Science.gov

Sample records for identify chemical compounds

  1. Antifungal chemical compounds identified using a C. elegans pathogenicity assay.

    PubMed

    Breger, Julia; Fuchs, Beth Burgwyn; Aperis, George; Moy, Terence I; Ausubel, Frederick M; Mylonakis, Eleftherios

    2007-02-01

    There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi. PMID:17274686

  2. Large-Scale Chemical Similarity Networks for Target Profiling of Compounds Identified in Cell-Based Chemical Screens

    PubMed Central

    Lo, Yu-Chen; Senese, Silvia; Li, Chien-Ming; Hu, Qiyang; Huang, Yong; Damoiseaux, Robert; Torres, Jorge Z.

    2015-01-01

    Target identification is one of the most critical steps following cell-based phenotypic chemical screens aimed at identifying compounds with potential uses in cell biology and for developing novel disease therapies. Current in silico target identification methods, including chemical similarity database searches, are limited to single or sequential ligand analysis that have limited capabilities for accurate deconvolution of a large number of compounds with diverse chemical structures. Here, we present CSNAP (Chemical Similarity Network Analysis Pulldown), a new computational target identification method that utilizes chemical similarity networks for large-scale chemotype (consensus chemical pattern) recognition and drug target profiling. Our benchmark study showed that CSNAP can achieve an overall higher accuracy (>80%) of target prediction with respect to representative chemotypes in large (>200) compound sets, in comparison to the SEA approach (6070%). Additionally, CSNAP is capable of integrating with biological knowledge-based databases (Uniprot, GO) and high-throughput biology platforms (proteomic, genetic, etc) for system-wise drug target validation. To demonstrate the utility of the CSNAP approach, we combined CSNAP's target prediction with experimental ligand evaluation to identify the major mitotic targets of hit compounds from a cell-based chemical screen and we highlight novel compounds targeting microtubules, an important cancer therapeutic target. The CSNAP method is freely available and can be accessed from the CSNAP web server (http://services.mbi.ucla.edu/CSNAP/). PMID:25826798

  3. A Chemical Screen Identifies Novel Compounds That Overcome Glial-Mediated Inhibition Of Neuronal Regeneration

    PubMed Central

    Usher, Lynn C.; Johnstone, Andrea; Ertürk, Ali; Hu, Ying; Strikis, Dinara; Wanner, Ina B.; Moorman, Sanne; Lee, Jae-Wook; Min, Jaeki; Ha, Hyung-Ho; Duan, Yuanli; Hoffman, Stanley; Goldberg, Jeffrey L.; Bradke, Frank; Chang, Young-Tae; Lemmon, Vance P.; Bixby, John L.

    2010-01-01

    A major barrier to regeneration of central nervous system (CNS) axons is the presence of growth-inhibitory proteins associated with myelin and the glial scar. To identify chemical compounds with the ability to overcome the inhibition of regeneration, we screened a novel triazine library, based on the ability of compounds to increase neurite outgrowth from cerebellar neurons on inhibitory myelin substrates. The screen produced 4 “hit compounds”, which act with nM potency on several different neuronal types, and on several distinct substrates relevant to glial inhibition. Moreover, the compounds selectively overcome inhibition rather than promote growth in general. The compounds do not affect neuronal cAMP levels, PKC activity, or EGFR activation. Interestingly, one of the compounds alters microtubule dynamics and increases microtubule density in both fibroblasts and neurons. This same compound promotes regeneration of dorsal column axons after acute lesions, and potentiates regeneration of optic nerve axons after nerve crush in vivo. These compounds should provide insight into the mechanisms through which glial-derived inhibitors of regeneration act, and could lead to the development of novel therapies for CNS injury. PMID:20357120

  4. 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...

  5. 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 Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. Environ Health Perspect 123:4956;?http://dx.doi.org/10.1289/ehp.1408642 PMID:25302578

  6. Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion

    PubMed Central

    Gallardo, Viviana E.; Varshney, Gaurav K.; Lee, Minnkyong; Bupp, Sujata; Xu, Lisha; Shinn, Paul; Crawford, Nigel P.; Inglese, James; Burgess, Shawn M.

    2015-01-01

    ABSTRACT In the last decade, high-throughput chemical screening has become the dominant approach for discovering novel compounds with therapeutic properties. Automated screening using in vitro or cultured cell assays have yielded thousands of candidate drugs for a variety of biological targets, but these approaches have not resulted in an increase in drug discovery despite major increases in expenditures. In contrast, phenotype-driven screens have shown a much stronger success rate, which is why we developed an in vivo assay using transgenic zebrafish with a GFP-marked migrating posterior lateral line primordium (PLLp) to identify compounds that influence collective cell migration. We then conducted a high-throughput screen using a compound library of 2160 annotated bioactive synthetic compounds and 800 natural products to identify molecules that block normal PLLp migration. We identified 165 compounds that interfere with primordium migration without overt toxicity in vivo. Selected compounds were confirmed in their migration-blocking activity by using additional assays for cell migration. We then proved the screen to be successful in identifying anti-metastatic compounds active in vivo by performing orthotopic tumor implantation assays in mice. We demonstrated that the Src inhibitor SU6656, identified in our screen, can be used to suppress the metastatic capacity of a highly aggressive mammary tumor cell line. Finally, we used CRISPR/Cas9-targeted mutagenesis in zebrafish to genetically validate predicted targets of compounds. This approach demonstrates that the migrating PLLp in zebrafish can be used for large-scale, high-throughput screening for compounds that inhibit collective cell migration and, potentially, anti-metastatic compounds. PMID:25810455

  7. Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion.

    PubMed

    Gallardo, Viviana E; Varshney, Gaurav K; Lee, Minnkyong; Bupp, Sujata; Xu, Lisha; Shinn, Paul; Crawford, Nigel P; Inglese, James; Burgess, Shawn M

    2015-06-01

    In the last decade, high-throughput chemical screening has become the dominant approach for discovering novel compounds with therapeutic properties. Automated screening using in vitro or cultured cell assays have yielded thousands of candidate drugs for a variety of biological targets, but these approaches have not resulted in an increase in drug discovery despite major increases in expenditures. In contrast, phenotype-driven screens have shown a much stronger success rate, which is why we developed an in vivo assay using transgenic zebrafish with a GFP-marked migrating posterior lateral line primordium (PLLp) to identify compounds that influence collective cell migration. We then conducted a high-throughput screen using a compound library of 2160 annotated bioactive synthetic compounds and 800 natural products to identify molecules that block normal PLLp migration. We identified 165 compounds that interfere with primordium migration without overt toxicity in vivo. Selected compounds were confirmed in their migration-blocking activity by using additional assays for cell migration. We then proved the screen to be successful in identifying anti-metastatic compounds active in vivo by performing orthotopic tumor implantation assays in mice. We demonstrated that the Src inhibitor SU6656, identified in our screen, can be used to suppress the metastatic capacity of a highly aggressive mammary tumor cell line. Finally, we used CRISPR/Cas9-targeted mutagenesis in zebrafish to genetically validate predicted targets of compounds. This approach demonstrates that the migrating PLLp in zebrafish can be used for large-scale, high-throughput screening for compounds that inhibit collective cell migration and, potentially, anti-metastatic compounds. PMID:25810455

  8. 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

  9. Devices for collecting chemical compounds

    SciTech Connect

    Scott, Jill R; Groenewold, Gary S

    2013-12-24

    A device for sampling chemical compounds from fixed surfaces and related methods are disclosed. The device may include a vacuum source, a chamber and a sorbent material. The device may utilize vacuum extraction to volatilize the chemical compounds from a fixed surface so that they may be sorbed by the sorbent material. The sorbent material may then be analyzed using conventional thermal desorption/gas chromatography/mass spectrometry (TD/GC/MS) instrumentation to determine presence of the chemical compounds. The methods may include detecting release and presence of one or more chemical compounds and determining the efficacy of decontamination. The device may be useful in collection and analysis of a variety of chemical compounds, such as residual chemical warfare agents, chemical attribution signatures and toxic industrial chemicals.

  10. 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...

  11. Automated compound classification using a chemical ontology

    PubMed Central

    2012-01-01

    Background Classification of chemical compounds into compound classes by using structure derived descriptors is a well-established method to aid the evaluation and abstraction of compound properties in chemical compound databases. MeSH and recently ChEBI are examples of chemical ontologies that provide a hierarchical classification of compounds into general compound classes of biological interest based on their structural as well as property or use features. In these ontologies, compounds have been assigned manually to their respective classes. However, with the ever increasing possibilities to extract new compounds from text documents using name-to-structure tools and considering the large number of compounds deposited in databases, automated and comprehensive chemical classification methods are needed to avoid the error prone and time consuming manual classification of compounds. Results In the present work we implement principles and methods to construct a chemical ontology of classes that shall support the automated, high-quality compound classification in chemical databases or text documents. While SMARTS expressions have already been used to define chemical structure class concepts, in the present work we have extended the expressive power of such class definitions by expanding their structure-based reasoning logic. Thus, to achieve the required precision and granularity of chemical class definitions, sets of SMARTS class definitions are connected by OR and NOT logical operators. In addition, AND logic has been implemented to allow the concomitant use of flexible atom lists and stereochemistry definitions. The resulting chemical ontology is a multi-hierarchical taxonomy of concept nodes connected by directed, transitive relationships. Conclusions A proposal for a rule based definition of chemical classes has been made that allows to define chemical compound classes more precisely than before. The proposed structure-based reasoning logic allows to translate chemistry expert knowledge into a computer interpretable form, preventing erroneous compound assignments and allowing automatic compound classification. The automated assignment of compounds in databases, compound structure files or text documents to their related ontology classes is possible through the integration with a chemical structure search engine. As an application example, the annotation of chemical structure files with a prototypic ontology is demonstrated. PMID:23273256

  12. Chemically engineered extracts: source of bioactive compounds.

    PubMed

    Ramallo, I Ayelen; Salazar, Mario O; Mendez, Luciana; Furlan, Ricardo L E

    2011-04-19

    Biological research and drug discovery critically depend on access to libraries of small molecules that have an affinity for biomacromolecules. By virtue of their sustained success as sources of lead compounds, natural products are recognized as "privileged" starting points in structural space for library development. Compared with synthetic compounds, natural products have distinguishing structural properties; indeed, researchers have begun to quantify and catalog the differences between the two classes of molecules. Measurable differences in the number of chiral centers, the degree of saturation, the presence of aromatic rings, and the number of the various heteroatoms are among the chief distinctions between natural and synthetic compounds. Natural products also include a significant proportion of recurring molecular scaffolds that are not present in currently marketed drugs: the bioactivity of these natural substructures has been refined over the long process of evolution. In this Account, we present our research aimed at preparing libraries of semisynthetic compounds, or chemically engineered extracts (CEEs), through chemical diversification of natural products mixtures. The approach relies on the power of numbers, that is, in the chemical alteration of a sizable fraction of the starting complex mixture. Major changes in composition can be achieved through the chemical transformation of reactive molecular fragments that are found in most natural products. If such fragments are common enough, their transformation represents an entry point for chemically altering a high proportion of the components of crude natural extracts. We have searched for common reactive fragments in the Dictionary of Natural Products (CRC Press) and identified several functional groups that are expected to be present in a large fraction of the components of an average natural crude extract. To date, we have used reactions that incorporate (i) nitrogen atoms through carbonyl groups, (ii) sulfur by transformation of -OH and amines, and (iii) bromine through double bonds and aromatic rings. The resulting CEEs had different composition and biomolecular properties than their natural progenitors. We isolated a semisynthetic β-glucosidase inhibitor from a CEE prepared by reaction with benzenesulfonyl chloride, an antifungal pyrazole from a CEE prepared by reaction with hydrazine, and an acetylcholinesterase inhibitor from a CEE prepared through bromination. Our results illustrate how biological activity can be generated through chemical diversification of natural product mixtures. Moreover, the level of control that can be asserted in the process by judicious design and experimental choices underscores the potential for further development of CEEs in both basic research and drug discovery. PMID:21355557

  13. Identifying chemicals that are planetary boundary threats.

    PubMed

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

    2014-10-01

    Rockstrm et al. proposed a set of planetary boundaries that delimit a "safe operating space for humanity". Many of the planetary boundaries that have so far been identified are determined by chemical agents. Other chemical pollution-related planetary boundaries likely exist, but are currently unknown. A chemical poses an unknown planetary boundary threat if it simultaneously fulfills three conditions: (1) it has an unknown disruptive effect on a vital Earth system process; (2) the disruptive effect is not discovered until it is a problem at the global scale, and (3) the effect is not readily reversible. In this paper, we outline scenarios in which chemicals could fulfill each of the three conditions, then use the scenarios as the basis to define chemical profiles that fit each scenario. The chemical profiles are defined in terms of the nature of the effect of the chemical and the nature of exposure of the environment to the chemical. Prioritization of chemicals in commerce against some of the profiles appears feasible, but there are considerable uncertainties and scientific challenges that must be addressed. Most challenging is prioritizing chemicals for their potential to have a currently unknown effect on a vital Earth system process. We conclude that the most effective strategy currently available to identify chemicals that are planetary boundary threats is prioritization against profiles defined in terms of environmental exposure combined with monitoring and study of the biogeochemical processes that underlie vital Earth system processes to identify currently unknown disruptive effects. PMID:25181298

  14. IDENTIFYING CHEMICAL COMPOUNDS IN THE ENVIRONMENT

    EPA Science Inventory

    The quality of drinking and recreational water is currently ascertained using indicator bacteria. The tests to analyze for these bacteria require a considerable length of time to complete, and do not discriminate between human and animal fecal material sources. To shorten the t...

  15. Quantum chemical studies of estrogenic compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantum chemical methods are potent tools to provide information on the chemical structure and electronic properties of organic molecules. Modern computational chemistry methods have provided a great deal of insight into the binding of estrogenic compounds to estrogenic receptors (ER), an important ...

  16. Chemical compound navigator: a web-based chem-BLAST, chemical taxonomy-based search engine for browsing compounds.

    PubMed

    Prasanna, M D; Vondrasek, Jiri; Wlodawer, Alexander; Rodriguez, H; Bhat, T N

    2006-06-01

    A novel technique to annotate, query, and analyze chemical compounds has been developed and is illustrated by using the inhibitor data on HIV protease-inhibitor complexes. In this method, all chemical compounds are annotated in terms of standard chemical structural fragments. These standard fragments are defined by using criteria, such as chemical classification; structural, chemical, or functional groups; and commercial, scientific or common names or synonyms. These fragments are then organized into a data tree based on their chemical substructures. Search engines have been developed to use this data tree to enable query on inhibitors of HIV protease (http://xpdb.nist.gov/hivsdb/hivsdb.html). These search engines use a new novel technique, Chemical Block Layered Alignment of Substructure Technique (Chem-BLAST) to search on the fragments of an inhibitor to look for its chemical structural neighbors. This novel technique to annotate and query compounds lays the foundation for the use of the Semantic Web concept on chemical compounds to allow end users to group, sort, and search structural neighbors accurately and efficiently. During annotation, it enables the attachment of "meaning" (i.e., semantics) to data in a manner that far exceeds the current practice of associating "metadata" with data by creating a knowledge base (or ontology) associated with compounds. Intended users of the technique are the research community and pharmaceutical industry, for which it will provide a new tool to better identify novel chemical structural neighbors to aid drug discovery. PMID:16508960

  17. Identifying interactions between chemical entities in biomedical text.

    PubMed

    Lamurias, Andre; Ferreira, Joo D; Couto, Francisco M

    2014-01-01

    Interactions between chemical compounds described in biomedical text can be of great importance to drug discovery and design, as well as pharmacovigilance. We developed a novel system, \\"Identifying Interactions between Chemical Entities\\" (IICE), to identify chemical interactions described in text. Kernel-based Support Vector Machines first identify the interactions and then an ensemble classifier validates and classifies the type of each interaction. This relation extraction module was evaluated with the corpus released for the DDI Extraction task of SemEval 2013, obtaining results comparable to state-of-the-art methods for this type of task. We integrated this module with our chemical named entity recognition module and made the whole system available as a web tool at www.lasige.di.fc.ul.pt/webtools/iice. PMID:25339081

  18. Identifying developmental vascular disruptor compounds using a predictive signature and alternative toxicity models

    EPA Science Inventory

    Identifying Developmental Vascular Disruptor Compounds Using a Predictive Signature and Alternative Toxicity Models Presenting Author: Tamara Tal Affiliation: U.S. EPA/ORD/ISTD, RTP, NC, USA Chemically induced vascular toxicity during embryonic development can result in a wide...

  19. Chemical defenses: from compounds to communities.

    PubMed

    Paul, Valerie J; Arthur, Karen E; Ritson-Williams, Raphael; Ross, Cliff; Sharp, Koty

    2007-12-01

    Marine natural products play critical roles in the chemical defense of many marine organisms and in some cases can influence the community structure of entire ecosystems. Although many marine natural products have been studied for biomedical activity, yielding important information about their biochemical effects and mechanisms of action, much less is known about ecological functions. The way in which marine consumers perceive chemical defenses can influence their health and survival and determine whether some natural products persist through a food chain. This article focuses on selected marine natural products, including okadaic acid, brevetoxins, lyngbyatoxin A, caulerpenyne, bryostatins, and isocyano terpenes, and examines their biosynthesis (sometimes by symbiotic microorganisms), mechanisms of action, and biological and ecological activity. We selected these compounds because their impacts on marine organisms and communities are some of the best-studied among marine natural products. We discuss the effects of these compounds on consumer behavior and physiology, with an emphasis on neuroecology. In addition to mediating a variety of trophic interactions, these compounds may be responsible for community-scale ecological impacts of chemically defended organisms, such as shifts in benthic and pelagic community composition. Our examples include harmful algal blooms; the invasion of the Mediterranean by Caulerpa taxifolia; overgrowth of coral reefs by chemically rich macroalgae and cyanobacteria; and invertebrate chemical defenses, including the role of microbial symbionts in compound production. PMID:18083964

  20. Identifying environmental chemicals causing mutations and cancer.

    PubMed

    Ames, B N

    1979-05-11

    Damage to DNA appears to be the major cause of most cancer and genetic birth defects and may contribute to aging and heart disease as well. The agents that cause this damage must be identified. Many of these agents are natural chemicals present in the human diet as complex mixtures. The tens of thousands of man-made chemicals that have been introduced into the environment in the last few decades must also be tested for their ability to damage DNA. Existing animal tests and human epidemiology alone are inadequate for this task because of time, expense, and the difficulty of dealing with complex mixtures, Newly developed short-term tests, most of them assaying for mutagenicity, are discussed as key tools in identifying environmental mutagens and carcinogens. PMID:373122

  1. Lifetime of a Chemically Bound Helium Compound

    NASA Technical Reports Server (NTRS)

    Chaban, Galina M.; Lundell, Jan; Gerber, R. Benny; Kwak, Dochan (Technical Monitor)

    2001-01-01

    The rare-gas atoms are chemically inert, to an extent unique among all elements. This is due to the stable electronic structure of the atoms. Stable molecules with chemically bound rare-gas atoms are, however, known. A first such compound, XePtF6, W2S prepared in 1962 and since then a range of molecules containing radon, xenon and krypton have been obtained. Most recently, a first stable chemically bound compound of argon was prepared, leaving neon and helium as the only elements for which stable chemically bound molecules are not yet known. Electronic structure calculations predict that a metastable species HHeF exists, but significance of the result depends on the unknown lifetime. Here we report quantum dynamics calculations of the lifetime of HHeF, using accurate interactions computed from electronic structure theory. HHeF is shown to disintegrate by tunneling through energy barriers into He + HF and H + He + F the first channel greatly dominating. The lifetime of HHeF is more than 120 picoseconds, that of DHeF is 14 nanoseconds. The relatively long lifetimes are encouraging for the preparation prospects of this first chemically bound helium compound.

