016-11-01

    Full Text Available The rapid progress in medicine, agriculture, and allied sciences has enabled the development of a large amount of potentially useful bioactive compounds, such as drugs and pesticides. However, there is another side of this phenomenon, which includes side effects and environmental pollution. To avoid or minimize the uncontrollable consequences of using the newly developed compounds, researchers seek a quick and effective means of their evaluation. In achieving this goal, the zebrafish (Danio rerio has proven to be a highly useful tool, mostly because of its fast growth and development, as well as the ability to absorb the molecules diluted in water through its skin and gills. In this review, we focus on the reports concerning the application of zebrafish as a model for assessing the impact of toxicants on skeletal muscles, which share many structural and functional similarities among vertebrates, including zebrafish and humans.

  9. Zebrafish: A Model for the Study of Toxicants Affecting Muscle Development and Function

    Science.gov (United States)

    Dubińska-Magiera, Magda; Daczewska, Małgorzata; Lewicka, Anna; Migocka-Patrzałek, Marta; Niedbalska-Tarnowska, Joanna; Jagla, Krzysztof

    2016-01-01

    The rapid progress in medicine, agriculture, and allied sciences has enabled the development of a large amount of potentially useful bioactive compounds, such as drugs and pesticides. However, there is another side of this phenomenon, which includes side effects and environmental pollution. To avoid or minimize the uncontrollable consequences of using the newly developed compounds, researchers seek a quick and effective means of their evaluation. In achieving this goal, the zebrafish (Danio rerio) has proven to be a highly useful tool, mostly because of its fast growth and development, as well as the ability to absorb the molecules diluted in water through its skin and gills. In this review, we focus on the reports concerning the application of zebrafish as a model for assessing the impact of toxicants on skeletal muscles, which share many structural and functional similarities among vertebrates, including zebrafish and humans. PMID:27869769

  10. Improved building up a model of toxicity towards Pimephales promelas by the Monte Carlo method.

    Science.gov (United States)

    Toropova, Alla P; Toropov, Andrey A; Raskova, Maria; Raska, Ivan

    2016-12-01

    By optimization of so-called correlation weights of attributes of simplified molecular input-line entry system (SMILES) quantitative structure - activity relationships (QSAR) for toxicity towards Pimephales promelas are established. A new SMILES attribute has been utilized in this work. This attribute is a molecular descriptor, which reflects (i) presence of different kinds of bonds (double, triple, and stereo chemical bonds); (ii) presence of nitrogen, oxygen, sulphur, and phosphorus atoms; and (iii) presence of fluorine, chlorine, bromine, and iodine atoms. The statistical characteristics of the best model are the following: n=226, r(2)=0.7630, RMSE=0.654 (training set); n=114, r(2)=0.7024, RMSE=0.766 (calibration set); n=226, r(2)=0.6292, RMSE=0.870 (validation set). A new criterion to select a preferable split into the training and validation sets are suggested and discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. QSAR modelling of the toxicity to Tetrahymena pyriformis by balance of correlations.

    Science.gov (United States)

    Toropov, A A; Toropova, A P; Benfenati, E; Manganaro, A

    2010-11-01

    Balance of correlations is an approach to build up quantitative structure-property/activity relationships (QSPR/QSAR). This approach is based on a split into the subtraining, calibration and test sets instead of classic split into training and test sets. The function of the calibration set is the preliminary check up of the model. In other words, the calibration set is like a preliminary test set. Computational experiments (with the Monte Carlo method) have shown that the statistical characteristics of the prediction for the toxicity to Tetrahymena pyriformis (the 50% growth inhibition concentration, IGC(50)) based on the balance of correlations are better than the statistical characteristics of the prediction based on the classic scheme.

  12. Quantitative model studies for interfaces in organic electronic devices

    Science.gov (United States)

    Gottfried, J. Michael

    2016-11-01

    In organic light-emitting diodes and similar devices, organic semiconductors are typically contacted by metal electrodes. Because the resulting metal/organic interfaces have a large impact on the performance of these devices, their quantitative understanding is indispensable for the further rational development of organic electronics. A study by Kröger et al (2016 New J. Phys. 18 113022) of an important single-crystal based model interface provides detailed insight into its geometric and electronic structure and delivers valuable benchmark data for computational studies. In view of the differences between typical surface-science model systems and real devices, a ‘materials gap’ is identified that needs to be addressed by future research to make the knowledge obtained from fundamental studies even more beneficial for real-world applications.

  13. Access Control Model for Sharing Composite Electronic Health Records

    Science.gov (United States)

    Jin, Jing; Ahn, Gail-Joon; Covington, Michael J.; Zhang, Xinwen

    The adoption of electronically formatted medical records, so called Electronic Health Records (EHRs), has become extremely important in healthcare systems to enable the exchange of medical information among stakeholders. An EHR generally consists of data with different types and sensitivity degrees which must be selectively shared based on the need-to-know principle. Security mechanisms are required to guarantee that only authorized users have access to specific portions of such critical record for legitimate purposes. In this paper, we propose a novel approach for modelling access control scheme for composite EHRs. Our model formulates the semantics and structural composition of an EHR document, from which we introduce a notion of authorized zones of the composite EHR at different granularity levels, taking into consideration of several important criteria such as data types, intended purposes and information sensitivities.

  14. Modeling Crabbing Dynamics in an Electron-Ion Collider

    Energy Technology Data Exchange (ETDEWEB)

    Castilla, Alejandro [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Old Dominion Univ., Norfolk, VA (United States); Univ. de Guanajuato (DCI-UG), Leon (Mexico); Morozov, Vasiliy S. [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Satogata, Todd J. [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Old Dominion Univ., Norfolk, VA (United States); Delayen, Jean R. [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Old Dominion Univ., Norfolk, VA (United States)

    2015-09-01

    A local crabbing scheme requires π/2 (mod π) horizontal betatron phase advances from an interaction point (IP) to the crab cavities on each side of it. However, realistic phase advances generated by sets of quadrupoles, or Final Focusing Blocks (FFB), between the crab cavities located in the expanded beam regions and the IP differ slightly from π/2. To understand the effect of crabbing on the beam dynamics in this case, a simple model of the optics of the Medium Energy Electron-Ion Collider (MEIC) including local crabbing was developed using linear matrices and then studied numerically over multiple turns (1000 passes) of both electron and proton bunches. The same model was applied to both local and global crabbing schemes to determine the linear-order dynamical effects of the synchro-betatron coupling induced by crabbing.

  15. Variability of Protein Structure Models from Electron Microscopy.

    Science.gov (United States)

    Monroe, Lyman; Terashi, Genki; Kihara, Daisuke

    2017-03-02

    An increasing number of biomolecular structures are solved by electron microscopy (EM). However, the quality of structure models determined from EM maps vary substantially. To understand to what extent structure models are supported by information embedded in EM maps, we used two computational structure refinement methods to examine how much structures can be refined using a dataset of 49 maps with accompanying structure models. The extent of structure modification as well as the disagreement between refinement models produced by the two computational methods scaled inversely with the global and the local map resolutions. A general quantitative estimation of deviations of structures for particular map resolutions are provided. Our results indicate that the observed discrepancy between the deposited map and the refined models is due to the lack of structural information present in EM maps and thus these annotations must be used with caution for further applications.

  16. MODEL PSEUDOPOTENTIAL OF THE ELECTRON - NEGATIVE ION INTERACTION

    Directory of Open Access Journals (Sweden)

    Yu.Rudavskii

    2003-01-01

    Full Text Available Generalization of the Anderson model to describe the states of electronegative impurities in liquid-metal alloys is the main aim of the present paper. The effects of the random inner field on the charge impurity states is accounted for selfconsistently. Qualitative and quantitative estimation of hamiltonian parameters has been carried out. The limits of the proposed model applicability to a description of real systems are considered. Especially, the case of the oxygen impurity in liquid sodium is studied. The modelling of the proper electron-ionic interaction potential is the main goal of the paper. The parameters of the proposed pseudopotential are analyzed in detail. The comparison with other model potentials have been carried out. Resistivity of liquid sodium containing the oxygen impurities is calculated with utilizing the form-factor of the proposed model potential. Dependence of the resistivity on impurity concentration and on the charge states is received.

  17. Biology-based modeling to analyze uranium toxicity data on Daphnia magna in a multigeneration study.

    Science.gov (United States)

    Massarin, Sandrine; Beaudouin, Remy; Zeman, Florence; Floriani, Magali; Gilbin, Rodolphe; Alonzo, Frederic; Pery, Alexandre R R

    2011-05-01

    Recent studies have investigated chronic toxicity of waterborne depleted uranium on the life cycle and physiology of Daphnia magna. In particular, a reduction in food assimilation was observed. Our aims here were to examine whether this reduction could fully account for observed effects on both growth and reproduction, for three successive generations, and to investigate through microscope analyses whether this reduction resulted from direct damage to the intestinal epithelium. We analyzed data obtained by exposing Daphnia magna to uranium over three successive generations. We used energy-based models, which are both able to fit simultaneously growth and reproduction and are biologically relevant. Two possible modes of action were compared - decrease in food assimilation rate and increase in maintenance costs. In our models, effects were related either to internal concentration or to exposure concentration. The model that fitted the data best represented a decrease in food assimilation related to exposure concentration. Furthermore, observations of consequent histological damage to the intestinal epithelium, together with uranium precipitates in the epithelial cells, supported the assumption that uranium has direct effects on the digestive tract. We were able to model the data in all generations and showed that sensitivity increased from one generation to the next, in particular through a significant increase of the intensity of effect, once the threshold for appearance of effects was exceeded.

  18. Modeling of an Electron Injector for the AWAKE Project

    CERN Document Server

    Mete, O; Apsimon, R; Burt, G; Doebert, S; Fiorito, R; Welsch, C

    2015-01-01

    Particle-in-cell simulations were performed by using PARMELA to characterise an electron injector with a booster linac for the AWAKE project in order to provide the baseline specifications required by the plasma wakefield experiments. Tolerances and errors were investigated. A 3 GHz travelling wave structure designed by using CST code. Particles were tracked by using the field maps acquired from these electromagnetic simulations. These results are pre- sented in comparison with the generic accelerating structure model within PARMELA.

  19. Electric Dipole Moments of Neutron and Electron in Supersymmetric Model

    OpenAIRE

    Aoki, Mayumi; Kadoyoshi, Tomoko; Sugamoto, Akio; Oshimo, Noriyuki

    1997-01-01

    The electric dipole moments (EDMs) of the neutron and the electron are reviewed within the framework of the supersymmetric standard model (SSM) based on grand unified theories coupled to N=1 supergravity. Taking into account one-loop and two-loop contributions to the EDMs, we explore SSM parameter space consistent with experiments and discuss predicted values for the EDMs. Implications of baryon asymmetry of our universe for the EDMs are also discussed.

  20. Predictive Modeling of Chemical Hazard by Integrating Numerical Descriptors of Chemical Structures and Short-term Toxicity Assay Data

    Science.gov (United States)

    Rusyn, Ivan; Sedykh, Alexander; Guyton, Kathryn Z.; Tropsha, Alexander

    2012-01-01

    Quantitative structure-activity relationship (QSAR) models are widely used for in silico prediction of in vivo toxicity of drug candidates or environmental chemicals, adding value to candidate selection in drug development or in a search for less hazardous and more sustainable alternatives for chemicals in commerce. The development of traditional QSAR models is enabled by numerical descriptors representing the inherent chemical properties that can be easily defined for any number of molecules; however, traditional QSAR models often have limited predictive power due to the lack of data and complexity of in vivo endpoints. Although it has been indeed difficult to obtain experimentally derived toxicity data on a large number of chemicals in the past, the results of quantitative in vitro screening of thousands of environmental chemicals in hundreds of experimental systems are now available and continue to accumulate. In addition, publicly accessible toxicogenomics data collected on hundreds of chemicals provide another dimension of molecular information that is potentially useful for predictive toxicity modeling. These new characteristics of molecular bioactivity arising from short-term biological assays, i.e., in vitro screening and/or in vivo toxicogenomics data can now be exploited in combination with chemical structural information to generate hybrid QSAR–like quantitative models to predict human toxicity and carcinogenicity. Using several case studies, we illustrate the benefits of a hybrid modeling approach, namely improvements in the accuracy of models, enhanced interpretation of the most predictive features, and expanded applicability domain for wider chemical space coverage. PMID:22387746

  1. Optimizing predictive performance of CASE Ultra expert system models using the applicability domains of individual toxicity alerts.

    Science.gov (United States)

    Chakravarti, Suman K; Saiakhov, Roustem D; Klopman, Gilles

    2012-10-22

    Fragment based expert system models of toxicological end points are primarily comprised of a set of substructures that are statistically related to the toxic property in question. These special substructures are often referred to as toxicity alerts, toxicophores, or biophores. They are the main building blocks/classifying units of the model, and it is important to define the chemical structural space within which the alerts are expected to produce reliable predictions. Furthermore, defining an appropriate applicability domain is required as part of the OECD guidelines for the validation of quantitative structure-activity relationships (QSARs). In this respect, this paper describes a method to construct applicability domains for individual toxicity alerts that are part of the CASE Ultra expert system models. Defining applicability domain for individual alerts was necessary because each CASE Ultra model is comprised of multiple alerts, and different alerts of a model usually represent different toxicity mechanisms and cover different structural space; the use of an applicability domain for the overall model is often not adequate. The domain for each alert was constructed using a set of fragments that were found to be statistically related to the end point in question as opposed to using overall structural similarity or physicochemical properties. Use of the applicability domains in reducing false positive predictions is demonstrated. It is now possible to obtain ROC (receiver operating characteristic) profiles of CASE Ultra models by applying domain adherence cutoffs on the alerts identified in test chemicals. This helps in optimizing the performance of a model based on their true positive-false positive prediction trade-offs and reduce drastic effects on the predictive performance caused by the active/inactive ratio of the model's training set. None of the major currently available commercial expert systems for toxicity prediction offer the possibility to explore a

  2. Monte Carlo model for electron degradation in xenon gas

    CERN Document Server

    Mukundan, Vrinda

    2016-01-01

    We have developed a Monte Carlo model for studying the local degradation of electrons in the energy range 9-10000 eV in xenon gas. Analytically fitted form of electron impact cross sections for elastic and various inelastic processes are fed as input data to the model. Two dimensional numerical yield spectrum, which gives information on the number of energy loss events occurring in a particular energy interval, is obtained as output of the model. Numerical yield spectrum is fitted analytically, thus obtaining analytical yield spectrum. The analytical yield spectrum can be used to calculate electron fluxes, which can be further employed for the calculation of volume production rates. Using yield spectrum, mean energy per ion pair and efficiencies of inelastic processes are calculated. The value for mean energy per ion pair for Xe is 22 eV at 10 keV. Ionization dominates for incident energies greater than 50 eV and is found to have an efficiency of 65% at 10 keV. The efficiency for the excitation process is 30%...

  3. Monte Carlo model for electron degradation in methane

    CERN Document Server

    Bhardwaj, Anil

    2015-01-01

    We present a Monte Carlo model for degradation of 1-10,000 eV electrons in an atmosphere of methane. The electron impact cross sections for CH4 are compiled and analytical representations of these cross sections are used as input to the model.model.Yield spectra, which provides information about the number of inelastic events that have taken place in each energy bin, is used to calculate the yield (or population) of various inelastic processes. The numerical yield spectra, obtained from the Monte Carlo simulations, is represented analytically, thus generating the Analytical Yield Spectra (AYS). AYS is employed to obtain the mean energy per ion pair and efficiencies of various inelastic processes.Mean energy per ion pair for neutral CH4 is found to be 26 (27.8) eV at 10 (0.1) keV. Efficiency calculation showed that ionization is the dominant process at energies >50 eV, for which more than 50% of the incident electron energy is used. Above 25 eV, dissociation has an efficiency of 27%. Below 10 eV, vibrational e...

  4. Atmospheric ionization induced by precipitating electrons: Comparison of CRAC:EPII model with parametrization model

    CERN Document Server

    Artamonov, A A; Usoskin, I G

    2016-01-01

    A new model CRAC:EPII (Cosmic Ray Atmospheric Cascade: Electron Precipitation Induced Ionization) is presented. The CRAC:EPII is based on Monte Carlo simulation of precipitating electrons propagation and interaction with matter in the Earth atmosphere. It explicitly considers energy deposit: ionization, pair production, Compton scattering, generation of Bremsstrahlung high energy photons, photo-ionization and annihilation of positrons, multiple scattering as physical processes accordingly. The propagation of precipitating electrons and their interactions with atmospheric molecules is carried out with the GEANT4 simulation tool PLANETOCOSMICS code using NRLMSISE 00 atmospheric model. The ionization yields is compared with an analytical parametrization for various energies of incident precipitating electron, using a flux of mono-energetic particles. A good agreement between the two models is achieved. Subsequently, on the basis of balloon-born measured spectra of precipitating electrons at 30.10.2002 and 07.01....

  5. Modelling the Impact of Fractionation on Late Urinary Toxicity After Postprostatectomy Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fiorino, Claudio, E-mail: fiorino.claudio@hsr.it [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Cozzarini, Cesare [Department of Radiotherapy, San Raffaele Scientific Institute, Milan (Italy); Rancati, Tiziana [Prostate Cancer Program, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan (Italy); Briganti, Alberto [Department of Urology, San Raffaele Scientific Institute, Milan (Italy); Cattaneo, Giovanni Mauro; Mangili, Paola [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Di Muzio, Nadia Gisella [Department of Radiotherapy, San Raffaele Scientific Institute, Milan (Italy); Calandrino, Riccardo [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy)

    2014-12-01

    Purpose: To fit urinary toxicity data of patients treated with postprostatectomy radiation therapy with the linear quadratic (LQ) model with/without introducing a time factor. Methods and Materials: Between 1993 and 2010, 1176 patients were treated with conventional fractionation (1.8 Gy per fraction, median 70.2 Gy, n=929) or hypofractionation (2.35-2.90 Gy per fraction, n=247). Data referred to 2004-2010 (when all schemes were in use, n=563; conventional fractionation: 316; hypofractionation: 247) were fitted as a logit function of biological equivalent dose (BED), according to the LQ model with/without including a time factor γ (fixing α/β = 5 Gy). The 3-year risks of severe urethral stenosis, incontinence, and hematuria were considered as endpoints. Best-fit parameters were derived, and the resulting BEDs were taken in multivariable backward logistic models, including relevant clinical variables, considering the whole population. Results: The 3-year incidences of severe stenosis, incontinence, and hematuria were, respectively, 6.6%, 4.8%, and 3.3% in the group treated in 2004-2010. The best-fitted α/β values were 0.81 Gy and 0.74 Gy for incontinence and hematuria, respectively, with the classic LQ formula. When fixing α/β = 5 Gy, best-fit values for γ were, respectively, 0.66 Gy/d and 0.85 Gy/d. Sensitivity analyses showed reasonable values for γ (0.6-1.0 Gy/d), with comparable goodness of fit for α/β values between 3.5 and 6.5 Gy. Likelihood ratio tests showed that the fits with/without including γ were equivalent. The resulting multivariable backward logistic models in the whole population included BED, pT4, and use of antihypertensives (area under the curve [AUC] = 0.72) for incontinence and BED, pT4, and year of surgery (AUC = 0.80) for hematuria. Stenosis data could not be fitted: a 4-variable model including only clinical factors (acute urinary toxicity, pT4, year of surgery, and use of antihypertensives) was suggested (AUC

  6. Computational electronics semiclassical and quantum device modeling and simulation

    CERN Document Server

    Vasileska, Dragica; Klimeck, Gerhard

    2010-01-01

    Starting with the simplest semiclassical approaches and ending with the description of complex fully quantum-mechanical methods for quantum transport analysis of state-of-the-art devices, Computational Electronics: Semiclassical and Quantum Device Modeling and Simulation provides a comprehensive overview of the essential techniques and methods for effectively analyzing transport in semiconductor devices. With the transistor reaching its limits and new device designs and paradigms of operation being explored, this timely resource delivers the simulation methods needed to properly model state-of

  7. Modeling of humidity-related reliability in enclosures with electronics

    DEFF Research Database (Denmark)

    Hygum, Morten Arnfeldt; Popok, Vladimir

    2015-01-01

    Reliability of electronics that operate outdoor is strongly affected by environmental factors such as temperature and humidity. Fluctuations of these parameters can lead to water condensation inside enclosures. Therefore, modelling of humidity distribution in a container with air and freely exposed...... to predict humidity-related reliability of a printed circuit board (PCB) located in a cabinet by combining structural reliability methods and non-linear diffusion models. This framework can, thus, be used for reliability prediction from a climatic point-of-view. The proposed numerical approach is then tested...

