The Use of Chemical-Chemical Interaction and Chemical Structure to Identify New Candidate Chemicals Related to Lung Cancer

PubMed Central

Zheng, Mingyue; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

2015-01-01

Lung cancer causes over one million deaths every year worldwide. However, prevention and treatment methods for this serious disease are limited. The identification of new chemicals related to lung cancer may aid in disease prevention and the design of more effective treatments. This study employed a weighted network, constructed using chemical-chemical interaction information, to identify new chemicals related to two types of lung cancer: non-small lung cancer and small-cell lung cancer. Then, a randomization test as well as chemical-chemical interaction and chemical structure information were utilized to make further selections. A final analysis of these new chemicals in the context of the current literature indicates that several chemicals are strongly linked to lung cancer. PMID:26047514

Chemical Manufacturers, Importers, and Exporters: Frequent Questions

EPA Pesticide Factsheets

Chemical manufacturers, importers, and exporters are required to operate within a system of allowances. This information will help those in the chemical industry understand their role in the phaseout of HCFCs in the United States.

40 CFR 799.19 - Chemical imports and exports.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Chemical imports and exports. 799.19 Section 799.19 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... General Provisions § 799.19 Chemical imports and exports. Persons who export or who intend to export...

Combining functional genomics and chemical biology to identify targets of bioactive compounds.

PubMed

Ho, Cheuk Hei; Piotrowski, Jeff; Dixon, Scott J; Baryshnikova, Anastasia; Costanzo, Michael; Boone, Charles

2011-02-01

Genome sequencing projects have revealed thousands of suspected genes, challenging researchers to develop efficient large-scale functional analysis methodologies. Determining the function of a gene product generally requires a means to alter its function. Genetically tractable model organisms have been widely exploited for the isolation and characterization of activating and inactivating mutations in genes encoding proteins of interest. Chemical genetics represents a complementary approach involving the use of small molecules capable of either inactivating or activating their targets. Saccharomyces cerevisiae has been an important test bed for the development and application of chemical genomic assays aimed at identifying targets and modes of action of known and uncharacterized compounds. Here we review yeast chemical genomic assays strategies for drug target identification. Copyright © 2010 Elsevier Ltd. All rights reserved.

TSCA Chemical Data Reporting Fact Sheet: Imported Articles

EPA Pesticide Factsheets

This fact sheet provides guidance and sample reporting scenarios on the reporting exemption for the import of a chemical substance as part of an article, for purposes of the Chemical Data Reporting (CDR) rule.

Can Zebrafish be used to Identify Developmentally Neurotoxic Chemicals

EPA Science Inventory

Can Zebrafish be Used to Identify Developmentally Neurotoxic Chemicals? The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental neurotoxicity. We are exploring behavioral methods using zebrafish by desig...

Identifying Candidate Chemical-Disease Linkages (Environmental and Epigenetic Determinants of IBD)

EPA Science Inventory

Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This h...

Ambiguity of non-systematic chemical identifiers within and between small-molecule databases.

PubMed

Akhondi, Saber A; Muresan, Sorel; Williams, Antony J; Kors, Jan A

2015-01-01

A wide range of chemical compound databases are currently available for pharmaceutical research. To retrieve compound information, including structures, researchers can query these chemical databases using non-systematic identifiers. These are source-dependent identifiers (e.g., brand names, generic names), which are usually assigned to the compound at the point of registration. The correctness of non-systematic identifiers (i.e., whether an identifier matches the associated structure) can only be assessed manually, which is cumbersome, but it is possible to automatically check their ambiguity (i.e., whether an identifier matches more than one structure). In this study we have quantified the ambiguity of non-systematic identifiers within and between eight widely used chemical databases. We also studied the effect of chemical structure standardization on reducing the ambiguity of non-systematic identifiers. The ambiguity of non-systematic identifiers within databases varied from 0.1 to 15.2 % (median 2.5 %). Standardization reduced the ambiguity only to a small extent for most databases. A wide range of ambiguity existed for non-systematic identifiers that are shared between databases (17.7-60.2 %, median of 40.3 %). Removing stereochemistry information provided the largest reduction in ambiguity across databases (median reduction 13.7 percentage points). Ambiguity of non-systematic identifiers within chemical databases is generally low, but ambiguity of non-systematic identifiers that are shared between databases, is high. Chemical structure standardization reduces the ambiguity to a limited extent. Our findings can help to improve database integration, curation, and maintenance.

Identifying new persistent and bioaccumulative organics among chemicals in commerce.

PubMed

Howard, Philip H; Muir, Derek C G

2010-04-01

The goal of this study was to identify commercial chemicals that might be persistent and bioaccumulative (P&B) and that were not being considered in current Great Lakes, North American, and Arctic contaminant measurement programs. We combined the Canadian Domestic Substance List (DSL), a list of 3059 substances of "unknown or variable composition complex reaction products and biological materials" (UVCBs), and the U.S. Environmental Protection Agency (U.S. EPA) Toxic Substances Control Act (TSCA) Inventory Update Rule (IUR) database for years 1986, 1990, 1994, 1998, 2002, and 2006 yielding a database of 22263 commercial chemicals. From that list, 610 chemicals were identified by estimates from U.S EPA EPISuite software and using expert judgment. This study has yielded some interesting and probable P&B chemicals that should be considered for further study. Recent studies, following up our initial reports and presentations on this work, have confirmed the presence of many of these chemicals in the environment.

Identifying Metabolically Active Chemicals Using a Consensus ...

EPA Pesticide Factsheets

Endocrine disrupting chemicals (EDCs) are abundant throughout the environment and can alter neurodevelopment, behavior, and reproductive success of humans and other species by perturbing signaling pathways related to the estrogen receptor (ER). A recent study compared results across 18 ER-related assays in the ToxCast™ in vitro screening program to predict the likelihood of a chemical exhibiting in vivo estrogenic activity, with the purpose of eliminating chemicals that may produce a false signal by interfering with the technological attributes of an individual assay. However, flaws in in vitro assay design can also prevent induction of signal activity by EDCs. Another reason for not observing activity for some EDCs in in vitro assays is that metabolic activation is required to perturb ER-related pathways. In the current study, 1,024 chemicals were identified as lacking ER activity after establishing a consensus across each of the 18 ER-related in vitro assays, and nearly 2,000 primary and 3,700 secondary unique metabolites were predicted for these chemicals. The ER binding activity for each metabolite was then predicted using an existing ER activity quantitative structure activity relationship (QSAR) consensus model. Binding activity was predicted for 2-3% of the metabolites within each generation. Of the inactive parent compounds generating at least one metabolite predicted to have ER-binding activity, nearly 30% were found to have metabolites from both gene

Indexing molecules with chemical graph identifiers.

PubMed

Gregori-Puigjané, Elisabet; Garriga-Sust, Rut; Mestres, Jordi

2011-09-01

Fast and robust algorithms for indexing molecules have been historically considered strategic tools for the management and storage of large chemical libraries. This work introduces a modified and further extended version of the molecular equivalence number naming adaptation of the Morgan algorithm (J Chem Inf Comput Sci 2001, 41, 181-185) for the generation of a chemical graph identifier (CGI). This new version corrects for the collisions recognized in the original adaptation and includes the ability to deal with graph canonicalization, ensembles (salts), and isomerism (tautomerism, regioisomerism, optical isomerism, and geometrical isomerism) in a flexible manner. Validation of the current CGI implementation was performed on the open NCI database and the drug-like subset of the ZINC database containing 260,071 and 5,348,089 structures, respectively. The results were compared with those obtained with some of the most widely used indexing codes, such as the CACTVS hash code and the new InChIKey. The analyses emphasize the fact that compound management activities, like duplicate analysis of chemical libraries, are sensitive to the exact definition of compound uniqueness and thus still depend, to a minor extent, on the type and flexibility of the molecular index being used. Copyright © 2011 Wiley Periodicals, Inc.

A Method for Identifying Prevalent Chemical Combinations in the U.S. Population

PubMed Central

Wambaugh, John F.; Ring, Caroline L.; Tornero-Velez, Rogelio; Setzer, R. Woodrow

2017-01-01

Background: Through the food and water they ingest, the air they breathe, and the consumer products with which they interact at home and at work, humans are exposed to tens of thousands of chemicals, many of which have not been evaluated to determine their potential toxicities. Furthermore, while current chemical testing tends to focus on individual chemicals, the exposures that people actually experience involve mixtures of chemicals. Unfortunately, the number of mixtures that can be formed from the thousands of environmental chemicals is enormous, and testing all of them would be impossible. Objectives: We seek to develop and demonstrate a method for identifying those mixtures that are most prevalent in humans. Methods: We applied frequent itemset mining, a technique traditionally used for market basket analysis, to biomonitoring data from the 2009–2010 cycle of the continuous National Health and Nutrition Examination Survey (NHANES) to identify combinations of chemicals that frequently co-occur in people. Results: We identified 90 chemical combinations consisting of relatively few chemicals that occur in at least 30% of the U.S. population, as well as three supercombinations consisting of relatively many chemicals that occur in a small but nonnegligible proportion of the U.S. population. Conclusions: We demonstrated how FIM can be used in conjunction with biomonitoring data to narrow a large number of possible chemical combinations down to a smaller set of prevalent chemical combinations. https://doi.org/10.1289/EHP1265 PMID:28858827

Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability.

PubMed

Ring, Caroline L; Pearce, Robert G; Setzer, R Woodrow; Wetmore, Barbara A; Wambaugh, John F

2017-09-01

The thousands of chemicals present in the environment (USGAO, 2013) must be triaged to identify priority chemicals for human health risk research. Most chemicals have little of the toxicokinetic (TK) data that are necessary for relating exposures to tissue concentrations that are believed to be toxic. Ongoing efforts have collected limited, in vitro TK data for a few hundred chemicals. These data have been combined with biomonitoring data to estimate an approximate margin between potential hazard and exposure. The most "at risk" 95th percentile of adults have been identified from simulated populations that are generated either using standard "average" adult human parameters or very specific cohorts such as Northern Europeans. To better reflect the modern U.S. population, we developed a population simulation using physiologies based on distributions of demographic and anthropometric quantities from the most recent U.S. Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES) data. This allowed incorporation of inter-individual variability, including variability across relevant demographic subgroups. Variability was analyzed with a Monte Carlo approach that accounted for the correlation structure in physiological parameters. To identify portions of the U.S. population that are more at risk for specific chemicals, physiologic variability was incorporated within an open-source high-throughput (HT) TK modeling framework. We prioritized 50 chemicals based on estimates of both potential hazard and exposure. Potential hazard was estimated from in vitro HT screening assays (i.e., the Tox21 and ToxCast programs). Bioactive in vitro concentrations were extrapolated to doses that produce equivalent concentrations in body tissues using a reverse dosimetry approach in which generic TK models are parameterized with: 1) chemical-specific parameters derived from in vitro measurements and predicted from chemical structure; and 2) with

Chemical cues identify gender and individuality in Giant pandas (Ailuropoda melanoleuca).

PubMed

Hagey, Lee; MacDonald, Edith

2003-06-01

The Giant panda communicates with conspecifics by depositing a mixture of volatile compounds (called scent marks) on trees and rocks. Using mass spectrometry, we identified 951 chemical components from scent glands, urine, vaginal secretions, and scent marks made by pandas. The scent marks of the two genders contained a similar array of chemicals but varied in concentration; specifically, males possessed a significantly greater amount of short chain fatty acids (F(1, 29) = 18.4, P = 0.002). Using stepwise discriminate analysis on the relative proportions of a subset of these chemicals, it was possible to classify gender (94% for males and females) and individuality (81% for males and 91% for females) from scent marks. The power to identify individual males was reduced due to the relatedness of two subjects. By cracking the identity code of Giant panda communication, we show insights into how these animals can match individuals with unique chemical profiles. Since radiocollaring is currently banned in China, the techniques described in this paper give field biologists a new means to identify and track pandas in the wild.

Identifying chemicals of concern in hydraulic fracturing fluids used for oil production.

PubMed

Stringfellow, William T; Camarillo, Mary Kay; Domen, Jeremy K; Sandelin, Whitney L; Varadharajan, Charuleka; Jordan, Preston D; Reagan, Matthew T; Cooley, Heather; Heberger, Matthew G; Birkholzer, Jens T

2017-01-01

Chemical additives used for hydraulic fracturing and matrix acidizing of oil reservoirs were reviewed and priority chemicals of concern needing further environmental risk assessment, treatment demonstration, or evaluation of occupational hazards were identified. We evaluated chemical additives used for well stimulation in California, the third largest oil producing state in the USA, by the mass and frequency of use, as well as toxicity. The most frequently used chemical additives in oil development were gelling agents, cross-linkers, breakers, clay control agents, iron and scale control agents, corrosion inhibitors, biocides, and various impurities and product stabilizers used as part of commercial mixtures. Hydrochloric and hydrofluoric acids, used for matrix acidizing and other purposes, were reported infrequently. A large number and mass of solvents and surface active agents were used, including quaternary ammonia compounds (QACs) and nonionic surfactants. Acute toxicity was evaluated and many chemicals with low hazard to mammals were identified as potentially hazardous to aquatic environments. Based on an analysis of quantities used, toxicity, and lack of adequate hazard evaluation, QACs, biocides, and corrosion inhibitors were identified as priority chemicals of concern that deserve further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identifying and designing chemicals with minimal acute aquatic toxicity

PubMed Central

Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T.; Zimmerman, Julie Beth

2015-01-01

Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure–activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical–chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard. PMID:24639521

Identifying and designing chemicals with minimal acute aquatic toxicity.

PubMed

Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T; Zimmerman, Julie Beth

2015-05-19

Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure-activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical-chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard.

Spectroscopy and reactions of molecules important in chemical evolution

NASA Technical Reports Server (NTRS)

Becker, R. S.

1974-01-01

The research includes: (1) hot hydrogen atom reactions in terms of the nature of products produced, mechanism of the reactions and the implication and application of such reactions for molecules existing in interstellar clouds, in planetary atmospheres, and in chemical evolution; (2) photochemical reactions that can lead to molecules important in chemical evolution, interstellar clouds and as constituents in planetary atmospheres; and (3) spectroscopic and theoretical properties of biomolecules and their precursors and where possible, use these to understand their photochemical behavior.

Identifying novel genes and chemicals related to nasopharyngeal cancer in a heterogeneous network.

PubMed

Li, Zhandong; An, Lifeng; Li, Hao; Wang, ShaoPeng; Zhou, You; Yuan, Fei; Li, Lin

2016-05-05

Nasopharyngeal cancer or nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The factors that induce nasopharyngeal cancer are still not clear. Additional information about the chemicals or genes related to nasopharyngeal cancer will promote a better understanding of the pathogenesis of this cancer and the factors that induce it. Thus, a computational method NPC-RGCP was proposed in this study to identify the possible relevant chemicals and genes based on the presently known chemicals and genes related to nasopharyngeal cancer. To extensively utilize the functional associations between proteins and chemicals, a heterogeneous network was constructed based on interactions of proteins and chemicals. The NPC-RGCP included two stages: the searching stage and the screening stage. The former stage is for finding new possible genes and chemicals in the heterogeneous network, while the latter stage is for screening and removing false discoveries and selecting the core genes and chemicals. As a result, five putative genes, CXCR3, IRF1, CDK1, GSTP1, and CDH2, and seven putative chemicals, iron, propionic acid, dimethyl sulfoxide, isopropanol, erythrose 4-phosphate, β-D-Fructose 6-phosphate, and flavin adenine dinucleotide, were identified by NPC-RGCP. Extensive analyses provided confirmation that the putative genes and chemicals have significant associations with nasopharyngeal cancer.

Identifying novel genes and chemicals related to nasopharyngeal cancer in a heterogeneous network

PubMed Central

Li, Zhandong; An, Lifeng; Li, Hao; Wang, ShaoPeng; Zhou, You; Yuan, Fei; Li, Lin

2016-01-01

Nasopharyngeal cancer or nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The factors that induce nasopharyngeal cancer are still not clear. Additional information about the chemicals or genes related to nasopharyngeal cancer will promote a better understanding of the pathogenesis of this cancer and the factors that induce it. Thus, a computational method NPC-RGCP was proposed in this study to identify the possible relevant chemicals and genes based on the presently known chemicals and genes related to nasopharyngeal cancer. To extensively utilize the functional associations between proteins and chemicals, a heterogeneous network was constructed based on interactions of proteins and chemicals. The NPC-RGCP included two stages: the searching stage and the screening stage. The former stage is for finding new possible genes and chemicals in the heterogeneous network, while the latter stage is for screening and removing false discoveries and selecting the core genes and chemicals. As a result, five putative genes, CXCR3, IRF1, CDK1, GSTP1, and CDH2, and seven putative chemicals, iron, propionic acid, dimethyl sulfoxide, isopropanol, erythrose 4-phosphate, β-D-Fructose 6-phosphate, and flavin adenine dinucleotide, were identified by NPC-RGCP. Extensive analyses provided confirmation that the putative genes and chemicals have significant associations with nasopharyngeal cancer. PMID:27149165

Laboratory Studies of Heterogeneous Chemical Processes of Atmospheric Importance

NASA Technical Reports Server (NTRS)

Molina, Mario J.

2004-01-01

The objective of this study is to conduct measurements of chemical kinetics parameters for heterogeneous reactions of importance in the stratosphere and the troposphere. It involves the elucidation of the mechanism of the interaction of HCl vapor with ice surfaces, which is the first step in the heterogeneous chlorine activation processes, as well as the investigation of the atmospheric oxidation mechanism of soot particles emitted by biomass and fossil fuels. The techniques being employed include turbulent flow-chemical ionization mass spectrometry and optical ellipsometry, among others.

Identifying Students with Chemical Health Problems: Background and Simulation.

ERIC Educational Resources Information Center

Maine State Dept. of Educational and Cultural Services, Augusta. Div. of Alcohol and Drug Education Services.

This document discusses the role of school personnel in identifying and referring students with chemical health problems. It introduces the topic by stating that school personnel should be aware of how to deal with students who have violated school rules and those who are seeking help. It states that they should know how to draw the line…

A Framework for Identifying Selective Chemical Applications for IPM in Dryland Agriculture

PubMed Central

Umina, Paul A.; Jenkins, Sommer; McColl, Stuart; Arthur, Aston; Hoffmann, Ary A.

2015-01-01

Shifts to Integrated Pest Management (IPM) in agriculture are assisted by the identification of chemical applications that provide effective control of pests relative to broad-spectrum pesticides but have fewer negative effects on natural enemy (beneficial) groups that assist in pest control. Here, we outline a framework for identifying such applications and apply this framework to field trials involving the crop establishment phase of Australian dryland cropping systems. Several chemicals, which are not presently available to farmers in Australia, were identified as providing moderate levels of pest control and seedling protection, with the potential to be less harmful to beneficial groups including predatory mites, predatory beetles and ants. This framework highlights the challenges involved in chemically controlling pests while maintaining non-target populations when pest species are present at damaging levels. PMID:26694469

Screening of chemical compound libraries identified new anti-Toxoplasma gondii agents.

PubMed

Adeyemi, Oluyomi Stephen; Sugi, Tatsuki; Han, Yongmei; Kato, Kentaro

2018-02-01

Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease that affects nearly one-third of the human population. The primary infection can be asymptomatic in healthy individuals but may prove fatal in immunocompromised individuals. Available treatment options for toxoplasmosis patients are limited, underscoring the urgent need to identify and develop new therapies. Non-biased screening of libraries of chemical compounds including the repurposing of well-characterized compounds is emerging as viable approach to achieving this goal. In the present investigation, we screened libraries of natural product and FDA-approved compounds to identify those that inhibited T. gondii growth. We identified 32 new compounds that potently inhibit T. gondii growth. Our findings are new and promising, and further strengthen the prospects of drug repurposing as well as the screening of a wide range of chemical compounds as a viable source of alternative anti-parasitic therapeutic agents.

A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer.

PubMed

Lagerweij, Tonny; Hiddingh, Lotte; Biesmans, Dennis; Crommentuijn, Matheus H W; Cloos, Jacqueline; Li, Xiao-Nan; Kogiso, Mari; Tannous, Bakhos A; Vandertop, W Peter; Noske, David P; Kaspers, Gertjan J L; Würdinger, Tom; Hulleman, Esther

2016-06-14

Treatment of medulloblastoma in children fails in approximately 30% of patients, and is often accompanied by severe late sequelae. Therefore, more effective drugs are needed that spare normal tissue and diminish long-term side effects. Since radiotherapy plays a pivotal role in the treatment of medulloblastoma, we set out to identify novel drugs that could potentiate the effect of ionizing radiation.Thereto, a small molecule library, consisting of 960 chemical compounds, was screened for its ability to sensitize towards irradiation. This small molecule screen identified the flavonoid quercetin as a novel radiosensitizer for the medulloblastoma cell lines DAOY, D283-med, and, to a lesser extent, D458-med at low micromolar concentrations and irradiation doses used in fractionated radiation schemes. Quercetin did not affect the proliferation of neural precursor cells or normal human fibroblasts. Importantly, in vivo experiments confirmed the radiosensitizing properties of quercetin. Administration of this flavonoid at the time of irradiation significantly prolonged survival in orthotopically xenografted mice. Together, these findings indicate that quercetin is a potent radiosensitizer for medulloblastoma cells that may be a promising lead for the treatment of medulloblastoma in patients.

78 FR 69131 - Importer of Controlled Substances, Notice of Registration, Chattem Chemicals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... Registration, Chattem Chemicals, Inc. By Notice dated August 15, 2013, and published in the Federal Register on August 26, 2013, 78 FR 52801, Chattem Chemicals, Inc., 3801 St. Elmo Avenue, Chattanooga, Tennessee 37409... registration of Chattem Chemicals, Inc., to import the basic classes of controlled substances is consistent...

21 CFR 1313.12 - Requirement of authorization to import.

Code of Federal Regulations, 2012 CFR

2012-04-01

... EXPORTATION OF LIST I AND LIST II CHEMICALS Importation of Listed Chemicals § 1313.12 Requirement of authorization to import. (a) Each regulated person who imports a listed chemical that meets or exceeds the threshold quantities identified in § 1310.04(f) or is a listed chemical for which no threshold has been...

21 CFR 1313.12 - Requirement of authorization to import.

Code of Federal Regulations, 2014 CFR

2014-04-01

... EXPORTATION OF LIST I AND LIST II CHEMICALS Importation of Listed Chemicals § 1313.12 Requirement of authorization to import. (a) Each regulated person who imports a listed chemical that meets or exceeds the threshold quantities identified in § 1310.04(f) or is a listed chemical for which no threshold has been...

21 CFR 1313.12 - Requirement of authorization to import.

Code of Federal Regulations, 2013 CFR

2013-04-01

... EXPORTATION OF LIST I AND LIST II CHEMICALS Importation of Listed Chemicals § 1313.12 Requirement of authorization to import. (a) Each regulated person who imports a listed chemical that meets or exceeds the threshold quantities identified in § 1310.04(f) or is a listed chemical for which no threshold has been...

76 FR 63304 - Guidance for Industry on Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-12

...] Guidance for Industry on Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage Form Drug... entitled ``Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage Form Drug Products for Anticounterfeiting.'' This guidance provides recommendations on design considerations for incorporating physical...

Laboratory Studies of Heterogeneous Chemical Processes of Atmospheric Importance

NASA Technical Reports Server (NTRS)

Molina, Mario J.

2003-01-01

The objective of this study is to conduct measurements of chemical kinetics parameters for heterogeneous reactions of importance in the stratosphere and the troposphere. It involves the elucidation of the mechanism of the interaction of HC1 vapor with ice surfaces, which is the first step in the heterogeneous chlorine activation processes, as well as the investigation of the atmospheric oxidation mechanism of soot particles emitted by biomass and fossil fuels. The techniques being employed include turbulent flow- chemical ionization mass spectrometry and optical ellipsometry, among others. The next section summarizes our research activities during the first year of the project, and the section that follows consists of the statement of work for the second year.

Chemical proteomics approaches for identifying the cellular targets of natural products

PubMed Central

Sieber, S. A.

2016-01-01

Covering: 2010 up to 2016 Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied “in situ” – in living systems rather than cell lysates. We also focus here on strategies that employ a click reaction, the copper-catalysed azide–alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. We also discuss ‘competitive mode’ approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed. PMID:27098809

Chemical proteomics approaches for identifying the cellular targets of natural products.

PubMed

Wright, M H; Sieber, S A

2016-05-04

Covering: 2010 up to 2016Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied "in situ" - in living systems rather than cell lysates. We also focus here on strategies that employ a click reaction, the copper-catalysed azide-alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. We also discuss 'competitive mode' approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed.

The importance of energetic particle precipitation on the chemical composition of the middle atmosphere

NASA Technical Reports Server (NTRS)

Thorne, R. M.

1980-01-01

The present review deals with the importance of three distinct classes of precipitation which directly deposit energy into the middle atmosphere, viz. galactic cosmic radiation, energetic solar protons and relativistic electron precipitation from the earth's radiation belts. Chemical considerations during particle precipitation are discussed, with special emphasis on the relative production rate of odd nitrogen and odd hydrogen species during ionizing particle precipitation. The long residence time of NO in the upper stratosphere, where catalytic interaction with O3 is most effective, requires that this mechanism be included in future modeling of global distribution of O3. Other situations causing O3 depletion are also identified.

Identifying marine Important Bird Areas using at-sea survey data

USGS Publications Warehouse

Smith, Melanie A.; Walker, Nathan J.; Free, Christopher M.; Kirchhoff, Matthew J.; Drew, Gary S.; Warnock, Nils; Stenhouse, Iain J.

2014-01-01

Effective marine bird conservation requires identification of at-sea locations used by populations for foraging, staging, and migration. Using an extensive database of at-sea survey data spanning over 30 years, we developed a standardized and data-driven spatial method for identifying globally significant marine Important Bird Areas in Alaska. To delineate these areas we developed a six-step process: binning data and accounting for unequal survey effort, filtering input data for persistence of species use, using a moving window analysis to produce maps representing a gradient from low to high abundance, drawing core area boundaries around major concentrations based on abundance thresholds, validating the results, and combining overlapping boundaries into important areas for multiple species. We identified 126 bird core areas which were merged into 59 pelagic sites important to 45 out of 57 species assessed. The final areas included approximately 34–38% of all marine birds in Alaska waters, within just 6% of the total area. We identified globally significant Important Bird Areas spanning 20 degrees of latitude and 56 degrees of longitude, in two different oceans, with climates ranging from temperate to polar. Although our maps did suffer from some data gaps, these gaps did not preclude us from identifying sites that incorporated 13% of the assessed continental waterbird population and 9% of the assessed global seabird population. The application of this technique over a large and productive region worked well for a wide range of birds, exhibiting a variety of foraging strategies and occupying a variety of ecosystem types.

An FTIR point sensor for identifying chemical WMD and hazardous materials

NASA Astrophysics Data System (ADS)

Norman, Mark L.; Gagnon, Aaron M.; Reffner, John A.; Schiering, David W.; Allen, Jeffrey D.

2004-03-01

A new point sensor for identifying chemical weapons of mass destruction and other hazardous materials based on Fourier transform infrared (FT-IR) spectroscopy is presented. The sensor is a portable, fully functional FT-IR system that features a miniaturized Michelson interferometer, an integrated diamond attenuated total reflection (ATR) sample interface, and an embedded on-board computer. Samples are identified by an automated search algorithm that compares their infrared spectra to digitized databases that include reference spectra of nerve and blister agents, toxic industrial chemicals, and other hazardous materials. The hardware and software are designed for use by technicians with no background in infrared spectroscopy. The unit, which is fully self-contained, can be hand-carried and used in a hot zone by personnel in Level A protective gear, and subsequently decontaminated by spraying or immersion. Wireless control by a remote computer is also possible. Details of the system design and performance, including results of field validation tests, are discussed.

15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS § 713.3 Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals. (a) Declarations and... requirements for exports and imports of Schedule 2 chemicals. 713.3 Section 713.3 Commerce and Foreign Trade...

Identifying Alternative Conceptions of Chemical Kinetics among Secondary School and Undergraduate Students in Turkey

ERIC Educational Resources Information Center

Cakmakci, Gultekin

2010-01-01

This study identifies some alternative conceptions of chemical kinetics held by secondary school and undergraduate students (N = 191) in Turkey. Undergraduate students who participated are studying to become chemistry teachers when they graduate. Students' conceptions about chemical kinetics were elicited through a series of written tasks and…

Anemonefishes rely on visual and chemical cues to correctly identify conspecifics

NASA Astrophysics Data System (ADS)

Johnston, Nicole K.; Dixson, Danielle L.

2017-09-01

Organisms rely on sensory cues to interpret their environment and make important life-history decisions. Accurate recognition is of particular importance in diverse reef environments. Most evidence on the use of sensory cues focuses on those used in predator avoidance or habitat recognition, with little information on their role in conspecific recognition. Yet conspecific recognition is essential for life-history decisions including settlement, mate choice, and dominance interactions. Using a sensory manipulated tank and a two-chamber choice flume, anemonefish conspecific response was measured in the presence and absence of chemical and/or visual cues. Experiments were then repeated in the presence or absence of two heterospecific species to evaluate whether a heterospecific fish altered the conspecific response. Anemonefishes responded to both the visual and chemical cues of conspecifics, but relied on the combination of the two cues to recognize conspecifics inside the sensory manipulated tank. These results contrast previous studies focusing on predator detection where anemonefishes were found to compensate for the loss of one sensory cue (chemical) by utilizing a second cue (visual). This lack of sensory compensation may impact the ability of anemonefishes to acclimate to changing reef environments in the future.

77 FR 24985 - Importer of Controlled Substances; Notice of Registration; ISP Freetown Fine Chemicals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... Registration; ISP Freetown Fine Chemicals By Notice dated October 8, 2010, and published in the Federal Register on October 20, 2010, 75 FR 64743, ISP Freetown Fine Chemicals, 238 South Main Street, Assonet... that the registration of ISP Freetown Fine Chemicals to import the basic class of controlled substance...

77 FR 64142 - Importer of Controlled Substances, Notice of Registration, ISP Freetown Fine Chemicals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-18

... Registration, ISP Freetown Fine Chemicals By Notice dated July 2, 2012, and published in the Federal Register on July 11, 2012, 77 FR 40910, ISP Freetown Fine Chemicals, 238 South Main Street, Assonet... that the registration of ISP Freetown Fine Chemicals to import the basic class of controlled substance...

78 FR 52801 - Importer of Controlled Substances; Notice of Application; Chattem Chemicals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-26

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances; Notice of Application; Chattem Chemicals, Inc. Pursuant to Title 21 Code of Federal Regulations 1301.34(a), this is notice that on June 21, 2013, Chattem Chemicals, Inc., 3801 St. Elmo Avenue, Chattanooga, Tennessee 37409...

77 FR 40086 - Importer of Controlled Substances, Notice of Application, Chattem Chemicals Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances, Notice of Application, Chattem Chemicals Inc. Pursuant to Title 21 Code of Federal Regulations 1301.34 (a), this is notice that on May 16, 2012, Chattem Chemicals Inc., 3801 St. Elmo Avenue, Chattanooga, Tennessee 37409...

Background and Discussion Questions for Identifying Priority Chemicals for Review and Assessment

EPA Pesticide Factsheets

This discussion guide is intended to be used to help structure public input during the September 2011 webinar and discussion forum addressing the prioritization factors and data sources EPA plans to use to identify priority chemicals for review.

Identifying new persistent and bioaccumulative organics among chemicals in commerce. III: byproducts, impurities, and transformation products.

PubMed

Howard, Philip H; Muir, Derek C G

2013-05-21

The goal of this series of studies was to identify commercial chemicals that might be persistent and bioaccumulative (PB) and that were not being considered in current wastewater and aquatic environmental measurement programs. In this study, we focus on chemicals that are not on commercial chemical lists such as U.S. EPA's Inventory Update Rule but may be found as byproducts or impurities in commercial chemicals or are likely transformation products from commercial chemical use. We evaluated the 610 chemicals from our earlier publication as well as high production volume chemicals and identified 320 chemicals (39 byproducts and impurities, and 281 transformation products) that could be potential PB chemicals. Four examples are discussed in detail; these chemicals had a fair amount of information on the commercial synthesis and byproducts and impurities that might be found in the commercial product. Unfortunately for many of the 610 chemicals, as well as the transformation products, little or no information was available. Use of computer-aided software to predict the transformation pathways in combination with the biodegradation rules of thumb and some basic organic chemistry has allowed 281 potential PB transformation products to be suggested for some of the 610 commercial chemicals; more PB transformation products were not selected since microbial degradation often results in less persistent and less bioaccumulative metabolites.

40 CFR 721.20 - Exports and imports.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Exports and imports. 721.20 Section... ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES General Provisions § 721.20 Exports and imports. Persons who intend to export a chemical substance identified in subpart E of this part, or in any proposed...

Important sources and chemical species of ambient fine particles related to adverse health effects

NASA Astrophysics Data System (ADS)

Heo, J.

2017-12-01

Although many epidemiological studies have reported that exposure to ambient fine particulate matter (PM2.5) has been linked to increases in mortality and mobidity health outcomes, the key question of which chemical species and sources of PM2.5 are most harmful to public health remains unanswered in the air pollution research area. This study was designed to address the key question with evaluating the risks of exposure to chemical species and source-specific PM2.5 mass on morbidity. Hourly measurements of PM2.5 mass and its major chemical species, including organic carbon, elemental carbon, ions, and trace elements, were observed from January 1 to December 31, 2013 at four of the PM2.5 supersites in urban environments in Korea and the reuslts were used in a positive matrix factorization to estimate source contributions to PM2.5 mass. Nine sources, including secondary sulfate, secondary nitrate, mobile, biomass burning, roadway emission, industry, oil combustion, soil, and aged sea salt, were identified and secondary inorganic aerosol factors (i.e. secondary sulfalte, and secondary nitrate) were the dominant sources contributing to 40% of the total PM2.5 mass in the study region. In order to evaluate the risks of exposure to chemical species and sources of PM2.5 on morbidity, emergency room visits for cardivascular disease and respiratory disease were considered. Hourly health outcomes were compared with hourly measurments of the PM2.5 chemical species and sources using a poission generalized linear model incorporating natural splines, as well as time-stratified case-crossover design. The PM2.5 mass and speveral chemical components, such as organic carbon, elemetal carbon, zinc, and potassium, were strongly associated with morbidity. Source-apporitionmened PM2.5 mass derived from biomass burning, and mobile sources, was significantly associated with cardiovascular and respiratory diseases. The findings represent that local combustion may be particularly important

Identifying Metabolically Active Chemicals Using a Consensus ...

EPA Pesticide Factsheets

Traditional toxicity testing provides insight into the mechanisms underlying toxicological responses but requires a high investment in a large number of resources. The new paradigm of testing approaches involves rapid screening studies able to evaluate thousands of chemicals across hundreds of biological targets through use of in vitro assays. Endocrine disrupting chemicals (EDCs) are of concern due to their ability to alter neurodevelopment, behavior, and reproductive success of humans and other species. A recent integrated computational model examined results across 18 ER-related assays in the ToxCast in vitro screening program to eliminate chemicals that produce a false signal by possibly interfering with the technological attributes of an individual assay. However, in vitro assays can also lead to false negatives when the complex metabolic processes that render a chemical bioactive in a living system might be unable to be replicated in an in vitro environment. In the current study, the influence of metabolism was examined for over 1,400 chemicals considered inactive using the integrated computational model. Over 2,000 first-generation and over 4,000 second-generation metabolites were generated for the inactive chemicals using in silico techniques. Next, a consensus model comprised of individual structure activity relationship (SAR) models was used to predict ER-binding activity for each of the metabolites. Binding activity was predicted for 8-10% of the meta

Development of a novel scoring system for identifying emerging chemical risks in the food chain.

PubMed

Oltmanns, J; Licht, O; Bitsch, A; Bohlen, M-L; Escher, S E; Silano, V; MacLeod, M; Serafimova, R; Kass, G E N; Merten, C

2018-02-21

The European Food Safety Authority (EFSA) is responsible for risk assessment of all aspects of food safety, including the establishment of procedures aimed at the identification of emerging risks to food safety. Here, a scoring system was developed for identifying chemicals registered under the European REACH Regulation that could be of potential concern in the food chain using the following parameters: (i) environmental release based on maximum aggregated tonnages and environmental release categories; (ii) biodegradation in the environment; (iii) bioaccumulation and in vivo and in vitro toxicity. The screening approach was tested on 100 data-rich chemicals registered under the REACH Regulation at aggregated volumes of at least 1000 tonnes per annum. The results show that substance-specific data generated under the REACH Regulation can be used to identify potential emerging risks in the food chain. After application of the screening procedure, priority chemicals can be identified as potentially emerging risk chemicals through the integration of exposure, environmental fate and toxicity. The default approach is to generate a single total score for each substance using a predefined weighting scenario. However, it is also possible to use a pivot table approach to combine the individual scores in different ways that reflect user-defined priorities, which enables a very flexible, iterative definition of screening criteria. Possible applications of the approaches are discussed using illustrative examples. Either approach can then be followed by in-depth evaluation of priority substances to ensure the identification of substances that present a real emerging chemical risk in the food chain.

A new multimedia contaminant fate model for China: how important are environmental parameters in influencing chemical persistence and long-range transport potential?

PubMed

Zhu, Ying; Price, Oliver R; Tao, Shu; Jones, Kevin C; Sweetman, Andy J

2014-08-01

We present a new multimedia chemical fate model (SESAMe) which was developed to assess chemical fate and behaviour across China. We apply the model to quantify the influence of environmental parameters on chemical overall persistence (POV) and long-range transport potential (LRTP) in China, which has extreme diversity in environmental conditions. Sobol sensitivity analysis was used to identify the relative importance of input parameters. Physicochemical properties were identified as more influential than environmental parameters on model output. Interactive effects of environmental parameters on POV and LRTP occur mainly in combination with chemical properties. Hypothetical chemicals and emission data were used to model POV and LRTP for neutral and acidic chemicals with different KOW/DOW, vapour pressure and pKa under different precipitation, wind speed, temperature and soil organic carbon contents (fOC). Generally for POV, precipitation was more influential than the other environmental parameters, whilst temperature and wind speed did not contribute significantly to POV variation; for LRTP, wind speed was more influential than the other environmental parameters, whilst the effects of other environmental parameters relied on specific chemical properties. fOC had a slight effect on POV and LRTP, and higher fOC always increased POV and decreased LRTP. Example case studies were performed on real test chemicals using SESAMe to explore the spatial variability of model output and how environmental properties affect POV and LRTP. Dibenzofuran released to multiple media had higher POV in northwest of Xinjiang, part of Gansu, northeast of Inner Mongolia, Heilongjiang and Jilin. Benzo[a]pyrene released to the air had higher LRTP in south Xinjiang and west Inner Mongolia, whilst acenaphthene had higher LRTP in Tibet and west Inner Mongolia. TCS released into water had higher LRTP in Yellow River and Yangtze River catchments. The initial case studies demonstrated that SESAMe

Using Ambystoma mexicanum (Mexican Axolotl) Embryos, Chemical Genetics, and Microarray Analysis to Identify Signaling Pathways Associated with Tissue Regeneration

PubMed Central

Ponomareva, Larissa V.; Athippozhy, Antony; Thorson, Jon S.; Voss, S. Randal

2015-01-01

Amphibian vertebrates are important models in regenerative biology because they present exceptional regenerative capabilities throughout life. However, it takes considerable effort to rear amphibians to juvenile and adult stages for regeneration studies and the relatively large sizes that frogs and salamanders achieve during development make them difficult to use in chemical screens. Here we introduce a new tail regeneration model using late stage Mexican axolotl embryos. We show that axolotl embryos completely regenerate amputated tails in 7 days before they exhaust their yolk supply and begin to feed. Further, we show that axolotl embryos can be efficiently reared in microtiter plates to achieve moderate throughput screening of soluble chemicals to investigate toxicity and identify molecules that alter regenerative outcome. As proof of principle, we identified integration 1 / wingless (Wnt), transforming growth factor beta (Tgf-β), and fibroblast growth factor (Fgf) pathway antagonists that completely block tail regeneration and additional chemicals that significantly affected tail outgrowth. Furthermore, we used microarray analysis to show that inhibition of Wnt signaling broadly affects transcription of genes associated with Wnt, Fgf, Tgf-β, epidermal growth factor (Egf), Notch, nerve growth factor (Ngf), homeotic gene (Hox), rat sarcoma/mitogen-activated protein kinase (Ras/Mapk), myelocytomatosis viral oncogene (Myc), tumor protein 53 (p53), and retinoic acid (RA) pathways. Punctuated changes in the expression of genes known to regulate vertebrate development were observed; this suggests the tail regeneration transcriptional program is hierarchically structured and temporally ordered. Our study establishes the axolotl as a chemical screening model to investigate signaling pathways associated with tissue regeneration. PMID:26092703

Identifying obstacles and ranking common biological control research priorities for Europe to manage most economically important pests in arable, vegetable and perennial crops.

PubMed

Lamichhane, Jay Ram; Bischoff-Schaefer, Monika; Bluemel, Sylvia; Dachbrodt-Saaydeh, Silke; Dreux, Laure; Jansen, Jean-Pierre; Kiss, Jozsef; Köhl, Jürgen; Kudsk, Per; Malausa, Thibaut; Messéan, Antoine; Nicot, Philippe C; Ricci, Pierre; Thibierge, Jérôme; Villeneuve, François

2017-01-01

EU agriculture is currently in transition from conventional crop protection to integrated pest management (IPM). Because biocontrol is a key component of IPM, many European countries recently have intensified their national efforts on biocontrol research and innovation (R&I), although such initiatives are often fragmented. The operational outputs of national efforts would benefit from closer collaboration among stakeholders via transnationally coordinated approaches, as most economically important pests are similar across Europe. This paper proposes a common European framework on biocontrol R&I. It identifies generic R&I bottlenecks and needs as well as priorities for three crop types (arable, vegetable and perennial crops). The existing gap between the market offers of biocontrol solutions and the demand of growers, the lengthy and expensive registration process for biocontrol solutions and their varying effectiveness due to variable climatic conditions and site-specific factors across Europe are key obstacles hindering the development and adoption of biocontrol solutions in Europe. Considering arable, vegetable and perennial crops, a dozen common target pests are identified for each type of crop and ranked by order of importance at European level. Such a ranked list indicates numerous topics on which future joint transnational efforts would be justified. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

In Silico Screening-Level Prioritization of 8468 Chemicals Produced in OECD Countries to Identify Potential Planetary Boundary Threats.

PubMed

Reppas-Chrysovitsinos, Efstathios; Sobek, Anna; MacLeod, Matthew

2018-01-01

Legislation such as the Stockholm Convention and REACH aim to identify and regulate the production and use of chemicals that qualify as persistent organic pollutants (POPs) and very persistent and very bioaccumulative (vPvB) chemicals, respectively. Recently, a series of studies on planetary boundary threats proposed seven chemical hazard profiles that are distinct from the POP and vPvB profiles. We previously defined two exposure-based hazard profiles; airborne persistent contaminants (APCs) and waterborne persistent contaminants (WPCs) that correspond to two profiles of chemicals that are planetary boundary threats. Here, we extend our method to screen a database of chemicals consisting of 8648 substances produced within the OECD countries. We propose a new scoring scheme to disentangle the POP, vPvB, APC and WPC profiles by focusing on the spatial range of exposure potential, discuss the relationship between high exposure hazard and elemental composition of chemicals, and identify chemicals with high exposure hazard potential.

The limits of two-year bioassay exposure regimens for identifying chemical carcinogens.

PubMed

Huff, James; Jacobson, Michael F; Davis, Devra Lee

2008-11-01

Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay. In this Commentary, we propose that the sensitivity of chemical carcinogenesis bio-assays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at up to about 3 years. Studies of three chemicals of different structures and uses-aspartame, cadmium, and toluene-suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies. Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives.

The Limits of Two-Year Bioassay Exposure Regimens for Identifying Chemical Carcinogens

PubMed Central

Huff, James; Jacobson, Michael F.; Davis, Devra Lee

2008-01-01

Background Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay. Objectives In this Commentary, we propose that the sensitivity of chemical carcinogenesis bio-assays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at up to about 3 years. Discussion Studies of three chemicals of different structures and uses—aspartame, cadmium, and toluene—suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies. Conclusions Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives. PMID:19057693

Identifying important nodes by adaptive LeaderRank

NASA Astrophysics Data System (ADS)

Xu, Shuang; Wang, Pei

2017-03-01

Spreading process is a common phenomenon in complex networks. Identifying important nodes in complex networks is of great significance in real-world applications. Based on the spreading process on networks, a lot of measures have been proposed to evaluate the importance of nodes. However, most of the existing measures are appropriate to static networks, which are fragile to topological perturbations. Many real-world complex networks are dynamic rather than static, meaning that the nodes and edges of such networks may change with time, which challenge numerous existing centrality measures. Based on a new weighted mechanism and the newly proposed H-index and LeaderRank (LR), this paper introduces a variant of the LR measure, called adaptive LeaderRank (ALR), which is a new member of the LR-family. Simulations on six real-world networks reveal that the new measure can well balance between prediction accuracy and robustness. More interestingly, the new measure can better adapt to the adjustment or local perturbations of network topologies, as compared with the existing measures. By discussing the detailed properties of the measures from the LR-family, we illustrate that the ALR has its competitive advantages over the other measures. The proposed algorithm enriches the measures to understand complex networks, and may have potential applications in social networks and biological systems.

Identifying geochemical processes using End Member Mixing Analysis to decouple chemical components for mixing ratio calculations

NASA Astrophysics Data System (ADS)

Pelizardi, Flavia; Bea, Sergio A.; Carrera, Jesús; Vives, Luis

2017-07-01

Mixing calculations (i.e., the calculation of the proportions in which end-members are mixed in a sample) are essential for hydrological research and water management. However, they typically require the use of conservative species, a condition that may be difficult to meet due to chemical reactions. Mixing calculation also require identifying end-member waters, which is usually achieved through End Member Mixing Analysis (EMMA). We present a methodology to help in the identification of both end-members and such reactions, so as to improve mixing ratio calculations. The proposed approach consists of: (1) identifying the potential chemical reactions with the help of EMMA; (2) defining decoupled conservative chemical components consistent with those reactions; (3) repeat EMMA with the decoupled (i.e., conservative) components, so as to identify end-members waters; and (4) computing mixing ratios using the new set of components and end-members. The approach is illustrated by application to two synthetic mixing examples involving mineral dissolution and cation exchange reactions. Results confirm that the methodology can be successfully used to identify geochemical processes affecting the mixtures, thus improving the accuracy of mixing ratios calculations and relaxing the need for conservative species.

Flow Tube Studies of Gas Phase Chemical Processes of Atmospheric Importance

NASA Technical Reports Server (NTRS)

Molina, Mario J.

1997-01-01

The objective of this project is to conduct measurements of elementary reaction rate constants and photochemistry parameters for processes of importance in the atmosphere. These measurements are being carried out under temperature and pressure conditions covering those applicable to the stratosphere and upper troposphere, using the chemical ionization mass spectrometry turbulent flow technique developed in our laboratory.

Pupicidal and repellent activities of Pogostemon cablin essential oil chemical compounds against medically important human vector mosquitoes

PubMed Central

Gokulakrishnan, J; Kuppusamy, Elumalai; Shanmugam, Dhanasekaran; Appavu, Anandan; Kaliyamoorthi, Krishnappa

2013-01-01

Objective To determine the repellent and pupicidal activities of Pogostemon cablin (P. cablin) chemical compositions were assayed for their toxicity against selected important vector mosquitoes, viz., Aedes aegypti (Ae. aegypti), Anopheles stephensi (An. stephensi) and Culex quinquefasciatus (Cx. quinquefasciatus) (Diptera: Culicidae). Methods The plants dry aerial parts were subjected to hydrodistillation using a modified Clevenger-type apparatus. The composition of the essential oil was analyzed by Gas Chromatography (GC) and GC mass spectrophotometry. Evaluation was carried out in a net cage (45 cm×30 cm×45 cm) containing 100 blood starved female mosquitoes and were assayed in the laboratory condition by using the protocol of WHO 2010. The repellent activity of P. cablin chemical compositions at concentration of 2mg/cm2were applied on skin of fore arm in man and exposed against adult female mosquitoes. The pupicidal activity was determined against selected important vector mosquitoes to concentration of 100 mg/L and mortality of each pupa was recorded after 24 h of exposure to the compounds. Results Chemical constituents of 15 compounds were identified in the oil of P.cablin compounds representing to 98.96%. The major components in essential oil were â-patchoulene, á-guaiene, ã-patchoulene, á-bulnesene and patchouli alcohol. The repellent activity of patchouli alcohol compound was found to be most effective for repellent activity and 2 mg/cm2 concentration provided 100% protection up to 280 min against Ae. aegypti, An. stephensi and Cx. quinquefasciatus, respectively. Similarly, pupae exposed to 100 mg/L concentrations of P. cablin chemical compositions. Among five compounds tested patchouli alcoholwas found to be most effective for pupicidal activity provided 28.44, 26.28 and 25.36 against Ae.aegypti, An.stephensi and Cx. quinquefasciatus, respectively. The percent adult emergence was inversely proportional to the concentration of compounds and directly

USE OF THE RIBONUCLEASE PROTECTION ASSAY FOR IDENTIFYING CHEMICALS WHICH ELLICIT HYPERSENSITIVITY RESPONSES

EPA Science Inventory

Use of the Ribonuclease Protection Assay (RPA) for Identifying Chemicals that Elicit Hypersensitivity Responses. L.M. Plitnick, 1, D.M. Sailstad, 2, and R.J. Smialowicz, 2 1UNC, Curriculum in Toxicology, Chapel Hill, NC and 2USEPA, NHEERL, RTP, NC.

The incidence of aller...

Chemical and non-chemical stressors affecting childhood obesity: a systematic scoping review.

PubMed

Lichtveld, Kim; Thomas, Kent; Tulve, Nicolle S

2018-01-01

Childhood obesity in the United States has doubled over the last three decades and currently affects 17% of children and adolescents. While much research has focused on individual behaviors impacting obesity, little research has emphasized the complex interactions of numerous chemical and non-chemical stressors found in a child's environment and how these interactions affect a child's health and well-being. The objectives of this systematic scoping review were to (1) identify potential chemical stressors in the context of non-chemical stressors that impact childhood obesity; and, (2) summarize our observations for chemical and non-chemical stressors in regards to child-specific environments within a community setting. A review was conducted to identify chemical and non-chemical stressors related to childhood obesity for the childhood life stages ranging from prenatal to adolescence. Stressors were identified and grouped into domains: individual behaviors, family/household behaviors, community stressors, and chemical exposures. Stressors were related to the child and the child's everyday environments and used to characterize child health and well-being. This review suggests that the interactions of chemical and non-chemical stressors are important for understanding a child's overall health and well-being. By considering these relationships, the exposure science research community can better design and implement strategies to reduce childhood obesity.