  2. USING AN ACCURATE MASS, TRIPLE QUADRUPOLE MASS SPECTROMETER AND AN ION CORRELATION PROGRAM TO IDENTIFY COMPOUNDS

    EPA Science Inventory

    Most compounds are not found in mass spectral libraries and must be identified by other means. Often, compound identities can be deduced from the compositions of the ions in their mass spectra and review of the chemical literature. Confirmation is provided by mass spectra and r...

  3. Chemical Proteomic Platform To Identify Citrullinated Proteins

    PubMed Central

    2015-01-01

    Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and are routinely used for disease diagnosis. Protein citrullination is also increased in cancer and other autoimmune disorders, suggesting that citrullinated proteins may serve as biomarkers for diseases beyond RA. To identify these citrullinated proteins, we developed biotin-conjugated phenylglyoxal (biotin-PG). Using this probe and our platform technology, we identified >50 intracellular citrullinated proteins. More than 20 of these are involved in RNA splicing, suggesting, for the first time, that citrullination modulates RNA biology. Overall, this chemical proteomic platform will play a key role in furthering our understanding of protein citrullination in rheumatoid arthritis and potentially a wider spectrum of inflammatory diseases. PMID:26360112

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

    SciTech Connect

    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 facility 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.

  5. Inhibitors of Tubulin Assembly Identified through Screening a Compound Library

    PubMed Central

    Morgan, Rachel E.; Ahn, Sunjoo; Nzimiro, Sandra; Fotie, Jean; Phelps, Mitch A.; Cotrill, Jeffrey; Yakovich, Adam J.; Sackett, Dan L.; Dalton, James T.; Werbovetz, Karl A.

    2013-01-01

    Tubulin is the proposed target for drugs against cancer and helminths and is also a validated target in kinetoplastid parasites. With the aim of identifying new lead compounds against Leishmania sp., tubulin isolated from L. tarentolae was used to screen a 10 000 compound library. One compound, Chembridge No. 7992831 (5), displayed an IC50 of 13 ?m against Leishmania tubulin in an in vitro assembly assay and showed a greater than threefold selectivity over mammalian tubulin. Another compound, Chembridge No. 9067250 (8), exhibited good activity against mammalian tubulin (IC50 = 5.0 ?m). This compound was also toxic to several cancer cell lines with IC50 values in the region of 1 ?M. Subsequent testing of analogues of 8 contained within the library identified two compounds with greater potency against mammalian tubulin (IC50 values of 1.1 and 2.8 ?M). The more potent antitubulin agent also showed promising activity against cancer cell lines in vitro, with IC50 values ranging from 0.18 to 0.73 ?M. PMID:19090918

  6. A staining protocol for identifying secondary compounds in Myrtaceae1

    PubMed Central

    Retamales, Hernan A.; Scharaschkin, Tanya

    2014-01-01

    Premise of the study: Here we propose a staining protocol using toluidine blue (TBO) and ruthenium red to reliably identify secondary compounds in the leaves of some species of Myrtaceae. Methods and Results: Leaves of 10 species representing 10 different genera of Myrtaceae were processed and stained using five different combinations of ruthenium red and TBO. Optimal staining conditions were determined as 1 min of ruthenium red (0.05% aqueous) and 45 s of TBO (0.1% aqueous). Secondary compounds clearly identified under this treatment include mucilage in the mesophyll, polyphenols in the cuticle, lignin in fibers and xylem, tannins and carboxylated polysaccharides in the epidermis, and pectic substances in the primary cell walls. Conclusions: Potential applications of this protocol include systematic, phytochemical, and ecological investigations in Myrtaceae. It might be applicable to other plant families rich in secondary compounds and could be used as a preliminary screening method for extraction of these elements. PMID:25309840

  7. Chemical Trends for Transition Metal Compound Bonding to Graphene

    NASA Astrophysics Data System (ADS)

    Lange, Bjoern; Blum, Volker

    2015-03-01

    Transition metal compounds are of interest as catalysts for the hydrogen evolution reaction (HER). However, a perfect candidate to replace expensive platinum has not yet been identified. To tailor a specific compound, several properties come into play. One is the bonding to the underlying substrate, for which ?-bonded carbon nanostructures are promising candidates. Here we analyze the bonding of small transition metal compound nanoclusters to a graphene layer for a range of chemical compositions: MxAy (M = Mo, Ti; A = S, O, B, N, C). The clusters are generated by an unbiased random search algorithm. We perform total energy calculations based on density functional theory to identify lowest energy clusters. We calculate binding energies using the PBE and HSE functionals with explicit van der Waals treatment and benchmark those against RPA cluster calculations. Our results indicate that molybdenum-carbides and -nitrides tend to bond tightly to graphene. Mo-oxides and -sulfides show small binding energies, indicating van der Waals bonding.

  8. ION COMPOSITION ELUCIDATION (ICE): A HIGH RESOLUTION MASS SPECTROMETRIC TECHNIQUE FOR IDENTIFYING COMPOUNDS IN COMPLEX MIXTURES

    EPA Science Inventory

    When tentatively identifying compounds in complex mixtures using mass spectral libraries, multiple matches or no plausible matches due to a high level of chemical noise or interferences can occur. Worse yet, most analytes are not in the libraries. In each case, Ion Composition El...

  9. Device for collecting chemical compounds and related methods

    DOEpatents

    Scott, Jill R.; Groenewold, Gary S.; Rae, Catherine

    2013-01-01

    A device for sampling chemical compounds from fixed surfaces and related methods are disclosed. The device may include a vacuum source, a chamber and a sorbent material. The device may utilize vacuum extraction to volatilize the chemical compounds from the fixed surfaces so that they may be sorbed by the sorbent material. The sorbent material may then be analyzed using conventional thermal desorption/gas chromatography/mass spectrometry (TD/GC/MS) instrumentation to determine presence of the chemical compounds. The methods may include detecting release and presence of one or more chemical compounds and determining the efficacy of decontamination. The device may be useful in collection and analysis of a variety of chemical compounds, such as residual chemical warfare agents, chemical attribution signatures and toxic industrial chemicals.

  10. High-throughput screening identifies compounds that enhance lentiviral transduction.

    PubMed

    Johnston, J M; Denning, G; Moot, R; Whitehead, D; Shields, J; Le Doux, J M; Doering, C B; Spencer, H T

    2014-12-01

    A difficulty in the field of gene therapy is the need to increase the susceptibility of hematopoietic stem cells (HSCs) to ex vivo genetic manipulation. To overcome this obstacle a high-throughput screen was performed to identify compounds that could enhance the transduction of target cells by lentiviral vectors. Of the 1280 compounds initially screened using the myeloid-erythroid-leukemic K562 cell line, 30 were identified as possible enhancers of viral transduction. Among the positive hits were known enhancers of transduction (camptothecin, etoposide and taxol), as well as the previously unidentified phorbol 12-myristate 13-acetate (PMA). The percentage of green fluorescent protein (GFP)-positive-expressing K562 cells was increased more than fourfold in the presence of PMA. In addition, the transduction of K562 cells with a lentiviral vector encoding fVIII was four times greater in the presence of PMA as determined by an increase in the levels of provirus in genetically modified cells. PMA did not enhance viral transduction of all cell types (for example, sca-1(+) mouse hematopoietic cells) but did enhance viral transduction of human bone marrow-derived CD34(+) cells. Notably, the percentage of GFP-positive CD34(+) cells was increased from 7% in the absence of PMA to greater than 22% in the presence of 1?nM PMA. PMA did not affect colony formation of CD34(+) cells or the expression of the hematopoietic markers CD34 and CD45. These data demonstrate that high-throughput screening can be used to identify compounds that increase the transduction efficiency of lentiviral vectors, identifying PMA as a potential enhancer of lentiviral HSC transduction. PMID:25231175

  11. How can Databases assist with the Prediction of Chemical Compounds?

    PubMed Central

    Schn, J Christian

    2014-01-01

    An overview is given on the ways databases can be employed to aid in the prediction of chemical compounds, in particular inorganic crystalline compounds. Methods currently employed and possible future approaches are discussed. PMID:26213422

  12. 30 CFR 47.21 - Identifying hazardous chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Identifying hazardous chemicals. 47.21 Section 47.21 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING HAZARD COMMUNICATION (HazCom) Hazard Determination § 47.21 Identifying hazardous chemicals. The operator must evaluate each chemical brought...

  13. Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions

    PubMed Central

    Huang, Tao; Cai, Yu-Dong; Chou, Kuo-Chen

    2011-01-01

    Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions. PMID:22220213

  14. 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...

  15. Structure-based drug design identifies polythiophenes as antiprion compounds.

    PubMed

    Herrmann, Uli S; Schtz, Anne K; Shirani, Hamid; Huang, Danzhi; Saban, Dino; Nuvolone, Mario; Li, Bei; Ballmer, Boris; slund, Andreas K O; Mason, Jeffrey J; Rushing, Elisabeth; Budka, Herbert; Nystrm, Sofie; Hammarstrm, Per; Bckmann, Anja; Caflisch, Amedeo; Meier, Beat H; Nilsson, K Peter R; Hornemann, Simone; Aguzzi, Adriano

    2015-08-01

    Prions cause transmissible spongiform encephalopathies for which no treatment exists. Prions consist of PrP(Sc), a misfolded and aggregated form of the cellular prion protein (PrP(C)). We explore the antiprion properties of luminescent conjugated polythiophenes (LCPs) that bind and stabilize ordered protein aggregates. By administering a library of structurally diverse LCPs to the brains of prion-infected mice via osmotic minipumps, we found that antiprion activity required a minimum of five thiophene rings bearing regularly spaced carboxyl side groups. Solid-state nuclear magnetic resonance analyses and molecular dynamics simulations revealed that anionic side chains interacted with complementary, regularly spaced cationic amyloid residues of model prions. These findings allowed us to extract structural rules governing the interaction between LCPs and protein aggregates, which we then used to design a new set of LCPs with optimized binding. The new set of LCPs showed robust prophylactic and therapeutic potency in prion-infected mice, with the lead compound extending survival by >80% and showing activity against both mouse and hamster prions as well as efficacy upon intraperitoneal administration into mice. These results demonstrate the feasibility of targeted chemical design of compounds that may be useful for treating diseases of aberrant protein aggregation such as prion disease. PMID:26246168

  16. Antiapicoplast and Gametocytocidal Screening To Identify the Mechanisms of Action of Compounds within the Malaria Box

    PubMed Central

    Bowman, Jessica D.; Merino, Emilio F.; Brooks, Carrie F.; Striepen, Boris; Carlier, Paul R.

    2014-01-01

    Malaria remains a significant infectious disease that causes millions of clinical cases and >800,000 deaths per year. The Malaria Box is a collection of 400 commercially available chemical entities that have antimalarial activity. The collection contains 200 drug-like compounds, based on their oral absorption and the presence of known toxicophores, and 200 probe-like compounds, which are intended to represent a broad structural diversity. These compounds have confirmed activities against the asexual intraerythrocytic stages of Plasmodium falciparum and low cytotoxicities, but their mechanisms of action and their activities in other stages of the parasite's life cycle remain to be determined. The apicoplast is considered to be a promising source of malaria-specific targets, and its main function during intraerythrocytic stages is to provide the isoprenoid precursor isopentenyl diphosphate, which can be used for phenotype-based screens to identify compounds targeting this organelle. We screened 400 compounds from the Malaria Box using apicoplast-targeting phenotypic assays to identify their potential mechanisms of action. We identified one compound that specifically targeted the apicoplast. Further analyses indicated that the molecular target of this compound may differ from those of the current antiapicoplast drugs, such as fosmidomycin. Moreover, in our efforts to elucidate the mechanisms of action of compounds from the Malaria Box, we evaluated their activities against other stages of the life cycle of the parasite. Gametocytes are the transmission stage of the malaria parasite and are recognized as a priority target in efforts to eradicate malaria. We identified 12 compounds that were active against gametocytes with 50% inhibitory concentration values of <1 ?M. PMID:24247137

  17. Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes

    PubMed Central

    Goldberg, Alexander A.; Richard, Vincent R.; Kyryakov, Pavlo; Bourque, Simon D.; Beach, Adam; Burstein, Michelle T.; Glebov, Anastasia; Koupaki, Olivia; Boukh-Viner, Tatiana; Gregg, Christopher; Juneau, Mylène; English, Ann M.; Thomas, David Y.; Titorenko, Vladimir I.

    2010-01-01

    In chronologically aging yeast, longevity can be extended by administering a caloric restriction (CR) diet or some small molecules. These life-extending interventions target the adaptable target of rapamycin (TOR) and cAMP/protein kinase A (cAMP/PKA) signaling pathways that are under the stringent control of calorie availability. We designed a chemical genetic screen for small molecules that increase the chronological life span of yeast under CR by targeting lipid metabolism and modulating housekeeping longevity pathways that regulate longevity irrespective of the number of available calories. Our screen identifies lithocholic acid (LCA) as one of such molecules. We reveal two mechanisms underlying the life-extending effect of LCA in chronologically aging yeast. One mechanism operates in a calorie availability-independent fashion and involves the LCA-governed modulation of housekeeping longevity assurance pathways that do not overlap with the adaptable TOR and cAMP/PKA pathways. The other mechanism extends yeast longevity under non-CR conditions and consists in LCA-driven unmasking of the previously unknown anti-aging potential of PKA. We provide evidence that LCA modulates housekeeping longevity assurance pathways by suppressing lipid-induced necrosis, attenuating mitochondrial fragmentation, altering oxidation-reduction processes in mitochondria, enhancing resistance to oxidative and thermal stresses, suppressing mitochondria-controlled apoptosis, and enhancing stability of nuclear and mitochondrial DNA. PMID:20622262

  18. Identifying organic nitrogen compounds in Rocky Mountain National Park aerosols

    NASA Astrophysics Data System (ADS)

    Beem, K. B.; Desyaterik, Y.; Ozel, M. Z.; Hamilton, J. F.; Collett, J. L.

    2010-12-01

    Nitrogen deposition is an important issue in Rocky Mountain National Park (RMNP). While inorganic nitrogen contributions to the ecosystems in this area have been studied, the sources of organic nitrogen are still largely unknown. To better understand the potential sources of organic nitrogen, filter samples were collected and analyzed for organic nitrogen species. Samples were collected in RMNP using a Thermo Fisher Scientific TSP (total suspended particulate) high-volume sampler with a PM2.5 impactor plate from April - November of 2008. The samples presented the opportunity to compare two different methods for identification of individual organic nitrogen species. The first type of analysis was performed with a comprehensive two dimensional gas chromatography (GCxGC) system using a nitrogen chemiluminescence detector (NCD). The filter samples were spiked with propanil in dichloromethane to use as an internal standard and were then extracted in water followed by solid phase extraction. The GCxGC system was comprised of a volatility based separation (DB5 column) followed by a polarity based separation (RXI-17 column). A NCD was used to specifically detect nitrogen compounds and remove the complex background matrix. Individual standards were used to identify peaks by comparing retention times. This method has the added benefit of an equimolar response for nitrogen so only a single calibration is needed for all species. In the second analysis, a portion of the same filter samples were extracted in DI water and analyzed with liquid chromatography coupled with mass spectroscopy (LC/MS). The separation was performed using a C18 column and a water-methanol gradient elution. Electrospray ionization into a time of flight mass spectrometer was used for detection. High accuracy mass measurement allowed unambiguous assignments of elemental composition of resulting ions. Positive and negative polarities were used since amines tend to show up in positive mode and nitrates in negative. The differences in the number of species and what species are identified between these two methods are important for planning future analyses of organic nitrogen compounds. In addition, these data provide new insight into the potential source of organic nitrogen in RMNP. Using the GCxGC method, 39 organic nitrogen species were detected and 20 were identified. Identified species include several types of amines and phenols. The LC/MS method identified several types of cresols, amines, and nitrates.