  8. The Empowerment of Plasma Modeling by Fundamental Electron Scattering Data

    Science.gov (United States)

    Kushner, Mark J.

    2015-09-01

    Modeling of low temperature plasmas addresses at least 3 goals - investigation of fundamental processes, analysis and optimization of current technologies, and prediction of performance of as yet unbuilt systems for new applications. The former modeling may be performed on somewhat idealized systems in simple gases, while the latter will likely address geometrically and electromagnetically intricate systems with complex gas mixtures, and now gases in contact with liquids. The variety of fundamental electron and ion scattering data (FSD) required for these activities increases from the former to the latter, while the accuracy required of that data probably decreases. In each case, the fidelity, depth and impact of the modeling depends on the availability of FSD. Modeling is, in fact, empowered by the availability and robustness of FSD. In this talk, examples of the impact of and requirements for FSD in plasma modeling will be discussed from each of these three perspectives using results from multidimensional and global models. The fundamental studies will focus on modeling of inductively coupled plasmas sustained in Ar/Cl2 where the electron scattering from feed gases and their fragments ultimately determine gas temperatures. Examples of the optimization of current technologies will focus on modeling of remote plasma etching of Si and Si3N4 in Ar/NF3/N2/O2 mixtures. Modeling of systems as yet unbuilt will address the interaction of atmospheric pressure plasmas with liquids Work was supported by the US Dept. of Energy (DE-SC0001939), National Science Foundation (CHE-124752), and the Semiconductor Research Corp.

  9. Molecular Models for Conductance in Junctions and Electrochemical Electron Transfer

    Science.gov (United States)

    Mazinani, Shobeir Khezr Seddigh

    This thesis develops molecular models for electron transport in molecular junctions and intra-molecular electron transfer. The goal is to identify molecular descriptors that afford a substantial simplification of these electronic processes. First, the connection between static molecular polarizability and the molecular conductance is examined. A correlation emerges whereby the measured conductance of a tunneling junction decreases as a function of the calculated molecular polarizability for several systems, a result consistent with the idea of a molecule as a polarizable dielectric. A model based on a macroscopic extension of the Clausius-Mossotti equation to the molecular domain and Simmon's tunneling model is developed to explain this correlation. Despite the simplicity of the theory, it paves the way for further experimental, conceptual and theoretical developments in the use of molecular descriptors to describe both conductance and electron transfer. Second, the conductance of several biologically relevant, weakly bonded, hydrogen-bonded systems is systematically investigated. While there is no correlation between hydrogen bond strength and conductance, the results indicate a relation between the conductance and atomic polarizability of the hydrogen bond acceptor atom. The relevance of these results to electron transfer in biological systems is discussed. Hydrogen production and oxidation using catalysts inspired by hydrogenases provides a more sustainable alternative to the use of precious metals. To understand electrochemical and spectroscopic properties of a collection of Fe and Ni mimics of hydrogenases, high-level density functional theory calculations are described. The results, based on a detailed analysis of the energies, charges and molecular orbitals of these metal complexes, indicate the importance of geometric constraints imposed by the ligand on molecular properties such as acidity and electrocatalytic activity. Based on model calculations of

  10. Timescale analysis of a mathematical model of acetaminophen metabolism and toxicity.

    Science.gov (United States)

    Reddyhoff, Dennis; Ward, John; Williams, Dominic; Regan, Sophie; Webb, Steven

    2015-12-01

    Acetaminophen is a widespread and commonly used painkiller all over the world. However, it can cause liver damage when taken in large doses or at repeated chronic doses. Current models of acetaminophen metabolism are complex, and limited to numerical investigation though provide results that represent clinical investigation well. We derive a mathematical model based on mass action laws aimed at capturing the main dynamics of acetaminophen metabolism, in particular the contrast between normal and overdose cases, whilst remaining simple enough for detailed mathematical analysis that can identify key parameters and quantify their role in liver toxicity. We use singular perturbation analysis to separate the different timescales describing the sequence of events in acetaminophen metabolism, systematically identifying which parameters dominate during each of the successive stages. Using this approach we determined, in terms of the model parameters, the critical dose between safe and overdose cases, timescales for exhaustion and regeneration of important cofactors for acetaminophen metabolism and total toxin accumulation as a fraction of initial dose.

  11. Reduced systemic toxicity and preserved vestibular toxicity following co-treatment with nitriles and CYP2E1 inhibitors: a mouse model for hair cell loss.

    Science.gov (United States)

    Saldaña-Ruíz, Sandra; Boadas-Vaello, Pere; Sedó-Cabezón, Lara; Llorens, Jordi

    2013-10-01

    Several nitriles, including allylnitrile and cis-crotononitrile, have been shown to be ototoxic and cause hair cell degeneration in the auditory and vestibular sensory epithelia of mice. However, these nitriles can also be lethal due in large part to the microsomal metabolic release of cyanide, which is mostly dependent on the activity of the 2E1 isoform of the cytochrome P450 (CYP2E1). In this study, we co-administered mice with a nitrile and, to reduce their lethal effects, a selective CYP2E1 inhibitor: diallylsulfide (DAS) or trans-1,2-dichloroethylene (TDCE). Both in female 129S1/SvImJ (129S1) mice co-treated with DAS and cis-crotononitrile and in male RjOrl:Swiss/CD-1 (Swiss) mice co-treated with TDCE and allylnitrile, the nitrile caused a dose-dependent loss of vestibular function, as assessed by a specific behavioral test battery, and of hair cells, as assessed by hair bundle counts using scanning electron microscopy. In the experiments, the CYP2E1 inhibitors provided significant protection against the lethal effects of the nitriles and did not diminish the vestibular toxicity as assessed by behavioral effects in comparison to animals receiving no inhibitor. Additional experiments using a single dose of allylnitrile demonstrated that TDCE does not cause hair cell loss on its own and does not modify the vestibular toxicity of the nitrile in either male or female 129S1 mice. In all the experiments, high vestibular dysfunction scores in the behavioral test battery predicted extensive to complete loss of hair cells in the utricles. This provides a means of selecting animals for subsequent studies of vestibular hair cell regeneration or replacement.

  12. Discovery of potent, novel, non-toxic anti-malarial compounds via quantum modelling, virtual screening and in vitro experimental validation

    Directory of Open Access Journals (Sweden)

    Kaludov Nikola

    2011-09-01

    Full Text Available Abstract Background Developing resistance towards existing anti-malarial therapies emphasize the urgent need for new therapeutic options. Additionally, many malaria drugs in use today have high toxicity and low therapeutic indices. Gradient Biomodeling, LLC has developed a quantum-model search technology that uses quantum similarity and does not depend explicitly on chemical structure, as molecules are rigorously described in fundamental quantum attributes related to individual pharmacological properties. Therapeutic activity, as well as toxicity and other essential properties can be analysed and optimized simultaneously, independently of one another. Such methodology is suitable for a search of novel, non-toxic, active anti-malarial compounds. Methods A set of innovative algorithms is used for the fast calculation and interpretation of electron-density attributes of molecular structures at the quantum level for rapid discovery of prospective pharmaceuticals. Potency and efficacy, as well as additional physicochemical, metabolic, pharmacokinetic, safety, permeability and other properties were characterized by the procedure. Once quantum models are developed and experimentally validated, the methodology provides a straightforward implementation for lead discovery, compound optimizzation and de novo molecular design. Results Starting with a diverse training set of 26 well-known anti-malarial agents combined with 1730 moderately active and inactive molecules, novel compounds that have strong anti-malarial activity, low cytotoxicity and structural dissimilarity from the training set were discovered and experimentally validated. Twelve compounds were identified in silico and tested in vitro; eight of them showed anti-malarial activity (IC50 ≤ 10 μM, with six being very effective (IC50 ≤ 1 μM, and four exhibiting low nanomolar potency. The most active compounds were also tested for mammalian cytotoxicity and found to be non-toxic, with a

  13. Cranberry extract supplementation exerts preventive effects through alleviating Aβ toxicity in Caenorhabditis elegans model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    GUO Hong; DONG Yu-Qing; YE Bo-Ping

    2016-01-01

    Cranberry extract (CBE) rich in polyphenols are potent to delay paralysis induced by alleviating β-amyloid (Aβ) toxicity in C.elegans model of Alzheimer's disease (AD).In order to better apply CBE as an anti-AD agent efficiently,we sought to deterrmine whether preventive or therapeutic effect contributes more prominently toward CBE's anti-AD activity.As the level of Aβ toxicity and memory health are two major pathological parameters in AD,in the present study,we compared the effects of CBE on Aβ toxicity and memory health in the C.elegans AD model treated with preventive and therapeutic protocols.Our results revealed that CBE prominently showed the preventive efficacy,providing a basis for further investigation of these effects in mammals.

  14. Acute and Subacute Toxicity study of the Acetone Leaf extract of Centella asiatica in Experimental Animal Models

    Institute of Scientific and Technical Information of China (English)

    PK Chauhan; V Singh

    2012-01-01

    Objective: To evaluate acute and subacute toxicity of the acetone extract of Centella asiatica (Brahmi). Methods: Toxicity of Centella asiatica was evaluated in Swiss mice after ingestion of the extract during one day (acute model) and during 15 days (subacute model). The Biochemical parameters evaluated included creatinine, calcium, inorganic phosphorous, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assessed using commercial kits. Results: The results of the present investigation revealed that the LD50 of the extract is higher than 4000mg/kg and subacute treatment did not shows any change in corporal weight and hematological parameters. However, a change in liver weight but not in hepatic enzymes was observed. This suggested that the liver function is not altered by Centella asiatica. Some changes in the creatinine content were observed but could not be relative with the extract dose.Conclusions:The results suggest that the plant seems to be destitute of toxic effects in mice.

  15. Intramuscular Cobinamide Sulfite in a Rabbit Model of Sub-Lethal Cyanide Toxicity

    Science.gov (United States)

    Brenner, Matthew; Kim, Jae G.; Mahon, Sari B.; Lee, Jangwoen; Kreuter, Kelly A.; Blackledge, William; Mukai, David; Patterson, Steve; Mohammad, Othman; Sharma, Vijay S.; Boss, Gerry R.

    2009-01-01

    Objective To determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity. Background Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B12) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigated the use of intramuscular cobinamide sulfite to reverse cyanide toxicity induced physiologic changes in a sublethal cyanide exposure animal model. Methods New Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous wave near infrared spectroscopy monitoring of tissue oxy- and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5). Results Intramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system was in a mean of 1032 minutes in the control group and 9 minutes in the cobinamide group with a difference of 1023 minutes (95% confidence interval [CI] 116, 1874 minutes). In muscle tissue, recovery times were 76 and 24 minutes with a difference of 52 minutes (95% CI 7, 98min). Red blood cell cyanide levels returned towards normal significantly faster in cobinamide sulfite-treated animals than in control animals. Conclusions Intramuscular

  16. Toxic volatile organic compounds in environmental tobacco smoke: Emission factors for modeling exposures of California populations

    Energy Technology Data Exchange (ETDEWEB)

    Daisey, J.M.; Mahanama, K.R.R.; Hodgson, A.T. [Lawrence Berkeley Lab., CA (United States)

    1994-10-01

    The primary objective of this study was to measure emission factors for selected toxic air contaminants in environmental tobacco smoke (ETS) using a room-sized environmental chamber. The emissions of 23 volatile organic compounds (VOCs), including, 1,3-butadiene, three aldehydes and two vapor-phase N-nitrosamines were determined for six commercial brands of cigarettes and reference cigarette 1R4F. The commercial brands were selected to represent 62.5% of the cigarettes smoked in California. For each brand, three cigarettes were machine smoked in the chamber. The experiments were conducted over four hours to investigate the effects of aging. Emission factors of the target compounds were also determined for sidestream smoke (SS). For almost all target compounds, the ETS emission factors were significantly higher than the corresponding SS values probably due to less favorable combustion conditions and wall losses in the SS apparatus. Where valid comparisons could be made, the ETS emission factors were generally in good agreement with the literature. Therefore, the ETS emission factors, rather than the SS values, are recommended for use in models to estimate population exposures from this source. The variabilities in the emission factors ({mu}g/cigarette) of the selected toxic air contaminants among brands, expressed as coefficients of variation, were 16 to 29%. Therefore, emissions among brands were Generally similar. Differences among brands were related to the smoked lengths of the cigarettes and the masses of consumed tobacco. Mentholation and whether a cigarette was classified as light or regular did not significantly affect emissions. Aging was determined not to be a significant factor for the target compounds. There were, however, deposition losses of the less volatile compounds to chamber surfaces.

  17. Modeling a Miniaturized Scanning Electron Microscope Focusing Column - Lessons Learned in Electron Optics Simulation

    Science.gov (United States)

    Loyd, Jody; Gregory, Don; Gaskin, Jessica

    2016-01-01

    This presentation discusses work done to assess the design of a focusing column in a miniaturized Scanning Electron Microscope (SEM) developed at the NASA Marshall Space Flight Center (MSFC) for use in-situ on the Moon-in particular for mineralogical analysis. The MSFC beam column design uses purely electrostatic fields for focusing, because of the severe constraints on mass and electrical power consumption imposed by the goals of lunar exploration and of spaceflight in general. The resolution of an SEM ultimately depends on the size of the focused spot of the scanning beam probe, for which the stated goal here is a diameter of 10 nanometers. Optical aberrations are the main challenge to this performance goal, because they blur the ideal geometrical optical image of the electron source, effectively widening the ideal spot size of the beam probe. In the present work the optical aberrations of the mini SEM focusing column were assessed using direct tracing of non-paraxial rays, as opposed to mathematical estimates of aberrations based on paraxial ray-traces. The geometrical ray-tracing employed here is completely analogous to ray-tracing as conventionally understood in the realm of photon optics, with the major difference being that in electron optics the lens is simply a smoothly varying electric field in vacuum, formed by precisely machined electrodes. Ray-tracing in this context, therefore, relies upon a model of the electrostatic field inside the focusing column to provide the mathematical description of the "lens" being traced. This work relied fundamentally on the boundary element method (BEM) for this electric field model. In carrying out this research the authors discovered that higher accuracy in the field model was essential if aberrations were to be reliably assessed using direct ray-tracing. This led to some work in testing alternative techniques for modeling the electrostatic field. Ultimately, the necessary accuracy was attained using a BEM

  18. Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster.

    Science.gov (United States)

    Meyer, S; Schulz, J; Jeibmann, A; Taleshi, M S; Ebert, F; Francesconi, K A; Schwerdtle, T

    2014-11-01

    Arsenic-containing hydrocarbons (AsHC) constitute one group of arsenolipids that have been identified in seafood. In this first in vivo toxicity study for AsHCs, we show that AsHCs exert toxic effects in Drosophila melanogaster in a concentration range similar to that of arsenite. In contrast to arsenite, however, AsHCs cause developmental toxicity in the late developmental stages of Drosophila melanogaster. This work illustrates the need for a full characterisation of the toxicity of AsHCs in experimental animals to finally assess the risk to human health related to the presence of arsenolipids in seafood.

  19. Repeat length and RNA expression level are not primary determinants in CUG expansion toxicity in Drosophila models.

    Directory of Open Access Journals (Sweden)

    Gwenn Le Mée

    Full Text Available Evidence for an RNA gain-of-function toxicity has now been provided for an increasing number of human pathologies. Myotonic dystrophies (DM belong to a class of RNA-dominant diseases that result from RNA repeat expansion toxicity. Specifically, DM of type 1 (DM1, is caused by an expansion of CUG repeats in the 3'UTR of the DMPK protein kinase mRNA, while DM of type 2 (DM2 is linked to an expansion of CCUG repeats in an intron of the ZNF9 transcript (ZNF9 encodes a zinc finger protein. In both pathologies the mutant RNA forms nuclear foci. The mechanisms that underlie the RNA pathogenicity seem to be rather complex and not yet completely understood. Here, we describe Drosophila models that might help unravelling the molecular mechanisms of DM1-associated CUG expansion toxicity. We generated transgenic flies that express inducible repeats of different type (CUG or CAG and length (16, 240, 480 repeats and then analyzed transgene localization, RNA expression and toxicity as assessed by induced lethality and eye neurodegeneration. The only line that expressed a toxic RNA has a (CTG(240 insertion. Moreover our analysis shows that its level of expression cannot account for its toxicity. In this line, (CTG(240.4, the expansion inserted in the first intron of CG9650, a zinc finger protein encoding gene. Interestingly, CG9650 and (CUG(240.4 expansion RNAs were found in the same nuclear foci. In conclusion, we suggest that the insertion context is the primary determinant for expansion toxicity in Drosophila models. This finding should contribute to the still open debate on the role of the expansions per se in Drosophila and in human pathogenesis of RNA-dominant diseases.

  20. Effect of water quality on mercury toxicity to Photobacterium phosphoreum: Model development and its application in natural waters.

    Science.gov (United States)

    Wang, Xinghao; Qu, Ruijuan; Wei, Zhongbo; Yang, Xi; Wang, Zunyao

    2014-06-01

    Mercury (Hg) compounds are widely distributed toxic environmental and industrial pollutants and they may bring danger to growth and development of aquatic organisms. The distribution of Hg species in the 3 percent NaCl solution was calculated using the chemical equilibrium model Visual MINTEQ, which demonstrated that Hg was mainly complexed by chlorides in the pH range 5.0-9.0 and the proportions of HgCl4(2-), HgCl3(-) and HgCl2(aq) reached to 95 percent of total Hg. Then the effects of cations (Ca(2+), Mg(2+), K(+) and H(+)), anions (HCO3(-), NO3(-), SO4(2-) and HPO4(2-)) and complexing agents (ethylene diamine tetraacetic acid (EDTA) and dissolved organic matter (DOM)) on Hg toxicity to Photobacterium phosphoreum were evaluated in standardized 15min acute toxicity tests. The significant increase of 6.3-fold in EC50 data with increasing pH was observed over the tested pH range of 5.0-8.0, which suggested the possible competition between hydroxyl and the negatively charged chloro-complex. By contrast, it was found that major cations (Ca(2+), Mg(2+) and K(+)) have little effect on Hg toxicity to P. phosphoreum. An interesting finding was that the addition of HPO4(2-) significantly increased Hg toxicity, which may imply that the addition of phosphate increased the soluble Hg-chloro complex species. Additions of complexing agents (EDTA and DOM) into the exposure water increased Hg bioavailability via complexation of Hg. Finally, a model which incorporated the effect of pH, HPO4(2-), HCO3(-), SO4(2-) and DOM on Hg toxicity was developed to predict acute Hg toxicity for P. phosphoreum, which may be a useful tool in setting realistic water quality criteria for different types of water.

  1. Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on in vitro toxicity data and in silico physiologycally based kinetic modeling

    NARCIS (Netherlands)

    Louisse, J.; Bosgra, S.; Blaauboer, B.J.; Rietjens, I.; Verwei, M.

    2015-01-01

    The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity d

  2. Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on in vitro toxicity data and in silico physiologically based kinetic modeling

    NARCIS (Netherlands)

    Louisse, Jochem; Bosgra, Sieto; Blaauboer, Bas J.; Rietjens, Ivonne M. C. M.; Verwei, Miriam

    2015-01-01

    The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity d

  3. Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on in vitro toxicity data and in silico physiologically based kinetic modeling

    NARCIS (Netherlands)

    Louisse, J.; Bosgra, S.; Blaauboer, B.J.; Rietjens, I.M.C.M.; Verwei, M.

    2015-01-01

    The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity

  4. Secondary production of toxic nitropolycyclic aromatic hydrocarbon during the Asian dust event: approached by model simulation

    Science.gov (United States)

    Inomata, Y.; Kajino, M.; Sato, K.