Genes Important for Schizosaccharomyces pombe Meiosis Identified Through a Functional Genomics Screen

PubMed Central

Blyth, Julie; Makrantoni, Vasso; Barton, Rachael E.; Spanos, Christos; Rappsilber, Juri; Marston, Adele L.

2018-01-01

Meiosis is a specialized cell division that generates gametes, such as eggs and sperm. Errors in meiosis result in miscarriages and are the leading cause of birth defects; however, the molecular origins of these defects remain unknown. Studies in model organisms are beginning to identify the genes and pathways important for meiosis, but the parts list is still poorly defined. Here we present a comprehensive catalog of genes important for meiosis in the fission yeast, Schizosaccharomyces pombe. Our genome-wide functional screen surveyed all nonessential genes for roles in chromosome segregation and spore formation. Novel genes important at distinct stages of the meiotic chromosome segregation and differentiation program were identified. Preliminary characterization implicated three of these genes in centrosome/spindle pole body, centromere, and cohesion function. Our findings represent a near-complete parts list of genes important for meiosis in fission yeast, providing a valuable resource to advance our molecular understanding of meiosis. PMID:29259000

Preventing, identifying, and managing cosmetic procedure complications, part 2: lasers and chemical peels.

PubMed

Brown, Megan

2016-08-01

Part 1 of this series highlighted some of the potential complications that have been associated with soft tissue augmentation and botulinum toxin injections. In part 2, tips for how dermatology residents may prevent, identify, and manage complications from lasers and chemical peels for optimal patient outcomes are provided.

Using Ambystoma mexicanum (Mexican axolotl) embryos, chemical genetics, and microarray analysis to identify signaling pathways associated with tissue regeneration.

PubMed

Ponomareva, Larissa V; Athippozhy, Antony; Thorson, Jon S; Voss, S Randal

2015-12-01

Amphibian vertebrates are important models in regenerative biology because they present exceptional regenerative capabilities throughout life. However, it takes considerable effort to rear amphibians to juvenile and adult stages for regeneration studies, and the relatively large sizes that frogs and salamanders achieve during development make them difficult to use in chemical screens. Here, we introduce a new tail regeneration model using late stage Mexican axolotl embryos. We show that axolotl embryos completely regenerate amputated tails in 7days before they exhaust their yolk supply and begin to feed. Further, we show that axolotl embryos can be efficiently reared in microtiter plates to achieve moderate throughput screening of soluble chemicals to investigate toxicity and identify molecules that alter regenerative outcome. As proof of principle, we identified integration 1 / wingless (Wnt), transforming growth factor beta (Tgf-β), and fibroblast growth factor (Fgf) pathway antagonists that completely block tail regeneration and additional chemicals that significantly affected tail outgrowth. Furthermore, we used microarray analysis to show that inhibition of Wnt signaling broadly affects transcription of genes associated with Wnt, Fgf, Tgf-β, epidermal growth factor (Egf), Notch, nerve growth factor (Ngf), homeotic gene (Hox), rat sarcoma/mitogen-activated protein kinase (Ras/Mapk), myelocytomatosis viral oncogene (Myc), tumor protein 53 (p53), and retinoic acid (RA) pathways. Punctuated changes in the expression of genes known to regulate vertebrate development were observed; this suggests the tail regeneration transcriptional program is hierarchically structured and temporally ordered. Our study establishes the axolotl as a chemical screening model to investigate signaling pathways associated with tissue regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... reports of exports and imports of Schedule 2 chemicals—(1) Declarations. A Schedule 2 plant site that is declared because it produced, processed or consumed a Schedule 2 chemical at one or more plants above the... plant site that same Schedule 2 chemical above the applicable threshold, must submit export and import...

15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... reports of exports and imports of Schedule 2 chemicals—(1) Declarations. A Schedule 2 plant site that is declared because it produced, processed or consumed a Schedule 2 chemical at one or more plants above the... plant site that same Schedule 2 chemical above the applicable threshold, must submit export and import...

15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

Code of Federal Regulations, 2012 CFR

2012-01-01

... reports of exports and imports of Schedule 2 chemicals—(1) Declarations. A Schedule 2 plant site that is declared because it produced, processed or consumed a Schedule 2 chemical at one or more plants above the... plant site that same Schedule 2 chemical above the applicable threshold, must submit export and import...

STUDY TO IDENTIFY IMPORTANT PARAMETERS FOR CHARACTERIZING PESTICIDE RESIDUE TRANSFER EFFICIENCIES

EPA Science Inventory

To reduce the uncertainty associated with current estimates of children's exposure to pesticides by dermal contact and non-dietary ingestion, residue transfer data are required. Prior to conducting exhaustive studies, a screening study to identify the important parameters for...

77 FR 41406 - Evaluation of In Vitro Tests for Identifying Eye Injury Hazard Potential of Chemicals and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Evaluation of In Vitro Tests for Identifying Eye Injury...-animal testing strategies proposed for identifying eye injury hazard potential of chemicals and products... Panel and submission of data from substances tested in in vitro tests for identifying eye injury hazard...

15 CFR 713.3 - Annual declaration and reporting requirements for exports and imports of Schedule 2 chemicals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... requirements for exports and imports of Schedule 2 chemicals. 713.3 Section 713.3 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS § 713.3 Annual...

76 FR 50220 - Availability of Draft ICCVAM Recommendations on Using Fewer Animals to Identify Chemical Eye...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

... Fewer Animals to Identify Chemical Eye Hazards: Revised Criteria Necessary to Maintain Equivalent Hazard... criteria using results from 3-animal tests that would provide eye hazard classification equivalent to... least 1 positive animal in a 3-animal test to identify eye hazards will provide the same or greater...

Chemical Safety Alert: Identifying Chemical Reactivity Hazards Preliminary Screening Method

EPA Pesticide Factsheets

Introduces small-to-medium-sized facilities to a method developed by Center for Chemical Process Safety (CCPS), based on a series of twelve yes-or-no questions to help determine hazards in warehousing, repackaging, blending, mixing, and processing.

Chemical screening platforms for autophagy drug discovery to identify therapeutic candidates for Huntington's disease and other neurodegenerative disorders.

PubMed

Sarkar, Sovan

2013-01-01

Autophagy is a cellular degradation process involved in the clearance of aggregate-prone proteins associated with neurodegenerative diseases. While the mTOR pathway has been known to be the major regulator of autophagy, recent advancements into the regulation of autophagy have identified mTOR-independent autophagy pathways that are amenable to chemical perturbations. Several chemical and genetic screens have been undertaken to identify small molecule and genetic regulators of autophagy, respectively. The small molecule autophagy enhancers offer great potential as therapeutic candidates not only for neurodegenerative diseases, but also for diverse human diseases where autophagy acts as a protective pathway. This review highlights the various chemical screening platforms for autophagy drug discovery pertinent for the treatment of neurodegenerative diseases.

15 CFR 712.6 - Advance notification and annual report of all exports and imports of Schedule 1 chemicals to, or...

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.6 Advance notification and annual report of all exports and imports of... of all exports and imports of Schedule 1 chemicals to, or from, other States Parties. 712.6 Section...

15 CFR 712.6 - Advance notification and annual report of all exports and imports of Schedule 1 chemicals to, or...

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.6 Advance notification and annual report of all exports and imports of... of all exports and imports of Schedule 1 chemicals to, or from, other States Parties. 712.6 Section...

Trust, but verify: On the importance of chemical structure curation in cheminformatics and QSAR modeling research

PubMed Central

Fourches, Denis; Muratov, Eugene; Tropsha, Alexander

2010-01-01

Molecular modelers and cheminformaticians typically analyze experimental data generated by other scientists. Consequently, when it comes to data accuracy, cheminformaticians are always at the mercy of data providers who may inadvertently publish (partially) erroneous data. Thus, dataset curation is crucial for any cheminformatics analysis such as similarity searching, clustering, QSAR modeling, virtual screening, etc., especially nowadays when the availability of chemical datasets in public domain has skyrocketed in recent years. Despite the obvious importance of this preliminary step in the computational analysis of any dataset, there appears to be no commonly accepted guidance or set of procedures for chemical data curation. The main objective of this paper is to emphasize the need for a standardized chemical data curation strategy that should be followed at the onset of any molecular modeling investigation. Herein, we discuss several simple but important steps for cleaning chemical records in a database including the removal of a fraction of the data that cannot be appropriately handled by conventional cheminformatics techniques. Such steps include the removal of inorganic and organometallic compounds, counterions, salts and mixtures; structure validation; ring aromatization; normalization of specific chemotypes; curation of tautomeric forms; and the deletion of duplicates. To emphasize the importance of data curation as a mandatory step in data analysis, we discuss several case studies where chemical curation of the original “raw” database enabled the successful modeling study (specifically, QSAR analysis) or resulted in a significant improvement of model's prediction accuracy. We also demonstrate that in some cases rigorously developed QSAR models could be even used to correct erroneous biological data associated with chemical compounds. We believe that good practices for curation of chemical records outlined in this paper will be of value to all

Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors Within the ToxCast Phase I and II Chemical Libraries

PubMed Central

Watt, Eric D.; Hornung, Michael W.; Hedge, Joan M.; Judson, Richard S.; Crofton, Kevin M.; Houck, Keith A.; Simmons, Steven O.

2016-01-01

High-throughput screening for potential thyroid-disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the U.S. Environmental Protection Agency ToxCast screening assay portfolio. To fill 1 critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast phase I and II chemical libraries, comprised of 1074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single-concentration screen were retested in concentration-response. Due to high false-positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed 2 additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using guaiacol as a substrate to confirm the activity profiles of putative TPO inhibitors. This effort represents the most extensive TPO inhibition screening campaign to date and illustrates a tiered screening approach that focuses resources, maximizes assay throughput, and reduces animal use. PMID:26884060

Identifying Outcomes that Are Important to Living Kidney Donors: A Nominal Group Technique Study.

PubMed

Hanson, Camilla S; Chapman, Jeremy R; Gill, John S; Kanellis, John; Wong, Germaine; Craig, Jonathan C; Teixeira-Pinto, Armando; Chadban, Steve J; Garg, Amit X; Ralph, Angelique F; Pinter, Jule; Lewis, Joshua R; Tong, Allison

2018-06-07

Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices. Previous donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically. Across 14 groups, 123 donors aged 27-78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0-1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility. Living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings. Copyright © 2018 by the American Society of Nephrology.

The Predatory Bird Monitoring Scheme: identifying chemical risks to top predators in Britain.

PubMed

Walker, Lee A; Shore, Richard F; Turk, Anthony; Pereira, M Glória; Best, Jennifer

2008-09-01

The Predatory Bird Monitoring Scheme (PBMS) is a long term (>40 y), UK-wide, exposure monitoring scheme that determines the concentration of selected pesticides and pollutants in the livers and eggs of predatory birds. This paper describes how the PBMS works, and in particular highlights some of the key scientific and policy drivers for monitoring contaminants in predatory birds and describes the specific aims, scope, and methods of the PBMS. We also present previously unpublished data that illustrates how the PBMS has been used to demonstrate the success of mitigation measures in reversing chemical-mediated impacts; identify and evaluate chemical threats to species of high conservation value; and finally to inform and refine monitoring methodologies. In addition, we discuss how such schemes can also address wider conservation needs.

Real World of Industrial Chemistry: Ethylene: The Organic Chemical Industry's Most Important Building Block.

ERIC Educational Resources Information Center

Fernelius, W. Conrad, Ed.; And Others

1979-01-01

The value of ethylene, as the organic chemical industry's most important building block, is discussed. The discussion focuses on the source of ethylene, its various forms and functions, and the ways in which the forms are made. (SA)

Data from Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors within the ToxCast Phase I and II Chemical Libraries

EPA Pesticide Factsheets

High-throughput screening for potential thyroid-disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the U.S. Environmental Protection Agency ToxCast screening assay portfolio. To fill 1 critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast phase I and II chemical libraries, comprised of 1074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single-concentration screen were retested in concentration-response. Due to high false-positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed 2 additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidat

Identifying new persistent and bioaccumulative organics among chemicals in commerce II: pharmaceuticals.

PubMed

Howard, Philip H; Muir, Derek C G

2011-08-15

The goal of this study was to identify commercial pharmaceuticals that might be persistent and bioaccumulative (P&B) and that were not being considered in current wastewater and aquatic environmental measurement programs. We developed a database of 3193 pharmaceuticals from two U.S. Food and Drug Administration (FDA) databases and some lists of top ranked or selling drugs. Of the 3193 pharmaceuticals, 275 pharmaceuticals have been found in the environment and 399 pharmaceuticals were, based upon production volumes, designated as high production volume (HPV) pharmaceuticals. All pharmaceuticals that had reported chemical structures were evaluated for potential bioaccumulation (B) or persistence (P) using quantitative structure property relationships (QSPR) or scientific judgment. Of the 275 drugs detected in the environment, 92 were rated as potentially bioaccumulative, 121 were rated as potentially persistent, and 99 were HPV pharmaceuticals. After removing the 275 pharmaceuticals previously detected in the environment, 58 HPV compounds were identified that were both P&B and 48 were identified as P only. Of the non-HPV compounds, 364 pharmaceuticals were identified that were P&B. This study has yielded some interesting and probable P&B pharmaceuticals that should be considered for further study.

Increasing the reliability and quality of important cast products made of chemically active metals and alloys

NASA Astrophysics Data System (ADS)

Varfolomeev, M. S.; Moiseev, V. S.; Shcherbakova, G. I.

2017-01-01

A technology is developed to produce highly thermoresistant ceramic monoxide corundum molds using investment casting and an aluminum-organic binder. This technology is a promising trend in creating ceramic molds for precision complex-shape casting of important ingots made of high-alloy steels, high-temperature and titanium alloys, and refractory metals. The use of the casting molds that have a high thermal and chemical resistance to chemically active metals and alloys under high-temperature casting minimizes the physicochemical interaction and substantially decreases the depth of the hard-to-remove metal oxide layer on important products, which increases their service properties.

Chemicals identified in human biological media: a data base. Third annual report, October 1981

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cone, M.V.; Baldauf, M.F.; Martin, F.M.

Data from almost 1600 of the 3800 body-burden documents collected to date have been entered in the data base as of October 1981. The emphasis on including recent literature and significant research documents has resulted in a chronological mix of articles from 1974 to the present. When body-burden articles are identified, data are extracted and entered in the data base by chemical and tissue/body fluid. Each data entry comprises a single record (or line entry) and is assigned a record number. If a particular document deals with more than one chemical and/or tissue, there will be multiple records for thatmore » document. For example, a study of 5 chemicals in each of 3 tissues has 15 different records (or 15 line entries) in the data base with 15 record numbers. Record numbers are assigned consecutively throughout the entire data base and appear in the upper left corner of the first column for each record.« less

Laboratory Studies of Homogeneous and Heterogeneous Chemical Processes of Importance in the Upper Atmosphere

NASA Technical Reports Server (NTRS)

Molina, Mario J.

2003-01-01

The objective of this study was to conduct measurements of chemical kinetics parameters for reactions of importance in the stratosphere and upper troposphere, and to study the interaction of trace gases with ice surfaces in order to elucidate the mechanism of heterogeneous chlorine activation processes, using both a theoretical and an experimental approach. The measurements were carried out under temperature and pressure conditions covering those applicable to the stratosphere and upper troposphere. The main experimental technique employed was turbulent flow-chemical ionization mass spectrometry, which is particularly well suited for investigations of radical-radical reactions.

Identification of sensory attributes, instrumental and chemical measurements important for consumer acceptability of grilled lamb Longissimus lumborum.

PubMed

Oltra, O R; Farmer, L J; Gordon, A W; Moss, B W; Birnie, J; Devlin, D J; Tolland, E L C; Tollerton, I J; Beattie, A M; Kennedy, J T; Farrell, D

2015-02-01

In this study, important eating quality attributes that influence consumer liking for grilled lamb loin have been identified using preference mapping techniques. The eating quality attributes identified as driving the consumer liking of lamb loin steaks were “tenderness”, “sweet flavour”, “meaty aftertaste”, “roast lamb flavour” and “roast lamb aftertaste”. In contrast, the texture attribute “rubbery” and the flavour attributes “bitter flavour” and "bitter aftertaste" had a negative influence on consumer perceptions. Associations were observed between eating quality and a number of instrumental and chemical measurements. Warner Bratzler Shear Force showed an association with “rubbery” texture and a negative association with “tenderness” and consumer liking scores. The compounds, glucose, glucose-6-phosphate, inosine, inosine monophosphate and adenosine monophosphate were associated with the attributes, “sweet flavour”,“meaty aftertaste”, “roast lamb flavour”, “roast lamb aftertaste” and with consumer scores for liking of lamb which is probably caused by the role some of these compounds play as precursors of flavour and as taste compounds.

Identifying New Candidate Genes and Chemicals Related to Prostate Cancer Using a Hybrid Network and Shortest Path Approach

PubMed Central

Wang, Meng; Wu, Kai; Lu, Changhong; Kong, Xiangyin

2015-01-01

Prostate cancer is a type of cancer that occurs in the male prostate, a gland in the male reproductive system. Because prostate cancer cells may spread to other parts of the body and can influence human reproduction, understanding the mechanisms underlying this disease is critical for designing effective treatments. The identification of as many genes and chemicals related to prostate cancer as possible will enhance our understanding of this disease. In this study, we proposed a computational method to identify new candidate genes and chemicals based on currently known genes and chemicals related to prostate cancer by applying a shortest path approach in a hybrid network. The hybrid network was constructed according to information concerning chemical-chemical interactions, chemical-protein interactions, and protein-protein interactions. Many of the obtained genes and chemicals are associated with prostate cancer. PMID:26504486

Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation

PubMed Central

Ackerman, Janet M.; Dairkee, Shanaz H.; Fenton, Suzanne E.; Johnson, Dale; Navarro, Kathleen M.; Osborne, Gwendolyn; Rudel, Ruthann A.; Solomon, Gina M.; Zeise, Lauren; Janssen, Sarah

2015-01-01

Background Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk. Methods Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC. Results The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist. Conclusions This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor β activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases. Citation Schwarzman MR, Ackerman JM, Dairkee SH, Fenton SE, Johnson D, Navarro KM, Osborne G, Rudel RA, Solomon GM, Zeise L, Janssen S. 2015

In vitro oral drug permeation models: the importance of taking physiological and physico-chemical factors into consideration.

PubMed

Joubert, Ruan; Steyn, Johan Dewald; Heystek, Hendrik Jacobus; Steenekamp, Jan Harm; Du Preez, Jan Lourens; Hamman, Josias Hendrik

2017-02-01

The assessment of intestinal membrane permeability properties of new chemical entities is a crucial step in the drug discovery and development process and a variety of in vitro models, methods and techniques are available to estimate the extent of oral drug absorption in humans. However, variations in certain physiological and physico-chemical factors are often not reflected in the results and the complex dynamic interplay between these factors is sometimes oversimplified with in vitro models. Areas covered: In vitro models to evaluate drug pharmacokinetics are briefly outlined, while both physiological and physico-chemical factors that may have an influence on these techniques are critically reviewed. The shortcomings identified for some of the in vitro techniques are discussed in conjunction with novel ways to improve and thereby overcome some challenges. Expert opinion: Although conventional in vitro methods and theories are used as basic guidelines to predict drug absorption, critical evaluations have identified some shortcomings. Advancements in technology have made it possible to investigate and understand the role of physiological and physico-chemical factors in drug delivery more clearly, which can be used to improve and refine the techniques to more closely mimic the in vivo environment.

Resampling procedures to identify important SNPs using a consensus approach.

PubMed

Pardy, Christopher; Motyer, Allan; Wilson, Susan

2011-11-29

Our goal is to identify common single-nucleotide polymorphisms (SNPs) (minor allele frequency > 1%) that add predictive accuracy above that gained by knowledge of easily measured clinical variables. We take an algorithmic approach to predict each phenotypic variable using a combination of phenotypic and genotypic predictors. We perform our procedure on the first simulated replicate and then validate against the others. Our procedure performs well when predicting Q1 but is less successful for the other outcomes. We use resampling procedures where possible to guard against false positives and to improve generalizability. The approach is based on finding a consensus regarding important SNPs by applying random forests and the least absolute shrinkage and selection operator (LASSO) on multiple subsamples. Random forests are used first to discard unimportant predictors, narrowing our focus to roughly 100 important SNPs. A cross-validation LASSO is then used to further select variables. We combine these procedures to guarantee that cross-validation can be used to choose a shrinkage parameter for the LASSO. If the clinical variables were unavailable, this prefiltering step would be essential. We perform the SNP-based analyses simultaneously rather than one at a time to estimate SNP effects in the presence of other causal variants. We analyzed the first simulated replicate of Genetic Analysis Workshop 17 without knowledge of the true model. Post-conference knowledge of the simulation parameters allowed us to investigate the limitations of our approach. We found that many of the false positives we identified were substantially correlated with genuine causal SNPs.

USE OF BIOASSAY-DIRECTED CHEMICAL ANALYSIS FOR IDENTIFYING MUTAGENIC COMPOUNDS IN URBAN AIR AND COMBUSTION EMISSIONS

EPA Science Inventory

Bioassay-directed chemical analysis fractionation has been used for 30 years to identify mutagenic classes of compounds in complex mixtures. Most studies have used the Salmonella (Ames) mutagenicity assay, and we have recently applied this methodology to two standard reference sa...

27 CFR 478.92 - How must licensed manufacturers and licensed importers identify firearms, armor piercing...

Code of Federal Regulations, 2010 CFR

2010-04-01

... Conduct of Business § 478.92 How must licensed manufacturers and licensed importers identify firearms... business; and (E) In the case of an imported firearm, the name of the country in which it was manufactured... place of business. For additional requirements relating to imported firearms, see Customs regulations at...

Flow Tube Studies of Gas Phase Chemical Processes of Atmospheric Importance

NASA Technical Reports Server (NTRS)

Molina, Mario J.

1998-01-01

The objective of this project is to conduct measurements of elementary reaction rate constants and photochemical parameters for processes of importance in the atmosphere. These measurements are being carried out under temperature and pressure conditions covering those applicable to the stratosphere and upper troposphere, using the chemical ionization mass spectrometry turbulent flow technique developed in our laboratory. The next section summarizes our research activities during the first year of the project, and the section that follows consists of the statement of work for the third year. Additional details concerning the projects listed in the statement of work were described in our original proposal.

Environmental Influences on Reproductive Health, the Importance of Chemical Exposures

PubMed Central

Wang, Aolin; Padula, Amy; Sirota, Marina; Woodruff, Tracey J.

2016-01-01

Unstructured Abstract Chemical exposures during pregnancy can have a profound and life-long impact on human health. Due to the omnipresence of chemicals in our daily life, there is continuous contact with chemicals in food, water, air and consumer products. Consequently, human biomonitoring studies show that pregnant women around the globe are exposed to a variety of chemicals. In this review, we provide a summary of current data on maternal and fetal exposure as well as health consequences from these exposures. We review several chemical classes including polychlorinated biphenyls (PCBs), perfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), phenols, phthalates, pesticides, and metals. Additionally, we discuss environmental disparities and vulnerable populations, and future research directions. We conclude by providing some recommendations for prevention of chemical exposure and its adverse reproductive health consequences. PMID:27513554

System and method for preconcentrating, identifying, and quantifying chemical and biological substances

DOEpatents

Yu, Conrad M.; Koo, Jackson C.

2000-01-01

A system and method for preconcentrating, identifying, and quantifying chemical and biological substances is disclosed. An input valve directs a first volume of a sample gas to a surface acoustic wave (SAW) device. The SAW device preconcentrates and detects a mass of a substance within the sample gas. An output valve receives a second volume of the sample gas containing the preconcentrated substance from the SAW device and directs the second volume to a gas chromatograph (GC). The GC identifies the preconcentrated substance within the sample gas. A shunt valve exhausts a volume of the sample gas equal to the first volume minus the second volume away from the SAW device and the GC. The method of the present invention includes the steps of opening an input valve for passing a first volume of a sample gas to a SAW device; preconcentrating and detecting a mass of a substance within the sample gas using the SAW device; opening an output valve for passing a second volume of the sample gas containing the preconcentrated substance to a gas chromatograph (GC); and then identifying the preconcentrated substance within the sample gas using the GC.

Identifying hub stations and important lines of bus networks: A case study in Xiamen, China

NASA Astrophysics Data System (ADS)

Zhang, Hui; Zhuge, Chengxiang; Yu, Xiaohua

2018-07-01

Hub stations and important lines play key roles in transfers between stations. In this paper, a node failure model is proposed to identify hub stations. In the model, we introduce two new indicators called neighborhood degree ratio and transfer index to evaluate the importance of stations, which consider neighborhood stations' degree of station and the initial transfer times between stations. Moreover, line accessibility is developed to measure the importance of lines in the bus network. Xiamen bus network in 2016 is utilized to test the model. The results show that the two introduced indicators are more effective to identify hub stations compared with traditional complex network indicators such as degree, clustering coefficient and betweenness.

THE IMPORTANCE OF SPATIAL ACCURACY FOR CHEMICAL INFORMATION MANAGEMENT

EPA Science Inventory

Information about chemicals can be critical to making timely decisions. The results of these decisions may not be realized for many years. In order to increase the value of chemical information and to create and utilize meaningful environmental models, the Environmental Prote...

Important caves to be identified

NASA Astrophysics Data System (ADS)

Criteria to identify significant caves on federal land are being developed by the Interior Department's Bureau of Land Management and the Agriculture Department's Forest Service under requirements of the Federal Cave Resources Protection Act of 1988. The departments gave advance notice of proposed rulemaking March 3 and invited suggestions and comments from the public for 30 days.The law requires protection, to the extent practical, of significant caves on lands administered by the Secretaries of Agriculture and Interior and includes authority to issue and revoke permits for collection and removal of cave resources and special provisions for regulation of cave resources on Indian lands. Final regulations must be published by August 18, 1989.

Identifying Rhodamine Dye Plume Sources in Near-Shore Oceanic Environments by Integration of Chemical and Visual Sensors

PubMed Central

Tian, Yu; Kang, Xiaodong; Li, Yunyi; Li, Wei; Zhang, Aiqun; Yu, Jiangchen; Li, Yiping

2013-01-01

This article presents a strategy for identifying the source location of a chemical plume in near-shore oceanic environments where the plume is developed under the influence of turbulence, tides and waves. This strategy includes two modules: source declaration (or identification) and source verification embedded in a subsumption architecture. Algorithms for source identification are derived from the moth-inspired plume tracing strategies based on a chemical sensor. The in-water test missions, conducted in November 2002 at San Clemente Island (California, USA) in June 2003 in Duck (North Carolina, USA) and in October 2010 at Dalian Bay (China), successfully identified the source locations after autonomous underwater vehicles tracked the rhodamine dye plumes with a significant meander over 100 meters. The objective of the verification module is to verify the declared plume source using a visual sensor. Because images taken in near shore oceanic environments are very vague and colors in the images are not well-defined, we adopt a fuzzy color extractor to segment the color components and recognize the chemical plume and its source by measuring color similarity. The source verification module is tested by images taken during the CPT missions. PMID:23507823

Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleijnen, J.P.C.; Helton, J.C.

1999-04-01

The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (1) linear relationships with correlation coefficients, (2) monotonic relationships with rank correlation coefficients, (3) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (4) trends in variability as defined by variances and interquartile ranges, and (5) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are consideredmore » for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (1) Type I errors are unavoidable, (2) Type II errors can occur when inappropriate analysis procedures are used, (3) physical explanations should always be sought for why statistical procedures identify variables as being important, and (4) the identification of important variables tends to be stable for independent Latin hypercube samples.« less

Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

PubMed Central

Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

2014-01-01

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases. Objectives: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. Results: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ≤ 3; p < 0.05]. More than 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP. Conclusions: Our multiplexed qHTS approach allowed us to generate a robust and reliable data set to evaluate the ability of thousands of drugs and environmental compounds to decrease MMP. The use of structure-based clustering analysis allowed us to identify molecular features that are likely responsible for the observed activity. Citation: Attene-Ramos MS, Huang R, Michael S, Witt KL, Richard A, Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox

Different approaches for identifying important concepts in probabilistic biomedical text summarization.

PubMed

Moradi, Milad; Ghadiri, Nasser

2018-01-01

Automatic text summarization tools help users in the biomedical domain to acquire their intended information from various textual resources more efficiently. Some of biomedical text summarization systems put the basis of their sentence selection approach on the frequency of concepts extracted from the input text. However, it seems that exploring other measures rather than the raw frequency for identifying valuable contents within an input document, or considering correlations existing between concepts, may be more useful for this type of summarization. In this paper, we describe a Bayesian summarization method for biomedical text documents. The Bayesian summarizer initially maps the input text to the Unified Medical Language System (UMLS) concepts; then it selects the important ones to be used as classification features. We introduce six different feature selection approaches to identify the most important concepts of the text and select the most informative contents according to the distribution of these concepts. We show that with the use of an appropriate feature selection approach, the Bayesian summarizer can improve the performance of biomedical summarization. Using the Recall-Oriented Understudy for Gisting Evaluation (ROUGE) toolkit, we perform extensive evaluations on a corpus of scientific papers in the biomedical domain. The results show that when the Bayesian summarizer utilizes the feature selection methods that do not use the raw frequency, it can outperform the biomedical summarizers that rely on the frequency of concepts, domain-independent and baseline methods. Copyright © 2017 Elsevier B.V. All rights reserved.

Identifying important motivational factors for professionals in Greek hospitals

PubMed Central

Kontodimopoulos, Nick; Paleologou, Victoria; Niakas, Dimitris

2009-01-01

Background The purpose of this study was to identify important motivational factors according to the views of health-care professionals in Greek hospitals and particularly to determine if these might differ in the public and private sectors. Methods A previously developed -and validated- instrument addressing four work-related motivators (job attributes, remuneration, co-workers and achievements) was used. Three categories of health care professionals, doctors (N = 354), nurses (N = 581) and office workers (N = 418), working in public and private hospitals, participated and motivation was compared across socio-demographic and occupational variables. Results The range of reported motivational factors was mixed and Maslow's conclusions that lower level motivational factors must be met before ascending to the next level were not confirmed. The highest ranked motivator for the entire sample, and by professional subgroup, was achievements (P < 0.001). Within subgroups, motivators were similar, and only one significant difference was observed, namely between doctors and nurses in respect to co-workers (P < 0.05). Remuneration (and salary in particular) was reported as a significant incentive only for professionals in managerial positions. Health professionals in private hospitals were motivated by all factors significantly more than their public-hospital counterparts. Conclusion The results are in agreement with the literature which focuses attention to management approaches employing both monetary and non-monetary incentives to motivate health care workers. This study showed that intrinsic factors are particularly important and should become a target for effective employee motivation. PMID:19754968

Identifying Hazards

EPA Pesticide Factsheets

The federal government has established a system of labeling hazardous materials to help identify the type of material and threat posed. Summaries of information on over 300 chemicals are maintained in the Envirofacts Master Chemical Integrator.

Laboratory Studies of Homogeneous and Heterogeneous Chemical Processes of Importance in the Upper Atmosphere

NASA Technical Reports Server (NTRS)

Molina, Mario J.

2001-01-01

The objective of this study is to conduct measurements of chemical kinetics parameters for reactions of importance in the stratosphere and upper troposphere, and to study the interaction of trace gases such as HCl with ice surfaces in order to elucidate the mechanism of heterogeneous chlorine activation processes, using both a theoretical and an experimental approach. The measurements will be carried out under temperature and pressure conditions covering those applicable to the stratosphere and upper troposphere. The techniques to be employed include turbulent flow - chemical ionization mass spectrometry, and optical ellipsometry. The next section summarizes our research activities during the second year of the project, and the section that follows consists of the statement of work for the third year.

The effects of chemical and physical factors on mammalian embryo culture and their importance for the practice of assisted human reproduction.

PubMed

Wale, Petra L; Gardner, David K

2016-01-01

Although laboratory procedures, along with culture media formulations, have improved over the past two decades, the issue remains that human IVF is performed in vitro (literally 'in glass'). Using PubMed, electronic searches were performed using keywords from a list of chemical and physical factors with no limits placed on time. Examples of keywords include oxygen, ammonium, volatile organics, temperature, pH, oil overlays and incubation volume/embryo density. Available clinical and scientific evidence surrounding physical and chemical factors have been assessed and presented here. Development of the embryo outside the body means that it is constantly exposed to stresses that it would not experience in vivo. Sources of stress on the human embryo include identified factors such as pH and temperature shifts, exposure to atmospheric (20%) oxygen and the build-up of toxins in the media due to the static nature of culture. However, there are other sources of stress not typically considered, such as the act of pipetting itself, or the release of organic compounds from the very tissue culture ware upon which the embryo develops. Further, when more than one stress is present in the laboratory, there is evidence that negative synergies can result, culminating in significant trauma to the developing embryo. It is evident that embryos are sensitive to both chemical and physical signals within their microenvironment, and that these factors play a significant role in influencing development and events post transfer. From the viewpoint of assisted human reproduction, a major concern with chemical and physical factors lies in their adverse effects on the viability of embryos, and their long-term effects on the fetus, even as a result of a relatively brief exposure. This review presents data on the adverse effects of chemical and physical factors on mammalian embryos and the importance of identifying, and thereby minimizing, them in the practice of human IVF. Hence, optimizing the

ASSESSMENT OF A FATHEAD MINNOW REPRODUCTION ASSAY FOR IDENTIFYING ENDOCRINE-DISRUPTING CHEMICALS WITH DIVERSE MODES OF ACTION

EPA Science Inventory

The US EPA has developed a short-term reproduction test with the fathead minnow to identify potential endocrine disrupting chemicals (EDCs). The assay is initiated by collecting baseline spawning data from reproductively-active adult fathead minnows for 21 d, followed by a 21 d e...

Risks and Chemical Substances.

ERIC Educational Resources Information Center

Blumberg, Avrom A.

1994-01-01

Examines exposure to chemicals within the home and three important ways in which hazardous substances can be identified and evaluated. Suggests a rational picture of human health risks and contains an introductory discussion of reasons for exposure, epidemiology, cancer causes and patterns, animal testing, toxins, and risk. (LZ)

CSI 3.0: a web server for identifying secondary and super-secondary structure in proteins using NMR chemical shifts

PubMed Central

Hafsa, Noor E.; Arndt, David; Wishart, David S.

2015-01-01

The Chemical Shift Index or CSI 3.0 (http://csi3.wishartlab.com) is a web server designed to accurately identify the location of secondary and super-secondary structures in protein chains using only nuclear magnetic resonance (NMR) backbone chemical shifts and their corresponding protein sequence data. Unlike earlier versions of CSI, which only identified three types of secondary structure (helix, β-strand and coil), CSI 3.0 now identifies total of 11 types of secondary and super-secondary structures, including helices, β-strands, coil regions, five common β-turns (type I, II, I′, II′ and VIII), β hairpins as well as interior and edge β-strands. CSI 3.0 accepts experimental NMR chemical shift data in multiple formats (NMR Star 2.1, NMR Star 3.1 and SHIFTY) and generates colorful CSI plots (bar graphs) and secondary/super-secondary structure assignments. The output can be readily used as constraints for structure determination and refinement or the images may be used for presentations and publications. CSI 3.0 uses a pipeline of several well-tested, previously published programs to identify the secondary and super-secondary structures in protein chains. Comparisons with secondary and super-secondary structure assignments made via standard coordinate analysis programs such as DSSP, STRIDE and VADAR on high-resolution protein structures solved by X-ray and NMR show >90% agreement between those made with CSI 3.0. PMID:25979265

CSI 3.0: a web server for identifying secondary and super-secondary structure in proteins using NMR chemical shifts.

PubMed

Hafsa, Noor E; Arndt, David; Wishart, David S

2015-07-01

The Chemical Shift Index or CSI 3.0 (http://csi3.wishartlab.com) is a web server designed to accurately identify the location of secondary and super-secondary structures in protein chains using only nuclear magnetic resonance (NMR) backbone chemical shifts and their corresponding protein sequence data. Unlike earlier versions of CSI, which only identified three types of secondary structure (helix, β-strand and coil), CSI 3.0 now identifies total of 11 types of secondary and super-secondary structures, including helices, β-strands, coil regions, five common β-turns (type I, II, I', II' and VIII), β hairpins as well as interior and edge β-strands. CSI 3.0 accepts experimental NMR chemical shift data in multiple formats (NMR Star 2.1, NMR Star 3.1 and SHIFTY) and generates colorful CSI plots (bar graphs) and secondary/super-secondary structure assignments. The output can be readily used as constraints for structure determination and refinement or the images may be used for presentations and publications. CSI 3.0 uses a pipeline of several well-tested, previously published programs to identify the secondary and super-secondary structures in protein chains. Comparisons with secondary and super-secondary structure assignments made via standard coordinate analysis programs such as DSSP, STRIDE and VADAR on high-resolution protein structures solved by X-ray and NMR show >90% agreement between those made with CSI 3.0. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Oparin's coacervates as an important milestone in chemical evolution

NASA Astrophysics Data System (ADS)

Kolb, Vera M.

2015-09-01

Although Oparin's coacervate model for the origin of life by chemical evolution is almost 100 years old, it is still valid. However, the structure of his originally proposed coacervate is not considered prebiotic, based on some recent developments in prebiotic chemistry. We have remedied this deficiency of the Oparin's model, by substituting his coacervate with a prebiotically feasible one. Oparin's coacervates are aqueous structures, but have a boundary with the rest of the aqueous medium. They exhibit properties of self-replication, and provide a path to a primitive metabolism, via chemical competition and thus a primitive selection. Thus, coacervates are good models for proto-cells. We review here some salient points of Oparin's model and address also some philosophical views on the beginning of natural selection in primitive chemical systems.

Chemical and Biological Defense: Designated Entity Needed to Identify, Align, and Manage DOD’s Infrastructure

DTIC Science & Technology

2015-06-01

Designated Leader, GAO-10-645 (Washington, D.C.: June 30, 2010). 35See GAO, Biological Defense: DOD Has Strengthened Coordination on Medical... on track to be designated a Leadership in Energy and Environmental Design facility. metabolic poisons, and pulmonary toxicants; nerve agent...CHEMICAL AND BIOLOGICAL DEFENSE Designated Entity Needed to Identify, Align, and Manage DOD’s Infrastructure

CON4EI: Selection of the reference chemicals for hazard identification and labelling of eye irritating chemicals.

PubMed

Adriaens, E; Alépée, N; Kandarova, H; Drzewieckac, A; Gruszka, K; Guest, R; Willoughby, J A; Verstraelen, S; Van Rompay, A R

2017-10-01

Assessment of the acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. In the past, several prospective and retrospective validation studies have taken place in the area of serious eye damage/eye irritation testing. Success in terms of complete replacement of the regulatory in vivo Draize rabbit eye test has not yet been achieved. A very important aspect to ensure development of successful alternative test methods and/or strategies for serious eye damage/eye irritation testing is the selection of appropriate reference chemicals. A set of 80 reference chemicals was selected for the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project, in collaboration with Cosmetics Europe, from the Draize Reference Database published by Cosmetics Europe based on key criteria that were set in their paper (e.g. balanced by important driver of classification and physical state). The most important goals of the CON4EI project were to identify the performance of eight in vitro alternative tests in terms of driver of classification and to identify similarities/differences between the methods in order the build a successful testing strategy that can discriminate between all UN GHS categories. This paper provides background on selection of the test chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

PTEN IDENTIFIED AS IMPORTANT RISK FACTOR OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

PubMed Central

Hosgood, H Dean; Menashe, Idan; He, Xingzhou; Chanock, Stephen; Lan, Qing

2009-01-01

Common genetic variation may play an important role in altering chronic obstructive pulmonary disease (COPD) risk. In Xuanwei, China, the COPD rate is more than twice the Chinese national average, and COPD is strongly associated with in-home coal use. To identify genetic variation that may be associated with COPD in a population with substantial in-home coal smoke exposures, we evaluated 1,261 single nucleotide polymorphisms (SNPs) in 380 candidate genes potentially relevant for cancer and other human diseases in a population-based case-control study in Xuanwei (53 cases; 107 controls). PTEN was the most significantly associated gene with COPD in a minP analysis using 20,000 permutations (P = 0.00005). SNP-based analyses found that homozygote variant carriers of PTEN rs701848 (ORTT = 0.12, 95%CI = 0.03 - 0.47) had a significant decreased risk of COPD. PTEN, or phosphatase and tensin homolog, is an important regulator of cell cycle progression and cellular survival via the AKT signaling pathway. Our exploratory analysis suggests that genetic variation in PTEN may be an important risk factor of COPD in Xuanwei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuanwei and other populations with coal smoke exposures. PMID:19625176

In vitro chemical screening assays to identify thyroid hormone disruptors.

EPA Science Inventory

Identification of chemicals with potential to impact thyroid hormone function is a priority of the US EPA’s Endocrine Disruptor Screening Program (EDSP). In vitro screening assays can be used to significantly reduce the number of chemicals that need to be considered for tes...

15 CFR 713.1 - Prohibition on exports and imports of Schedule 2 chemicals to and from States not Party to the CWC.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS § 713.1 Prohibition on exports and imports of Schedule 2 chemicals to and from States not Party to the... Schedule 2 chemicals to and from States not Party to the CWC. 713.1 Section 713.1 Commerce and Foreign...

Screening and prioritisation of chemical risks from metal mining operations, identifying exposure media of concern.

PubMed

Pan, Jilang; Oates, Christopher J; Ihlenfeld, Christian; Plant, Jane A; Voulvoulis, Nikolaos

2010-04-01

Metals have been central to the development of human civilisation from the Bronze Age to modern times, although in the past, metal mining and smelting have been the cause of serious environmental pollution with the potential to harm human health. Despite problems from artisanal mining in some developing countries, modern mining to Western standards now uses the best available mining technology combined with environmental monitoring, mitigation and remediation measures to limit emissions to the environment. This paper develops risk screening and prioritisation methods previously used for contaminated land on military and civilian sites and engineering systems for the analysis and prioritisation of chemical risks from modern metal mining operations. It uses hierarchical holographic modelling and multi-criteria decision making to analyse and prioritise the risks from potentially hazardous inorganic chemical substances released by mining operations. A case study of an active platinum group metals mine in South Africa is used to demonstrate the potential of the method. This risk-based methodology for identifying, filtering and ranking mining-related environmental and human health risks can be used to identify exposure media of greatest concern to inform risk management. It also provides a practical decision-making tool for mine acquisition and helps to communicate risk to all members of mining operation teams.

Challenges to studying the health effects of early life environmental chemical exposures on children's health.

PubMed

Braun, Joseph M; Gray, Kimberly

2017-12-01

Epidemiological studies play an important role in quantifying how early life environmental chemical exposures influence the risk of childhood diseases. These studies face at least four major challenges that can produce noise when trying to identify signals of associations between chemical exposure and childhood health. Challenges include accurately estimating chemical exposure, confounding from causes of both exposure and disease, identifying periods of heightened vulnerability to chemical exposures, and determining the effects of chemical mixtures. We provide recommendations that will aid in identifying these signals with more precision.

Titan's Interior Chemical Composition: Possible Important Phase Transitions

NASA Astrophysics Data System (ADS)

Howard, Michael; Fried, L. E.; Khare, B. N.; McKay, C. P.

2008-09-01

We study the interior composition of Titan using thermal chemical equilibrium calculations that are valid to high pressures and temperatures. The equations of state are based on exponential-6 fluid theory and have been validated against experimental data up to a few Mbars in pressure and approximately 20000K in temperature. In addition to CHNO molecules, we account for multi-phases of carbon, water and a variety of metals such as Al and Fe, and their oxides. With these fluid equations of state, chemical equilibrium is calculated for a set of product species. As the temperature and pressure evolves for increasing depth in the interior, the chemical equilibrium shifts. We assume that Titan is initially composed of comet material, which we assume to be solar, except for hydrogen, which we take to be depleted by a factor 1/1000. We find that a significant amount of nitrogen is in the form of N2, rather than NH3. Moreover, above 12 kbars pressure, as is the interior pressure of Titan, a significant amount of the carbon is in the form of graphite, rather than CO2 and CH4. We discuss the implications of these results for understanding the atmospheric and surface composition of Titan. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

The Architecture of Chemical Alternatives Assessment.

PubMed

Geiser, Kenneth; Tickner, Joel; Edwards, Sally; Rossi, Mark

2015-12-01

Chemical alternatives assessment is a method rapidly developing for use by businesses, governments, and nongovernment organizations seeking to substitute chemicals of concern in production processes and products. Chemical alternatives assessment is defined as a process for identifying, comparing, and selecting safer alternatives to chemicals of concern (including those in materials, processes, or technologies) on the basis of their hazards, performance, and economic viability. The process is intended to provide guidance for assuring that chemicals of concern are replaced with safer alternatives that are not likely to be later regretted. Conceptually, the assessment methods are developed from a set of three foundational pillars and five common principles. Based on a number of emerging alternatives assessment initiatives, in this commentary, we outline a chemical alternatives assessment blueprint structured around three broad steps: Scope, Assessment, and Selection and Implementation. Specific tasks and tools are identified for each of these three steps. While it is recognized that on-going practice will further refine and develop the method and tools, it is important that the structure of the assessment process remain flexible, adaptive, and focused on the substitution of chemicals of concern with safer alternatives. © 2015 Society for Risk Analysis.

Triacylglycerols profiling in plant oils important in food industry, dietetics and cosmetics using high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

PubMed

Lísa, Miroslav; Holcapek, Michal

2008-07-11

Optimized non-aqueous reversed-phase high-performance liquid chromatography method using acetonitrile-2-propanol gradient elution and the column coupling in the total length of 45 cm has been applied for the high resolution separation of plant oils important in food industry, dietetics and cosmetics. Positive-ion atmospheric pressure chemical ionization mass spectrometry is used for the unambiguous identification and also the reliable quantitation with the response factors approach. Based on the precise determination of individual triacyglycerol concentrations, the calculation of average parameters important in the nutrition is performed, i.e. average carbon number, average double bond number, relative concentrations of essential, saturated, monounsaturated and polyunsaturated fatty acids. Results are reported in the form of both chromatographic fingerprints and tables containing relative concentrations for all triacylglycerols and fatty acids in individual samples. In total, 264 triacylglycerols consisting of 28 fatty acids with the alkyl chain length from 6 to 26 carbon atoms and 0 to 4 double bonds have been identified in 26 industrial important plant oils.

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

PubMed Central

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using random forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers were 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the ScoreCard database of possible skin or sense organ toxicants as primary candidates for experimental validation. PMID:25560674

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis.

PubMed

Fazly, Ahmed; Jain, Charu; Dehner, Amie C; Issi, Luca; Lilly, Elizabeth A; Ali, Akbar; Cao, Hong; Fidel, Paul L; Rao, Reeta P; Kaufman, Paul D

2013-08-13

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis

PubMed Central

Fazly, Ahmed; Jain, Charu; Dehner, Amie C.; Issi, Luca; Lilly, Elizabeth A.; Ali, Akbar; Cao, Hong; Fidel, Paul L.; P. Rao, Reeta; Kaufman, Paul D.

2013-01-01

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis. PMID:23904484

Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer.

PubMed

Bar-Peled, Liron; Kemper, Esther K; Suciu, Radu M; Vinogradova, Ekaterina V; Backus, Keriann M; Horning, Benjamin D; Paul, Thomas A; Ichu, Taka-Aki; Svensson, Robert U; Olucha, Jose; Chang, Max W; Kok, Bernard P; Zhu, Zhou; Ihle, Nathan T; Dix, Melissa M; Jiang, Ping; Hayward, Matthew M; Saez, Enrique; Shaw, Reuben J; Cravatt, Benjamin F

2017-10-19

The transcription factor NRF2 is a master regulator of the cellular antioxidant response, and it is often genetically activated in non-small-cell lung cancers (NSCLCs) by, for instance, mutations in the negative regulator KEAP1. While direct pharmacological inhibition of NRF2 has proven challenging, its aberrant activation rewires biochemical networks in cancer cells that may create special vulnerabilities. Here, we use chemical proteomics to map druggable proteins that are selectively expressed in KEAP1-mutant NSCLC cells. Principal among these is NR0B1, an atypical orphan nuclear receptor that we show engages in a multimeric protein complex to regulate the transcriptional output of KEAP1-mutant NSCLC cells. We further identify small molecules that covalently target a conserved cysteine within the NR0B1 protein interaction domain, and we demonstrate that these compounds disrupt NR0B1 complexes and impair the anchorage-independent growth of KEAP1-mutant cancer cells. Our findings designate NR0B1 as a druggable transcriptional regulator that supports NRF2-dependent lung cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Reprint of "CON4EI: Selection of the reference chemicals for hazard identification and labelling of eye irritating chemicals".

PubMed

Adriaens, E; Alépée, N; Kandarova, H; Drzewieckac, A; Gruszka, K; Guest, R; Willoughby, J A; Verstraelen, S; Van Rompay, A R

2018-06-01

Assessment of the acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. In the past, several prospective and retrospective validation studies have taken place in the area of serious eye damage/eye irritation testing. Success in terms of complete replacement of the regulatory in vivo Draize rabbit eye test has not yet been achieved. A very important aspect to ensure development of successful alternative test methods and/or strategies for serious eye damage/eye irritation testing is the selection of appropriate reference chemicals. A set of 80 reference chemicals was selected for the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project, in collaboration with Cosmetics Europe, from the Draize Reference Database published by Cosmetics Europe based on key criteria that were set in their paper (e.g. balanced by important driver of classification and physical state). The most important goals of the CON4EI project were to identify the performance of eight in vitro alternative tests in terms of driver of classification and to identify similarities/differences between the methods in order the build a successful testing strategy that can discriminate between all UN GHS categories. This paper provides background on selection of the test chemicals. Copyright © 2018. Published by Elsevier Ltd.

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alves, Vinicius M.; Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599; Muratov, Eugene

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putativemore » sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. �

Estimate variable importance for recurrent event outcomes with an application to identify hypoglycemia risk factors.

PubMed

Duan, Ran; Fu, Haoda

2015-08-30

Recurrent event data are an important data type for medical research. In particular, many safety endpoints are recurrent outcomes, such as hypoglycemic events. For such a situation, it is important to identify the factors causing these events and rank these factors by their importance. Traditional model selection methods are not able to provide variable importance in this context. Methods that are able to evaluate the variable importance, such as gradient boosting and random forest algorithms, cannot directly be applied to recurrent events data. In this paper, we propose a two-step method that enables us to evaluate the variable importance for recurrent events data. We evaluated the performance of our proposed method by simulations and applied it to a data set from a diabetes study. Copyright © 2015 John Wiley & Sons, Ltd.

Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroids.