  19. Hedonic Judgments of Chemical Compounds Are Correlated with Molecular Size

    PubMed Central

    Zarzo, Manuel

    2011-01-01

    Different psychophysical works have reported that, when a wide range of odors is assessed, the hedonic dimension is the most salient. Hence, pleasantness is the most basic attribute of odor perception. Recent studies suggest that the molecular size of a given odorant is positively correlated with its hedonic character. This correlation was confirmed in the present study, but further basic molecular features affecting pleasantness were identified by means of multiple linear regression for the compounds contained in five chemical sets. For three of them, hedonic judgments are available in the literature. For a further two chemical sets, hedonic scores were estimated from odor character descriptions based on numerical profiles. Generally speaking, fairly similar equations were obtained for the prediction of hedonic judgments in the five chemical sets, with R2 values ranging from 0.46 to 0.71. The results suggest that larger molecules containing oxygen are more likely to be perceived as pleasant, while the opposite applies to carboxylic acids and sulfur compounds. PMID:22163815

  20. InChI - the worldwide chemical structure identifier standard

    PubMed Central

    2013-01-01

    Since its public introduction in 2005 the IUPAC InChI chemical structure identifier standard has become the international, worldwide standard for defined chemical structures. This article will describe the extensive use and dissemination of the InChI and InChIKey structure representations by and for the world-wide chemistry community, the chemical information community, and major publishers and disseminators of chemical and related scientific offerings in manuscripts and databases. PMID:23343401

  1. InChI - the worldwide chemical structure identifier standard.

    PubMed

    Heller, Stephen; McNaught, Alan; Stein, Stephen; Tchekhovskoi, Dmitrii; Pletnev, Igor

    2013-01-01

    Since its public introduction in 2005 the IUPAC InChI chemical structure identifier standard has become the international, worldwide standard for defined chemical structures. This article will describe the extensive use and dissemination of the InChI and InChIKey structure representations by and for the world-wide chemistry community, the chemical information community, and major publishers and disseminators of chemical and related scientific offerings in manuscripts and databases. PMID:23343401

  2. A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase

    PubMed Central

    Wong, Lai Hong; Unciti-Broceta, Asier; Spitzer, Michaela; White, Rachel; Tyers, Mike; Harrington, Lea

    2013-01-01

    Summary Telomerase comprises a reverse transcriptase and an internal RNA template that maintains telomeres in many eukaryotes, and it is a well-validated cancer target. However, there is a dearth of small molecules with efficacy against human telomerase in vivo. We developed a surrogate yeast high-throughput assay to identify human telomerase inhibitors. The reversibility of growth arrest induced by active human telomerase was assessed against a library of 678 compounds preselected for bioactivity in S. cerevisiae. Four of eight compounds identified reproducibly restored growth to strains expressing active human telomerase, and three of these four compounds also specifically inhibited purified human telomerase in vitro. These compounds represent probes for human telomerase function, and potential entry points for development of lead compounds against telomerase-positive cancers. PMID:23521791

  3. Analysis of Pfizer compounds in EPA's ToxCast chemicals-assay space.

    PubMed

    Shah, Falgun; Greene, Nigel

    2014-01-21

    The U.S. Environmental Protection Agency (EPA) launched the ToxCast program in 2007 with the goal of evaluating high-throughput in vitro assays to prioritize chemicals that need toxicity testing. Their goal was to develop predictive bioactivity signatures for toxic compounds using a set of in vitro assays and/or in silico properties. In 2009, Pfizer joined the ToxCast initiative by contributing 52 compounds with preclinical and clinical data for profiling across the multiple assay platforms available. Here, we describe the initial analysis of the Pfizer subset of compounds within the ToxCast chemical (n = 1814) and in vitro assay (n = 486) space. An analysis of the hit rate of Pfizer compounds in the ToxCast assay panel allowed us to focus our mining of assays potentially most relevant to the attrition of our compounds. We compared the bioactivity profile of Pfizer compounds to other compounds in the ToxCast chemical space to gain insights into common toxicity pathways. Additionally, we explored the similarity in the chemical and biological spaces between drug-like compounds and environmental chemicals in ToxCast and compared the in vivo profiles of a subset of failed pharmaceuticals having high similarity in both spaces. We found differences in the chemical and biological spaces of pharmaceuticals compared to environmental chemicals, which may question the applicability of bioactivity signatures developed exclusively based on the latter to drug-like compounds if used without prior validation with the ToxCast Phase-II chemicals. Finally, our analysis has allowed us to identify novel interactions for our compounds in particular with multiple nuclear receptors that were previously not known. This insight may help us to identify potential liabilities with future novel compounds. PMID:24328225

  4. 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

  5. Artificial neural network cascade identifies multi-P450 inhibitors in natural compounds

    PubMed Central

    Li, Zhangming; Li, Yan; Sun, Lu; Tang, Yun; Liu, Lanru

    2015-01-01

    Substantial evidence has shown that most exogenous substances are metabolized by multiple cytochrome P450 (P450) enzymes instead of by merely one P450 isoform. Thus, multi-P450 inhibition leads to greater drug-drug interaction risk than specific P450 inhibition. Herein, we innovatively established an artificial neural network cascade (NNC) model composed of 23 cascaded networks in a ladder-like framework to identify potential multi-P450 inhibitors among natural compounds by integrating 12 molecular descriptors into a P450 inhibition score (PIS). Experimental data reporting in vitro inhibition of five P450 isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) were obtained for 8,148 compounds from the Cytochrome P450 Inhibitors Database (CPID). The results indicate significant positive correlation between the PIS values and the number of inhibited P450 isoforms (Spearman’s ρ = 0.684, p < 0.0001). Thus, a higher PIS indicates a greater possibility for a chemical to inhibit the enzyme activity of at least three P450 isoforms. Ten-fold cross-validation of the NNC model suggested an accuracy of 78.7% for identifying whether a compound is a multi-P450 inhibitor or not. Using our NNC model, 22.2% of the approximately 160,000 natural compounds in TCM Database@Taiwan were identified as potential multi-P450 inhibitors. Furthermore, chemical similarity calculations suggested that the prevailing parent structures of natural multi-P450 inhibitors were alkaloids. Our findings show that dissection of chemical structure contributes to confident identification of natural multi-P450 inhibitors and provides a feasible method for virtually evaluating multi-P450 inhibition risk for a known structure. PMID:26719820

  6. Helping Students Distinguish between Mixtures and Chemical Compounds.

    ERIC Educational Resources Information Center

    Papageorgiou, George

    2002-01-01

    Describes a model demonstrating the difference between mixtures and chemical compounds in which two different colors of clay are used to represent two different elements. Makes connections to real world situations. (YDS)

  7. Malaria Parasite Metabolic Pathways (MPMP) Upgraded with Targeted Chemical Compounds.

    PubMed

    Ginsburg, Hagai; Abdel-Haleem, Alyaa M

    2016-01-01

    Malaria Parasite Metabolic Pathways (MPMP) is the website for the functional genomics of intraerythrocytic Plasmodium falciparum. All the published information about targeted chemical compounds has now been added. Users can find the drug target and publication details linked to a drug database for further information about the medicinal properties of each compound. PMID:26530861

  8. Chemical and Radiological Toxicity of Uranium and Its Compounds

    SciTech Connect

    Tansky, R.R.

    2001-07-26

    The concentration of uranyl nitrate required to deliver the radiation dose limit for soluble uranium compounds is larger than the toxicity-based concentration limits. Therefore, for soluble uranium compounds, health consequences of exposure are primarily due to their chemical toxicity. For insoluble compounds of uranium, health consequences (e.g., fibrosis and/or carcinogenesis of the lung) are primarily due to irradiation of pulmonary tissues from inhaled respirable particles.

  9. Systematic mining of generally recognized as safe (GRAS) flavor chemicals for bioactive compounds.

    PubMed

    Martinez-Mayorga, Karina; Peppard, Terry L; Lpez-Vallejo, Fabian; Yongye, Austin B; Medina-Franco, Jos L

    2013-08-01

    Bioactive food compounds can be both therapeutically and nutritionally relevant. Screening strategies are widely employed to identify bioactive compounds from edible plants. Flavor additives contained in the so-called FEMA GRAS (generally recognized as safe) list of approved flavoring ingredients is an additional source of potentially bioactive compounds. This work used the principles of molecular similarity to identify compounds with potential mood-modulating properties. The ability of certain GRAS molecules to inhibit histone deacetylase-1 (HDAC1), proposed as an important player in mood modulation, was assayed. Two GRAS chemicals were identified as HDAC1 inhibitors in the micromolar range, results similar to what was observed for the structurally related mood prescription drug valproic acid. Additional studies on bioavailability, toxicity at higher concentrations, and off-target effects are warranted. The methodology described in this work could be employed to identify potentially bioactive flavor chemicals present in the FEMA GRAS list. PMID:23848473

  10. LOSS OF ORGANIC CHEMICALS IN SOIL: PURE COMPOUND TREATABILITY STUDIES

    EPA Science Inventory

    Comprehensive screening data on the treatability of 32 organic chemicals in soil were developed. Of the evaluated chemicals, 22 were phenolic compounds. Aerobic batch laboratory microcosm experiments were conducted using two soils: an acidic clay soil with <1% organic matter and ...

  11. IDENTIFYING COMPOUNDS DESPITE CHROMATOGRAPHY LIMITATIONS: ORGANOPHOSPHATES IN TREATED SEWAGE

    EPA Science Inventory

    Highly concentrated extracts of sewage treatment plant (STP) effluents contain detectable
    levels of dozens of compounds resulting from human activities. Recent concern over use and
    disposal of Pharmaceuticals and Personal Care Products (PPCPS) (1) has stimulated interest ...

  12. Studying a Drug-like, RNA-Focused Small Molecule Library Identifies Compounds That Inhibit RNA Toxicity in Myotonic Dystrophy.

    PubMed

    Rzuczek, Suzanne G; Southern, Mark R; Disney, Matthew D

    2015-12-18

    There are many RNA targets in the transcriptome to which small molecule chemical probes and lead therapeutics are desired. However, identifying compounds that bind and modulate RNA function in cellulo is difficult. Although rational design approaches have been developed, they are still in their infancies and leave many RNAs "undruggable". In an effort to develop a small molecule library that is biased for binding RNA, we computationally identified "drug-like" compounds from screening collections that have favorable properties for binding RNA and for suitability as lead drugs. As proof-of-concept, this collection was screened for binding to and modulating the cellular dysfunction of the expanded repeating RNA (r(CUG)(exp)) that causes myotonic dystrophy type 1. Hit compounds bind the target in cellulo, as determined by the target identification approach Competitive Chemical Cross-Linking and Isolation by Pull-down (C-ChemCLIP), and selectively improve several disease-associated defects. The best compounds identified from our 320-member library are more potent in cellulo than compounds identified by high-throughput screening (HTS) campaigns against this RNA. Furthermore, the compound collection has a higher hit rate (9% compared to 0.01-3%), and the bioactive compounds identified are not charged; thus, RNA can be "drugged" with compounds that have favorable pharmacological properties. Finally, this RNA-focused small molecule library may serve as a useful starting point to identify lead "drug-like" chemical probes that affect the biological (dys)function of other RNA targets by direct target engagement. PMID:26414664

  13. A Chemical Screen Identifies Small Molecules that Regulate Hepcidin Expression

    PubMed Central

    Gaun, Vera; Patchen, Bonnie; Volovetz, Josephine; Zhen, Aileen W.; Andreev, Aleksandr; Pollastri, Michael P.; Fraenkel, Paula G.

    2014-01-01

    Hepcidin, a peptide hormone produced in the liver, decreases intestinal iron absorption and macrophage iron release via effects on ferroportin. Bone morphogenic protein and Stat3 signaling regulate Hepcidin's transcription. Hepcidin is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. To generate a tool for identifying small molecules that modulate Hepcidin expression, we stably transfected human hepatocytes (HepG2) cells with a reporter construct containing 2.7 kilobases of the human Hepcidin promoter upstream of a firefly reporter gene. We used high throughput methods to screen 10,169 chemicals in duplicate for their effect on Hepcidin expression and cell viability. Regulators were identified as chemicals that caused a change >3 standard deviations above or >1.5 standard deviations below the mean of the other chemicals (z-score >3 or <-1.5), while not adversely affecting cell viability, quantified by fluorescence assay. Following validation assays, we identified 16 chemicals in a broad range of functional classes that promote Hepcidin expression. All of the chemicals identified increased expression of bone morphogenic protein-dependent and/or Stat3-dependent genes, however none of them strongly increased phosphorylation of Smad1,5,8 or Stat3. PMID:24998898

  14. Compounds with species and cell type specific toxicity identified in a 2,000 compound drug screen of neural stem cells and rat mixed cortical neurons

    PubMed Central

    Malik, Nasir; Efthymiou, Anastasia G.; Mather, Karly; Chester, Nathaniel; Wang, Xiantao; Nath, Avindra; Rao, Mahendra S.; Steiner, Joseph P.

    2015-01-01

    Human primary neural tissue is a vital component for the quick and simple determination of chemical compound neurotoxicity in vitro. In particular, such tissue would be ideal for high-throughput screens that can be used to identify novel neurotoxic or neurotherapeutic compounds. We have previously established a high-throughput screening platform using human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) and neurons. In this study, we conducted a 2,000 compound screen with human NSCs and rat cortical cells to identify compounds that are selectively toxic to each group. Approximately 100 of the tested compounds showed specific toxicity to human NSCs. A secondary screen of a small subset of compounds from the primary screen on human iPSCs, NSC-derived neurons, and fetal astrocytes validated the results from >80% of these compounds with some showing cell specific toxicity. Amongst those compounds were several cardiac glycosides, all of which were selectively toxic to the human cells. As the screen was able to reliably identify neurotoxicants, many with species and cell-type specificity, this study demonstrates the feasibility of this NSC-driven platform for higher-throughput neurotoxicity screens. PMID:25454721

  15. Thermodynamic analysis of chemical compatibility of several compounds with Fe-Cr-Al alloys

    NASA Technical Reports Server (NTRS)

    Misra, Ajay K.

    1993-01-01

    Chemical compatibility between Fe-19.8Cr-4.8Al (weight percent), which is the base composition for the commercial superalloy MA956, and several carbides, borides, nitrides, oxides, and silicides was analyzed from thermodynamic considerations. The effect of addition of minor alloying elements, such as Ti, Y, and Y2O3, to the Fe-Cr-Al alloy on chemical compatibility between the alloy and various compounds was also analyzed. Several chemically compatible compounds that can be potential reinforcement materials and/or interface coating materials for Fe-Cr-Al based composites were identified.

  16. STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS

    PubMed Central

    Landsteiner, K.; Di Somma, A. A.

    1938-01-01

    With the view of making new types of chemicals accessible for investigations on drug hypersensitiveness, methods have been devised for sensitizing animals with diazomethane and mustard oil, two non-aromatic compounds. Guinea pigs have been sensitized to diazomethane, a substance of high reactivity and known to cause severe allergic effects in man. With the second substance, allylisothiocyanate, likewise capable of forming conjugates with substances in the animal body, sensitization effects have been obtained in man and in hogs. Sensitization in human beings was successful with one out of six individuals treated. The observations indicate species and individual differences as regards the ability to become sensitized to various chemical compounds. PMID:19870801

  17. 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…

  18. Consistency of systematic chemical identifiers within and between small-molecule databases

    PubMed Central

    2012-01-01

    Background Correctness of structures and associated metadata within public and commercial chemical databases greatly impacts drug discovery research activities such as quantitative structure–property relationships modelling and compound novelty checking. MOL files, SMILES notations, IUPAC names, and InChI strings are ubiquitous file formats and systematic identifiers for chemical structures. While interchangeable for many cheminformatics purposes there have been no studies on the inconsistency of these structure identifiers due to various approaches for data integration, including the use of different software and different rules for structure standardisation. We have investigated the consistency of systematic identifiers of small molecules within and between some of the commonly used chemical resources, with and without structure standardisation. Results The consistency between systematic chemical identifiers and their corresponding MOL representation varies greatly between data sources (37.2%-98.5%). We observed the lowest overall consistency for MOL-IUPAC names. Disregarding stereochemistry increases the consistency (84.8% to 99.9%). A wide variation in consistency also exists between MOL representations of compounds linked via cross-references (25.8% to 93.7%). Removing stereochemistry improved the consistency (47.6% to 95.6%). Conclusions We have shown that considerable inconsistency exists in structural representation and systematic chemical identifiers within and between databases. This can have a great influence especially when merging data and if systematic identifiers are used as a key index for structure integration or cross-querying several databases. Regenerating systematic identifiers starting from their MOL representation and applying well-defined and documented chemistry standardisation rules to all compounds prior to creating them can dramatically increase internal consistency. PMID:23237381

  19. Chemical reactions of organic compounds on clay surfaces.

    PubMed Central

    Soma, Y; Soma, M

    1989-01-01

    Chemical reactions of organic compounds including pesticides at the interlayer and exterior surfaces of clay minerals and with soil organic matter are reviewed. Representative reactions under moderate conditions possibly occurring in natural soils are described. Attempts have been made to clarify the importance of the chemical nature of molecules, their structures and their functional groups, and the Brnsted or Lewis acidity of clay minerals. PMID:2533556

  20. Chemical procedures to detect carcinogenic compound in domestic wastewater

    NASA Astrophysics Data System (ADS)

    S, Abd Manan T.; A, Malakahmad

    2013-06-01

    This review presents chemical methods to detect carcinogenic compound in wastewater. Atomic absorption spectroscopy (AAS), high performance liquid chromatography (HPLC) and gas chromatography mass spectroscopy (GCMS) and their alternative attached equipments were discussed. The application of each method is elaborated using related studies in the field.

  1. Loss of organic chemicals in soil: Pure compound treatability studies

    SciTech Connect

    Loehr, R.C.; Matthews, J.E.

    1992-01-01

    Comprehensive screening data on the treatability of 32 organic chemicals in soil were developed. Of the evaluated chemicals, 22 were phenolic compounds. Aerobic batch laboratory microcosm experiments were conducted using two soils: an acidic clay soil with <1 percent organic matter and a slightly basic sandy loam soil containing 3.25 percent organic matter. Loss rates were determined for the 32 chemicals with each soil and were higher in the basic soil. The loss rates were compared with chemical structure. Chlorophenols with chlorine substituted in the meta-position had greater half-lives and lower loss rates. Chemicals with a nitro group substituted in the phenol ring appeared to have a lower loss rate.

  2. Compound prioritization methods increase rates of chemical probe discovery in model organisms

    PubMed Central

    Wallace, Iain M; Urbanus, Malene L; Luciani, Genna M; Burns, Andrew R; Han, Mitchell KL; Wang, Hao; Arora, Kriti; Heisler, Lawrence E; Proctor, Michael; St. Onge, Robert P; Roemer, Terry; Roy, Peter J; Cummins, Carolyn L; Bader, Gary D; Nislow, Corey; Giaever, Guri

    2011-01-01

    SUMMARY Pre-selection of compounds that are more likely to induce a phenotype can increase the efficiency and reduce the costs for model organism screening. To identify such molecules, we screened ~81,000 compounds in S. cerevisiae and identified ~7,500 that inhibit cell growth. Screening these growth-inhibitory molecules across a diverse panel of model organisms resulted in an increased phenotypic hit-rate. This data was used to build a model to predict compounds that inhibit yeast growth. Empirical and in silico application of the model enriched the discovery of bioactive compounds in diverse model organisms. To demonstrate the potential of these molecules as lead chemical probes we used chemogenomic profiling in yeast and identified specific inhibitors of lanosterol synthase and of stearoyl-CoA 9-desaturase. As community resources, the ~7,500 growth-inhibitory molecules has been made commercially available and the computational model and filter used are provided. PMID:22035796

  3. Identifying non-point sources of endocrine active compounds and their biological impacts in freshwater lakes.

    PubMed

    Baker, Beth H; Martinovic-Weigelt, Dalma; Ferrey, Mark; Barber, Larry B; Writer, Jeffery H; Rosenberry, Donald O; Kiesling, Richard L; Lundy, James R; Schoenfuss, Heiko L

    2014-10-01

    Contaminants of emerging concern, particularly endocrine active compounds (EACs), have been identified as a threat to aquatic wildlife. However, little is known about the impact of EACs on lakes through groundwater from onsite wastewater treatment systems (OWTS). This study aims to identify specific contributions of OWTS to Sullivan Lake, Minnesota, USA. Lake hydrology, water chemistry, caged bluegill sunfish (Lepomis macrochirus), and larval fathead minnow (Pimephales promelas) exposures were used to assess whether EACs entered the lake through OWTS inflow and the resultant biological impact on fish. Study areas included two OWTS-influenced near-shore sites with native bluegill spawning habitats and two in-lake control sites without nearby EAC sources. Caged bluegill sunfish were analyzed for plasma vitellogenin concentrations, organosomatic indices, and histological pathologies. Surface and porewater was collected from each site and analyzed for EACs. Porewater was also collected for laboratory exposure of larval fathead minnow, before analysis of predator escape performance and gene expression profiles. Chemical analysis showed EACs present at low concentrations at each study site, whereas discrete variations were reported between sites and between summer and fall samplings. Body condition index and liver vacuolization of sunfish were found to differ among study sites as did gene expression in exposed larval fathead minnows. Interestingly, biological exposure data and water chemistry did not match. Therefore, although results highlight the potential impacts of seepage from OWTS, further investigation of mixture effects and life history factor as well as chemical fate is warranted. PMID:24974177

  4. Deactivation of explosive/shock-sensitive chemical compounds

    SciTech Connect

    Uzzo, T.K.