    2016-12-01

    Nitrated polycyclic aromatic hydrocarbons (NPAHs) are one of toxic compounds in the atmospheric particles. NPAHs are emitted in the atmosphere through the combustion of fossil fuels such as coal and diesel. Furthermore, it is produced by heterogeneous reactions such as the surface on the mineral dust aerosols. 1-nitoropyrene (1-NP) is one of the most abundant NPAHs and considered as a probable carcinogen. It is found that the production of 1-NP occurred during the heavy Asian dust event in Beijing and Japan. In this study, we estimated production of 1-NP by heterogeneous reactions by using model simulations in Northeast Asia. The model was three dimensional chemical transport model, Regional Air Quality Model for POPs version. The model performance was investigated the comparison with the observations. We focused on heavy Asian dust event observed in Beijing on 18-20 March 2010. Several sensitivity calculations are conducted under the existence of Asian dust in order to investigate the effect of relative humidity and photolysis. On 18-20 March 2010, primary 1-NP concentrations are about 50 fg/m3. Under the existence of the Asian dust, secondary production of 1-NP is estimated to 7 times against the concentrations of primary emission. Horizontal distributions indicate that decrease of Pyr and increase of 1-NP is significant around Beijing in this Asian dust event. Secondary production of 1-NP was large in this area as well as the downwind region such as the East China Sea. It is found that secondary production of 1-NP is minor in dessert region because of lower concentrations of Pyrene (Pyr). Distribution of secondary produced 1-NP varied with concentrations of Pyr, transport of Asian dust. Secondary production of 1-NP in March 2010 was larger than the primary emission of 1-NP, whereas the secondary production was smaller than those of the primary emission in April and May, 2011.

  5. Electron distribution in polar heterojunctions within a realistic model

    Energy Technology Data Exchange (ETDEWEB)

    Tien, Nguyen Thanh, E-mail: thanhtienctu@gmail.com [College of Natural Science, Can Tho University, 3-2 Road, Can Tho City (Viet Nam); Thao, Dinh Nhu [Center for Theoretical and Computational Physics, College of Education, Hue University, 34 Le Loi Street, Hue City (Viet Nam); Thao, Pham Thi Bich [College of Natural Science, Can Tho University, 3-2 Road, Can Tho City (Viet Nam); Quang, Doan Nhat [Institute of Physics, Vietnamese Academy of Science and Technology, 10 Dao Tan Street, Hanoi (Viet Nam)

    2015-12-15

    We present a theoretical study of the electron distribution, i.e., two-dimensional electron gas (2DEG) in polar heterojunctions (HJs) within a realistic model. The 2DEG is confined along the growth direction by a triangular quantum well with a finite potential barrier and a bent band figured by all confinement sources. Therein, interface polarization charges take a double role: they induce a confining potential and, furthermore, they can make some change in other confinements, e.g., in the Hartree potential from ionized impurities and 2DEG. Confinement by positive interface polarization charges is necessary for the ground state of 2DEG existing at a high sheet density. The 2DEG bulk density is found to be increased in the barrier, so that the scattering occurring in this layer (from interface polarization charges and alloy disorder) becomes paramount in a polar modulation-doped HJ.

  6. Electron distribution in polar heterojunctions within a realistic model

    Science.gov (United States)

    Tien, Nguyen Thanh; Thao, Dinh Nhu; Thao, Pham Thi Bich; Quang, Doan Nhat

    2015-12-01

    We present a theoretical study of the electron distribution, i.e., two-dimensional electron gas (2DEG) in polar heterojunctions (HJs) within a realistic model. The 2DEG is confined along the growth direction by a triangular quantum well with a finite potential barrier and a bent band figured by all confinement sources. Therein, interface polarization charges take a double role: they induce a confining potential and, furthermore, they can make some change in other confinements, e.g., in the Hartree potential from ionized impurities and 2DEG. Confinement by positive interface polarization charges is necessary for the ground state of 2DEG existing at a high sheet density. The 2DEG bulk density is found to be increased in the barrier, so that the scattering occurring in this layer (from interface polarization charges and alloy disorder) becomes paramount in a polar modulation-doped HJ.

  7. Electron electric dipole moment in Inverse Seesaw models

    CERN Document Server

    Abada, Asmaa

    2016-01-01

    We consider the contribution of sterile neutrinos to the electric dipole moment of charged leptons in the most minimal realisation of the Inverse Seesaw mechanism, in which the Standard Model is extended by two right-handed neutrinos and two sterile fermion states. Our study shows that the two pairs of (heavy) pseudo-Dirac mass eigenstates can give significant contributions to the electron electric dipole moment, lying close to future experimental sensitivity if their masses are above the electroweak scale. The major contribution comes from two-loop diagrams with pseudo-Dirac neutrino states running in the loops. In our analysis we further discuss the possibility of having a successful leptogenesis in this framework, compatible with a large electron electric dipole moment.

  8. Electronic Commerce Success Model: A Search for Multiple Criteria

    Directory of Open Access Journals (Sweden)

    Didi Achjari

    2004-01-01

    Full Text Available The current study attempts to develop and examine framework of e-commerce success. In order to obtain comprehensive and robust measures, the framework accomodates key factors that are identified in the literature concerning the success of electronic commerce. The structural model comprises of four exogenous variables (Internal Driver, Internal Impediment, External Driver and Exgternal Impediment and one endogenous variable (Electornic Commerce Success eith 24 observed variables. The study that was administered within large Australian companies using questionaire survey concluded that benefits for both internal organization and external parties from the use of e-commerce were the main factor tro predict perceived and/or expected success of electronic commerce.

  9. Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Harper, Bryan [Oregon State University (United States); Thomas, Dennis; Chikkagoudar, Satish; Baker, Nathan [Pacific Northwest National Laboratory (United States); Tang, Kaizhi [Intelligent Automation, Inc. (United States); Heredia-Langner, Alejandro [Pacific Northwest National Laboratory (United States); Lins, Roberto [CPqAM, Oswaldo Cruz Foundation, FIOCRUZ-PE (Brazil); Harper, Stacey, E-mail: stacey.harper@oregonstate.edu [Oregon State University (United States)

    2015-06-15

    The integration of rapid assays, large datasets, informatics, and modeling can overcome current barriers in understanding nanomaterial structure–toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here, we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality in developing embryonic zebrafish, were established at realistic exposure levels and used to develop a hazard ranking of diverse nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both the core composition and outermost surface chemistry of nanomaterials. The resulting clusters guided the development of a surface chemistry-based model of gold nanoparticle toxicity. Our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. Research should continue to focus on methodologies for determining nanomaterial hazard based on multiple sub-lethal responses following realistic, low-dose exposures, thus increasing the availability of quantitative measures of nanomaterial hazard to support the development of nanoparticle structure–activity relationships.

  10. Galleria mellonella as a novel in vivo model for assessment of the toxicity of 1-alkyl-3-methylimidazolium chloride ionic liquids.

    Science.gov (United States)

    Megaw, Julianne; Thompson, Thomas P; Lafferty, Ryan A; Gilmore, Brendan F

    2015-11-01

    The larval form of the Greater Wax Moth (Galleria mellonella) was evaluated as a model system for the study of the acute in vivo toxicity of 1-alkyl-3-methylimidazolium chloride ionic liquids. 24-h median lethal dose (LD50) values for nine of these ionic liquids bearing alkyl chain substituents ranging from 2 to 18 carbon atoms were determined. The in vivo toxicity of the ionic liquids was found to correlate directly with the length of the alkyl chain substituent, and the pattern of toxicity observed was in accordance with previous studies of ionic liquid toxicity in other living systems, including a characteristic toxicity 'cut-off' effect. However, G. mellonella appeared to be more susceptible to the toxic effects of the ionic liquids tested, possibly as a result of their high body fat content. The results obtained in this study indicate that G. mellonella represents a sensitive, reliable and robust in vivo model organism for the evaluation of ionic liquid toxicity.

  11. Modeling chronic dietary cadmium bioaccumulation and toxicity from periphyton to Hyalella azteca.

    Science.gov (United States)

    Golding, Lisa A; Borgmann, Uwe; Dixon, D George

    2011-07-01

    A chronic (28-d) Cd saturation bioaccumulation model was developed to quantify the Cd contribution from a natural periphyton diet to Cd in the freshwater amphipod Hyalella azteca. Bioaccumulation was then linked to chronic toxic effects. Juvenile H. azteca were exposed to treatments of Cd in water (3.13-100 nmol/L nominal) and food (389-26,300 nmol/g ash-free dry mass). Cadmium bioaccumulation, survival, and growth were recorded. Dietary Cd was estimated to contribute 21 to 31, 59 to 94, and 40 to 55% to bioaccumulated Cd in H. azteca exposed to treatments of Cd primarily in water, food, and food + water, respectively. Survival as a function of Cd lethal body concentration (679 nmol/g; 95% confidence limits, 617-747) was the most robust endpoint. Body concentration integrated all exposure routes. Based on the lethal body concentration, dietary Cd was predicted to contribute markedly (26-90%) to Cd in H. azteca. Cadmium concentration and food nutritional quality (biomass, chlorophyll a, total lipid, fatty acids, total protein) had no effect on H. azteca nutritional quality (total lipid, fatty acids, total protein) but did influence H. azteca dry weight. This research highlighted the importance of including a dietary component when modeling chronic effects of Cd and when refining endpoints for use in ecological risk assessment and water quality guidelines.

  12. Systemic cytokine response in moribund mice of streptococcal toxic shock syndrome model.

    Science.gov (United States)

    Saito, Mitsumasa; Kajiwara, Hideko; Iida, Ken-ichiro; Hoshina, Takayuki; Kusuhara, Koichi; Hara, Toshiro; Yoshida, Shin-ichi

    2011-02-01

    Streptococcus pyogenes causes severe invasive disease in humans, including streptococcal toxic shock syndrome (STSS). We previously reported a mouse model that is similar to human STSS. When mice were infected intramuscularly with 10(7) CFU of S. pyogenes, all of them survived acute phase of infection. After 20 or more days of infection, a number of them died suddenly accompanied by S. pyogenes bacteremia. We call this phenomenon "delayed death". We analyzed the serum cytokine levels of mice with delayed death, and compared them with those of mice who died in the acute phase of intravenous S. pyogenes infection. The serum levels of TNF-α and IFN-γ in mice of delayed death were more than 100 times higher than those in acute death mice. IL-10 and IL-12, which were not detected in acute death, were also significantly higher in mice of delayed death. IL-6 and MCP-1 (CCL-2) were elevated in both groups of mice. It was noteworthy that not only pro-inflammatory cytokines but also anti-inflammatory cytokines were elevated in delayed death. We also found that intravenous TNF-α injection accelerated delayed death, suggesting that an increase of serum TNF-α induced S. pyogenes bacteremia in our mouse model.

  13. Multiple discrete soluble aggregates influence polyglutamine toxicity in a Huntington’s disease model system

    Science.gov (United States)

    Xi, Wen; Wang, Xin; Laue, Thomas M.; Denis, Clyde L.

    2016-01-01

    Huntington’s disease (HD) results from expansions of polyglutamine stretches (polyQ) in the huntingtin protein (Htt) that promote protein aggregation, neurodegeneration, and death. Since the diversity and sizes of the soluble Htt-polyQ aggregates that have been linked to cytotoxicity are unknown, we investigated soluble Htt-polyQ aggregates using analytical ultracentrifugation. Soon after induction in a yeast HD model system, non-toxic Htt-25Q and cytotoxic Htt-103Q both formed soluble aggregates 29S to 200S in size. Because current models indicate that Htt-25Q does not form soluble aggregates, reevaluation of previous studies may be necessary. Only Htt-103Q aggregation behavior changed, however, with time. At 6 hr mid-sized aggregates (33S to 84S) and large aggregates (greater than 100S) became present while at 24 hr primarily only mid-sized aggregates (20S to 80S) existed. Multiple factors that decreased cytotoxicity of Htt-103Q (changing the length of or sequences adjacent to the polyQ, altering ploidy or chaperone dosage, or deleting anti-aging factors) altered the Htt-103Q aggregation pattern in which the suite of mid-sized aggregates at 6 hr were most correlative with cytotoxicity. Hence, the amelioration of HD and other neurodegenerative diseases may require increased attention to and discrimination of the dynamic alterations in soluble aggregation processes. PMID:27721444

  14. CORAL: quantitative structure-activity relationship models for estimating toxicity of organic compounds in rats.

    Science.gov (United States)

    Toropova, A P; Toropov, A A; Benfenati, E; Gini, G; Leszczynska, D; Leszczynski, J

    2011-09-01

    For six random splits, one-variable models of rat toxicity (minus decimal logarithm of the 50% lethal dose [pLD50], oral exposure) have been calculated with CORAL software (http://www.insilico.eu/coral/). The total number of considered compounds is 689. New additional global attributes of the simplified molecular input line entry system (SMILES) have been examined for improvement of the optimal SMILES-based descriptors. These global SMILES attributes are representing the presence of some chemical elements and different kinds of chemical bonds (double, triple, and stereochemical). The "classic" scheme of building up quantitative structure-property/activity relationships and the balance of correlations (BC) with the ideal slopes were compared. For all six random splits, best prediction takes place if the aforementioned BC along with the global SMILES attributes are included in the modeling process. The average statistical characteristics for the external test set are the following: n = 119 ± 6.4, R(2) = 0.7371 ± 0.013, and root mean square error = 0.360 ± 0.037. Copyright © 2011 Wiley Periodicals, Inc.

  15. Modeling of electron time variations in the radiation belts

    Science.gov (United States)

    Chan, K. W.; Teague, M. J.; Schofield, N. J.; Vette, J. I.

    1979-01-01

    A review of the temporal variation in the trapped electron population of the inner and outer radiation zones is presented. Techniques presently used for modeling these zones are discussed and their deficiencies identified. An intermediate region is indicated between the zones in which the present modeling techniques are inadequate due to the magnitude and frequency of magnetic storms. Future trends are examined, and it is suggested that modeling of individual magnetic storms may be required in certain L bands. An analysis of seven magnetic storms is presented, establishing the independence of the depletion time of the storm flux and the storm magnitude. Provisional correlation between the storm magnitude and the Dst index is demonstrated.

  16. Modelling of electron transport and of sawtooth activity in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Angioni, C

    2001-10-01

    Transport phenomena in tokamak plasmas strongly limit the particle and energy confinement and represent a crucial obstacle to controlled thermonuclear fusion. Within the vast framework of transport studies, three topics have been tackled in the present thesis: first, the computation of neoclassical transport coefficients for general axisymmetric equilibria and arbitrary collisionality regime; second, the analysis of the electron temperature behaviour and transport modelling of plasma discharges in the Tokamak a configuration Variable (TCV); third, the modelling and simulation of the sawtooth activity with different plasma heating conditions. The work dedicated to neoclassical theory has been undertaken in order to first analytically identify a set of equations suited for implementation in existing Fokker-Planck codes. Modifications of these codes enabled us to compute the neoclassical transport coefficients considering different realistic magnetic equilibrium configurations and covering a large range of variation of three key parameters: aspect ratio, collisionality, and effective charge number. A comparison of the numerical results with an analytical limit has permitted the identification of two expressions for the trapped particle fraction, capable of encapsulating the geometrical effects and thus enabling each transport coefficient to be fitted with a single analytical function. This has allowed us to provide simple analytical formulae for all the neoclassical transport coefficients valid for arbitrary aspect ratio and collisionality in general realistic geometry. This work is particularly useful for a correct evaluation of the neoclassical contribution in tokamak scenarios with large bootstrap cur- rent fraction, or improved confinement regimes with low anomalous transport and for the determination of the plasma current density profile, since the plasma conductivity is usually assumed neoclassical. These results have been included in the plasma transport code

  17. Simple predictive electron transport models applied to sawtoothing plasmas

    Science.gov (United States)

    Kim, D.; Merle, A.; Sauter, O.; Goodman, T. P.

    2016-05-01

    In this work, we introduce two simple transport models to evaluate the time evolution of electron temperature and density profiles during sawtooth cycles (i.e. over a sawtooth period time-scale). Since the aim of these simulations is to estimate reliable profiles within a short calculation time, two simplified ad-hoc models have been developed. The goal for these models is to rely on a few easy-to-check free parameters, such as the confinement time scaling factor and the profiles’ averaged scale-lengths. Due to the simplicity and short calculation time of the models, it is expected that these models can also be applied to real-time transport simulations. We show that it works well for Ohmic and EC heated L- and H-mode plasmas. The differences between these models are discussed and we show that their predictive capabilities are similar. Thus only one model is used to reproduce with simulations the results of sawtooth control experiments on the TCV tokamak. For the sawtooth pacing, the calculated time delays between the EC power off and sawtooth crash time agree well with the experimental results. The map of possible locking range is also well reproduced by the simulation.

  18. Dynamic Characterization and Modeling of Potting Materials for Electronics Assemblies

    Science.gov (United States)

    Joshi, Vasant; Lee, Gilbert; Santiago, Jaime

    2015-06-01

    Prediction of survivability of encapsulated electronic components subject to impact relies on accurate modeling. Both static and dynamic characterization of encapsulation material is needed to generate a robust material model. Current focus is on potting materials to mitigate high rate loading on impact. In this effort, encapsulation scheme consists of layers of polymeric material Sylgard 184 and Triggerbond Epoxy-20-3001. Experiments conducted for characterization of materials include conventional tension and compression tests, Hopkinson bar, dynamic material analyzer (DMA) and a non-conventional accelerometer based resonance tests for obtaining high frequency data. For an ideal material, data can be fitted to Williams-Landel-Ferry (WLF) model. A new temperature-time shift (TTS) macro was written to compare idealized temperature shift factor (WLF model) with experimental incremental shift factors. Deviations can be observed by comparison of experimental data with the model fit to determine the actual material behavior. Similarly, another macro written for obtaining Ogden model parameter from Hopkinson Bar tests indicates deviations from experimental high strain rate data. In this paper, experimental results for different materials used for mitigating impact, and ways to combine data from resonance, DMA and Hopkinson bar together with modeling refinements will be presented.

  19. RCCtrust: A Combined Trust Model for Electronic Community

    Institute of Scientific and Technical Information of China (English)

    Yu Zhang; Hua-Jun Chen; Xiao-Hong Jiang; Hao Sheng; Zhao-Hui Wu

    2009-01-01

    Previous trust models are mainly focused on reputational mechanism based on explicit trust ratings.However,the large amount of user-generated content and community context published on Web is often ignored.Without enough information,there are several problems with previous trust models:first,they cannot determine in which field one user trusts in another,so many models assume that trust exists in all fields.Second some models are not able to delineate the variation of trust SCales,therefore they regard each user trusts all his friends to the same extent.Third,since these models only focus on explicit trust ratings,so the trust matrix is very sparse.To Solve these problems,we present RCCtrust-a trust model which combines Reputation-,Content-and Context-based mechanisms to provide more accurate,fine-grained and efficient trust management for the electronic community.We extract trust-related information from user-generated content and community context from Web to extend reputation-based trust models. We introduce role-based and behavior-based reasoning functionalities to infer users'i nterests and category-specific trust relationships.Following the study in sociology, RCCtrust exploits similarities between pairs of users to depict difierentiated trust scales.The experimental results show that RCCtrust outperforin8 pure user similarity method and linear decay trust-aware technique in both accuracy and coverage for a Recommender System.

  20. Precision-cut intestinal slices as an in vitro model to predict NSAID induced intestinal toxicity

    NARCIS (Netherlands)

    Niu, Xiaoyu; van der Bijl, Henk; Groothuis, Geny; de Graaf, Inge

    2013-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with high prevalence of gastro-intestinal side-effects. In vivo studies suggest that uncoupling of oxidative phosphorylation is an important cause of the toxicity and that the toxicity is aggravated by enterohepatic circulation. Precision

  1. Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data

    Science.gov (United States)

    EPA's ToxCast™ project is profiling the in vitro bioactivity of chemicals to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesized that developmental toxicity in guideline animal studies captured in the ToxRefDB database wou...