PubMed

Strajhar, Petra; Tonoli, David; Jeanneret, Fabienne; Imhof, Raphaella M; Malagnino, Vanessa; Patt, Melanie; Kratschmar, Denise V; Boccard, Julien; Rudaz, Serge; Odermatt, Alex

2017-04-15

The validated OECD test guideline 456 based on human adrenal H295R cells promotes measurement of testosterone and estradiol production as read-out to identify potential endocrine disrupting chemicals. This study aimed to establish optimal conditions for using H295R cells to detect chemicals interfering with the production of key adrenal steroids. H295R cells' supernatants were characterized by liquid chromatography-mass spectrometry (LC-MS)-based steroid profiling, and the influence of experimental conditions including time and serum content was assessed. Steroid profiles were determined before and after incubation with reference compounds and chemicals to be tested for potential disruption of adrenal steroidogenesis. The H295R cells cultivated according to the OECD test guideline produced progestins, glucocorticoids, mineralocorticoids and adrenal androgens but only very low amounts of testosterone. However, testosterone contained in Nu-serum was metabolized during the 48h incubation. Thus, inclusion of positive and negative controls and a steroid profile of the complete medium prior to the experiment (t=0h) was necessary to characterize H295R cells' steroid production and indicate alterations caused by exposure to chemicals. Among the tested chemicals, octyl methoxycinnamate and acetyl tributylcitrate resembled the corticosteroid induction pattern of the positive control torcetrapib. Gene expression analysis revealed that octyl methoxycinnamate and acetyl tributylcitrate enhanced CYP11B2 expression, although less pronounced than torcetrapib. Further experiments need to assess the toxicological relevance of octyl methoxycinnamate- and acetyl tributylcitrate-induced corticosteroid production. In conclusion, the extended profiling and appropriate controls allow detecting chemicals that act on steroidogenesis and provide initial mechanistic evidence for prioritizing chemicals for further investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

Regional chemical setting of the Apollo 16 landing site and the importance of the Kant Plateau

NASA Technical Reports Server (NTRS)

Andre, C. G.; El-Baz, F.

1982-01-01

Orbital X-ray data from the Apollo 16 region indicate that physiographic units identified before the lunar mission can be classified as chemical units as well. The Descartes Mountains, however, appear to be an extension of the Kant Plateau composition that is unusually anorthositic and resembles farside terra. The Cayley Plains have closer affinities to basaltic materials than terra materials, physically, spectrally and chemically. The Theophilus impact, 330 km east of the landing site, excavated magnesium-rich basalts from below less-magnesian flows in Mare Nectaris; but, mafic ejecta was substantially blocked from the Apollo 16 site by the Kant Plateau that rises 5 km above the level of the mare. Apollo 16 soil samples from stations selected to collect either Descartes Mountains material or Cayley Plains material were surprisingly similar. However, they do, indeed, show the chemical trends indicative of the two units as defined by the orbiting geochemistry detectors. The Kant Plateau and Descartes Mountains material may be among the rare nearside examples of a plagioclase-rich cumulate of the primordial magma ocean.

Chemicals identified in feral and food animals: a data base. First annual report, October 1981. Volume I. Records 1-532

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cone, M.V.; Faust, R.A.; Baldauf, M.F.

This data file is a companion to Chemicals Identified in Human Biological Media, A Data Base, and follows basically the same format. The data base on human burden is in its third year of publication. This is the first annual report for the feral and food animal file. Data were obtained primarily from the open literature through manual searches (retrospective to 1979) of the journals listed in Appendix A. The data base now contains information on 60 different substances. Chemicals are listed by Chemical Abstracts Service (CAS) registry numbers and preferred names in Appendix B. For the user's convenience, cross-referencedmore » chemical lists of CAS preferred and common names are provided in Appendix C. The animals, tissues, and body fluids found to be contaminated by these chemicals are listed in Appendix D. The data base is published annually in tabular format with indices and chemical listings that allow specific searching. A limited number of custom computer searches of the data base are available in special cases when the published format does not allow for retrieval of needed information.« less

The phytochemical and genetic survey of common and dwarf juniper (Juniperus communis and Juniperus nana) identifies chemical races and close taxonomic identity of the species.

PubMed

Filipowicz, Natalia; Piotrowski, Arkadiusz; Ochocka, J Renata; Asztemborska, Monika

2006-07-01

Juniperus communis L. (= J. communis var. communis) and Juniperus nana Willd. (= J. communis var. SAXATILIS) are subspecies of juniper. J. communis grows widely in both hemispheres, primarily in lower elevations while J. nana is mainly observed in high mountains. Although they can be distinguished by morphological features, it is not known whether they are genetically and phytochemically distinct entities. We aimed to check whether it is possible to distinguish these two plants (i) by pharmaceutically important chemical traits and (ii) on the basis of intraspecifically highly polymorphic fragment of chloroplast DNA. We used GC with achiral as well as with enantioselective stationary phase columns to identify the main monoterpenes of the essential oil. Sequence analysis of the TRNL (UAA)- TRNF (GAA) intergenic spacer of the chloroplast genome was used as a genetic marker of taxonomic identity between these two subspecies. The chromatographic analysis showed the existence of three chemical races - the alpha-pinene type, the sabinene type and one with intermediate contents of these terpenes among both J. communis and J. nana. Surprisingly, sequence analysis of TRNL (UAA)- TRNF (GAA) revealed 100 % similarity between the common and the dwarf juniper. Thus, the monoterpene pattern is related to geographical origin, and not to the species identity. We suggest that the three chemical races identified in the present study should be considered as separate sources of pharmaceutical raw material. Our results demonstrate that the contents of alpha-pinene and sabinene may be applied as a quick diagnostic test for preliminary evaluation of plant material.

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure

PubMed Central

Nath, Anjali K.; Roberts, Lee D.; Liu, Yan; Mahon, Sari B.; Kim, Sonia; Ryu, Justine H.; Werdich, Andreas; Januzzi, James L.; Boss, Gerry R.; Rockwood, Gary A.; MacRae, Calum A.; Brenner, Matthew; Gerszten, Robert E.; Peterson, Randall T.

2013-01-01

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.—Nath, A. K., Roberts, L. D., Liu, Y., Mahon, S. B., Kim, S., Ryu, J. H., Werdich, A., Januzzi, J. L., Boss, G. R., Rockwood, G. A., MacRae, C. A., Brenner, M., Gerszten, R. E., Peterson, R. T. Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure. PMID:23345455

Atom-scale depth localization of biologically important chemical elements in molecular layers.

PubMed

Schneck, Emanuel; Scoppola, Ernesto; Drnec, Jakub; Mocuta, Cristian; Felici, Roberto; Novikov, Dmitri; Fragneto, Giovanna; Daillant, Jean

2016-08-23

In nature, biomolecules are often organized as functional thin layers in interfacial architectures, the most prominent examples being biological membranes. Biomolecular layers play also important roles in context with biotechnological surfaces, for instance, when they are the result of adsorption processes. For the understanding of many biological or biotechnologically relevant phenomena, detailed structural insight into the involved biomolecular layers is required. Here, we use standing-wave X-ray fluorescence (SWXF) to localize chemical elements in solid-supported lipid and protein layers with near-Ångstrom precision. The technique complements traditional specular reflectometry experiments that merely yield the layers' global density profiles. While earlier work mostly focused on relatively heavy elements, typically metal ions, we show that it is also possible to determine the position of the comparatively light elements S and P, which are found in the most abundant classes of biomolecules and are therefore particularly important. With that, we overcome the need of artificial heavy atom labels, the main obstacle to a broader application of high-resolution SWXF in the fields of biology and soft matter. This work may thus constitute the basis for the label-free, element-specific structural investigation of complex biomolecular layers and biological surfaces.

A Review of Non-Chemical Stressors and Their Importance in Cumulative Risk Assessment

EPA Science Inventory

Cumulative exposure/risk assessments need to include non-chemical stressors as well as human activities and chemical data. Multiple stressor research can offer information on the interactions between chemical and non-chemical stressors needed for cumulative risk assessment resea...

Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important Biological Properties.

PubMed

Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Rahman, M Aminur; Islam, Mohamad Tofazzal

2017-10-17

Sea cucumbers belonging to echinoderm are traditionally used as tonic food in China and other Asian countries. They produce abundant biologically active triterpene glycosides. More than 300 triterpene glycosides have been isolated and characterized from various species of sea cucumbers, which are classified as holostane and nonholostane depending on the presence or absence of a specific structural unit γ(18,20)-lactone in the aglycone. Triterpene glycosides contain a carbohydrate chain up to six monosaccharide units mainly consisting of d-xylose, 3-O-methy-d-xylose, d-glucose, 3-O-methyl-d-glucose, and d-quinovose. Cytotoxicity is the common biological property of triterpene glycosides isolated from sea cucumbers. Besides cytotoxicity, triterpene glycosides also exhibit antifungal, antiviral and hemolytic activities. This review updates and summarizes our understanding on diverse chemical structures of triterpene glycosides from various species of sea cucumbers and their important biological activities. Mechanisms of action and structural-activity relationships (SARs) of sea cucumber glycosides are also discussed briefly.

Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important Biological Properties

PubMed Central

Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Rahman, M. Aminur; Islam, Mohamad Tofazzal

2017-01-01

Sea cucumbers belonging to echinoderm are traditionally used as tonic food in China and other Asian countries. They produce abundant biologically active triterpene glycosides. More than 300 triterpene glycosides have been isolated and characterized from various species of sea cucumbers, which are classified as holostane and nonholostane depending on the presence or absence of a specific structural unit γ(18,20)-lactone in the aglycone. Triterpene glycosides contain a carbohydrate chain up to six monosaccharide units mainly consisting of d-xylose, 3-O-methy-d-xylose, d-glucose, 3-O-methyl-d-glucose, and d-quinovose. Cytotoxicity is the common biological property of triterpene glycosides isolated from sea cucumbers. Besides cytotoxicity, triterpene glycosides also exhibit antifungal, antiviral and hemolytic activities. This review updates and summarizes our understanding on diverse chemical structures of triterpene glycosides from various species of sea cucumbers and their important biological activities. Mechanisms of action and structural–activity relationships (SARs) of sea cucumber glycosides are also discussed briefly. PMID:29039760

Valorisation of softwood bark through extraction of utilizable chemicals. A review.

PubMed

Jablonsky, M; Nosalova, J; Sladkova, A; Haz, A; Kreps, F; Valka, J; Miertus, S; Frecer, V; Ondrejovic, M; Sima, J; Surina, I

2017-11-01

Softwood bark is an important source for producing chemicals and materials as well as bioenergy. Extraction is regarded as a key technology for obtaining chemicals in general, and valorizing bark as a source of such chemicals in particular. In this paper, properties of 237 compounds identified in various studies dealing with extraction of softwood bark were described. Finally, some challenges and perspectives on the production of chemicals from bark are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying Elements of ICU Care That Families Report as Important But Unsatisfactory

PubMed Central

Osborn, Tristan R.; Curtis, J. Randall; Nielsen, Elizabeth L.; Back, Anthony L.; Shannon, Sarah E.

2012-01-01

Background: One in five deaths in the United States occurs in the ICU, and many of these deaths are experienced as less than optimal by families of dying people. The current study investigated the relationship between family satisfaction with ICU care and overall ratings of the quality of dying as a means of identifying targets for improving end-of-life experiences for patients and families. Methods: This multisite cross-sectional study surveyed families of patients who died in the ICU in one of 15 hospitals in western Washington State. Measures included the Family Satisfaction in the ICU (FS-ICU) and the Single-Item Quality of Dying (QOD-1) questionnaires. Associations between FS-ICU items and the QOD-1 were examined using multivariate linear regression controlling for patient and family demographics and hospital site. Results: Questionnaires were returned for 1,290 of 2,850 decedents (45%). Higher QOD-1 scores were significantly associated (all P < .05) with (1) perceived nursing skill and competence (β = 0.15), (2) support for family as decision-makers (β = 0.10), (3) family control over the patient’s care (β = 0.18), and (4) ICU atmosphere (β = 0.12). FS-ICU items that received low ratings and correlated with higher QOD-1 scores (ie, important items with room for improvement) were (1) support of family as decision-maker, (2) family control over patient’s care, and (3) ICU atmosphere. Conclusions: Increased support for families as decision-makers and for their desired level of control over patient care along with improvements in the ICU atmosphere were identified as aspects of the ICU experience that may be important targets for quality improvement. Trial registry: ClinicalTrials.gov; No.: NCT00685893; URL: www.clinicaltrials.gov. PMID:22661455

The use of functional chemical-protein associations to identify multi-pathway renoprotectants.

PubMed

Xu, Jia; Meng, Kexin; Zhang, Rui; Yang, He; Liao, Chang; Zhu, Wenliang; Jiao, Jundong

2014-01-01

Typically, most nephropathies can be categorized as complex human diseases in which the cumulative effect of multiple minor genes, combined with environmental and lifestyle factors, determines the disease phenotype. Thus, multi-target drugs would be more likely to facilitate comprehensive renoprotection than single-target agents. In this study, functional chemical-protein association analysis was performed to retrieve multi-target drugs of high pathway wideness from the STITCH 3.1 database. Pathway wideness of a drug evaluated the efficiency of regulation of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in quantity. We identified nine experimentally validated renoprotectants that exerted remarkable impact on KEGG pathways by targeting a limited number of proteins. We selected curcumin as an illustrative compound to display the advantage of multi-pathway drugs on renoprotection. We compared curcumin with hemin, an agonist of heme oxygenase-1 (HO-1), which significantly affects only one KEGG pathway, porphyrin and chlorophyll metabolism (adjusted p = 1.5×10-5). At the same concentration (10 µM), both curcumin and hemin equivalently mitigated oxidative stress in H2O2-treated glomerular mesangial cells. The benefit of using hemin was derived from its agonistic effect on HO-1, providing relief from oxidative stress. Selective inhibition of HO-1 completely blocked the action of hemin but not that of curcumin, suggesting simultaneous multi-pathway intervention by curcumin. Curcumin also increased cellular autophagy levels, enhancing its protective effect; however, hemin had no effects. Based on the fact that the dysregulation of multiple pathways is implicated in the etiology of complex diseases, we proposed a feasible method for identifying multi-pathway drugs from compounds with validated targets. Our efforts will help identify multi-pathway agents capable of providing comprehensive protection against renal injuries.

Chemical Screening Identifies EUrd as a Novel Inhibitor Against Temozolomide-Resistant Glioblastoma-Initiating Cells.

PubMed

Tsukamoto, Yoshihiro; Ohtsu, Naoki; Echizenya, Smile; Otsuguro, Satoko; Ogura, Ryosuke; Natsumeda, Manabu; Isogawa, Mizuho; Aoki, Hiroshi; Ichikawa, Satoshi; Sakaitani, Masahiro; Matsuda, Akira; Maenaka, Katsumi; Fujii, Yukihiko; Kondo, Toru

2016-08-01

Glioblastoma (GBM), one of the most malignant human cancers, frequently recurs despite multimodal treatment with surgery and chemo/radiotherapies. GBM-initiating cells (GICs) are the likely cell-of-origin in recurrences, as they proliferate indefinitely, form tumors in vivo, and are resistant to chemo/radiotherapies. It is therefore crucial to find chemicals that specifically kill GICs. We established temozolomide (the standard medicine for GBM)-resistant GICs (GICRs) and used the cells for chemical screening. Here, we identified 1-(3-C-ethynyl-β-d-ribopentofuranosyl) uracil (EUrd) as a selective drug for targeting GICRs. EUrd induced the death in GICRs more effectively than their parental GICs, while it was less toxic to normal neural stem cells. We demonstrate that the cytotoxic effect of EUrd on GICRs partly depended on the increased expression of uridine-cytidine kinase-like 1 (UCKL1) and the decreased one of 5'-nucleotidase cytosolic III (NT5C3), which regulate uridine-monophosphate synthesis positively and negatively respectively. Together, these findings suggest that EUrd can be used as a new therapeutic drug for GBM with the expression of surrogate markers UCKL1 and NT5C3. Stem Cells 2016;34:2016-2025. © 2016 AlphaMed Press.

Genomic Models of Short-Term Exposure Accurately Predict Long-Term Chemical Carcinogenicity and Identify Putative Mechanisms of Action

PubMed Central

Gusenleitner, Daniel; Auerbach, Scott S.; Melia, Tisha; Gómez, Harold F.; Sherr, David H.; Monti, Stefano

2014-01-01

Background Despite an overall decrease in incidence of and mortality from cancer, about 40% of Americans will be diagnosed with the disease in their lifetime, and around 20% will die of it. Current approaches to test carcinogenic chemicals adopt the 2-year rodent bioassay, which is costly and time-consuming. As a result, fewer than 2% of the chemicals on the market have actually been tested. However, evidence accumulated to date suggests that gene expression profiles from model organisms exposed to chemical compounds reflect underlying mechanisms of action, and that these toxicogenomic models could be used in the prediction of chemical carcinogenicity. Results In this study, we used a rat-based microarray dataset from the NTP DrugMatrix Database to test the ability of toxicogenomics to model carcinogenicity. We analyzed 1,221 gene-expression profiles obtained from rats treated with 127 well-characterized compounds, including genotoxic and non-genotoxic carcinogens. We built a classifier that predicts a chemical's carcinogenic potential with an AUC of 0.78, and validated it on an independent dataset from the Japanese Toxicogenomics Project consisting of 2,065 profiles from 72 compounds. Finally, we identified differentially expressed genes associated with chemical carcinogenesis, and developed novel data-driven approaches for the molecular characterization of the response to chemical stressors. Conclusion Here, we validate a toxicogenomic approach to predict carcinogenicity and provide strong evidence that, with a larger set of compounds, we should be able to improve the sensitivity and specificity of the predictions. We found that the prediction of carcinogenicity is tissue-dependent and that the results also confirm and expand upon previous studies implicating DNA damage, the peroxisome proliferator-activated receptor, the aryl hydrocarbon receptor, and regenerative pathology in the response to carcinogen exposure. PMID:25058030

An experimental path to constraining the origin of Jupiter’s Trojan asteroids by identifying chemical fingerprints

NASA Astrophysics Data System (ADS)

Blacksberg, Jordana; Mahjoub, Ahmed; Poston, Michael; Brown, Mike; Eiler, John; Ehlmann, Bethany; Hand, Kevin; Carlson, Robert W.; Hodyss, Robert; Wong, Ian

2015-11-01

We present an experimental study aimed at exploring the hypothesis suggested by recent dynamical models - that the Jupiter Trojan asteroids originated in the outer solar system, were scattered by the same instability responsibility for the radical rearrangement of the giant planets, and were subsequently captured in their current location (e.g. Morbidelli et al., 2005, Nesvorny et al., 2013). We seek to identify spectroscopic, chemical and isotopic properties that can tie the Trojan populations to these evolutionary pathways, providing experimental support of dynamical models, and providing testable hypotheses that can feed into the design of experiments that might be performed on potential future missions to these and other primitive bodies.We present the results of experiments devised to explore the hypothesis that Kuiper Belt Objects (KBOs) represent the parent populations of the Trojan asteroids. Numerous thin ice films composed of select solar system volatiles (H2O, H2S, CH3OH, NH3) were grown in various mixtures to simulate compositional changes of icy bodies as a function of volatility and radial distance of formation from the Sun. Subsequent processing of these icy bodies was simulated using electron irradiation and heating. Visible reflectance spectra show significant reddening when H2S is present. Mid-infrared spectra confirm the formation of non-volatile sulfur-containing molecules in the products of H2S-containing ices. These experiments suggest that the presence of specific sulfur-bearing chemical species may play an important role in the colors of both the KBOs and Trojans today. Finally, we discuss the role of the silicate component expected on the surface of the Trojan asteroids (Emery et al., 2006), and the implications of a surface composed of silicates in intimate contact with the nonvolatile organic residues generated by ice irradiation.This work has been supported by the Keck Institute for Space Studies (KISS). The research described here was

Identifying pneumonia outbreaks of public health importance: can emergency department data assist in earlier identification?

PubMed

Hope, Kirsty; Durrheim, David N; Muscatello, David; Merritt, Tony; Zheng, Wei; Massey, Peter; Cashman, Patrick; Eastwood, Keith

2008-08-01

To retrospectively review the performance of a near real-time Emergency Department (ED) Syndromic Surveillance System operating in New South Wales for identifying pneumonia outbreaks of public health importance. Retrospective data was obtained from the NSW Emergency Department data collection for a rural hospital that has experienced a cluster of pneumonia diagnoses among teenage males in August 2006. ED standard reports were examined for signals in the overall count for each respiratory syndrome, and for elevated counts in individual subgroups including; age, sex and admission to hospital status. Using the current thresholds, the ED syndromic surveillance system would have trigged a signal for pneumonia syndrome in children aged 5-16 years four days earlier than the notification by a paediatrician and this signal was maintained for 14 days. If the ED syndromic surveillance system had been operating it could have identified the outbreak earlier than the paediatrician's notification. This may have permitted an earlier public health response. By understanding the behaviour of syndromes during outbreaks of public health importance, response protocols could be developed to facilitate earlier implementation of control measures.

Biogeographical Analysis of Chemical Co-Occurrence Data to Identify Priorities for Mixtures Research

EPA Science Inventory

A challenge with multiple chemical risk assessment is the need to consider the joint behavior of chemicals in mixtures. To address this need, pharmacologists and toxicologists have developed methods over the years to evaluate and test chemical interaction. In practice, however, t...

On the importance of identifying, characterizing, and predicting fundamental phenomena towards microbial electrochemistry applications.

PubMed

Torres, César Iván

2014-06-01

The development of microbial electrochemistry research toward technological applications has increased significantly in the past years, leading to many process configurations. This short review focuses on the need to identify and characterize the fundamental phenomena that control the performance of microbial electrochemical cells (MXCs). Specifically, it discusses the importance of recent efforts to discover and characterize novel microorganisms for MXC applications, as well as recent developments to understand transport limitations in MXCs. As we increase our understanding of how MXCs operate, it is imperative to continue modeling efforts in order to effectively predict their performance, design efficient MXC technologies, and implement them commercially. Thus, the success of MXC technologies largely depends on the path of identifying, understanding, and predicting fundamental phenomena that determine MXC performance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Karrikins Identified in Biochars Indicate Post-Fire Chemical Cues Can Influence Community Diversity and Plant Development

PubMed Central

Kochanek, Jitka; Flematti, Gavin R.

2016-01-01

Background Karrikins are smoke-derived compounds that provide strong chemical cues to stimulate seed germination and seedling growth. The recent discovery in Arabidopsis that the karrikin perception system may be present throughout angiosperms implies a fundamental plant function. Here, we identify the most potent karrikin, karrikinolide (KAR1), in biochars and determine its role in species unique plant responses. Methods Biochars were prepared by three distinct commercial-scale pyrolysis technologies using systematically selected source material and their chemical properties, including karrikinolide, were quantified. Dose-response assays determined the effects of biochar on seed germination for two model species that require karrikinolide to break dormancy (Solanum orbiculatum, Brassica tourneforttii) and on seedling growth using two species that display plasticity to karrikins, biochar and phytotoxins (Lactuca sativa, Lycopersicon esculentum). Multivariate analysis examined relationships between biochar properties and the plant phenotype. Findings and Conclusions Results showed that karrikin abundant biochars stimulated dormant seed germination and seedling growth via mechanisms analogous to post-fire chemical cues. The individual species response was associated with its sensitivity to karrikinolide and inhibitory compounds within the biochars. These findings are critical for understanding why biochar influences community composition and plant physiology uniquely for different species and reaffirms that future pyrolysis technologies promise by-products that concomitantly sequester carbon and enhance plant growth for ecological and broader plant related applications. PMID:27536995

Karrikins Identified in Biochars Indicate Post-Fire Chemical Cues Can Influence Community Diversity and Plant Development.

PubMed

Kochanek, Jitka; Long, Rowena L; Lisle, Allan T; Flematti, Gavin R

2016-01-01

Karrikins are smoke-derived compounds that provide strong chemical cues to stimulate seed germination and seedling growth. The recent discovery in Arabidopsis that the karrikin perception system may be present throughout angiosperms implies a fundamental plant function. Here, we identify the most potent karrikin, karrikinolide (KAR1), in biochars and determine its role in species unique plant responses. Biochars were prepared by three distinct commercial-scale pyrolysis technologies using systematically selected source material and their chemical properties, including karrikinolide, were quantified. Dose-response assays determined the effects of biochar on seed germination for two model species that require karrikinolide to break dormancy (Solanum orbiculatum, Brassica tourneforttii) and on seedling growth using two species that display plasticity to karrikins, biochar and phytotoxins (Lactuca sativa, Lycopersicon esculentum). Multivariate analysis examined relationships between biochar properties and the plant phenotype. Results showed that karrikin abundant biochars stimulated dormant seed germination and seedling growth via mechanisms analogous to post-fire chemical cues. The individual species response was associated with its sensitivity to karrikinolide and inhibitory compounds within the biochars. These findings are critical for understanding why biochar influences community composition and plant physiology uniquely for different species and reaffirms that future pyrolysis technologies promise by-products that concomitantly sequester carbon and enhance plant growth for ecological and broader plant related applications.

Atom-scale depth localization of biologically important chemical elements in molecular layers

PubMed Central

Schneck, Emanuel; Scoppola, Ernesto; Drnec, Jakub; Mocuta, Cristian; Felici, Roberto; Novikov, Dmitri; Fragneto, Giovanna; Daillant, Jean

2016-01-01

In nature, biomolecules are often organized as functional thin layers in interfacial architectures, the most prominent examples being biological membranes. Biomolecular layers play also important roles in context with biotechnological surfaces, for instance, when they are the result of adsorption processes. For the understanding of many biological or biotechnologically relevant phenomena, detailed structural insight into the involved biomolecular layers is required. Here, we use standing-wave X-ray fluorescence (SWXF) to localize chemical elements in solid-supported lipid and protein layers with near-Ångstrom precision. The technique complements traditional specular reflectometry experiments that merely yield the layers’ global density profiles. While earlier work mostly focused on relatively heavy elements, typically metal ions, we show that it is also possible to determine the position of the comparatively light elements S and P, which are found in the most abundant classes of biomolecules and are therefore particularly important. With that, we overcome the need of artificial heavy atom labels, the main obstacle to a broader application of high-resolution SWXF in the fields of biology and soft matter. This work may thus constitute the basis for the label-free, element-specific structural investigation of complex biomolecular layers and biological surfaces. PMID:27503887

Novel Abscisic Acid Antagonists Identified with Chemical Array Screening.

PubMed

Ito, Takuya; Kondoh, Yasumitsu; Yoshida, Kazuko; Umezawa, Taishi; Shimizu, Takeshi; Shinozaki, Kazuo; Osada, Hiroyuki

2015-11-01

Abscisic acid (ABA) signaling is involved in multiple processes in plants, such as water stress control and seed dormancy. Major regulators of ABA signaling are the PYR/PYL/RCAR family receptor proteins, group A protein phosphatases 2C (PP2Cs), and subclass III of SNF1-related protein kinase 2 (SnRK2). Novel ABA agonists and antagonists to modulate the functions of these proteins would not only contribute to clarification of the signaling mechanisms but might also be used to improve crop yields. To obtain small molecules that interact with Arabidopsis ABA receptor PYR1, we screened 24 275 compounds from a chemical library at the RIKEN Natural Products Depository by using a chemical array platform. Subsequent SnRK2 and PP2C assays narrowed down the candidates to two molecules. One antagonized ABA in a competitive manner and inhibited the formation of the PYR1-ABA-PP2C ternary complex. These compounds might have potential as bioprobes to analyze ABA signaling. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON ...

EPA Pesticide Factsheets

Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database. Standardizing chemical structure annotation of public toxicity databases

A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity.

PubMed

Das, Bhaskar C; McCartin, Kellie; Liu, Ting-Chun; Peterson, Randall T; Evans, Todd

2010-04-02

Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model. We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80-92% yields. A small library of these compounds was screened for bioactivity in living zebrafish embryos. We found that several structurally related compounds significantly affect development. Distinct phenotypes are generated depending on time of exposure, and we characterize one compound (BT10) that produces specific cardiovascular defects when added 1 day post fertilization. When compared to retinoic acid (ATRA), BT10 shows similar but not identical changes in the expression pattern of embryonic genes that are known targets of the retinoid pathway. Reporter assays determined that BT10 interacts with all three RAR receptor sub-types, but has no activity for RXR receptors, at all concentrations tested. Our screen has identified a novel retinoid with specificity for retinoid receptors. This lead compound may be useful for manipulating components of retinoid signaling networks, and may be further derivatized for enhanced activity.

Global Sensitivity Analysis for Identifying Important Parameters of Nitrogen Nitrification and Denitrification under Model and Scenario Uncertainties

NASA Astrophysics Data System (ADS)

Ye, M.; Chen, Z.; Shi, L.; Zhu, Y.; Yang, J.

2017-12-01

Nitrogen reactive transport modeling is subject to uncertainty in model parameters, structures, and scenarios. While global sensitivity analysis is a vital tool for identifying the parameters important to nitrogen reactive transport, conventional global sensitivity analysis only considers parametric uncertainty. This may result in inaccurate selection of important parameters, because parameter importance may vary under different models and modeling scenarios. By using a recently developed variance-based global sensitivity analysis method, this paper identifies important parameters with simultaneous consideration of parametric uncertainty, model uncertainty, and scenario uncertainty. In a numerical example of nitrogen reactive transport modeling, a combination of three scenarios of soil temperature and two scenarios of soil moisture leads to a total of six scenarios. Four alternative models are used to evaluate reduction functions used for calculating actual rates of nitrification and denitrification. The model uncertainty is tangled with scenario uncertainty, as the reduction functions depend on soil temperature and moisture content. The results of sensitivity analysis show that parameter importance varies substantially between different models and modeling scenarios, which may lead to inaccurate selection of important parameters if model and scenario uncertainties are not considered. This problem is avoided by using the new method of sensitivity analysis in the context of model averaging and scenario averaging. The new method of sensitivity analysis can be applied to other problems of contaminant transport modeling when model uncertainty and/or scenario uncertainty are present.

Neonatal chemical hypoglycemia in newborns from pregnancies complicated by type 2 and gestational diabetes mellitus - the importance of neonatal ponderal index.

PubMed

Ramos, Gladys A; Hanley, Alethea A; Aguayo, Jennifer; Warshak, Carri R; Kim, Jae H; Moore, Thomas R

2012-03-01

To determine the frequency and risk factors associated with neonatal chemical hypoglycemia in neonates of mothers with type 2 diabetes and gestational diabetes mellitus (GDM). A retrospective cohort study of women with type 2 diabetes or GDM and their singleton neonates. The primary outcome measure was the presence of neonatal chemical hypoglycemia (capillary plasma equivalent glucose <45 mg/dl) within 1 h of birth. Statistical methods included bivariate and multivariate analyses. 242 mother infant dyads were identified. Sixty-eight (28%) were treated with diet, 110 (46%) with glyburide, and 64 (26%) with insulin. The incidence of neonatal chemical hypoglycemia was 18% (44/242). The incidence was significantly higher in those requiring pharmacotherapy (25% vs. 3%, p < 0.001). The frequency of neonatal chemical hypoglycemia between the glyburide and insulin-treated pregnancies did not differ significantly (23% vs. 27%, p = 0.58). The frequency of neonatal chemical hypoglycemia was statistically associated with birth weight, macrosomia and ponderal index (p < 0.001). Neonatal ponderal index was the strongest predictor of hypoglycemia (adjusted Odds ratio 5.59). Neonatal chemical hypoglycemia occurs more frequently in infants from women with type 2 diabetes and GDM treated with glyburide or insulin. An increased neonatal ponderal index is a strong predictor of significant neonatal chemical hypoglycemia.

78 FR 64016 - Importer of Controlled Substances, Notice of Registration, Boehringer Ingelheim Chemicals

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... Registration, Boehringer Ingelheim Chemicals By Notice dated June 18, 2013, and published in the Federal Register on July 1, 2013, 78 FR 39337, Boehringer Ingelheim Chemicals, 2820 N. Normandy Drive, Petersburg...) and determined that the registration of Boehringer Ingelheim Chemicals is consistent with the public...

Engineering propionibacteria as versatile cell factories for the production of industrially important chemicals: advances, challenges, and prospects.

PubMed

Guan, Ningzi; Zhuge, Xin; Li, Jianghua; Shin, Hyun-Dong; Wu, Jing; Shi, Zhongping; Liu, Long

2015-01-01

Propionibacteria are actinobacteria consisting of two principal groups: cutaneous and dairy. Cutaneous propionibacteria are considered primary pathogens to humans, whereas dairy propionibacteria are widely used in the food and pharmaceutical industries. Increasing attention has been focused on improving the performance of dairy propionibacteria for the production of industrially important chemicals, and significant advances have been made through strain engineering and process optimization in the production of flavor compounds, nutraceuticals, and antimicrobial compounds. In addition, genome sequencing of several propionibacteria species has been completed, deepening understanding of the metabolic and physiological features of these organisms. However, the metabolic engineering of propionibacteria still faces several challenges owing to the lack of efficient genome manipulation tools and the existence of various types of strong restriction-modification systems. The emergence of systems and synthetic biology provides new opportunities to overcome these bottlenecks. In this review, we first introduce the major species of propionibacteria and their properties and provide an overview of their functions and applications. We then discuss advances in the genome sequencing and metabolic engineering of these bacteria. Finally, we discuss systems and synthetic biology approaches for engineering propionibacteria as efficient and robust cell factories for the production of industrially important chemicals.

Barcode Identifiers as a Practical Tool for Reliable Species Assignment of Medically Important Black Yeast Species

PubMed Central

Heinrichs, Guido; de Hoog, G. Sybren

2012-01-01

Herpotrichiellaceous black yeasts and relatives comprise severe pathogens flanked by nonpathogenic environmental siblings. Reliable identification by conventional methods is notoriously difficult. Molecular identification is hampered by the sequence variability in the internal transcribed spacer (ITS) domain caused by difficult-to-sequence homopolymeric regions and by poor taxonomic attribution of sequences deposited in GenBank. Here, we present a potential solution using short barcode identifiers (27 to 50 bp) based on ITS2 ribosomal DNA (rDNA), which allows unambiguous definition of species-specific fragments. Starting from proven sequences of ex-type and authentic strains, we were able to describe 103 identifiers. Multiple BLAST searches of these proposed barcode identifiers in GenBank revealed uniqueness for 100 taxonomic entities, whereas the three remaining identifiers each matched with two entities, but the species of these identifiers could easily be discriminated by differences in the remaining ITS regions. Using the proposed barcode identifiers, a 4.1-fold increase of 100% matches in GenBank was achieved in comparison to the classical approach using the complete ITS sequences. The proposed barcode identifiers will be made accessible for the diagnostic laboratory in a permanently updated online database, thereby providing a highly practical, reliable, and cost-effective tool for identification of clinically important black yeasts and relatives. PMID:22785187

Identifying 1st instar larvae for three forensically important blowfly species using "fingerprint" cuticular hydrocarbon analysis.

PubMed

Moore, Hannah E; Adam, Craig D; Drijfhout, Falko P

2014-07-01

Calliphoridae are known to be the most forensically important insects when it comes to establishing the minimum post mortem interval (PMImin) in criminal investigations. The first step in calculating the PMImin is to identify the larvae present to species level. Accurate identification which is conventionally carried out by morphological analysis is crucial because different insects have different life stage timings. Rapid identification in the immature larvae stages would drastically cut time in criminal investigations as it would eliminate the need to rear larvae to adult flies to determine the species. Cuticular hydrocarbon analysis on 1st instar larvae has been applied to three forensically important blowflies; Lucilia sericata, Calliphora vicina and Calliphora vomitoria, using gas chromatography-mass spectrometry (GC-MS) and principal component analysis (PCA). The results show that each species holds a distinct "fingerprint" hydrocarbon profile, allowing for accurate identification to be established in 1-day old larvae, when it can be challenging to apply morphological criteria. Consequently, this GC-MS based technique could accelerate and strengthen the identification process, not only for forensically important species, but also for other entomological samples which are hard to identify using morphological features. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Importance of Considering Non-Chemical Stressors in Interpreting Pesticide Exposures in Children

EPA Science Inventory

Children are exposed to chemical and non-chemical stressors from their total environment, which is comprised of the built, natural, and social environments from places where they spend their time, including home, school, and daycare. Evidence in the literature suggests that the ...

Report: EPA Can Better Reduce Risks From Illegal Pesticides by Effectively Identifying Imports for Inspection and Sampling

EPA Pesticide Factsheets

Report #17-P-0412, September 28, 2017. Low rates of inspections and sampling can create a risk that the EPA may not be identifying and deterring the import of pesticides harmful to people or the environment.

In Vitro Screening of Environmental Chemicals Identifies Zearalenone as a Novel Substrate of the Placental BCRP/ABCG2 Transporter

PubMed Central

Xiao, Jingcheng; Wang, Qi; Bircsak, Kristin M.; Wen, Xia; Aleksunes, Lauren M.

2015-01-01

The BCRP (ABCG2) transporter is responsible for the efflux of chemicals from the placenta to the maternal circulation. Inhibition of BCRP activity could enhance exposure of offspring to environmental chemicals leading to altered reproductive, endocrine, and metabolic development. The purpose of this study was to characterize environmental chemicals as potential substrates and inhibitors of the human placental BCRP transporter. The interaction of BCRP with a panel of environmental chemicals was assessed using the ATPase and inverted plasma membrane vesicle assays as well as a cell-based fluorescent substrate competition assay. Human HEK cells transfected with wild-type BCRP or the Q141K genetic variant, as well as BeWo placental cells that endogenously express BCRP were used to further test inhibitor and substrate interactions. To varying degrees, the eleven chemicals inhibited BCRP activity in activated ATPase membranes and inverted membrane vesicles. Further, genistein, zearalenone, and tributyltin increased the retention of the fluorescent BCRP substrate, Hoechst 33342, between 50–100% in BeWo cells. Additional experiments characterized the mycotoxin and environmental estrogen, zearalenone, as a novel substrate and inhibitor of BCRP in WT-BCRP and BeWo cells. Interestingly, the BCRP genetic variant Q141K exhibited reduced efflux of zearalenone compared to the wild-type protein. Taken together, screening assays and direct quantification experiments identified zearalenone as a novel human BCRP substrate. Additional in vivo studies are needed to directly determine whether placental BCRP prevents fetal exposure to zearalenone. PMID:26052432

Metal Oxide Nanoparticles: The Importance of Size, Shape, Chemical Composition, and Valence State in Determining Toxicity

NASA Astrophysics Data System (ADS)

Dunnick, Katherine

Nanoparticles, which are defined as a structure with at least one dimension between 1 and 100 nm, have the potential to be used in a variety of consumer products due to their improved functionality compared to similar particles of larger size. Their small size is associated with increased strength, improved catalytic properties, and increased reactivity; however, their size is also associated with increased toxicity in vitro and in vivo. Numerous toxicological studies have been conducted to determine the properties of nanomaterials that increase their toxicity in order to manufacture new nanomaterials with decreased toxicity. Data indicates that size, shape, chemical composition, and valence state of nanomaterials can dramatically alter their toxicity profile. Therefore, the purpose of this dissertation was to determine how altering the shape, size, and chemical composition of various metal oxide nanoparticles would affect their toxicity. Metal oxides are used in variety of consumer products, from spray-sun screens, to food coloring agents; thus, understanding the toxicity of metal oxides and determining which aspects affect their toxicity may provide safe alternatives nanomaterials for continued use in manufacturing. Tungstate nanoparticles toxicity was assessed in an in vitro model using RAW 264.7 cells. The size, shape, and chemical composition of these nanomaterials were altered and the effect on reactive oxygen species and general cytotoxicity was determined using a variety of techniques. Results demonstrate that shape was important in reactive oxygen species production as wires were able to induce significant reactive oxygen species compared to spheres. Shape, size, and chemical composition did not have much effect on the overall toxicity of these nanoparticles in RAW 264.7 cells over a 72 hour time course, implicating that the base material of the nanoparticles was not toxic in these cells. To further assess how chemical composition can affect toxicity

Chemical perturbation of secondary metabolism demonstrates important links to primary metabolism.

PubMed

Craney, Arryn; Ozimok, Cory; Pimentel-Elardo, Sheila Marie; Capretta, Alfredo; Nodwell, Justin R

2012-08-24

Bacterially produced secondary metabolites are used as antibiotics, anticancer drugs, and for many other medicinal applications. The mechanisms that limit the production of these molecules in the laboratory are not well understood, and this has impeded the discovery of many important compounds. We have identified small molecules that remodel the yields of secondary metabolites in many actinomycetes and show that one set of these molecules does so by inhibiting fatty acid biosynthesis. This demonstrates a particularly intimate relationship between this primary metabolic pathway and secondary metabolism and suggests an approach to enhance the yields of metabolites for discovery and biochemical characterization. Copyright © 2012 Elsevier Ltd. All rights reserved.

Physical, Chemical and Mineralogical Characteristics of Important Mississippi Soils

Treesearch

R. R. Bruce; W. A. Raney; W. M. Broadfoot; H. B. Vanderford

1958-01-01

To realize the crop production potential of soils it is necessary to first have a knowledge of their chemical, physical and biological properties and reactions and then to so alter these properties and reactions to effect a medium optimum for plant growth. In the past, soils have been classified primarily on the basis of physical characteristics observable in the field...

Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities.

PubMed

Patham, Bhargavi; Duffy, Josh; Lane, Ariel; Davis, Richard C; Wipf, Peter; Fewell, Sheara W; Brodsky, Jeffrey L; Mensa-Wilmot, Kojo

2009-04-15

HAT (human African trypanosomiasis), caused by the protozoan parasite Trypanosoma brucei, is an emerging disease for which new drugs are needed. Expression of plasma membrane proteins [e.g. VSG (variant surface glycoprotein)] is crucial for the establishment and maintenance of an infection by T. brucei. Transport of a majority of proteins to the plasma membrane involves their translocation into the ER (endoplasmic reticulum). Thus inhibition of protein import into the ER of T. brucei would be a logical target for discovery of lead compounds against trypanosomes. We have developed a TbRM (T. brucei microsome) system that imports VSG_117 post-translationally. Using this system, MAL3-101, equisetin and CJ-21,058 were discovered to be small molecule inhibitors of VSG_117 translocation into the ER. These agents also killed bloodstream T. brucei in vitro; the concentrations at which 50% of parasites were killed (IC50) were 1.5 microM (MAL3-101), 3.3 microM (equisetin) and 7 microM (CJ-21,058). Thus VSG_117 import into TbRMs is a rapid and novel assay to identify 'new chemical entities' (e.g. MAL3-101, equisetin and CJ-21,058) for anti-trypanosome drug development.

Using the Developmental Gene Bicoid to Identify Species of Forensically Important Blowflies (Diptera: Calliphoridae)

PubMed Central

Park, Seong Hwan; Park, Chung Hyun; Zhang, Yong; Piao, Huguo; Chung, Ukhee; Kim, Seong Yoon; Ko, Kwang Soo; Yi, Cheong-Ho; Jo, Tae-Ho; Hwang, Juck-Joon

2013-01-01

Identifying species of insects used to estimate postmortem interval (PMI) is a major subject in forensic entomology. Because forensic insect specimens are morphologically uniform and are obtained at various developmental stages, DNA markers are greatly needed. To develop new autosomal DNA markers to identify species, partial genomic sequences of the bicoid (bcd) genes, containing the homeobox and its flanking sequences, from 12 blowfly species (Aldrichina grahami, Calliphora vicina, Calliphora lata, Triceratopyga calliphoroides, Chrysomya megacephala, Chrysomya pinguis, Phormia regina, Lucilia ampullacea, Lucilia caesar, Lucilia illustris, Hemipyrellia ligurriens and Lucilia sericata; Calliphoridae: Diptera) were determined and analyzed. This study first sequenced the ten blowfly species other than C. vicina and L. sericata. Based on the bcd sequences of these 12 blowfly species, a phylogenetic tree was constructed that discriminates the subfamilies of Calliphoridae (Luciliinae, Chrysomyinae, and Calliphorinae) and most blowfly species. Even partial genomic sequences of about 500 bp can distinguish most blowfly species. The short intron 2 and coding sequences downstream of the bcd homeobox in exon 3 could be utilized to develop DNA markers for forensic applications. These gene sequences are important in the evolution of insect developmental biology and are potentially useful for identifying insect species in forensic science. PMID:23586044

iSS-PC: Identifying Splicing Sites via Physical-Chemical Properties Using Deep Sparse Auto-Encoder.

PubMed

Xu, Zhao-Chun; Wang, Peng; Qiu, Wang-Ren; Xiao, Xuan

2017-08-15

Gene splicing is one of the most significant biological processes in eukaryotic gene expression, such as RNA splicing, which can cause a pre-mRNA to produce one or more mature messenger RNAs containing the coded information with multiple biological functions. Thus, identifying splicing sites in DNA/RNA sequences is significant for both the bio-medical research and the discovery of new drugs. However, it is expensive and time consuming based only on experimental technique, so new computational methods are needed. To identify the splice donor sites and splice acceptor sites accurately and quickly, a deep sparse auto-encoder model with two hidden layers, called iSS-PC, was constructed based on minimum error law, in which we incorporated twelve physical-chemical properties of the dinucleotides within DNA into PseDNC to formulate given sequence samples via a battery of cross-covariance and auto-covariance transformations. In this paper, five-fold cross-validation test results based on the same benchmark data-sets indicated that the new predictor remarkably outperformed the existing prediction methods in this field. Furthermore, it is expected that many other related problems can be also studied by this approach. To implement classification accurately and quickly, an easy-to-use web-server for identifying slicing sites has been established for free access at: http://www.jci-bioinfo.cn/iSS-PC.

History of chemically and radiatively important atmospheric gases from the Advanced Global Atmospheric Gases Experiment (AGAGE)

NASA Astrophysics Data System (ADS)

Prinn, Ronald G.; Weiss, Ray F.; Arduini, Jgor; Arnold, Tim; Langley DeWitt, H.; Fraser, Paul J.; Ganesan, Anita L.; Gasore, Jimmy; Harth, Christina M.; Hermansen, Ove; Kim, Jooil; Krummel, Paul B.; Li, Shanlan; Loh, Zoë M.; Lunder, Chris R.; Maione, Michela; Manning, Alistair J.; Miller, Ben R.; Mitrevski, Blagoj; Mühle, Jens; O'Doherty, Simon; Park, Sunyoung; Reimann, Stefan; Rigby, Matt; Saito, Takuya; Salameh, Peter K.; Schmidt, Roland; Simmonds, Peter G.; Steele, L. Paul; Vollmer, Martin K.; Wang, Ray H.; Yao, Bo; Yokouchi, Yoko; Young, Dickon; Zhou, Lingxi

2018-06-01

We present the organization, instrumentation, datasets, data interpretation, modeling, and accomplishments of the multinational global atmospheric measurement program AGAGE (Advanced Global Atmospheric Gases Experiment). AGAGE is distinguished by its capability to measure globally, at high frequency, and at multiple sites all the important species in the Montreal Protocol and all the important non-carbon-dioxide (non-CO2) gases assessed by the Intergovernmental Panel on Climate Change (CO2 is also measured at several sites). The scientific objectives of AGAGE are important in furthering our understanding of global chemical and climatic phenomena. They are the following: (1) to accurately measure the temporal and spatial distributions of anthropogenic gases that contribute the majority of reactive halogen to the stratosphere and/or are strong infrared absorbers (chlorocarbons, chlorofluorocarbons - CFCs, bromocarbons, hydrochlorofluorocarbons - HCFCs, hydrofluorocarbons - HFCs and polyfluorinated compounds (perfluorocarbons - PFCs), nitrogen trifluoride - NF3, sulfuryl fluoride - SO2F2, and sulfur hexafluoride - SF6) and use these measurements to determine the global rates of their emission and/or destruction (i.e., lifetimes); (2) to accurately measure the global distributions and temporal behaviors and determine the sources and sinks of non-CO2 biogenic-anthropogenic gases important to climate change and/or ozone depletion (methane - CH4, nitrous oxide - N2O, carbon monoxide - CO, molecular hydrogen - H2, methyl chloride - CH3Cl, and methyl bromide - CH3Br); (3) to identify new long-lived greenhouse and ozone-depleting gases (e.g., SO2F2, NF3, heavy PFCs (C4F10, C5F12, C6F14, C7F16, and C8F18) and hydrofluoroolefins (HFOs; e.g., CH2 = CFCF3) have been identified in AGAGE), initiate the real-time monitoring of these new gases, and reconstruct their past histories from AGAGE, air archive, and firn air measurements; (4) to determine the average concentrations and

American Bird conservancy's approach to the U.S. Important Bird Area Program - identifying the top 500 global sites

Treesearch

Robert M. Chipley

2005-01-01

The idea for the Important Bird Area Program originated in a series of studies in the early 1980s conducted by BirdLife International. Recognizing that these studies could become a powerful tool for conservation, BirdLife International began an effort to identify and gather data regarding the most important areas for birds in Europe and to make this information...

Chemical genetic screening identifies a novel inhibitor of parallel alignment of cortical microtubules and cellulose microfibrils.

PubMed

Yoneda, Arata; Higaki, Takumi; Kutsuna, Natsumaro; Kondo, Yoichi; Osada, Hiroyuki; Hasezawa, Seiichiro; Matsui, Minami

2007-10-01

It is a well-known hypothesis that cortical microtubules control the direction of cellulose microfibril deposition, and that the parallel cellulose microfibrils determine anisotropic cell expansion and plant cell morphogenesis. However, the molecular mechanism by which cortical microtubules regulate the orientation of cellulose microfibrils is still unclear. To investigate this mechanism, chemical genetic screening was performed. From this screening, 'SS compounds' were identified that induced a spherical swelling phenotype in tobacco BY-2 cells. The SS compounds could be categorized into three classes: those that disrupted the cortical microtubules; those that reduced cellulose microfibril content; and thirdly those that had neither of these effects. In the last class, a chemical designated 'cobtorin' was found to induce the spherical swelling phenotype at the lowest concentration, suggesting strong binding activity to the putative target. Examining cellulose microfibril regeneration using taxol-treated protoplasts revealed that the cobtorin compound perturbed the parallel alignment of pre-existing cortical microtubules and nascent cellulose microfibrils. Thus, cobtorin could be a novel inhibitor and an attractive tool for further investigation of the mechanism that enables cortical microtubules to guide the parallel deposition of cellulose microfibrils.

The importance of proper crystal-chemical and geometrical reasoning demonstrated using layered single and double hydroxides

PubMed Central

Richardson, Ian G.

2013-01-01

Atomistic modelling techniques and Rietveld refinement of X-ray powder diffraction data are widely used but often result in crystal structures that are not realistic, presumably because the authors neglect to check the crystal-chemical plausibility of their structure. The purpose of this paper is to reinforce the importance and utility of proper crystal-chemical and geometrical reasoning in structural studies. It is achieved by using such reasoning to generate new yet fundamental information about layered double hydroxides (LDH), a large, much-studied family of compounds. LDH phases are derived from layered single hydroxides by the substitution of a fraction (x) of the divalent cations by trivalent. Equations are derived that enable calculation of x from the a parameter of the unit cell and vice versa, which can be expected to be of widespread utility as a sanity test for extant and future structure determinations and computer simulation studies. The phase at x = 0 is shown to be an α form of divalent metal hydroxide rather than the β polymorph. Crystal-chemically sensible model structures are provided for β-Zn(OH)2 and Ni- and Mg-based carbonate LDH phases that have any trivalent cation and any value of x, including x = 0 [i.e. for α-M(OH)2·mH2O phases]. PMID:23719702

Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fischer, L.; Deppert, W.R.; Pfeifer, D.

Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As workingmore » basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

In vitro screening for potential chemical inhibitors of ...

EPA Pesticide Factsheets

Control of thyroid hormone (TH) signaling in vertebrates is dependent upon multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper homeostasis of the hormones. Deiodinase enzymes interconvert THs between less active and more active forms via release of iodide from the substrate hormones. The activity of deiodinases has been identified as an important endpoint to include in the context of screening chemicals for thyroid hormone disruption. To address the lack of data regarding the potential for chemicals to inhibit these enzymes a research effort was initially focused on human deiodinase type 1 (D1). We utilized an adenovirus expression system for production of D1 enzyme, established robust assay parameters for non-radioactive determination of iodide release by the Sandell-Kolthoff method, and employed a 96-well plate format for screening chemical libraries. An initial set of 19 chemicals was used to establish the assay. Included in this set was the known D1 inhibitor 6-propylthiouracil (used as a positive control). Over 1800 unique chemicals primarily from the EPA’s ToxCast phase 1_v2, phase 2, and e1K chemical libraries were tested in the screening assay. Chemicals were initially screened at a single high concentration of 200 µM to identify potential D1 inhibitors. The majority of the chemicals did not inhibit D1 activity in this initial screen as defined as a response of less than 20% inhibition c

Relative importance of microplastics as a pathway for the transfer of hydrophobic organic chemicals to marine life.

PubMed

Bakir, Adil; O'Connor, Isabel A; Rowland, Steven J; Hendriks, A Jan; Thompson, Richard C

2016-12-01

It has been hypothesised that, if ingested, plastic debris could act as vector for the transfer of chemical contaminants from seawater to organisms, yet modelling suggest that, in the natural environment, chemical transfer would be negligible compared to other routes of uptake. However, to date, the models have not incorporated consideration of the role of gut surfactants, or the influence of pH or temperature on desorption, whilst experimental work has shown that these factors can enhance desorption of sorbed contaminants several fold. Here, we modelled the transfer of sorbed organic contaminants dichlorodiphenyltrichloroethane (DDT), phenanthrene (Phe) and bis-2-ethylhexyl phthalate (DEHP) from microscopic particles of polyvinylchloride (PVC) and polyethylene (PE) to a benthic invertebrate, a fish and a seabird using a one-compartment model OMEGA (Optimal Modelling for EcotoxicoloGical Applications) with different conditions of pH, temperature and gut surfactants. Environmental concentrations of contaminants at the bottom and the top of published ranges were considered, in combination with ingestion of either 1 or 5% by weight of plastic. For all organisms, the combined intake from food and water was the main route of exposure for Phe, DEHP and DDT with a negligible input from plastic. For the benthic invertebrate, predictions including the presence of contaminated plastic resulted in very small increases in the internal concentrations of DDT and DEHP, while the net change in the transfer of Phe was negligible. While there may be scenarios in which the presence of plastic makes a more important contribution, our modelling study suggests that ingestion of microplastic does not provide a quantitatively important additional pathway for the transfer of adsorbed chemicals from seawater to biota via the gut. Copyright © 2016. Published by Elsevier Ltd.

Identifying anthropogenic uranium compounds using soft X-ray near-edge absorption spectroscopy

NASA Astrophysics Data System (ADS)

Ward, Jesse D.; Bowden, Mark; Tom Resch, C.; Eiden, Gregory C.; Pemmaraju, C. D.; Prendergast, David; Duffin, Andrew M.

2017-01-01

Uranium ores mined for industrial use are typically acid-leached to produce yellowcake and then converted into uranium halides for enrichment and purification. These anthropogenic chemical forms of uranium are distinct from their mineral counterparts. The purpose of this study is to use soft X-ray absorption spectroscopy to characterize several common anthropogenic uranium compounds important to the nuclear fuel cycle. Chemical analyses of these compounds are important for process and environmental monitoring. X-ray absorption techniques have several advantages in this regard, including element-specificity, chemical sensitivity, and high spectral resolution. Oxygen K-edge spectra were collected for uranyl nitrate, uranyl fluoride, and uranyl chloride, and fluorine K-edge spectra were collected for uranyl fluoride and uranium tetrafluoride. Interpretation of the data is aided by comparisons to calculated spectra. The effect of hydration state on the sample, a potential complication in interpreting oxygen K-edge spectra, is discussed. These compounds have unique spectral signatures that can be used to identify unknown samples.

Identifying anthropogenic uranium compounds using soft X-ray near-edge absorption spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, Jesse D.; Bowden, Mark; Tom Resch, C.

2017-01-01

Uranium ores mined for industrial use are typically acid-leached to produce yellowcake and then converted into uranium halides for enrichment and purification. These anthropogenic chemical forms of uranium are distinct from their mineral counterparts. The purpose of this study is to use soft X-ray absorption spectroscopy to characterize several common anthropogenic uranium compounds important to the nuclear fuel cycle. Non-destructive chemical analyses of these compounds is important for process and environmental monitoring and X-ray absorption techniques have several advantages in this regard, including element-specificity, chemical sensitivity, and high spectral resolution. Oxygen K-edge spectra were collected for uranyl nitrate, uranyl fluoride,more » and uranyl chloride, and fluorine K-edge spectra were collected for uranyl fluoride and uranium tetrafluoride. Interpretation of the data is aided by comparisons to calculated spectra. These compounds have unique spectral signatures that can be used to identify unknown samples.« less

A Workflow for Identifying Metabolically Active Chemicals to Complement in vitro Toxicity Screening

EPA Science Inventory

The new paradigm of toxicity testing approaches involves rapid screening of thousands of chemicals across hundreds of biological targets through use of in vitro assays. Such assays may lead to false negatives when the complex metabolic processes that render a chemical bioactive i...

Tiered High-Throughput Screening Approach to Identify ...

EPA Pesticide Factsheets

High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the US EPA ToxCast screening assay portfolio. To fill one critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast Phase I and II chemical libraries, comprised of 1,074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single concentration screen were retested in concentration-response. Due to high false positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed two additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using

Volatile chemicals identified in extracts from leaves of Japanese mugwort (Artemisia princeps pamp.).

PubMed

Umano, K; Hagi, Y; Nakahara, K; Shoji, A; Shibamoto, T

2000-08-01

Extracts from leaves of Japanese mugwort (Artemisia princeps Pamp.) were obtained using two methods: steam distillation under reduced pressure followed by dichloromethane extraction (DRP) and simultaneous purging and extraction (SPSE). A total of 192 volatile chemicals were identified in the extracts obtained by both methods using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). They included 47 monoterpenoids (oxygenated monoterpenes), 26 aromatic compounds, 19 aliphatic esters, 18 aliphatic alcohols, 17 monoterpenes (hydrocarbon monoterpenes), 17 sesquiterpenes (hydrocarbon sesquiterpenes), 13 sesquiterpenoids (oxygenated sesquiterpenes), 12 aliphatic aldehydes, 8 aliphatic hydrocarbons, 7 aliphatic ketones, and 9 miscellaneous compounds. The major volatile constituents of the extract by DRP were borneol (10.27 ppm), alpha-thujone (3.49 ppm), artemisia alcohol (2.17 ppm), verbenone (1.85 ppm), yomogi alcohol (1.50 ppm), and germacren-4-ol (1.43 ppm). The major volatile constituents of the extract by SPSE were 1,8-cineole (8.12 ppm), artemisia acetate (4.22 ppm), alpha-thujone (3.20 ppm), beta-caryophyllene (2.39 ppm), bornyl acetate (2.05 ppm), borneol (1.80 ppm), and trans-beta-farnesene (1. 78 ppm).

Global surveillance for chemical incidents of international public health concern.

PubMed Central

Olowokure, B.; Pooransingh, S.; Tempowski, J.; Palmer, S.; Meredith, T.

2005-01-01

OBJECTIVE: In December 2001, an expert consultation convened by WHO identified strengthening national and global chemical incident preparedness and response as a priority. WHO is working towards this objective by developing a surveillance and response system for chemical incidents. This report describes the frequency, nature and geographical location of acute chemical incidents of potential international concern from August 2002 to December 2003. METHODS: Acute chemical incidents were actively identified through several informal (e.g. Internet-based resources) and formal (e.g. various networks of organizations) sources and assessed against criteria for public health emergencies of international concern using the then proposed revised International Health Regulations (IHR). WHO regional and country offices were contacted to obtain additional information regarding identified incidents. FINDINGS: Altogether, 35 chemical incidents from 26 countries met one or more of the IHR criteria. The WHO European Region accounted for 43% (15/35) of reports. The WHO Regions for Africa, Eastern Mediterranean and Western Pacific each accounted for 14% (5/35); South-East Asia and the Americas accounted for 9% (3/35) and 6% (2/35), respectively. Twenty-three (66%) events were identified within 24 hours of their occurrence. CONCLUSION: To our knowledge this is the first global surveillance system for chemical incidents of potential international concern. Limitations such as geographical and language bias associated with the current system are being addressed. Nevertheless, the system has shown that it can provide early detection of important events, as well as information on the magnitude and geographical distribution of such incidents. It can therefore contribute to improving global public health preparedness. PMID:16462985

Importance of analytically verifying chemical treatments

USGS Publications Warehouse

Rach, J.J.; Gaikowski, M.P.; Olson, J.J.

1997-01-01

Hydrogen peroxide is considered a low regulatory priority compound by the U.S. Food and Drug Administration. It is used to control fungal infections on fish eggs. We studied the treatment profiles of hydrogen peroxide in Heath, McDonald egg jar, and Clark-Williamson incubators during treatments intended to deliver an effective regimen of at least 500 ??L hydrogen peroxide/L (i.e., treatments of 500 and 1,000 ??L/L) for 15 min. Hydrogen peroxide concentrations decreased with increasing distance from the influent water in both Heath and Clark-Williamson incubators. The top treatment tray (tray 2) of the Heath incubator received more than 90% of the intended regimen during the 500 ??L/L treatment, whereas at 1,000 ??L/L, all trays had hydrogen peroxide concentrations at or above 500 ??L/L for 15 min. None of the compartments in the Clark-Williamson incubator received the intended therapeutic regimen when treated at 500 ??L/L. The McDonald egg jar system distributed the intended concentration for the designated treatment period in all jars, except those located directly below the influent water. Our results indicate that dilution of therapeutants applied through certain egg incubation systems significantly decreases the efficacy of treatments and may render them ineffective. The dilution characteristics of egg incubation systems should be assessed in order to ensure proper delivery of all intended chemical concentrations and exposure regimens. Suggestions for maintaining the minimum effective concentrations in evaluated incubators are included.

Using in Vitro High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals

EPA Science Inventory

Over the past 20 years, an increased focus on detecting environmental chemicals posing a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. EPA Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP, whic...

78 FR 5498 - Importer of Controlled Substances; Notice of Registration; Chattem Chemicals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... Registration; Chattem Chemicals, Inc. By Notice dated June 28, 2012, and published in the Federal Register on July 6, 2012, 77 FR 40086, Chattem Chemicals, Inc., 3801 St. Elmo Avenue, Chattanooga, Tennessee 37409... [[Page 5499

Micro-Spectroscopic Chemical Imaging of Individual Identified Marine Biogenic and Ambient Organic Ice Nuclei (Invited)

NASA Astrophysics Data System (ADS)

Knopf, D. A.; Alpert, P. A.; Wang, B.; OBrien, R. E.; Moffet, R. C.; Aller, J. Y.; Laskin, A.; Gilles, M.

2013-12-01

Atmospheric ice formation represents one of the least understood atmospheric processes with important implications for the hydrological cycle and climate. Current freezing descriptions assume that ice active sites on the particle surface initiate ice nucleation, however, the nature of these sites remains elusive. Here, we present a new experimental method that allows us to relate physical and chemical properties of individual particles with observed water uptake and ice nucleation ability using a combination of micro-spectroscopic and optical single particle analytical techniques. We apply this method to field-collected particles and particles generated via bursting of bubbles produced by glass frit aeration and plunging water impingement jets in a mesocosm containing artificial sea water and bacteria and/or phytoplankton. The most efficient ice nuclei (IN) within a particle population are identified and characterized. Single particle characterization is achieved by computer controlled scanning electron microscopy with energy dispersive analysis of X-rays (CCSEM/EDX) and scanning transmission X-ray microscopy with near edge X-ray absorption fine structure spectroscopy. A vapor controlled cooling-stage coupled to an optical microscope is used to determine the onsets of water uptake, immersion freezing, and deposition ice nucleation of the individual particles as a function of temperature (T) as low as 200 K and relative humidity (RH) up to water saturation. In addition, we perform CCSEM/EDX to obtain on a single particle level the elemental composition of the entire particle population. Thus, we can determine if the IN are exceptional in nature or belong to a major particle type class with respect to composition and size. We find that ambient and sea spray particles are coated by organic material and can induce ice formation under tropospheric relevant conditions. Micro-spectroscopic single particle analysis of the investigated particle samples invokes a potential

Applying industrial symbiosis to chemical industry: A literature review

NASA Astrophysics Data System (ADS)

Cui, Hua; Liu, Changhao

2017-08-01

Chemical industry plays an important role in promoting the development of global economy and human society. However, the negative effects caused by chemical production cannot be ignored, which often leads to serious resource consumption and environmental pollution. It is essential for chemical industry to achieve a sustainable development. Industrial symbiosis is one of the key topics in the field of industrial ecology and circular economy, which has been identified as a creative path leading to sustainability. Based on an extensively searching for literatures on linking industrial symbiosis with chemical industry, this paper aims to review the literatures which involves three aspects: (1) economic and environmental benefits achieved by chemical industry through implementing industrial symbiosis, (2) chemical eco-industrial parks, (3) and safety issues for chemical industry. An outlook is also provided. This paper concludes that: (1) chemical industry can achieve both economic and environmental benefits by implementing industrial symbiosis, (2) establishing eco-industrial parks is essential for chemical industry to implement and improve industrial symbiosis, and (3) there is a close relationship between IS and safety issues of chemical industry.

An Event-Related Potentials Study of Mental Rotation in Identifying Chemical Structural Formulas

ERIC Educational Resources Information Center

Huang, Chin-Fei; Liu, Chia-Ju

2012-01-01

The purpose of this study was to investigate how mental rotation strategies affect the identification of chemical structural formulas. This study conducted event-related potentials (ERPs) experiments. In addition to the data collected in the ERPs, a Chemical Structure Conceptual Questionnaire and interviews were also admin-istered for data…

[Threshold values for chemical agents in the light of the REACH regulation].

PubMed

Cavallo, Domenico Maria; Cattaneo, Andrea; Colosio, Claudio; Moretto, Angelo; Carrer, Paolo; Bartolucci, Giovanni Battista

2011-01-01

The European Regulation 1907/2006 (REACH--Registration, Evaluation, Authorization and Restriction of Chemicals) obliges manufacture companies and import chemicals to assess the risks arising from their use and to take the necessary measures to manage the risks identified. The Chemical Safety Report provides an accurate assessment of hazards to human health and the environment necessary to prepare an exposure scenario for the "identified uses" of the substance. An exposure scenario is the set of conditions that describe how the substance is manufactured or used during its life cycle and how the manufacturer or importer controls, or recommends downstream users to control the 'exposure to humans and the environment. Firms therefore need specific skills. The spectrum of toxicological risk is extremely large, the information required in some cases are very complex and undoubtedly require a thorough knowledge in toxicology and environmental industry. The expertise and experience in toxicology of the occupational physician in this case may become useful in the environmental field as well as another familiar figure of relevant importance is the occupational hygienist who develop exposure scenarios for workers and their uses experience for the exposure scenarios for the consumer. It provides an obvious involvement of medical toxicologists and occupational hygienists for public tasks of control and inspection of chemical safety reports and, locally, even the accuracy of risk that arise from this.

The relative importance of prey-borne and predator-borne chemical cues for inducible antipredator responses in tadpoles.

PubMed

Hettyey, Attila; Tóth, Zoltán; Thonhauser, Kerstin E; Frommen, Joachim G; Penn, Dustin J; Van Buskirk, Josh

2015-11-01

Chemical cues that evoke anti-predator developmental changes have received considerable attention, but it is not known to what extent prey use information from the smell of predators and from cues released through digestion. We conducted an experiment to determine the importance of various types of cues for the adjustment of anti-predator defences. We exposed tadpoles (common frog, Rana temporaria) to water originating from predators (caged dragonfly larvae, Aeshna cyanea) that were fed different types and quantities of prey outside of tadpole-rearing containers. Variation among treatments in the magnitude of morphological and behavioural responses was highly consistent. Our results demonstrate that tadpoles can assess the threat posed by predators through digestion-released, prey-borne cues and continually released predator-borne cues. These cues may play an important role in the fine-tuning of anti-predator responses and significantly affect the outcome of interactions between predators and prey in aquatic ecosystems. There has been much confusion regards terminology used in the literature, and therefore we also propose a more precise and consistent binomial nomenclature based on the timing of chemical cue release (stress-, attack-, capture-, digestion- or continually released cues) and the origin of cues (prey-borne or predator-borne cues). We hope that this new nomenclature will improve comparisons among studies on this topic.

Scanning genomic areas under selection sweep and association mapping as tools to identify horticultural important genes in watermelon

USDA-ARS?s Scientific Manuscript database

Watermelon (Citrullus lanatus var. lanatus) contains 88% water, sugars, and several important health-related compounds, including lycopene, citrulline, arginine, and glutathione. The current genetic diversity study uses microsatellites with known map positions to identify genomic regions that under...

Chemical compositions of primitive solar system particles

NASA Technical Reports Server (NTRS)

Sutton, Steve R.; Bajt, S.

1994-01-01

Chemical studies of micrometeorites are of fundamental importance primarily because atmospheric entry selection effects (such as destruction of friable objects) are less significant than those for conventional meteorites. As a result, particles that have experienced very little postaccretional processing have a significant chance of surviving the Earth encounter and subsequent collection. Thus, chemical analyses of these relatively unaltered micrometeorites may lead to a better understanding of the compositions of the most primitive materials in the solar system and thereby constrain the conditions (physical and chemical) that existed in the early solar nebula. Micrometeorites have been collected from the stratosphere, polar ices, and ocean sediments, but the stratospheric collection is the best source for the most unaltered material because they are small and are not heated to their melting points. Despite the fact that the stratospheric micrometeorites have masses in the nanogram range, a variety of microanalytical techniques have been applied to bulk chemical analyses with part-per-million sensitivity. In some cases, multi-disciplinary studies (e.g., chemistry and mineralogy) have been performed on individual particles. The first-order conclusion is that the chondrite-like particles are chemically similar to carbonaceous chondrites but in detail are distinct from members of the conventional meteorite collection. The purpose of this paper is to provide an overview of the results to date and identify important areas for further study.

Chemical and UV Mutagenesis.

PubMed

Bose, Jeffrey L

2016-01-01

The ability to create mutations is an important step towards understanding bacterial physiology and virulence. While targeted approaches are invaluable, the ability to produce genome-wide random mutations can lead to crucial discoveries. Transposon mutagenesis is a useful approach, but many interesting mutations can be missed by these insertions that interrupt coding and noncoding sequences due to the integration of an entire transposon. Chemical mutagenesis and UV-based random mutagenesis are alternate approaches to isolate mutations of interest with the potential of only single nucleotide changes. Once a standard method, difficulty in identifying mutation sites had decreased the popularity of this technique. However, thanks to the recent emergence of economical whole-genome sequencing, this approach to making mutations can once again become a viable option. Therefore, this chapter provides an overview protocol for random mutagenesis using UV light or DNA-damaging chemicals.

Chemicals Reported for the 2012 Chemical Data Reporting (CDR) in Alphabetical Order

EPA Pesticide Factsheets

For the 2012 CDR, 7,674 unique chemicals were reported by manufacturers (including importers).Chemicals are listed in alphabetical order by CA Index Name (for non-confidential chemicals) or by generic chemical name.

The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies.

PubMed

Laptoš, Tomislav; Omersel, Jasna

2018-04-01

The present review specifies the various chemical and physical factors that can influence drug stability and immunogenicity, and the treatment outcomes of antibody biologicals. Although monoclonal antibodies (mAbs) are known to be more resistant to environmental changes compared with other proteins, the molecules themselves can be subjected to chemical and physical processes that promote their degradation and transformation into their specific amino-acid moieties. With increasing use of medicinal products that contain mAbs, and their self-administration by the patients, the issue of the correct manipulation of these drugs is of increasing importance. This review summarises the correct handling of mAb biologicals from the point of view of the pharmacist, clinical biochemist and patient, as is supported by relevant cases from the literature and our own data and experience. In particular, if there is a break in the cold chain, both healthcare professionals and patients need to be aware of the potential pharmacokinetics and pharmacodynamics alterations to these biologicals. Furthermore, any alterations in the protein structure can induce harmful immune reactions, including anaphylaxis and cytokine storms, or result in the production of neutralising or blocking Abs. Overall, considering also that treatment costs usually remain high, drug stability can have a tremendous effect on the clinical, humanistic and economic outcomes of such treatments.

Identifying the domains of context important to implementation science: a study protocol.

PubMed

Squires, Janet E; Graham, Ian D; Hutchinson, Alison M; Michie, Susan; Francis, Jill J; Sales, Anne; Brehaut, Jamie; Curran, Janet; Ivers, Noah; Lavis, John; Linklater, Stefanie; Fenton, Shannon; Noseworthy, Thomas; Vine, Jocelyn; Grimshaw, Jeremy M

2015-09-28

There is growing recognition that "context" can and does modify the effects of implementation interventions aimed at increasing healthcare professionals' use of research evidence in clinical practice. However, conceptual clarity about what exactly comprises "context" is lacking. The purpose of this research program is to develop, refine, and validate a framework that identifies the key domains of context (and their features) that can facilitate or hinder (1) healthcare professionals' use of evidence in clinical practice and (2) the effectiveness of implementation interventions. A multi-phased investigation of context using mixed methods will be conducted. The first phase is a concept analysis of context using the Walker and Avant method to distinguish between the defining and irrelevant attributes of context. This phase will result in a preliminary framework for context that identifies its important domains and their features according to the published literature. The second phase is a secondary analysis of qualitative data from 13 studies of interviews with 312 healthcare professionals on the perceived barriers and enablers to their application of research evidence in clinical practice. These data will be analyzed inductively using constant comparative analysis. For the third phase, we will conduct semi-structured interviews with key health system stakeholders and change agents to elicit their knowledge and beliefs about the contextual features that influence the effectiveness of implementation interventions and healthcare professionals' use of evidence in clinical practice. Results from all three phases will be synthesized using a triangulation protocol to refine the context framework drawn from the concept analysis. The framework will then be assessed for content validity using an iterative Delphi approach with international experts (researchers and health system stakeholders/change agents). This research program will result in a framework that identifies the

Use of FRTL-5 Cell Line as a Complementary Assay for Chemicals Identified During High-Throughput Screening as Sodium/Iodide Symporter (NIS) Inhibitors

EPA Science Inventory

Confirmation of Test Chemicals Identified by a High-Throughput Screen (HTPS) as Sodium Iodide Symporter (NIS) Inhibitors in FRTL-5 Model S. Laws1, A. Buckalew1, J. Wang2, D. Hallinger1, A. Murr1, and T. Stoker1. 1Endocrin...

Identifying New Chemical Entities that Treat and Prevent Relapsing Vivax and Drug-Resistant Falciparum Malaria in U.S. Military Personnel

DTIC Science & Technology

2017-10-01

metabolic stability, membrane permeability and compound solubility). From this extensive work, we now have six chemotypes that we have prioritized for...18th month. We successfully completed this work, and identified a set of six novel chemical series with dual blood and liver stage activity that merit...In the second year, we revised our work plan to devote more resources to pursuing medicinal chemistry to optimize our six prioritized series. This

Chemical Recycling of Molecules in Cometary Comae

NASA Astrophysics Data System (ADS)

Boice, Daniel C.; Kawakita, Hideyo; Shinnaka, Yoshiharu; Kobayashi, Hitomi

2015-08-01

Modeling is essential to understand the important physical and chemical processes that occur in cometary comae, especially the relationship between native and sibling molecules, such as, HCN and CN. Photochemistry is a major source of ions and electrons that further initiate key gas-phase reactions, leading to the plethora of molecules and atoms observed in comets. The effects of photoelectrons that react via impacts are important to the overall ionization in the inner coma. We have found that many molecules undergo protonation reactions with primarily water, followed by electron recombination resulting in the original molecules in a vibrationally excited state. These excited molecules spontaneously emit photons back to the ground state. We identify this series of reactions as chemical “recycling.” We discuss the importance of this mechanism for HCN, NH3, and water in comets. We also identify other relevant processes in the collision-dominated, inner coma of a comet within a global modeling framework to better understand observations and in situ measurements of cometary species, especially relationships between native and sibling molecules for the Rosetta Mission to Comet 67P/Churyumov-Gerasimenko.Acknowledgements: We appreciate support from the NSF Planetary Astronomy Program under Grant No. 0908529. This program is partially supported by the MEXT Supported Program for the Strategic Research Foundation at Private Universities, 2014-2018.

IARC classes 1 and 2 carcinogens are successfully identified by an alternative strategy that detects DNA-reactivity and cell transformation ability of chemicals.

PubMed

Benigni, Romualdo; Bossa, Cecilia; Battistelli, Chiara Laura; Tcheremenskaia, Olga

2013-12-12

For decades, traditional toxicology has been the ultimate source of information on the carcinogenic potential of chemicals; however with increasing demand on regulation of chemicals and decreasing resources for testing, opportunities to accept "alternative" approaches have dramatically expanded. The need for tools able to identify carcinogens in shorter times and at a lower cost in terms of animal lives and money is still an open issue, and the present strategies and regulations for carcinogenicity pre-screening do not adequately protect human health. In previous papers, we have proposed an integrated in vitro/in silico strategy that detects DNA-reactivity and tissue disorganization/disruption by chemicals, and we have shown that the combination of Salmonella and Structural Alerts for the DNA-reactive carcinogens, and in vitro cell transformation assays for nongenotoxic carcinogens permits the identification of a very large proportion (up to 95%) of rodent carcinogens, while having a considerable specificity with the rodent noncarcinogens. In the present paper we expand the previous investigation and show that this alternative strategy identifies correctly IARC Classes 1 and 2 carcinogens. If implemented, this alternative strategy can contribute to improve the protection of human health while decreasing the use of animals. Copyright © 2013 Elsevier B.V. All rights reserved.

40 CFR 712.25 - Exempt manufacturers and importers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (1100 pounds) of the chemical substance at a single plant site are not subject to reporting for that... SUBSTANCES CONTROL ACT CHEMICAL INFORMATION RULES Manufacturers Reporting-Preliminary Assessment Information § 712.25 Exempt manufacturers and importers. (a) Persons who manufactured or imported the chemical...

40 CFR 712.25 - Exempt manufacturers and importers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (1100 pounds) of the chemical substance at a single plant site are not subject to reporting for that... SUBSTANCES CONTROL ACT CHEMICAL INFORMATION RULES Manufacturers Reporting-Preliminary Assessment Information § 712.25 Exempt manufacturers and importers. (a) Persons who manufactured or imported the chemical...

40 CFR 712.25 - Exempt manufacturers and importers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (1100 pounds) of the chemical substance at a single plant site are not subject to reporting for that... SUBSTANCES CONTROL ACT CHEMICAL INFORMATION RULES Manufacturers Reporting-Preliminary Assessment Information § 712.25 Exempt manufacturers and importers. (a) Persons who manufactured or imported the chemical...

40 CFR 712.25 - Exempt manufacturers and importers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (1100 pounds) of the chemical substance at a single plant site are not subject to reporting for that... SUBSTANCES CONTROL ACT CHEMICAL INFORMATION RULES Manufacturers Reporting-Preliminary Assessment Information § 712.25 Exempt manufacturers and importers. (a) Persons who manufactured or imported the chemical...

Assessing Plausibility of Tentative Chemical Identifications from Suspect Screening Analyses via Chemical Function

EPA Science Inventory

Suspect screening (SSA) and non-targeted analysis (NTA) have become increasingly useful methods for identifying chemicals in indoor environments, which is where many chemical exposures occur. However, the tentative chemical identifications from these analyses must be confirmed. T...

An integrated chemical biology approach identifies specific vulnerability of Ewing's sarcoma to combined inhibition of Aurora kinases A and B.

PubMed

Winter, Georg E; Rix, Uwe; Lissat, Andrej; Stukalov, Alexey; Müllner, Markus K; Bennett, Keiryn L; Colinge, Jacques; Nijman, Sebastian M; Kubicek, Stefan; Kovar, Heinrich; Kontny, Udo; Superti-Furga, Giulio

2011-10-01

Ewing's sarcoma is a pediatric cancer of the bone that is characterized by the expression of the chimeric transcription factor EWS-FLI1 that confers a highly malignant phenotype and results from the chromosomal translocation t(11;22)(q24;q12). Poor overall survival and pronounced long-term side effects associated with traditional chemotherapy necessitate the development of novel, targeted, therapeutic strategies. We therefore conducted a focused viability screen with 200 small molecule kinase inhibitors in 2 different Ewing's sarcoma cell lines. This resulted in the identification of several potential molecular intervention points. Most notably, tozasertib (VX-680, MK-0457) displayed unique nanomolar efficacy, which extended to other cell lines, but was specific for Ewing's sarcoma. Furthermore, tozasertib showed strong synergies with the chemotherapeutic drugs etoposide and doxorubicin, the current standard agents for Ewing's sarcoma. To identify the relevant targets underlying the specific vulnerability toward tozasertib, we determined its cellular target profile by chemical proteomics. We identified 20 known and unknown serine/threonine and tyrosine protein kinase targets. Additional target deconvolution and functional validation by RNAi showed simultaneous inhibition of Aurora kinases A and B to be responsible for the observed tozasertib sensitivity, thereby revealing a new mechanism for targeting Ewing's sarcoma. We further corroborated our cellular observations with xenograft mouse models. In summary, the multilayered chemical biology approach presented here identified a specific vulnerability of Ewing's sarcoma to concomitant inhibition of Aurora kinases A and B by tozasertib and danusertib, which has the potential to become a new therapeutic option.

Identification of Chemical Toxicity Using Ontology Information of Chemicals.

PubMed

Jiang, Zhanpeng; Xu, Rui; Dong, Changchun

2015-01-01

With the advance of the combinatorial chemistry, a large number of synthetic compounds have surged. However, we have limited knowledge about them. On the other hand, the speed of designing new drugs is very slow. One of the key causes is the unacceptable toxicities of chemicals. If one can correctly identify the toxicity of chemicals, the unsuitable chemicals can be discarded in early stage, thereby accelerating the study of new drugs and reducing the R&D costs. In this study, a new prediction method was built for identification of chemical toxicities, which was based on ontology information of chemicals. By comparing to a previous method, our method is quite effective. We hope that the proposed method may give new insights to study chemical toxicity and other attributes of chemicals.

Mining Human Biomonitoring Data to Identify Prevalent Chemical Mixtures (SOT abstract)

EPA Science Inventory

Through food, water, air, and consumer products, humans are exposed to tens of thousands of environmental chemicals, and most of these have not been evaluated to determine their potential toxicities. In recent years, high-throughput screening (HTS) methods have been developed tha...

Triangulating Principal Effectiveness: How Perspectives of Parents, Teachers, and Assistant Principals Identify the Central Importance of Managerial Skills

ERIC Educational Resources Information Center

Grissom, Jason A.; Loeb, Susanna

2011-01-01

While the importance of effective principals is undisputed, few studies have identified specific skills that principals need to promote school success. This study draws on unique data combining survey responses from principals, assistant principals, teachers, and parents with rich administrative data to determine which principal skills correlate…

Identifying Cellular and Molecular Mechanisms for Magnetosensation

PubMed Central

Clites, Benjamin L.; Pierce, Jonathan T.

2017-01-01

Diverse animals ranging from worms and insects to birds and turtles perf orm impressive journeys using the magnetic field of the earth as a cue. Although major cellular and molecular mechanisms for sensing mechanical and chemical cues have been elucidated over the past three decades, the mechanisms that animals use to sense magnetic fields remain largely mysterious. Here we survey progress on the search for magnetosensory neurons and magnetosensitive molecules important for animal behaviors. Emphasis is placed on magnetosensation in insects and birds, as well as on the magnetosensitive neuron pair AFD in the nematode Caenorhabditis elegans. We also review conventional criteria used to define animal magnetoreceptors and suggest how approaches used to identify receptors for other sensory modalities may be adapted for magnetoreceptors. Finally, we discuss prospects for under-utilized and novel approaches to identify the elusive magnetoreceptors in animals. PMID:28772099

On-bead combinatorial synthesis and imaging of chemical exchange saturation transfer magnetic resonance imaging agents to identify factors that influence water exchange.

PubMed

Napolitano, Roberta; Soesbe, Todd C; De León-Rodríguez, Luis M; Sherry, A Dean; Udugamasooriya, D Gomika

2011-08-24

The sensitivity of magnetic resonance imaging (MRI) contrast agents is highly dependent on the rate of water exchange between the inner sphere of a paramagnetic ion and bulk water. Normally, identifying a paramagnetic complex that has optimal water exchange kinetics is done by synthesizing and testing one compound at a time. We report here a rapid, economical on-bead combinatorial synthesis of a library of imaging agents. Eighty different 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid (DOTA)-tetraamide peptoid derivatives were prepared on beads using a variety of charged, uncharged but polar, hydrophobic, and variably sized primary amines. A single chemical exchange saturation transfer image of the on-bead library easily distinguished those compounds having the most favorable water exchange kinetics. This combinatorial approach will allow rapid screening of libraries of imaging agents to identify the chemical characteristics of a ligand that yield the most sensitive imaging agents. This technique could be automated and readily adapted to other types of MRI or magnetic resonance/positron emission tomography agents as well.

Quantifying chemical uncertainties in simulations of the ISM

NASA Astrophysics Data System (ADS)

Glover, Simon

2018-06-01

The ever-increasing power of large parallel computers now makes it possible to include increasingly sophisticated chemical models in three-dimensional simulations of the interstellar medium (ISM). This allows us to study the role that chemistry plays in the thermal balance of a realistically-structured, turbulent ISM, as well as enabling us to generated detailed synthetic observations of important atomic or molecular tracers. However, one major constraint on the accuracy of these models is the accuracy with which the input chemical rate coefficients are known. Uncertainties in these chemical rate coefficients inevitably introduce uncertainties into the model predictions. In this talk, I will review some of the methods we can use to quantify these uncertainties and to identify the key reactions where improved chemical data is most urgently required. I will also discuss a few examples, ranging from the local ISM to the high-redshift universe.

A Method for Identifying Prevalent Chemical Combinations in the US Population

EPA Science Inventory

Through the food and water they ingest, the air they breathe, and the consumer products with which they interact at home and at work, humans are exposed to tens of thousands of chemicals, many of which have not been evaluated to determine their potential toxicities. In recent yea...

Genome-Wide Association Study Identifying Candidate Genes Influencing Important Agronomic Traits of Flax (Linum usitatissimum L.) Using SLAF-seq

PubMed Central

Xie, Dongwei; Dai, Zhigang; Yang, Zemao; Sun, Jian; Zhao, Debao; Yang, Xue; Zhang, Liguo; Tang, Qing; Su, Jianguang

2018-01-01

Flax (Linum usitatissimum L.) is an important cash crop, and its agronomic traits directly affect yield and quality. Molecular studies on flax remain inadequate because relatively few flax genes have been associated with agronomic traits or have been identified as having potential applications. To identify markers and candidate genes that can potentially be used for genetic improvement of crucial agronomic traits, we examined 224 specimens of core flax germplasm; specifically, phenotypic data for key traits, including plant height, technical length, number of branches, number of fruits, and 1000-grain weight were investigated under three environmental conditions before specific-locus amplified fragment sequencing (SLAF-seq) was employed to perform a genome-wide association study (GWAS) for these five agronomic traits. Subsequently, the results were used to screen single nucleotide polymorphism (SNP) loci and candidate genes that exhibited a significant correlation with the important agronomic traits. Our analyses identified a total of 42 SNP loci that showed significant correlations with the five important agronomic flax traits. Next, candidate genes were screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then analyzed by a more stringent screening via co-identification using both a general linear model (GLM) and a mixed linear model (MLM) as well as co-occurrences in at least two of the three environments, whereby 15 final candidate genes were obtained. Based on these results, we determined that UGT and PL are candidate genes for plant height, GRAS and XTH are candidate genes for the number of branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits, and PHO1 is a candidate gene for the 1000-seed weight. We propose that the identified SNP loci and corresponding candidate genes might serve as a biological basis for improving crucial agronomic flax traits. PMID:29375606

Genome-Wide Association Study Identifying Candidate Genes Influencing Important Agronomic Traits of Flax (Linum usitatissimum L.) Using SLAF-seq.

PubMed

Xie, Dongwei; Dai, Zhigang; Yang, Zemao; Sun, Jian; Zhao, Debao; Yang, Xue; Zhang, Liguo; Tang, Qing; Su, Jianguang

2017-01-01

Flax ( Linum usitatissimum L.) is an important cash crop, and its agronomic traits directly affect yield and quality. Molecular studies on flax remain inadequate because relatively few flax genes have been associated with agronomic traits or have been identified as having potential applications. To identify markers and candidate genes that can potentially be used for genetic improvement of crucial agronomic traits, we examined 224 specimens of core flax germplasm; specifically, phenotypic data for key traits, including plant height, technical length, number of branches, number of fruits, and 1000-grain weight were investigated under three environmental conditions before specific-locus amplified fragment sequencing (SLAF-seq) was employed to perform a genome-wide association study (GWAS) for these five agronomic traits. Subsequently, the results were used to screen single nucleotide polymorphism (SNP) loci and candidate genes that exhibited a significant correlation with the important agronomic traits. Our analyses identified a total of 42 SNP loci that showed significant correlations with the five important agronomic flax traits. Next, candidate genes were screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then analyzed by a more stringent screening via co-identification using both a general linear model (GLM) and a mixed linear model (MLM) as well as co-occurrences in at least two of the three environments, whereby 15 final candidate genes were obtained. Based on these results, we determined that UGT and PL are candidate genes for plant height, GRAS and XTH are candidate genes for the number of branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits, and PHO1 is a candidate gene for the 1000-seed weight. We propose that the identified SNP loci and corresponding candidate genes might serve as a biological basis for improving crucial agronomic flax traits.

Crowd-sourced Ontology for Photoleukocoria: Identifying Common Internet Search Terms for a Potentially Important Pediatric Ophthalmic Sign.

PubMed

Staffieri, Sandra E; Kearns, Lisa S; Sanfilippo, Paul G; Craig, Jamie E; Mackey, David A; Hewitt, Alex W

2018-02-01

Leukocoria is the most common presenting sign for pediatric eye disease including retinoblastoma and cataract, with worse outcomes if diagnosis is delayed. We investigated whether individuals could identify leukocoria in photographs (photoleukocoria) and examined their subsequent Internet search behavior. Using a web-based questionnaire, in this cross-sectional study we invited adults aged over 18 years to view two photographs of a child with photoleukocoria, and then search the Internet to determine a possible diagnosis and action plan. The most commonly used search terms and websites accessed were recorded. The questionnaire was completed by 1639 individuals. Facebook advertisement was the most effective recruitment strategy. The mean age of all respondents was 38.95 ± 14.59 years (range, 18-83), 94% were female, and 59.3% had children. An abnormality in the images presented was identified by 1613 (98.4%) participants. The most commonly used search terms were: "white," "pupil," "photo," and "eye" reaching a variety of appropriate websites or links to print or social media articles. Different words or phrases were used to describe the same observation of photoleukocoria leading to a range of websites. Variations in the description of observed signs and search words influenced the sites reached, information obtained, and subsequent help-seeking intentions. Identifying the most commonly used search terms for photoleukocoria is an important step for search engine optimization. Being directed to the most appropriate websites informing of the significance of photoleukocoria and the appropriate actions to take could improve delays in diagnosis of important pediatric eye disease such as retinoblastoma or cataract.

Is the hibiscus harlequin bug aposematic? The importance of testing multiple predators

PubMed Central

Fabricant, Scott A; Smith, Carolynn L

2014-01-01

Aposematism involves predators learning conspicuous signals of defended prey. However, prey species utilize a wide range of chemical (or physical) defenses, which are not likely to be equally aversive to all predators. Aposematism may therefore only be effective against a physiologically sensitive subset of potential predators, and this can only be identified through behavioral testing. We studied the emerging model organism Tectocoris diophthalmus (Heteroptera: Scutelleridae), an aposematically colored but weakly defended shieldback stinkbug, to test the efficacy of its defenses against a suite of predator types. We predicted the bugs' defenses would be ineffectual against both experienced and naïve birds but aversive to predaceous insects. Surprisingly, the opposite pattern was found. Both habituated wild passerines and naïve chickens avoided the bugs, the chickens after only one or two encounters. To avian predators, T. diophthalmus is aposematic. However, praying mantids showed no repellency, aversion, or toxicity associated with adult or juvenile bugs after multiple trials. Comparison with prior studies on mantids using bugs with chemically similar but more concentrated defenses underscores the importance of dose in addition to chemical identity in the efficacy of chemical defenses. Our results also emphasize the importance of behavioral testing with multiple ecologically relevant predators to understand selective pressures shaping aposematic signals and chemical defenses. PMID:24558567

The use of IRMS, (1)H NMR and chemical analysis to characterise Italian and imported Tunisian olive oils.

PubMed

Camin, Federica; Pavone, Anita; Bontempo, Luana; Wehrens, Ron; Paolini, Mauro; Faberi, Angelo; Marianella, Rosa Maria; Capitani, Donatella; Vista, Silvia; Mannina, Luisa

2016-04-01

Isotope Ratio Mass Spectrometry (IRMS), (1)H Nuclear Magnetic Resonance ((1)H NMR), conventional chemical analysis and chemometric elaboration were used to assess quality and to define and confirm the geographical origin of 177 Italian PDO (Protected Denomination of Origin) olive oils and 86 samples imported from Tunisia. Italian olive oils were richer in squalene and unsaturated fatty acids, whereas Tunisian olive oils showed higher δ(18)O, δ(2)H, linoleic acid, saturated fatty acids β-sitosterol, sn-1 and 3 diglyceride values. Furthermore, all the Tunisian samples imported were of poor quality, with a K232 and/or acidity values above the limits established for extra virgin olive oils. By combining isotopic composition with (1)H NMR data using a multivariate statistical approach, a statistical model able to discriminate olive oil from Italy and those imported from Tunisia was obtained, with an optimal differentiation ability arriving at around 98%. Copyright © 2015 Elsevier Ltd. All rights reserved.

ICMS. Chemical Tracking, Management, and Reporting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bramlette, J.; Miles, R.; Carlson, M.

1997-10-10

The ICMS provides: management and system users a cost-effective method for identifying, reporting, and tracking chemicals from identifying the chemical when it is received until it enters a waste stream for a facility or area.

Chemical Discrimination of Cortex Phellodendri amurensis and Cortex Phellodendri chinensis by Multivariate Analysis Approach.

PubMed

Sun, Hui; Wang, Huiyu; Zhang, Aihua; Yan, Guangli; Han, Ying; Li, Yuan; Wu, Xiuhong; Meng, Xiangcai; Wang, Xijun

2016-01-01

As herbal medicines have an important position in health care systems worldwide, their current assessment, and quality control are a major bottleneck. Cortex Phellodendri chinensis (CPC) and Cortex Phellodendri amurensis (CPA) are widely used in China, however, how to identify species of CPA and CPC has become urgent. In this study, multivariate analysis approach was performed to the investigation of chemical discrimination of CPA and CPC. Principal component analysis showed that two herbs could be separated clearly. The chemical markers such as berberine, palmatine, phellodendrine, magnoflorine, obacunone, and obaculactone were identified through the orthogonal partial least squared discriminant analysis, and were identified tentatively by the accurate mass of quadruple-time-of-flight mass spectrometry. A total of 29 components can be used as the chemical markers for discrimination of CPA and CPC. Of them, phellodenrine is significantly higher in CPC than that of CPA, whereas obacunone and obaculactone are significantly higher in CPA than that of CPC. The present study proves that multivariate analysis approach based chemical analysis greatly contributes to the investigation of CPA and CPC, and showed that the identified chemical markers as a whole should be used to discriminate the two herbal medicines, and simultaneously the results also provided chemical information for their quality assessment. Multivariate analysis approach was performed to the investigate the herbal medicineThe chemical markers were identified through multivariate analysis approachA total of 29 components can be used as the chemical markers. UPLC-Q/TOF-MS-based multivariate analysis method for the herbal medicine samples Abbreviations used: CPC: Cortex Phellodendri chinensis, CPA: Cortex Phellodendri amurensis, PCA: Principal component analysis, OPLS-DA: Orthogonal partial least squares discriminant analysis, BPI: Base peaks ion intensity.

PINS chemical identification software

DOEpatents

Caffrey, Augustine J.; Krebs, Kennth M.

2004-09-14

An apparatus and method for identifying a chemical compound. A neutron source delivers neutrons into the chemical compound. The nuclei of chemical elements constituting the chemical compound emit gamma rays upon interaction with the neutrons. The gamma rays are characteristic of the chemical elements constituting the chemical compound. A spectrum of the gamma rays is generated having a detection count and an energy scale. The energy scale is calibrated by comparing peaks in the spectrum to energies of pre-selected chemical elements in the spectrum. A least-squares fit completes the calibration. The chemical elements constituting the chemical compound can be readily determined, which then allows for identification of the chemical compound.

An integrated multi-label classifier with chemical-chemical interactions for prediction of chemical toxicity effects.

PubMed

Liu, Tao; Chen, Lei; Pan, Xiaoyong

2018-05-31

Chemical toxicity effect is one of the major reasons for declining candidate drugs. Detecting the toxicity effects of all chemicals can accelerate the procedures of drug discovery. However, it is time-consuming and expensive to identify the toxicity effects of a given chemical through traditional experiments. Designing quick, reliable and non-animal-involved computational methods is an alternative way. In this study, a novel integrated multi-label classifier was proposed. First, based on five types of chemical-chemical interactions retrieved from STITCH, each of which is derived from one aspect of chemicals, five individual classifiers were built. Then, several integrated classifiers were built by integrating some or all individual classifiers. By testing the integrated classifiers on a dataset with chemicals and their toxicity effects in Accelrys Toxicity database and non-toxic chemicals with their performance evaluated by jackknife test, an optimal integrated classifier was selected as the proposed classifier, which provided quite high prediction accuracies and wide applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pipeline of Known Chemical Classes of Antibiotics

PubMed Central

d’Urso de Souza Mendes, Cristina; de Souza Antunes, Adelaide Maria

2013-01-01

Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to the same chemical classes as antibiotics discovered in the 1950s and 1960s. Even though the discovery of new classes of antibiotics is urgently needed, the chemical modification of antibiotics in known classes is still widely used to discover new antibiotics, resulting in a great number of compounds in the discovery and clinical pipeline that belong to existing classes. In this scenario, the present article presents an overview of the R&D pipeline of new antibiotics in known classes of antibiotics, from discovery to clinical trial, in order to map out the technological trends in this type of antibiotic R&D, aiming to identify the chemical classes attracting most interest, their spectrum of activity, and the new subclasses under development. The result of the study shows that the new antibiotics in the pipeline belong to the following chemical classes: quinolones, aminoglycosides, macrolides, oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides, polymyxins and cyclic lipopeptides. PMID:27029317

Method for identifying biochemical and chemical reactions and micromechanical processes using nanomechanical and electronic signal identification

DOEpatents

Holzrichter, J.F.; Siekhaus, W.J.

1997-04-15

A scanning probe microscope, such as an atomic force microscope (AFM) or a scanning tunneling microscope (STM), is operated in a stationary mode on a site where an activity of interest occurs to measure and identify characteristic time-varying micromotions caused by biological, chemical, mechanical, electrical, optical, or physical processes. The tip and cantilever assembly of an AFM is used as a micromechanical detector of characteristic micromotions transmitted either directly by a site of interest or indirectly through the surrounding medium. Alternatively, the exponential dependence of the tunneling current on the size of the gap in the STM is used to detect micromechanical movement. The stationary mode of operation can be used to observe dynamic biological processes in real time and in a natural environment, such as polymerase processing of DNA for determining the sequence of a DNA molecule. 6 figs.

Method for identifying biochemical and chemical reactions and micromechanical processes using nanomechanical and electronic signal identification

DOEpatents

Holzrichter, John F.; Siekhaus, Wigbert J.

1997-01-01

A scanning probe microscope, such as an atomic force microscope (AFM) or a scanning tunneling microscope (STM), is operated in a stationary mode on a site where an activity of interest occurs to measure and identify characteristic time-varying micromotions caused by biological, chemical, mechanical, electrical, optical, or physical processes. The tip and cantilever assembly of an AFM is used as a micromechanical detector of characteristic micromotions transmitted either directly by a site of interest or indirectly through the surrounding medium. Alternatively, the exponential dependence of the tunneling current on the size of the gap in the STM is used to detect micromechanical movement. The stationary mode of operation can be used to observe dynamic biological processes in real time and in a natural environment, such as polymerase processing of DNA for determining the sequence of a DNA molecule.

Role of drosophila in chemical mutagenesis testing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nix, C.E.; Brewen, B.

1978-01-01

An important question facing our society is the impact of numerous chemical insults on the health of man and his environment. Faced with a staggering array of chemicals and enormous testing costs, only a few chemicals can be tested for possible carcinogenic effects. Recent results with the Salmonella/mammalian microsome mutagenesis bioassay system demonstrate a striking correlation between carcinogenicity and mutagenicity of many chemical compounds and offer the possibility that mutagenesis assay systems can provide a quick identification of potential carcinogens. Results from microbial assays can serve as a guideline for further mutagenesis testing as well as identify those compounds requiringmore » more extensive analysis in mammalian systems. Reliance on the results from a single mutagenic assay system is rather risky. It would be preferable to use a battery of tests (the tier approach) which would include the rapid microbial assays as well as mammalian systems. Also the use of Drosophila as a bridge between the microbial and mammalian assays has many desirable features which are discussed.« less

Chemical etching of nitinol stents.