    1994-12-31

    A change has occurred in how the environmental industry and scientific community view the safe handling and environmentally-protective disposal of explosive, shock-sensitive, and highly reactive chemical compounds. Until recently, the most common disposal technology for the removal of explosive chemicals such as dry picric acid or peroxidized ether compounds, was open air detonation--usually conducted by a state or local bomb squad. With the advent of more stringent environmental regulations and a heightened awareness of environmental liability and personal health and safety, uncontrolled detonation is no longer the preferred disposal option. The new standard for deactivation technologies emphasizes on-site stabilization followed by off-site incineration. Utilizing remotely-actuated equipment mounted in an explosion containment chamber, the explosive/shock-sensitive chemicals are deactivated on-site by physical or chemical means, and then disposed of off-site via incineration. Not only does this methodology minimize the risk of releasing chemical contaminants to air, water, or land, it also provides an increased level of personal protection through remote handling within an enclosed chamber, and allows for complete, documented thermal destruction at a permitted TSDF. This paper discusses available deactivation technologies and considers their practical application in the field. It also provides some insight into the High Hazard Remediation industry, and summarizes the types of high hazard materials typically encountered in laboratory and field remediation settings.

  5. Identification and deactivation of explosive/shock-sensitive chemical compounds

    SciTech Connect

    Uzzo, T.K.; Hoverkamp, F.J.

    1995-12-31

    A change has occurred in how the environmental industry and scientific community view the safe handling and environmentally-protective disposal of explosive, shock-sensitive, and highly reactive chemical compounds. Until recently, the most common disposal technology for the removal of explosive chemicals such as dry picric acid or peroxidized ether compounds, was open air detonation usually conducted by a state or local bomb squad. With the advent of more stringent environmental regulations and a heightened awareness of environmental liability and personal health and safety, uncontrolled detonation is no longer the preferred disposal option. The new standard for deactivation technologies emphasizes on-site stabilization followed by off-site incineration. Utilizing remotely-actuated equipment mounted in an explosion containment chamber, the explosive/shock-sensitive chemicals are deactivated on-site by physical or chemical means, and then disposed of off-site via incineration. Not only does this methodology minimize the risk of releasing chemical contaminants to air, water, or land, it also provides an increased level of personal protection through remote handling within an enclosed chamber, and allows for complete, documented thermal destruction at a permitted TSDF. This paper discusses available deactivation technologies and considers their practical application in the field. It also provides some insight into the High Hazard Remediation industry, and summarizes the types of high hazard materials typically encountered in laboratory and field remediation settings.

  6. International chemical identifier for reactions (RInChI).

    PubMed

    Grethe, Guenter; Goodman, Jonathan M; Allen, Chad Hg

    2013-01-01

    The IUPAC International Chemical Identifier (InChI) provides a method to generate a unique text descriptor of molecular structures. Building on this work, we report a process to generate a unique text descriptor for reactions, RInChI. By carefully selecting the information that is included and by ordering the data carefully, different scientists studying the same reaction should produce the same RInChI. If differences arise, these are most likely the minor layers of the InChI, and so may be readily handled. RInChI provides a concise description of the key data in a chemical reaction, and will help enable the rapid searching and analysis of reaction databases. PMID:24152584

  7. GPU Accelerated Chemical Similarity Calculation for Compound Library Comparison

    PubMed Central

    Ma, Chao; Wang, Lirong; Xie, Xiang-Qun

    2012-01-01

    Chemical similarity calculation plays an important role in compound library design, virtual screening, and lead optimization. In this manuscript, we present a novel GPU-accelerated algorithm for all-vs-all Tanimoto matrix calculation and nearest neighbor search. By taking advantage of multi-core GPU architecture and CUDA parallel programming technology, the algorithm is up to 39 times superior to the existing commercial software that runs on CPUs. Because of the utilization of intrinsic GPU instructions, this approach is nearly 10 times faster than existing GPU-accelerated sparse vector algorithm, when Unity fingerprints are used for Tanimoto calculation. The GPU program that implements this new method takes about 20 minutes to complete the calculation of Tanimoto coefficients between 32M PubChem compounds and 10K Active Probes compounds, i.e., 324G Tanimoto coefficients, on a 128-CUDA-core GPU. PMID:21692447

  8. Chemical impurity produces extra compound eyes and heads in crickets

    SciTech Connect

    Walton, B.T.

    1981-04-03

    A chemical impurity isolated from commercially purchased acridine causes cricket embryos to develop extra compound eyes, branched antennae, extra antennae, and extra heads. Purified acridine does not produce similar duplications of cricket heads or head structures nor do the substituted acridines proflavine, acriflavine, or acridine orange. A dose-response relation exists such that the number and severity of abnormalities increase with increasing concentration of the teratogen.

  9. Quantum Chemical Study of the Thermochemical Properties of Organophosphorous Compounds.

    PubMed

    Khalfa, A; Ferrari, M; Fournet, R; Sirjean, B; Verdier, L; Glaude, P A

    2015-10-22

    Organophosphorous compounds are involved in many toxic compounds such as fungicides, pesticides, or chemical warfare nerve agents. The understanding of the decomposition chemistry of these compounds in the environment is largely limited by the scarcity of thermochemical data. Because of the high toxicity of many of these molecules, experimental determination of their thermochemical properties is very difficult. In this work, standard gas-phase thermodynamic data, i.e., enthalpies of formation (?fH298), standard entropies (S298), and heat capacities (Cp(T)), were determined using quantum chemical calculations and more specifically the CBS-QB3 composite method, which was found to be the best compromise between precision and calculation time among high accuracy composite methods. A large number of molecules was theoretically investigated, involving trivalent and pentavalent phosphorus atoms, and C, H, O, N, S, and F atoms. These data were used to propose 83 original groups, used in the semiempirical group contribution method proposed by Benson. Thanks to these latter group values, thermochemical properties of several nerve agents, common pesticides and herbicides have been evaluated. Bond dissociations energies (BDE), useful for the analysis the thermal stability of the compounds, were also determined in several molecules of interest. PMID:26434606

  10. Applications of swept-frequency acoustic interferometer for nonintrusive detection and identification of chemical warfare compounds

    SciTech Connect

    Sinha, D.N.; Springer, K.; Han, W.; Lizon, D.; Kogan, S.

    1997-12-01

    Swept-Frequency Acoustic Interferometry (SFAI) is a nonintrusive liquid characterization technique developed specifically for detecting and identifying chemical warfare (CW) compounds inside sealed munitions. The SFAI technique can rapidly (less than 20 seconds) and accurately determine sound speed and sound attenuation of a liquid inside a container over a wide frequency range (1 kHz-15 MHz). From the frequency-dependent sound attenuation measurement, liquid density is determined. These three physical properties are used to uniquely identify the CW compounds. In addition, various chemical relaxation processes in liquids and particle size distribution in emulsions can also be determined from the frequency-dependent attenuation measurement. The SFAI instrument is battery-operated and highly portable (< 6 lb.). The instrument has many potential application in industry ranging from sensitive detection (ppm level) of contamination to process control. The theory of the technique will be described and examples of several chemical industry applications will be presented.

  11. Integration of chemical and RNAi multiparametric profiles identifies triggers of intracellular mycobacterial killing.

    PubMed

    Sundaramurthy, Varadharajan; Barsacchi, Rico; Samusik, Nikolay; Marsico, Giovanni; Gilleron, Jerome; Kalaidzidis, Inna; Meyenhofer, Felix; Bickle, Marc; Kalaidzidis, Yannis; Zerial, Marino

    2013-02-13

    Pharmacological modulators of host-microbial interactions can in principle be identified using high-content screens. However, a severe limitation of this approach is the lack of insights into the mode of action of compounds selected during the primary screen. To overcome this problem, we developed a combined experimental and computational approach. We designed a quantitative multiparametric image-based assay to measure intracellular mycobacteria in primary human macrophages, screened a chemical library containing FDA-approved drugs, and validated three compounds for intracellular killing of M. tuberculosis. By integrating the multiparametric profiles of the chemicals with those of siRNAs from a genome-wide survey on endocytosis, we predicted and experimentally verified that two compounds modulate autophagy, whereas the third accelerates endosomal progression. Our findings demonstrate the value of integrating small molecules and genetic screens for identifying cellular mechanisms modulated by chemicals. Furthermore, selective pharmacological modulation of host trafficking pathways can be applied to intracellular pathogens beyond mycobacteria. PMID:23414754

  12. Reactivity of target compounds for chemical coal desulfurization. Technical report, March 1, 1994--May 31, 1994

    SciTech Connect

    Buchanan, D.H.; Amin, M.; Cunningham, R.; Galyen, J.; Ho, K.K.

    1994-09-01

    This project seeks to identify representative organosulfur compounds which are removed by known coal desulfurization reactions. Demineralized coals are solvent extracted and the extracts fractionated to concentrate organosulfur compounds for analysis by Gas Chromatography/Mass Spectroscopy. After sulfur compounds are characterized, the parent extracts are subjected to reactions previously shown to reduce the organic sulfur content of Illinois coals, fractionated and again analyzed for organosulfur content to determine if the identified compounds reacted during the chemical treatment. The original coal also will be subjected to chemical desulfurization, extraction, fractionation and analysis in order to correlate changes in organic sulfur content of the coal with reactions of specific sulfur compounds. These compounds can thus be reliably considered as target molecules for the next generation of desulfurization processes. Work during this quarter has shown that fractionation and chromatography of pyridine extracts to isolate suitable samples for GC/MS analysis, although time-consuming, appears to be better than direct toluene extraction in terms of providing a representative set of compounds for analysis. The toluene soluble fractions prepared by this route contain aromatic sulfur compounds and O, N, S-containing hetrocycles. A set of these compounds has been identified and their fate following desulfurization of the parent coal extracts is under investigation. Previously studied desulfurization reactions using the single electron transfer reagent, K/THF/naphthalene, and the reactive nickel boride reagent have been repeated and analyzed by GC/MS. SET and nickel boride reactions of the THF soluble portions of pyridine coal are currently in progress.

  13. Chemical Biology Drug Sensitivity Screen Identifies Sunitinib as Synergistic Agent with Disulfiram in Prostate Cancer Cells

    PubMed Central

    Ketola, Kirsi; Kallioniemi, Olli; Iljin, Kristiina

    2012-01-01

    Background Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects. Methods and Findings In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression. Conclusions Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell growth. Disulfiram-sunitinib combination was identified as one of the potent synergistic approaches. Since sunitinib alone has been reported to lack efficacy in prostate cancer clinical trials, our results provide a rationale for novel combinatorial approach to target prostate cancer more efficiently. PMID:23251544

  14. Neural network analysis of chemical compounds in nonrebreathing Fisher-344 rat breath

    NASA Astrophysics Data System (ADS)

    Sackett, Robert E.; Rogers, Steven K.; DeSimio, Martin P.; Raymer, James H.; Ruck, Dennis W.; Kabrisky, Matthew; Bleckmann, Charles A.

    1996-03-01

    This research applies statistical and artificial neural network analysis to data obtained from measurement of organic compounds in the breath of Fisher-344 rats. The Research Triangle Institute (RTI) developed a breath collection system for use with rates in order to collect and measure volatile organic compounds (VOCs) exhaled. The RTI study tested the hypothesis that VOCs, including endogenous compounds, in breath can serve as markers to exposure to various chemicals such as drugs, pesticides, or carcinogens. A comparative analysis of chromatograms showed that the administration of carbon tetrachloride dramatically altered the VOCs measured in breath; both the compounds detected and their concentrations were greatly impacted. This research demonstrated that neural network analysis and classification discriminates between exposure to carbon tetrachloride versus no exposure. It also identified the chemical compounds in rat breath that best discriminate between carbon tetrachloride exposure and either a vehicle control or no dose. For the data set analyzed, 100 percent classification accuracy was achieved in classifying cases of exposure versus no exposure. The top three marker compounds were identified. The results obtained show that neural networks can be effectively used to analyze complex chromatographic data.

  15. Identifying Bioaccumulative Halogenated Organic Compounds Using a Nontargeted Analytical Approach: Seabirds as Sentinels

    PubMed Central

    Millow, Christopher J.; Mackintosh, Susan A.; Lewison, Rebecca L.; Dodder, Nathan G.; Hoh, Eunha

    2015-01-01

    Persistent organic pollutants (POPs) are typically monitored via targeted mass spectrometry, which potentially identifies only a fraction of the contaminants actually present in environmental samples. With new anthropogenic compounds continuously introduced to the environment, novel and proactive approaches that provide a comprehensive alternative to targeted methods are needed in order to more completely characterize the diversity of known and unknown compounds likely to cause adverse effects. Nontargeted mass spectrometry attempts to extensively screen for compounds, providing a feasible approach for identifying contaminants that warrant future monitoring. We employed a nontargeted analytical method using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS) to characterize halogenated organic compounds (HOCs) in California Black skimmer (Rynchops niger) eggs. Our study identified 111 HOCs; 84 of these compounds were regularly detected via targeted approaches, while 27 were classified as typically unmonitored or unknown. Typically unmonitored compounds of note in bird eggs included tris(4-chlorophenyl)methane (TCPM), tris(4-chlorophenyl)methanol (TCPMOH), triclosan, permethrin, heptachloro-1'-methyl-1,2'-bipyrrole (MBP), as well as four halogenated unknown compounds that could not be identified through database searching or the literature. The presence of these compounds in Black skimmer eggs suggests they are persistent, bioaccumulative, potentially biomagnifying, and maternally transferring. Our results highlight the utility and importance of employing nontargeted analytical tools to assess true contaminant burdens in organisms, as well as to demonstrate the value in using environmental sentinels to proactively identify novel contaminants. PMID:26020245

  16. Identifying bioaccumulative halogenated organic compounds using a nontargeted analytical approach: seabirds as sentinels.

    PubMed

    Millow, Christopher J; Mackintosh, Susan A; Lewison, Rebecca L; Dodder, Nathan G; Hoh, Eunha

    2015-01-01

    Persistent organic pollutants (POPs) are typically monitored via targeted mass spectrometry, which potentially identifies only a fraction of the contaminants actually present in environmental samples. With new anthropogenic compounds continuously introduced to the environment, novel and proactive approaches that provide a comprehensive alternative to targeted methods are needed in order to more completely characterize the diversity of known and unknown compounds likely to cause adverse effects. Nontargeted mass spectrometry attempts to extensively screen for compounds, providing a feasible approach for identifying contaminants that warrant future monitoring. We employed a nontargeted analytical method using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GCGC/TOF-MS) to characterize halogenated organic compounds (HOCs) in California Black skimmer (Rynchops niger) eggs. Our study identified 111 HOCs; 84 of these compounds were regularly detected via targeted approaches, while 27 were classified as typically unmonitored or unknown. Typically unmonitored compounds of note in bird eggs included tris(4-chlorophenyl)methane (TCPM), tris(4-chlorophenyl)methanol (TCPMOH), triclosan, permethrin, heptachloro-1'-methyl-1,2'-bipyrrole (MBP), as well as four halogenated unknown compounds that could not be identified through database searching or the literature. The presence of these compounds in Black skimmer eggs suggests they are persistent, bioaccumulative, potentially biomagnifying, and maternally transferring. Our results highlight the utility and importance of employing nontargeted analytical tools to assess true contaminant burdens in organisms, as well as to demonstrate the value in using environmental sentinels to proactively identify novel contaminants. PMID:26020245

  17. Physical, chemical, and biological characteristics of compounds used in hydraulic fracturing.

    PubMed

    Stringfellow, William T; Domen, Jeremy K; Camarillo, Mary Kay; Sandelin, Whitney L; Borglin, Sharon

    2014-06-30

    Hydraulic fracturing (HF), a method to enhance oil and gas production, has become increasingly common throughout the U.S. As such, it is important to characterize the chemicals found in HF fluids to evaluate potential environmental fate, including fate in treatment systems, and human health impacts. Eighty-one common HF chemical additives were identified and categorized according to their functions. Physical and chemical characteristics of these additives were determined using publicly available chemical information databases. Fifty-five of the compounds are organic and twenty-seven of these are considered readily or inherently biodegradable. Seventeen chemicals have high theoretical chemical oxygen demand and are used in concentrations that present potential treatment challenges. Most of the HF chemicals evaluated are non-toxic or of low toxicity and only three are classified as Category 2 oral toxins according to standards in the Globally Harmonized System of Classification and Labeling of Chemicals; however, toxicity information was not located for thirty of the HF chemicals evaluated. Volatilization is not expected to be a significant exposure pathway for most HF chemicals. Gaps in toxicity and other chemical properties suggest deficiencies in the current state of knowledge, highlighting the need for further assessment to understand potential issues associated with HF chemicals in the environment. PMID:24853136

  18. Physical and Chemical Aspects of Stabilization of Compounds in Silk

    PubMed Central

    Pritchard, Eleanor M.; Dennis, Patrick B.; Omenetto, Fiorenzo; Naik, Rajesh R.; Kaplan, David L.