  2. Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans

    Science.gov (United States)

    Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)

  3. Methoxyethylamino-numonafide Is an Efficacious and Minimally Toxic Amonafide Derivative in Murine Models of Human Cancer

    Directory of Open Access Journals (Sweden)

    Yanning Liu

    2011-05-01

    Full Text Available Amonafide is a DNA intercalator in clinical development for the treatment of cancer. The drug has a 5-position amine that is variably acetylated to form a toxic metabolite in humans, increasing adverse effects and complicating the dosing of amonafide. Numonafides, 6-amino derivatives of amonafide that avoid the toxic acetylation, also show in vitro anticancer activity, as we have previously described. Here, we report the in vitro and in vivo activities of two numonafides, 6-methoxyethylamino-numonafide (MEAN and 6-amino-numonafide (AN with comparisons to amonafide. The in vitro potencies and cellular anticancer mechanisms are similar for the two numonafides and amonafide. Results from several mouse models of human cancer demonstrate that AN and MEAN require slightly higher doses than amonafide for equal efficacy in short-term dosing models, but the same dose of all three compounds in long-term dosing models are equally efficacious. MEAN is tolerated much better than amonafide and AN at equally efficacious doses based on weight change, activity, stool consistency, and dose tolerance with survival as the end point. The studies presented here demonstrate that MEAN is much less toxic than amonafide or AN in mouse models of human liver and gastric cancers while being equally efficacious in vivo and inhibiting cancer cells through similar mechanisms. These findings demonstrate that numonafides can be less toxic than amonafide and support further preclinical development and novel anticancer agents or as replacements or amonafide.

  4. The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-response curves for in vivo developmental toxicity of glycol ethers in rat and man.

    Science.gov (United States)

    Louisse, Jochem; de Jong, Esther; van de Sandt, Johannes J M; Blaauboer, Bas J; Woutersen, Ruud A; Piersma, Aldert H; Rietjens, Ivonne M C M; Verwei, Miriam

    2010-12-01

    At present, regulatory assessment of systemic toxicity is almost solely carried out using animal models. The European Commission's REACH legislation stimulates the use of animal-free approaches to obtain information on the toxicity of chemicals. In vitro toxicity tests provide in vitro concentration-response curves for specific target cells, whereas in vivo dose-response curves are regularly used for human risk assessment. The present study shows an approach to predict in vivo dose-response curves for developmental toxicity by combining in vitro toxicity data and in silico kinetic modeling. A physiologically based kinetic (PBK) model was developed, describing the kinetics of four glycol ethers and their embryotoxic alkoxyacetic acid metabolites in rat and man. In vitro toxicity data of these metabolites derived in the embryonic stem cell test were used as input in the PBK model to extrapolate in vitro concentration-response curves to predicted in vivo dose-response curves for developmental toxicity of the parent glycol ethers in rat and man. The predicted dose-response curves for rat were found to be in concordance with the embryotoxic dose levels measured in reported in vivo rat studies. Therefore, predicted dose-response curves for rat could be used to set a point of departure for deriving safe exposure limits in human risk assessment. Combining the in vitro toxicity data with a human PBK model allows the prediction of dose-response curves for human developmental toxicity. This approach could therefore provide a means to reduce the need for animal testing in human risk assessment practices.

  5. Modeling nitrogen plasmas produced by intense electron beams

    Energy Technology Data Exchange (ETDEWEB)

    Angus, J. R.; Swanekamp, S. B.; Schumer, J. W.; Hinshelwood, D. D. [Plasma Physics Division, Naval Research Laboratory, Washington, DC 20375 (United States); Mosher, D.; Ottinger, P. F. [Independent contractors for NRL through Engility, Inc., Alexandria, Virginia 22314 (United States)

    2016-05-15

    A new gas–chemistry model is presented to treat the breakdown of a nitrogen gas with pressures on the order of 1 Torr from intense electron beams with current densities on the order of 10 kA/cm{sup 2} and pulse durations on the order of 100 ns. For these parameter regimes, the gas transitions from a weakly ionized molecular state to a strongly ionized atomic state on the time scale of the beam pulse. The model is coupled to a 0D–circuit model using the rigid–beam approximation that can be driven by specifying the time and spatial profiles of the beam pulse. Simulation results are in good agreement with experimental measurements of the line–integrated electron density from experiments done using the Gamble II generator at the Naval Research Laboratory. It is found that the species are mostly in the ground and metastable states during the atomic phase, but that ionization proceeds predominantly through thermal ionization of optically allowed states with excitation energies close to the ionization limit.

  6. Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yongfei; Feng, Jianfeng, E-mail: fengjf@nankai.edu.cn; Zhu, Lin, E-mail: zhulin@nankai.edu.cn

    2015-12-15

    Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H{sup +}. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10{sup −6} M Cd and 10{sup −6} M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H{sup +} in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

  7. Modeling of pharmaceuticals mixtures toxicity with deviation ratio and best-fit functions models.

    Science.gov (United States)

    Wieczerzak, Monika; Kudłak, Błażej; Yotova, Galina; Nedyalkova, Miroslava; Tsakovski, Stefan; Simeonov, Vasil; Namieśnik, Jacek

    2016-11-15

    The present study deals with assessment of ecotoxicological parameters of 9 drugs (diclofenac (sodium salt), oxytetracycline hydrochloride, fluoxetine hydrochloride, chloramphenicol, ketoprofen, progesterone, estrone, androstenedione and gemfibrozil), present in the environmental compartments at specific concentration levels, and their mutual combinations by couples against Microtox® and XenoScreen YES/YAS® bioassays. As the quantitative assessment of ecotoxicity of drug mixtures is an complex and sophisticated topic in the present study we have used two major approaches to gain specific information on the mutual impact of two separate drugs present in a mixture. The first approach is well documented in many toxicological studies and follows the procedure for assessing three types of models, namely concentration addition (CA), independent action (IA) and simple interaction (SI) by calculation of a model deviation ratio (MDR) for each one of the experiments carried out. The second approach used was based on the assumption that the mutual impact in each mixture of two drugs could be described by a best-fit model function with calculation of weight (regression coefficient or other model parameter) for each of the participants in the mixture or by correlation analysis. It was shown that the sign and the absolute value of the weight or the correlation coefficient could be a reliable measure for the impact of either drug A on drug B or, vice versa, of B on A. Results of studies justify the statement, that both of the approaches show similar assessment of the mode of mutual interaction of the drugs studied. It was found that most of the drug mixtures exhibit independent action and quite few of the mixtures show synergic or dependent action. Copyright © 2016. Published by Elsevier B.V.

  8. Modeling and Control of a teletruck using electronic load sensing

    DEFF Research Database (Denmark)

    Hansen, Rico Hjerm; Iversen, Asger Malte; Jensen, Mads Schmidt;

    2010-01-01

    system is most commonly controlled using a hydro-mechanical control scheme called Hydraulic Load Sensing (HLS). However, with the demands for increased efficiency and controllability the HLS solutions are reaching their limits. Motivated by availability of electronic controllable fluid power...... the controller design for the ELS system, a complete model of the teletruck’s articulated arm and fluid power system is developed. To show the feasibility, a preliminary control structure for the ELS system is developed. The controller is tested on the machine, validating that features such as pump pressure...

  9. An experimental electronic model for a neuronal cell

    Science.gov (United States)

    Campos-Cantón, I.; Rangel-López, A.; Martel-Gallegos, G.; Zarazúa, S.; Vertiz-Hérnandez, A.

    2014-04-01

    Over the last two decades, the study of information transmission in living beings has acquired great relevance, because it regulates and conducts the functioning of all of the organs in the body. In information transmission pathways, the neuron plays an important role in that it receives, transmits, and processes electrical signals from different parts of the human body; these signals are transmitted as electrical impulses called action potentials, and they transmit information from one neuron to another. In this work, and with the aim of developing experiments for teaching biological processes, we implemented an electronic circuit of the neuron cell device and its mathematical model based on piecewise linear functions.

  10. Confocal Microscopy for Modeling Electron Microbeam Irradiation of Skin

    Energy Technology Data Exchange (ETDEWEB)

    Miller, John H.; Chrisler, William B.; Wang, Xihai; Sowa, Marianne B.

    2011-08-01

    For radiation exposures employing targeted sources such as particle microbeams, the deposition of energy and dose will depend on the spatial heterogeneity of the spample. Although cell structural variations are relatively minor for two-dimensional cell cultures, they can vary significantly for fully differential tissues. Employing high-resolution confocal microscopy, we have determined the spatial distribution, size, and shape of epidermal kerantinocyte nuclei for the full-thickness EpiDerm skin model (MatTek, Ashland, VA). Application of these data to claculate the microdosimetry and microdistribution of energy deposition by an electron microbeam is discussed.

  11. Adherence to guidelines for the management of local anesthetic systemic toxicity is improved by an electronic decision support tool and designated "Reader".

    Science.gov (United States)

    McEvoy, Matthew D; Hand, William R; Stoll, W David; Furse, Cory M; Nietert, Paul J

    2014-01-01

    A hardcopy or paper cognitive aid has been shown to improve performance during the management of simulated local anesthetic systemic toxicity (LAST) when given to the team leader. However, there remains room for improvement to ensure a system that can achieve perfect adherence to the published guidelines for LAST management. Recent research has shown that implementing a checklist via a designated reader may be of benefit. Accordingly, we sought to investigate the effect of an electronic decision support tool (DST) and designated "Reader" role on team performance during an in situ simulation of LAST. Participants were randomized to Reader + DST (n = 16, rDST) and Control (n = 15, memory alone). The rDST group received the assistance of a dedicated Reader on the response team who was equipped with an electronic DST. The primary outcome measure was adherence to guidelines. For overall and critical percent correct scores, the rDST group scored higher than Control (99.3% vs 72.2%, P Reader with an electronic DST improved adherence to guidelines in the management of an in situ simulation of LAST. Such tools are promising in the future of medicine, but further research is needed to ensure the best methods for implementing them in the clinical arena.

  12. Toxicity evaluation of e-juice and its soluble aerosols generated by electronic cigarettes using recombinant bioluminescent bacteria responsive to specific cellular damages.

    Science.gov (United States)

    Bharadwaj, Shiv; Mitchell, Robert J; Qureshi, Anjum; Niazi, Javed H

    2017-04-15

    Electronic-cigarettes (e-cigarette) are widely used as an alternative to traditional cigarettes but their safety is not well established. Herein, we demonstrate and validate an analytical method to discriminate the deleterious effects of e-cigarette refills (e-juice) and soluble e-juice aerosol (SEA) by employing stress-specific bioluminescent recombinant bacterial cells (RBCs) as whole-cell biosensors. These RBCs carry luxCDABE-operon tightly controlled by promoters that specifically induced to DNA damage (recA), superoxide radicals (sodA), heavy metals (copA) and membrane damage (oprF). The responses of the RBCs following exposure to various concentrations of e-juice/SEA was recorded in real-time that showed dose-dependent stress specific-responses against both the e-juice and vaporized e-juice aerosols produced by the e-cigarette. We also established that high doses of e-juice (4-folds diluted) lead to cell death by repressing the cellular machinery responsible for repairing DNA-damage, superoxide toxicity, ion homeostasis and membrane damage. SEA also caused the cellular damages but the cells showed enhanced bioluminescence expression without significant growth inhibition, indicating that the cells activated their global defense system to repair these damages. DNA fragmentation assay also revealed the disintegration of total cellular DNA at sub-toxic doses of e-juice. Despite their state of matter, the e-juice and its aerosols induce cytotoxicity and alter normal cellular functions, respectively that raises concerns on use of e-cigarettes as alternative to traditional cigarette. The ability of RBCs in detecting both harmful effects and toxicity mechanisms provided a fundamental understanding of biological response to e-juice and aerosols.

  13. Electronic Processes at Organic−Organic Interfaces: Insight from Modeling and Implications for Opto-electronic Devices †

    KAUST Repository

    Beljonne, David

    2011-02-08

    We report on the recent progress achieved in modeling the electronic processes that take place at interfaces between π-conjugated materials in organic opto-electronic devices. First, we provide a critical overview of the current computational techniques used to assess the morphology of organic: organic heterojunctions; we highlight the compromises that are necessary to handle large systems and multiple time scales while preserving the atomistic details required for subsequent computations of the electronic and optical properties. We then review some recent theoretical advances in describing the ground-state electronic structure at heterojunctions between donor and acceptor materials and highlight the role played by charge-transfer and long-range polarization effects. Finally, we discuss the modeling of the excited-state electronic structure at organic:organic interfaces, which is a key aspect in the understanding of the dynamics of photoinduced electron-transfer processes. © 2010 American Chemical Society.

  14. Ana insect model for assessing arsenic toxicity: Arsenic elevated glutathione content in the musca domestica and trichoplusia ni

    Energy Technology Data Exchange (ETDEWEB)

    Zaman, K.; Pardini, R.S. [Univ. of Nevada, Reno, NV (United States)

    1995-12-01

    Throughout history, arsenic has acquired an unparalled reputation as a poison. Arsenic was used as a poison as early as 2000 B.C. The toxicity of arsenic (As) extends to mammals, fish, insects, plants and fungi. According to epidemiological evidence, inorganic arsenic compounds have been strongly suggested as human carcinogens. Human exposure to arsenic through various means is correlated with an increased incidence of skin, lung, and possibly liver cancers. Inorganic trivalent arsenic is systematically more poisonous than the pentavalent form and it is possible that pentavalent arsenic is reduced to the trivalent form before exerting any toxic effects. This study focuses on the potential to use two insect species, the housefly, Musca domestica and the cabbage looper moth, Trichoplusia ni, and a model for the study of arsenic toxicity. After 48 hours of exposure to Arsenic, a significant induction of Glutathione level and subsequent decrease in the level of GSSG in both species were observed. 21 refs., 2 figs., 1 tab.

  15. Evaluation of CADASTER QSAR models for the aquatic toxicity of (benzo)triazoles and prioritisation by consensus prediction.

    Science.gov (United States)

    Cassani, Stefano; Kovarich, Simona; Papa, Ester; Roy, Partha Pratim; Rahmberg, Magnus; Nilsson, Sara; Sahlin, Ullrika; Jeliazkova, Nina; Kochev, Nikolay; Pukalov, Ognyan; Tetko, Igor; Brandmaier, Stefan; Durjava, Mojca Kos; Kolar, Boris; Peijnenburg, Willie; Gramatica, Paola

    2013-03-01

    QSAR regression models of the toxicity of triazoles and benzotriazoles ([B]TAZs) to an alga (Pseudokirchneriella subcapitata), Daphnia magna and a fish (Onchorhynchus mykiss), were developed by five partners in the FP7-EU Project, CADASTER. The models were developed by different methods - Ordinary Least Squares (OLS), Partial Least Squares (PLS), Bayesian regularised regression and Associative Neural Network (ASNN) - by using various molecular descriptors (DRAGON, PaDEL-Descriptor and QSPR-THESAURUS web). In addition, different procedures were used for variable selection, validation and applicability domain inspection. The predictions of the models developed, as well as those obtained in a consensus approach by averaging the data predicted from each model, were compared with the results of experimental tests that were performed by two CADASTER partners. The individual and consensus models were able to correctly predict the toxicity classes of the chemicals tested in the CADASTER project, confirming the utility of the QSAR approach. The models were also used for the prediction of aquatic toxicity of over 300 (B)TAZs, many of which are included in the REACH pre-registration list, and were without experimental data. This highlights the importance of QSAR models for the screening and prioritisation of untested chemicals, in order to reduce and focus experimental testing. 2013 FRAME.

  16. Electronic microscopy evidence for mitochondria as targets for Cd/Se/Te-based quantum dot 705 toxicity in vivo

    Directory of Open Access Journals (Sweden)

    Chia-Hua Lin

    2012-07-01

    Full Text Available The safety of quantum dots (QDs 705 was evaluated in this study. Mice were treated with QD705 (intravenous at a single dose of (40 pmol for 4, 12, 16, and 24 weeks. Effects of QD705 on kidneys were examined. While there was a lack of histopathology, reduction in renal functions was detected at 16 weeks. Electron microscopic examination revealed alterations in proximal convoluted tubule (PCT cell mitochondria at even much earlier time, including disorientation and reduction of mitochondrial number (early change, mitochondrial swelling, and later compensatory mitochondrial hypertrophy (enlargement mitochondria: giant mitochondria with hyperplastic inner cristae as well as mitochondrial hyperplasia (increase in mitochondrial biogenesis and numbers were observed. Such changes probably represent compensatory attempts of the mitochondria for functional loss or reduction of mitochondria in QD705 treated animals. Moreover, degeneration of mitochondria (myelin-figure and cytoplasmic membranous body formation and degradation of cytoplasmic materials (isolated cytoplasmic pockets of degenerated materials and focal cytoplasmic degradation also occurred in later time points (16–24 weeks. Such mitochondrial changes were not identical with those induced by pure cadmium. Taken together, we suggest that mitochondria appeared to be the target of QD705 toxicity and specific mitochondrial markers may be useful parameters for toxicity assessments of QDs or other metal-based nanomaterials.

  17. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  18. Atmospheric ionization induced by precipitating electrons: Comparison of CRAC:EPII model with a parametrization model

    Science.gov (United States)

    Artamonov, A. A.; Mishev, A. L.; Usoskin, I. G.

    2016-11-01

    Results of a comparison of a new model CRAC:EPII (Cosmic Ray Atmospheric Cascade: Electron Precipitation Induced Ionization) with a commonly used parametric model of atmospheric ionization is presented. The CRAC:EPII is based on a Monte Carlo simulation of precipitating electrons propagation and interaction with matter in the Earth's atmosphere. It explicitly considers energy deposit: ionization, pair production, Compton scattering, generation of Bremsstrahlung high energy photons, photo-ionization and annihilation of positrons, multiple scattering as physical processes accordingly. Propagation of precipitating electrons and their interactions with air is simulated with the GEANT4 simulation tool PLANETOCOSMICS code using NRLMSISE-00 atmospheric model. Ionization yields are computed and compared with a parametrization model for different energies of incident precipitating energetic electrons, using simulated fluxes of mono-energetic particles. A good agreement between the two models is achieved in the mesosphere but the contribution of Bremsstrahlung in the stratosphere, which is not accounted for in the parametric models, is found significant. As an example, we calculated profiles of the ion production rates in the middle and upper atmosphere (below 100 km) on the basis of balloon-born measured spectra of precipitating electrons for 30-October-2002 and 07-January-2004.

  19. Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models

    Directory of Open Access Journals (Sweden)

    Maggie Folkesson

    2016-07-01

    Full Text Available Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development.

  20. Use of the Biotic Ligand Model to predict metal toxicity to aquatic biota in areas of differing geology

    Science.gov (United States)

    Smith, Kathleen S.

    2005-01-01

    This work evaluates the use of the biotic ligand model (BLM), an aquatic toxicity model, to predict toxic effects of metals on aquatic biota in areas underlain by different rock types. The chemical composition of water, soil, and sediment is largely derived from the composition of the underlying rock. Geologic source materials control key attributes of water chemistry that affect metal toxicity to aquatic biota, including: 1) potentially toxic elements, 2) alkalinity, 3) total dissolved solids, and 4) soluble major elements, such as Ca and Mg, which contribute to water hardness. Miller (2002) compiled chemical data for water samples collected in watersheds underlain by ten different rock types, and in a mineralized area in western Colorado. He found that each rock type has a unique range of water chemistry. In this study, the ten rock types were grouped into two general categories, igneous and sedimentary. Water collected in watersheds underlain by sedimentary rock has higher mean pH, alkalinity, and calcium concentrations than water collected in watersheds underlain by igneous rock. Water collected in the mineralized area had elevated concentrations of calcium and sulfate in addition to other chemical constituents. Miller's water-chemistry data were used in the BLM (computer program) to determine copper and zinc toxicity to Daphnia magna. Modeling results show that waters from watersheds underlain by different rock types have characteristic ranges of predicted LC 50 values (a measurement of aquatic toxicity) for copper and zinc, with watersheds underlain by igneous rock having lower predicted LC 50 values than watersheds underlain by sedimentary rock. Lower predicted LC 50 values suggest that aquatic biota in watersheds underlain by igneous rock may be more vulnerable to copper and zinc inputs than aquatic biota in watersheds underlain by sedimentary rock. For both copper and zinc, there is a trend of increasing predicted LC 50 values with increasing dissolved

  1. Protein folding: the optically induced electronic excitations model

    Energy Technology Data Exchange (ETDEWEB)

    Jeknic-Dugic, J [Department of Physics, Faculty of Science, Nis (Serbia)], E-mail: jjeknic@pmf.ni.ac.yu

    2009-07-15

    The large-molecules conformational transitions problem (the 'protein folding problem') is an open issue of vivid current science research work of fundamental importance for a number of modern science disciplines as well as for nanotechnology. Here, we elaborate the recently proposed quantum-decoherence-based approach to the issue. First, we emphasize a need for detecting the elementary quantum mechanical processes (whose combinations may give a proper description of the realistic experimental situations) and then we design such a model. As distinct from the standard approach that deals with the conformation system, we investigate the optically induced transitions in the molecule electrons system that, in effect, may give rise to a conformation change in the molecule. Our conclusion is that such a model may describe the comparatively slow conformational transitions.