PubMed

Katona, Bálint; Bognár, Eszter; Berta, Balázs; Nagy, Péter; Hirschberg, Kristóf

2013-01-01

At present the main cause of death originates from cardiovascular diseases. Primarily the most frequent cause is vessel closing thus resulting in tissue damage. The stent can help to avoid this. It expands the narrowed vessel section and allows free blood flow. The good surface quality of stents is important. It also must have adequate mechanical characteristics or else it can be damaged which can easily lead to the fracture of the implant. Thus, we have to consider the importance of the surface treatment of these implants. In our experiments the appropriate design was cut from a 1.041 mm inner diameter and 0.100 mm wall thickness nitinol tube by using Nd:YAG laser device. Then, the stent was subjected to chemical etching. By doing so, the burr created during the laser cutting process can be removed and the surface quality refined. In our research, we changed the time of chemical etching and monitored the effects of this parameter. The differently etched stents were subjected to microscopic analysis, mass measurement and in vivo environment tests. The etching times that gave suitable surface and mechanical features were identified.

Risk-Based High-Throughput Chemical Screening and Prioritization using Exposure Models and in Vitro Bioactivity Assays.

PubMed

Shin, Hyeong-Moo; Ernstoff, Alexi; Arnot, Jon A; Wetmore, Barbara A; Csiszar, Susan A; Fantke, Peter; Zhang, Xianming; McKone, Thomas E; Jolliet, Olivier; Bennett, Deborah H

2015-06-02

We present a risk-based high-throughput screening (HTS) method to identify chemicals for potential health concerns or for which additional information is needed. The method is applied to 180 organic chemicals as a case study. We first obtain information on how the chemical is used and identify relevant use scenarios (e.g., dermal application, indoor emissions). For each chemical and use scenario, exposure models are then used to calculate a chemical intake fraction, or a product intake fraction, accounting for chemical properties and the exposed population. We then combine these intake fractions with use scenario-specific estimates of chemical quantity to calculate daily intake rates (iR; mg/kg/day). These intake rates are compared to oral equivalent doses (OED; mg/kg/day), calculated from a suite of ToxCast in vitro bioactivity assays using in vitro-to-in vivo extrapolation and reverse dosimetry. Bioactivity quotients (BQs) are calculated as iR/OED to obtain estimates of potential impact associated with each relevant use scenario. Of the 180 chemicals considered, 38 had maximum iRs exceeding minimum OEDs (i.e., BQs > 1). For most of these compounds, exposures are associated with direct intake, food/oral contact, or dermal exposure. The method provides high-throughput estimates of exposure and important input for decision makers to identify chemicals of concern for further evaluation with additional information or more refined models.

Importance analysis for Hudson River PCB transport and fate model parameters using robust sensitivity studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, S.; Toll, J.; Cothern, K.

1995-12-31

The authors have performed robust sensitivity studies of the physico-chemical Hudson River PCB model PCHEPM to identify the parameters and process uncertainties contributing the most to uncertainty in predictions of water column and sediment PCB concentrations, over the time period 1977--1991 in one segment of the lower Hudson River. The term ``robust sensitivity studies`` refers to the use of several sensitivity analysis techniques to obtain a more accurate depiction of the relative importance of different sources of uncertainty. Local sensitivity analysis provided data on the sensitivity of PCB concentration estimates to small perturbations in nominal parameter values. Range sensitivity analysismore » provided information about the magnitude of prediction uncertainty associated with each input uncertainty. Rank correlation analysis indicated which parameters had the most dominant influence on model predictions. Factorial analysis identified important interactions among model parameters. Finally, term analysis looked at the aggregate influence of combinations of parameters representing physico-chemical processes. The authors scored the results of the local and range sensitivity and rank correlation analyses. The authors considered parameters that scored high on two of the three analyses to be important contributors to PCB concentration prediction uncertainty, and treated them probabilistically in simulations. They also treated probabilistically parameters identified in the factorial analysis as interacting with important parameters. The authors used the term analysis to better understand how uncertain parameters were influencing the PCB concentration predictions. The importance analysis allowed us to reduce the number of parameters to be modeled probabilistically from 16 to 5. This reduced the computational complexity of Monte Carlo simulations, and more importantly, provided a more lucid depiction of prediction uncertainty and its causes.« less

Identifying known unknowns using the US EPA's CompTox ...

EPA Pesticide Factsheets

Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most likely candidate “known unknowns,” which are those chemicals unknown to an investigator but contained within a reference database or literature source, rise to the top of a chemical list when rank-ordered by the number of associated data sources. The U.S. EPA’s CompTox Chemistry Dashboard is a curated and freely available resource for chemistry and computational toxicology research, containing more than 720,000 chemicals of relevance to environmental health science. In this research, the performance of the Dashboard for identifying “known unknowns” was evaluated against that of the online ChemSpider database, one of the primary resources used by mass spectrometrists, using multiple previously studied datasets reported in the peer-reviewed literature totaling 162 chemicals. These chemicals were examined using both applications via molecular formula and monoisotopic mass searches followed by rank-ordering of candidate compounds by associated references or data sources. A greater percentage of chemicals ranked in the top position when using the Dashboard, indicating an advantage of this application over ChemSpider for identifying known unknowns using data source ranking. Addition

Genetic and chemical diversity of high mucilaginous plants of Sida complex by ISSR markers and chemical fingerprinting.

PubMed

Thul, Sanjog T; Srivastava, Ankit K; Singh, Subhash C; Shanker, Karuna

2011-09-01

A method was developed based on multiple approaches wherein DNA and chemical analysis was carried out toward differentiation of important species of Sida complex that is being used for commercial preparation. Isolated DNA samples were successfully performed through PCR amplification using ISSR markers and degree of genetic diversity among the different species of Sida is compared with that of chemical diversity. For genetic fingerprint investigation, selected 10 ISSR primers generating reproducible banding patterns were used. Among the total of 63 amplicons, 62 were recorded as polymorphic, genetic similarity index deduced from ISSR profiles ranged from 12 to 51%. Based on similarity index, S. acuta and S. rhombifolia found to be most similar (51%). High number of species-specific bands played pivotal role to delineate species at genetic level. Investigation based on HPTLC fingerprints analysis revealed 23 bands representing to characteristic chemicals and similarity index ranged from 73 to 91%. Prominent distinguishable bands were observed only in S. acuta, while S. cordifolia and S. rhombifolia shared most bands making them difficult to identify on chemical fingerprint basis. This report summarizes the genotypic and chemotypic diversity and the use of profiles for authentication of species of Sida complex.

Importance of asparagine on the conformational stability and chemical reactivity of selected anti-inflammatory peptides

NASA Astrophysics Data System (ADS)

Soriano-Correa, Catalina; Barrientos-Salcedo, Carolina; Campos-Fernández, Linda; Alvarado-Salazar, Andres; Esquivel, Rodolfo O.

2015-08-01

Inflammatory response events are initiated by a complex series of molecular reactions that generate chemical intermediaries. The structure and properties of peptides and proteins are determined by the charge distribution of their side chains, which play an essential role in its electronic structure and physicochemical properties, hence on its biological functionality. The aim of this study was to analyze the effect of changing one central amino acid, such as substituting asparagine for aspartic acid, from Cys-Asn-Ser in aqueous solution, by assessing the conformational stability, physicochemical properties, chemical reactivity and their relationship with anti-inflammatory activity; employing quantum-chemical descriptors at the M06-2X/6-311+G(d,p) level. Our results suggest that asparagine plays a more critical role than aspartic acid in the structural stability, physicochemical features, and chemical reactivity of these tripeptides. Substituent groups in the side chain cause significant changes on the conformational stability and chemical reactivity, and consequently on their anti-inflammatory activity.

Are chemicals in articles an obstacle for reaching environmental goals? - Missing links in EU chemical management.

PubMed

Molander, Linda; Breitholtz, Magnus; Andersson, Patrik L; Rybacka, Aleksandra; Rudén, Christina

2012-10-01

It is widely acknowledged that the management of risks associated with chemicals in articles needs to be improved. The EU environmental policy states that environmental damage should be rectified at source. It is therefore motivated that the risk management of substances in articles also takes particular consideration to those substances identified as posing a risk in different environmental compartments. The primary aim of the present study was to empirically analyze to what extent the regulation of chemicals in articles under REACH is coherent with the rules concerning chemicals in the Sewage Sludge Directive (SSD) and the Water Framework Directive (WFD). We also analyzed the chemical variation of the organic substances regulated under these legislations in relation to the most heavily used chemicals. The results show that 16 of 24 substances used in or potentially present in articles and regulated by the SSD or the WFD are also identified under REACH either as a substance of very high concern (SVHC) or subject to some restrictions. However, for these substances we conclude that there is limited coherence between the legislations, since the identification as an SVHC does not in itself encompass any use restrictions, and the restrictions in REACH are in many cases limited to a particular use, and thus all other uses are allowed. Only a minor part of chemicals in commerce is regulated and these show a chemical variation that deviates from classical legacy pollutants. This warrants new tools to identify potentially hazardous chemicals in articles. We also noted that chemicals monitored in the environment under the WFD deviate in their chemistry from the ones regulated by REACH. In summary, we argue that to obtain improved resource efficiency and a sustainable development it is necessary to minimize the input of chemicals identified as hazardous to health or the environment into articles. Copyright © 2012 Elsevier B.V. All rights reserved.

Enhancement of Chemical Entity Identification in Text Using Semantic Similarity Validation

PubMed Central

Grego, Tiago; Couto, Francisco M.

2013-01-01

With the amount of chemical data being produced and reported in the literature growing at a fast pace, it is increasingly important to efficiently retrieve this information. To tackle this issue text mining tools have been applied, but despite their good performance they still provide many errors that we believe can be filtered by using semantic similarity. Thus, this paper proposes a novel method that receives the results of chemical entity identification systems, such as Whatizit, and exploits the semantic relationships in ChEBI to measure the similarity between the entities found in the text. The method assigns a single validation score to each entity based on its similarities with the other entities also identified in the text. Then, by using a given threshold, the method selects a set of validated entities and a set of outlier entities. We evaluated our method using the results of two state-of-the-art chemical entity identification tools, three semantic similarity measures and two text window sizes. The method was able to increase precision without filtering a significant number of correctly identified entities. This means that the method can effectively discriminate the correctly identified chemical entities, while discarding a significant number of identification errors. For example, selecting a validation set with 75% of all identified entities, we were able to increase the precision by 28% for one of the chemical entity identification tools (Whatizit), maintaining in that subset 97% the correctly identified entities. Our method can be directly used as an add-on by any state-of-the-art entity identification tool that provides mappings to a database, in order to improve their results. The proposed method is included in a freely accessible web tool at www.lasige.di.fc.ul.pt/webtools/ice/. PMID:23658791

Computer language for identifying chemicals with comprehensive two-dimensional gas chromatography and mass spectrometry.

PubMed

Reichenbach, Stephen E; Kottapalli, Visweswara; Ni, Mingtian; Visvanathan, Arvind

2005-04-15

This paper describes a language for expressing criteria for chemical identification with comprehensive two-dimensional gas chromatography paired with mass spectrometry (GC x GC-MS) and presents computer-based tools implementing the language. The Computer Language for Indentifying Chemicals (CLIC) allows expressions that describe rules (or constraints) for selecting chemical peaks or data points based on multi-dimensional chromatographic properties and mass spectral characteristics. CLIC offers chromatographic functions of retention times, functions of mass spectra, numbers for quantitative and relational evaluation, and logical and arithmetic operators. The language is demonstrated with the compound-class selection rules described by Welthagen et al. [W. Welthagen, J. Schnelle-Kreis, R. Zimmermann, J. Chromatogr. A 1019 (2003) 233-249]. A software implementation of CLIC provides a calculator-like graphical user-interface (GUI) for building and applying selection expressions. From the selection calculator, expressions can be used to select chromatographic peaks that meet the criteria or create selection chromatograms that mask data points inconsistent with the criteria. Selection expressions can be combined with graphical, geometric constraints in the retention-time plane as a powerful component for chemical identification with template matching or used to speed and improve mass spectrum library searches.

Comparison of Microbial and Chemical Source Tracking Markers To Identify Fecal Contamination Sources in the Humber River (Toronto, Ontario, Canada) and Associated Storm Water Outfalls

PubMed Central

Grabuski, Josey; Sverko, Ed; Edge, Thomas A.

2016-01-01

ABSTRACT Storm water runoff is a major source of pollution, and understanding the components of storm water discharge is essential to remediation efforts and proper assessment of risks to human and ecosystem health. In this study, culturable Escherichia coli and ampicillin-resistant E. coli levels were quantified and microbial source tracking (MST) markers (including markers for general Bacteroidales spp., human, ruminant/cow, gull, and dog) were detected in storm water outfalls and sites along the Humber River in Toronto, Ontario, Canada, and enumerated via endpoint PCR and quantitative PCR (qPCR). Additionally, chemical source tracking (CST) markers specific for human wastewater (caffeine, carbamazepine, codeine, cotinine, acetaminophen, and acesulfame) were quantified. Human and gull fecal sources were detected at all sites, although concentrations of the human fecal marker were higher, particularly in outfalls (mean outfall concentrations of 4.22 log10 copies, expressed as copy numbers [CN]/100 milliliters for human and 0.46 log10 CN/100 milliliters for gull). Higher concentrations of caffeine, acetaminophen, acesulfame, E. coli, and the human fecal marker were indicative of greater raw sewage contamination at several sites (maximum concentrations of 34,800 ng/liter, 5,120 ng/liter, 9,720 ng/liter, 5.26 log10 CFU/100 ml, and 7.65 log10 CN/100 ml, respectively). These results indicate pervasive sewage contamination at storm water outfalls and throughout the Humber River, with multiple lines of evidence identifying Black Creek and two storm water outfalls with prominent sewage cross-connection problems requiring remediation. Limited data are available on specific sources of pollution in storm water, though our results indicate the value of using both MST and CST methodologies to more reliably assess sewage contamination in impacted watersheds. IMPORTANCE Storm water runoff is one of the most prominent non-point sources of biological and chemical contaminants

High-throughput screening of chemicals as functional ...

EPA Pesticide Factsheets

Identifying chemicals that provide a specific function within a product, yet have minimal impact on the human body or environment, is the goal of most formulation chemists and engineers practicing green chemistry. We present a methodology to identify potential chemical functional substitutes from large libraries of chemicals using machine learning based models. We collect and analyze publicly available information on the function of chemicals in consumer products or industrial processes to identify a suite of harmonized function categories suitable for modeling. We use structural and physicochemical descriptors for these chemicals to build 41 quantitative structure–use relationship (QSUR) models for harmonized function categories using random forest classification. We apply these models to screen a library of nearly 6400 chemicals with available structure information for potential functional substitutes. Using our Functional Use database (FUse), we could identify uses for 3121 chemicals; 4412 predicted functional uses had a probability of 80% or greater. We demonstrate the potential application of the models to high-throughput (HT) screening for “candidate alternatives” by merging the valid functional substitute classifications with hazard metrics developed from HT screening assays for bioactivity. A descriptor set could be obtained for 6356 Tox21 chemicals that have undergone a battery of HT in vitro bioactivity screening assays. By applying QSURs, we wer

Physical and Chemical Properties of Some Imported Woods and their Degradation by Termites

PubMed Central

Shanbhag, Rashmi R.; Sundararaj, R.

2013-01-01

The influence of physical and chemical properties of 20 species of imported wood on degradation of the wood by termites under field conditions was studied. The wood species studied were: Sycamore maple, Acer pseudoplatanus L. (Sapindales: Sapindaceae) (from two countries), Camphor, Dryobalanops aromatic C.F.Gaertner (Malvales: Dipterocarpaceae), Beech, Fagus grandifolia Ehrhart (Fagales: Fagaceae), F. sylvatica L. (from two countries), Oak, Quercus robur L., Ash, Fraxinus angustifolia Vahl (Lamiales: Oleaceae), F. excelsior L., Padauk, Pterocarpus soyauxii Taubert (Fabales: Fabaceae), (from two countries), Jamba, Xylia dolabrifiormis Roxburgh, Shorea laevis Ridley (Malvales: Dipterocarpaceae), S. macoptera Dyer, S. robusta Roth, Teak, Tectona grandis L.f. (Lamiales: Lamiaceae) (from five countries), and rubber tree, Hevea brasiliensis Müller Argoviensis (Malpighiales: Euphorbiaceae) from India. The termites present were: Odontotermes horni (Wasmann) (Isoptera: Termitidae), O. feae, O. wallonensis, and O. obeus (Rambur). A significant conelation was found between density, cellulose, lignin, and total phenolic contents of the wood and degradation by termites. The higher the density of the wood, the lower the degradation. Similarly, higher amount of lignin and total phenolic contents ensured higher resistance, whereas cellulose drives the termites towards the wood. PMID:23906349

Prioritizing Chemicals and Data Requirements for Screening-Level Exposure and Risk Assessment

PubMed Central

Brown, Trevor N.; Wania, Frank; Breivik, Knut; McLachlan, Michael S.

2012-01-01

Background: Scientists and regulatory agencies strive to identify chemicals that may cause harmful effects to humans and the environment; however, prioritization is challenging because of the large number of chemicals requiring evaluation and limited data and resources. Objectives: We aimed to prioritize chemicals for exposure and exposure potential and obtain a quantitative perspective on research needs to better address uncertainty in screening assessments. Methods: We used a multimedia mass balance model to prioritize > 12,000 organic chemicals using four far-field human exposure metrics. The propagation of variance (uncertainty) in key chemical information used as model input for calculating exposure metrics was quantified. Results: Modeled human concentrations and intake rates span approximately 17 and 15 orders of magnitude, respectively. Estimates of exposure potential using human concentrations and a unit emission rate span approximately 13 orders of magnitude, and intake fractions span 7 orders of magnitude. The actual chemical emission rate contributes the greatest variance (uncertainty) in exposure estimates. The human biotransformation half-life is the second greatest source of uncertainty in estimated concentrations. In general, biotransformation and biodegradation half-lives are greater sources of uncertainty in modeled exposure and exposure potential than chemical partition coefficients. Conclusions: Mechanistic exposure modeling is suitable for screening and prioritizing large numbers of chemicals. By including uncertainty analysis and uncertainty in chemical information in the exposure estimates, these methods can help identify and address the important sources of uncertainty in human exposure and risk assessment in a systematic manner. PMID:23008278

Modeling the effects of chemical exposure on avian seasonal productivity: Importance of differences in breeding strategies

EPA Science Inventory

Agencies that regulate the use of chemicals are increasingly interested in understanding the magnitude of effects of those chemicals on wildlife populations. While laboratory toxicity tests provide insights into the types of effects caused by chemical exposure, they do not alway...

Performance metrics for the evaluation of hyperspectral chemical identification systems

NASA Astrophysics Data System (ADS)

Truslow, Eric; Golowich, Steven; Manolakis, Dimitris; Ingle, Vinay

2016-02-01

Remote sensing of chemical vapor plumes is a difficult but important task for many military and civilian applications. Hyperspectral sensors operating in the long-wave infrared regime have well-demonstrated detection capabilities. However, the identification of a plume's chemical constituents, based on a chemical library, is a multiple hypothesis testing problem which standard detection metrics do not fully describe. We propose using an additional performance metric for identification based on the so-called Dice index. Our approach partitions and weights a confusion matrix to develop both the standard detection metrics and identification metric. Using the proposed metrics, we demonstrate that the intuitive system design of a detector bank followed by an identifier is indeed justified when incorporating performance information beyond the standard detection metrics.

IDENTIFYING INDICATORS OF REACTIVITY FOR CHEMICAL REDUCTANTS IN ANOXIC AND ANAEROBIC SEDIMENTS

EPA Science Inventory

To develop reaction transport models describing the movement of redox-active organic contaminants through contaminated sediments and aquifers, it is imperative to know the identity and reactivity of chemical reductants in natural sediments and to associate their reactivity with p...

Cheminformatics Analysis of EPA ToxCast Chemical Libraries to Identify Domains of Applicability for Predictive Toxicity Models and Prioritize Compounds for Toxicity Testing

EPA Science Inventory

An important goal of toxicology research is the development of robust methods that use in vitro and chemical structure information to predict in vivo toxicity endpoints. The US EPA ToxCast program is addressing this goal using ~600 in vitro assays to create bioactivity profiles o...

Chemicals from Biomass: A Market Assessment of Bioproducts with Near-Term Potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biddy, Mary J.; Scarlata, Christopher; Kinchin, Christopher

Production of chemicals from biomass offers a promising opportunity to reduce U.S. dependence on imported oil, as well as to improve the overall economics and sustainability of an integrated biorefinery. Given the increasing momentum toward the deployment and scale-up of bioproducts, this report strives to: (1) summarize near-term potential opportunities for growth in biomass-derived products; (2) identify the production leaders who are actively scaling up these chemical production routes; (3) review the consumers and market champions who are supporting these efforts; (4) understand the key drivers and challenges to move biomass-derived chemicals to market; and (5) evaluate the impact thatmore » scale-up of chemical strategies will have on accelerating the production of biofuels.« less

Evaluation of the scientific underpinnings for identifying estrogenic chemicals in nonmammalian taxa using mammalian test systems.

PubMed

Ankley, Gerald T; LaLone, Carlie A; Gray, L Earl; Villeneuve, Daniel L; Hornung, Michael W

2016-11-01

The US Environmental Protection Agency has responsibility for assessing endocrine activity of more than 10 000 chemicals, a task that cannot reasonably be achieved solely through use of available mammalian and nonmammalian in vivo screening assays. Hence, it has been proposed that chemicals be prioritized for in vivo testing using data from in vitro high-throughput assays for specific endocrine system targets. Recent efforts focused on potential estrogenic chemicals-specifically those that activate estrogen receptor-alpha (ERα)-have broadly demonstrated feasibility of the approach. However, a major uncertainty is whether prioritization based on mammalian (primarily human) high-throughput assays accurately reflects potential chemical-ERα interactions in nonmammalian species. The authors conducted a comprehensive analysis of cross-species comparability of chemical-ERα interactions based on information concerning structural attributes of estrogen receptors, in vitro binding and transactivation data for ERα, and the effects of a range of chemicals on estrogen-signaling pathways in vivo. Overall, this integrated analysis suggests that chemicals with moderate to high estrogenic potency in mammalian systems also should be priority chemicals in nonmammalian vertebrates. However, the degree to which the prioritization approach might be applicable to invertebrates is uncertain because of a lack of knowledge of the biological role(s) of possible ERα orthologs found in phyla such as annelids. Further, comparative analysis of in vitro data for fish and reptiles suggests that mammalian-based assays may not effectively capture ERα interactions for low-affinity chemicals in all vertebrate classes. Environ Toxicol Chem 2016;35:2806-2816. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is

Integrated Model of Chemical Perturbations of a Biological ...

EPA Pesticide Factsheets

We demonstrate a computational network model that integrates 18 in vitro, high-throughput screening assays measuring estrogen receptor (ER) binding, dimerization, chromatin binding, transcriptional activation and ER-dependent cell proliferation. The network model uses activity patterns across the in vitro assays to predict whether a chemical is an ER agonist or antagonist, or is otherwise influencing the assays through a manner dependent on the physics and chemistry of the technology platform (“”assay interference”). The method is applied to a library of 1812 commercial and environmental chemicals, including 45 ER positive and negative reference chemicals. Among the reference chemicals, the network model correctly identified the agonists and antagonists with the exception of very weak compounds whose activity was outside the concentration range tested. The model agonist score also correlated with the expected potency class of the active reference chemicals. Of the 1812 chemicals evaluated, 52 (2.8%) were predicted to be strongly ER active in agonist or antagonist mode. This dataset and model were also used to begin a systematic investigation of assay interference. The most prominent cause of false-positive activity (activity in an assay that is likely not due to interaction of the chemical with ER) is cytotoxicity. The model provides the ability to prioritize a large set of important environmental chemicals with human exposure potential for additional in v

Genetic and Chemical Screenings Identify HDAC3 as a Key Regulator in Hepatic Differentiation of Human Pluripotent Stem Cells.

PubMed

Li, Shuang; Li, Mushan; Liu, Xiaojian; Yang, Yuanyuan; Wei, Yuda; Chen, Yanhao; Qiu, Yan; Zhou, Tingting; Feng, Zhuanghui; Ma, Danjun; Fang, Jing; Ying, Hao; Wang, Hui; Musunuru, Kiran; Shao, Zhen; Zhao, Yongxu; Ding, Qiurong

2018-05-24

Hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) offer a promising cell resource for disease modeling and transplantation. However, differentiated HLCs exhibit an immature phenotype and comprise a heterogeneous population. Thus, a better understanding of HLC differentiation will improve the likelihood of future application. Here, by taking advantage of CRISPR-Cas9-based genome-wide screening technology and a high-throughput hPSC screening platform with a reporter readout, we identified several potential genetic regulators of HLC differentiation. By using a chemical screening approach within our platform, we also identified compounds that can further promote HLC differentiation and preserve the characteristics of in vitro cultured primary hepatocytes. Remarkably, both screenings identified histone deacetylase 3 (HDAC3) as a key regulator in hepatic differentiation. Mechanistically, HDAC3 formed a complex with liver transcriptional factors, e.g., HNF4, and co-regulated the transcriptional program during hepatic differentiation. This study highlights a broadly useful approach for studying and optimizing hPSC differentiation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Identifying the needs of elderly, hearing-impaired persons: the importance and utility of hearing aid attributes.

PubMed

Meister, Hartmut; Lausberg, Isabel; Kiessling, Juergen; von Wedel, Hasso; Walger, Martin

2002-11-01

Older patients represent the majority of hearing-aid users. The needs of elderly, hearing-impaired subjects are not entirely identified. The present study aims to determine the importance of fundamental hearing-aid attributes and to elicit the utility of associated hypothetical hearing aids for older patients. This was achieved using a questionnaire-based conjoint analysis--a decompositional approach to preference measurement offering a realistic study design. A random sample of 200 experienced hearing-aid users participated in the study. Though three out of the six examined attributes revealed age-related dependencies, the only significant effect was found for the attribute "handling", which was considerably more important for older than younger hearing-aid users. A trend of decreasing importance of speech intelligibility in noise and increasing significance of speech in quiet was observed for subjects older than 70 years. In general, the utility of various hypothetical hearing aids was similar for older and younger subjects. Apart from the attribute "handling", older and younger subjects have comparable needs regarding hearing-aid features. On the basis of the examined attributes, there is no requirement for hearing aids designed specifically for elderly hearing-aid users, provided that ergonomic features are considered and the benefits of modern technology are made fully available for older patients.

A chemical proteomic atlas of brain serine hydrolases identifies cell type-specific pathways regulating neuroinflammation

PubMed Central

Viader, Andreu; Ogasawara, Daisuke; Joslyn, Christopher M; Sanchez-Alavez, Manuel; Mori, Simone; Nguyen, William; Conti, Bruno; Cravatt, Benjamin F

2016-01-01

Metabolic specialization among major brain cell types is central to nervous system function and determined in large part by the cellular distribution of enzymes. Serine hydrolases are a diverse enzyme class that plays fundamental roles in CNS metabolism and signaling. Here, we perform an activity-based proteomic analysis of primary mouse neurons, astrocytes, and microglia to furnish a global portrait of the cellular anatomy of serine hydrolases in the brain. We uncover compelling evidence for the cellular compartmentalization of key chemical transmission pathways, including the functional segregation of endocannabinoid (eCB) biosynthetic enzymes diacylglycerol lipase-alpha (DAGLα) and –beta (DAGLβ) to neurons and microglia, respectively. Disruption of DAGLβ perturbed eCB-eicosanoid crosstalk specifically in microglia and suppressed neuroinflammatory events in vivo independently of broader effects on eCB content. Mapping the cellular distribution of metabolic enzymes thus identifies pathways for regulating specialized inflammatory responses in the brain while avoiding global alterations in CNS function. DOI: http://dx.doi.org/10.7554/eLife.12345.001 PMID:26779719

Suspect screening of maternal serum to identify new environmental chemical biomonitoring targets using liquid chromatography-quadrupole time-of-flight mass spectrometry.

PubMed

Gerona, Roy R; Schwartz, Jackie M; Pan, Janet; Friesen, Matthew M; Lin, Thomas; Woodruff, Tracey J

2018-03-01

The use and advantages of high-resolution mass spectrometry (MS) as a discovery tool for environmental chemical monitoring has been demonstrated for environmental samples but not for biological samples. We developed a method using liquid chromatography-quadrupole time-of-flight MS (LC-QTOF/MS) for discovery of previously unmeasured environmental chemicals in human serum. Using non-targeted data acquisition (full scan MS analysis) we were able to screen for environmental organic acids (EOAs) in 20 serum samples from second trimester pregnant women. We define EOAs as environmental organic compounds with at least one dissociable proton which are utilized in commerce. EOAs include environmental phenols, phthalate metabolites, perfluorinated compounds, phenolic metabolites of polybrominated diphenyl ethers and polychlorinated biphenyls, and acidic pesticides and/or predicted acidic pesticide metabolites. Our validated method used solid phase extraction, reversed-phase chromatography in a C18 column with gradient elution, electrospray ionization in negative polarity and automated tandem MS (MS/MS) data acquisition to maximize true positive rates. We identified "suspect EOAs" using Agilent MassHunter Qualitative Analysis software, to match chemical formulas generated from each sample run with molecular formulas in our unique database of 693 EOAs assembled from multiple environmental literature sources. We found potential matches for 282 (41%) of the EOAs in our database. Sixty-five of these suspect EOAs were detected in at least 75% of the samples; only 19 of these compounds are currently biomonitored in National Health and Nutrition Examination Survey. We confirmed two of three suspect EOAs by LC-QTOF/MS using a targeted method developed through LC-MS/MS, reporting the first confirmation of benzophenone-1 and bisphenol S in pregnant women's sera. Our suspect screening workflow provides an approach to comprehensively scan environmental chemical exposures in humans. This

Systematic reviews identify important methodological flaws in stroke rehabilitation therapy primary studies: review of reviews.

PubMed

Santaguida, Pasqualina; Oremus, Mark; Walker, Kathryn; Wishart, Laurie R; Siegel, Karen Lohmann; Raina, Parminder

2012-04-01

A "review of reviews" was undertaken to assess methodological issues in studies evaluating nondrug rehabilitation interventions in stroke patients. MEDLINE, CINAHL, PsycINFO, and the Cochrane Database of Systematic Reviews were searched from January 2000 to January 2008 within the stroke rehabilitation setting. Electronic searches were supplemented by reviews of reference lists and citations identified by experts. Eligible studies were systematic reviews; excluded citations were narrative reviews or reviews of reviews. Review characteristics and criteria for assessing methodological quality of primary studies within them were extracted. The search yielded 949 English-language citations. We included a final set of 38 systematic reviews. Cochrane reviews, which have a standardized methodology, were generally of higher methodological quality than non-Cochrane reviews. Most systematic reviews used standardized quality assessment criteria for primary studies, but not all were comprehensive. Reviews showed that primary studies had problems with randomization, allocation concealment, and blinding. Baseline comparability, adverse events, and co-intervention or contamination were not consistently assessed. Blinding of patients and providers was often not feasible and was not evaluated as a source of bias. The eligible systematic reviews identified important methodological flaws in the evaluated primary studies, suggesting the need for improvement of research methods and reporting. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of Chemical Features Linked to Thyroperoxidase ...

EPA Pesticide Factsheets

Disruption of maternal serum thyroid hormone (TH) adversely affects fetal neurodevelopment. Therefore, assay development within the US EPA ToxCast program is ongoing to enable screening for chemicals that may disrupt TH, in support of the Endocrine Disruption Screening Program (EDSP21). The AUR-TPO assay was recently developed to screen >1,000 ToxCast chemicals for potential thyroperoxidase (TPO) inhibition activity. TPO is critical for TH synthesis and is a known target of thyroid-disrupting chemicals. The bioactivity results from the AUR-TPO assay were used to identify chemical substructures associated with in vitro TPO inhibition. Substructure profiles were generated for each chemical in the ToxCast test set using the publicly-available ToxPrint 2.0 chemotypes. Chemotypes enriched among the putative TPO inhibitors were identified using a cumulative hypergeometric probability (p < 0.01). Of the total 729 chemotypes evaluated, 31 were overrepresented among TPO inhibitors. Examination of those 31 chemotypes revealed four basic pharmacophores that accounted for 70% of the ToxCast chemicals active in the AUR-TPO assay: aromatic alcohols, aromatic amines, thiocarbonyls and phosphothioates. Chemico-structural analysis of AUR-TPO screening results enabled the identification of chemical features that likely drive TPO inhibition in the AUR-TPO assay. This highlights the potential to identify thyroid-disrupting chemicals in silico using structural alerts identified by

Risk-based high-throughput chemical screening and prioritization using exposure models and in vitro bioactivity assays

DOE PAGES

Shin, Hyeong -Moo; Ernstoff, Alexi; Arnot, Jon A.; ...

2015-05-01

We present a risk-based high-throughput screening (HTS) method to identify chemicals for potential health concerns or for which additional information is needed. The method is applied to 180 organic chemicals as a case study. We first obtain information on how the chemical is used and identify relevant use scenarios (e.g., dermal application, indoor emissions). For each chemical and use scenario, exposure models are then used to calculate a chemical intake fraction, or a product intake fraction, accounting for chemical properties and the exposed population. We then combine these intake fractions with use scenario-specific estimates of chemical quantity to calculate dailymore » intake rates (iR; mg/kg/day). These intake rates are compared to oral equivalent doses (OED; mg/kg/day), calculated from a suite of ToxCast in vitro bioactivity assays using in vitro-to-in vivo extrapolation and reverse dosimetry. Bioactivity quotients (BQs) are calculated as iR/OED to obtain estimates of potential impact associated with each relevant use scenario. Of the 180 chemicals considered, 38 had maximum iRs exceeding minimum OEDs (i.e., BQs > 1). For most of these compounds, exposures are associated with direct intake, food/oral contact, or dermal exposure. The method provides high-throughput estimates of exposure and important input for decision makers to identify chemicals of concern for further evaluation with additional information or more refined models.« less

Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches

PubMed Central

Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

2016-01-01

The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

Screening the ToxCast Phase 1 Chemical Library for Inhibition of Deiodinase Type 1 Activity.

PubMed

Hornung, Michael W; Korte, Joseph J; Olker, Jennifer H; Denny, Jeffrey S; Knutsen, Carsten; Hartig, Phillip C; Cardon, Mary C; Degitz, Sigmund J

2018-04-01

Thyroid hormone (TH) homeostasis is dependent upon coordination of multiple key events including iodide uptake, hormone synthesis, metabolism, and elimination, to maintain proper TH signaling. Deiodinase enzymes catalyze iodide release from THs to interconvert THs between active and inactive forms, and are integral to hormone metabolism. The activity of deiodinases has been identified as an important endpoint to include in the context of screening chemicals for TH disruption. To begin to address the potential for chemicals to inhibit these enzymes an adenovirus expression system was used to produce human deiodinase type 1 (DIO1) enzyme, established robust assay parameters for nonradioactive determination of iodide release by the Sandell-Kolthoff method, and employed a 96-well plate format for screening chemical libraries. An initial set of 18 chemicals was used to establish the assay, along with the known DIO1 inhibitor 6-propylthiouracil as a positive control. An additional 292 unique chemicals from the EPA's ToxCast phase 1_v2 chemical library were screened. Chemicals were initially screened at a single high concentration of 200 µM to identify potential DIO1 inhibitors. There were 50 chemicals, or 17% of the TCp1_v2 chemicals tested, that produced >20% inhibition of DIO1 activity. Eighteen of these inhibited DIO1 activity >50% and were further tested in concentration-response mode to determine IC50s. This work presents an initial effort toward identifying chemicals with potential for affecting THs via inhibition of deiodinases and sets the foundation for further testing of large chemical libraries against DIO1 and the other deiodinase enzymes involved in TH function.

Revision of Import and Export Requirements for Controlled Substances, Listed Chemicals, and Tableting and Encapsulating Machines, Including Changes To Implement the International Trade Data System (ITDS); Revision of Reporting Requirements for Domestic Transactions in Listed Chemicals and Tableting and Encapsulating Machines; and Technical Amendments. Final rule.

PubMed

2016-12-30

The Drug Enforcement Administration is updating its regulations for the import and export of tableting and encapsulating machines, controlled substances, and listed chemicals, and its regulations relating to reports required for domestic transactions in listed chemicals, gamma-hydroxybutyric acid, and tableting and encapsulating machines. In accordance with Executive Order 13563, the Drug Enforcement Administration has reviewed its import and export regulations and reporting requirements for domestic transactions in listed chemicals (and gamma-hydroxybutyric acid) and tableting and encapsulating machines, and evaluated them for clarity, consistency, continued accuracy, and effectiveness. The amendments clarify certain policies and reflect current procedures and technological advancements. The amendments also allow for the implementation, as applicable to tableting and encapsulating machines, controlled substances, and listed chemicals, of the President's Executive Order 13659 on streamlining the export/import process and requiring the government-wide utilization of the International Trade Data System (ITDS). This rule additionally contains amendments that implement recent changes to the Controlled Substances Import and Export Act (CSIEA) for reexportation of controlled substances among members of the European Economic Area made by the Improving Regulatory Transparency for New Medical Therapies Act. The rule also includes additional substantive and technical and stylistic amendments.

Hierarchical cluster analysis of technical replicates to identify interferents in untargeted mass spectrometry metabolomics.

PubMed

Caesar, Lindsay K; Kvalheim, Olav M; Cech, Nadja B

2018-08-27

Mass spectral data sets often contain experimental artefacts, and data filtering prior to statistical analysis is crucial to extract reliable information. This is particularly true in untargeted metabolomics analyses, where the analyte(s) of interest are not known a priori. It is often assumed that chemical interferents (i.e. solvent contaminants such as plasticizers) are consistent across samples, and can be removed by background subtraction from blank injections. On the contrary, it is shown here that chemical contaminants may vary in abundance across each injection, potentially leading to their misidentification as relevant sample components. With this metabolomics study, we demonstrate the effectiveness of hierarchical cluster analysis (HCA) of replicate injections (technical replicates) as a methodology to identify chemical interferents and reduce their contaminating contribution to metabolomics models. Pools of metabolites with varying complexity were prepared from the botanical Angelica keiskei Koidzumi and spiked with known metabolites. Each set of pools was analyzed in triplicate and at multiple concentrations using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). Before filtering, HCA failed to cluster replicates in the data sets. To identify contaminant peaks, we developed a filtering process that evaluated the relative peak area variance of each variable within triplicate injections. These interferent peaks were found across all samples, but did not show consistent peak area from injection to injection, even when evaluating the same chemical sample. This filtering process identified 128 ions that appear to originate from the UPLC-MS system. Data sets collected for a high number of pools with comparatively simple chemical composition were highly influenced by these chemical interferents, as were samples that were analyzed at a low concentration. When chemical interferent masses were removed, technical replicates clustered in

Chemical plant innovative safety investments decision-support methodology.

PubMed

Reniers, G L L; Audenaert, A

2009-01-01

This article examines the extent to which investing in safety during the creation of a new chemical installation proves profitable. The authors propose a management supporting cost-benefit model that identifies and evaluates investments in safety within a chemical company. This innovative model differentiates between serious accidents and less serious accidents, thus providing an authentic image of prevention-related costs and benefits. In classic cost-benefit analyses, which do not make such differentiations, only a rudimentary image of potential profitability resulting from investments in safety is obtained. The resulting management conclusions that can be drawn from such classical analyses are of a very limited nature. The proposed model, however, is applied to a real case study and the proposed investments in safety at an appointed chemical installation are weighed against the estimated hypothetical benefits resulting from the preventive measures to be installed at the installation. In the case-study carried out in question, it would appear that the proposed prevention investments are justified. Such an economic exercise may be very important to chemical corporations trying to (further) improve their safety investments.

Integrating Exposure into Chemical Alternatives Assessment ...

EPA Pesticide Factsheets

Most alternatives assessments (AA) published to date are largely hazard-based rankings, and as such may not represent a fully informed consideration of the advantages and disadvantages of possible alternatives. With an assessment goal of identifying an alternative chemical that is more sustainable, other attributes beyond hazard are also important, including exposure, risk, life-cycle impacts, performance, cost, and social responsibility. Building on the 2014 recommendations by the U.S. National Academy of Sciences to improve AA decisions by including comparative exposure assessment, the HESISustainable Chemical Alternatives Technical Committee, which consists of scientists from academia, industry, government, and NGOs, has developed a qualitative comparative exposure approach. Conducting such a comparison can screen for alternatives that are expected to have a higher exposure potential, which could trigger a higher-tiered, more quantitative exposure assessment on the alternatives being considered. This talk will demonstrate an approach for including chemical- and product-related exposure information in a qualitative AA comparison. Starting from existing hazard AAs, a series of four chemical-product application scenarios were examined to test the concept, to understand the effort required, and to determine the value of exposure data in AA decision-making. The group has developed a classification approach for ingredient and product parameters to support compariso

Identifying important comorbidity among cancer populations using administrative data: Prevalence and impact on survival.

PubMed

Sarfati, Diana; Gurney, Jason; Lim, Bee Teng; Bagheri, Nasser; Simpson, Andrew; Koea, Jonathan; Dennett, Elizabeth

2016-03-01

Our study sought to optimize the identification and investigate the impact of comorbidity in cancer patients using routinely collected hospitalization data. We undertook an iterative process of classification of important clinical conditions involving evaluation of relevant literature and consultation with clinicians. Patients diagnosed with colon, rectal, breast, ovarian, uterine, stomach, liver, renal or bladder cancers (n = 14,096) between 2006 and 2008 were identified from the New Zealand Cancer Registry. Conditions were identified using data on diagnoses from hospital admissions for 5 years prior to cancer diagnosis. Patients were followed up until end of 2009 using routine mortality data. Prevalence estimates for each condition by site were calculated. All-cause mortality impact of common conditions was investigated using Cox regression models adjusted for age and stage at diagnosis. Patients with liver and stomach cancers tended to have higher comorbidity and those with breast cancer, lower comorbidity than other cancer patients. Of the 50 conditions, the most common were hypertension (prevalence 8.0-20.9%), cardiac conditions (2.1-13.5%) and diabetes with (2.3-13.3%) and without (2.9-12.9%) complications. Comorbidity was associated with higher all-cause mortality but the impact varied by condition and across cancer site, with impact less for cancers with poor prognoses. Conditions most consistently associated with adverse outcomes across all cancer sites were renal disease, coagulopathies and congestive heart failure. Comorbidity is highly prevalent in cancer populations, but prevalence and impact of conditions differ markedly by cancer type. © 2013 Wiley Publishing Asia Pty Ltd.

A FRAMEWORK TO DESIGN AND OPTIMIZE CHEMICAL FLOODING PROCESSES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mojdeh Delshad; Gary A. Pope; Kamy Sepehrnoori

2005-07-01

The goal of this proposed research is to provide an efficient and user friendly simulation framework for screening and optimizing chemical/microbial enhanced oil recovery processes. The framework will include (1) a user friendly interface to identify the variables that have the most impact on oil recovery using the concept of experimental design and response surface maps, (2) UTCHEM reservoir simulator to perform the numerical simulations, and (3) an economic model that automatically imports the simulation production data to evaluate the profitability of a particular design. Such a reservoir simulation framework is not currently available to the oil industry. The objectivesmore » of Task 1 are to develop three primary modules representing reservoir, chemical, and well data. The modules will be interfaced with an already available experimental design model. The objective of the Task 2 is to incorporate UTCHEM reservoir simulator and the modules with the strategic variables and developing the response surface maps to identify the significant variables from each module. The objective of the Task 3 is to develop the economic model designed specifically for the chemical processes targeted in this proposal and interface the economic model with UTCHEM production output. Task 4 is on the validation of the framework and performing simulations of oil reservoirs to screen, design and optimize the chemical processes.« less

A Framework to Design and Optimize Chemical Flooding Processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mojdeh Delshad; Gary A. Pope; Kamy Sepehrnoori

2006-08-31

The goal of this proposed research is to provide an efficient and user friendly simulation framework for screening and optimizing chemical/microbial enhanced oil recovery processes. The framework will include (1) a user friendly interface to identify the variables that have the most impact on oil recovery using the concept of experimental design and response surface maps, (2) UTCHEM reservoir simulator to perform the numerical simulations, and (3) an economic model that automatically imports the simulation production data to evaluate the profitability of a particular design. Such a reservoir simulation framework is not currently available to the oil industry. The objectivesmore » of Task 1 are to develop three primary modules representing reservoir, chemical, and well data. The modules will be interfaced with an already available experimental design model. The objective of the Task 2 is to incorporate UTCHEM reservoir simulator and the modules with the strategic variables and developing the response surface maps to identify the significant variables from each module. The objective of the Task 3 is to develop the economic model designed specifically for the chemical processes targeted in this proposal and interface the economic model with UTCHEM production output. Task 4 is on the validation of the framework and performing simulations of oil reservoirs to screen, design and optimize the chemical processes.« less

A FRAMEWORK TO DESIGN AND OPTIMIZE CHEMICAL FLOODING PROCESSES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mojdeh Delshad; Gary A. Pope; Kamy Sepehrnoori

2004-11-01

The goal of this proposed research is to provide an efficient and user friendly simulation framework for screening and optimizing chemical/microbial enhanced oil recovery processes. The framework will include (1) a user friendly interface to identify the variables that have the most impact on oil recovery using the concept of experimental design and response surface maps, (2) UTCHEM reservoir simulator to perform the numerical simulations, and (3) an economic model that automatically imports the simulation production data to evaluate the profitability of a particular design. Such a reservoir simulation framework is not currently available to the oil industry. The objectivesmore » of Task 1 are to develop three primary modules representing reservoir, chemical, and well data. The modules will be interfaced with an already available experimental design model. The objective of the Task 2 is to incorporate UTCHEM reservoir simulator and the modules with the strategic variables and developing the response surface maps to identify the significant variables from each module. The objective of the Task 3 is to develop the economic model designed specifically for the chemical processes targeted in this proposal and interface the economic model with UTCHEM production output. Task 4 is on the validation of the framework and performing simulations of oil reservoirs to screen, design and optimize the chemical processes.« less

iNR-PhysChem: A Sequence-Based Predictor for Identifying Nuclear Receptors and Their Subfamilies via Physical-Chemical Property Matrix

PubMed Central

Xiao, Xuan; Wang, Pu; Chou, Kuo-Chen

2012-01-01

Nuclear receptors (NRs) form a family of ligand-activated transcription factors that regulate a wide variety of biological processes, such as homeostasis, reproduction, development, and metabolism. Human genome contains 48 genes encoding NRs. These receptors have become one of the most important targets for therapeutic drug development. According to their different action mechanisms or functions, NRs have been classified into seven subfamilies. With the avalanche of protein sequences generated in the postgenomic age, we are facing the following challenging problems. Given an uncharacterized protein sequence, how can we identify whether it is a nuclear receptor? If it is, what subfamily it belongs to? To address these problems, we developed a predictor called iNR-PhysChem in which the protein samples were expressed by a novel mode of pseudo amino acid composition (PseAAC) whose components were derived from a physical-chemical matrix via a series of auto-covariance and cross-covariance transformations. It was observed that the overall success rate achieved by iNR-PhysChem was over 98% in identifying NRs or non-NRs, and over 92% in identifying NRs among the following seven subfamilies: NR1thyroid hormone like, NR2HNF4-like, NR3estrogen like, NR4nerve growth factor IB-like, NR5fushi tarazu-F1 like, NR6germ cell nuclear factor like, and NR0knirps like. These rates were derived by the jackknife tests on a stringent benchmark dataset in which none of protein sequences included has pairwise sequence identity to any other in a same subset. As a user-friendly web-server, iNR-PhysChem is freely accessible to the public at either http://www.jci-bioinfo.cn/iNR-PhysChem or http://icpr.jci.edu.cn/bioinfo/iNR-PhysChem. Also a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated mathematics involved in developing the predictor. It is anticipated that iNR-PhysChem may become a useful high throughput tool

Identifying and Quantifying Chemical Forms of Sediment-Bound Ferrous Iron.

NASA Astrophysics Data System (ADS)

Kohler, M.; Kent, D. B.; Bekins, B. A.; Cozzarelli, I.; Ng, G. H. C.

2015-12-01

Aqueous Fe(II) produced by dissimilatory iron reduction comprises only a small fraction of total biogenic Fe(II) within an aquifer. Most biogenic Fe(II) is bound to sediments on ion exchange sites; as surface complexes and, possibly, surface precipitates; or incorporated into solid phases (e.g., siderite, magnetite). Different chemical forms of sediment-bound Fe(II) have different reactivities (e.g., with dissolved oxygen) and their formation or destruction by sorption/desorption and precipitation/dissolution is coupled to different solutes (e.g., major cations, H+, carbonate). We are quantifying chemical forms of sediment-bound Fe(II) using previously published extractions, novel extractions, and experimental studies (e.g., Fe isotopic exchange). Sediments are from Bemidji, Minnesota, where biodegradation of hydrocarbons from a burst oil pipeline has driven extensive dissimilatory Fe(III) reduction, and sites potentially impacted by unconventional oil and gas development. Generally, minimal Fe(II) was mobilized from ion exchange sites (batch desorption with MgCl2 and repeated desorption with NH4Cl). A < 2mm sediment fraction from the iron-reducing zone at Bemidji had 1.8umol/g Fe(II) as surface complexes or carbonate phases (sodium acetate at pH 5) of which ca. 13% was present as surface complexes (FerroZine extractions). Total bioavailable Fe(III) and biogenic Fe(II) (HCl extractions) was 40-50 umole/g on both background and iron-reducing zone sediments . Approximately half of the HCl-extractable Fe from Fe-reducing zone sediments was Fe(II) whereas 12 - 15% of Fe extracted from background sediments was present as Fe(II). One-third to one-half of the total biogenic Fe(II) extracted from sediments collected from a Montana prairie pothole located downgradient from a produced-water disposal pit was present as surface-complexed Fe(II).

Identification of candidate reference chemicals for in vitro steroidogenesis assays.

PubMed

Pinto, Caroline Lucia; Markey, Kristan; Dix, David; Browne, Patience

2018-03-01

The Endocrine Disruptor Screening Program (EDSP) is transitioning from traditional testing methods to integrating ToxCast/Tox21 in vitro high-throughput screening assays for identifying chemicals with endocrine bioactivity. The ToxCast high-throughput H295R steroidogenesis assay may potentially replace the low-throughput assays currently used in the EDSP Tier 1 battery to detect chemicals that alter the synthesis of androgens and estrogens. Herein, we describe an approach for identifying in vitro candidate reference chemicals that affect the production of androgens and estrogens in models of steroidogenesis. Candidate reference chemicals were identified from a review of H295R and gonad-derived in vitro assays used in methods validation and published in the scientific literature. A total of 29 chemicals affecting androgen and estrogen levels satisfied all criteria for positive reference chemicals, while an additional set of 21 and 15 chemicals partially fulfilled criteria for positive reference chemicals for androgens and estrogens, respectively. The identified chemicals included pesticides, pharmaceuticals, industrial and naturally-occurring chemicals with the capability to increase or decrease the levels of the sex hormones in vitro. Additionally, 14 and 15 compounds were identified as potential negative reference chemicals for effects on androgens and estrogens, respectively. These candidate reference chemicals will be informative for performance-based validation of in vitro steroidogenesis models. Copyright © 2017. Published by Elsevier Ltd.