    2015-01-01

    The challenge of stabilization of small molecules and proteins has received considerable interest. The biological activity of small molecules can be lost as a consequence of chemical modifications, while protein activity may be lost due to chemical or structural degradation, such as a change in macromolecular conformation or aggregation. In these cases stabilization is required to preserve therapeutic and bioactivity efficacy and safety. In addition to use in therapeutic applications, strategies to stabilize small molecules and proteins also have applications in industrial processes, diagnostics, and consumer products like food and cosmetics. Traditionally, therapeutic drug formulation efforts have focused on maintaining stability during product preparation and storage. However, with growing interest in the fields of encapsulation, tissue engineering and controlled release drug delivery systems, new stabilization challenges are being addressed; the compounds or protein of interest must be stabilized during: (1) fabrication of the protein or small molecule loaded carrier, (2) device storage, and (3) for the duration of intended release needs in vitro or in vivo. We review common mechanisms of compound degradation for small molecules and proteins during biomaterial preparation (including tissue engineering scaffolds and drug delivery systems), storage and in vivo implantation. We also review the physical and chemical aspects of polymer-based stabilization approaches, with a particular focus on the stabilizing properties of silk fibroin biomaterials. PMID:22270942

  19. Identifying Unexpected Therapeutic Targets via Chemical-Protein Interactome

    PubMed Central

    Yang, Lun; Chen, Jian; Shi, Leming; Hudock, Michael P.; Wang, Kejian; He, Lin

    2010-01-01

    Drug medications inevitably affect not only their intended protein targets but also other proteins as well. In this study we examined the hypothesis that drugs that share the same therapeutic effect also share a common therapeutic mechanism by targeting not only known drug targets, but also by interacting unexpectedly on the same cryptic targets. By constructing and mining an Alzheimer's disease (AD) drug-oriented chemical-protein interactome (CPI) using a matrix of 10 drug molecules known to treat AD towards 401 human protein pockets, we found that such cryptic targets exist. We recovered from CPI the only validated therapeutic target of AD, acetylcholinesterase (ACHE), and highlighted several other putative targets. For example, we discovered that estrogen receptor (ER) and histone deacetylase (HDAC), which have recently been identified as two new therapeutic targets of AD, might already have been targeted by the marketed AD drugs. We further established that the CPI profile of a drug can reflect its interacting character towards multi-protein sets, and that drugs with the same therapeutic attribute will share a similar interacting profile. These findings indicate that the CPI could represent the landscape of chemical-protein interactions and uncover behind-the-scenes aspects of the therapeutic mechanisms of existing drugs, providing testable hypotheses of the key nodes for network pharmacology or brand new drug targets for one-target pharmacology paradigm. PMID:20221449

  20. Novel Chemical Suppressors of Long QT Syndrome Identified by an in vivo Functional Screen

    PubMed Central

    Peal, David S.; Mills, Robert W.; Lynch, Stacey N.; Mosley, Janet M.; Lim, Evi; Elllinor, Patrick T.; January, Craig T.; Peterson, Randall T.; Milan, David J.

    2010-01-01

    Background Genetic long QT (LQT) syndrome is a life-threatening disorder caused by mutations that result in prolongation of cardiac repolarization. Recent work has demonstrated that a zebrafish model of LQT syndrome faithfully recapitulates several features of human disease including prolongation of ventricular action potential duration (APD), spontaneous early after-depolarizations, and 2:1 atrioventricular (AV) block in early stages of development. Due to their transparency, small size, and absorption of small molecules from their environment, zebrafish are amenable to high throughput chemical screens. We describe a small molecule screen using the zebrafish KCNH2 mutant breakdance to identify compounds that can rescue the LQT type 2 phenotype. Methods and Results Zebrafish breakdance embryos were exposed to test compounds at 48 hours of development and scored for rescue of 2:1 AV block at 72 hours in a 96-well format. Only compounds that suppressed the LQT phenotype in three of three fish were considered hits. Screen compounds were obtained from commercially available small molecule libraries (Prestwick and Chembridge). Initial hits were confirmed with dose response testing and time course studies. Optical mapping using the voltage sensitive dye di-4 ANEPPS was performed to measure compound effects on cardiac APDs. Screening of 1200 small molecules resulted in the identification of flurandrenolide and 2-methoxy-N-(4-methylphenyl) benzamide (2-MMB) as compounds that reproducibly suppressed the LQT phenotype. Optical mapping confirmed that treatment with each compound caused shortening of ventricular APDs. Structure activity studies and steroid receptor knockdown suggest that flurandrenolide functions via the glucocorticoid signaling pathway. Conclusions Using a zebrafish model of LQT type 2 syndrome in a high throughput chemical screen, we have identified two compounds, flurandrenolide and the novel compound, 2-MMB, as small molecules that rescue the zebrafish LQTS 2 by shortening the ventricular action potential duration. We provide evidence that flurandrenolide functions via the glucocorticoid receptor mediated pathway. These two molecules, and future discoveries from this screen, should yield novel tools for the study of cardiac electrophysiology and may lead to novel therapeutics for human LQT patients. PMID:21098441

  1. Electrolytic photodissociation of chemical compounds by iron oxide photochemical diodes

    DOEpatents

    Somorjai, Gabor A. (Berkeley, CA); Leygraf, Christofer H. (Berkeley, CA)

    1985-01-01

    Chemical compounds can be dissociated by contacting the same with a p/n type semi-conductor photochemical diode having visible light as its sole source of energy. The photochemical diode consists of low cost, readily available materials, specifically polycrystalline iron oxide doped with silicon in the case of the n-type semi-conductor electrode, and polycrystalline iron oxide doped with magnesium in the case of the p-type electrode. So long as the light source has an energy greater than 2.2 electron volts, no added energy source is needed to achieve dissociation.

  2. Electrolytic photodissociation of chemical compounds by iron oxide electrodes

    DOEpatents

    Somorjai, Gabor A. (Berkeley, CA); Leygraf, Christofer H. (Berkeley, CA)

    1984-01-01

    Chemical compounds can be dissociated by contacting the same with a p/n type semi-conductor diode having visible light as its sole source of energy. The diode consists of low cost, readily available materials, specifically polycrystalline iron oxide doped with silicon in the case of the n-type semi-conductor electrode, and polycrystalline iron oxide doped with magnesium in the case of the p-type electrode. So long as the light source has an energy greater than 2.2 electron volts, no added energy source is needed to achieve dissociation.

  3. Indoor Volatile Organic Compounds and Chemical Sensitivity Reactions

    PubMed Central

    Win-Shwe, Tin-Tin; Arashidani, Keiichi; Kunugita, Naoki

    2013-01-01

    Studies of unexplained symptoms observed in chemically sensitive subjects have increased the awareness of the relationship between neurological and immunological diseases due to exposure to volatile organic compounds (VOCs). However, there is no direct evidence that links exposure to low doses of VOCs and neurological and immunological dysfunction. We review animal model data to clarify the role of VOCs in neuroimmune interactions and discuss our recent studies that show a relationship between chronic exposure of C3H mice to low levels of formaldehyde and the induction of neural and immune dysfunction. We also consider the possible mechanisms by which VOC exposure can induce the symptoms presenting in patients with a multiple chemical sensitivity. PMID:24228055

  4. Propolis volatile compounds: chemical diversity and biological activity: a review.

    PubMed

    Bankova, Vassya; Popova, Milena; Trusheva, Boryana

    2014-01-01

    Propolis is a sticky material collected by bees from plants, and used in the hive as building material and defensive substance. It has been popular as a remedy in Europe since ancient times. Nowadays, propolis use in over-the-counter preparations, "bio"-cosmetics and functional foods, etc., increases. Volatile compounds are found in low concentrations in propolis, but their aroma and significant biological activity make them important for propolis characterisation. Propolis is a plant-derived product: its chemical composition depends on the local flora at the site of collection, thus it offers a significant chemical diversity. The role of propolis volatiles in identification of its plant origin is discussed. The available data about chemical composition of propolis volatiles from different geographic regions are reviewed, demonstrating significant chemical variability. The contribution of volatiles and their constituents to the biological activities of propolis is considered. Future perspectives in research on propolis volatiles are outlined, especially in studying activities other than antimicrobial. PMID:24812573

  5. Propolis volatile compounds: chemical diversity and biological activity: a review

    PubMed Central

    2014-01-01

    Propolis is a sticky material collected by bees from plants, and used in the hive as building material and defensive substance. It has been popular as a remedy in Europe since ancient times. Nowadays, propolis use in over-the-counter preparations, “bio”-cosmetics and functional foods, etc., increases. Volatile compounds are found in low concentrations in propolis, but their aroma and significant biological activity make them important for propolis characterisation. Propolis is a plant-derived product: its chemical composition depends on the local flora at the site of collection, thus it offers a significant chemical diversity. The role of propolis volatiles in identification of its plant origin is discussed. The available data about chemical composition of propolis volatiles from different geographic regions are reviewed, demonstrating significant chemical variability. The contribution of volatiles and their constituents to the biological activities of propolis is considered. Future perspectives in research on propolis volatiles are outlined, especially in studying activities other than antimicrobial. PMID:24812573

  6. Chemical analysis of uranium compounds. [For Fe, Ni, fluoride

    SciTech Connect

    Jarabek, R.J.

    1987-10-01

    Research and development studies relating to gaseous diffusion plants require expertise in the analysis of uranium and its compounds. Synthesis of these compounds along with subsequent use necessitates a means of identification in addition to X-ray diffraction patterns normally obtained. Analyses for fluoride, nickel, and iron have been developed to supplement the analysis for U/sup +4/ and U total previously developed. The fluoride is determined by pyrolysis, with subsequent acid-base titration. Nickel is analyzed by precipitation with dimethylglyoxime following complexation of the uranium with citric acid. Iron is analyzed iodometrically following an ammonium hydroxide-ammonium carbonate separation process from the uranium. High precision and accuracy can be obtained on these procedures using low-cost, wet chemical methods. Expensive computerized equipment is not needed. Uranium compounds analyzed include UF/sub 5/, UO/sub 2/F/sub 2/, U/sub 3/O/sub 8/, and U/sub 2/F/sub 9/.

  7. A Chemical Rescue Screen Identifies a Plasmodium falciparum Apicoplast Inhibitor Targeting MEP Isoprenoid Precursor Biosynthesis

    PubMed Central

    Wu, Wesley; Herrera, Zachary; Ebert, Danny; Baska, Katie; Cho, Seok H.

    2014-01-01

    The apicoplast is an essential plastid organelle found in Plasmodium parasites which contains several clinically validated antimalarial-drug targets. A chemical rescue screen identified MMV-08138 from the “Malaria Box” library of growth-inhibitory antimalarial compounds as having specific activity against the apicoplast. MMV-08138 inhibition of blood-stage Plasmodium falciparum growth is stereospecific and potent, with the most active diastereomer demonstrating a 50% effective concentration (EC50) of 110 nM. Whole-genome sequencing of 3 drug-resistant parasite populations from two independent selections revealed E688Q and L244I mutations in P. falciparum IspD, an enzyme in the MEP (methyl-d-erythritol-4-phosphate) isoprenoid precursor biosynthesis pathway in the apicoplast. The active diastereomer of MMV-08138 directly inhibited PfIspD activity in vitro with a 50% inhibitory concentration (IC50) of 7.0 nM. MMV-08138 is the first PfIspD inhibitor to be identified and, together with heterologously expressed PfIspD, provides the foundation for further development of this promising antimalarial drug candidate lead. Furthermore, this report validates the use of the apicoplast chemical rescue screen coupled with target elucidation as a discovery tool to identify specific apicoplast-targeting compounds with new mechanisms of action. PMID:25367906

  8. Privacy-preserving search for chemical compound databases

    PubMed Central

    2015-01-01

    Background Searching for similar compounds in a database is the most important process for in-silico drug screening. Since a query compound is an important starting point for the new drug, a query holder, who is afraid of the query being monitored by the database server, usually downloads all the records in the database and uses them in a closed network. However, a serious dilemma arises when the database holder also wants to output no information except for the search results, and such a dilemma prevents the use of many important data resources. Results In order to overcome this dilemma, we developed a novel cryptographic protocol that enables database searching while keeping both the query holder's privacy and database holder's privacy. Generally, the application of cryptographic techniques to practical problems is difficult because versatile techniques are computationally expensive while computationally inexpensive techniques can perform only trivial computation tasks. In this study, our protocol is successfully built only from an additive-homomorphic cryptosystem, which allows only addition performed on encrypted values but is computationally efficient compared with versatile techniques such as general purpose multi-party computation. In an experiment searching ChEMBL, which consists of more than 1,200,000 compounds, the proposed method was 36,900 times faster in CPU time and 12,000 times as efficient in communication size compared with general purpose multi-party computation. Conclusion We proposed a novel privacy-preserving protocol for searching chemical compound databases. The proposed method, easily scaling for large-scale databases, may help to accelerate drug discovery research by making full use of unused but valuable data that includes sensitive information. PMID:26678650

  9. High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage

    PubMed Central

    Gergely, Szabolcs; Heged?s, Csaba; Lakatos, Petra; Kovcs, Katalin; Gspr, Renta; Csont, Tams; Virg, Lszl

    2015-01-01

    Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge's DIVERSet compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. The most effective compound proved protective in doxorubicin-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death and inhibited doxorubicin-induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of doxorubicin. In fact the compound identified as 3-[2-(4-ethylphenyl)-2-oxoethyl]-1,2-dimethyl-1H-3,1-benzimidazol-3-ium bromide was toxic to all tumor cell lines tested even without doxorubicine treatment. This benzimidazole compound may lead, through further optimalization, to the development of a drug candidate protecting the heart from doxorubicin-induced injury. PMID:26137186

  10. High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage.

    PubMed

    Gergely, Szabolcs; Heged?s, Csaba; Lakatos, Petra; Kovcs, Katalin; Gspr, Renta; Csont, Tams; Virg, Lszl

    2015-01-01

    Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge's DIVERSet compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. The most effective compound proved protective in doxorubicin-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death and inhibited doxorubicin-induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of doxorubicin. In fact the compound identified as 3-[2-(4-ethylphenyl)-2-oxoethyl]-1,2-dimethyl-1H-3,1-benzimidazol-3-ium bromide was toxic to all tumor cell lines tested even without doxorubicine treatment. This benzimidazole compound may lead, through further optimalization, to the development of a drug candidate protecting the heart from doxorubicin-induced injury. PMID:26137186

  11. Screening of Pharmacologically Active Small Molecule Compounds Identifies Antifungal Agents Against Candida Biofilms

    PubMed Central

    Watamoto, Takao; Egusa, Hiroshi; Sawase, Takashi; Yatani, Hirofumi

    2015-01-01

    Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using Candida albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC1280TM) using an antifungal susceptibility test (AST). To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF) cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and nine compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration. Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal candidiasis. PMID:26733987

  12. Chemically peculiar stars identified in large photometric surveys

    NASA Astrophysics Data System (ADS)

    Paunzen, Ernst; Netopil, Martin; Bernhard, Klaus; Hümmerich, Stefan

    2016-01-01

    The chemically peculiar (CP) stars of the upper main sequence are mainly characterized by strong overabundances of heavy elements. Two subgroups (CP2 and CP4) have strong local magnetic fields which make them interesting targets for astrophysical studies. This star group, in general, is often used for the analysis of stellar formation and evolution in the context of diffusion as well as meridional circulation. The overabundant elements in CP2/4 star atmospheres are concentrated into large spot regions that persist for decades to centuries. Periodic variations of the brightness, spectrum, and magnetic field are observed. The stars are slow rotators and it is believed that the slow rotation is owed to the strong magnetic field. Recent and future surveys that aim to obtain photometric time series are ideally suited to provide a detailed view of the stars' rotational behaviour. We present our efforts to analyze the rotational periods of CP stars and to identify new candidates in the Kepler, SuperWASP, and ASAS-3 surveys, but also in the photometric data that were extracted as valuable by-product of the STEREO satellite mission.

  13. Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation.

    PubMed

    Rovira, Meritxell; Huang, Wei; Yusuff, Shamila; Shim, Joong Sup; Ferrante, Anthony A; Liu, Jun O; Parsons, Michael J

    2011-11-29

    Pancreatic ?-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing ?-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of ?-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in ?-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis. PMID:22084084

  14. Chemical and sensory profiles of makgeolli, Korean commercial rice wine, from descriptive, chemical, and volatile compound analyses.

    PubMed

    Jung, Heeyong; Lee, Seung-Joo; Lim, Jeong Ho; Kim, Bum Keun; Park, Kee Jai

    2014-01-01

    The chemical and sensory profiles of 12 commercial samples of makgeolli, a Korean rice wine, were determined using descriptive sensory, chemical, and volatile components analyses. The sample wines were analysed for their titratable acidity, ethanol content, pH, Hunter colour value and total reducing sugars. The chemical compositions of the makgeolli samples were found to be significantly different. The volatile compounds were extracted with solid-phase microextraction and analysed by gas chromatography time-of-flight mass spectrometry. In all, 45 major volatile compounds, consisting of 33 esters, 8 alcohols, 1 aldehyde, 1 acid, 1 phenol and 1 terpene, were identified; each makgeolli sample included 28-35 volatile compounds. Based on principal component analysis of the sensory data, samples RW1, RW2, RW5, RW8 and RW12 were associated with roasted cereal, mouldy, bubbles, sweet and sour attributes; the other samples were associated with sensory attributes of yellowness, yeast, full body, turbidity, continuation, swallow, alcohol, fruit aroma and whiteness. PMID:24444985

  15. Identifying Sources of Volatile Organic Compounds and Aldehydes in a High Performance Building

    SciTech Connect

    Ortiz, Anna C.; Russell, Marion; Lee, Wen-Yee; Apte, Michael; Maddalena, Randy

    2010-09-20

    The developers of the Paharpur Business Center (PBC) and Software Technology Incubator Park in New Delhi, India offer an environmentally sustainable building with a strong emphasis on energy conservation, waste minimization and superior indoor air quality (IAQ). To achieve the IAQ goal, the building utilizes a series of air cleaning technologies for treating the air entering the building. These technologies include an initial water wash followed by ultraviolet light treatment and biolfiltration using a greenhouse located on the roof and numerous plants distributed throughout the building. Even with the extensive treatment of makeup air and room air in the PBC, a recent study found that the concentrations of common volatile organic compounds and aldehydes appear to rise incrementally as the air passes through the building from the supply to the exhaust. This finding highlights the need to consider the minimization of chemical sources in buildings in combination with the use of advanced air cleaning technologies when seeking to achieve superior IAQ. The goal of this project was to identify potential source materials for indoor chemicals in the PBC. Samples of building materials, including wood paneling (polished and unpolished), drywall, and plastic from a hydroponic drum that was part of the air cleaning system, were collected from the building for testing. All materials were collected from the PBC building and shipped to the Lawrence Berkeley National Laboratory (LBNL) for testing. The materials were pre-conditioned for two different time periods before measuring material and chemical specific emission factors for a range of VOCs and Aldehydes. Of the six materials tested, we found that the highest emitter of formaldehyde was new plywood paneling. Although polish and paint contribute to some VOC emissions, the main influence of the polish was in altering the capacity of the surface to accumulate formaldehyde. Neither the new nor aged polish contributed significantly to formaldehyde emissions. The VOC emission stream (excluding formaldehyde) was composed of up to 18 different chemicals and the total VOC emissions ranged in magnitude from 7 mu g/m2/h (old wood with old polish) to>500 mu g/m2/h (painted drywall). The formaldehyde emissions from drywall and old wood with either new or old polish were ~;;15 mu g/m2/h while the new wood material emitted>100 mu g/m2/h. However, when the projected surface area of each material in the building was considered, the new wood, old wood and painted drywall material all contributed substantially to the indoor formaldehyde loading while the coatings contributed primarily to the VOCs.