  2. The Dismantling of the Japanese Model in Consumer Electronics

    DEFF Research Database (Denmark)

    Frøslev Christensen, Jens; Holm Olesen, Michael; Kjær, Jonas

    This paper addresses an issue of great importance for the future organization of the consumerelectronics industry: the "battle" of control over component-based digitization. We are now witnessing the dismantling of the Japanese Model that has prevailed in consumer electronicsover the past 30 year...... technology. Aframework is developed to explain the reluctance of most of the large consumer electronicsgiants in developing/adopting this new technology.Key words: Consumer electronics, Industrial dynamics, Open InnovationJEL Codes: L6, L68, O32......This paper addresses an issue of great importance for the future organization of the consumerelectronics industry: the "battle" of control over component-based digitization. We are now witnessing the dismantling of the Japanese Model that has prevailed in consumer electronicsover the past 30 years...

  3. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  4. Insects as biological models to assay spider and scorpion venom toxicity

    Directory of Open Access Journals (Sweden)

    M. F. Manzoli-Palma

    2003-01-01

    Full Text Available This study was undertaken to develop an experimental protocol using insects as biological models to assay venom toxicity of the following spiders Loxosceles gaucho, Phoneutria nigriventer, Nephilengys cruentata and Tityus serrulatus scorpion. Three different insect species were bioassayed: Apis mellifera (Hymenoptera, Grillus assimilis (Orthoptera, and Diatraea saccharalis (Lepidoptera. Venoms were injected into the hemocele of insects with a microsyringe at concentrations that caused dose/weight-dependent effects; doses causing either paralysis (ED50 or death (LD50 were recorded for each venom and insect test-species. T. serrulatus and L. gaucho venoms were lethal to all tested species, while P. nigriventer venom caused paralysis and death, and N. cruentata venom caused only paralysis at the doses assayed. A comparison between the insect test species described above revealed that A. mellifera was highly sensitive to all venoms tested; even a tiny amount of N. cruentata non-lethal venom caused a change in the walking pattern leading to transient paralysis. D. saccharalis larvae were very resistant to all four venoms.

  5. Onset of streptococcal toxic shock syndrome is accelerated by bruising in a mouse model.

    Science.gov (United States)

    Seki, Masanori; Saito, Mitsumasa; Iida, Ken-Ichiro; Taniai, Hiroaki; Soejima, Takashi; Nakayama, Hiroaki; Yoshida, Shin-Ichi

    2008-04-01

    Streptococcal toxic shock syndrome (STSS) is the severest form of human infections caused by Streptococcus pyogenes. In our animal model of STSS [Saito M, Kajiwara H, Ishikawa T, et al. Delayed onset of systemic bacterial dissemination and subsequent death in mice injected intramuscularly with Streptococcus pyogenes. Microbiol Immunol 2001;45:777-86], mice inoculated intramuscularly with S. pyogenes strains initially suffer from a short illness, then recover and remain healthy for about 20 days, and finally become sick and incur a sudden death. Here we report that the death during the convalescent period was facilitated by artificially bruising an extremity remote from the site of the initial inoculation. Bacterial burden was found to be higher in the bruised site than in a non-bruised control extremity of each mouse examined. Bacteremia started to occur approximately 20 days after infection. These findings imply that a fresh bruise serves as a focus for bacterial multiplication in the presence of bacteremia, thereby facilitating the development of STSS.

  6. Genetic Mechanisms of Coffee Extract Protection in a Caenorhabditis elegans Model of β-Amyloid Peptide Toxicity

    OpenAIRE

    Dostal, Vishantie; Roberts, Christine M; Link, Christopher D

    2010-01-01

    Epidemiological studies have reported that coffee and/or caffeine consumption may reduce Alzheimer's disease (AD) risk. We found that coffee extracts can similarly protect against β-amyloid peptide (Aβ) toxicity in a transgenic Caenorhabditis elegans Alzheimer's disease model. The primary protective component(s) in this model is not caffeine, although caffeine by itself can show moderate protection. Coffee exposure did not decrease Aβ transgene expression and did not need to be present during...

  7. Weighted Feature Significance: A Simple, Interpretable Model of Compound Toxicity Based on the Statistical Enrichment of Structural Features

    OpenAIRE

    Huang, Ruili; Southall, Noel; Xia, Menghang; Cho, Ming-Hsuang; Jadhav, Ajit; Nguyen, Dac-Trung; Inglese, James; Tice, Raymond R.; Austin, Christopher P.

    2009-01-01

    In support of the U.S. Tox21 program, we have developed a simple and chemically intuitive model we call weighted feature significance (WFS) to predict the toxicological activity of compounds, based on the statistical enrichment of structural features in toxic compounds. We trained and tested the model on the following: (1) data from quantitative high–throughput screening cytotoxicity and caspase activation assays conducted at the National Institutes of Health Chemical Genomics Center, (2) dat...

  8. Reliable modeling of the electronic spectra of realistic uranium complexes

    Science.gov (United States)

    Tecmer, Paweł; Govind, Niranjan; Kowalski, Karol; de Jong, Wibe A.; Visscher, Lucas

    2013-07-01

    We present an EOMCCSD (equation of motion coupled cluster with singles and doubles) study of excited states of the small [UO2]2+ and [UO2]+ model systems as well as the larger UVIO2(saldien) complex. In addition, the triples contribution within the EOMCCSDT and CR-EOMCCSD(T) (completely renormalized EOMCCSD with non-iterative triples) approaches for the [UO2]2+ and [UO2]+ systems as well as the active-space variant of the CR-EOMCCSD(T) method—CR-EOMCCSd(t)—for the UVIO2(saldien) molecule are investigated. The coupled cluster data were employed as benchmark to choose the "best" appropriate exchange-correlation functional for subsequent time-dependent density functional (TD-DFT) studies on the transition energies for closed-shell species. Furthermore, the influence of the saldien ligands on the electronic structure and excitation energies of the [UO2]+ molecule is discussed. The electronic excitations as well as their oscillator dipole strengths modeled with TD-DFT approach using the CAM-B3LYP exchange-correlation functional for the [UVO2(saldien)]- with explicit inclusion of two dimethyl sulfoxide molecules are in good agreement with the experimental data of Takao et al. [Inorg. Chem. 49, 2349 (2010), 10.1021/ic902225f].

  9. Modelling the cosmic ray electron propagation in M 51

    CERN Document Server

    Mulcahy, D D; Beck, R; Mitra, D; Scaife, A M M

    2016-01-01

    Cosmic ray electrons (CREs) are a crucial part of the ISM and are observed via synchrotron emission. While much modelling has been carried out on the CRE distribution and propagation of the Milky Way, little has been done on normal external star-forming galaxies. Recent spectral data from a new generation of radio telescopes enable us to find more robust estimations of the CRE propagation. We model the synchrotron spectral index of M 51 using the time-dependent diffusion energy-loss equation and to compare the model results with the observed spectral index determined from recent low-frequency observations with LOFAR. This is the first time that this model for CRE propagation has been solved for a realistic distribution of CRE sources, which we derive from the observed star formation rate, in an external galaxy. The radial variation of the synchrotron spectral index and scale-length produced by the model are compared to recent LOFAR and older VLA observational data and also to new observations of M 51 at 325MH...

  10. Evaluation of cationic polyamidoamine dendrimers’ dermal toxicity in the rat skin model

    Directory of Open Access Journals (Sweden)

    Winnicka K

    2015-03-01

    Full Text Available Katarzyna Winnicka,1 Magdalena Wroblewska,1 Katarzyna Sosnowska,1 Halina Car,2 Irena Kasacka3 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Bialystok, Bialystok, Poland; 2Department of Experimental Pharmacology, Faculty of Health Sciences, Medical University of Bialystok, Bialystok, Poland; 3Department of Histology and Cytophysiology, Faculty of Pharmacy, Medical University of Bialystok, Bialystok, Poland Abstract: Polyamidoamine (PAMAM dendrimers are multi-branched, three-dimensional polymers with unique architecture, which makes these molecules attractive for medical and pharmaceutical applications. Using PAMAM as drug carriers for topical delivery might be beneficial as they only produce a transient effect without skin irritation. To evaluate the dermal toxicity of cationic PAMAM dendrimers generation 2 and generation 3, skin irritation studies were performed in vivo in the rat skin model. After 10 days topical application of various concentrations of PAMAM-NH2 (0.3 mg/mL, 3 mg/mL, 6 mg/mL, 30 mg/mL, 300 mg/mL, skin irritation was evaluated by visual, histopathological, and immunohistochemical examination. Microscopic assessment after hematoxylin-eosin staining revealed significant morphological changes of epidermal cells after application of PAMAM-NH2 at a concentration of ≥6 mg/mL. Morphological alterations of epidermal cells included cytoplasmic vacuolization of keratinocytes in the basal and spinous layers. Cytomorphological changes in keratinocytes, overall picture of the epidermis, and histopathological changes in the dermis were dose dependent. Detected alterations concerned hyperplasia of connective tissue fibers and leukocyte infiltration. Visible granulocyte infiltration in the upper dermis and sockets formed by necrotic, cornified cells in the hyperplastic foci of epithelium were also noted. Immunohistochemical analyses revealed that increased nuclear immunoreactivity to PCNA correlated with

  11. Modeling of electron-electron collisions for particle-in-cell simulations

    Energy Technology Data Exchange (ETDEWEB)

    Andrea, D. d' ; Munz, C.D.; Schneider, R.

    2006-09-15

    The modeling of the physics of pulsed plasma thrusters requires the numerical solution of the Boltzmann equation for rarefied plasma flows where continuum assumptions fail. To tackle this challenging task, a cooperation between several institutes has been formed with the goal to develop a hybrid code based on Particle-In-Cell and Direct Simulation Monte Carlo techniques. These development activities are bundled in the project ''Numerische Simulation und Auslegung eines instationaeren gepulsten magnetoplasmadynamischen Triebwerks fuer eine Mondsonde'' which is funded by the Landesstiftung Baden-Wuerttemberg within the subject area ''Modellierung und Simulation auf Hochleistungscomputern''. In the frame of this project, the IHM is in charge to develop suitable physical-mathematical and numerical models to include charged particle collisions into the simulation. which can significantly affect the Parameters of such plasma devices. The intention of the present report is to introduce the Fokker-Planck approach for electron-electron interaction in Standard charged particle simulations. where the impact Parameter is usually large resulting in a small deflection angle. The theoretical and applicative framework is discussed in detail paying particular attention to the Particle-In-Cell approach in velocity space. a new technique which allows the self-consistent computation of the friction and diffusion coefficients arising from the Fokker-Planck treatment of collisions. These velocity-dependent coefficients thernselves are responsible for the change in velocity of the simulation particles, which is determined by the numerical solution of a Langevin-type equation. Simulation results for typical numerical experiments computed with the new developed Fokker-Planck solver are presented. demonstrating the quality. property and reliability of the applied numerical methods. (orig.)

  12. Computational studies of model disordered and strongly correlated electronic systems

    Science.gov (United States)

    Johri, Sonika

    The theory of non-interacting electrons in perfect crystals was completed soon after the advent of quantum mechanics. Though capable of describing electron behaviour in most simple solid state physics systems, this approach falls woefully short of describing condensed matter systems of interest today, and designing the quantum devices of the future. The reason is that nature is never free of disorder, and emergent properties arising from interactions can be clearly seen in the pure, low-dimensional materials that can be engineered today. In this thesis, I address some salient problems in disordered and correlated electronic systems using modern numerical techniques like sparse matrix diagonalization, density matrix renormalization group (DMRG), and large disorder renormalization group (LDRG) methods. The pioneering work of P. W. Anderson, in 1958, led to an understanding of how an electron can stop diffusing and become localized in a region of space when a crystal is sufficiently disordered. Thus disorder can lead to metal-insulator transitions, for instance, in doped semiconductors. Theoretical research on the Anderson disorder model since then has mostly focused on the localization-delocalization phase transition. The localized phase in itself was not thought to exhibit any interesting physics. Our work has uncovered a new singularity in the disorder-averaged inverse participation ratio of wavefunctions within the localized phase, arising from resonant states. The effects of system size, dimension and disorder distribution on the singularity have been studied. A novel wavefunction-based LDRG technique has been designed for the Anderson model which captures the singular behaviour. While localization is well established for a single electron in a disordered potential, the situation is less clear in the case of many interacting particles. Most studies of a many-body localized phase are restricted to a system which is isolated from its environment. Such a condition

  13. Multi-Information Model for PCB-Based ElectronicsProduct Manufacturing

    Institute of Scientific and Technical Information of China (English)

    李春泉; 周德俭; 余涛

    2004-01-01

    Most electronics products use PCB to carry electronic circuits. This paper classifies information contained in PCB-based electronic circuits into several models: geometry model, physics model, performance model and function model. Based on this classification, a multi-information model of product is established. A composite model of product is also created based on object-orientation and characteristics of the product. The model includes a 3D geometry model, a physics model with integrated information that can be divided into microscopic and macroscopic information, a generalized performance model and a function model that are from top to bottom. Finally, a multi-unit analysis is briefly discussed.

  14. Establishing a Th17 based mouse model for preclinical assessment of the toxicity of candidate microbicides

    Institute of Scientific and Technical Information of China (English)

    LI Liang-zhu; YANG Yu; YUAN Song-hua; WAN Yan-min; QIU Chao; FENG Yan-ling; XU Jian-qing; ZHANG Xiao-yan

    2010-01-01

    Background To effectively block the invasion of human immunodeficiency virus (HIV)-1 on mucosal surface, vaginal anti-HIV-1 microbicides should avoid inflammatory responses and disruption of mucosa integrity because these will facilitate transepithelial viral penetration and replication. However, existing models fail to predict and evaluate vaginal mucosal toxicity induced by microbicides, and most importantly, they are unable to identify subtle or subclinical inflammatory reactions. This study was designed to develop a cost-effective in vivo model to evaluate microbicide safety in a preclinical study which can recapitulate the mucosal topical reaction.Methods A murine model was employed with nonoxynol-9 (N-9) as the topical stimulant within the vagina. Different concentrations of N-9 (1%, 3%, and 4%) were topically applied to the vagina for five consecutive days. A panel of inflammatory cytokines including interleukine-2 (IL-2), IL-4, IL-6, IL-17A, interferon-Y (IFN-Y), tumor necrosis factor-α (TNF-α), and immuno-regulatory IL-10 were assayed in vaginal lavage. Cytokines were quantified by using cytometric bead array (CBA) and reverse transcript (RT) real-time PCR. Histopathological evaluation of vaginal tissues was conducted on hematoxylin-eosin stained slides and scored with a semi-quantitative system according to the severity of epithelial disruption, leucocyte infiltration, edema, and vascular injection. The association between the cytokines and histopathological scores was assessed by linear regression analysis.Results All three concentrations of N-9 induced inflammatory cytokine production. The 4% N-9 application resulted in a consistent production of cytokines in a time-dependent manner. The cytokines reached peak expression on day three with the exception of IL-4 which reached its peak on day one. Histopathological examination of 4% N-9 treated cervicovaginal tissues on day three showed intensive damage in four mice (sores: 10-13) and moderate damage in

  15. Application of Bayesian Network modeling on the stability and toxicity of engineered nanomaterials in aquatic ecosystems

    CSIR Research Space (South Africa)

    Ondiaka, M

    2013-08-01

    Full Text Available The stability of engineered nanomaterials (ENMs) in the aquatic systems influences their eventual interactions with aquatic biota – and subsequently the observed toxic effects. Increasing data suggests that physicochemical properties of ENMs...

  16. Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function

    Directory of Open Access Journals (Sweden)

    Swapnalee Sarmah

    2016-12-01

    Full Text Available Environmental pollution is a serious problem of the modern world that possesses a major threat to public health. Exposure to environmental pollutants during embryonic development is particularly risky. Although many pollutants have been verified as potential toxicants, there are new chemicals in the environment that need assessment. Heart development is an extremely sensitive process, which can be affected by environmentally toxic molecule exposure during embryonic development. Congenital heart defects are the most common life-threatening global health problems, and the etiology is mostly unknown. The zebrafish has emerged as an invaluable model to examine substance toxicity on vertebrate development, particularly on cardiac development. The zebrafish offers numerous advantages for toxicology research not found in other model systems. Many laboratories have used the zebrafish to study the effects of widespread chemicals in the environment on heart development, including pesticides, nanoparticles, and various organic pollutants. Here, we review the uses of the zebrafish in examining effects of exposure to external molecules during embryonic development in causing cardiac defects, including chemicals ubiquitous in the environment and illicit drugs. Known or potential mechanisms of toxicity and how zebrafish research can be used to provide mechanistic understanding of cardiac defects are discussed.

  17. Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function

    Science.gov (United States)

    Sarmah, Swapnalee; Marrs, James A.

    2016-01-01

    Environmental pollution is a serious problem of the modern world that possesses a major threat to public health. Exposure to environmental pollutants during embryonic development is particularly risky. Although many pollutants have been verified as potential toxicants, there are new chemicals in the environment that need assessment. Heart development is an extremely sensitive process, which can be affected by environmentally toxic molecule exposure during embryonic development. Congenital heart defects are the most common life-threatening global health problems, and the etiology is mostly unknown. The zebrafish has emerged as an invaluable model to examine substance toxicity on vertebrate development, particularly on cardiac development. The zebrafish offers numerous advantages for toxicology research not found in other model systems. Many laboratories have used the zebrafish to study the effects of widespread chemicals in the environment on heart development, including pesticides, nanoparticles, and various organic pollutants. Here, we review the uses of the zebrafish in examining effects of exposure to external molecules during embryonic development in causing cardiac defects, including chemicals ubiquitous in the environment and illicit drugs. Known or potential mechanisms of toxicity and how zebrafish research can be used to provide mechanistic understanding of cardiac defects are discussed. PMID:27999267

  18. The MICROSCOPE Inertial sensors and their flight models electronics

    Science.gov (United States)

    Touboul, Pierre; Boulanger, Damien; Liorzou, Françoise

    2012-07-01

    Dedicated space inertial sensors have been developed for the payload of the MICROSCOPE mission which scientific objective is the test of the universality of free fall at level better than 10-15. This accuracy requires the operation of four inertial sensors on board a specific drag-free satellite, exhibiting resolution of better than 1 femto-g for data integrating period over 20 orbits. Such an outstanding resolution requires the fine electrostatic servo-control of each sensor test mass motion, free of any perturbation along its six degrees of freedom. In addition to a very accurate geometrical sensor core, highly performing electronics architecture is necessary to provide the measurement of the weak electrostatic forces and torques applied to the mass. Capacitive sensing provides the linear and attitude motion of the mass with respect to gold coated electrodes silica parts. Charges are controlled on the electrodes all around the mass to generate adequate electrical field and so electrostatic pressures in order to maintain the mass motionless with respect to the instrument structure. Digital control laws are implemented to deal with both the instrument operation flexibility and the preservation of the weak position sensor noise. The flight model electronics units have been produced and tested. All characteristics have been verified as well as the thermal sensitivities. Description of these units and test results are presented in the paper. These electronics provide not only the scientific data for the General Relativity test but also the data for the satellite orbit and attitude control. The satellite is now under production for a launch in 2016.