A new process sensitivity index to identify important system processes under process model and parametric uncertainty

DOE PAGES

Dai, Heng; Ye, Ming; Walker, Anthony P.; ...

2017-03-28

A hydrological model consists of multiple process level submodels, and each submodel represents a process key to the operation of the simulated system. Global sensitivity analysis methods have been widely used to identify important processes for system model development and improvement. The existing methods of global sensitivity analysis only consider parametric uncertainty, and are not capable of handling model uncertainty caused by multiple process models that arise from competing hypotheses about one or more processes. To address this problem, this study develops a new method to probe model output sensitivity to competing process models by integrating model averaging methods withmore » variance-based global sensitivity analysis. A process sensitivity index is derived as a single summary measure of relative process importance, and the index includes variance in model outputs caused by uncertainty in both process models and their parameters. Here, for demonstration, the new index is used to assign importance to the processes of recharge and geology in a synthetic study of groundwater reactive transport modeling. The recharge process is simulated by two models that convert precipitation to recharge, and the geology process is simulated by two models of hydraulic conductivity. Each process model has its own random parameters. Finally, the new process sensitivity index is mathematically general, and can be applied to a wide range of problems in hydrology and beyond.« less

A new process sensitivity index to identify important system processes under process model and parametric uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Heng; Ye, Ming; Walker, Anthony P.

A hydrological model consists of multiple process level submodels, and each submodel represents a process key to the operation of the simulated system. Global sensitivity analysis methods have been widely used to identify important processes for system model development and improvement. The existing methods of global sensitivity analysis only consider parametric uncertainty, and are not capable of handling model uncertainty caused by multiple process models that arise from competing hypotheses about one or more processes. To address this problem, this study develops a new method to probe model output sensitivity to competing process models by integrating model averaging methods withmore » variance-based global sensitivity analysis. A process sensitivity index is derived as a single summary measure of relative process importance, and the index includes variance in model outputs caused by uncertainty in both process models and their parameters. Here, for demonstration, the new index is used to assign importance to the processes of recharge and geology in a synthetic study of groundwater reactive transport modeling. The recharge process is simulated by two models that convert precipitation to recharge, and the geology process is simulated by two models of hydraulic conductivity. Each process model has its own random parameters. Finally, the new process sensitivity index is mathematically general, and can be applied to a wide range of problems in hydrology and beyond.« less

The Impact of Chemical Probes in Drug Discovery: A Pharmaceutical Industry Perspective.

PubMed

Garbaccio, Robert M; Parmee, Emma R

2016-01-21

Chemical probes represent an important component of both academic and pharmaceutical drug discovery research. As a complement to prior reviews that have defined this scientific field, we aim to provide an industry perspective on the value of having high-quality chemical probes throughout the course of preclinical research. By studying examples from the internal Merck pipeline, we recognize that these probes require significant collaborative investment to realize their potential impact in clarifying the tractability and translation of a given therapeutic target. This perspective concludes with recommendations for chemical probe discovery aimed toward maximizing their potential to identify targets that result in the successful delivery of novel therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Global sensitivity analysis for identifying important parameters of nitrogen nitrification and denitrification under model uncertainty and scenario uncertainty

NASA Astrophysics Data System (ADS)

Chen, Zhuowei; Shi, Liangsheng; Ye, Ming; Zhu, Yan; Yang, Jinzhong

2018-06-01

Nitrogen reactive transport modeling is subject to uncertainty in model parameters, structures, and scenarios. By using a new variance-based global sensitivity analysis method, this paper identifies important parameters for nitrogen reactive transport with simultaneous consideration of these three uncertainties. A combination of three scenarios of soil temperature and two scenarios of soil moisture creates a total of six scenarios. Four alternative models describing the effect of soil temperature and moisture content are used to evaluate the reduction functions used for calculating actual reaction rates. The results show that for nitrogen reactive transport problem, parameter importance varies substantially among different models and scenarios. Denitrification and nitrification process is sensitive to soil moisture content status rather than to the moisture function parameter. Nitrification process becomes more important at low moisture content and low temperature. However, the changing importance of nitrification activity with respect to temperature change highly relies on the selected model. Model-averaging is suggested to assess the nitrification (or denitrification) contribution by reducing the possible model error. Despite the introduction of biochemical heterogeneity or not, fairly consistent parameter importance rank is obtained in this study: optimal denitrification rate (Kden) is the most important parameter; reference temperature (Tr) is more important than temperature coefficient (Q10); empirical constant in moisture response function (m) is the least important one. Vertical distribution of soil moisture but not temperature plays predominant role controlling nitrogen reaction. This study provides insight into the nitrogen reactive transport modeling and demonstrates an effective strategy of selecting the important parameters when future temperature and soil moisture carry uncertainties or when modelers face with multiple ways of establishing nitrogen

A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects

PubMed Central

Bramsen, Jesper B.; Pakula, Malgorzata M.; Hansen, Thomas B.; Bus, Claus; Langkjær, Niels; Odadzic, Dalibor; Smicius, Romualdas; Wengel, Suzy L.; Chattopadhyaya, Jyoti; Engels, Joachim W.; Herdewijn, Piet; Wengel, Jesper; Kjems, Jørgen

2010-01-01

Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5′-end) and complementary sequences in the 3′UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low. PMID:20453030

Ligand binding analysis and screening by chemical denaturation shift.

PubMed

Schön, Arne; Brown, Richard K; Hutchins, Burleigh M; Freire, Ernesto

2013-12-01

The identification of small molecule ligands is an important first step in drug development, especially drugs that target proteins with no intrinsic activity. Toward this goal, it is important to have access to technologies that are able to measure binding affinities for a large number of potential ligands in a fast and accurate way. Because ligand binding stabilizes the protein structure in a manner dependent on concentration and binding affinity, the magnitude of the protein stabilization effect elicited by binding can be used to identify and characterize ligands. For example, the shift in protein denaturation temperature (Tm shift) has become a popular approach to identify potential ligands. However, Tm shifts cannot be readily transformed into binding affinities, and the ligand rank order obtained at denaturation temperatures (≥60°C) does not necessarily coincide with the rank order at physiological temperature. An alternative approach is the use of chemical denaturation, which can be implemented at any temperature. Chemical denaturation shifts allow accurate determination of binding affinities with a surprisingly wide dynamic range (high micromolar to sub nanomolar) and in situations where binding changes the cooperativity of the unfolding transition. In this article, we develop the basic analytical equations and provide several experimental examples. Copyright © 2013 Elsevier Inc. All rights reserved.

Ligand Binding Analysis and Screening by Chemical Denaturation Shift

PubMed Central

Sch n, Arne; Brown, Richard K.; Hutchins, Burleigh M.; Freire, Ernesto

2013-01-01

The identification of small molecule ligands is an important first step in drug development, especially drugs that target proteins with no intrinsic activity. Towards this goal, it is important to have access to technologies that are able to measure binding affinities for a large number of potential ligands in a fast and accurate way. Since ligand binding stabilizes the protein structure in a manner dependent on concentration and binding affinity, the magnitude of the protein stabilization effect elicited by binding can be used to identify and characterize ligands. For example, the shift in protein denaturation temperature (Tm shift) has become a popular approach to identify potential ligands. However, Tm shifts cannot be readily transformed into binding affinities and the ligand rank order obtained at denaturation temperatures (60°C or higher) does not necessarily coincide with the rank order at physiological temperature. An alternative approach is the use of chemical denaturation, which can be implemented at any temperature. Chemical denaturation shifts allow accurate determination of binding affinities with a surprisingly wide dynamic range (high micromolar to sub nanomolar) and in situations in which binding changes the cooperativity of the unfolding transition. In this paper we develop the basic analytical equations and provide several experimental examples. PMID:23994566

The comparative toxicity to soil invertebrates of natural chemicals and their synthetic analogues.

PubMed

Whitaker, J; Chaplow, J S; Potter, E; Scott, W A; Hopkin, S; Harman, M; Sims, I; Sorokin, N

2009-07-01

The introduction of Registration, Evaluation and Authorisation of Chemicals (REACH), requires companies to register and risk assess all substances produced or imported in volumes of >1 tonne per year. Extrapolation methods which use existing data for estimating the effects of chemicals are attractive to industry, and comparative data are therefore increasingly in demand. Data on natural toxic chemicals could be used for extrapolation methods such as read-across. To test this hypothesis, the toxicity of natural chemicals and their synthetic analogues were compared using standardised toxicity tests. Two chemical pairs: the napthoquinones, juglone (natural) and 1,4-naphthoquinone (synthetic); and anthraquinones, emodin (natural) and quinizarin (synthetic) were chosen, and their comparative effects on the survival and reproduction of collembolans, earthworms, enchytraeids and predatory mites were assessed. Differences in sensitivity between the species were observed with the predatory mite (Hypoaspis aculeifer) showing the least sensitivity. Within the chemical pairs, toxicity to lethal and sub-lethal endpoints was very similar for the four invertebrate species. The exception was earthworm reproduction, which showed differential sensitivity to the chemicals in both naphthoquinone and anthraquinone pairs. Differences in toxicity identified in the present study may be related to degree of exposure and/or subtle differences in the mode of toxic action for the chemicals and species tested. It may be possible to predict differences by identifying functional groups which infer increased or decreased toxicity in one or other chemical. The development of such techniques would enable the use of read-across from natural to synthetic chemicals for a wider group of compounds.

A bootstrap based Neyman-Pearson test for identifying variable importance.

PubMed

Ditzler, Gregory; Polikar, Robi; Rosen, Gail

2015-04-01

Selection of most informative features that leads to a small loss on future data are arguably one of the most important steps in classification, data analysis and model selection. Several feature selection (FS) algorithms are available; however, due to noise present in any data set, FS algorithms are typically accompanied by an appropriate cross-validation scheme. In this brief, we propose a statistical hypothesis test derived from the Neyman-Pearson lemma for determining if a feature is statistically relevant. The proposed approach can be applied as a wrapper to any FS algorithm, regardless of the FS criteria used by that algorithm, to determine whether a feature belongs in the relevant set. Perhaps more importantly, this procedure efficiently determines the number of relevant features given an initial starting point. We provide freely available software implementations of the proposed methodology.

Uses of NHANES biomarker data for chemical risk ...

EPA Pesticide Factsheets

Background. Each year, the US NHANES measures hundreds of chemical biomarkers in samples from thousands of study participants. These biomarker measurements are meant to track trends and identify subsets of the US population with elevated exposures. There is now interest in further utilizing the NHANES data to inform chemical risk assessments. Objectives. This article highlights: 1) the extent to which NHANES chemical biomarker data have been evaluated, 2) groups of chemicals that have been studied, 3) data analysis approaches, and 4) opportunities for using these data to inform chemical risk assessments.Methods. A literature search (1999-2013) was performed to identify publications in which NHANES data were reported. Manual curation identified only the subset of publications that clearly utilized chemical biomarker data. This subset was evaluated for chemical groupings, data analysis approaches, and overall trends.Results. A small percentage of yearly NHANES-related publications reported on chemical biomarkers (8% yearly average). Of eleven chemical groups, metals/metalloids were most frequently evaluated (49%), followed by pesticides (9%) and environmental phenols (7%). Studies of multiple chemical groups were also common (8%). Publications linking chemical biomarkers to health metrics have increased dramatically in recent years. New studies are addressing challenges related to NHANES data interpretation in health risk contexts.Conclusions. This articl

Chemical Hygiene Program

NASA Technical Reports Server (NTRS)

Mayor, Antoinette C.

1999-01-01

The Chemical Management Team is responsible for ensuring compliance with the OSHA Laboratory Standard. The program at Lewis Research Center (LeRC) evolved over many years to include training, developing Standard Operating Procedures (SOPS) for each laboratory process, coordinating with other safety and health organizations and teams at the Center, and issuing an SOP binder. The Chemical Hygiene Policy was first established for the Center. The Chemical Hygiene Plan was established and reviewed by technical, laboratory and management for viability and applicability to the Center. A risk assessment was conducted for each laboratory. The laboratories were prioritized by order of risk, higher risk taking priority. A Chemical Management Team staff member interviewed the lead researcher for each laboratory process to gather the information needed to develop the SOP for the process. A binder containing the Chemical Hygiene Plan, the SOP, a map of the laboratory identifying the personal protective equipment and best egress, and glove guides, as well as other guides for safety and health. Each laboratory process has been captured in the form of an SOP. The chemicals used in the procedure have been identified and the information is used to reduce the number of chemicals in the lab. The Chemical Hygiene Plan binder is used as a training tool for new employees. LeRC is in compliance with the OSHA Standard. The program was designed to comply with the OSHA standard. In the process, we have been able to assess the usage of chemicals in the laboratories, as well as reduce or relocate the chemicals being stored in the laboratory. Our researchers are trained on the hazards of the materials they work with and have a better understanding of the hazards of the process and what is needed to prevent any incident. From the SOP process, we have been able to reduce our chemical inventory, determine and implement better hygiene procedures and equipment in the laboratories, and provide

Time-resolved resonance fluorescence spectroscopy for study of chemical reactions in laser-induced plasmas.

PubMed

Liu, Lei; Deng, Leimin; Fan, Lisha; Huang, Xi; Lu, Yao; Shen, Xiaokang; Jiang, Lan; Silvain, Jean-François; Lu, Yongfeng

2017-10-30

Identification of chemical intermediates and study of chemical reaction pathways and mechanisms in laser-induced plasmas are important for laser-ablated applications. Laser-induced breakdown spectroscopy (LIBS), as a promising spectroscopic technique, is efficient for elemental analyses but can only provide limited information about chemical products in laser-induced plasmas. In this work, time-resolved resonance fluorescence spectroscopy was studied as a promising tool for the study of chemical reactions in laser-induced plasmas. Resonance fluorescence excitation of diatomic aluminum monoxide (AlO) and triatomic dialuminum monoxide (Al 2 O) was used to identify these chemical intermediates. Time-resolved fluorescence spectra of AlO and Al 2 O were used to observe the temporal evolution in laser-induced Al plasmas and to study their formation in the Al-O 2 chemistry in air.

Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard.

PubMed

McEachran, Andrew D; Sobus, Jon R; Williams, Antony J

2017-03-01

Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most likely candidate "known unknowns," which are those chemicals unknown to an investigator but contained within a reference database or literature source, rise to the top of a chemical list when rank-ordered by the number of associated data sources. The U.S. EPA's CompTox Chemistry Dashboard is a curated and freely available resource for chemistry and computational toxicology research, containing more than 720,000 chemicals of relevance to environmental health science. In this research, the performance of the Dashboard for identifying known unknowns was evaluated against that of the online ChemSpider database, one of the primary resources used by mass spectrometrists, using multiple previously studied datasets reported in the peer-reviewed literature totaling 162 chemicals. These chemicals were examined using both applications via molecular formula and monoisotopic mass searches followed by rank-ordering of candidate compounds by associated references or data sources. A greater percentage of chemicals ranked in the top position when using the Dashboard, indicating an advantage of this application over ChemSpider for identifying known unknowns using data source ranking. Additional approaches are being developed for inclusion into a non-targeted analysis workflow as part of the CompTox Chemistry Dashboard. This work shows the potential for use of the Dashboard in exposure assessment and risk decision-making through significant improvements in non-targeted chemical identification. Graphical abstract Identifying known unknowns in the US EPA's CompTox Chemistry Dashboard from molecular formula and monoisotopic mass inputs.

Chemical suppressors of mlo-mediated powdery mildew resistance

PubMed Central

Wu, Hongpo; Kwaaitaal, Mark; Strugala, Roxana; Schaffrath, Ulrich; Bednarek, Paweł

2017-01-01

Loss-of-function of barley mildew locus o (Mlo) confers durable broad-spectrum penetration resistance to the barley powdery mildew pathogen, Blumeria graminis f. sp. hordei (Bgh). Given the importance of mlo mutants in agriculture, surprisingly few molecular components have been identified to be required for this type of resistance in barley. With the aim to identify novel cellular factors contributing to mlo-based resistance, we devised a pharmacological inhibitor screen. Of the 41 rationally chosen compounds tested, five caused a partial suppression of mlo resistance in barley, indicated by increased levels of Bgh host cell entry. These chemicals comprise brefeldin A (BFA), 2′,3′-dideoxyadenosine (DDA), 2-deoxy-d-glucose, spermidine, and 1-aminobenzotriazole. Further inhibitor analysis corroborated a key role for both anterograde and retrograde endomembrane trafficking in mlo resistance. In addition, all four ribonucleosides, some ribonucleoside derivatives, two of the five nucleobases (guanine and uracil), some guanine derivatives as well as various polyamines partially suppress mlo resistance in barley via yet unknown mechanisms. Most of the chemicals identified to be effective in partially relieving mlo resistance in barley also to some extent compromised powdery mildew resistance in an Arabidopsis mlo2 mlo6 double mutant. In summary, our study identified novel suppressors of mlo resistance that may serve as valuable probes to unravel further the molecular processes underlying this unusual type of disease resistance. PMID:29127104

Importance of Physico-Chemical Properties of Aerosols in the Formation of Arctic Ice Clouds

NASA Astrophysics Data System (ADS)

Keita, S. A.; Girard, E.

2014-12-01

Ice clouds play an important role in the Arctic weather and climate system but interactions between aerosols, clouds and radiation are poorly understood. Consequently, it is essential to fully understand their properties and especially their formation process. Extensive measurements from ground-based sites and satellite remote sensing reveal the existence of two Types of Ice Clouds (TICs) in the Arctic during the polar night and early spring. TIC-1 are composed by non-precipitating very small (radar-unseen) ice crystals whereas TIC-2 are detected by both sensors and are characterized by a low concentration of large precipitating ice crystals. It is hypothesized that TIC-2 formation is linked to the acidification of aerosols, which inhibit the ice nucleating properties of ice nuclei (IN). As a result, the IN concentration is reduced in these regions, resulting to a smaller concentration of larger ice crystals. Over the past 10 years, several parameterizations of homogeneous and heterogeneous ice nucleation have been developed to reflect the various physical and chemical properties of aerosols. These parameterizations are derived from laboratory studies on aerosols of different chemical compositions. The parameterizations are also developed according to two main approaches: stochastic (that nucleation is a probabilistic process, which is time dependent) and singular (that nucleation occurs at fixed conditions of temperature and humidity and time-independent). This research aims to better understand the formation process of TICs using a newly-developed ice nucleation parameterizations. For this purpose, we implement some parameterizations (2 approaches) into the Limited Area version of the Global Multiscale Environmental Model (GEM-LAM) and use them to simulate ice clouds observed during the Indirect and Semi-Direct Arctic Cloud (ISDAC) in Alaska. We use both approaches but special attention is focused on the new parameterizations of the singular approach. Simulation

Passive in-situ chemical sensor

DOEpatents

Morrell, Jonathan S [Farragut, TN; Ripley, Edward B [Knoxville, TN

2012-02-14

A chemical sensor for assessing a chemical of interest. In typical embodiments the chemical sensor includes a first thermocouple and second thermocouple. A reactive component is typically disposed proximal to the second thermal couple, and is selected to react with the chemical of interest and generate a temperature variation that may be detected by a comparison of a temperature sensed by the second thermocouple compared with a concurrent temperature detected by the first thermocouple. Further disclosed is a method for assessing a chemical of interest and a method for identifying a reaction temperature for a chemical of interest in a system.

Confronting unknown planetary boundary threats from chemical pollution.

PubMed

Persson, Linn M; Breitholtz, Magnus; Cousins, Ian T; de Wit, Cynthia A; MacLeod, Matthew; McLachlan, Michael S

2013-11-19

Rockström et al. proposed a set of planetary boundaries that delimitate a "safe operating space for humanity". One of the planetary boundaries is determined by "chemical pollution", however no clear definition was provided. Here, we propose that there is no single chemical pollution planetary boundary, but rather that many planetary boundary issues governed by chemical pollution exist. We identify three conditions that must be simultaneously met for chemical pollution to pose a planetary boundary threat. We then discuss approaches to identify chemicals that could fulfill those conditions, and outline a proactive hazard identification strategy that considers long-range transport and the reversibility of chemical pollution.

76 FR 1067 - Testing of Certain High Production Volume Chemicals; Second Group of Chemicals

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

... 2070-AD16 Testing of Certain High Production Volume Chemicals; Second Group of Chemicals AGENCY... processors of certain high production volume (HPV) chemical substances to conduct testing to obtain screening... potentially affected by this action if you manufacture (defined by statute to include import) or process any...

Identifying specific beliefs to target to improve restaurant employees' intentions for performing three important food safety behaviors.

PubMed

Pilling, Valerie K; Brannon, Laura A; Shanklin, Carol W; Howells, Amber D; Roberts, Kevin R

2008-06-01

Current national food safety training programs appear ineffective at improving food safety practices in foodservice operations, given the substantial number of Americans affected by foodborne illnesses after eating in restaurants each year. The Theory of Planned Behavior (TpB) was used to identify important beliefs that may be targeted to improve foodservice employees' intentions for three food safety behaviors that have the most substantial affect on public health: hand washing, using thermometers, and proper handling of food contact surfaces. In a cross-sectional design, foodservice employees (n=190) across three midwestern states completed a survey assessing TpB components and knowledge for the three food safety behaviors. Multiple regression analyses were performed on the TpB components for each behavior. Independent-samples t tests identified TpB beliefs that discriminated between participants who absolutely intend to perform the behaviors and those with lower intention. Employees' attitudes were the one consistent predictor of intentions for performing all three behaviors. However, a unique combination of important predictors existed for each separate behavior. Interventions for improving employees' behavioral intentions for food safety should focus on TpB components that predict intentions for each behavior and should bring all employees' beliefs in line with those of the employees who already intend to perform the food safety behaviors. Registered dietitians; dietetic technicians, registered; and foodservice managers can use these results to enhance training sessions and motivational programs to improve employees' food safety behaviors. Results also assist these professionals in recognizing their responsibility for enforcing and providing adequate resources for proper food safety behaviors.

Imported Wines: Identifying and Removing Wines Contaminated with Diethylene Glycol.

DTIC Science & Technology

1986-03-01

at controlling health risks, BATF has used its labeling authority to prohibit the marketing of alcoholic beverages that are mislabeled by virtue of...or beverages contaminated with harmful substances into the U.S. market . DEG, a toxic substance, would be such a contaminant. The BATF’S authority in...representing a significant risk to health are identified and removed from k the market . BATF did not conduct a risk assessment or seek an assess- ment from

Quantitative CRISPR interference screens in yeast identify chemical-genetic interactions and new rules for guide RNA design.

PubMed

Smith, Justin D; Suresh, Sundari; Schlecht, Ulrich; Wu, Manhong; Wagih, Omar; Peltz, Gary; Davis, Ronald W; Steinmetz, Lars M; Parts, Leopold; St Onge, Robert P

2016-03-08

Genome-scale CRISPR interference (CRISPRi) has been used in human cell lines; however, the features of effective guide RNAs (gRNAs) in different organisms have not been well characterized. Here, we define rules that determine gRNA effectiveness for transcriptional repression in Saccharomyces cerevisiae. We create an inducible single plasmid CRISPRi system for gene repression in yeast, and use it to analyze fitness effects of gRNAs under 18 small molecule treatments. Our approach correctly identifies previously described chemical-genetic interactions, as well as a new mechanism of suppressing fluconazole toxicity by repression of the ERG25 gene. Assessment of multiple target loci across treatments using gRNA libraries allows us to determine generalizable features associated with gRNA efficacy. Guides that target regions with low nucleosome occupancy and high chromatin accessibility are clearly more effective. We also find that the best region to target gRNAs is between the transcription start site (TSS) and 200 bp upstream of the TSS. Finally, unlike nuclease-proficient Cas9 in human cells, the specificity of truncated gRNAs (18 nt of complementarity to the target) is not clearly superior to full-length gRNAs (20 nt of complementarity), as truncated gRNAs are generally less potent against both mismatched and perfectly matched targets. Our results establish a powerful functional and chemical genomics screening method and provide guidelines for designing effective gRNAs, which consider chromatin state and position relative to the target gene TSS. These findings will enable effective library design and genome-wide programmable gene repression in many genetic backgrounds.

19 CFR 12.34 - Importation prohibited; certificate of inspection; importer's declaration.

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE White Phosphorus... importation into the United States of white phosphorus matches is prohibited. (b) Invoices covering matches... chemical analysis made by me the matches described below do not contain white or yellow phosphorus and that...

19 CFR 12.34 - Importation prohibited; certificate of inspection; importer's declaration.

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE White Phosphorus... importation into the United States of white phosphorus matches is prohibited. (b) Invoices covering matches... chemical analysis made by me the matches described below do not contain white or yellow phosphorus and that...

19 CFR 12.34 - Importation prohibited; certificate of inspection; importer's declaration.

Code of Federal Regulations, 2012 CFR

2012-04-01

... importation into the United States of white phosphorus matches is prohibited. (b) Invoices covering matches... OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE White Phosphorus... chemical analysis made by me the matches described below do not contain white or yellow phosphorus and that...

19 CFR 12.34 - Importation prohibited; certificate of inspection; importer's declaration.

Code of Federal Regulations, 2013 CFR

2013-04-01

... importation into the United States of white phosphorus matches is prohibited. (b) Invoices covering matches... OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE White Phosphorus... chemical analysis made by me the matches described below do not contain white or yellow phosphorus and that...

19 CFR 12.34 - Importation prohibited; certificate of inspection; importer's declaration.

Code of Federal Regulations, 2014 CFR

2014-04-01

... importation into the United States of white phosphorus matches is prohibited. (b) Invoices covering matches... OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE White Phosphorus... chemical analysis made by me the matches described below do not contain white or yellow phosphorus and that...

A rational approach to selecting and ranking some pharmaceuticals of concern for the aquatic environment and their relative importance compared with other chemicals.

PubMed

Donnachie, Rachel L; Johnson, Andrew C; Sumpter, John P

2016-04-01

Aquatic organisms can be exposed to thousands of chemicals discharged by the human population. Many of these chemicals are considered disruptive to aquatic wildlife, and the literature on the impacts of these chemicals grows daily. However, because time and resources are not infinite, research must focus on the chemicals that represent the greatest threat. One group of chemicals of increasing concern is pharmaceuticals, for which the primary challenge is to identify which represent the greatest threat. In the present study, a list of 12 pharmaceuticals was compiled based on scoring the prevalence of different compounds from previous prioritization reviews. These included rankings based on prescription data, environmental concentrations, predicted environmental concentration/predicted no-effect concentration (PEC/PNEC) ratios, persistency/bioaccumulation/(eco)toxicity (PBT), and fish plasma model approaches. The most frequently cited were diclofenac, paracetamol, ibuprofen, carbamazepine, naproxen, atenolol, ethinyl estradiol, aspirin, fluoxetine, propranolol, metoprolol, and sulfamethoxazole. For each pharmaceutical, literature on effect concentrations was compiled and compared with river concentrations in the United Kingdom. The pharmaceuticals were ranked by degree of difference between the median effect and median river concentrations. Ethinyl estradiol was ranked as the highest concern, followed by fluoxetine, propranolol, and paracetamol. The relative risk of these pharmaceuticals was compared with those of metals and some persistent organic pollutants. Pharmaceuticals appear to be less of a threat to aquatic organisms than some metals (Cu, Al, Zn) and triclosan, using this ranking approach. © 2015 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

SMALL FISH MODELS FOR IDENTIFYING AND ASSESSING THE EFFECTS OF ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

Endocrine-disrupting chemicals (EDCs), in particular those which affect the hypothalamic-pituitary-gonadal (HPG) axis of vertebrates, have become a focus of regulatory screening and testing throughout the world. Small fish species, principally the fathead minnow (Pimephales prom...

Suspect Screening Analysis of Chemicals in Consumer Products.

PubMed

Phillips, Katherine A; Yau, Alice; Favela, Kristin A; Isaacs, Kristin K; McEachran, Andrew; Grulke, Christopher; Richard, Ann M; Williams, Antony J; Sobus, Jon R; Thomas, Russell S; Wambaugh, John F

2018-03-06

A two-dimensional gas chromatography-time-of-flight/mass spectrometry (GC×GC-TOF/MS) suspect screening analysis method was used to rapidly characterize chemicals in 100 consumer products-which included formulations (e.g., shampoos, paints), articles (e.g., upholsteries, shower curtains), and foods (cereals)-and therefore supports broader efforts to prioritize chemicals based on potential human health risks. Analyses yielded 4270 unique chemical signatures across the products, with 1602 signatures tentatively identified using the National Institute of Standards and Technology 2008 spectral database. Chemical standards confirmed the presence of 119 compounds. Of the 1602 tentatively identified chemicals, 1404 were not present in a public database of known consumer product chemicals. Reported data and model predictions of chemical functional use were applied to evaluate the tentative chemical identifications. Estimated chemical concentrations were compared to manufacturer-reported values and other measured data. Chemical presence and concentration data can now be used to improve estimates of chemical exposure, and refine estimates of risk posed to human health and the environment.

Bridging the gap between sample collection and laboratory analysis: using dried blood spots to identify human exposure to chemical agents

NASA Astrophysics Data System (ADS)

Hamelin, Elizabeth I.; Blake, Thomas A.; Perez, Jonas W.; Crow, Brian S.; Shaner, Rebecca L.; Coleman, Rebecca M.; Johnson, Rudolph C.

2016-05-01

Public health response to large scale chemical emergencies presents logistical challenges for sample collection, transport, and analysis. Diagnostic methods used to identify and determine exposure to chemical warfare agents, toxins, and poisons traditionally involve blood collection by phlebotomists, cold transport of biomedical samples, and costly sample preparation techniques. Use of dried blood spots, which consist of dried blood on an FDA-approved substrate, can increase analyte stability, decrease infection hazard for those handling samples, greatly reduce the cost of shipping/storing samples by removing the need for refrigeration and cold chain transportation, and be self-prepared by potentially exposed individuals using a simple finger prick and blood spot compatible paper. Our laboratory has developed clinical assays to detect human exposures to nerve agents through the analysis of specific protein adducts and metabolites, for which a simple extraction from a dried blood spot is sufficient for removing matrix interferents and attaining sensitivities on par with traditional sampling methods. The use of dried blood spots can bridge the gap between the laboratory and the field allowing for large scale sample collection with minimal impact on hospital resources while maintaining sensitivity, specificity, traceability, and quality requirements for both clinical and forensic applications.

Sepiapterin Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells*

PubMed Central

Yang, Shaojun; Jan, Yi-Hua; Gray, Joshua P.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

2013-01-01

In the lung, chemical redox cycling generates highly toxic reactive oxygen species that can cause alveolar inflammation and damage to the epithelium, as well as fibrosis. In this study, we identified a cytosolic NADPH-dependent redox cycling activity in mouse lung epithelial cells as sepiapterin reductase (SPR), an enzyme important for the biosynthesis of tetrahydrobiopterin. Human SPR was cloned and characterized. In addition to reducing sepiapterin, SPR mediated chemical redox cycling of bipyridinium herbicides and various quinones; this activity was greatest for 1,2-naphthoquinone followed by 9,10-phenanthrenequinone, 1,4-naphthoquinone, menadione, and 2,3-dimethyl-1,4-naphthoquinone. Whereas redox cycling chemicals inhibited sepiapterin reduction, sepiapterin had no effect on redox cycling. Additionally, inhibitors such as dicoumarol, N-acetylserotonin, and indomethacin blocked sepiapterin reduction, with no effect on redox cycling. Non-redox cycling quinones, including benzoquinone and phenylquinone, were competitive inhibitors of sepiapterin reduction but noncompetitive redox cycling inhibitors. Site-directed mutagenesis of the SPR C-terminal substrate-binding site (D257H) completely inhibited sepiapterin reduction but had minimal effects on redox cycling. These data indicate that SPR-mediated reduction of sepiapterin and redox cycling occur by distinct mechanisms. The identification of SPR as a key enzyme mediating chemical redox cycling suggests that it may be important in generating cytotoxic reactive oxygen species in the lung. This activity, together with inhibition of sepiapterin reduction by redox-active chemicals and consequent deficiencies in tetrahydrobiopterin, may contribute to tissue injury. PMID:23640889

Ecotoxicity testing of chemicals with particular reference to pesticides.

PubMed

Walker, Colin H

2006-07-01

Ecotoxicity tests are performed on vertebrates and invertebrates for the environmental risk assessment of pesticides and other chemicals and for a variety of ecotoxicological studies in the laboratory and in the field. Existing practices and strategies in ecotoxicity testing are reviewed, including an account of current requirements of the European Commission for the testing of pesticides and the recent REACH (Registration, Evaluation, Authorisation and Restrictions of Chemicals) proposals for industrial chemicals. Criticisms of existing practices have been made on both scientific and ethical grounds, and these are considered before dealing with the question of possible alternative methods and strategies both for environmental risk assessment and for ecotoxicological studies more generally. New approaches from an ecological point of view are compared with recent developments in laboratory-based methods such as toxicity tests, biomarker assays and bioassays. With regard to the development of new strategies for risk assessment, it is suggested that full consideration should be given to the findings of earlier long-term studies of pollution, which identified mechanisms of action by which environmental chemicals can cause natural populations to decline. Neurotoxicity and endocrine disruption are two cases in point, and biomarker assays for them could have an important role in testing new chemicals suspected of having these properties. In a concluding discussion, possible ways of improving testing protocols are discussed, having regard for current issues in the field of environmental risk assessment as exemplified by the debate over the REACH proposals. The importance of flexibility and the roles of ecologists and ecotoxicologists are stressed in the context of environmental risk assessment.

Alternatives Assessment Frameworks: Research Needs for the Informed Substitution of Hazardous Chemicals

PubMed Central

Jacobs, Molly M.; Malloy, Timothy F.; Tickner, Joel A.; Edwards, Sally

2015-01-01

Background Given increasing pressures for hazardous chemical replacement, there is growing interest in alternatives assessment to avoid substituting a toxic chemical with another of equal or greater concern. Alternatives assessment is a process for identifying, comparing, and selecting safer alternatives to chemicals of concern (including those used in materials, processes, or technologies) on the basis of their hazards, performance, and economic viability. Objectives The purposes of this substantive review of alternatives assessment frameworks are to identify consistencies and differences in methods and to outline needs for research and collaboration to advance science policy practice. Methods This review compares methods used in six core components of these frameworks: hazard assessment, exposure characterization, life-cycle impacts, technical feasibility evaluation, economic feasibility assessment, and decision making. Alternatives assessment frameworks published from 1990 to 2014 were included. Results Twenty frameworks were reviewed. The frameworks were consistent in terms of general process steps, but some differences were identified in the end points addressed. Methodological gaps were identified in the exposure characterization, life-cycle assessment, and decision–analysis components. Methods for addressing data gaps remain an issue. Discussion Greater consistency in methods and evaluation metrics is needed but with sufficient flexibility to allow the process to be adapted to different decision contexts. Conclusion Although alternatives assessment is becoming an important science policy field, there is a need for increased cross-disciplinary collaboration to refine methodologies in support of the informed substitution and design of safer chemicals, materials, and products. Case studies can provide concrete lessons to improve alternatives assessment. Citation Jacobs MM, Malloy TF, Tickner JA, Edwards S. 2016. Alternatives assessment frameworks: research

Prospects for Chemically Tagging Stars in the Galaxy

NASA Astrophysics Data System (ADS)

Ting, Yuan-Sen; Conroy, Charlie; Goodman, Alyssa

2015-07-01

It is now well-established that the elemental abundance patterns of stars hold key clues not only to their formation, but also to the assembly histories of galaxies. One of the most exciting possibilities is the use of stellar abundance patterns as “chemical tags” to identify stars that were born in the same molecular cloud. In this paper, we assess the prospects of chemical tagging as a function of several key underlying parameters. We show that in the fiducial case of 104 distinct cells in chemical space and {10}5-{10}6 stars in the survey, one can expect to detect ∼ {10}2-{10}3 groups that are ≥slant 5σ overdensities in the chemical space. However, we find that even very large overdensities in chemical space do not guarantee that the overdensity is due to a single set of stars from a common birth cloud. In fact, for our fiducial model parameters, the typical 5σ overdensity is comprised of stars from a wide range of clusters with the most dominant cluster contributing only 25% of the stars. The most important factors limiting the identification of disrupted clusters via chemical tagging are the number of chemical cells in the chemical space and the survey sampling rate of the underlying stellar population. Both of these factors can be improved through strategic observational plans. While recovering individual clusters through chemical tagging may prove challenging, we show, in agreement with previous work, that different CMFs imprint different degrees of clumpiness in chemical space. These differences provide the opportunity to statistically reconstruct the slope and high-mass cutoff of CMF and its evolution through cosmic time.

Phenotypic chemical screening using a zebrafish neural crest EMT reporter identifies retinoic acid as an inhibitor of epithelial morphogenesis

PubMed Central

Jimenez, Laura; Wang, Jindong; Morrison, Monique A.; Whatcott, Clifford; Soh, Katherine K.; Warner, Steven; Bearss, David; Jette, Cicely A.; Stewart, Rodney A.

2016-01-01

ABSTRACT The epithelial-to-mesenchymal transition (EMT) is a highly conserved morphogenetic program essential for embryogenesis, regeneration and cancer metastasis. In cancer cells, EMT also triggers cellular reprogramming and chemoresistance, which underlie disease relapse and decreased survival. Hence, identifying compounds that block EMT is essential to prevent or eradicate disseminated tumor cells. Here, we establish a whole-animal-based EMT reporter in zebrafish for rapid drug screening, called Tg(snai1b:GFP), which labels epithelial cells undergoing EMT to produce sox10-positive neural crest (NC) cells. Time-lapse and lineage analysis of Tg(snai1b:GFP) embryos reveal that cranial NC cells delaminate from two regions: an early population delaminates adjacent to the neural plate, whereas a later population delaminates from within the dorsal neural tube. Treating Tg(snai1b:GFP) embryos with candidate small-molecule EMT-inhibiting compounds identified TP-0903, a multi-kinase inhibitor that blocked cranial NC cell delamination in both the lateral and medial populations. RNA sequencing (RNA-Seq) analysis and chemical rescue experiments show that TP-0903 acts through stimulating retinoic acid (RA) biosynthesis and RA-dependent transcription. These studies identify TP-0903 as a new therapeutic for activating RA in vivo and raise the possibility that RA-dependent inhibition of EMT contributes to its prior success in eliminating disseminated cancer cells. PMID:26794130

An approach in building a chemical compound search engine in oracle database.

PubMed

Wang, H; Volarath, P; Harrison, R

2005-01-01

A searching or identifying of chemical compounds is an important process in drug design and in chemistry research. An efficient search engine involves a close coupling of the search algorithm and database implementation. The database must process chemical structures, which demands the approaches to represent, store, and retrieve structures in a database system. In this paper, a general database framework for working as a chemical compound search engine in Oracle database is described. The framework is devoted to eliminate data type constrains for potential search algorithms, which is a crucial step toward building a domain specific query language on top of SQL. A search engine implementation based on the database framework is also demonstrated. The convenience of the implementation emphasizes the efficiency and simplicity of the framework.

Frontiers, Opportunities, and Challenges in Biochemical and Chemical Catalysis of CO2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appel, Aaron M.; Bercaw, John E.; Bocarsly, Andrew B.

2013-08-14

Our central premise is that catalytic scientists can learn by studying how these important metabolic processes occur in nature. Complementarily, biochemists can learn by studying how catalytic scientists view these same chemical transformations promoted by synthetic catalysts. From these studies, hypotheses can be developed and tested through manipulation of enzyme structure and by synthesizing simple molecular catalysts to incorporate different structural features of the enzymes. It is hoped that these studies will lead to new and useful concepts in catalyst design for fuel production and utilization. This paper describes the results of a workshop held to explore these concepts inmore » regard to the development of new and more efficient catalytic processes for the conversion of CO2 to a variety of carbon-based fuels. The organization of this overview/review is as follows: 1) The first section briefly explores how interactions between the catalysis and biological communities have been fruitful in developing new catalysts for the reduction of protons to hydrogen, the simplest fuel generation reaction. 2) The second section assesses the state of the art in both biological and chemical reduction of CO2 by two electrons to form either carbon monoxide (CO) or formate (HCOO-). It also attempts to identify common principles between biological and synthetic catalysts and productive areas for future research. 3) The third section explores both biological and chemical processes that result in the reduction of CO2 beyond the level of CO and formate, again seeking to identify common principles and productive areas of future research. 4) The fourth section explores the formation of carbon-carbon bonds in biological and chemical systems in the same vein as the other sections. 5) A fifth section addresses the role of non-redox reactions of CO2 in biological systems and their role in carbon metabolism, with a parallel discussion of chemical systems. 6) In section 6, the topics

Genomic Analyses Yield Markers for Identifying Agronomically Important Genes in Potato

USDA-ARS?s Scientific Manuscript database

This study explores the genetic architecture underling the potato evolution through a comprehensive assessment of wild and cultivated potato species based on the re-sequencing of 201 accessions of Solanum section Petota with >12 × genome coverage. We identified 450 domesticated genes, which showed e...

Prioritizing Environmental Chemicals for Obesity and Diabetes ...

EPA Pesticide Factsheets

Background: Diabetes and obesity are major threats to public health in the US and abroad. Understanding the role chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is a challenge. This review is intended to help researchers generate hypotheses about chemicals potentially contributing to diabetes and obesity-related health outcomes by summarizing relevant findings from the US Environmental Protection Agency (EPA) ToxCast high-throughput screening (HTS) program. Objectives: To develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high throughput screening data. Methods: Identify ToxCast assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and beta cell function, adipocyte dierentiation, and feeding behavior) and present chemical screening data against those assay targets to identify chemicals of potential interest. Discussion: Results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated from research papers and reviews published in the peer-reviewed literature. Testing of hypotheses based on ToxCast data will a

THP-1 monocytes but not macrophages as a potential alternative for CD34{sup +} dendritic cells to identify chemical skin sensitizers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lambrechts, Nathalie; Verstraelen, Sandra; Lodewyckx, Hanne

2009-04-15

Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34{sup +} progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expressionmore » profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin sensitizers (ammonium hexachloroplatinate IV, 1-chloro-2,4-dinitrobenzene, eugenol, para-phenylenediamine, and tetramethylthiuram disulfide) and 5 non-sensitizers (L-glutamic acid, methyl salicylate, sodium dodecyl sulfate, tributyltin chloride, and zinc sulfate) for 6, 10, and 24 h, and mRNA expression of the 13 genes was analyzed using real-time RT-PCR. The transcriptional response of 7 out of 13 genes in THP-1 monocytes was significantly correlated with DC, whereas only 2 out of 13 genes in THP-1 macrophages. After a cross-validation of a discriminant analysis of the gene expression profiles in the THP-1 monocytes, this cell model demonstrated to also have a capacity to distinguish skin sensitizers from non-sensitizers. However, the DC model was superior to the monocyte model for discrimination of (non-)sensitizing chemicals.« less

Assessment of Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk

PubMed Central

Czarnota, Jenna; Gennings, Chris; Wheeler, David C

2015-01-01

In evaluation of cancer risk related to environmental chemical exposures, the effect of many chemicals on disease is ultimately of interest. However, because of potentially strong correlations among chemicals that occur together, traditional regression methods suffer from collinearity effects, including regression coefficient sign reversal and variance inflation. In addition, penalized regression methods designed to remediate collinearity may have limitations in selecting the truly bad actors among many correlated components. The recently proposed method of weighted quantile sum (WQS) regression attempts to overcome these problems by estimating a body burden index, which identifies important chemicals in a mixture of correlated environmental chemicals. Our focus was on assessing through simulation studies the accuracy of WQS regression in detecting subsets of chemicals associated with health outcomes (binary and continuous) in site-specific analyses and in non-site-specific analyses. We also evaluated the performance of the penalized regression methods of lasso, adaptive lasso, and elastic net in correctly classifying chemicals as bad actors or unrelated to the outcome. We based the simulation study on data from the National Cancer Institute Surveillance Epidemiology and End Results Program (NCI-SEER) case–control study of non-Hodgkin lymphoma (NHL) to achieve realistic exposure situations. Our results showed that WQS regression had good sensitivity and specificity across a variety of conditions considered in this study. The shrinkage methods had a tendency to incorrectly identify a large number of components, especially in the case of strong association with the outcome. PMID:26005323

Assessment of weighted quantile sum regression for modeling chemical mixtures and cancer risk.

PubMed

Czarnota, Jenna; Gennings, Chris; Wheeler, David C

2015-01-01

In evaluation of cancer risk related to environmental chemical exposures, the effect of many chemicals on disease is ultimately of interest. However, because of potentially strong correlations among chemicals that occur together, traditional regression methods suffer from collinearity effects, including regression coefficient sign reversal and variance inflation. In addition, penalized regression methods designed to remediate collinearity may have limitations in selecting the truly bad actors among many correlated components. The recently proposed method of weighted quantile sum (WQS) regression attempts to overcome these problems by estimating a body burden index, which identifies important chemicals in a mixture of correlated environmental chemicals. Our focus was on assessing through simulation studies the accuracy of WQS regression in detecting subsets of chemicals associated with health outcomes (binary and continuous) in site-specific analyses and in non-site-specific analyses. We also evaluated the performance of the penalized regression methods of lasso, adaptive lasso, and elastic net in correctly classifying chemicals as bad actors or unrelated to the outcome. We based the simulation study on data from the National Cancer Institute Surveillance Epidemiology and End Results Program (NCI-SEER) case-control study of non-Hodgkin lymphoma (NHL) to achieve realistic exposure situations. Our results showed that WQS regression had good sensitivity and specificity across a variety of conditions considered in this study. The shrinkage methods had a tendency to incorrectly identify a large number of components, especially in the case of strong association with the outcome.

IN CASE YOU MISSED IT: EPA Releases New Chemical Safety Guidelines Aimed at Curbing Animal Testing, Tracking Mercury Imports, and Facilitating the Sharing of Confidential Business Information

EPA Pesticide Factsheets

EPA News Release: IN CASE YOU MISSED IT: EPA Releases New Chemical Safety Guidelines Aimed at Curbing Animal Testing, Tracking Mercury Imports, and Facilitating the Sharing of Confidential Business Information

Chemical Fingerprinting Program for RSRM Critical Materials

NASA Technical Reports Server (NTRS)

McClennen, William H.; Fife, Dennis J.; Killpack, Michael O.; Golde, Rick P.; Cash, Steve (Technical Monitor)

2002-01-01

This viewgraph presentation provides information on the chemical fingerprinting of RSRM (Reusable Sold Rocket Motor) components. A chemical fingerprint can be used to identify a material, to differentiate it from similar looking materials, or lead to its source. It can also identify unexpected changes to a vendor or supplier's material, and monitor aging.

Chemical footprint: a methodological framework for bridging life cycle assessment and planetary boundaries for chemical pollution.

PubMed

Sala, Serenella; Goralczyk, Malgorzata

2013-10-01

The development and use of footprint methodologies for environmental assessment are increasingly important for both the scientific and political communities. Starting from the ecological footprint, developed at the beginning of the 1990s, several other footprints were defined, e.g., carbon and water footprint. These footprints-even though based on a different meaning of "footprint"-integrate life cycle thinking, and focus on some challenging environmental impacts including resource consumption, CO2 emission leading to climate change, and water consumption. However, they usually neglect relevant sources of impacts, as those related to the production and use of chemicals. This article presents and discusses the need and relevance of developing a methodology for assessing the chemical footprint, coupling a life cycle-based approach with methodologies developed in other contexts, such as ERA and sustainability science. Furthermore, different concepts underpin existing footprint and this could be the case also of chemical footprint. At least 2 different approaches and steps to chemical footprint could be envisaged, applicable at the micro- as well as at the meso- and macroscale. The first step (step 1) is related to the account of chemicals use and emissions along the life cycle of a product, sector, or entire economy, to assess potential impacts on ecosystems and human health. The second step (step 2) aims at assessing to which extent actual emission of chemicals harm the ecosystems above their capability to recover (carrying capacity of the system). The latter step might contribute to the wide discussion on planetary boundaries for chemical pollution: the thresholds that should not be surpassed to guarantee a sustainable use of chemicals from an environmental safety perspective. The definition of what the planetary boundaries for chemical pollution are and how the boundaries should be identified is an on-going scientific challenge for ecotoxicology and ecology. In

Exposure Levels for Chemical Threat Compounds; Information to Facilitate Chemical Incident Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hauschild, Veronique; Watson, Annetta Paule

2013-01-01

Exposure Standards, Limits and Guidelines for Chemical Threat Compunds ABSTRACT Exposure criteria for chemical warfare (CW) agents and certain toxic industrial chemicals (TICs) used as CW agents (such as chlorine fill in an improvised explosive device) have been developed for protection of the civilian general public, civilian employees in chemical agent processing facilities and deployed military populations. In addition, compound-specific concentrations have been developed to serve as how clean is clean enough clearance criteria guiding facility recovery following chemical terrorist or other hazardous release events. Such criteria are also useful to verify compound absence, identify containment boundaries and expedite facilitymore » recovery following chemical threat release. There is no single right value or concentration appropriate for all chemical hazard control applications. It is acknowledged that locating and comparing the many sources of CW agent and TIC exposure criteria has not been previously well-defined. This paper summarizes many of these estimates and assembles critical documentation regarding their derivation and use.« less

Wastewater Treatment Plants as Chemical Observatories to Forecast Ecological and Human Health Risks of Manmade Chemicals

PubMed Central

Venkatesan, Arjun K.; Halden, Rolf U.

2014-01-01

Thousands of chemicals have been identified as contaminants of emerging concern (CECs), but prioritizing them concerning ecological and human health risks is challenging. We explored the use of sewage treatment plants as chemical observatories to conveniently identify persistent and bioaccumulative CECs, including toxic organohalides. Nationally representative samples of sewage sludge (biosolids) were analyzed for 231 CECs, of which 123 were detected. Ten of the top 11 most abundant CECs in biosolids were found to be high-production volume chemicals, eight of which representing priority chemicals, including three flame retardants, three surfactants and two antimicrobials. A comparison of chemicals detected in nationally representative biological specimens from humans and municipal biosolids revealed 70% overlap. This observed co-occurrence of contaminants in both matrices suggests that the analysis of sewage sludge can inform human health risk assessments by providing current information on toxic exposures in human populations and associated body burdens of harmful environmental pollutants. PMID:24429544

21 CFR 1310.12 - Exempt chemical mixtures.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Exempt chemical mixtures. 1310.12 Section 1310.12... CHEMICALS AND CERTAIN MACHINES § 1310.12 Exempt chemical mixtures. (a) The chemical mixtures meeting the..., or importation of listed chemicals contained in the exempt chemical mixture or the civil liability...

21 CFR 1310.12 - Exempt chemical mixtures.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Exempt chemical mixtures. 1310.12 Section 1310.12... CHEMICALS AND CERTAIN MACHINES § 1310.12 Exempt chemical mixtures. (a) The chemical mixtures meeting the..., or importation of listed chemicals contained in the exempt chemical mixture or the civil liability...