  16. New Compound Sets Identified from High Throughput Phenotypic Screening Against Three Kinetoplastid Parasites: An Open Resource

    PubMed Central

    Peña, Imanol; Pilar Manzano, M.; Cantizani, Juan; Kessler, Albane; Alonso-Padilla, Julio; Bardera, Ana I.; Alvarez, Emilio; Colmenarejo, Gonzalo; Cotillo, Ignacio; Roquero, Irene; de Dios-Anton, Francisco; Barroso, Vanessa; Rodriguez, Ana; Gray, David W.; Navarro, Miguel; Kumar, Vinod; Sherstnev, Alexander; Drewry, David H.; Brown, James R.; Fiandor, Jose M.; Julio Martin, J.

    2015-01-01

    Using whole-cell phenotypic assays, the GlaxoSmithKline high-throughput screening (HTS) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted, and the potential for non-specific cytotoxicity determined. Hit compounds were chemically clustered and triaged for desirable physicochemical properties. The hypothetical biological target space covered by these diversity sets was investigated through bioinformatics methodologies. Consequently, three anti-kinetoplastid chemical boxes of ~200 compounds each were assembled. Functional analyses of these compounds suggest a wide array of potential modes of action against kinetoplastid kinases, proteases and cytochromes as well as potential host–pathogen targets. This is the first published parallel high throughput screening of a pharma compound collection against kinetoplastids. The compound sets are provided as an open resource for future lead discovery programs, and to address important research questions. PMID:25740547

  17. A Yeast/Drosophila Screen to Identify New Compounds Overcoming Frataxin Deficiency

    PubMed Central

    Seguin, Alexandra; Monnier, Véronique; Palandri, Amandine; Bihel, Frédéric; Rera, Michael; Schmitt, Martine; Camadro, Jean-Michel; Tricoire, Hervé; Lesuisse, Emmanuel

    2015-01-01

    Friedreich's ataxia (FA) is a rare neurodegenerative disease which is very debilitating for the patients who progressively lose their autonomy. The lack of efficient therapeutic treatment of the disease strongly argues for urgent need to search for new active compounds that may stop the progression of the disease or prevent the appearance of the symptoms when the genetic defect is diagnosed early enough. In the present study, we used a yeast strain with a deletion of the frataxin homologue gene as a model of FA cells in a primary screen of two chemical libraries, a fraction of the French National Chemical Library (5500 compounds) and the Prestwick collection (880 compounds). We ran a secondary screen on Drosophila melanogaster flies expressing reduced levels of frataxin during larval development. Half of the compounds selected in yeast appeared to be active in flies in this developmental paradigm, and one of the two compounds with highest activities in this assay partially rescued the heart dilatation phenotype resulting from heart specific depletion of frataxin. The unique complementarity of these two frataxin-deficient models, unicellular and multicellular, appears to be very efficient to select new compounds with improved selectivity, bringing significant perspectives towards improvements in FA therapy. PMID:26523199

  18. Volatile compounds emitted by Triatoma dimidiata, a vector of Chagas disease: chemical analysis and behavioural evaluation.

    PubMed

    May-Concha, I; Rojas, J C; Cruz-Lpez, L; Millar, J G; Ramsey, J M

    2013-06-01

    In this study, we evaluated the responses of Triatoma dimidiata Latreille (Hemiptera: Reduviidae) to volatiles emitted by conspecific females, males, mating pairs and metasternal gland (MG) extracts with a Y-tube olfactometer. The volatile compounds released by mating pairs and MGs of T. dimidiata were identified using solid-phase microextraction and coupled gas chromatography-mass spectrometry (GC-MS). Females were not attracted to volatiles emitted by males or MG extracts; however, they preferred clean air to their own volatiles or those from mating pairs. Males were attracted to volatiles emitted by males, females, mating pairs, pairs in which the male had the MG orifices occluded or MG extracts of both sexes. However, males were not attracted to volatiles emitted by pairs in which the female had the MG orifices occluded. The chemical analyses showed that 14 and 15 compounds were detected in the headspace of mating pairs and MG, respectively. Most of the compounds identified from MG except for isobutyric acid were also detected in the headspace of mating pairs. Both females and males were attracted to octanal and 6-methyl-5-hepten-2-one, and males were attracted to 3,5-dimethyl-2-hexanol. Males but not females were attracted to a seven-compound blend, formulated from compounds identified in attractive MG extracts. PMID:23205718

  19. Chemical characterisation of semi-volatile and aerosol compounds from the photooxidation of toluene and NOx

    NASA Astrophysics Data System (ADS)

    White, Stephen J.; Jamie, Ian M.; Angove, Dennys E.

    2014-02-01

    The chemical composition of a gas phase and secondary organic aerosol (SOA) mixture from toluene photooxidation in NOx was determined. Aerosol from toluene photooxidation was generated in a smog chamber and was collected onto glass fibre filters along with those gas phase compounds which adhered to the filter. The filter bound organic material was extracted, derivatised with O-2,3,4,5,6-pentafluorobenzyl hydroxylamine (PFBHA) and N,O-bistrimethylsilyl-trifluoroacetamide (BSTFA), then analysed using gas chromatography-mass spectrometry (GC-MS). Compound identification was aided by the use of isotopically-labelled toluene. The effect of humidity on product formation was investigated by raising water vapour concentration in one experiment. Sixty compounds were identified, of which twenty had not been identified from toluene photooxidation previously. Small carboxylic acids and dicarbonyls provided the highest proportion of identifiable compounds by relative response. The use of water to extract the filter samples resulted in much higher relative responses for oxocarboxylic acids, such as glyoxylic acid and pyruvic acid, than has been observed in previous studies. The formation of levulinic acid was determined to be due to the reaction of water with aromatic photooxidation products in the gas phase or particle phase of the chamber experiment. Nuclear magnetic resonance (NMR) was used to determine the functional groups of water-extracted organic material, which indicated that the water-soluble components were comprised of compounds which contain similar functional groups, primarily alcohols and carboxylic acids.

  20. Efficacy of potential chemical control compounds for removing invasive American bullfrogs (Rana catesbeiana).

    PubMed

    Witmer, Gary W; Snow, Nathan P; Moulton, Rachael S

    2015-01-01

    Invasive American bullfrogs [Rana catesbeiana (Lithobates catesbeianus)] are outcompeting and predating on native biota and contributing to reductions in biodiversity worldwide. Current methods for controlling American bullfrogs are incapable of stopping their expansion, thus more cost-effective and broadly applicable methods are needed. Although chemical control compounds have been identified as effective for removing other invasive amphibians, none have been tested for American bullfrogs. Our objective was to expand on previous research and test the efficacy of 10 potential chemical control compounds for removing invasive American bullfrogs. After a dermal spray-application of 4ml, we found 3 compounds (i.e., chloroxylenol, rotenone with permethrin, and caffeine) at 5-10% concentrations in water were 100% lethal for adult American bullfrogs. Chloroxylenol and rotenone with permethrin were fast acting with time-to-death <2h. This research presents a first-step toward incorporating chemical control as part of integrated pest management strategy for controlling invasive American bullfrogs. Follow-up studies on delivery systems and reducing non-target hazards should ensue with these compounds to confirm their effectiveness and safety for removing invasive American bullfrogs. PMID:26389022

  1. Cyclodextrin-based chemical microsensors for Volatile Organic Compounds (VOCs)

    SciTech Connect

    Li, DeQuan

    1998-12-31

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). This project addressed the development of surface-acoustic-wave (SAW)-based chemical sensors for remote, real-time sensing in air, groundwater, and possibly soil, of chlorinated and aromatic hydrocarbons using innovative molecular self-assembly techniques. Our goal is parts per billion (ppb) sensitivity to specific aromatic and chlorinated hydrocarbons using cyclodextrin as the selective layer of a SAW-based mass sensor. We have demonstrated that SAW sensors can differentiate between compounds with similar composition, structure, and polarity. These efforts, however, can be enhanced by using sensor arrays and smart data processing systems. Secondly, ionic interactions provide a convenient way to fabricate thin films for sensor applications. The potential of these thin films for sensor applications is currently being evaluated. 3 figs.

  2. A chemical genetic approach identifies piperazine antipsychotics as promoters of CNS neurite growth on inhibitory substrates

    PubMed Central

    Johnstone, AL; Reierson, GW; Smith, RP; Goldberg, JL; Lemmon, VP; Bixby, JL

    2012-01-01

    Injury to the central nervous system (CNS) can result in lifelong loss of function due in part to the regenerative failure of CNS neurons. Inhibitory proteins derived from myelin and the astroglial scar are major barriers for the successful regeneration of injured CNS neurons. Previously, we described the identification of a novel compound, F05, which promotes neurite growth from neurons challenged with inhibitory substrates in vitro, and promotes axonal regeneration in vivo (Usher et al., 2010). To identify additional regeneration-promoting compounds, we used F05-induced gene expression profiles to query the Broad Institute Connectivity Map, a gene expression database of cells treated with >1,300 compounds. Despite no shared chemical similarity, F05-induced changes in gene expression were remarkably similar to those seen with a group of piperazine phenothiazine antipsychotics (PhAPs). In contrast to antipsychotics of other structural classes, PhAPs promoted neurite growth of CNS neurons challenged with two different glial derived inhibitory substrates. Our pharmacological studies suggest a mechanism whereby PhAPs promote growth through antagonism of calmodulin signaling, independent of dopamine receptor antagonism. These findings shed light on mechanisms underlying neurite-inhibitory signaling, and suggest that clinically approved antipsychotic compounds may be repurposed for use in CNS injured patients. PMID:22561309

  3. A chemical genetic approach identifies piperazine antipsychotics as promoters of CNS neurite growth on inhibitory substrates.

    PubMed

    Johnstone, Andrea L; Reierson, Gillian W; Smith, Robin P; Goldberg, Jeffrey L; Lemmon, Vance P; Bixby, John L

    2012-06-01

    Injury to the central nervous system (CNS) can result in lifelong loss of function due in part to the regenerative failure of CNS neurons. Inhibitory proteins derived from myelin and the astroglial scar are major barriers for the successful regeneration of injured CNS neurons. Previously, we described the identification of a novel compound, F05, which promotes neurite growth from neurons challenged with inhibitory substrates in vitro, and promotes axonal regeneration in vivo (Usher et al., 2010). To identify additional regeneration-promoting compounds, we used F05-induced gene expression profiles to query the Broad Institute Connectivity Map, a gene expression database of cells treated with >1300 compounds. Despite no shared chemical similarity, F05-induced changes in gene expression were remarkably similar to those seen with a group of piperazine phenothiazine antipsychotics (PhAPs). In contrast to antipsychotics of other structural classes, PhAPs promoted neurite growth of CNS neurons challenged with two different glial derived inhibitory substrates. Our pharmacological studies suggest a mechanism whereby PhAPs promote growth through antagonism of calmodulin signaling, independent of dopamine receptor antagonism. These findings shed light on mechanisms underlying neurite-inhibitory signaling, and suggest that clinically approved antipsychotic compounds may be repurposed for use in CNS injured patients. PMID:22561309

  4. [Physical, chemical and bioactive compounds of tree tomato (Cyphomandra betacea)].

    PubMed

    Torres, Alexia

    2012-12-01

    Tree tomato (Cyphomandra betacea) is appreciated for its excellent nutritional qualities, being considered a good source of antioxidants compounds, calcium, phosphorus, potassium and iron, sugars, organic acids, pectins and flavonoids. In this study, were evaluated physical parameters (weight, size, compression strength and humidity) and chemical (degrees Brix, titratable acidity, pH, protein, dietary fiber, ash, minerals and their bioaccesibility, pectin, antioxidants compounds) of the fruit from the Aragua State, Venezuela, as a contribution to stimulate and diversify the consumption of the tree tomato. The characterization showed that the fruits were at the ripening stage for consumption (degrees Brix 10.51, pH 3.5, acidity 0.02 g/100ml and 4.32 Kgf/cm2 compression strength) gave a yield of 74% pulp. The analytical results of the ripped pulp showed a content of 30 Kcal/100 g, dietary fiber (4.10 g/100 g), and minerals such as phosphorous, calcium, magnesium, potassium and iron (331.32, 21.25, 21.18, 17.03 and 7.44 mg/100 g, respectively). Bioaccesibility values of 6.71 and 1.86% were reported for calcium and iron. The extracted pectin (1.00 g/100 g) was classified as high methoxyl with high degree of esterification. The antioxidant capacity of the ripped pulp (EC50 of 165.00 g/g DPPH and reducing power of 0.07 mmol Fe +2/100 g), could be attributed to the presence of ascorbic acid (23.32 mg/100 g), lycopene (1.22 mg/100 g), and phenolic compounds (1.39 mg GAE/g), anthocyanins (0.29 mg cyanidin/g) and tannins (0.40 mg catechin/100 g).The results obtained encourage the nutritional benefits and suggest applications as a functional ingredient in food product development. PMID:24020259

  5. Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

    PubMed Central

    2014-01-01

    Background Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates. Results We studied the composition and fermentability of 24 different biomass hydrolysates. To create diversity, the 24 hydrolysates were prepared from six different biomass types, namely sugar cane bagasse, corn stover, wheat straw, barley straw, willow wood chips and oak sawdust, and with four different pretreatment methods, i.e. dilute acid, mild alkaline, alkaline/peracetic acid and concentrated acid. Their composition and that of fermentation samples generated with these hydrolysates were analyzed with two GC-MS methods. Either ethyl acetate extraction or ethyl chloroformate derivatization was used before conducting GC-MS to prevent sugars are overloaded in the chromatograms, which obscure the detection of less abundant compounds. Using multivariate PLS-2CV and nPLS-2CV data analysis models, potential inhibitors were identified through establishing relationship between fermentability and composition of the hydrolysates. These identified compounds were tested for their effects on the growth of the model yeast, Saccharomyces. cerevisiae CEN.PK 113-7D, confirming that the majority of the identified compounds were indeed inhibitors. Conclusion Inhibitory compounds in lignocellulosic biomass hydrolysates were successfully identified using a non-targeted systematic approach: metabolomics. The identified inhibitors include both known ones, such as furfural, HMF and vanillin, and novel inhibitors, namely sorbic acid and phenylacetaldehyde. PMID:24655423

  6. High-Throughput Chemical Screens Identify Disulfiram as an Inhibitor of Human Glioblastoma Stem Cells

    PubMed Central

    Hothi, Parvinder; Martins, Timothy J.; Chen, LiPing; Deleyrolle, Loic; Yoon, Jae-Geun; Reynolds, Brent; Foltz, Greg

    2012-01-01

    Glioblastoma Multiforme (GBM) continues to have a poor patient prognosis despite optimal standard of care. Glioma stem cells (GSCs) have been implicated as the presumed cause of tumor recurrence and resistance to therapy. With this in mind, we screened a diverse chemical library of 2,000 compounds to identify therapeutic agents that inhibit GSC proliferation and therefore have the potential to extend patient survival. High-throughput screens (HTS) identified 78 compounds that repeatedly inhibited cellular proliferation, of which 47 are clinically approved for other indications and 31 are experimental drugs. Several compounds (such as digitoxin, deguelin, patulin and phenethyl caffeate) exhibited high cytotoxicity, with half maximal inhibitory concentrations (IC50) in the low nanomolar range. In particular, the FDA approved drug for the treatment of alcoholism, disulfiram (DSF), was significantly potent across multiple patient samples (IC50 of 31.1 nM). The activity of DSF was potentiated by copper (Cu), which markedly increased GSC death. DSFCu inhibited the chymotrypsin-like proteasomal activity in cultured GSCs, consistent with inactivation of the ubiquitin-proteasome pathway and the subsequent induction of tumor cell death. Given that DSF is a relatively non-toxic drug that can penetrate the blood-brain barrier, we suggest that DSF should be tested (as either a monotherapy or as an adjuvant) in pre-clinical models of human GBM. Data also support targeting of the ubiquitin-proteasome pathway as a therapeutic approach in the treatment of GBM. PMID:23165409

  7. Sensitivity of animals to chemical compounds links to metabolic rate.

    PubMed

    Baas, Jan; Kooijman, Sebastiaan A L M

    2015-04-01

    Ecotoxicological studies have shown considerable variation in species sensitivity for chemical compounds, but general patterns in sensitivity are still not known. A better understanding of this sensitivity is important in the context of environmental risk assessment but also in a more general ecological and evolutionary one. We investigated the metabolic rate or more precise the specific somatic maintenance (expressed in J cm(-3) d(-1), at a standardised body temperature of 20 °C) on the sensitivity of a species to chemical poisoning. The sensitivity of a species was expressed in terms of its threshold concentration for survival, the no effect concentrations (NEC, in µmol/L). Somatic maintenance data were based on the 'add-my-pet' database hosted by the VU University of Amsterdam. NECs were derived from the US-EPA ECOTOX database. We focussed on four pesticides; two that need a metabolic activation, Chlorpyrifos and Malathion, and two without metabolic activation, carbofuran and carbaryl. All four pesticides showed a similar response: a strong negative correlation between the specific somatic maintenance and the NEC. We discuss possible explanations, deviations and ecological implications. PMID:25564013

  8. Is the toxicity of pesticide mixtures on river biofilm accounted for solely by the major compounds identified?

    PubMed

    Kim Tiam, Sandra; Morin, Soizic; Bonet, Berta; Guasch, Helena; Feurtet-Mazel, Agns; Eon, Mlissa; Gonzalez, Patrice; Mazzella, Nicolas

    2015-03-01

    Comparative effects of long-term exposure to Polar Organic Chemical Integrative Sampler (POCIS) extracts (PE) and to a reconstituted mixture based on the major compounds quantified in the PE were evaluated on river biofilm communities. The study aimed to characterize the effects of long-term and low-dose exposure to pesticides on natural biofilm communities and to evaluate if the effects due to PE exposure could be explained solely by the major compounds identified in the extracts. Biofilms from an uncontaminated site were exposed in artificial channels to realistic environmental concentrations using diluted PE, with the 12 major compounds quantified in the extracts (Mix) or with water not containing pesticides (Ctr). Significant differences between biofilms exposed to pesticides or not were observed with regard to diatom density, biomass (dry weight and ash-free dry mass), photosynthetic efficiency (?psII) and antioxidant enzyme activities. After 14days of exposure to the different treatments, the observed trend towards a decrease of mean diatom cell biovolumes in samples exposed to pesticides was related to the control biofilms' higher relative abundance of large species like Cocconeis placentula or Amphora copulata and lower relative abundance of small species like Eolimna minima compared to the contaminated ones. Principal component analyses clearly separated contaminated (PE and Mix) from non-contaminated (Ctr) biofilms; on the contrary, the analyses did not reveal separation between biofilms exposed to PE or to the 12 major compounds identified in the extract. PMID:25077658

  9. A framework for identifying characteristic odor compounds in municipal wastewater effluent.

    PubMed

    Agus, Eva; Zhang, Lifeng; Sedlak, David L

    2012-11-15

    Municipal wastewater often contains trace amounts of organic compounds that can compromise aesthetics of drinking water and undermine public confidence if a small amount of effluent enters the raw water source of a potable water supply. To efficiently identify compounds responsible for odors in wastewater effluent, an analytical framework consisting of gas chromatography with mass spectrometry (GC-MS) and gas chromatography with olfactometry detection (GC-Olf) coupled with flavor profile analysis (FPA) was used to identify and monitor compounds that could affect the aesthetics of drinking water. After prioritizing odor peaks detected in wastewater effluent by GC-Olf, the odorous components were tentatively identified using retention indices, mass spectra and odor descriptors. Wastewater effluent samples were typically dominated by earthy-musty odors with additional odors in the amine, sulfidic and fragrant categories. 2,4,6-trichloroanisole (246TCA), geosmin and 2-methylisoborneol (2MIB) were the main sources of the earthy/musty odors in wastewater effluent. The other odors were attributable to a suite of compounds, which were detected in some but not all of the wastewater effluents at levels well in excess of their odor thresholds. In most cases, the identities of odorants were confirmed using authentic standards. The fate of these odorous compounds, including 2-pyrrolidone, methylnaphthalenes, vanillin and 5-hydroxyvanillin (5-OH-vanillin), should be considered in future studies of water systems that receive effluent from upstream sources. PMID:22981490

  10. Method for halogenating or radiohalogenating a chemical compound

    DOEpatents

    Kabalka, George W.