  19. Atomistic modeling of electronic structure and transport in disordered nanostructures

    Science.gov (United States)

    Kharche, Neerav

    As the Si-CMOS technology approaches the end of the International Technology Roadmap for Semiconductors (ITRS), the semiconductor industry faces a formidable challenge to continue the transistor scaling according to Moore's law. To continue the scaling of classical devices, alternative channel materials such as SiGe, carbon nanotubes, nanowires, and III-V based materials are being investigated along with novel 3D device geometries. Researchers are also investigating radically new quantum computing devices, which are expected to perform calculations faster than the existing classical Si-CMOS based structures. Atomic scale disorders such as interface roughness, alloy randomness, non-uniform strain, and dopant fluctuations are routinely present in the experimental realization of such devices. These disorders now play an increasingly important role in determining the electronic structure and transport properties as device sizes enter the nanometer regime. This work employs the atomistic tight-binding technique, which is ideally suited for modeling systems with local disorders on an atomic scale. High-precision multi-million atom electronic structure calculations of (111) Si surface quantum wells and (100) SiGe/Si/SiGe heterostructure quantum wells are performed to investigate the modulation of valley splitting induced by atomic scale disorders. The calculations presented here resolve the existing discrepancies between theoretically predicted and experimentally measured valley splitting, which is an important design parameter in quantum computing devices. Supercell calculations and the zone-unfolding method are used to compute the bandstructures of inhomogeneous nanowires made of AlGaAs and SiGe and their connection with the transmission coefficients computed using non-equilibrium Green's function method is established. A unified picture of alloy nanowires emerges, in which the nanodevice (transmission) and nanomaterials (bandstructure) viewpoints complement each other

  20. Review of Quantitative Structure - Activity Relationships for Acute Mammalian Toxicity

    Directory of Open Access Journals (Sweden)

    Iglika Lessigiarska

    2006-12-01

    Full Text Available This paper reviews Quantitative Structure-Activity Relationship (QSAR models for acute mammalian toxicity published in the last decade. A number of QSAR models based on cytotoxicity data from mammalian cell lines are also included because of their possible use as a surrogate system for predicting acute toxicity to mammals. On the basis of the review, the following conclusions can be made: i a relatively small number of models for in vivo toxicity are published in the literature. This is due to the nature of the endpoint - acute systemic toxicity is usually related to whole body phenomena and therefore is very complex. The complexity of the mechanisms involved leads to difficulties in the QSAR modelling; ii most QSAR models identify hydrophobicity as a parameter of high importance for the modelled toxicity. In addition, many models indicate the role of the electronic and steric effects; iii most of the literature-based models are restricted to single chemical classes. Models based on more heterogeneous data sets are those incorporated in expert systems. In general, the QSAR models for mammalian toxicity identified in this review are considered useful for investigating the mechanisms of toxicity of defined chemical classes. However, for predictive purposes in the regulatory assessment of chemicals most of the models require additional information to satisfy internationally agreed validation principles. In addition, the development of new models covering larger chemical domains would be useful for the regulatory assessment of chemicals.

  1. Use of a statistical model to predict the potential for repeated dose and developmental toxicity of dermally administered crude oil and relation to reproductive toxicity.

    Science.gov (United States)

    McKee, Richard H; Nicolich, Mark; Roy, Timothy; White, Russell; Daughtrey, Wayne C

    2014-01-01

    Petroleum (commonly called crude oil) is a complex substance primarily composed of hydrocarbon constituents. Based on the results of previous toxicological studies as well as occupational experience, the principal acute toxicological hazards are those associated with exposure by inhalation to volatile hydrocarbon constituents and hydrogen sulfide, and chronic hazards are associated with inhalation exposure to benzene and dermal exposure to polycyclic aromatic compounds. The current assessment was an attempt to characterize the potential for repeated dose and/or developmental effects of crude oils following dermal exposures and to generalize the conclusions across a broad range of crude oils from different sources. Statistical models were used to predict the potential for repeated dose and developmental toxicity from compositional information. The model predictions indicated that the empirical data from previously tested crude oils approximated a "worst case" situation, and that the data from previously tested crude oils could be used as a reasonable basis for characterizing the repeated dose and developmental toxicological hazards of crude oils in general.

  2. Monte Carlo modeling of ion beam induced secondary electrons

    Energy Technology Data Exchange (ETDEWEB)

    Huh, U., E-mail: uhuh@vols.utk.edu [Biochemistry & Cellular & Molecular Biology, University of Tennessee, Knoxville, TN 37996-0840 (United States); Cho, W. [Electrical and Computer Engineering, University of Tennessee, Knoxville, TN 37996-2100 (United States); Joy, D.C. [Biochemistry & Cellular & Molecular Biology, University of Tennessee, Knoxville, TN 37996-0840 (United States); Center for Nanophase Materials Science, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States)

    2016-09-15

    Ion induced secondary electrons (iSE) can produce high-resolution images ranging from a few eV to 100 keV over a wide range of materials. The interpretation of such images requires knowledge of the secondary electron yields (iSE δ) for each of the elements and materials present and as a function of the incident beam energy. Experimental data for helium ions are currently limited to 40 elements and six compounds while other ions are not well represented. To overcome this limitation, we propose a simple procedure based on the comprehensive work of Berger et al. Here we show that between the energy range of 10–100 keV the Berger et al. data for elements and compounds can be accurately represented by a single universal curve. The agreement between the limited experimental data that is available and the predictive model is good, and has been found to provide reliable yield data for a wide range of elements and compounds. - Highlights: • The Universal ASTAR Yield Curve was derived from data recently published by NIST. • IONiSE incorporated with the Curve will predict iSE yield for elements and compounds. • This approach can also handle other ion beams by changing basic scattering profile.

  3. A Model of Electron-Positron Pair Formation

    Directory of Open Access Journals (Sweden)

    Lehnert B.

    2008-01-01

    Full Text Available The elementary electron-positron pair formation process is consideredin terms of a revised quantum electrodynamic theory, with specialattention to the conservation of energy, spin, and electric charge.The theory leads to a wave-packet photon model of narrow line widthand needle-radiation properties, not being available from conventionalquantum electrodynamics which is based on Maxwell's equations. Themodel appears to be consistent with the observed pair productionprocess, in which the created electron and positron form two raysthat start within a very small region and have original directionsalong the path of the incoming photon. Conservation of angular momentum requires the photon to possess a spin, as given by the present theory but not by the conventional one. The nonzero electric field divergence further gives rise to a local intrinsic electric charge density within the photon body, whereas there is a vanishing total charge of the latter. This may explain the observed fact that the photon decays on account of the impact from an external electric field. Such a behaviour should not become possible for a photon having zero local electric charge density.

  4. Model of Improving Customer Loyalty in Electronic Stores

    Directory of Open Access Journals (Sweden)

    Ali Attafar

    2011-12-01

    Today, due to the growth and diversity of e-commerce technologies, the number of virtual stores is exponentially increasing and this has created new challenges in business. Therefore, improving customer loyalty is critically important for sustaining success of electronic stores. In this regard, an attempt has been made to propose an appropriate model for improving loyalty of customers in electronic stores. The study population includes faculty and students of Yazd University who have had experience of buying books from online bookstores. Due to non-normal distribution of data, nonparametric methods (sign test, Mann-Whitney, Friedman and Kruskal-Wallis have been used for data analysis. Findings imply that 21 components have been extracted in three general categories, i.e. customer service, design and trust influence e-loyalty, which explain totally 70% of the structure of factors influencing e-loyalty in online bookstores. Findings indicate that from the viewpoint of faculty and students of Yazd University, indicators related to "trust" have the highest influence on improving e-loyalty.

  5. Model of Improving Customer Loyalty in Electronic Stores

    Directory of Open Access Journals (Sweden)

    Ali Atafar

    2011-01-01

    Full Text Available Today, due to the growth and diversity of e-commerce technologies, the number of virtual stores is exponentially increasing and this has created new challenges in business. Therefore, improving customer loyalty is critically important for sustaining success of electronic stores. In this regard, an attempt has been made to propose an appropriate model for improving loyalty of customers in electronic stores. The study population includes faculty and students of Yazd University who have had experience of buying books from online bookstores. Due to non-normal distribution of data, nonparametric methods (sign test, Mann-Whitney, Friedman and Kruskal-Wallis have been used for data analysis. Findings imply that 21 components have been extracted in three general categories, i.e. customer service, design and trust influence e-loyalty, which explain totally 70% of the structure of factors influencing e-loyalty in online bookstores. Findings indicate that from the viewpoint of faculty and students of Yazd University, indicators related to "trust" have the highest influence on improving e-loyalty.

  6. A proposed model of e-trust for electronic banking

    Directory of Open Access Journals (Sweden)

    Neda Yousefi

    2015-11-01

    Full Text Available Customer’s trust is the most important and one of the key factors of success in e-commerce. However, trust is the essential aspects of e-banking adoption and the main element for building long-term relationships with the bank's customers. So the purpose of this research is to investigate the factors influencing on customer′s trust in e-banking services and prioritize them. Therefore, designed questionnaire was distributed among 177 electronic service customers in number of banks in the city of Karaj, Iran. Likert quintuplet scales were used to measure the variables. After collecting the questionnaires, the data were analyzed by structural equation modeling (by using LISREL 8.5. The results revealed that quality of electronic services such as ease of use, privacy and security, individual characteristics of customers such as disposition to trust and features of bank such as reputation, size and dependence on government, have had the greatest effect on customer′s trust in e-banking services.

  7. Numerical model of electron cyclotron resonance ion source

    Directory of Open Access Journals (Sweden)

    V. Mironov

    2015-12-01

    Full Text Available Important features of the electron cyclotron resonance ion source (ECRIS operation are accurately reproduced with a numerical code. The code uses the particle-in-cell technique to model the dynamics of ions in ECRIS plasma. It is shown that a gas dynamical ion confinement mechanism is sufficient to provide the ion production rates in ECRIS close to the experimentally observed values. Extracted ion currents are calculated and compared to the experiment for a few sources. Changes in the simulated extracted ion currents are obtained with varying the gas flow into the source chamber and the microwave power. Empirical scaling laws for ECRIS design are studied and the underlying physical effects are discussed.

  8. Bioenergetics-based matrix population modeling enhances life-cycle toxicity assessment of tilapia Oreochromis mossambicus exposed to arsenic.

    Science.gov (United States)

    Liao, Chung-Min; Chiang, Kuo-Chih; Tsai, Jeng-Wei

    2006-04-01

    The objective of this study was to integrate a bioenergetics-based modeling approach into a population stage structure to enhance life-cycle toxicity assessments of the effects of waterborne arsenic (As) on the population dynamics of the tilapia Oreochromis mossambicus. The proposed mathematical model links a Leslie matrix population model and a universal ontogenetic growth model embedding the population-level growth rate and stage-specific modes of toxic action. We present data analyses of key parameters and distributions and discuss the processes of data capture and analysis and the impact of acute/chronic As toxicity responses on population-level effects. We employed a three-parameter Hill equation model to describe the relationship between tilapia whole-body burden and mortality in order to estimate the probability of stage-specific vital rate of survival. Using the DEBtox theory, we distinguished three modes of toxic action (MOA): direct effects on growth and indirect effects via maintenance and food consumption on inhibition by arsenic of the growth of a tilapia population. The asymptotic population growth rate decreased from lambda = 1.0027 for the control group to lambda = 0.9935 for tilapia population exposed to 4 microg mL(-1) As, indicating a potential risk of population intrinsic growth rates for tilapia exposed to higher levels of waterborne As. Our results estimated that an As concentration of 1.02 microg mL(-1) would cause a 50% reduction in the tilapia population. We found that the interplay between external stressors of waterborne As concentration and internally generated modes of action decreasing feeding in the juvenile stage and increasing the maintenance cost in the adult stage had a pronounced influence on the population stage structure of tilapia.

  9. Finite Element Models for Electron Beam Freeform Fabrication Process

    Science.gov (United States)

    Chandra, Umesh

    2012-01-01

    Electron beam freeform fabrication (EBF3) is a member of an emerging class of direct manufacturing processes known as solid freeform fabrication (SFF); another member of the class is the laser deposition process. Successful application of the EBF3 process requires precise control of a number of process parameters such as the EB power, speed, and metal feed rate in order to ensure thermal management; good fusion between the substrate and the first layer and between successive layers; minimize part distortion and residual stresses; and control the microstructure of the finished product. This is the only effort thus far that has addressed computer simulation of the EBF3 process. The models developed in this effort can assist in reducing the number of trials in the laboratory or on the shop floor while making high-quality parts. With some modifications, their use can be further extended to the simulation of laser, TIG (tungsten inert gas), and other deposition processes. A solid mechanics-based finite element code, ABAQUS, was chosen as the primary engine in developing these models whereas a computational fluid dynamics (CFD) code, Fluent, was used in a support role. Several innovative concepts were developed, some of which are highlighted below. These concepts were implemented in a number of new computer models either in the form of stand-alone programs or as user subroutines for ABAQUS and Fluent codes. A database of thermo-physical, mechanical, fluid, and metallurgical properties of stainless steel 304 was developed. Computing models for Gaussian and raster modes of the electron beam heat input were developed. Also, new schemes were devised to account for the heat sink effect during the deposition process. These innovations, and others, lead to improved models for thermal management and prediction of transient/residual stresses and distortions. Two approaches for the prediction of microstructure were pursued. The first was an empirical approach involving the

  10. Diffusion dynamics and concentration of toxic materials from quantum dots-based nanotechnologies: an agent-based modeling simulation framework

    Energy Technology Data Exchange (ETDEWEB)

    Agusdinata, Datu Buyung, E-mail: bagusdinata@niu.edu; Amouie, Mahbod [Northern Illinois University, Department of Industrial & Systems Engineering and Environment, Sustainability, & Energy Institute (United States); Xu, Tao [Northern Illinois University, Department of Chemistry and Biochemistry (United States)

    2015-01-15

    Due to their favorable electrical and optical properties, quantum dots (QDs) nanostructures have found numerous applications including nanomedicine and photovoltaic cells. However, increased future production, use, and disposal of engineered QD products also raise concerns about their potential environmental impacts. The objective of this work is to establish a modeling framework for predicting the diffusion dynamics and concentration of toxic materials released from Trioctylphosphine oxide-capped CdSe. To this end, an agent-based model simulation with reaction kinetics and Brownian motion dynamics was developed. Reaction kinetics is used to model the stability of surface capping agent particularly due to oxidation process. The diffusion of toxic Cd{sup 2+} ions in aquatic environment was simulated using an adapted Brownian motion algorithm. A calibrated parameter to reflect sensitivity to reaction rate is proposed. The model output demonstrates the stochastic spatial distribution of toxic Cd{sup 2+} ions under different values of proxy environmental factor parameters. With the only chemistry considered was oxidation, the simulation was able to replicate Cd{sup 2+} ion release from Thiol-capped QDs in aerated water. The agent-based method is the first to be developed in the QDs application domain. It adds both simplicity of the solubility and rate of release of Cd{sup 2+} ions and complexity of tracking of individual atoms of Cd at the same time.

  11. Sulfanegen Sodium Treatment in a Rabbit Model of Sub-Lethal Cyanide Toxicity

    Science.gov (United States)

    Brenner, Matthew; Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Lemor, Daniel; Ahdout, Rebecca; Boss, Gerry R.; Blackledge, William; Jann, Lauren; Nagasawa, Herbert T.; Patterson, Steven E.

    2010-01-01

    The aim of this study is to investigate the ability of intramuscular and intravenous sulfanegen sodium treatment to reverse cyanide effects in a rabbit model as a potential treatment for mass casualty resulting from cyanide exposure. Cyanide poisoning is a serious chemical threat from accidental or intentional exposures. Current cyanide exposure treatments, including direct binding agents, methemoglobin donors, and sulfur donors, have several limitations. Non-rhodanese mediated sulfur transferase pathways, including 3-mercaptopyruvate sulfurtransferase (3-MPST) catalyze the transfer of sulfur from 3-MP to cyanide, forming pyruvate and less toxic thiocyanate. We developed a water soluble 3-MP prodrug, 3-mercaptopyruvatedithiane (sulfanegen sodium), with the potential to provide a continuous supply of substrate for CN detoxification. In addition to developing a mass casualty cyanide reversal agent, methods are needed to rapidly and reliably diagnose and monitor cyanide poisoning and reversal. We use non-invasive technology, diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS) to monitor physiologic changes associated with cyanide exposure and reversal. A total of 35 animals were studied. Sulfanegen sodium was shown to reverse the effects of cyanide exposure on oxyhemoglobin and deoxyhemoglobin rapidly, significantly faster than control animals when administered by intravenous or intramuscular routes. RBC cyanide levels also returned to normal faster following both intramuscular and intravenous sulfanegen sodium treatment than controls. These studies demonstrate the clinical potential for the novel approach of supplying substrate for non-rhodanese mediated sulfur transferase pathways for cyanide detoxification. DOS and CWNIRS demonstrated their usefulness in optimizing the dose of sulfanegen sodium treatment. PMID:20705081

  12. Evaluation of cationic polyamidoamine dendrimers' dermal toxicity in the rat skin model.

    Science.gov (United States)

    Winnicka, Katarzyna; Wroblewska, Magdalena; Sosnowska, Katarzyna; Car, Halina; Kasacka, Irena

    2015-01-01

    Polyamidoamine (PAMAM) dendrimers are multi-branched, three-dimensional polymers with unique architecture, which makes these molecules attractive for medical and pharmaceutical applications. Using PAMAM as drug carriers for topical delivery might be beneficial as they only produce a transient effect without skin irritation. To evaluate the dermal toxicity of cationic PAMAM dendrimers generation 2 and generation 3, skin irritation studies were performed in vivo in the rat skin model. After 10 days topical application of various concentrations of PAMAM-NH2 (0.3 mg/mL, 3 mg/mL, 6 mg/mL, 30 mg/mL, 300 mg/mL), skin irritation was evaluated by visual, histopathological, and immunohistochemical examination. Microscopic assessment after hematoxylin-eosin staining revealed significant morphological changes of epidermal cells after application of PAMAM-NH2 at a concentration of ≥6 mg/mL. Morphological alterations of epidermal cells included cytoplasmic vacuolization of keratinocytes in the basal and spinous layers. Cytomorphological changes in keratinocytes, overall picture of the epidermis, and histopathological changes in the dermis were dose dependent. Detected alterations concerned hyperplasia of connective tissue fibers and leukocyte infiltration. Visible granulocyte infiltration in the upper dermis and sockets formed by necrotic, cornified cells in the hyperplastic foci of epithelium were also noted. Immunohistochemical analyses revealed that increased nuclear immunoreactivity to PCNA correlated with the concentration of PAMAM-NH2, but no significant differences in the cell proliferation activity in skin treated with PAMAM-NH2 generation 2 or generation 3 were observed. Significantly higher expression of PCNA extended throughout the skin layers might suggest abnormal cell proliferation, which, as a consequence, might even lead to neoplastic changes.

  13. Evaluation of cationic polyamidoamine dendrimers’ dermal toxicity in the rat skin model

    Science.gov (United States)

    Winnicka, Katarzyna; Wroblewska, Magdalena; Sosnowska, Katarzyna; Car, Halina; Kasacka, Irena

    2015-01-01

    Polyamidoamine (PAMAM) dendrimers are multi-branched, three-dimensional polymers with unique architecture, which makes these molecules attractive for medical and pharmaceutical applications. Using PAMAM as drug carriers for topical delivery might be beneficial as they only produce a transient effect without skin irritation. To evaluate the dermal toxicity of cationic PAMAM dendrimers generation 2 and generation 3, skin irritation studies were performed in vivo in the rat skin model. After 10 days topical application of various concentrations of PAMAM-NH2 (0.3 mg/mL, 3 mg/mL, 6 mg/mL, 30 mg/mL, 300 mg/mL), skin irritation was evaluated by visual, histopathological, and immunohistochemical examination. Microscopic assessment after hematoxylin-eosin staining revealed significant morphological changes of epidermal cells after application of PAMAM-NH2 at a concentration of ≥6 mg/mL. Morphological alterations of epidermal cells included cytoplasmic vacuolization of keratinocytes in the basal and spinous layers. Cytomorphological changes in keratinocytes, overall picture of the epidermis, and histopathological changes in the dermis were dose dependent. Detected alterations concerned hyperplasia of connective tissue fibers and leukocyte infiltration. Visible granulocyte infiltration in the upper dermis and sockets formed by necrotic, cornified cells in the hyperplastic foci of epithelium were also noted. Immunohistochemical analyses revealed that increased nuclear immunoreactivity to PCNA correlated with the concentration of PAMAM-NH2, but no significant differences in the cell proliferation activity in skin treated with PAMAM-NH2 generation 2 or generation 3 were observed. Significantly higher expression of PCNA extended throughout the skin layers might suggest abnormal cell proliferation, which, as a consequence, might even lead to neoplastic changes. PMID:25834395

  14. QSAR modeling of estrogenic alkylphenols using bulk and electronic parameters

    Directory of Open Access Journals (Sweden)

    Mukherjee S

    2007-01-01

    Full Text Available Broad range of structurally diverse alkylphenols has been found to be considerably potential estrogenic agents in combating estrogen-linked pathologies, but their mechanism of action in mimicking responses of endogenous hormones is still to be understood. The present work explores pharmacophore signals of some varied alkylphenols and predicts estrogenic activities through generated linear relations implementing theoretical molecular modeling techniques. The binding affinity to estrogen receptor of alkylphenols has been modeled investigating large data set of whole molecular and atomic descriptors. Univariate and multivariate relationships were estimated using correlation analysis and statistical significance of the generated relations assessed. The predictive ability of the generated models was further verified using ′Leave-One-Out′ cross validation. The relationships with molecular properties could be developed with a maximum correlation exceeding 94%, with explained variance as high as 87% and cross-validated variances> 0.8. It was inferred that increased molecular bulk, enhanced molecular ionization potential, presence of electron donating groups in para position and branched chain terminal atoms might have influence on binding affinity to the receptor.