21 CFR 1310.12 - Exempt chemical mixtures.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Exempt chemical mixtures. 1310.12 Section 1310.12... CHEMICALS AND CERTAIN MACHINES § 1310.12 Exempt chemical mixtures. (a) The chemical mixtures meeting the..., or importation of listed chemicals contained in the exempt chemical mixture or the civil liability...

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

EPA Science Inventory

Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultur...

[Chemical Constituents from Mallotus paniculatus (II)].

PubMed

Zhu, Chun-ling

2015-04-01

To study the chemical constituents of Mallotus paniculaus radix. The compounds were isolated with column chromatography. The chemical structures were identified by spectral and spectroscopic technology. Seven compounds were isolated from the n-BuOH extract and identified as scopoletin(1), isoscopletin(2), erythordiol(3), apigenin(4), 4-methoxybenzoic acid(5), acetylaleuritolic acid(6) and β-daucosterol (7). compounds 2 - 6 are isolated from this plant for the first time.

Identifying selectively important amino acid positions associated with alternative habitat environments in fish mitochondrial genomes.

PubMed

Xia, Jun Hong; Li, Hong Lian; Zhang, Yong; Meng, Zi Ning; Lin, Hao Ran

2018-05-01

Fish species inhabitating seawater (SW) or freshwater (FW) habitats have to develop genetic adaptations to alternative environment factors, especially salinity. Functional consequences of the protein variations associated with habitat environments in fish mitochondrial genomes have not yet received much attention. We analyzed 829 complete fish mitochondrial genomes and compared the amino acid differences of 13 mitochondrial protein families between FW and SW fish groups. We identified 47 specificity determining sites (SDS) that associated with FW or SW environments from 12 mitochondrial protein families. Thirty-two (68%) of the SDS sites are hydrophobic, 13 (28%) are neutral, and the remaining sites are acidic or basic. Seven of those SDS from ND1, ND2 and ND5 were scored as probably damaging to the protein structures. Furthermore, phylogenetic tree based Bayes Empirical Bayes analysis also detected 63 positive sites associated with alternative habitat environments across ten mtDNA proteins. These signatures could be important for studying mitochondrial genetic variation relevant to fish physiology and ecology.

Comparison of physical, chemical, and sensorial characteristics between U.S.-imported and Northwestern Mexico retail beef.

PubMed

González-Rios, H; Peña-Ramos, A; Valenzuela, M; Zamorano-García, L; Cumplido-Barbeitia, G; González-Méndez, N F; Huerta-Leidenz, N

2010-01-01

To compare beef from Northwestern Mexico (NMEX) and that imported from the United States in physical-chemical (PC) and sensory traits, samples of ribeye (m. Longissimus dorsi thoracis, LDT) and knuckle (m. Vastus lateralis, VL) of Mexican (64 LDT; 51 VL) and U.S. (28 LDT; 25 VL) origin were purchased randomly from select retail stores located in 3 cities of NMEX. PC evaluation measured contents of moisture, fat and cholesterol, Warner-Bratzler shear force (WBSF), pH, CIE L*, a*, and b*, cooking loss, and normalized fatty acid profile (FAP). Trained panelists evaluated raw and cooked samples for 2 and 6 different organoleptic traits, respectively. Mexican and U.S.-imported LDT steaks did not differ (P>0.05) in PC traits. VL samples differed in L*, b*, hue*, WBSF, and fat content by country of origin (COO). The WBSF for cooked VL samples from the United States was lower (P < 0.05) and fat content was greater (P<0.05) than those for NMEX steaks. The FAP varied between muscles; Mexican LDT had a higher content of C18:0, while VL from the United States had a higher proportion of polyunsaturated fatty acids (PUFA) and a higher PUFA/Saturated ratio (P<0.05). Although sensory traits tended to be rated higher for Mexican LDT and VL steaks, no statistical differences with U.S.-imported samples were detected (P > 0.05). Results indicated that domestic and U.S. retail steaks sold in the NMEX are similar in eating quality and PC, whereas differences observed in FAP deserve further attention from a nutritional standpoint. © 2010 Institute of Food Technologists®

Safety, security and dual-use chemicals

DOE PAGES

Walters, Douglas B.; Ho, Pauline; Hardesty, Jasper

2014-12-18

Many chemicals that are frequently used in laboratories and industries can be harmful if not handled properly. Chemical safety best practices are designed to protect people from accidentally being exposed to hazardous chemicals. On the other hand, chemical security best practices are designed to protect people from someone deliberately exposing others to hazardous chemicals. Finally, many chemical safety best practices overlap with chemical security best practices, but there are important differences, as will be discussed in this paper.

21 CFR 1310.12 - Exempt chemical mixtures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exempt chemical mixtures. 1310.12 Section 1310.12... CHEMICALS AND CERTAIN MACHINES § 1310.12 Exempt chemical mixtures. (a) The chemical mixtures meeting the... importation of listed chemicals contained in the exempt chemical mixture or the civil liability for unlawful...

21 CFR 1310.12 - Exempt chemical mixtures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Exempt chemical mixtures. 1310.12 Section 1310.12... CHEMICALS AND CERTAIN MACHINES § 1310.12 Exempt chemical mixtures. (a) The chemical mixtures meeting the... importation of listed chemicals contained in the exempt chemical mixture or the civil liability for unlawful...

Triangulating Principal Effectiveness: How Perspectives of Parents, Teachers, and Assistant Principals Identify the Central Importance of Managerial Skills. Working Paper 35

ERIC Educational Resources Information Center

Grissom, Jason A.; Loeb, Susanna

2009-01-01

While the importance of effective principals is undisputed, few studies have addressed what specific skills principals need to promote school success. This study draws on unique data combining survey responses from principals, assistant principals, teachers and parents with rich administrative data to identify which principal skills matter most…

Exploring the planetary boundary for chemical pollution.

PubMed

Diamond, Miriam L; de Wit, Cynthia A; Molander, Sverker; Scheringer, Martin; Backhaus, Thomas; Lohmann, Rainer; Arvidsson, Rickard; Bergman, Åke; Hauschild, Michael; Holoubek, Ivan; Persson, Linn; Suzuki, Noriyuki; Vighi, Marco; Zetzsch, Cornelius

2015-05-01

Rockström et al. (2009a, 2009b) have warned that humanity must reduce anthropogenic impacts defined by nine planetary boundaries if "unacceptable global change" is to be avoided. Chemical pollution was identified as one of those boundaries for which continued impacts could erode the resilience of ecosystems and humanity. The central concept of the planetary boundary (or boundaries) for chemical pollution (PBCP or PBCPs) is that the Earth has a finite assimilative capacity for chemical pollution, which includes persistent, as well as readily degradable chemicals released at local to regional scales, which in aggregate threaten ecosystem and human viability. The PBCP allows humanity to explicitly address the increasingly global aspects of chemical pollution throughout a chemical's life cycle and the need for a global response of internationally coordinated control measures. We submit that sufficient evidence shows stresses on ecosystem and human health at local to global scales, suggesting that conditions are transgressing the safe operating space delimited by a PBCP. As such, current local to global pollution control measures are insufficient. However, while the PBCP is an important conceptual step forward, at this point single or multiple PBCPs are challenging to operationalize due to the extremely large number of commercial chemicals or mixtures of chemicals that cause myriad adverse effects to innumerable species and ecosystems, and the complex linkages between emissions, environmental concentrations, exposures and adverse effects. As well, the normative nature of a PBCP presents challenges of negotiating pollution limits amongst societal groups with differing viewpoints. Thus, a combination of approaches is recommended as follows: develop indicators of chemical pollution, for both control and response variables, that will aid in quantifying a PBCP(s) and gauging progress towards reducing chemical pollution; develop new technologies and technical and social

An Experimental Framework for Generating Evolvable Chemical Systems in the Laboratory

NASA Astrophysics Data System (ADS)

Baum, David A.; Vetsigian, Kalin

2017-12-01

Most experimental work on the origin of life has focused on either characterizing the chemical synthesis of particular biochemicals and their precursors or on designing simple chemical systems that manifest life-like properties such as self-propagation or adaptive evolution. Here we propose a new class of experiments, analogous to artificial ecosystem selection, where we select for spontaneously forming self-propagating chemical assemblages in the lab and then seek evidence of a response to that selection as a key indicator that life-like chemical systems have arisen. Since surfaces and surface metabolism likely played an important role in the origin of life, a key experimental challenge is to find conditions that foster nucleation and spread of chemical consortia on surfaces. We propose high-throughput screening of a diverse set of conditions in order to identify combinations of "food," energy sources, and mineral surfaces that foster the emergence of surface-associated chemical consortia that are capable of adaptive evolution. Identification of such systems would greatly advance our understanding of the emergence of self-propagating entities and the onset of adaptive evolution during the origin of life.

Concept of REACH and impact on evaluation of chemicals.

PubMed

Foth, H; Hayes, Aw

2008-01-01

Industrial chemicals have been in use for many decades and new products are regularly invented and introduced to the market. Also for decades, many different chemical laws have been introduced to regulate safe handling of chemicals in different use patterns. The patchwork of current regulation in the European Union is to be replaced by the new regulation on industrial chemical control, REACH. REACH stands for registration, evaluation, and authorization of chemicals. REACH entered force on June 1, 2007. REACH aims to overcome limitations in testing requirements of former regulation on industrial chemicals to enhance competitiveness and innovation with regard to manufacture safer substances and to promote the development of alternative testing methods. A main task of REACH is to address data gaps regarding the properties and uses of industrial chemicals. Producers, importers, and downstream users will have to compile and communicate standard information for all chemicals. Information sets to be prepared include safety data sheets (SDS), chemical safety reports (CSR), and chemical safety assessments (CSA). These are designed to guarantee adequate handling in the production chain, in transport and in use and to prevent the substances from being released to and distributed within the environment. Another important aim is to identify the most harmful chemicals and to set incentives to substitute them with safer alternatives. On one hand, REACH will have substantial impact on the basic understanding of the evaluation of chemicals. However, the toxicological sciences can also substantially influence the workability of REACH that supports the transformation of data to the information required to understand and manage acceptable and non acceptable risks in the use of industrial chemicals. The REACH regulation has been laid down in the main document and 17 Annexes of more than 849 pages. Even bigger technical guidance documents will follow and will inform about the rules for

Haz-Mat Refresher: Chemical Precautions

ERIC Educational Resources Information Center

Caliendo, Louis A.

2012-01-01

It is important that first responders remain aware of the possible hazards resulting from chemical accidents or the intentional use of chemicals in destructive devices. Chemical components can be utilized in the manufacturing of improvised explosive devices (IEDs), can enhance the effect of a more conventional device, or can pose hazards based on…

Heteropteran chemical repellents identified in the citrus odor of a seabird (crested auklet: Aethia cristatella): evolutionary convergence in chemical ecology

NASA Astrophysics Data System (ADS)

Douglas, H. D.; Co, J. E.; Jones, T. H.; Conner, W. E.

2001-08-01

The exogenous application of chemical repellents is widespread in birds, but endogenous production is exceedingly rare. We herein report a new class of avian defensive compounds isolated from the feathers and volatile odor of the crested auklet ( Aethia cristatella). Mass spectra indicate that n-hexanal, n-octanal, n-decanal, Z-4-decenal and a 12-carbon unsaturated aldehyde comprise the auklet odorant. Octanal and hexanal are also secreted in the repugnant metasternal gland emissions of heteropteran insects and are known to be potent invertebrate repellents. We suggest that the auklet odorant functions as an ectoparasite repellent and a signal of mate quality. This would represent a rare and direct link between vigor, quality and parasite resistance, one of several putative bases for mate selection. This is the first report of defensive compounds produced by a seabird or colonial bird and one of the few examples of chemical defense in a polar or subpolar marine vertebrate.

Chemical hazards in aeromedical aircraft.

PubMed

Tupper, C R

1989-01-01

Several potentially hazardous chemicals are required to make modern military aircraft fly. With each airevac mission, the possibility exists for structural failure of a fluid system, resulting in contamination to flight/medical crews, patients, and passengers. Aeromedical Evacuation Crewmembers (AECMs) need to be aware of the hazardous chemicals used in aircraft and areas where there is an increased risk to those in and around the aircraft. This study identified potential areas for chemical leakage, such as refuel receptacles, hydraulic reservoirs, hydraulic motors, doors, ramps, engines, and more. Further, it identified the basic first aid procedures to perform on people contaminated with jet fuel, hydraulic fluid, engine oil, fire extinguisher agents, LOX and other fluids. First aid procedures are basic and can be performed with supplies and equipment on a routine aeromedical evacuation mission, AECMs trained in a basic awareness of hazardous aircraft chemicals will result in crews better prepared to cope with the unique risks of transporting patients in a complicated military aircraft.

Application of Chemical Genomics to Plant-Bacteria Communication: A High-Throughput System to Identify Novel Molecules Modulating the Induction of Bacterial Virulence Genes by Plant Signals.

PubMed

Vandelle, Elodie; Puttilli, Maria Rita; Chini, Andrea; Devescovi, Giulia; Venturi, Vittorio; Polverari, Annalisa

2017-01-01

The life cycle of bacterial phytopathogens consists of a benign epiphytic phase, during which the bacteria grow in the soil or on the plant surface, and a virulent endophytic phase involving the penetration of host defenses and the colonization of plant tissues. Innovative strategies are urgently required to integrate copper treatments that control the epiphytic phase with complementary tools that control the virulent endophytic phase, thus reducing the quantity of chemicals applied to economically and ecologically acceptable levels. Such strategies include targeted treatments that weaken bacterial pathogens, particularly those inhibiting early infection steps rather than tackling established infections. This chapter describes a reporter gene-based chemical genomic high-throughput screen for the induction of bacterial virulence by plant molecules. Specifically, we describe a chemical genomic screening method to identify agonist and antagonist molecules for the induction of targeted bacterial virulence genes by plant extracts, focusing on the experimental controls required to avoid false positives and thus ensuring the results are reliable and reproducible.

Optical filter selection for high confidence discrimination of strongly overlapping infrared chemical spectra.

PubMed

Major, Kevin J; Poutous, Menelaos K; Ewing, Kenneth J; Dunnill, Kevin F; Sanghera, Jasbinder S; Aggarwal, Ishwar D

2015-09-01

importance of choosing the proper filter set and chemicals for comparative discrimination, in order to identify the target chemical of interest in the presence of closely matched chemical interferents. These findings are an integral step in the development of experimental prototype sensors, which will utilize CDSD.

A Chemical Model of the Coma of Comet C/2009 P1 (Garradd)

NASA Astrophysics Data System (ADS)

Boice, Daniel C.; Kawakita, H.; Kobayashi, H.; Naka, C.; Phelps, L.

2012-10-01

Modeling is essential to understand the important physical and chemical processes that occur in cometary comae. Photochemistry is a major source of ions and electrons that further initiate key gas-phase reactions, leading to the plethora of molecules and atoms observed in comets. The effects of photoelectrons that react via impacts are important to the overall ionization. We identify the relevant processes within a global modeling framework to understand simultaneous observations in the visible and near-IR of Comet C/2009 (Garradd) and to provide valuable insights into the intrinsic properties of its nucleus. Details of these processes are presented in the collision-dominated, inner coma of the comet to evaluate the relative chemical pathways and the relationship between parent and sibling molecules. Acknowledgements: We appreciate support from the NSF Planetary Astronomy Program.

[Chemical constituents of Changium smyrnioides].

PubMed

Ren, Dong-chun; Qian, Shi-hui; Yang, Nian-yun; Xie, Ning; Duan, Jin-ao

2008-01-01

To study chemical constituents of Changium smyrnioides Wolff. The chemical components were isolated and purified by silica gel column and recrystallization. The chemical structures were elucidated on the basis of physico-chemical properties and spectral data. Ten compounds were isolated and identified as lignoceric acid (1), beta-sitosterol (2), stigmasterol (3), 5-hydroxy-8-methoxypsoralen (4), glycerylmonopalmitate (5), L-pyroglutamic acid (6), succinic acid (7), vanillic acid-4-O-beta-D-glucopyranoside (8 ), vanillic acid (9), daucosterol (10). Compounds 1, 4, 5, 6, 8 and 9 are obtained from the plant for the first time.

Comparing results of X-ray diffraction, µ-Raman spectroscopy and neutron diffraction when identifying chemical phases in seized nuclear material, during a comparative nuclear forensics exercise

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rondahl, Stina Holmgren; Pointurier, Fabien; Ahlinder, Linnea

This work presents the results for identification of chemical phases obtained by several laboratories as a part of an international nuclear forensic round-robin exercise. In this work powder X-ray diffraction (p-XRD) is regarded as the reference technique. Neutron diffraction produced a superior high-angle diffraction pattern relative to p-XRD. Requiring only small amounts of sample, µ-Raman spectroscopy was used for the first time in this context as a potentially complementary technique to p-XRD. The chemical phases were identified as pure UO 2 in two materials, and as a mixture of UO 2, U 3O 8 and an intermediate species U 3Omore » 7 in the third material.« less

Comparing results of X-ray diffraction, µ-Raman spectroscopy and neutron diffraction when identifying chemical phases in seized nuclear material, during a comparative nuclear forensics exercise

DOE PAGES

Rondahl, Stina Holmgren; Pointurier, Fabien; Ahlinder, Linnea; ...

2018-01-24

This work presents the results for identification of chemical phases obtained by several laboratories as a part of an international nuclear forensic round-robin exercise. In this work powder X-ray diffraction (p-XRD) is regarded as the reference technique. Neutron diffraction produced a superior high-angle diffraction pattern relative to p-XRD. Requiring only small amounts of sample, µ-Raman spectroscopy was used for the first time in this context as a potentially complementary technique to p-XRD. The chemical phases were identified as pure UO 2 in two materials, and as a mixture of UO 2, U 3O 8 and an intermediate species U 3Omore » 7 in the third material.« less

Comparing results of X-ray diffraction, µ-Raman spectroscopy and neutron diffraction when identifying chemical phases in seized nuclear material, during a comparative nuclear forensics exercise.

PubMed

Rondahl, Stina Holmgren; Pointurier, Fabien; Ahlinder, Linnea; Ramebäck, Henrik; Marie, Olivier; Ravat, Brice; Delaunay, François; Young, Emma; Blagojevic, Ned; Hester, James R; Thorogood, Gordon; Nelwamondo, Aubrey N; Ntsoane, Tshepo P; Roberts, Sarah K; Holliday, Kiel S

2018-01-01

This work presents the results for identification of chemical phases obtained by several laboratories as a part of an international nuclear forensic round-robin exercise. In this work powder X-ray diffraction (p-XRD) is regarded as the reference technique. Neutron diffraction produced a superior high-angle diffraction pattern relative to p-XRD. Requiring only small amounts of sample, µ-Raman spectroscopy was used for the first time in this context as a potentially complementary technique to p-XRD. The chemical phases were identified as pure UO 2 in two materials, and as a mixture of UO 2 , U 3 O 8 and an intermediate species U 3 O 7 in the third material.

Intermolecular CH···O/N H-bonds in the biologically important pairs of natural nucleobases: a thorough quantum-chemical study.

PubMed

Brovarets', Ol'ha O; Yurenko, Yevgen P; Hovorun, Dmytro M

2014-01-01

This study aims to cast light on the physico-chemical nature and energetic of the non-conventional CH···O/N H-bonds in the biologically important natural nucleobase pairs using a comprehensive quantum-chemical approach. As a whole, the 36 biologically important pairs, involving canonical and rare tautomers of nucleobases, were studied by means of all available up-to-date state-of-the-art quantum-chemical techniques along with quantum theory "Atoms in molecules" (QTAIM), Natural Bond Orbital (NBO) analysis, Grunenberg's compliance constants theory, geometrical and vibrational analyses to identify the CH···O/N interactions, reveal their physico-chemical nature and estimate their strengths as well as contribution to the overall base-pairs stability. It was shown that all the 38 CH···O/N contacts (25 CH···O and 13 CH···N H-bonds) completely satisfy all classical geometrical, electron-topological, in particular Bader's and "two-molecule" Koch and Popelier's, and vibrational criteria of H-bonding. The positive values of Grunenberg's compliance constants prove that the CH···O/N contacts in nucleobase pairs are stabilizing interactions unlike electrostatic repulsion and anti-H-bonds. NBO analysis indicates the electron density transfer from the lone electron pair of the acceptor atom (O/N) to the antibonding orbital corresponding to the donor group σ(∗)(CH). Moreover, significant increase in the frequency of the out-of-plane deformation modes γ (CH) under the formation of the CH···O (by 17.2÷81.3/10.8÷84.7 cm(-1)) and CH···N (by 32.7÷85.9/9.0÷77.9 cm(-1)) H-bonds at the density functional theory (DFT)/second-order Møller-Plesset (MP2) levels of theory, respectively, and concomitant changes of their intensities can be considered as reliable indicators of H-bonding. The strengths of the CH···O/N interactions, evaluated by means of Espinosa-Molins-Lecomte formula, lie within the range 0.45÷3.89/0.62÷4.10 kcal/mol for the CH�

Chemical hydrogen storage material property guidelines for automotive applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Semelsberger, Troy; Brooks, Kriston P.

2015-04-01

Chemical hydrogen storage is the sought after hydrogen storage media for automotive applications because of the expected low pressure operation (<20 atm), moderate temperature operation (<200 C), system gravimetric capacities (>0.05 kg H2/kg system), and system volumetric capacities (>0.05 kg H2/L system). Currently, the primary shortcomings of chemical hydrogen storage are regeneration efficiency, fuel cost and fuel phase (i.e., solid or slurry phase). Understanding the required material properties to meet the DOE Technical Targets for Onboard Hydrogen Storage Systems is a critical knowledge gap in the hydrogen storage research community. This study presents a set of fluid-phase chemical hydrogen storagemore » material property guidelines for automotive applications meeting the 2017 DOE technical targets. Viable material properties were determined using a boiler-plate automotive system design. The fluid phase chemical hydrogen storage media considered in this study were neat liquids, solutions, and non-settling homogeneous slurries. Material properties examined include kinetics, heats of reaction, fuel-cell impurities, gravimetric and volumetric hydrogen storage capacities, and regeneration efficiency. The material properties, although not exhaustive, are an essential first step in identifying viable chemical hydrogen storage material propertiesdand most important, their implications on system mass, system volume and system performance.« less

Chemical hydrogen storage material property guidelines for automotive applications

NASA Astrophysics Data System (ADS)

Semelsberger, Troy A.; Brooks, Kriston P.

2015-04-01

Chemical hydrogen storage is the sought after hydrogen storage media for automotive applications because of the expected low pressure operation (<20 atm), moderate temperature operation (<200 °C), system gravimetric capacities (>0.05 kg H2/kgsystem), and system volumetric capacities (>0.05 kg H2/Lsystem). Currently, the primary shortcomings of chemical hydrogen storage are regeneration efficiency, fuel cost and fuel phase (i.e., solid or slurry phase). Understanding the required material properties to meet the DOE Technical Targets for Onboard Hydrogen Storage Systems is a critical knowledge gap in the hydrogen storage research community. This study presents a set of fluid-phase chemical hydrogen storage material property guidelines for automotive applications meeting the 2017 DOE technical targets. Viable material properties were determined using a boiler-plate automotive system design. The fluid-phase chemical hydrogen storage media considered in this study were neat liquids, solutions, and non-settling homogeneous slurries. Material properties examined include kinetics, heats of reaction, fuel-cell impurities, gravimetric and volumetric hydrogen storage capacities, and regeneration efficiency. The material properties, although not exhaustive, are an essential first step in identifying viable chemical hydrogen storage material properties-and most important, their implications on system mass, system volume and system performance.

Summaries of FY 1979 research in the chemical sciences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1980-05-01

The purpose of this report is to help those interested in research supported by the Department of Energy's Division of Chemical Sciences, which is one of six Divisions of the Office of Basic Energy Sciences in the Office of Energy Research. Chemists, physicists, chemical engineers and others who are considering the possibility of proposing research for support by this Division wll find the booklet useful for gauging the scope of the program in basic research, and the relationship of their interests to the overall program. These smmaries are intended to provide a rapid means for becoming acquainted with the Chemicalmore » Sciences program for members of the scientific and technological public, and interested persons in the Legislative and Executive Branches of the Government, in order to indicate the areas of research supported by the Division and energy technologies which may be advanced by use of basic knowledge discovered in this program. Scientific excellence is a major criterion applied in the selection of research supported by Chemical Sciences. Another important consideration is the identifying of chemical, physical and chemical engineering subdisciplines which are advancing in ways which produce new information related to energy, needed data, or new ideas.« less

Chemical warfare agents.

PubMed

Kuca, Kamil; Pohanka, Miroslav

2010-01-01

Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

Chemically-induced mouse lung tumors: applications to ...

EPA Pesticide Factsheets

A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to discuss issues related to the use of mouse lung tumor data in human health assessments. Naphthalene, styrene, and ethylbenzene were chosen for the analysis due to the commonality of mouse lung tumors in all these three environmental chemicals. The goals of the workshop were to: identify the evidence, from multiple scientific disciplines, regarding formation of chemically-induced lung tumors in mice; discuss analysis and interpretation of the evidence; discuss how such evidence informs human health assessments; and identify commonalities, linkages, or differences between the evidence from various disciplines and across the chemicals. Evidence informing the association between occupational exposure to styrene, ethylbenzene, or naphthalene and lung cancer; comparative biology of mouse lung tumors, associated pathologic effects, issues related to tissue and species concordance; mode of action analysis and biological mechanisms including pharmacokinetics and pharmacodynamics; and evidence from cellular, genetic and molecular toxicity was discussed. In summary, although consensus was not sought, the panelists agreed that data showing mouse lung tumors with chemical exposures can be relevant for human health risk evaluation on an individual chemical basis. Key data gaps were identified that would assist in further understanding the mechanism

Chemically-induced Mouse Lung Tumors: Applications to ...

EPA Pesticide Factsheets

A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to better understand the mouse lung tumor data’s role in human health assessments. Three environmental chemicals - naphthalene, styrene, and ethylbenzene were chosen for the analysis due to the commonality of mouse lung tumors in all three chemicals. The goals of the workshop were to: identify the evidence, from multiple scientific disciplines, regarding formation of chemically-induced lung tumors in mice; discuss analysis and interpretation of the evidence; discuss how such evidence informs human health assessments; and identify commonalities, linkages, or differences between the evidence from various disciplines and across the chemicals. Evidence informing the association between occupational exposure to styrene, ethylbenzene, or naphthalene and lung cancer; comparative biology of mouse lung tumors, associated pathologic effects, issues related to tissue and species concordance; mode of action analysis and biological mechanisms including pharmacokinetics and pharmacodynamics; and evidence from cellular, genetic and molecular toxicity was discussed. In summary, although consensus was not sought, the panelists agreed that available mouse lung tumor data should be considered for human health risk evaluation on an individual chemical basis. Key data gaps were identified that would assist in further understanding the mechanism and relevan

Mapping student thinking in chemical synthesis

NASA Astrophysics Data System (ADS)

Weinrich, Melissa

In order to support the development of learning progressions about central ideas and practices in different disciplines, we need detailed analyses of the implicit assumptions and reasoning strategies that guide students' thinking at different educational levels. In the particular case of chemistry, understanding how new chemical substances are produced (chemical synthesis) is of critical importance. Thus, we have used a qualitative research approach based on individual interviews with first semester general chemistry students (n = 16), second semester organic chemistry students (n = 15), advanced undergraduates (n = 9), first year graduate students (n = 15), and PhD candidates (n = 16) to better characterize diverse students' underlying cognitive elements (conceptual modes and modes of reasoning) when thinking about chemical synthesis. Our results reveal a great variability in the cognitive resources and strategies used by students with different levels of training in the discipline to make decisions, particularly at intermediate levels of expertise. The specific nature of the task had a strong influence on the conceptual sophistication and mode of reasoning that students exhibited. Nevertheless, our data analysis has allowed us to identify common modes of reasoning and assumptions that seem to guide students' thinking at different educational levels. Our results should facilitate the development of learning progressions that help improve chemistry instruction, curriculum, and assessment.

Sex-Specific Effects of Combined Exposure to Chemical and Non-chemical Stressors on Neuroendocrine Development: a Review of Recent Findings and Putative Mechanisms.

PubMed

Cowell, Whitney J; Wright, Rosalind J

2017-12-01

Environmental toxicants and psychosocial stressors share many biological substrates and influence overlapping physiological pathways. Increasing evidence indicates stress-induced changes to the maternal milieu may prime rapidly developing physiological systems for disruption by concurrent or subsequent exposure to environmental chemicals. In this review, we highlight putative mechanisms underlying sex-specific susceptibility of the developing neuroendocrine system to the joint effects of stress or stress correlates and environmental toxicants (bisphenol A, alcohol, phthalates, lead, chlorpyrifos, and traffic-related air pollution). We provide evidence indicating that concurrent or tandem exposure to chemical and non-chemical stressors during windows of rapid development is associated with sex-specific synergistic, potentiated and reversed effects on several neuroendocrine endpoints related to hypothalamic-pituitary-adrenal axis function, sex steroid levels, neurotransmitter circuits, and innate immune function. We additionally identify gaps, such as the role that the endocrine-active placenta plays, in our understanding of these complex interactions. Finally, we discuss future research needs, including the investigation of non-hormonal biomarkers of stress. We demonstrate multiple physiologic systems are impacted by joint exposure to chemical and non-chemical stressors differentially among males and females. Collectively, the results highlight the importance of evaluating sex-specific endpoints when investigating the neuroendocrine system and underscore the need to examine exposure to chemical toxicants within the context of the social environment.

Chemical reaction fouling model for single-phase heat transfer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panchal, C.B.; Watkinson, A.P.

1993-08-01

A fouling model was developed on the premise that the chemical reaction for generation of precursor can take place in the bulk fluid, in the thermalboundary layer, or at the fluid/wall interface, depending upon the interactive effects of flu id dynamics, heat and mass transfer, and the controlling chemical reaction. The analysis was used to examine the experimental data for fouling deposition of polyperoxides produced by autoxidation of indene in kerosene. The effects of fluid and wall temperatures for two flow geometries were analyzed. The results showed that the relative effects of physical parameters on the fouling rate would differmore » for the three fouling mechanisms; therefore, it is important to identify the controlling mechanism in applying the closed-flow-loop data to industrial conditions.« less

A computational method for the identification of new candidate carcinogenic and non-carcinogenic chemicals.

PubMed

Chen, Lei; Chu, Chen; Lu, Jing; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

2015-09-01

Cancer is one of the leading causes of human death. Based on current knowledge, one of the causes of cancer is exposure to toxic chemical compounds, including radioactive compounds, dioxin, and arsenic. The identification of new carcinogenic chemicals may warn us of potential danger and help to identify new ways to prevent cancer. In this study, a computational method was proposed to identify potential carcinogenic chemicals, as well as non-carcinogenic chemicals. According to the current validated carcinogenic and non-carcinogenic chemicals from the CPDB (Carcinogenic Potency Database), the candidate chemicals were searched in a weighted chemical network constructed according to chemical-chemical interactions. Then, the obtained candidate chemicals were further selected by a randomization test and information on chemical interactions and structures. The analyses identified several candidate carcinogenic chemicals, while those candidates identified as non-carcinogenic were supported by a literature search. In addition, several candidate carcinogenic/non-carcinogenic chemicals exhibit structural dissimilarity with validated carcinogenic/non-carcinogenic chemicals.

The Chemical Evolution of Phosphorus

NASA Astrophysics Data System (ADS)

Jacobson, Heather R.; Thanathibodee, Thanawuth; Frebel, Anna; Roederer, Ian U.; Cescutti, Gabriele; Matteucci, Francesca

2014-12-01

Phosphorus is one of the few remaining light elements for which little is known about its nucleosynthetic origin and chemical evolution, given the lack of optical absorption lines in the spectra of long-lived FGK-type stars. We have identified a P I doublet in the near-ultraviolet (2135/2136 Å) that is measurable in stars of low metallicity. Using archival Hubble Space Telescope-Space Telescope Imaging Spectrograph spectra, we have measured P abundances in 13 stars spanning -3.3 <= [Fe/H] <= -0.2, and obtained an upper limit for a star with [Fe/H] ~ -3.8. Combined with the only other sample of P abundances in solar-type stars in the literature, which spans a range of -1 <= [Fe/H] <= +0.2, we compare the stellar data to chemical evolution models. Our results support previous indications that massive-star P yields may need to be increased by a factor of a few to match stellar data at all metallicities. Our results also show that hypernovae were important contributors to the P production in the early universe. As P is one of the key building blocks of life, we also discuss the chemical evolution of the important elements to life, C-N-O-P-S, together. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. This work is supported through program AR-13246. Other portions of this work are based on data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile, and the McDonald Observatory of the University of Texas at Austin.

Joint Chemical Agent Detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.; Owen, Jeffery L.

2002-06-01

The Joint Chemical Agent Detector (JCAD) will provide state of the art chemical warfare agent detection capability to ground vehicle operators. Intelligence sources estimate that over twenty counties have active chemical weapons programs. The spread of chemical weapons to third world nations, coupled with the potential for US involvement in these areas in an operational or support capacity, increases the probability that the Joint Services may encounter chemical agents and toxic industrial materials anywhere in the world. Currently, fielded chemical agent detectors are bulky, labor intensive, and subject to false readings. No legacy detector is sensitive enough to provide detection and warning of the low dose hazards associated with miosis contamination. The JCAD will provide a small, lightweight chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection components across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD will detect, identify, quantify, and warn of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector will provide local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD will also be capable of being upgraded to protect against future chemical agent threats. The JCAD will provide the vehicle operators with the warning necessary to survive and fight in a chemical warfare agent threat environment.

A chemical genetic strategy identify the PHOSTIN, a synthetic molecule that triggers phosphate starvation responses in Arabidopsis thaliana.

PubMed

Bonnot, Clémence; Pinson, Benoît; Clément, Mathilde; Bernillon, Stéphane; Chiarenza, Serge; Kanno, Satomi; Kobayashi, Natsuko; Delannoy, Etienne; Nakanishi, Tomoko M; Nussaume, Laurent; Desnos, Thierry

2016-01-01

Plants display numerous strategies to cope with phosphate (Pi)-deficiency. Despite multiple genetic studies, the molecular mechanisms of low-Pi-signalling remain unknown. To validate the interest of chemical genetics to investigate this pathway we discovered and analysed the effects of PHOSTIN (PSN), a drug mimicking Pi-starvation in Arabidopsis. We assessed the effects of PSN and structural analogues on the induction of Pi-deficiency responses in mutants and wild-type and followed their accumulation in plants organs by high pressure liquid chromotography (HPLC) or mass-spectrophotometry. We show that PSN is cleaved in the growth medium, releasing its active motif (PSN11), which accumulates in plants roots. Despite the overaccumulation of Pi in the roots of treated plants, PSN11 elicits both local and systemic Pi-starvation effects. Nevertheless, albeit that the transcriptional activation of low-Pi genes by PSN11 is lost in the phr1;phl1 double mutant, neither PHO1 nor PHO2 are required for PSN11 effects. The range of local and systemic responses to Pi-starvation elicited, and their dependence on the PHR1/PHL1 function suggests that PSN11 affects an important and early step of Pi-starvation signalling. Its independence from PHO1 and PHO2 suggest the existence of unknown pathway(s), showing the usefulness of PSN and chemical genetics to bring new elements to this field. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

High-resolution linkage analyses to identify genes that influence Varroa sensitive hygiene behavior in honey bees.

PubMed

Tsuruda, Jennifer M; Harris, Jeffrey W; Bourgeois, Lanie; Danka, Robert G; Hunt, Greg J

2012-01-01

Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera) and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Varroa sensitive hygiene behavior is one of two behaviors identified that are most important for controlling the growth of Varroa populations in bee hives. To identify genes influencing this trait, a study was conducted to map quantitative trait loci (QTL). Individual workers of a backcross family were observed and evaluated for their VSH behavior in a mite-infested observation hive. Bees that uncapped or removed pupae were identified. The genotypes for 1,340 informative single nucleotide polymorphisms were used to construct a high-resolution genetic map and interval mapping was used to analyze the association of the genotypes with the performance of Varroa sensitive hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21) and a suggestive QTL on chromosome 1 (LOD = 1.95). The QTL confidence interval on chromosome 9 contains the gene 'no receptor potential A' and a dopamine receptor. 'No receptor potential A' is involved in vision and olfaction in Drosophila, and dopamine signaling has been previously shown to be required for aversive olfactory learning in honey bees, which is probably necessary for identifying mites within brood cells. Further studies on these candidate genes may allow for breeding bees with this trait using marker-assisted selection.

Chemical-induced Vitiligo

PubMed Central

Harris, John E.

2016-01-01

Synopsis Chemical-induced depigmentation of the skin has been recognized for over 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. The importance of recognizing this phenomenon was highlighted during an outbreak of vitiligo in Japan during the summer of 2013, when over 16,000 users of a new skin lightening cosmetic cream developed skin depigmentation at the site of contact with the cream and many in remote areas as well. Depigmenting chemicals appear to be analogs of the amino acid tyrosine that disrupt melanogenesis and result in autoimmunity and melanocyte destruction. Because chemical-induced depigmentation is clinically and histologically indistinguishable from non-chemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as “chemical-induced vitiligo”, rather than less accurate terms that have been previously used. PMID:28317525

Finding Chemical Structures Corresponding to a Set of Coordinates in Chemical Descriptor Space.

PubMed

Miyao, Tomoyuki; Funatsu, Kimito

2017-08-01

When chemical structures are searched based on descriptor values, or descriptors are interpreted based on values, it is important that corresponding chemical structures actually exist. In order to consider the existence of chemical structures located in a specific region in the chemical space, we propose to search them inside training data domains (TDDs), which are dense areas of a training dataset in the chemical space. We investigated TDDs' features using diverse and local datasets, assuming that GDB11 is the chemical universe. These two analyses showed that considering TDDs gives higher chance of finding chemical structures than a random search-based method, and that novel chemical structures actually exist inside TDDs. In addition to those findings, we tested the hypothesis that chemical structures were distributed on the limited areas of chemical space. This hypothesis was confirmed by the fact that distances among chemical structures in several descriptor spaces were much shorter than those among randomly generated coordinates in the training data range. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative DNA Methylation Analysis Identifies a Single CpG Dinucleotide Important for ZAP-70 Expression and Predictive of Prognosis in Chronic Lymphocytic Leukemia

PubMed Central

Claus, Rainer; Lucas, David M.; Stilgenbauer, Stephan; Ruppert, Amy S.; Yu, Lianbo; Zucknick, Manuela; Mertens, Daniel; Bühler, Andreas; Oakes, Christopher C.; Larson, Richard A.; Kay, Neil E.; Jelinek, Diane F.; Kipps, Thomas J.; Rassenti, Laura Z.; Gribben, John G.; Döhner, Hartmut; Heerema, Nyla A.; Marcucci, Guido; Plass, Christoph; Byrd, John C.

2012-01-01

Purpose Increased ZAP-70 expression predicts poor prognosis in chronic lymphocytic leukemia (CLL). Current methods for accurately measuring ZAP-70 expression are problematic, preventing widespread application of these tests in clinical decision making. We therefore used comprehensive DNA methylation profiling of the ZAP-70 regulatory region to identify sites important for transcriptional control. Patients and Methods High-resolution quantitative DNA methylation analysis of the entire ZAP-70 gene regulatory regions was conducted on 247 samples from patients with CLL from four independent clinical studies. Results Through this comprehensive analysis, we identified a small area in the 5′ regulatory region of ZAP-70 that showed large variability in methylation in CLL samples but was universally methylated in normal B cells. High correlation with mRNA and protein expression, as well as activity in promoter reporter assays, revealed that within this differentially methylated region, a single CpG dinucleotide and neighboring nucleotides are particularly important in ZAP-70 transcriptional regulation. Furthermore, by using clustering approaches, we identified a prognostic role for this site in four independent data sets of patients with CLL using time to treatment, progression-free survival, and overall survival as clinical end points. Conclusion Comprehensive quantitative DNA methylation analysis of the ZAP-70 gene in CLL identified important regions responsible for transcriptional regulation. In addition, loss of methylation at a specific single CpG dinucleotide in the ZAP-70 5′ regulatory sequence is a highly predictive and reproducible biomarker of poor prognosis in this disease. This work demonstrates the feasibility of using quantitative specific ZAP-70 methylation analysis as a relevant clinically applicable prognostic test in CLL. PMID:22564988

A new process sensitivity index to identify important system processes under process model and parametric uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Heng; Ye, Ming; Walker, Anthony P.

Hydrological models are always composed of multiple components that represent processes key to intended model applications. When a process can be simulated by multiple conceptual-mathematical models (process models), model uncertainty in representing the process arises. While global sensitivity analysis methods have been widely used for identifying important processes in hydrologic modeling, the existing methods consider only parametric uncertainty but ignore the model uncertainty for process representation. To address this problem, this study develops a new method to probe multimodel process sensitivity by integrating the model averaging methods into the framework of variance-based global sensitivity analysis, given that the model averagingmore » methods quantify both parametric and model uncertainty. A new process sensitivity index is derived as a metric of relative process importance, and the index includes variance in model outputs caused by uncertainty in both process models and model parameters. For demonstration, the new index is used to evaluate the processes of recharge and geology in a synthetic study of groundwater reactive transport modeling. The recharge process is simulated by two models that converting precipitation to recharge, and the geology process is also simulated by two models of different parameterizations of hydraulic conductivity; each process model has its own random parameters. The new process sensitivity index is mathematically general, and can be applied to a wide range of problems in hydrology and beyond.« less

Antidromic-rectifying gap junctions amplify chemical transmission at functionally mixed electrical-chemical synapses

PubMed Central

Liu, Ping; Chen, Bojun; Mailler, Roger; Wang, Zhao-Wen

2017-01-01

Neurons communicate through chemical synapses and electrical synapses (gap junctions). Although these two types of synapses often coexist between neurons, little is known about whether they interact, and whether any interactions between them are important to controlling synaptic strength and circuit functions. By studying chemical and electrical synapses between premotor interneurons (AVA) and downstream motor neurons (A-MNs) in the Caenorhabditis elegans escape circuit, we found that disrupting either the chemical or electrical synapses causes defective escape response. Gap junctions between AVA and A-MNs only allow antidromic current, but, curiously, disrupting them inhibits chemical transmission. In contrast, disrupting chemical synapses has no effect on the electrical coupling. These results demonstrate that gap junctions may serve as an amplifier of chemical transmission between neurons with both electrical and chemical synapses. The use of antidromic-rectifying gap junctions to amplify chemical transmission is potentially a conserved mechanism in circuit functions. PMID:28317880

Chemical Conversions of Biomass-Derived Platform Chemicals over Copper-Silica Nanocomposite Catalysts.

PubMed

Upare, Pravin P; Hwang, Young Kyu; Lee, Jong-Min; Hwang, Dong Won; Chang, Jong-San

2015-07-20

Biomass and biomass-derived carbohydrates have a high extent of functionality, unlike petroleum, which has limited functionality. In biorefinery applications, the development of methods to control the extent of functionality in final products intended for use as fuels and chemicals is a challenge. In the chemical industry, heterogeneous catalysis is an important tool for the defunctionalization of functionalized feedstocks and biomass-derived platform chemicals to produce value-added chemicals. Herein, we review the recent progress in this field, mainly of vapor phase chemical conversion of biomass-derived C4 -C6 carboxylic acids and esters using copper-silica nanocomposite catalysts. We also demonstrate that these nanocomposite catalysts very efficiently convert biomass-derived platform chemicals into cyclic compounds, such as lactones and hydrofurans, with high selectivities and yields. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Why Physical Activity Is Important (for Girls)

MedlinePlus

... Home Fitness Why physical activity is important Why physical activity is important You may wonder if being physically ... you are to be around. That's partly because physical activity gets your brain to make "feel-good" chemicals ...

Olefins and chemical regulation in Europe: REACH.

PubMed

Penman, Mike; Banton, Marcy; Erler, Steffen; Moore, Nigel; Semmler, Klaus

2015-11-05

REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) is the European Union's chemical regulation for the management of risk to human health and the environment (European Chemicals Agency, 2006). This regulation entered into force in June 2007 and required manufacturers and importers to register substances produced in annual quantities of 1000 tonnes or more by December 2010, with further deadlines for lower tonnages in 2013 and 2018. Depending on the type of registration, required information included the substance's identification, the hazards of the substance, the potential exposure arising from the manufacture or import, the identified uses of the substance, and the operational conditions and risk management measures applied or recommended to downstream users. Among the content developed to support this information were Derived No-Effect Levels or Derived Minimal Effect Levels (DNELs/DMELs) for human health hazard assessment, Predicted No Effect Concentrations (PNECs) for environmental hazard assessment, and exposure scenarios for exposure and risk assessment. Once registered, substances may undergo evaluation by the European Chemicals Agency (ECHA) or Member State authorities and be subject to requests for additional information or testing as well as additional risk reduction measures. To manage the REACH registration and related activities for the European olefins and aromatics industry, the Lower Olefins and Aromatics REACH Consortium was formed in 2008 with administrative and technical support provided by Penman Consulting. A total of 135 substances are managed by this group including 26 individual chemical registrations (e.g. benzene, 1,3-butadiene) and 13 categories consisting of 5-26 substances. This presentation will describe the content of selected registrations prepared for 2010 in addition to the significant post-2010 activities. Beyond REACH, content of the registrations may also be relevant to other European activities, for

Identifying the Most Important 21st Century Workforce Competencies: An Analysis of the Occupational Information Network (O*NET). Research Report. ETS RR-13-21

ERIC Educational Resources Information Center

Burrus, Jeremy; Jackson, Teresa; Xi, Nuo; Steinberg, Jonathan

2013-01-01

To identify the most important competencies for college graduates to succeed in the 21st century workforce, we conducted an analysis of the Occupational Information Network (O*NET) database. O*NET is a large job analysis operated and maintained by the U.S. Department of Labor. We specifically analyzed ratings of the importance of abilities (52…

The use of chemical and molecular microbial indicators for faecal source identification.

PubMed

Gilpin, B; James, T; Nourozi, F; Saunders, D; Scholes, P; Savill, M

2003-01-01

Identifying the source of faecal pollution is important to enable appropriate management of faecal pollution of water. We are developing and evaluating a combination of these microbial and chemical indicators better able to identify the source of faecal pollution. These assays make use of a combination of direct PCR, culturing, and colony hybridisation to identify source specific species of Bifidobacterium, Rhodococcus and Bacteroides. In conjunction with assays for (a) fluorescent whitening agents and (b) faecal sterols and stanols, these indicators were able to identify human derived faecal pollution in river water containing inputs from septic tanks, municipal oxidation ponds, farmed animals and feral animals. Differentiating amongst the animal sources was more difficult and will require development of molecular assays for organisms specific to each animal group.

Chemical potential shift in organic field-effect transistors identified by soft X-ray operando nano-spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagamura, Naoka, E-mail: NAGAMURA.Naoka@nims.go.jp; Kitada, Yuta; Honma, Itaru

2015-06-22

A chemical potential shift in an organic field effect transistor (OFET) during operation has been revealed by soft X-ray operando nano-spectroscopy analysis performed using a three-dimensional nanoscale electron-spectroscopy chemical analysis system. OFETs were fabricated using ultrathin (3 ML or 12 nm) single-crystalline C10-DNBDT-NW films on SiO{sub 2} (200 nm)/Si substrates with a backgate electrode and top source/drain Au electrodes, and C 1s line profiles under biasing at the backgate and drain electrodes were measured. When applying −30 V to the backgate, there is C 1s core level shift of 0.1 eV; this shift can be attributed to a chemical potential shift correspondingmore » to band bending by the field effect, resulting in p-type doping.« less

Chemical communication threatened by endocrine-disrupting chemicals.

PubMed Central

Fox, Jennifer E

2004-01-01

Communication on a cellular level--defined as chemical signaling, sensing, and response--is an essential and universal component of all living organisms and the framework that unites all ecosystems. Evolutionarily conserved signaling "webs," existing both within an organism and between organisms, rely on efficient and accurate interpretation of chemical signals by receptors. Therefore, endocrine-disrupting chemicals (EDCs), which have been shown to disrupt hormone signaling in laboratory animals and exposed wildlife, may have broader implications for disrupting signaling webs that have yet to be identified as possible targets. In this article, I explore common evolutionary themes of chemical signaling (e.g., estrogen signaling in vertebrates and phytoestrogen signaling from plants to symbiotic soil bacteria) and show that such signaling systems are targets of disruption by EDCs. Recent evolutionary phylogenetic data have shown that the estrogen receptor (ER) is the ancestral receptor from which all other steroid receptors have evolved. In addition to binding endogenous estrogens, ERs also bind phytoestrogens, an ability shared in common with nodulation D protein (NodD) receptors found in Rhizobium soil bacteria. Recent data have shown that many of the same synthetic and natural environmental chemicals that disrupt endocrine signaling in vertebrates also disrupt phytoestrogen-NodD receptor signaling in soil bacteria, which is necessary for nitrogen-fixing symbiosis. Bacteria-plant symbiosis is an unexpected target of EDCs, and other unexpected nontarget species may also be vulnerable to EDCs found in the environment. PMID:15121505

Environmental/chemical thesaurus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shriner, C.R.; Dailey, N.S.; Jordan, A.C.

The Environmental/Chemical Thesaurus approaches scientific language control problems from a multidisciplinary view. The Environmental/Biomedical Terminology Index (EBTI) was used as a base for the present thesaurus. The Environmental/Chemical Thesaurus, funded by the Environmental Protection Agency, used as its source of new terms those major terms found in 13 Environmental Protection Agency data bases. The scope of this thesaurus includes not only environmental and biomedical sciences, but also the physical sciences with emphasis placed on chemistry. Specific chemical compounds are not included; only classes of chemicals are given. To adhere to this level of classification, drugs and pesticides are identified bymore » class rather than by specific chemical name. An attempt was also made to expand the areas of sociology and economics. Terminology dealing with law, demography, and geography was expanded. Proper names of languages and races were excluded. Geographic terms were expanded to include proper names for oceans, continents, major lakes, rivers, and islands. Political divisions were added to allow for proper names of countries and states. With such a broad scope, terminology for specific sciences does not provide for indexing to the lowest levels in plant, animal, or chemical classifications.« less

An efficient approach to identify different chemical markers between fibrous root and rhizome of Anemarrhena asphodeloides by ultra high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry with multivariate statistical analysis.