    2006-05-09

    A method for obtaining a halogenated organic compound, whereby an organotrifluoroborate compound is reacted with a halide ion in the presence of an oxidizing agent to produce the corresponding halogenated organic compound. The method may be used for producing radiohalogenated organic compounds.

  11. Next-generation NAMPT inhibitors identified by sequential high-throughput phenotypic chemical and functional genomic screens

    PubMed Central

    Matheny, Christina J.; Wei, Michael C.; Bassik, Michael C.; Donnelly, Alicia J.; Kampmann, Martin; Iwasaki, Masayuki; Piloto, Obdulio; Solow-Cordero, David E.; Bouley, Donna M.; Rau, Rachel; Brown, Patrick; McManus, Michael T.; Weissman, Jonathan S.; Cleary, Michael L.

    2013-01-01

    Summary Phenotypic high-throughput chemical screens allow for discovery of small molecules that modulate complex phenotypes and provide lead compounds for novel therapies; however, identification of the mechanistically relevant targets remains a major experimental challenge. We report the application of sequential unbiased high-throughput chemical and ultracomplex shRNA screens to identify a novel class of inhibitors that target nicotinamide phosphoribosyl transferase (NAMPT), a rate-limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a crucial cofactor in many biochemical processes. The lead compound STF-118804 is a highly specific NAMPT inhibitor, improves survival in an orthotopic xenotransplant model of high-risk acute lymphoblastic leukemia, and targets leukemia stem cells. Tandem high-throughput screening using chemical and ultracomplex shRNA libraries, therefore, provides a rapid chemical genetics approach for seamless progression from small molecule lead identification to target discovery and validation. PMID:24183972

  12. Risk assessment of endocrine active chemicals: identifying chemicals of regulatory concern.

    PubMed

    Bars, Remi; Fegert, Ivana; Gross, Melanie; Lewis, Dick; Weltje, Lennart; Weyers, Arnd; Wheeler, James R; Galay-Burgos, Malyka

    2012-10-01

    The European regulation on plant protection products (1107/2009) (EC, 2009a), the revisions to the biocides Directive (COM[2009]267) (EC, 2009b), and the regulation concerning chemicals (Regulation (EC) No. 1907/2006 'REACH') (EC.2006) only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or wildlife species. In the absence of agreed guidance on how to identify and evaluate endocrine activity and disruption within these pieces of legislation a European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. The resulting ECETOC technical report (ECETOC, 2009a) and the associated workshop (ECETOC, 2009b) presented a science-based concept on how to identify endocrine activity and disrupting properties of chemicals for both human health and the environment. The synthesis of the technical report and the workshop report was published by the ECETOC task force (Bars et al., 2011a,b). Specific scientific criteria for the determination of endocrine activity and disrupting properties that integrate information from both regulatory (eco)toxicity studies and mechanistic/screening studies were proposed. These criteria combined the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. A key element in the data evaluation is the consideration of all available information in a weight-of-evidence approach. However, to be able to discriminate chemicals with endocrine properties of low concern from those of higher concern (for regulatory purposes), the task force recognised that the concept needed further refinement. Following a discussion of the key factors at a second workshop of invited regulatory, academic and industry scientists (ECETOC, 2011), the task force developed further guidance, which is presented in this paper. For human health assessments these factors include the relevance to humans of the endocrine mechanism of toxicity, the specificity of the endocrine effects with respect to other potential toxic effects, the potency of the chemical to induce endocrine toxicity and consideration of exposure levels. For ecotoxicological assessments the key considerations include specificity and potency, but also extend to the consideration of population relevance and negligible exposure. It is intended that these complement and reinforce the approach originally described and previously published in this journal (Bars et al., 2011a,b). PMID:22735369

  13. A NEW MASS SPECTROMETRIC TECHNIQUE FOR IDENTIFYING TRACE-LEVEL ORGANIC COMPOUNDS IN COMPLEX MIXTURES

    EPA Science Inventory



    Most organic compounds are not found in mass spectral libraries and cannot be easily identified from low resolution mass spectra. Ion Composition Elucidation (ICE) utilizes selected ion recording with a double focusing mass spectrometer in a new way to determine exact mas...

  14. IDENTIFYING COMPOUNDS USING SOURCE CID ON AN ORTHOGONAL ACCELERATION TIME-OF-FLIGHT MASS SPECTROMETER

    EPA Science Inventory

    Exact mass libraries of ESI and APCI mass spectra are not commercially available In-house libraries are dependent on CID parameters and are instrument specific. The ability to identify compounds without reliance on mass spectral libraries is therefore more crucial for liquid sam...

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

    PubMed Central

    Rotroff, Daniel M.; Dix, David J.; Houck, Keith A.; Knudsen, Thomas B.; Martin, Matthew T.; McLaurin, Keith W.; Reif, David M.; Crofton, Kevin M.; Singh, Amar V.; Xia, Menghang; Huang, Ruili

    2012-01-01

    Background: Over the past 20 years, an increased focus on detecting environmental chemicals that pose a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP; thus, processing these chemicals using current test batteries could require millions of dollars and decades. A need for increased throughput and efficiency motivated the development of methods using in vitro high throughput screening (HTS) assays to prioritize chemicals for EDSP Tier 1 screening (T1S). Objective: In this study we used U.S. EPA ToxCast HTS assays for estrogen, androgen, steroidogenic, and thyroid-disrupting mechanisms to classify compounds and compare ToxCast results to in vitro and in vivo data from EDSP T1S assays. Method: We implemented an iterative model that optimized the ability of endocrine-related HTS assays to predict components of EDSP T1S and related results. Balanced accuracy was used as a measure of model performance. Results: ToxCast estrogen receptor and androgen receptor assays predicted the results of relevant EDSP T1S assays with balanced accuracies of 0.91 (p < 0.001) and 0.92 (p < 0.001), respectively. Uterotrophic and Hershberger assay results were predicted with balanced accuracies of 0.89 (p < 0.001) and 1 (p < 0.001), respectively. Models for steroidogenic and thyroid-related effects could not be developed with the currently published ToxCast data. Conclusions: Overall, results suggest that current ToxCast assays can accurately identify chemicals with potential to interact with the estrogenic and androgenic pathways, and could help prioritize chemicals for EDSP T1S assays. PMID:23052129

  16. Machine learning of molecular electronic properties in chemical compound space

    NASA Astrophysics Data System (ADS)

    Montavon, Grégoire; Rupp, Matthias; Gobre, Vivekanand; Vazquez-Mayagoitia, Alvaro; Hansen, Katja; Tkatchenko, Alexandre; Müller, Klaus-Robert; Anatole von Lilienfeld, O.

    2013-09-01

    The combination of modern scientific computing with electronic structure theory can lead to an unprecedented amount of data amenable to intelligent data analysis for the identification of meaningful, novel and predictive structure-property relationships. Such relationships enable high-throughput screening for relevant properties in an exponentially growing pool of virtual compounds that are synthetically accessible. Here, we present a machine learning model, trained on a database of ab initio calculation results for thousands of organic molecules, that simultaneously predicts multiple electronic ground- and excited-state properties. The properties include atomization energy, polarizability, frontier orbital eigenvalues, ionization potential, electron affinity and excitation energies. The machine learning model is based on a deep multi-task artificial neural network, exploiting the underlying correlations between various molecular properties. The input is identical to ab initio methods, i.e. nuclear charges and Cartesian coordinates of all atoms. For small organic molecules, the accuracy of such a ‘quantum machine’ is similar, and sometimes superior, to modern quantum-chemical methods—at negligible computational cost.

  17. UniChem: a unified chemical structure cross-referencing and identifier tracking system.

    PubMed

    Chambers, Jon; Davies, Mark; Gaulton, Anna; Hersey, Anne; Velankar, Sameer; Petryszak, Robert; Hastings, Janna; Bellis, Louisa; McGlinchey, Shaun; Overington, John P

    2013-01-01

    UniChem is a freely available compound identifier mapping service on the internet, designed to optimize the efficiency with which structure-based hyperlinks may be built and maintained between chemistry-based resources. In the past, the creation and maintenance of such links at EMBL-EBI, where several chemistry-based resources exist, has required independent efforts by each of the separate teams. These efforts were complicated by the different data models, release schedules, and differing business rules for compound normalization and identifier nomenclature that exist across the organization. UniChem, a large-scale, non-redundant database of Standard InChIs with pointers between these structures and chemical identifiers from all the separate chemistry resources, was developed as a means of efficiently sharing the maintenance overhead of creating these links. Thus, for each source represented in UniChem, all links to and from all other sources are automatically calculated and immediately available for all to use. Updated mappings are immediately available upon loading of new data releases from the sources. Web services in UniChem provide users with a single simple automatable mechanism for maintaining all links from their resource to all other sources represented in UniChem. In addition, functionality to track changes in identifier usage allows users to monitor which identifiers are current, and which are obsolete. Lastly, UniChem has been deliberately designed to allow additional resources to be included with minimal effort. Indeed, the recent inclusion of data sources external to EMBL-EBI has provided a simple means of providing users with an even wider selection of resources with which to link to, all at no extra cost, while at the same time providing a simple mechanism for external resources to link to all EMBL-EBI chemistry resources. PMID:23317286

  18. UniChem: a unified chemical structure cross-referencing and identifier tracking system

    PubMed Central

    2013-01-01

    UniChem is a freely available compound identifier mapping service on the internet, designed to optimize the efficiency with which structure-based hyperlinks may be built and maintained between chemistry-based resources. In the past, the creation and maintenance of such links at EMBL-EBI, where several chemistry-based resources exist, has required independent efforts by each of the separate teams. These efforts were complicated by the different data models, release schedules, and differing business rules for compound normalization and identifier nomenclature that exist across the organization. UniChem, a large-scale, non-redundant database of Standard InChIs with pointers between these structures and chemical identifiers from all the separate chemistry resources, was developed as a means of efficiently sharing the maintenance overhead of creating these links. Thus, for each source represented in UniChem, all links to and from all other sources are automatically calculated and immediately available for all to use. Updated mappings are immediately available upon loading of new data releases from the sources. Web services in UniChem provide users with a single simple automatable mechanism for maintaining all links from their resource to all other sources represented in UniChem. In addition, functionality to track changes in identifier usage allows users to monitor which identifiers are current, and which are obsolete. Lastly, UniChem has been deliberately designed to allow additional resources to be included with minimal effort. Indeed, the recent inclusion of data sources external to EMBL-EBI has provided a simple means of providing users with an even wider selection of resources with which to link to, all at no extra cost, while at the same time providing a simple mechanism for external resources to link to all EMBL-EBI chemistry resources. PMID:23317286

  19. A Chemical Mutagenesis Screen Identifies Mouse Models with ERG Defects.

    PubMed

    Charette, Jeremy R; Samuels, Ivy S; Yu, Minzhong; Stone, Lisa; Hicks, Wanda; Shi, Lan Ying; Krebs, Mark P; Naggert, Jrgen K; Nishina, Patsy M; Peachey, Neal S

    2016-01-01

    Mouse models provide important resources for many areas of vision research, pertaining to retinal development, retinal function and retinal disease. The Translational Vision Research Models (TVRM) program uses chemical mutagenesis to generate new mouse models for vision research. In this chapter, we report the identification of mouse models for Grm1, Grk1 and Lrit3. Each of these is characterized by a primary defect in the electroretinogram. All are available without restriction to the research community. PMID:26427409

  20. Chemical Composition and Characteristic Odor Compounds in Essential Oil from Alismatis Rhizoma (Tubers of Alisma orientale).

    PubMed

    Miyazawa, Mitsuo; Yoshinaga, Seiji; Kashima, Yusei; Nakahashi, Hiroshi; Hara, Nobuyuki; Nakagawa, Hiroki; Usami, Atsushi

    2016-01-01

    Chemical composition and potent odorants that contribute to the characteristic odor of essential oil from Alismatis Rhizoma (tubers of Alisma orientale) were investigated by gas chromatography-mass spectrometry (GC-MS), GC-olfactometry (GC-O), aroma extract dilution analysis (AEDA) and relative flavor activity (RFA) methods. Fifty components, representing 94.5% of the total oil, were identified. In this study, we newly identified thirty-nine compounds in the oil from tubers of A. orientale. The major constituents of the essential oil were khusinol (36.2%), δ-elemene (12.4%), germacron (4.1%), alismol (3.8%), β-elemene (3.1%), and α-bisabolol (1.9%). Through sensory analysis, sixteen aroma-active compounds were detected and the key contributing aroma-active compounds were δ-elemene (woody, flavor dilution (FD)-factor = 4, RFA = 0.3) β-elemene (spicy, FD = 5, RFA = 0.7), spathulenol (green, FD = 5, RFA = 1.0), γ-eudesmol (woody, FD = 6, RFA = 1.5), and γ-cadinol (woody, FD = 5, RFA = 1.0). These compounds are thought to contribute to the odor from tubers of A. orientale. These results imply that the essential oil from the tubers of A. orientale deserve further investigations in the phytochemical and medicinal fields. PMID:26666273

  1. A high content screen identifies novel compounds that inhibit stress-induced TDP-43 cellular aggregation and associated cytotoxicity

    PubMed Central

    Zauur, Nava; Liu, Min; Concannon, John; Ebata, Atsushi; Wolozin, Benjamin; Glicksman, Marcie A.

    2014-01-01

    TDP-43 is an RNA binding protein found to accumulate in the cytoplasm of brain and spinal cord from patients affected with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Nuclear TDP-43 protein regulates transcription through several mechanisms, and under stressed conditions it forms cytoplasmic aggregates that co-localize with stress granule (SG) proteins in cell culture. These granules are also found in the brain and spinal cord of patients affected with ALS and FTLD. The mechanism through which TDP-43 might contribute to neurodegenerative diseases is poorly understood. In order to investigate the pathophysiology of TDP-43 aggregation and to isolate potential therapeutic targets, we screened a chemical library of 75,000 compounds using high content analysis with PC12 cells that inducibly express human TDP-43 tagged with GFP. The screen identified 16 compounds that dose-dependently decreased the TDP-43 inclusions without significant cellular toxicity or changes in total TDP-43 expression levels. To validate the effect of the compounds, we tested compounds by Western Blot analysis and in a model that replicates some of the relevant disease phenotypes. The hits from this assay will be useful for elucidating regulation of TDP-43, stress granule response, and possible ALS therapeutics. PMID:24019256

  2. Bioautography and chemical characterization of antimicrobial compound(s) in commercial water-soluble annatto extracts.

    PubMed

    Galindo-Cuspinera, Veronica; Rankin, Scott A

    2005-04-01

    Annatto preparations based on extracts of the seed of tropical bush Bixa orellana L consist of carotenoid-type pigments. Previous reports indicate that commercial annatto extracts have biological activities against microorganisms of significance to food fermentation, preservation, and safety. The objective of this study was to separate and identify the compound(s) responsible for the antimicrobial activity of annatto preparations. Commercial water-soluble annatto extracts were screened by thin-layer chromatography and bioautography followed by liquid chromatography/photodiode array/mass spectrometry (LC/PDA/MS) analysis of active fractions. Bioautography revealed two fractions with antimicrobial activity against Staphylococcus aureus. LC/PDA/MS analysis of both fractions revealed 9'-cis-norbixin (UV(max) 460 and 489 nm) and all-trans-norbixin (UV(max) 287, 470, and 494 nm) as the major components. Structure confirmation was achieved by (1)H NMR spectroscopy. Results indicate that 9'-cis-norbixin and all-trans-norbixin are responsible for the antimicrobial properties of annatto. PMID:15796589

  3. High-Throughput Screening Using a Whole-Cell Virus Replication Reporter Gene Assay to Identify Inhibitory Compounds against Rift Valley Fever Virus Infection.

    PubMed

    Islam, Md Koushikul; Baudin, Maria; Eriksson, Jonas; Öberg, Christopher; Habjan, Matthias; Weber, Friedemann; Överby, Anna K; Ahlm, Clas; Evander, Magnus

    2016-04-01

    Rift Valley fever virus (RVFV) is an emerging virus that causes serious illness in humans and livestock. There are no approved vaccines or treatments for humans. The purpose of the study was to identify inhibitory compounds of RVFV infection without any preconceived idea of the mechanism of action. A whole-cell-based high-throughput drug screening assay was developed to screen 28,437 small chemical compounds targeting RVFV infection. To accomplish both speed and robustness, a replication-competent NSs-deleted RVFV expressing a fluorescent reporter gene was developed. Inhibition of fluorescence intensity was quantified by spectrophotometry and related to virus infection in human lung epithelial cells (A549). Cell toxicity was assessed by the Resazurin cell viability assay. After primary screening, 641 compounds were identified that inhibited RVFV infection by ≥80%, with ≥50% cell viability at 50 µM concentration. These compounds were subjected to a second screening regarding dose-response profiles, and 63 compounds with ≥60% inhibition of RVFV infection at 3.12 µM compound concentration and ≥50% cell viability at 25 µM were considered hits. Of these, six compounds with high inhibitory activity were identified. In conclusion, the high-throughput assay could efficiently and safely identify several promising compounds that inhibited RVFV infection. PMID:26762502

  4. A Chemical Screening Approach to Identify Novel Key Mediators of Erythroid Enucleation.

    PubMed

    Wölwer, Christina B; Pase, Luke B; Pearson, Helen B; Gödde, Nathan J; Lackovic, Kurt; Huang, David C S; Russell, Sarah M; Humbert, Patrick O

    2015-01-01

    Erythroid enucleation is critical for terminal differentiation of red blood cells, and involves extrusion of the nucleus by orthochromatic erythroblasts to produce reticulocytes. Due to the difficulty of synchronizing erythroblasts, the molecular mechanisms underlying the enucleation process remain poorly understood. To elucidate the cellular program governing enucleation, we utilized a novel chemical screening approach whereby orthochromatic cells primed for enucleation were enriched ex vivo and subjected to a functional drug screen using a 324 compound library consisting of structurally diverse, medicinally active and cell permeable drugs. Using this approach, we have confirmed the role of HDACs, proteasomal regulators and MAPK in erythroid enucleation and introduce a new role for Cyclin-dependent kinases, in particular CDK9, in this process. Importantly, we demonstrate that when coupled with imaging analysis, this approach provides a powerful means to identify and characterize rate limiting steps involved in the erythroid enucleation process. PMID:26569102

  5. A Chemical Screening Approach to Identify Novel Key Mediators of Erythroid Enucleation

    PubMed Central

    Wölwer, Christina B.; Pase, Luke B.; Pearson, Helen B.; Gödde, Nathan J.; Lackovic, Kurt; Huang, David C. S.; Russell, Sarah M.; Humbert, Patrick O.