  15. Model-based optimization of tapered free-electron lasers

    Directory of Open Access Journals (Sweden)

    Alan Mak

    2015-04-01

    Full Text Available The energy extraction efficiency is a figure of merit for a free-electron laser (FEL. It can be enhanced by the technique of undulator tapering, which enables the sustained growth of radiation power beyond the initial saturation point. In the development of a single-pass x-ray FEL, it is important to exploit the full potential of this technique and optimize the taper profile a_{w}(z. Our approach to the optimization is based on the theoretical model by Kroll, Morton, and Rosenbluth, whereby the taper profile a_{w}(z is not a predetermined function (such as linear or exponential but is determined by the physics of a resonant particle. For further enhancement of the energy extraction efficiency, we propose a modification to the model, which involves manipulations of the resonant particle’s phase. Using the numerical simulation code GENESIS, we apply our model-based optimization methods to a case of the future FEL at the MAX IV Laboratory (Lund, Sweden, as well as a case of the LCLS-II facility (Stanford, USA.

  16. The mysid Siriella armata as a model organism in marine ecotoxicology: comparative acute toxicity sensitivity with Daphnia magna.

    Science.gov (United States)

    Pérez, Sara; Beiras, Ricardo

    2010-01-01

    Siriella armata (Crustacea, Mysidacea) is a component of the coastal zooplankton that lives in swarms in the shallow waters of the European neritic zone, from the North Sea to the Mediterranean. Juveniles of this species were examined as standard test organisms for use in marine acute toxicity tests. The effects of reference toxicants, three trace metals (Copper, Cadmium and Zinc), and one surfactant, sodium dodecyl sulfate (SDS) were studied on S. armata neonates (\\24 h) reared in the laboratory. Acute toxicity tests were carried out with filtered sea water on individual chambers (microplate wells for metals or glass vials for SDS) incubated in an isothermal room at 20 degrees C, with 16 h light: 8 h dark photoperiod for 96 h. Each neonate was fed daily with 10-15 nauplii of Artemia salina. Acute (96 h) LC50 values, in increasing order, were 46.9 lg/L for Cu, 99.3 lg/L for Cd, 466.7 lg/L for Zn and 8.5 mg/L for SDS. The LC(10), NOEC and LOEC values were also calculated. Results were compared with Daphnia magna, a freshwater cladoceran widely used as a standard ecotoxicological test organism. Acute (48 h) LC(50) values were 56.2 lg/L for Cu, 571.5 lg/L for Cd, 1.3 mg/L for Zn and 27.3 mg/L for SDS. For all the reference toxicants studied, the marine mysid Siriella armata showed higher sensitivity than the freshwater model organism Daphnia magna, validating the use of Siriella mysids as model organisms in marine acute toxicity tests.

  17. Building up a QSAR model for toxicity toward Tetrahymena pyriformis by the Monte Carlo method: A case of benzene derivatives.

    Science.gov (United States)

    Toropova, Alla P; Schultz, Terry W; Toropov, Andrey A

    2016-03-01

    Data on toxicity toward Tetrahymena pyriformis is indicator of applicability of a substance in ecologic and pharmaceutical aspects. Quantitative structure-activity relationships (QSARs) between the molecular structure of benzene derivatives and toxicity toward T. pyriformis (expressed as the negative logarithms of the population growth inhibition dose, mmol/L) are established. The available data were randomly distributed three times into the visible training and calibration sets, and invisible validation sets. The statistical characteristics for the validation set are the following: r(2)=0.8179 and s=0.338 (first distribution); r(2)=0.8682 and s=0.341 (second distribution); r(2)=0.8435 and s=0.323 (third distribution). These models are built up using only information on the molecular structure: no data on physicochemical parameters, 3D features of the molecular structure and quantum mechanics descriptors are involved in the modeling process. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Stochastic periodic solution of a non-autonomous toxic-producing phytoplankton allelopathy model with environmental fluctuation

    Science.gov (United States)

    Zhao, Yu; Yuan, Sanling; Zhang, Tonghua

    2017-03-01

    Phytoplankton allelopathy is an ecological phenomenon that concerns the interaction among toxic-producing phytoplankton. Recently, researchers pay great attention to whether the cyclic outbreaks of the harmful algal blooms are related with the allelopathy in a random fluctuating environment. In this paper, we are particularly interested in a non-autonomous toxic-producing phytoplankton allelopathy model with environmental fluctuation. For the model, we first consider the existence of the global positive solution and the boundary periodic solution. Then, by using Khasminskii's method and Lyapunov function, we derive the sufficient conditions for the existence of the nontrivial positive stochastically periodic solution. Our results show that the allelopathic effect plays an important role in the existence of the stochastic periodic solution, for example it can lead to the decrease of the peaks of the cyclic outbreaks of the harmful algal blooms. Numerical simulations are carried out to support our theoretical results.

  19. Hydra as a model organism to decipher the toxic effects of copper oxide nanorod: Eco-toxicogenomics approach

    Science.gov (United States)

    Murugadas, Anbazhagan; Zeeshan, Mohammed; Thamaraiselvi, Kaliannan; Ghaskadbi, Surendra; Akbarsha, Mohammad Abdulkader

    2016-07-01

    Nanotechnology has emerged as a powerful field of applied research. However, the potential toxicity of nano-materials is a cause of concern. A thorough toxicological investigation is required before a nanomaterial is evaluated for application of any kind. In this context, there is concerted effort to find appropriate test systems to assess the toxicity of nanomaterials. Toxicity of a nanomaterial greatly depends on its physicochemical properties and the biological system with which it interacts. The present research was carried out with a view to generate data on eco-toxicological impacts of copper oxide nanorod (CuO NR) in Hydra magnipapillata 105 at organismal, cellular and molecular levels. Exposure of hydra to CuO NR resulted in severe morphological alterations in a concentration- as well as duration-dependent manner. Impairment of feeding, population growth, and regeneration was also observed. In vivo and in vitro analyses revealed induction of oxidative stress, genotoxicity, and molecular machinery of apoptotic cell death, accompanied by disruption of cell cycle progression. Taken together, CuO nanorod is potentially toxic to the biological systems. Also, hydra offers potential to be used as a convenient model organism for aquatic ecotoxicological risk assessment of nanomaterials.

  20. Hydra as a model organism to decipher the toxic effects of copper oxide nanorod: Eco-toxicogenomics approach

    Science.gov (United States)

    Murugadas, Anbazhagan; Zeeshan, Mohammed; Thamaraiselvi, Kaliannan; Ghaskadbi, Surendra; Akbarsha, Mohammad Abdulkader

    2016-01-01

    Nanotechnology has emerged as a powerful field of applied research. However, the potential toxicity of nano-materials is a cause of concern. A thorough toxicological investigation is required before a nanomaterial is evaluated for application of any kind. In this context, there is concerted effort to find appropriate test systems to assess the toxicity of nanomaterials. Toxicity of a nanomaterial greatly depends on its physicochemical properties and the biological system with which it interacts. The present research was carried out with a view to generate data on eco-toxicological impacts of copper oxide nanorod (CuO NR) in Hydra magnipapillata 105 at organismal, cellular and molecular levels. Exposure of hydra to CuO NR resulted in severe morphological alterations in a concentration- as well as duration-dependent manner. Impairment of feeding, population growth, and regeneration was also observed. In vivo and in vitro analyses revealed induction of oxidative stress, genotoxicity, and molecular machinery of apoptotic cell death, accompanied by disruption of cell cycle progression. Taken together, CuO nanorod is potentially toxic to the biological systems. Also, hydra offers potential to be used as a convenient model organism for aquatic ecotoxicological risk assessment of nanomaterials. PMID:27417574

  1. SIRT1 modulates aggregation and toxicity through deacetylation of the androgen receptor in cell models of SBMA.

    Science.gov (United States)

    Montie, Heather L; Pestell, Richard G; Merry, Diane E

    2011-11-30

    Posttranslational protein modifications can play a major role in disease pathogenesis; phosphorylation, sumoylation, and acetylation modulate the toxicity of a variety of proteotoxic proteins. The androgen receptor (AR) is substantially modified, in response to hormone binding, by phosphorylation, sumoylation, and acetylation; these modifications might thus contribute to DHT-dependent polyglutamine (polyQ)-expanded AR proteotoxicity in spinal and bulbar muscular atrophy (SBMA). SIRT1, a nuclear protein and deacetylase of the AR, is neuroprotective in many neurodegenerative disease models. Our studies reveal that SIRT1 also offers protection against polyQ-expanded AR by deacetylating the AR at lysines 630/632/633. This finding suggested that nuclear AR acetylation plays a role in the aberrant metabolism and toxicity of polyQ-expanded AR. Subsequent studies revealed that the polyQ-expanded AR is hyperacetylated and that pharmacologic reduction of acetylation reduces mutant AR aggregation. Moreover, genetic mutation to inhibit polyQ-expanded AR acetylation of lysines 630/632/633 substantially decreased its aggregation and completely abrogated its toxicity in cell lines and motor neurons. Our studies also reveal one means by which the AR acetylation state likely modifies polyQ-expanded AR metabolism and toxicity, through its effect on DHT-dependent AR stabilization. Overall, our findings reveal a neuroprotective function of SIRT1 that operates through its deacetylation of polyQ-expanded AR and highlight the potential of both SIRT1 and AR acetylation as powerful therapeutic targets in SBMA.

  2. Dynamical analysis of a five-dimensioned chemostat model with impulsive diffusion and pulse input environmental toxicant

    Energy Technology Data Exchange (ETDEWEB)

    Jiao Jianjun, E-mail: jiaojianjun05@126.co [Guizhou Key Laboratory of Economic System Simulation, Guizhou College of Finance and Economics, Guiyang 550004 (China); Ye Kaili [School of Economics and Management, Xinyang Normal University, Xinyang 464000, Henan (China); Chen Lansun [Institute of Mathematics, Academy of Mathematics and System Sciences, Beijing 100080 (China)

    2011-01-15

    Research Highlights: This work improves on existing chemostat models. The proposed model accounts for natural phenomena. This work improves on the existing mathematical methods. - Abstract: In this paper, we consider a five-dimensioned chemostat model with impulsive diffusion and pulse input environmental toxicant. Using the discrete dynamical system determined by the stroboscopic map, we obtain a microorganism-extinction periodic solution. Further, it is globally asymptotically stable. The permanent condition of the investigated system is also analyzed by the theory on impulsive differential equation. Our results reveal that the chemostat environmental changes play an important role on the outcome of the chemostat.

  3. Applying mixture toxicity modelling to predict bacterial bioluminescence inhibition by non-specifically acting pharmaceuticals and specifically acting antibiotics.

    Science.gov (United States)

    Neale, Peta A; Leusch, Frederic D L; Escher, Beate I

    2017-04-01

    Pharmaceuticals and antibiotics co-occur in the aquatic environment but mixture studies to date have mainly focused on pharmaceuticals alone or antibiotics alone, although differences in mode of action may lead to different effects in mixtures. In this study we used the Bacterial Luminescence Toxicity Screen (BLT-Screen) after acute (0.5 h) and chronic (16 h) exposure to evaluate how non-specifically acting pharmaceuticals and specifically acting antibiotics act together in mixtures. Three models were applied to predict mixture toxicity including concentration addition, independent action and the two-step prediction (TSP) model, which groups similarly acting chemicals together using concentration addition, followed by independent action to combine the two groups. All non-antibiotic pharmaceuticals had similar EC50 values at both 0.5 and 16 h, indicating together with a QSAR (Quantitative Structure-Activity Relationship) analysis that they act as baseline toxicants. In contrast, the antibiotics' EC50 values decreased by up to three orders of magnitude after 16 h, which can be explained by their specific effect on bacteria. Equipotent mixtures of non-antibiotic pharmaceuticals only, antibiotics only and both non-antibiotic pharmaceuticals and antibiotics were prepared based on the single chemical results. The mixture toxicity models were all in close agreement with the experimental results, with predicted EC50 values within a factor of two of the experimental results. This suggests that concentration addition can be applied to bacterial assays to model the mixture effects of environmental samples containing both specifically and non-specifically acting chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. A dynamic approach for the impact of a toxic gas dispersion hazard considering human behaviour and dispersion modelling.

    Science.gov (United States)

    Lovreglio, Ruggiero; Ronchi, Enrico; Maragkos, Georgios; Beji, Tarek; Merci, Bart

    2016-11-15

    The release of toxic gases due to natural/industrial accidents or terrorist attacks in populated areas can have tragic consequences. To prevent and evaluate the effects of these disasters different approaches and modelling tools have been introduced in the literature. These instruments are valuable tools for risk managers doing risk assessment of threatened areas. Despite the significant improvements in hazard assessment in case of toxic gas dispersion, these analyses do not generally include the impact of human behaviour and people movement during emergencies. This work aims at providing an approach which considers both modelling of gas dispersion and evacuation movement in order to improve the accuracy of risk assessment for disasters involving toxic gases. The approach is applied to a hypothetical scenario including a ship releasing Nitrogen dioxide (NO2) on a crowd attending a music festival. The difference between the results obtained with existing static methods (people do not move) and a dynamic approach (people move away from the danger) which considers people movement with different degrees of sophistication (either a simple linear path or more complex behavioural modelling) is discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Numerical Modeling of Microbial Fuel Cell Based on Redox Electron Mediator

    Institute of Scientific and Technical Information of China (English)

    Nanqi Ren

    2015-01-01

    To investigate the behavior of redox electron mediator and its impact to power generation of microbial fuel cell ( MFC ) , this study carries out the numerical modeling of a typical two⁃chamber MFC based on assumption of interfacial electron transfer via redox electron mediator and acetate as sole electron donor. The model simulates the development of cell voltage, current, substrate concentration, redox electron mediator concentration, polarization and power density output under defined conditions. The results demonstrate that the developed models can fit the experimental results well on a qualitative basis, and concentration of electron reduced mediator plays a dominant role in electron transfer process, and the mass transfer may constitute the limiting step when its concentration is at a relatively low level. This study not only provides a better understanding of electron redox mediator behavior during power generation, but also suggests a strategy to improve electron transfer in the anode of MFC.

  6. Expression of the alternative oxidase mitigates beta-amyloid production and toxicity in model systems.

    Science.gov (United States)

    El-Khoury, Riyad; Kaulio, Eveliina; Lassila, Katariina A; Crowther, Damian C; Jacobs, Howard T; Rustin, Pierre

    2016-07-01

    Mitochondrial dysfunction has been widely associated with the pathology of Alzheimer's disease, but there is no consensus on whether it is a cause or consequence of disease, nor on the precise mechanism(s). We addressed these issues by testing the effects of expressing the alternative oxidase AOX from Ciona intestinalis, in different models of AD pathology. AOX can restore respiratory electron flow when the cytochrome segment of the mitochondrial respiratory chain is inhibited, supporting ATP synthesis, maintaining cellular redox homeostasis and mitigating excess superoxide production at respiratory complexes I and III. In human HEK293-derived cells, AOX expression decreased the production of beta-amyloid peptide resulting from antimycin inhibition of respiratory complex III. Because hydrogen peroxide was neither a direct product nor substrate of AOX, the ability of AOX to mimic antioxidants in this assay must be indirect. In addition, AOX expression was able to partially alleviate the short lifespan of Drosophila models neuronally expressing human beta-amyloid peptides, whilst abrogating the induction of markers of oxidative stress. Our findings support the idea of respiratory chain dysfunction and excess ROS production as both an early step and as a pathologically meaningful target in Alzheimer's disease pathogenesis, supporting the concept of a mitochondrial vicious cycle underlying the disease.

  7. Lumped Parameter Modeling for Rapid Vibration Response Prototyping and Test Correlation for Electronic Units

    Science.gov (United States)

    Van Dyke, Michael B.

    2013-01-01

    Present preliminary work using lumped parameter models to approximate dynamic response of electronic units to random vibration; Derive a general N-DOF model for application to electronic units; Illustrate parametric influence of model parameters; Implication of coupled dynamics for unit/board design; Demonstrate use of model to infer printed wiring board (PWB) dynamics from external chassis test measurement.

  8. A Massless-Point-Charge Model for the Electron

    Directory of Open Access Journals (Sweden)

    Daywitt W. C.

    2010-04-01

    Full Text Available “It is rather remarkable that the modern concept of electrodynamics is not quite 100 years old and yet still does not rest firmly upon uniformly accepted theoretical foun- dations. Maxwell’s theory of the electromagnetic field is firmly ensconced in modern physics, to be sure, but the details of how charged particles are to be coupled to this field remain somewhat uncertain, despite the enormous advances in quantum electrody- namics over the past 45 years. Our theories remain mathematically ill-posed and mired in conceptual ambiguities which quantum mechanics has only moved to another arena rather than resolve. Fundamentally, we still do not understand just what is a charged particle” [1, p.367]. As a partial answer to the preceeding quote, this paper presents a new model for the electron that combines the seminal work of Puthoff [2] with the theory of the Planck vacuum (PV [3], the basic idea for the model following from [2] with the PV theory adding some important details.

  9. A Massless-Point-Charge Model for the Electron

    Directory of Open Access Journals (Sweden)

    Daywitt W. C.

    2010-04-01

    Full Text Available "It is rather remarkable that the modern concept of electrodynamics is not quite 100 years old and yet still does not rest firmly upon uniformly accepted theoretical foundations. Maxwell's theory of the electromagnetic field is firmly ensconced in modern physics, to be sure, but the details of how charged particles are to be coupled to this field remain somewhat uncertain, despite the enormous advances in quantum electrodynamics over the past 45 years. Our theories remain mathematically ill-posed and mired in conceptual ambiguities which quantum mechanics has only moved to another arena rather than resolve. Fundamentally, we still do not understand just what is a charged particle" (Grandy W.T. Jr. Relativistic quantum mechanics of leptons and fields. Kluwer Academic Publishers, Dordrecht-London, 1991, p.367. As a partial answer to the preceeding quote, this paper presents a new model for the electron that combines the seminal work of Puthoff with the theory of the Planck vacuum (PV, the basic idea for the model following from Puthoff with the PV theory adding some important details.

  10. Electron percolation in realistic models of carbon nanotube networks

    Science.gov (United States)

    Simoneau, Louis-Philippe; Villeneuve, Jérémie; Rochefort, Alain

    2015-09-01

    The influence of penetrable and curved carbon nanotubes (CNT) on the charge percolation in three-dimensional disordered CNT networks have been studied with Monte-Carlo simulations. By considering carbon nanotubes as solid objects but where the overlap between their electron cloud can be controlled, we observed that the structural characteristics of networks containing lower aspect ratio CNT are highly sensitive to the degree of penetration between crossed nanotubes. Following our efficient strategy to displace CNT to different positions to create more realistic statistical models, we conclude that the connectivity between objects increases with the hard-core/soft-shell radii ratio. In contrast, the presence of curved CNT in the random networks leads to an increasing percolation threshold and to a decreasing electrical conductivity at saturation. The waviness of CNT decreases the effective distance between the nanotube extremities, hence reducing their connectivity and degrading their electrical properties. We present the results of our simulation in terms of thickness of the CNT network from which simple structural parameters such as the volume fraction or the carbon nanotube density can be accurately evaluated with our more realistic models.