PubMed

Wang, Fang-Xu; Yuan, Jian-Chao; Kang, Li-Ping; Pang, Xu; Yan, Ren-Yi; Zhao, Yang; Zhang, Jie; Sun, Xin-Guang; Ma, Bai-Ping

2016-09-10

An ultra high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry approach coupled with multivariate statistical analysis was established and applied to rapidly distinguish the chemical differences between fibrous root and rhizome of Anemarrhena asphodeloides. The datasets of tR-m/z pairs, ion intensity and sample code were processed by principal component analysis and orthogonal partial least squares discriminant analysis. Chemical markers could be identified based on their exact mass data, fragmentation characteristics, and retention times. And the new compounds among chemical markers could be isolated rapidly guided by the ultra high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and their definitive structures would be further elucidated by NMR spectra. Using this approach, twenty-four markers were identified on line including nine new saponins and five new steroidal saponins of them were obtained in pure form. The study validated this proposed approach as a suitable method for identification of the chemical differences between various medicinal parts in order to expand medicinal parts and increase the utilization rate of resources. Copyright © 2016 Elsevier B.V. All rights reserved.

Raman chemical imaging of explosive-contaminated fingerprints.

PubMed

Emmons, E D; Tripathi, A; Guicheteau, J A; Christesen, S D; Fountain, A W

2009-11-01

Raman chemical imaging (RCI) has been used to detect and identify explosives in contaminated fingerprints. Bright-field imaging is used to identify regions of interest within a fingerprint, which can then be examined to determine their chemical composition using RCI and fluorescence imaging. Results are presented where explosives in contaminated fingerprints are identified and their spatial distributions are obtained. Identification of explosives is obtained using Pearson's cosine cross-correlation technique using the characteristic region (500-1850 cm(-1)) of the spectrum. This study shows the ability to identify explosives nondestructively so that the fingerprint remains intact for further biometric analysis. Prospects for forensic examination of contaminated fingerprints are discussed.

ToxiFly: Can Fruit Flies be Used to Identify Toxicity Pathways for Airborne Chemicals?

EPA Science Inventory

Current high-throughput and alternative screening assays for chemical toxicity are unable to test volatile organic compounds (VOCs), thus limiting their scope. Further, the data generated by these assays require mechanistic information to link effects at molecular targets to adve...

Isolated severe tricuspid regurgitation: the importance of identifying underlying mechanism.

PubMed

Poh, Kian Keong; Solis, Jorge; Hung, Judy

2008-07-21

An 88-year-old woman presented with right heart failure, history of diarrhoea, abdominal pain, weight lost, dyspnoea over several weeks and a new pan-systolic murmur. Echocardiography showed retracted tricuspid leaflets with incomplete coaptation resulting in severe regurgitation. Subcostal view showed an adjacent hepatic cyst leading to biopsy, which revealed neoplastic neuroendocrine cells. Her 24-hour urinary 5-hydroxyindoleacetic acid level was elevated. The unifying diagnosis was carcinoid syndrome for which she was treated. Echocardiography is an important tool for diagnosis, management and prognosis of carcinoid heart disease.

Perceived cultural importance and actual self-importance of values in cultural identification.

PubMed

Wan, Ching; Chiu, Chi-yue; Tam, Kim-pong; Lee, Sau-lai; Lau, Ivy Yee-man; Peng, Siqing

2007-02-01

Cross-cultural psychologists assume that core cultural values define to a large extent what a culture is. Typically, core values are identified through an actual self-importance approach, in which core values are those that members of the culture as a group strongly endorse. In this article, the authors propose a perceived cultural importance approach to identifying core values, in which core values are values that members of the culture as a group generally believe to be important in the culture. In 5 studies, the authors examine the utility of the perceived cultural importance approach. Results consistently showed that, compared with values of high actual self-importance, values of high perceived cultural importance play a more important role in cultural identification. These findings have important implications for conceptualizing and measuring cultures. ((c) 2007 APA, all rights reserved).

Multiple plagioclase crystal populations identified by crystal size distribution and in situ chemical data: Implications for timescales of magma chamber processes associated with the 1915 eruption of Lassen Peak, CA

USGS Publications Warehouse

Salisbury, M.J.; Bohrson, W.A.; Clynne, M.A.; Ramos, F.C.; Hoskin, P.

2008-01-01

Products of the 1915 Lassen Peak eruption reveal evidence for a magma recharge-magma mixing event that may have catalyzed the eruption and from which four compositional members were identified: light dacite, black dacite, andesitic inclusion, and dark andesite. Crystal size distribution, textural, and in situ chemical (major and trace element and Sr isotope) data for plagioclase from these compositional products define three crystal populations that have distinct origins: phenocrysts (long axis > 0??5 mm) that typically have core An contents between 34 and 36 mol %, microphenocrysts (long axis between 0??1 and 0??5 mm) that have core An contents of 66-69, and microlites (long axis < 0??1 mm) with variable An core contents from 64 to 52. Phenocrysts are interpreted to form in an isolated dacitic magma chamber that experienced slow cooling. Based on textural, compositional, and isotopic data for the magma represented by the dacitic component, magma recharge was not an important process until just prior to the 1915 eruption. Average residence times for phenocrysts are in the range of centuries to millennia. Microphenocrysts formed in a hybrid layer that resulted from mixing between end-member reservoir dacite and recharge magma of basaltic andesite composition. High thermal contrast between the two end-member magmas led to relatively high degrees of undercooling, which resulted in faster crystal growth rates and acicular and swallowtail crystal habits. Some plagioclase phenocrysts from the dacitic chamber were incorporated into the hybrid layer and underwent dissolution-precipitation, seen in both crystal textures and rim compositions. Average microphenocryst residence times are of the order of months. Microlites may have formed in response to decompression and/ or syn-eruptive degassing as magma ascended from the chamber through the volcanic conduit. Chemical distinctions in plagioclase microlite An contents reveal that melt of the dark andesite was more mafic than

Environmentally relevant chemical mixtures of concern in waters of United States tributaries to the Great Lakes

USGS Publications Warehouse

Elliott, Sarah M.; Brigham, Mark E.; Kiesling, Richard L.; Schoenfuss, Heiko L.; Jorgenson, Zachary G.

2018-01-01

The North American Great Lakes are a vital natural resource that provide fish and wildlife habitat, as well as drinking water and waste assimilation services for millions of people. Tributaries to the Great Lakes receive chemical inputs from various point and nonpoint sources, and thus are expected to have complex mixtures of chemicals. However, our understanding of the co‐occurrence of specific chemicals in complex mixtures is limited. To better understand the occurrence of specific chemical mixtures in the US Great Lakes Basin, surface water from 24 US tributaries to the Laurentian Great Lakes was collected and analyzed for diverse suites of organic chemicals, primarily focused on chemicals of concern (e.g., pharmaceuticals, personal care products, fragrances). A total of 181 samples and 21 chemical classes were assessed for mixture compositions. Basin wide, 1664 mixtures occurred in at least 25% of sites. The most complex mixtures identified comprised 9 chemical classes and occurred in 58% of sampled tributaries. Pharmaceuticals typically occurred in complex mixtures, reflecting pharmaceutical‐use patterns and wastewater facility outfall influences. Fewer mixtures were identified at lake or lake‐influenced sites than at riverine sites. As mixture complexity increased, the probability of a specific mixture occurring more often than by chance greatly increased, highlighting the importance of understanding source contributions to the environment. This empirically based analysis of mixture composition and occurrence may be used to focus future sampling efforts or mixture toxicity assessments. 

Attempts to identify a control system for chemical reactivity in the living state using virtual energy.

PubMed

Reid, B L; Bourke, C

2001-07-01

This thesis explores the activation of chemicals in metabolic systems from the viewpoint that this activation is under the control of elements of the space-sea in which the chemicals are immersed. Themselves inert, the chemicals are theorised to exploit a force or action issuing from space (fluctuation) and characterized by the homogeneity (termed symmetry) of this medium. The fluctuation is heterogenized upon collision with matter from the intervention of well recognized fields of gravity and electromagnetism at the instant of its issue to form the near field of radiation. Fractions of original space waves and of their intrinsic spin are produced resulting in the activation of the orbitals (valency) in the chemical itself. The thesis continues: the disturbed fluctuation must return to space, obliging in turn, a prior return to the homogeneous state requiring special restorative wave rearrangements known as resonance. The success of the restorative resonance is signalled by a singularity of the fluctuation now propelled to infinity (space), and the contingent chemical reactions thereby terminated. Compromise to this return can occur from many causes and, in its presence, activation of the orbitals continues. They now effectively constitute autonomous reactions alienated from the system as a whole. The thesis is supported from evidence from diverse fields such as space theory, history of quantum field theory in attempts to derive its meaning, dielectrics and the near field of electromagnetic radiation, electron-space interactions at the Fermi surface during phase transitions and evolution of equilibrium conditions in resonance phenomena. The utility of the hypothesis rests on recognition of the resonance condition at various points in the system sufficiently macroscopic as to be available clinically as an abrupt interface between physiology and pathology. Copyright 2001 Harcourt Publishers Ltd.

Chemical-Gene Interactions from ToxCast Bioactivity Data ...

EPA Pesticide Factsheets

Characterizing the effects of chemicals in biological systems is often summarized by chemical-gene interactions, which have sparse coverage in the literature. The ToxCast chemical screening program has produced bioactivity data for nearly 2000 chemicals and over 450 gene targets. To evaluate the information gained from the ToxCast project, a ToxCast bioactivity network was created comprising ToxCast chemical-gene interactions based on assay data and compared to a chemical-gene association network from literature. The literature network was compiled from PubMed articles, excluding ToxCast publications, mapped to genes and chemicals. Genes were identified by curated associations available from NCBI while chemicals were identified by PubChem submissions. The frequencies of chemical-gene associations from the literature network were log-scaled and then compared to the ToxCast bioactivity network. In total, 140 times more chemical-gene associations were present in the ToxCast network in comparison to the literature-derived network highlighting the vast increase in chemical-gene interactions putatively elucidated by the ToxCast research program. There were 165 associations found in the literature network that were reproduced by ToxCast bioactivity data, and 336 associations in the literature network were not reproduced by the ToxCast bioactivity network. The literature network relies on the assumption that chemical-gene associations represent a true chemical-gene inte

Characteristics, chemical compositions and biological activities of propolis from Al-Bahah, Saudi Arabia

NASA Astrophysics Data System (ADS)

Elnakady, Yasser A.; Rushdi, Ahmed I.; Franke, Raimo; Abutaha, Nael; Ebaid, Hossam; Baabbad, Mohannad; Omar, Mohamed O. M.; Al Ghamdi, Ahmad A.

2017-02-01

Propolis has been used to treat several diseases since ancient times, and is an important source of bioactive natural compounds and drug derivatives. These properties have kept the interest of investigators around the world, leading to the investigation of the chemical and biological properties and application of propolis. In this report, the chemical constituents that are responsible for the anticancer activities of propolis were analyzed. The propolis was sourced from Al-Baha in the southern part of the Kingdom of Saudi Arabia. Standard protocols for chemical fractionation and bioactivity-guided chemical analysis were used to identify the bio-active ethyl acetate fraction. The extraction was performed in methanol and then analyzed by gas chromatography-mass spectrometry (GC-MS). The major compounds are triterpenoids, with a relative concentration of 74.0%; steroids, with a relative concentration of 9.8%; and diterpenoids, with a relative concentration of 7.9%. The biological activity was characterized using different approaches and cell-based assays. Propolis was found to inhibit the proliferation of cancer cells in a concentration-dependent manner through apoptosis. Immunofluorescence staining with anti-α-tubulin antibodies and cell cycle analysis indicated that tubulin and/or microtubules are the cellular targets of the L-acetate fraction. This study demonstrates the importance of Saudi propolis as anti-cancer drug candidates.

Desorption kinetics of organic chemicals from albumin.

PubMed

Krause, Sophia; Ulrich, Nadin; Goss, Kai-Uwe

2018-03-01

When present in blood, most chemicals tend to bind to the plasma protein albumin. For distribution into surrounding tissues, desorption from albumin is necessary, because only the unbound form of a chemical is assumed to be able to cross cell membranes. For metabolism of chemicals, the liver is a particularly important organ. One potentially limiting step for hepatic uptake of the chemicals is desorption from albumin, because blood passes the human liver within seconds. Desorption kinetics from albumin can thus be an important parameter for our pharmacokinetic and toxicokinetic understanding of chemicals. This work presents a dataset of measured desorption rate constants and reveals a possibility for their prediction. Additionally, the obtained extraction profiles directly indicate physiological relevance of desorption kinetics, because desorption of the test chemicals is still incomplete after time frames comparable to the residence time of blood in the liver.

Selective chemical binding enhances cesium tolerance in plants through inhibition of cesium uptake

PubMed Central

Adams, Eri; Chaban, Vitaly; Khandelia, Himanshu; Shin, Ryoung

2015-01-01

High concentrations of cesium (Cs+) inhibit plant growth but the detailed mechanisms of Cs+ uptake, transport and response in plants are not well known. In order to identify small molecules with a capacity to enhance plant tolerance to Cs+, chemical library screening was performed using Arabidopsis. Of 10,000 chemicals tested, five compounds were confirmed as Cs+ tolerance enhancers. Further investigation and quantum mechanical modelling revealed that one of these compounds reduced Cs+ concentrations in plants and that the imidazole moiety of this compound bound specifically to Cs+. Analysis of the analogous compounds indicated that the structure of the identified compound is important for the effect to be conferred. Taken together, Cs+ tolerance enhancer isolated here renders plants tolerant to Cs+ by inhibiting Cs+ entry into roots via specific binding to the ion thus, for instance, providing a basis for phytostabilisation of radiocesium-contaminated farmland. PMID:25740624

Selective chemical binding enhances cesium tolerance in plants through inhibition of cesium uptake.

PubMed

Adams, Eri; Chaban, Vitaly; Khandelia, Himanshu; Shin, Ryoung

2015-03-05

High concentrations of cesium (Cs(+)) inhibit plant growth but the detailed mechanisms of Cs(+) uptake, transport and response in plants are not well known. In order to identify small molecules with a capacity to enhance plant tolerance to Cs(+), chemical library screening was performed using Arabidopsis. Of 10,000 chemicals tested, five compounds were confirmed as Cs(+) tolerance enhancers. Further investigation and quantum mechanical modelling revealed that one of these compounds reduced Cs(+) concentrations in plants and that the imidazole moiety of this compound bound specifically to Cs(+). Analysis of the analogous compounds indicated that the structure of the identified compound is important for the effect to be conferred. Taken together, Cs(+) tolerance enhancer isolated here renders plants tolerant to Cs(+) by inhibiting Cs(+) entry into roots via specific binding to the ion thus, for instance, providing a basis for phytostabilisation of radiocesium-contaminated farmland.

Neural processing, perception, and behavioral responses to natural chemical stimuli by fish and crustaceans.

PubMed

Derby, Charles D; Sorensen, Peter W

2008-07-01

This manuscript reviews the chemical ecology of two of the major aquatic animal models, fish and crustaceans, in the study of chemoreception. By necessity, it is restricted in scope, with most emphasis placed on teleost fish and decapod crustaceans. First, we describe the nature of the chemical world perceived by fish and crustaceans, giving examples of the abilities of these animals to analyze complex natural odors. Fish and crustaceans share the same environments and have evolved some similar chemosensory features: the ability to detect and discern mixtures of small metabolites in highly variable backgrounds and to use this information to identify food, mates, predators, and habitat. Next, we give examples of the molecular nature of some of these natural products, including a description of methodologies used to identify them. Both fish and crustaceans use their olfactory and gustatory systems to detect amino acids, amines, and nucleotides, among many other compounds, while fish olfactory systems also detect mixtures of sex steroids and prostaglandins with high specificity and sensitivity. Third, we discuss the importance of plasticity in chemical sensing by fish and crustaceans. Finally, we conclude with a description of how natural chemical stimuli are processed by chemosensory systems. In both fishes and crustaceans, the olfactory system is especially adept at mixture discrimination, while gustation is well suited to facilitate precise localization and ingestion of food. The behaviors of both fish and crustaceans can be defined by the chemical worlds in which they live and the abilities of their nervous systems to detect and identify specific features in their domains. An understanding of these worlds and the sensory systems that provide the animals with information about them provides insight into the chemical ecology of these species.

Evidence for a Trade-Off Strategy in Stone Oak (Lithocarpus) Seeds between Physical and Chemical Defense Highlights Fiber as an Important Antifeedant

PubMed Central

Chen, Xi; Cannon, Charles H.; Conklin-Brittan, Nancy Lou

2012-01-01

Trees in the beech or oak family (Fagaceae) have a mutualistic relationship with scatter-hoarding rodents. Rodents obtain nutrients and energy by consuming seeds, while providing seed dispersal for the tree by allowing some cached seeds to germinate. Seed predation and caching behavior of rodents is primarily affected by seed size, mechanical protection, macronutrient content, and chemical antifeedants. To enhance seed dispersal, trees must optimize trade-offs in investment between macronutrients and antifeedants. Here, we examine this important chemical balance in the seeds of tropical stone oak species with two substantially different fruit morphologies. These two distinct fruit morphologies in Lithocarpus differ in the degree of mechanical protection of the seed. For ‘acorn’ fruit, a thin exocarp forms a shell around the seed while for ‘enclosed receptacle’ (ER) fruit, the seed is embedded in a woody receptacle. We compared the chemical composition of numerous macronutrient and antifeedant in seeds from several Lithocarpus species, focusing on two pairs of sympatric species with different fruit morphologies. We found that macronutrients, particularly total non-structural carbohydrate, was more concentrated in seeds of ER fruits while antifeedants, primarily fibers, were more concentrated in seeds of acorn fruits. The trade-off in these two major chemical components was more evident between the two sympatric lowland species than between two highland species. Surprisingly, no significant difference in overall tannin concentrations in the seeds was observed between the two fruit morphologies. Instead, the major trade-off between macronutrients and antifeedants involved indigestible fibers. Future studies of this complex mutualism should carefully consider the role of indigestible fibers in the foraging behavior of scatter-hoarding rodents. PMID:22457722

Identifying Important Career Indicators of Undergraduate Geoscience Students Upon Completion of Their Degree

NASA Astrophysics Data System (ADS)

Wilson, C. E.; Keane, C. M.; Houlton, H. R.

2012-12-01

The American Geosciences Institute (AGI) decided to create the National Geoscience Student Exit Survey in order to identify the initial pathways into the workforce for these graduating students, as well as assess their preparedness for entering the workforce upon graduation. The creation of this survey stemmed from a combination of experiences with the AGI/AGU Survey of Doctorates and discussions at the following Science Education Research Center (SERC) workshops: "Developing Pathways to Strong Programs for the Future", "Strengthening Your Geoscience Program", and "Assessing Geoscience Programs". These events identified distinct gaps in understanding the experiences and perspectives of geoscience students during one of their most profound professional transitions. Therefore, the idea for the survey arose as a way to evaluate how the discipline is preparing and educating students, as well as identifying the students' desired career paths. The discussions at the workshops solidified the need for this survey and created the initial framework for the first pilot of the survey. The purpose of this assessment tool is to evaluate student preparedness for entering the geosciences workforce; identify student decision points for entering geosciences fields and remaining in the geosciences workforce; identify geosciences fields that students pursue in undergraduate and graduate school; collect information on students' expected career trajectories and geosciences professions; identify geosciences career sectors that are hiring new graduates; collect information about salary projections; overall effectiveness of geosciences departments regionally and nationally; demonstrate the value of geosciences degrees to future students, the institutions, and employers; and establish a benchmark to perform longitudinal studies of geosciences graduates to understand their career pathways and impacts of their educational experiences on these decisions. AGI's Student Exit Survey went through

Experimental assessment of the importance of amino acid positions identified by an entropy-based correlation analysis of multiple-sequence alignments.

PubMed

Dietrich, Susanne; Borst, Nadine; Schlee, Sandra; Schneider, Daniel; Janda, Jan-Oliver; Sterner, Reinhard; Merkl, Rainer

2012-07-17

The analysis of a multiple-sequence alignment (MSA) with correlation methods identifies pairs of residue positions whose occupation with amino acids changes in a concerted manner. It is plausible to assume that positions that are part of many such correlation pairs are important for protein function or stability. We have used the algorithm H2r to identify positions k in the MSAs of the enzymes anthranilate phosphoribosyl transferase (AnPRT) and indole-3-glycerol phosphate synthase (IGPS) that show a high conn(k) value, i.e., a large number of significant correlations in which k is involved. The importance of the identified residues was experimentally validated by performing mutagenesis studies with sAnPRT and sIGPS from the archaeon Sulfolobus solfataricus. For sAnPRT, five H2r mutant proteins were generated by replacing nonconserved residues with alanine or the prevalent residue of the MSA. As a control, five residues with conn(k) values of zero were chosen randomly and replaced with alanine. The catalytic activities and conformational stabilities of the H2r and control mutant proteins were analyzed by steady-state enzyme kinetics and thermal unfolding studies. Compared to wild-type sAnPRT, the catalytic efficiencies (k(cat)/K(M)) were largely unaltered. In contrast, the apparent thermal unfolding temperature (T(M)(app)) was lowered in most proteins. Remarkably, the strongest observed destabilization (ΔT(M)(app) = 14 °C) was caused by the V284A exchange, which pertains to the position with the highest correlation signal [conn(k) = 11]. For sIGPS, six H2r mutant and four control proteins with alanine exchanges were generated and characterized. The k(cat)/K(M) values of four H2r mutant proteins were reduced between 13- and 120-fold, and their T(M)(app) values were decreased by up to 5 °C. For the sIGPS control proteins, the observed activity and stability decreases were much less severe. Our findings demonstrate that positions with high conn(k) values have an

Chemical quality and regulatory compliance of drinking water in Iceland.

PubMed

Gunnarsdottir, Maria J; Gardarsson, Sigurdur M; Jonsson, Gunnar St; Bartram, Jamie

2016-11-01

Assuring sufficient quality of drinking water is of great importance for public wellbeing and prosperity. Nations have developed regulatory system with the aim of providing drinking water of sufficient quality and to minimize the risk of contamination of the water supply in the first place. In this study the chemical quality of Icelandic drinking water was evaluated by systematically analyzing results from audit monitoring where 53 parameters were assessed for 345 samples from 79 aquifers, serving 74 water supply systems. Compliance to the Icelandic Drinking Water Regulation (IDWR) was evaluated with regard to parametric values, minimum requirement of sampling, and limit of detection. Water quality compliance was divided according to health-related chemicals and indicators, and analyzed according to size. Samples from few individual locations were benchmarked against natural background levels (NBLs) in order to identify potential pollution sources. The results show that drinking compliance was 99.97% in health-related chemicals and 99.44% in indicator parameters indicating that Icelandic groundwater abstracted for drinking water supply is generally of high quality with no expected health risks. In 10 water supply systems, of the 74 tested, there was an indication of anthropogenic chemical pollution, either at the source or in the network, and in another 6 water supplies there was a need to improve the water intake to prevent surface water intrusion. Benchmarking against the NBLs proved to be useful in tracing potential pollution sources, providing a useful tool for identifying pollution at an early stage. Copyright © 2016 Elsevier GmbH. All rights reserved.

Chemical Data Reporting rule (CDR)

EPA Pesticide Factsheets

This dataset contains information on chemicals that company's produce domestically or import into the United States during the principal reporting year. For the 2012 submission period, reporters provided 2011 manufacturing, processing, and use data and 2010 production volume data for their reportable chemical substances.

High-Resolution Linkage Analyses to Identify Genes That Influence Varroa Sensitive Hygiene Behavior in Honey Bees

PubMed Central

Tsuruda, Jennifer M.; Harris, Jeffrey W.; Bourgeois, Lanie; Danka, Robert G.; Hunt, Greg J.

2012-01-01

Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera) and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Varroa sensitive hygiene behavior is one of two behaviors identified that are most important for controlling the growth of Varroa populations in bee hives. To identify genes influencing this trait, a study was conducted to map quantitative trait loci (QTL). Individual workers of a backcross family were observed and evaluated for their VSH behavior in a mite-infested observation hive. Bees that uncapped or removed pupae were identified. The genotypes for 1,340 informative single nucleotide polymorphisms were used to construct a high-resolution genetic map and interval mapping was used to analyze the association of the genotypes with the performance of Varroa sensitive hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21) and a suggestive QTL on chromosome 1 (LOD = 1.95). The QTL confidence interval on chromosome 9 contains the gene ‘no receptor potential A’ and a dopamine receptor. ‘No receptor potential A’ is involved in vision and olfaction in Drosophila, and dopamine signaling has been previously shown to be required for aversive olfactory learning in honey bees, which is probably necessary for identifying mites within brood cells. Further studies on these candidate genes may allow for breeding bees with this trait using marker-assisted selection. PMID:23133626

Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard

EPA Science Inventory

Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most li...

Development of estrogen receptor beta binding prediction model using large sets of chemicals.

PubMed

Sakkiah, Sugunadevi; Selvaraj, Chandrabose; Gong, Ping; Zhang, Chaoyang; Tong, Weida; Hong, Huixiao

2017-11-03

We developed an ER β binding prediction model to facilitate identification of chemicals specifically bind ER β or ER α together with our previously developed ER α binding model. Decision Forest was used to train ER β binding prediction model based on a large set of compounds obtained from EADB. Model performance was estimated through 1000 iterations of 5-fold cross validations. Prediction confidence was analyzed using predictions from the cross validations. Informative chemical features for ER β binding were identified through analysis of the frequency data of chemical descriptors used in the models in the 5-fold cross validations. 1000 permutations were conducted to assess the chance correlation. The average accuracy of 5-fold cross validations was 93.14% with a standard deviation of 0.64%. Prediction confidence analysis indicated that the higher the prediction confidence the more accurate the predictions. Permutation testing results revealed that the prediction model is unlikely generated by chance. Eighteen informative descriptors were identified to be important to ER β binding prediction. Application of the prediction model to the data from ToxCast project yielded very high sensitivity of 90-92%. Our results demonstrated ER β binding of chemicals could be accurately predicted using the developed model. Coupling with our previously developed ER α prediction model, this model could be expected to facilitate drug development through identification of chemicals that specifically bind ER β or ER α .

Probabilistic Health Risk Assessment of Chemical Mixtures: Importance of Travel Times and Connectivity

NASA Astrophysics Data System (ADS)

Henri, Christopher V.; Fernàndez-Garcia, Daniel; de Barros, Felipe P. J.

2014-05-01

Subsurface contamination cases giving rise to groundwater pollutions are extensively found in all industrialized countries. Under this pressure, risk assessment methods play an important role in population protection by (1) quantifying the potential impact on human health of an aquifer contamination and (2) helping and driving decisions of groundwater-resource managers. Many reactive components such as chlorinated solvents or nitrates potentially experience attenuation processes under common geochemical conditions. This represents an attractive and extensively used remediation solution but leads often to the production of by-products before to reach a harmless chemical form. This renders mixtures of contaminants a common issue for groundwater resources managers. In this case, the threat posed by these contaminants to human health at a given sensitive location greatly depends on the competition between reactive and advective-dispersive characteristic times. However, hydraulic properties of the aquifer are known to be spatially variable, which can lead to the formation of preferential flow channels and fast contamination pathways. Therefore, the uncertainty on the spatial distribution of the aquifer properties controlling the plume travel time may then play a particular role in the human health risk assessment of chemical mixtures. We investigate here the risk related to a multispecies system in response to different degrees of heterogeneity of the hydraulic conductivity (K or Y =ln(K)). This work focuses on a Perchloroethylene (PCE) contamination problem followed by the sequential first-order production/biodegradation of its daughter species Trichloroethylene (TCE), Dichloroethylene (DCE) and Vinyl Chlorine (VC). For this specific case, VC is known to be a highly toxic contaminant. By performing numerical experiments, we evaluate transport through three-dimensional mildly (σY 2=1.0) and highly (σY 2=4.0) heterogeneous aquifers. Uncertainty on the hydraulic

Anti-inflammatory activity and chemical profile of Galphimia glauca.

PubMed

González-Cortazar, Manasés; Herrera-Ruiz, Maribel; Zamilpa, Alejandro; Jiménez-Ferrer, Enrique; Marquina, Silvia; Alvarez, Laura; Tortoriello, Jaime

2014-01-01

Galphimia glauca, commonly known as "flor de estrella", is a plant species used in Mexican traditional medicine for the treatment of different diseases that have an acute or chronic inflammatory process in common. Aerial parts of this plant contain nor-seco-triterpenoids with anxiolytic properties, which have been denominated galphimines. Other compounds identified in the plant are tetragalloyl-quinic acid, gallic acid, and quercetin, which are able to inhibit the bronchial obstruction induced by platelet-activating factor. The objective of this work was to evaluate the anti-inflammatory effect of crude extracts from G. glauca and, by means of bioguided chemical separation, to identify the compounds responsible for this pharmacological activity. n-Hexane, ethyl acetate, dichloromethane, and methanol extracts showed an important anti-inflammatory effect. Chemical separation of the active methanol extract allowed us to identify the nor-seco-triterpenes galphimine-A (1) and galphimine-E (3) as the anti-inflammatory principles. Analysis of structure-activity relationships evidenced that the presence of an oxygenated function in C6 is absolutely necessary to show activity. In this work, the isolation and structural elucidation of two new nor-seco-triterpenes denominated as galphimine-K (4) and galphimine-L (5), together with different alkanes, fatty acids, as well as three flavonoids (17-19), are described, to our knowledge for the first time, from Galphimia glauca. Georg Thieme Verlag KG Stuttgart · New York.

Identifying stereoisomers by ab-initio calculation of secondary isotope shifts on NMR chemical shieldings.

PubMed

Böhm, Karl-Heinz; Banert, Klaus; Auer, Alexander A

2014-04-23

We present ab-initio calculations of secondary isotope effects on NMR chemical shieldings. The change of the NMR chemical shift of a certain nucleus that is observed if another nucleus is replaced by a different isotope can be calculated by computing vibrational corrections on the NMR parameters using electronic structure methods. We demonstrate that the accuracy of the computational results is sufficient to even distinguish different conformers. For this purpose, benchmark calculations for fluoro(2-2H)ethane in gauche and antiperiplanar conformation are carried out at the HF, MP2 and CCSD(T) level of theory using basis sets ranging from double- to quadruple-zeta quality. The methodology is applied to the secondary isotope shifts for 2-fluoronorbornane in order to resolve an ambiguity in the literature on the assignment of endo- and exo-2-fluoronorbornanes with deuterium substituents in endo-3 and exo-3 positions, also yielding insight into mechanistic details of the corresponding synthesis.

The need for a life-cycle based aging paradigm for nanomaterials: importance of real-world test systems to identify realistic particle transformations

NASA Astrophysics Data System (ADS)

Mitrano, Denise M.; Nowack, Bernd

2017-02-01

Assessing the risks of manufactured nanomaterials (MNM) has been almost exclusively focused on the pristine, as-produced materials with far fewer studies delving into more complex, real world scenarios. However, when considering a life-cycle perspective, it is clear that MNM released from commercial products during manufacturing, use and disposal are far more relevant both in terms of more realistic environmental fate and transport as well as environmental risk. The quantity in which the particles are released and their (altered) physical and chemical form should be identified and it is these metrics that should be used to assess the exposure and hazard the materials pose. The goal of this review is to (1) provide a rationale for using a life-cycle based approach when dealing with MNM transformations, (2) to elucidate the different chemical and physical forces which age and transform MNM and (3) assess the pros and cons of current analytical techniques as they pertain to the measurement of aged and transformed MNM in these complex release scenarios. Specifically, we will describe the possible transformations common MNM may undergo during the use or disposal of nano-products based on how these products will be used by the consumer by taking stock of the current nano-enabled products on the market. Understanding the impact of these transformations may help forecast the benefits and/or risks associated with the use of products containing MNM.

A landscape ecology approach identifies important drivers of urban biodiversity.

PubMed

Turrini, Tabea; Knop, Eva

2015-04-01

Cities are growing rapidly worldwide, yet a mechanistic understanding of the impact of urbanization on biodiversity is lacking. We assessed the impact of urbanization on arthropod diversity (species richness and evenness) and abundance in a study of six cities and nearby intensively managed agricultural areas. Within the urban ecosystem, we disentangled the relative importance of two key landscape factors affecting biodiversity, namely the amount of vegetated area and patch isolation. To do so, we a priori selected sites that independently varied in the amount of vegetated area in the surrounding landscape at the 500-m scale and patch isolation at the 100-m scale, and we hold local patch characteristics constant. As indicator groups, we used bugs, beetles, leafhoppers, and spiders. Compared to intensively managed agricultural ecosystems, urban ecosystems supported a higher abundance of most indicator groups, a higher number of bug species, and a lower evenness of bug and beetle species. Within cities, a high amount of vegetated area increased species richness and abundance of most arthropod groups, whereas evenness showed no clear pattern. Patch isolation played only a limited role in urban ecosystems, which contrasts findings from agro-ecological studies. Our results show that urban areas can harbor a similar arthropod diversity and abundance compared to intensively managed agricultural ecosystems. Further, negative consequences of urbanization on arthropod diversity can be mitigated by providing sufficient vegetated space in the urban area, while patch connectivity is less important in an urban context. This highlights the need for applying a landscape ecological approach to understand the mechanisms shaping urban biodiversity and underlines the potential of appropriate urban planning for mitigating biodiversity loss. © 2015 John Wiley & Sons Ltd.

Zebrafish: an important tool for liver disease research.

PubMed

Goessling, Wolfram; Sadler, Kirsten C

2015-11-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Zebrafish: An Important Tool for Liver Disease Research

PubMed Central

Goessling, Wolfram; Sadler, Kirsten C.

2016-01-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. PMID:26319012

Joint chemical agent detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.

2003-08-01

The Joint Chemical Agent Detector (JCAD) has continued development through 2002. The JCAD has completed Contractor Validation Testing (CVT) that included chemical warfare agent testing, environmental testing, electromagnetic interferent testing, and platform integration validation. The JCAD provides state of the art chemical warfare agent detection capability to military and homeland security operators. Intelligence sources estimate that over twenty countries have active chemical weapons programs. The spread of weapons of mass destruction (and the industrial capability for manufacture of these weapons) to third world nations and terrorist organizations has greatly increased the chemical agent threat to U.S. interests. Coupled with the potential for U.S. involvement in localized conflicts in an operational or support capacity, increases the probability that the military Joint Services may encounter chemical agents anywhere in the world. The JCAD is a small (45 in3), lightweight (2 lb.) chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection component across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD detects, identifies, quantifies, and warns of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector provides local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew and other personnel in the local area with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD is capable of being upgraded to protect against future chemical agent threats. The JCAD provides the operator with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Bridging the Gap between Chemical Flooding and Independent Oil Producers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stan McCool; Tony Walton; Paul Whillhite

2012-03-31

Ten Kanas oil reservoirs/leases were studied through geological and engineering analysis to assess the potential performance of chemical flooding to recover oil. Reservoirs/leases that have been efficiently waterflooded have the highest performance potential for chemical flooding. Laboratory work to identify efficient chemical systems and to test the oil recovery performance of the systems was the major effort of the project. Efficient chemical systems were identified for crude oils from nine of the reservoirs/leases. Oil recovery performance of the identified chemical systems in Berea sandstone rocks showed 90+ % recoveries of waterflood residual oil for seven crude oils. Oil recoveries increasedmore » with the amount of chemical injected. Recoveries were less in Indiana limestone cores. One formulation recovered 80% of the tertiary oil in the limestone rock. Geological studies for nine of the oil reservoirs are presented. Pleasant Prairie, Trembley, Vinland and Stewart Oilfields in Kansas were the most favorable of the studied reservoirs for a pilot chemical flood from geological considerations. Computer simulations of the performance of a laboratory coreflood were used to predict a field application of chemical flooding for the Trembley Oilfield. Estimates of field applications indicated chemical flooding is an economically viable technology for oil recovery.« less

21 CFR 1313.31 - Advance notice of importation for transshipment or transfer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... International Transactions Involving Listed Chemicals § 1313.31 Advance notice of importation for transshipment... approved. (d) No waiver of the 15-day advance notice will be given for imports of listed chemicals in... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Advance notice of importation for transshipment or...

[Chemical hazards arising from shale gas extraction].

PubMed

Pakulska, Daria

2015-01-01

The development of the shale industry is gaining momentum and hence the analysis of chemical hazards to the environment and health of the local population is extreiely timely and important. Chemical hazards are created during the exploitation of all minerals, but in the case of shale gas production, there is much more uncertainty as regards to the effects of new technologies application. American experience suggests the increasing risk of environmental contamination, mainly groundwater. The greatest, concern is the incomplete knowledge of the composition of fluids used for fracturing shale rock and unpredictability of long-term effects of hydraulic fracturing for the environment and health of residents. High population density in the old continent causes the problem of chemical hazards which is much larger than in the USA. Despite the growing public discontent data on this subject are limited. First of all, there is no epidemiological studies to assess the relationship between risk factors, such as air and water pollution, and health effects in populations living in close proximity to gas wells. The aim of this article is to identify and discuss existing concepts on the sources of environmental contamination, an indication of the environment elements under pressure and potential health risks arising from shale gas extraction.

Chemical Safety Research Advances in Support of Lautenberg Act

EPA Pesticide Factsheets

EPA researchers are developing new ways to identify which chemicals to prioritize for further testing, to provide better access to information about chemicals, and to understand what potential risks chemicals may pose to humans and the environment.

SAM Chemical Methods Query

EPA Pesticide Factsheets

Laboratories measuring target chemical, radiochemical, pathogens, and biotoxin analytes in environmental samples can use this online query tool to identify analytical methods in EPA's Selected Analytical Methods for Environmental Remediation and Recovery

Kelvin probe microscopy and electronic transport measurements in reduced graphene oxide chemical sensors

NASA Astrophysics Data System (ADS)

Kehayias, Christopher E.; MacNaughton, Samuel; Sonkusale, Sameer; Staii, Cristian

2013-06-01

Reduced graphene oxide (RGO) is an electronically hybrid material that displays remarkable chemical sensing properties. Here, we present a quantitative analysis of the chemical gating effects in RGO-based chemical sensors. The gas sensing devices are patterned in a field-effect transistor geometry, by dielectrophoretic assembly of RGO platelets between gold electrodes deposited on SiO2/Si substrates. We show that these sensors display highly selective and reversible responses to the measured analytes, as well as fast response and recovery times (tens of seconds). We use combined electronic transport/Kelvin probe microscopy measurements to quantify the amount of charge transferred to RGO due to chemical doping when the device is exposed to electron-acceptor (acetone) and electron-donor (ammonia) analytes. We demonstrate that this method allows us to obtain high-resolution maps of the surface potential and local charge distribution both before and after chemical doping, to identify local gate-susceptible areas on the RGO surface, and to directly extract the contact resistance between the RGO and the metallic electrodes. The method presented is general, suggesting that these results have important implications for building graphene and other nanomaterial-based chemical sensors.

Kelvin probe microscopy and electronic transport measurements in reduced graphene oxide chemical sensors.

PubMed

Kehayias, Christopher E; MacNaughton, Samuel; Sonkusale, Sameer; Staii, Cristian

2013-06-21

Reduced graphene oxide (RGO) is an electronically hybrid material that displays remarkable chemical sensing properties. Here, we present a quantitative analysis of the chemical gating effects in RGO-based chemical sensors. The gas sensing devices are patterned in a field-effect transistor geometry, by dielectrophoretic assembly of RGO platelets between gold electrodes deposited on SiO2/Si substrates. We show that these sensors display highly selective and reversible responses to the measured analytes, as well as fast response and recovery times (tens of seconds). We use combined electronic transport/Kelvin probe microscopy measurements to quantify the amount of charge transferred to RGO due to chemical doping when the device is exposed to electron-acceptor (acetone) and electron-donor (ammonia) analytes. We demonstrate that this method allows us to obtain high-resolution maps of the surface potential and local charge distribution both before and after chemical doping, to identify local gate-susceptible areas on the RGO surface, and to directly extract the contact resistance between the RGO and the metallic electrodes. The method presented is general, suggesting that these results have important implications for building graphene and other nanomaterial-based chemical sensors.

[Chemical components from essential oil of Pandanus amaryllifolius leaves].

PubMed

Chen, Xiao-Kai; Ge, Fa-Huan

2014-04-01

To analyze the chemical compositions of Pandanus amaryllifolius leaves essential oil extracted by steam distillation. The essential oil of Pandanus amaryllifolius leaves was analyzed by gas chromatography-mass spectrum, and the relative content of each component was determined by area normalization method. 128 peaks were separated and 95 compounds were identified, which weighed 97.75%. The main chemical components of the essential oil were phytol (42.15%), squalene (16.81%), what's more pentadecanal (6.17%), pentadecanoic acid (4.49%), 3, 7, 11, 15-tetramethyl-2-hexadecen-1-ol (3.83%), phytone (2.05%) and the other 74 chemical compositions were firstly identified from the essential oil of Pandanus amaryllifolius leaves. The chemical compositions of Pandanu samaryllifolius leaves essential oil was systematically, deeply isolated and identified for the first time. This experiment has provided scientific foundation for further utilization of Pandanus amaryllifolius leaves.

Building an R&D chemical registration system.

PubMed

Martin, Elyette; Monge, Aurélien; Duret, Jacques-Antoine; Gualandi, Federico; Peitsch, Manuel C; Pospisil, Pavel

2012-05-31

Small molecule chemistry is of central importance to a number of R&D companies in diverse areas such as the pharmaceutical, nutraceutical, food flavoring, and cosmeceutical industries. In order to store and manage thousands of chemical compounds in such an environment, we have built a state-of-the-art master chemical database with unique structure identifiers. Here, we present the concept and methodology we used to build the system that we call the Unique Compound Database (UCD). In the UCD, each molecule is registered only once (uniqueness), structures with alternative representations are entered in a uniform way (normalization), and the chemical structure drawings are recognizable to chemists and to a cartridge. In brief, structural molecules are entered as neutral entities which can be associated with a salt. The salts are listed in a dictionary and bound to the molecule with the appropriate stoichiometric coefficient in an entity called "substance". The substances are associated with batches. Once a molecule is registered, some properties (e.g., ADMET prediction, IUPAC name, chemical properties) are calculated automatically. The UCD has both automated and manual data controls. Moreover, the UCD concept enables the management of user errors in the structure entry by reassigning or archiving the batches. It also allows updating of the records to include newly discovered properties of individual structures. As our research spans a wide variety of scientific fields, the database enables registration of mixtures of compounds, enantiomers, tautomers, and compounds with unknown stereochemistries.

A Dynamic Laplacian for Identifying Lagrangian Coherent Structures on Weighted Riemannian Manifolds

NASA Astrophysics Data System (ADS)

Froyland, Gary; Kwok, Eric

2017-06-01

Transport and mixing in dynamical systems are important properties for many physical, chemical, biological, and engineering processes. The detection of transport barriers for dynamics with general time dependence is a difficult, but important problem, because such barriers control how rapidly different parts of phase space (which might correspond to different chemical or biological agents) interact. The key factor is the growth of interfaces that partition phase space into separate regions. The paper Froyland (Nonlinearity 28(10):3587-3622, 2015) introduced the notion of dynamic isoperimetry: the study of sets with persistently small boundary size (the interface) relative to enclosed volume, when evolved by the dynamics. Sets with this minimal boundary size to volume ratio were identified as level sets of dominant eigenfunctions of a dynamic Laplace operator. In this present work we extend the results of Froyland (Nonlinearity 28(10):3587-3622, 2015) to the situation where the dynamics (1) is not necessarily volume preserving, (2) acts on initial agent concentrations different from uniform concentrations, and (3) occurs on a possibly curved phase space. Our main results include generalised versions of the dynamic isoperimetric problem, the dynamic Laplacian, Cheeger's inequality, and the Federer-Fleming theorem. We illustrate the computational approach with some simple numerical examples.

Recent trends and important developments in propolis research

PubMed Central

2005-01-01

The newest developments in propolis pharmacological research are summarized. The problem regarding biological studies, caused by the chemical variability of propolis, is discussed. The most important trends and developments in recent propolis research are outlined: biological studies performed with chemically characterized samples, bioassay-guided studies of active principles and comparative biological studies of propolis of different origin and chemical composition. These types of studies are extremely valuable with respect to propolis standardization and practical applications in therapy. They will allow scientists to connect a particular chemical propolis type to a specific type of biological activity and formulate recommendations for practitioners. PMID:15841275

[Study on the chemical constituents of Rhizoma Cyperi].

PubMed

Wu, Xi; Xia, Hou-Lin; Huang, Li-Hua; Chen, Dan-Dan; Chen, Jin-Yu; Weng, Hai-Ting

2008-07-01

To study the chemical constituents of Rhizoma Cyperi. The constituents were separated and purified by silica gel column chromatography, their structures were identified on the basis of physico-chemical properties and spectral data. Six compounds were isolated and identified as physicion (1), hexadecanoic acid (2), beta-sitosterol (3), stigmasterol (4), catenarin (5), daucosterol (6). Compounds 1, 4, 5 were isolated from this plant for the first fime.

The Importance of Sample Return in Establishing Chemical Evidence for Life on Mars or Other Solar System Bodies

NASA Technical Reports Server (NTRS)

Glavin, D. P.; Conrad, P.; Dworkin, J. P.; Eigenbrode, J.; Mahaffy, P. R.

2011-01-01

The search for evidence of life on Mars and elsewhere will continue to be one of the primary goals of NASA s robotic exploration program over the next decade. NASA and ESA are currently planning a series of robotic missions to Mars with the goal of understanding its climate, resources, and potential for harboring past or present life. One key goal will be the search for chemical biomarkers including complex organic compounds important in life on Earth. These include amino acids, the monomer building blocks of proteins and enzymes, nucleobases and sugars which form the backbone of DNA and RNA, and lipids, the structural components of cell membranes. Many of these organic compounds can also be formed abiotically as demonstrated by their prevalence in carbonaceous meteorites [1], though, their molecular characteristics may distinguish a biological source [2]. It is possible that in situ instruments may reveal such characteristics, however, return of the right sample (i.e. one with biosignatures or having a high probability of biosignatures) to Earth would allow for more intensive laboratory studies using a broad array of powerful instrumentation for bulk characterization, molecular detection, isotopic and enantiomeric compositions, and spatially resolved chemistry that may be required for confirmation of extant or extinct Martian life. Here we will discuss the current analytical capabilities and strategies for the detection of organics on the Mars Science Laboratory (MSL) using the Sample Analysis at Mars (SAM) instrument suite and how sample return missions from Mars and other targets of astrobiological interest will help advance our understanding of chemical biosignatures in the solar system.

Exploration of the Chemical Space of Public Genomic ...

EPA Pesticide Factsheets

The current project aims to chemically index the content of public genomic databases to make these data accessible in relation to other publicly available, chemically-indexed toxicological information. By evaluating the chemical space of public genomic data in relation to public toxicological data, it is possible to identify classes of chemicals on which to develop methodologies for the integration of chemogenomic data into predictive toxicology.

[The key problems in the population exposure assessment of hazardous chemicals accidents].

PubMed

Pan, L J; Liu, F P; Zhang, X; Bai, X T; Shi, X M

2016-07-06

Serious accidents of hazardous chemicals can cause a variety of acute or chronic impairment in human health. The effects of hazardous chemicals on human health can be identified by carrying on population exposure assessment. Through analyzing the domestic and overseas population exposure assessment cases related to hazardous chemicals accidents, we summarized that the base and key of the population exposure assessment were to identify the characteristics of the chemicals , delimit the area and the population exposed to the chemicals, and collect the data of the monitored chemicals and the population health in the polluted area.

Neural network processing of microbial fuel cell signals for the identification of chemicals present in water.

PubMed

Feng, Yinghua; Barr, William; Harper, W F

2013-05-15

Biosensing is emerging as an important element of water quality monitoring. This research demonstrated that microbial fuel cell (MFC)-based biosensing can be integrated with artificial neural networks (ANNs) to identify specific chemicals present in water samples. The non-fermentable substrates, acetate and butyrate, induced peak areas (PA) and peak heights (PH) that were generally larger than those caused by the injection of fermentable substrates, glucose and corn starch. The ANN successfully identified peaks associated with these four chemicals under a variety of experimental conditions and for two MFCs that had different levels of sensitivity. ANNs that employ the hyperbolic tangent sigmoid transfer function performed better than those using non-continuous transfer functions. ANNs should be integrated into water quality monitoring efforts for smart biosensing. Published by Elsevier Ltd.

Detection of chemical contraband using spectroscopic microwave imaging

NASA Astrophysics Data System (ADS)

Falconer, David G.; Watters, David G.

1994-02-01

We have developed and demonstrated a microwave technique for detecting high explosives, illegal drugs, and other chemical contraband in checked airline baggage. Our technique isolates suspicious materials using microwave tomography and identifies chemical contraband using microwave spectroscopy. Measurements in the frequency range 2 - 18 GHz indicate that microwave energy will penetrate nonmetallic suitcases and that contraband materials feature distinct dielectric spectra at these wavelengths. We have also formed microwave images of a soft-sided suitcase and its contents. After manually segmenting the microwave imagery, we successfully identified chemical simulants for both high explosives and illegal drugs.

Incorporating zebrafish omics into chemical biology and toxicology.

PubMed

Sukardi, Hendrian; Ung, Choong Yong; Gong, Zhiyuan; Lam, Siew Hong

2010-03-01

In this communication, we describe the general aspects of omics approaches for analyses of transcriptome, proteome, and metabolome, and how they can be strategically incorporated into chemical screening and perturbation studies using the zebrafish system. Pharmacological efficacy and selectivity of chemicals can be evaluated based on chemical-induced phenotypic effects; however, phenotypic observation has limitations in identifying mechanistic action of chemicals. We suggest adapting gene-expression-based high-throughput screening as a complementary strategy to zebrafish-phenotype-based screening for mechanistic insights about the mode of action and toxicity of a chemical, large-scale predictive applications and comparative analysis of chemical-induced omics signatures, which are useful to identify conserved biological responses, signaling pathways, and biomarkers. The potential mechanistic, predictive, and comparative applications of omics approaches can be implemented in the zebrafish system. Examples of these using the omics approaches in zebrafish, including data of ours and others, are presented and discussed. Omics also facilitates the translatability of zebrafish studies across species through comparison of conserved chemical-induced responses. This review is intended to update interested readers with the current omics approaches that have been applied in chemical studies on zebrafish and their potential in enhancing discovery in chemical biology.

Forge into the Future: Identifying Core Competencies and Important Skills, Knowledge, and Abilities (SKAs) for Junior Navy Medical Service Corps Officers

DTIC Science & Technology

2008-10-20

operations and business practices, drug therapy management, and leadership, where as senior pharmacists placed a greater emphasis on the importance of SKAs...Commanders reviewed , sorted, and identified competencies from Wave I into 11 domains. From the expert analysis, the researcher developed a ...Y, a force of as many as 70 million are now beginning to embark on their career including the military health system. This generation as suggested

21 CFR 1313.08 - Requirements for establishing a record as an importer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... IMPORTATION AND EXPORTATION OF LIST I AND LIST II CHEMICALS § 1313.08 Requirements for establishing a record... Administrator with the following information in accordance with the waiver of the 15-day advance notice... FR 17407, Apr. 9, 2007] Importation of Listed Chemicals ...

21 CFR 1313.08 - Requirements for establishing a record as an importer.

Code of Federal Regulations, 2013 CFR