  11. Python framework for kinetic modeling of electronically excited reaction pathways

    Science.gov (United States)

    Verboncoeur, John; Parsey, Guy; Guclu, Yaman; Christlieb, Andrew

    2012-10-01

    The use of plasma energy to enhance and control the chemical reactions during combustion, a technology referred to as ``plasma assisted combustion'' (PAC), can result in a variety of beneficial effects: e.g. stable lean operation, pollution reduction, and wider range of p-T operating conditions. While experimental evidence abounds, theoretical understanding of PAC is at best incomplete, and numerical tools still lack in reliable predictive capabilities. In the context of a joint experimental-numerical effort at Michigan State University, we present here an open-source modular Python framework dedicated to the dynamic optimization of non-equilibrium PAC systems. Multiple sources of experimental reaction data, e.g. reaction rates, cross-sections and oscillator strengths, are used in order to quantify the effect of data uncertainty and limiting assumptions. A collisional-radiative model (CRM) is implemented to organize reactions by importance and as a potential means of measuring a non-Maxwellian electron energy distribution function (EEDF), when coupled to optical emission spectroscopy data. Finally, we explore scaling laws in PAC parameter space using a kinetic global model (KGM) accelerated with CRM optimized reaction sequences and sparse stiff integrators.

  12. Spatial analysis of toxic emissions in LCA: a sub-continental nested USEtox model with freshwater archetypes.

    Science.gov (United States)

    Kounina, Anna; Margni, Manuele; Shaked, Shanna; Bulle, Cécile; Jolliet, Olivier

    2014-08-01

    This paper develops continent-specific factors for the USEtox model and analyses the accuracy of different model architectures, spatial scales and archetypes in evaluating toxic impacts, with a focus on freshwater pathways. Inter-continental variation is analysed by comparing chemical fate and intake fractions between sub-continental zones of two life cycle impact assessment models: (1) the nested USEtox model parameterized with sub-continental zones and (2) the spatially differentiated IMPACTWorld model with 17 interconnected sub-continental regions. Substance residence time in water varies by up to two orders of magnitude among the 17 zones assessed with IMPACTWorld and USEtox, and intake fraction varies by up to three orders of magnitude. Despite this variation, the nested USEtox model succeeds in mimicking the results of the spatially differentiated model, with the exception of very persistent volatile pollutants that can be transported to polar regions. Intra-continental variation is analysed by comparing fate and intake fractions modelled with the a-spatial (one box) IMPACT Europe continental model vs. the spatially differentiated version of the same model. Results show that the one box model might overestimate chemical fate and characterisation factors for freshwater eco-toxicity of persistent pollutants by up to three orders of magnitude for point source emissions. Subdividing Europe into three archetypes, based on freshwater residence time (how long it takes water to reach the sea), improves the prediction of fate and intake fractions for point source emissions, bringing them within a factor five compared to the spatial model. We demonstrated that a sub-continental nested model such as USEtox, with continent-specific parameterization complemented with freshwater archetypes, can thus represent inter- and intra-continental spatial variations, whilst minimizing model complexity.

  13. Short-Range Correlation Models in Electronic Structure Theory

    Science.gov (United States)

    Goldey, Matthew Bryant

    Correlation methods within electronic structure theory focus on recovering the exact electron-electron interaction from the mean-field reference. For most chemical systems, including dynamic correlation, the correlation of the movement of electrons proves to be sufficient, yet exact methods for capturing dynamic correlation inherently scale polynomially with system size despite the locality of the electron cusp. This work explores a new family of methods for enhancing the locality of dynamic correlation methodologies with an aim toward improving accuracy and scalability. The introduction of range-separation into ab initio wavefunction methods produces short-range correlation methodologies, which can be supplemented with much faster approximate methods for long-range interactions. First, I examine attenuation of second-order Moller-Plesset perturbation theory (MP2) in the aug-cc-pVDZ basis. MP2 treats electron correlation at low computational cost, but suffers from basis set superposition error (BSSE) and fundamental inaccuracies in long-range contributions. The cost differential between complete basis set (CBS) and small basis MP2 restricts system sizes where BSSE can be removed. Range-separation of MP2 could yield more tractable and/or accurate forms for short- and long-range correlation. Retaining only short-range contributions proves to be effective for MP2 in the small aug-cc-pVDZ (aDZ) basis. Using one range-separation parameter within either the complementary error function (erfc) or a sum of two error functions (terfc), superior behavior is obtained versus both MP2/aDZ and MP2/CBS for inter- and intra-molecular test sets. Attenuation of the long-range helps to cancel both BSSE and intrinsic MP2 errors. Direct scaling of the MP2 correlation energy (SMP2) proves useful as well. The resulting SMP2/aDZ, MP2(erfc, aDZ), and MP2(terfc, aDZ) methods perform far better than MP2/aDZ across systems with hydrogen-bonding, dispersion, and mixed interactions at a

  14. Electron Beam Melting and Refining of Metals: Computational Modeling and Optimization

    National Research Council Canada - National Science Library

    Katia Vutova; Veliko Donchev

    2013-01-01

    ..., instrument engineering, electronics, etc. A time-dependent 3D axis-symmetrical heat model for simulation of thermal transfer in metal ingots solidified in a water-cooled crucible at electron beam melting and refining (EBMR) is developed...

  15. Indocyanine green clearance varies as a function of N-acetylcysteine treatment in a murine model of acetaminophen toxicity.

    Science.gov (United States)

    Milesi-Hallé, Alessandra; Abdel-Rahman, Susan M; Brown, Aliza; McCullough, Sandra S; Letzig, Lynda; Hinson, Jack A; James, Laura P

    2011-02-01

    Standard assays to assess acetaminophen (APAP) toxicity in animal models include determination of ALT (alanine aminotransferase) levels and examination of histopathology of liver sections. However, these assays do not reflect the functional capacity of the injured liver. To examine a functional marker of liver injury, the pharmacokinetics of indocyanine green (ICG) were examined in mice treated with APAP, saline, or APAP followed by N-acetylcysteine (NAC) treatment.Male B6C3F1 mice were administered APAP (200 mg/kg IP) or saline. Two additional groups of mice received APAP followed by NAC at 1 or 4 h after APAP. At 24 h, mice were injected with ICG (10 mg/kg IV) and serial blood samples (0, 2, 10, 30, 50 and 75 min) were obtained for determination of serum ICG concentrations and ALT. Mouse livers were removed for measurement of APAP protein adducts and examination of histopathology. Toxicity (ALT values and histology) was significantly increased above saline treated mice in the APAP and APAP/NAC 4 h mice. Mice treated with APAP/NAC 1 h had complete protection from toxicity. APAP protein adducts were increased in all APAP treated groups and were highest in the APAP/NAC 1 h group. Pharmacokinetic analysis of ICG demonstrated that the total body clearance (Cl(T)) of ICG was significantly decreased and the mean residence time (MRT) was significantly increased in the APAP mice compared to the saline mice. Mice treated with NAC at 1 h had Cl(T) and MRT values similar to those of saline treated mice. Conversely, mice that received NAC at 4 h had a similar ICG pharmacokinetic profile to that of the APAP only mice. Prompt treatment with NAC prevented loss of functional activity while late treatment with NAC offered no improvement in ICG clearance at 24 h. ICG clearance in mice with APAP toxicity can be utilized in future studies testing the effects of novel treatments for APAP toxicity.

  16. Label-free detection of protein molecules secreted from an organ-on-a-chip model for drug toxicity assays

    Science.gov (United States)

    Morales, Andres W.; Zhang, Yu S.; Aleman, Julio; Alerasool, Parissa; Dokmeci, Mehmet R.; Khademhosseini, Ali; Ye, Jing Yong

    2016-03-01

    Clinical attrition is about 30% from failure of drug candidates due to toxic side effects, increasing the drug development costs significantly and slowing down the drug discovery process. This partly originates from the fact that the animal models do not accurately represent human physiology. Hence there is a clear unmet need for developing drug toxicity assays using human-based models that are complementary to traditional animal models before starting expensive clinical trials. Organ-on-a-chip techniques developed in recent years have generated a variety of human organ models mimicking different human physiological conditions. However, it is extremely challenging to monitor the transient and long-term response of the organ models to drug treatments during drug toxicity tests. First, when an organ-on-a-chip model interacts with drugs, a certain amount of protein molecules may be released into the medium due to certain drug effects, but the amount of the protein molecules is limited, since the organ tissue grown inside microfluidic bioreactors have minimum volume. Second, traditional fluorescence techniques cannot be utilized for real-time monitoring of the concentration of the protein molecules, because the protein molecules are continuously secreted from the tissue and it is practically impossible to achieve fluorescence labeling in the dynamically changing environment. Therefore, direct measurements of the secreted protein molecules with a label-free approach is strongly desired for organs-on-a-chip applications. In this paper, we report the development of a photonic crystal-based biosensor for label-free assays of secreted protein molecules from a liver-on-a-chip model. Ultrahigh detection sensitivity and specificity have been demonstrated.

  17. A survey of catfish pond water chemistry parameters for copper toxicity modelling

    Science.gov (United States)

    Water samples were collected from 20 catfish ponds in 2015 to obtain data useful in predicting copper toxicity and chemical behavior. Ponds were located in major catfish producing areas of west Alabama, east Arkansas, and Mississippi. Pond types included traditional levee ponds, split-ponds, water...

  18. Modeling of Magnetite Nanoparticles Behavior under Conditions of Microcirculation and Analysis of In Vivo Toxicity.

    Science.gov (United States)

    Sakharov, D A; Rudakovskaya, P G; Maltseva, D V; Trushkin, E V; Tonevitskaya, S A

    2016-05-01

    The behavior of magnetite nanoparticles was studied in the cell chip microcapillaries. No aggregation of magnetite nanoparticles under conditions of long-term circulation was noted. Biodistribution and toxicity of magnetite nanoparticles (14 nm) and aminated magnetite after their intragastric administration to mice were studied in vivo. According to mass spectrometry and microscopy data, accumulation of nanoparticles occurred mainly in the liver cells.

  19. Toxicity evaluation of prodigiosin from Serratia marcescens in a Caenorhabditis elegans model

    Science.gov (United States)

    Seah, Siew-Wei; Nathan, Sheila; Wan, Kiew-Lian

    2016-11-01

    Serratia marcescens produces several secondary metabolites, including a red antimicrobial pigment, prodigiosin. There is considerable interest in prodigiosin and its derivatives due to their anticancer and immunosuppressive properties. Prodigiosin has also become the main choice of red dye in textiles. As prodigiosin has potentially high commercial value, there is a demand to develop high-throughput and cost-effective bioprocesses for prodigiosin production. However little is still known about its toxicity. This study was carried out to investigate the toxicity effect of prodigiosin. To determine if prodigiosin was potentially toxic to eukaryotic systems, the S. marcescens ATCC 274 wild type (Sma 274) and the non-prodigiosin producer S. marcescens Bizio WF mutant ATCC 29635 (WF mutant) were grown under the optimised conditions for prodigiosin production and fed to the nematode Caenorhabditis elegans. The mean time to death (TDmean) for Sma 274-infected worms assayed on agar was 112.6 hours while the WF mutant culture had a TDmean of 104.4 hours. However, the nematode killing kinetics were not significantly different between the prodigiosin-producing and non-producing S. marcescens strains (p>0.05). In lieu of its non-toxic property, prodigiosin has the potential to be developed for safe therapeutic applications and as a safe environmental friendly bio-dye.

  20. EXAMINATION OF QUINONE TOXICITY USING YEAST SACCHAROMYCES CEREVISIAE MODEL SYSTEM. (R827352C007)

    Science.gov (United States)

    The toxicity of quinones is generally thought to occur by two mechanisms: the formation of covalent bonds with biological molecules by Michael addition chemistry and the catalytic reduction of oxygen to superoxide and other reactive oxygen species (ROS) (redox cycling). In an ...

  1. CREATION OF THE INFORMATIONAL MODEL OF TOXIC MYOCARDITIS OCCURRED UNDER THE INFLUENCE OF PESTICIDES

    Directory of Open Access Journals (Sweden)

    Sayora Akhmedova

    2015-12-01

    Full Text Available Creation of productive knowledge is important whereas on the base of this knowledge we can diagnose morphologic and morphometric properties of vascular stromal tissues of myocardium under toxic myocarditis on the bases of clinical symptoms. Consequence of this is a proper therapeutic strategy that will have a life importance for the patients.

  2. The toxicity test and hypothetical model of Bacillus thuringiensis Cry1Aa helix4

    Institute of Scientific and Technical Information of China (English)

    SU; Yanhui(苏彦辉); QU; Hong(曲红); Vachon; Vincent; LUO; Jingchu(罗静初); ZHANG; Jie(张杰); Laprade; Raynald; ZHU; Yuxian(朱玉贤)

    2002-01-01

    Development of targeted biological agents against agricultural insect pests is of prime importance for the elaboration and implementation of integrated pest management strategies that are environment-friendly, respectful of bio-diversity and safer to human health through reduced use of chemical pesticides. A major goal to understand how Bt toxins work is to elucidate the functions of their three domains. Domains II and III are involved in binding specificity and structural integrity, but the function of Domain I remains poorly understood. Using a Manduca sexta BBMV (brush border membrane vesicles) system, we analyzed its responses to Cry1Aa 15 single-point mutations with altered Domain I helix 4 residues. Light scattering assay showed that toxicity was almost lost in 3 mutants, and we observed significantly reduced toxicity in other 7 mutants. However, 5 mutants retained wild-type toxicity. Using computer software, we simulated the three-dimensional structures of helix 4. Both experimental and bioinformatic analysis showed that residues in Cry1Aa Domain I helix 4 were involved in the formation of ion channels that is critical for its insect toxicity.

  3. Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

    Science.gov (United States)

    Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive signature was constructed from U.S. EPA ToxCast high-throughput screening (HTS) assays that map to...

  4. The Prediction of Radiotherapy Toxicity Using Single Nucleotide Polymorphism-Based Models: A Step Toward Prevention

    NARCIS (Netherlands)

    S.L. Kerns (Sarah L.); S. Kundu (Suman); J.H. Oh (Jung Hun); S.K. Singhal (Sandeep K.); M. Janelsins (Michelle); L.B. Travis (Lois B.); J.O. Deasy (Joseph O.); A.C.J.W. Janssens (Cécile); H. Ostrer (Harry); M. Parliament (Matthew); N. Usmani (Nawaid); B.S. Rosenstein (Barry S.)

    2015-01-01

    textabstractRadiotherapy is a mainstay of cancer treatment, used in either a curative or palliative manner to treat approximately 50% of patients with cancer. Normal tissue toxicity limits the doses used in standard radiation therapy protocols and impedes improvements in radiotherapy efficacy. Damag

  5. Intravenous Cobinamide, a Novel Cyanide Antidote, versus Hydroxocobalamin in the Treatment of Acute Cyanide Toxicity and Apnea in a Swine (Sus scrofa) Model

    Science.gov (United States)

    2013-02-12

    treatment of acute, severe cyanide induced cardiotoxicity of severe hypotension and of cardiac arrest in a swine (Sus Scrofa ) model Intravenous...cobinamide, a novel cyanide antidote, versus hydroxocobalamin in the treatment of acute cyanide toxicity and apnea in a swine (Sus Scrofa ) model...hydroxocobalamin in the treatment of acute cyanide toxicity and apnea in a swine (Sus Scrofa ) model Background: Hydroxocobalamin (HOC) is an FDA approved

  6. Modeling High Altitude EMP using a Non-Equilibrium Electron Swarm Model to Monitor Conduction Electron Evolution (LA-UR-15-26151)

    Science.gov (United States)

    Pusateri, E. N.; Morris, H. E.; Nelson, E.; Ji, W.

    2015-12-01

    Electromagnetic pulse (EMP) events in the atmosphere are important physical phenomena that occur through both man-made and natural processes, such as lightning, and can be disruptive to surrounding electrical systems. Due to the disruptive nature of EMP, it is important to accurately predict EMP evolution and propagation with computational models. In EMP, low-energy conduction electrons are produced from Compton electron or photoelectron ionizations with air. These conduction electrons continue to interact with the surrounding air and alter the EMP waveform. Many EMP simulation codes use an equilibrium ohmic model for computing the conduction current. The equilibrium model works well when the equilibration time is short compared to the rise time or duration of the EMP. However, at high altitude, the conduction electron equilibration time can be comparable to or longer than the rise time or duration of the EMP. This matters, for example, when calculating the EMP propagating upward toward a satellite. In these scenarios, the equilibrium ionization rate becomes very large for even a modest electric field. The ohmic model produces an unphysically large number of conduction electrons that prematurely and abruptly short the EMP in the simulation code. An electron swarm model, which simulates the time evolution of conduction electrons, can be used to overcome the limitations exhibited by the equilibrium ohmic model. We have developed and validated an electron swarm model in an environment characterized by electric field and pressure previously in Pusateri et al. (2015). This swarm model has been integrated into CHAP-LA, a state-of-the-art EMP code developed by researchers at Los Alamos National Laboratory, which previously calculated conduction current using an ohmic model. We demonstrate the EMP damping behavior caused by the ohmic model at high altitudes and show improvements on high altitude EMP modeling obtained by employing the swarm model.

  7. An unconventional space-time model of electrons and its application to the many-electron problem

    CERN Document Server

    Hofer, Werner A

    2010-01-01

    We present a space-time model of extended electrons, which is formulated in terms of geometric algebra. Wave properties of the electron are referred to mass density oscillations. We provide a comprehensive and non-statistical interpretation of wavefunctions, referring them to mass density components and internal field components. It is shown that these wavefunctions comply with the Schr\\"odinger equation, for the free electron as well as for the electron in electrostatic and vector potentials. Spin-properties of the electron are referred to intrinsic field components and it is established that a measurement of spin in an external field yields exactly two possible results. It is found that the model also agrees with the results of standard theory concerning the hydrogen atom. Finally, we analyze many-electron systems and derive a set of coupled equations suitable to characterize the system without any reference to single electron states. It is found that this set of equations is a natural extension for spin-po...

  8. Measured and modeled toxicokinetics in cultured fish cells and application to in vitro-in vivo toxicity extrapolation.

    Science.gov (United States)

    Stadnicka-Michalak, Julita; Tanneberger, Katrin; Schirmer, Kristin; Ashauer, Roman

    2014-01-01

    Effect concentrations in the toxicity assessment of chemicals with fish and fish cells are generally based on external exposure concentrations. External concentrations as dose metrics, may, however, hamper interpretation and extrapolation of toxicological effects because it is the internal concentration that gives rise to the biological effective dose. Thus, we need to understand the relationship between the external and internal concentrations of chemicals. The objectives of this study were to: (i) elucidate the time-course of the concentration of chemicals with a wide range of physicochemical properties in the compartments of an in vitro test system, (ii) derive a predictive model for toxicokinetics in the in vitro test system, (iii) test the hypothesis that internal effect concentrations in fish (in vivo) and fish cell lines (in vitro) correlate, and (iv) develop a quantitative in vitro to in vivo toxicity extrapolation method for fish acute toxicity. To achieve these goals, time-dependent amounts of organic chemicals were measured in medium, cells (RTgill-W1) and the plastic of exposure wells. Then, the relation between uptake, elimination rate constants, and log KOW was investigated for cells in order to develop a toxicokinetic model. This model was used to predict internal effect concentrations in cells, which were compared with internal effect concentrations in fish gills predicted by a Physiologically Based Toxicokinetic model. Our model could predict concentrations of non-volatile organic chemicals with log KOW between 0.5 and 7 in cells. The correlation of the log ratio of internal effect concentrations in fish gills and the fish gill cell line with the log KOW was significant (r>0.85, p = 0.0008, F-test). This ratio can be predicted from the log KOW of the chemical (77% of variance explained), comprising a promising model to predict lethal effects on fish based on in vitro data.

  9. Modeling Photovoltaic Module-Level Power Electronics in the System Advisor Model; NREL (National Renewable Energy Laboratory)

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-07-01

    Module-level power electronics, such as DC power optimizers, microinverters, and those found in AC modules, are increasing in popularity in smaller-scale photovoltaic (PV) systems as their prices continue to decline. Therefore, it is important to provide PV modelers with guidelines about how to model these distributed power electronics appropriately in PV modeling software. This paper extends the work completed at NREL th