    2015-01-01

    Erythroid enucleation is critical for terminal differentiation of red blood cells, and involves extrusion of the nucleus by orthochromatic erythroblasts to produce reticulocytes. Due to the difficulty of synchronizing erythroblasts, the molecular mechanisms underlying the enucleation process remain poorly understood. To elucidate the cellular program governing enucleation, we utilized a novel chemical screening approach whereby orthochromatic cells primed for enucleation were enriched ex vivo and subjected to a functional drug screen using a 324 compound library consisting of structurally diverse, medicinally active and cell permeable drugs. Using this approach, we have confirmed the role of HDACs, proteasomal regulators and MAPK in erythroid enucleation and introduce a new role for Cyclin-dependent kinases, in particular CDK9, in this process. Importantly, we demonstrate that when coupled with imaging analysis, this approach provides a powerful means to identify and characterize rate limiting steps involved in the erythroid enucleation process. PMID:26569102

  6. Historical trends in organochlorine compounds in river basins identified using sediment cores from reservoirs

    USGS Publications Warehouse

    Van Metre, P.C.; Callender, E.; Fuller, C.C.

    1997-01-01

    This study used chemical analyses of dated sediment cores from reservoirs to define historical trends in water quality in the influent river basins. This work applies techniques from paleolimnology to reservoirs, and in the process, highlights differences between sediment-core interpretations for reservoirs and natural lakes. Sediment cores were collected from six reservoirs in the central and southeastern United States, sectioned, and analyzed for 137Cs and organochlorine compounds. 137Cs analyses were used to demonstrate limited post-depositional mixing, to indicate sediment deposition dates, and to estimate sediment focusing factors. Relative lack of mixing, high sedimentation rates, and high focusing factors distinguish reservoir sediment cores from cores collected in natural lakes. Temporal trends in concentrations of PCBs, total DDT (DDT + DDD + DDE), and chlordane reflect historical use and regulation of these compounds and differences in land use between reservoir drainages. PCB and total DDT core burdens, normalized for sediment focusing, greatly exceed reported cumulative regional atmospheric fallout of PCBs and total DDT estimated using cores from peat hogs and natural lakes, indicating the dominance of fluvial inputs of both groups of compounds to the reservoirs.This study used chemical analyses of dated sediment cores from reservoirs to define historical trends in water quality in the influent river basins. This work applies techniques from paleolimnology to reservoirs, and in the process, highlights differences between sediment-core interpretations for reservoirs and natural lakes. Sediment cores were collected from six reservoirs in the central and southeastern United States, sectioned, and analyzed for 137Cs and organochlorine compounds. 137Cs analyses were used to demonstrate limited post-depositional mixing, to indicate sediment deposition dates, and to estimate sediment focusing factors. Relative lack of mixing, high sedimentation rates, and high focusing factors distinguish reservoir sediment cores from cores collected in natural lakes. Temporal trends in concentrations of PCBs, total DOT (DDT+DDD+DDE), and chlordane reflect historical use and regulation of these compounds and differences in land use between reservoir drainages. PCB and total DDT core burdens, normalized for sediment focusing, greatly exceed reported cumulative regional atmospheric fallout of PCBs and total DDT estimated using cores from peat bogs and natural lakes, indicating the dominance of fluvial inputs of both groups of compounds to the reservoirs.

  7. REVIEW OF VOLATILE ORGANIC COMPOUND SOURCE APPORTIONMENT BY CHEMICAL MASS BALANCE. (R826237)

    EPA Science Inventory

    The chemical mass balance (CMB) receptor model has apportioned volatile organic compounds (VOCs) in more than 20 urban areas, mostly in the United States. These applications differ in terms of the total fraction apportioned, the calculation method, the chemical compounds used ...

  8. Tailoring of a photoactive compound for non-chemically amplified 248-nm resist formulations

    NASA Astrophysics Data System (ADS)

    Leeson, Michael J.; Pawloski, Adam R.; Levering, Vrad; Yueh, Wang; Willson, C. Grant

    1997-07-01

    Several approaches toward the design of non-chemically amplified deep UV resists have been reported using different photoactive compounds and resins. Diazo-dione chromophores are particularly attractive for this application, but the keto- ketenes derived from their photolysis are more reactive than those derived from the analogous diazonaphthoquinones. Specifically, the 30-diazo-4-ketocoumarin chromophore has been identified as a promising candidate around which to design a non-chemically amplified 248 nm resist. In order to optimize the design of this system, the influence of both electronic and steric influences on the rate of reaction of the ketene with novolac resin has been studied. These experiments were carried out using a low temperature matrix isolation FT-IR technique similar to that previously reported. The reaction of the ketene with the resin hydroxyl group follows pseudo first order kinetics and the rate constant is dependent on the substituents and the substitution pattern on the coumarin.

  9. Exposure levels for chemical threat compounds: information to facilitate chemical incident response.

    PubMed

    Hauschild, Veronique D; Watson, Annetta

    2013-01-01

    Although not widely known, a robust set of peer-reviewed public health and occupational exposure levels presently exist for key chemical warfare agents (CWAs) and certain acutely toxic industrial chemicals (TICs) identified as terrorist attack threats. Familiarity with these CWA and TIC exposure levels and their historic applications has facilitated emergency management decision-making by public and environmental health decision-makers. Specifically, multiple air, soil, and water exposure levels for CWAs and TICs summarized here have been extensively peer-reviewed and published; many have been recognized and are in use by federal and state health agencies as criteria for hazard zone prediction and assessment, occupational safety, and "how clean is clean enough" decisions. The key, however, is to know which criteria are most appropriate for specific decisions. While public safety is critical, high levels of concern often associated with perceived or actual proximity to extremely toxic chemical agents could result in overly cautious decisions that generate excessive delays, expenditure of scarce resources, and technological difficulties. Rapid selection of the most appropriate chemical exposure criteria is recommended to avoid such problems and expedite all phases of chemical incident response and recovery. PMID:24340456

  10. 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; Gmez, 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

  11. In situ Analysis of Organic Compounds on Mars using Chemical Derivatization and Gas Chromatography Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Glavin, D. P.; Buch, A.; Cabane, M.; Coll, P.; Navarro-Gonzalez, R.; Mahaffy, P. R.

    2005-01-01

    One of the core science objectives of NASA's 2009 Mars Science Laboratory (MSL) mission is to determine the past or present habitability of Mars. The search for key organic compounds relevant to terrestrial life will be an important part of that assessment. We have developed a protocol for the analysis of amino acids and carboxylic acids in Mars analogue materials using gas chromatography mass spectrometry (GCMS). As shown, a variety of carboxylic acids were readily identified in soil collected from the Atacama Desert in Chile at part-per-billion levels by GCMS after extraction and chemical derivatization using the reagent N,N-tert.-butyl (dimethylsilyl) trifluoroacetamide (MTBSTFA). Several derivatized amino acids including glycine and alanine were also detected by GCMS in the Atacama soil at lower concentrations (chromatogram not shown). Lacking derivatization capability, the Viking pyrolysis GCMS instruments could not have detected amino acids and carboxylic acids, since these non-volatile compounds require chemical transformation into volatile species that are stable in a GC column. We are currently optimizing the chemical extraction and derivatization technique for in situ GCMS analysis on Mars. Laboratory results of analyses of Atacama Desert samples and other Mars analogue materials using this protocol will be presented.

  12. Oxidative properties and chemical stability of fluoronanotubes in matrixes of binary inorganic compounds.

    PubMed

    Peng, Haiqing; Gu, Zhenning; Liu, Yu; Chiang, Ivana W; Smalley, Richard E; Hauge, Robert H; Khabashesku, Valery N; Margrave, John L

    2003-01-01

    The chemical stability of fluoronanotubes in selected solid inorganic matrixes has been studied by initially mixing and mechanically grinding the components and subsequently heating them at temperatures ranging from 35 to 600 degrees C. The inorganic compounds selected for matrixes included halides (KBr, KI, Lil, LiBr, LiCl, NaCl, Znl2), oxides (Li2O, Fe2O3, PbO, MnO), lithium peroxide (Li2O2), potassium superoxide (KO2), sulfides (Li2S and ZnS), zinc selenide (ZnSe), lithium nitride (Li3N), and aluminum phosphide (AIP). Solid products, resulting from the proceeding chemical reactions, were analyzed by X-ray diffraction, Raman spectroscopy, and SEM/EDX elemental analysis. Gaseous and volatile products were identified with the help of the TGA/MS technique. Experimental data presented in this paper provide clear evidence that fluoronanotubes are not chemically inert toward the solid matrixes studied and exhibit significant oxidative properties in the redox reactions occurring under various temperatures, depending on the nature of the inorganic compound. PMID:12908234

  13. Gas chromatograph-mass spectrometer (GC/MS) system for quantitative analysis of reactive chemical compounds

    DOEpatents

    Grindstaff, Quirinus G. (Oak Ridge, TN)

    1992-01-01

    Described is a new gas chromatograph-mass spectrometer (GC/MS) system and method for quantitative analysis of reactive chemical compounds. All components of such a GC/MS system external to the oven of the gas chromatograph are programmably temperature controlled to operate at a volatilization temperature specific to the compound(s) sought to be separated and measured.

  14. From Leaf Metabolome to In Vivo Testing: Identifying Antifeedant Compounds for Ecological Studies of Marsupial Diets.

    PubMed

    Marsh, Karen J; Yin, Baofa; Singh, Inder Pal; Saraf, Isha; Choudhary, Alka; Au, Jessie; Tucker, David J; Foley, William J

    2015-06-01

    Identifying specific plant secondary metabolites that influence feeding behavior can be challenging, but a solid understanding of animal preferences can guide efforts. Common brushtail possums (Trichosurus vulpecula) predominantly eat Eucalyptus species belonging to the subgenus Symphyomyrtus, and avoid eating those belonging to the Monocalyptus subgenus (also called subgenus Eucalyptus). Using an unbiased (1)H NMR metabolomics approach, a previous study identified unsubstituted B ring flavanones in most species of monocalypts examined, whereas these compounds were absent from symphyomyrtles. We hypothesised that unsubstituted B ring flavanones act as feeding deterrents for common brushtail possums. In the current study, we tested this hypothesis by comparing how much possums ate of a basal diet, with diets containing one of four structurally related compounds; pinocembrin, flavanone (unsubstituted B ring flavanones), chrysin (the flavone analogue of pinocembrin), and naringenin (a flavanone with B ring substitution). We found that pinocembrin and flavanone deterred feeding relative to the basal diet, but that chrysin and naringenin did not at equivalent concentrations. Thus, unsubstituted B-ring flavanones may explain why brushtail possums avoid eating monocalypt species. Furthermore, small differences in the structure of secondary compounds can have a large impact on antifeedant properties. These results demonstrate that metabolomics can be a valuable tool for ecologists seeking to understand herbivore feeding preferences. PMID:25994224

  15. Chemical genomic profiling via barcode sequencing to predict compound mode of action.

    PubMed

    Piotrowski, Jeff S; Simpkins, Scott W; Li, Sheena C; Deshpande, Raamesh; McIlwain, Sean J; Ong, Irene M; Myers, Chad L; Boone, Charlie; Andersen, Raymond J

    2015-01-01

    Chemical genomics is an unbiased, whole-cell approach to characterizing novel compounds to determine mode of action and cellular target. Our version of this technique is built upon barcoded deletion mutants of Saccharomyces cerevisiae and has been adapted to a high-throughput methodology using next-generation sequencing. Here we describe the steps to generate a chemical genomic profile from a compound of interest, and how to use this information to predict molecular mechanism and targets of bioactive compounds. PMID:25618354

  16. Microwave spectra of some sulfur and nitrogen compounds. [for chemical analysis

    NASA Technical Reports Server (NTRS)

    White, W. F.

    1974-01-01

    A computer-controlled microwave spectrometer was used to catalog reference spectra for chemical analysis. The apparatus, software, and experimental procedures are described. Tables of absorption frequencies, peak absorption coefficients, and integrated intensities are included for 13 sulfur compounds, 14 nitrogen compounds, and 1 compound containing both sulfur and nitrogen. The frequency range covered was 26,500 to 40,000 MHz for most compounds and 18,000 to 40,000 MHz for some.

  17. Microscopic physical and chemical properties of graphite intercalation compounds

    SciTech Connect

    Eklund, P.C.

    1992-08-24

    Optical spectroscopy (Raman, FTIR and Reflection ) was used to study a variety of acceptor- and donor-type compounds synthesized to determine the microscopic models consistent with the spectrocsopic results. General finding is that the electrical conduction properties of these compounds can be understood on the basis that the intercalation of atomic and/or molecular species between the host graphite layers either raises or lowers the Fermi level (E{sub F)} in a graphitic band structure. This movement of E{sub F} is accomplished via a charge transfer of electrons from the intercalate layers to the graphitic layers (donor compounds), or vice versa (acceptor compounds). Furthermore, the band structure must be modified to take into account the layers of charge that occur as a result of the charge transfer. This charge layering introduces additional bands of states near E{sub F}, which are discussed. Charge-transfer also induces a perturbation of the graphitic normal mode frequencies which can be understood as the result of a contraction (acceptor compounds) or expansion (donor compounds) of the intralayer C-C bonds. Ab-initio calculations support this view and are in reasonable agreement with experimental data.

  18. Calcium Imaging of Neuronal Activity in Drosophila Can Identify Anticonvulsive Compounds

    PubMed Central

    Streit, Anne K.; Fan, Yuen Ngan; Masullo, Laura; Baines, Richard A.

    2016-01-01

    Although there are now a number of antiepileptic drugs (AEDs) available, approximately one-third of epilepsy patients respond poorly to drug intervention. The reasons for this are complex, but are probably reflective of the increasing number of identified mutations that predispose individuals to this disease. Thus, there is a clear requirement for the development of novel treatments to address this unmet clinical need. The existence of gene mutations that mimic a seizure-like behaviour in the fruit fly, Drosophila melanogaster, offers the possibility to exploit the powerful genetics of this insect to identify novel cellular targets to facilitate design of more effective AEDs. In this study we use neuronal expression of GCaMP, a potent calcium reporter, to image neuronal activity using a non-invasive and rapid method. Expression in motoneurons in the isolated CNS of third instar larvae shows waves of calcium-activity that pass between segments of the ventral nerve cord. Time between calcium peaks, in the same neurons, between adjacent segments usually show a temporal separation of greater than 200 ms. Exposure to proconvulsants (picrotoxin or 4-aminopyridine) reduces separation to below 200 ms showing increased synchrony of activity across adjacent segments. Increased synchrony, characteristic of epilepsy, is similarly observed in genetic seizure mutants: bangsenseless1 (bss1) and paralyticK1270T (paraK1270T). Exposure of bss1 to clinically-used antiepileptic drugs (phenytoin or gabapentin) significantly reduces synchrony. In this study we use the measure of synchronicity to evaluate the effectiveness of known and novel anticonvulsive compounds (antipain, isethionate, etopiside rapamycin and dipyramidole) to reduce seizure-like CNS activity. We further show that such compounds also reduce the Drosophila voltage-gated persistent Na+ current (INaP) in an identified motoneuron (aCC). Our combined assays provide a rapid and reliable method to screen unknown compounds for potential to function as anticonvulsants. PMID:26863447

  19. Differential nuclear staining assay for high-throughput screening to identify cytotoxic compounds

    PubMed Central

    LEMA, Carolina; VARELA-RAMIREZ, Armando; AGUILERA, Renato J.

    2016-01-01

    As large quantities of novel synthetic molecules continue to be generated there is a challenge to identify therapeutic agents with cytotoxic activity. Here we introduce a Differential Nuclear Staining (DNS) assay adapted to live-cell imaging for high throughput screening (HTS) that utilizes two fluorescent DNA intercalators, Hoechst 33342 and Propidium iodide (PI). Since Hoechst can readily cross cell membranes to stain DNA of living and dead cells, it was used to label the total number of cells. In contrast, PI only enters cells with compromised plasma membranes, thus selectively labeling dead cells. The DNS assay was successfully validated by utilizing well known cytotoxic agents with fast or slow cytotoxic activities. The assay was found to be suitable for HTS with Z′ factors ranging from 0.86 to 0.60 for 96 and 384-well formats, respectively. Furthermore, besides plate-to-plate reproducibility, assay quality performance was evaluated by determining ratios of signal-to-noise and signal-to-background, as well as coefficient of variation, which resulted in adequate values and validated the assay for HTS initiatives. As proof of concept, eighty structurally diverse compounds from a small molecule library were screened in a 96-well plate format using the DNS assay. Using this DNS assay, six hits with cytotoxic properties were identified and all of them were also successfully identified by using the commercially available MTS assay (CellTiter 96® Cell Proliferation Assay). In addition, the DNS and a flow cytometry assay were used to validate the activity of the cytotoxic compounds. The DNS assay was also used to generate dose-response curves and to obtain CC50 values. The results indicate that the DNS assay is reliable and robust and suitable for primary and secondary screens of compounds with potential cytotoxic activity.

  20. Identifying the macromolecular targets of de novo-designed chemical entities through self-organizing map consensus

    PubMed Central

    Reker, Daniel; Rodrigues, Tiago; Schneider, Petra; Schneider, Gisbert

    2014-01-01

    De novo molecular design and in silico prediction of polypharmacological profiles are emerging research topics that will profoundly affect the future of drug discovery and chemical biology. The goal is to identify the macromolecular targets of new chemical agents. Although several computational tools for predicting such targets are publicly available, none of these methods was explicitly designed to predict target engagement by de novo-designed molecules. Here we present the development and practical application of a unique technique, self-organizing map–based prediction of drug equivalence relationships (SPiDER), that merges the concepts of self-organizing maps, consensus scoring, and statistical analysis to successfully identify targets for both known drugs and computer-generated molecular scaffolds. We discovered a potential off-target liability of fenofibrate-related compounds, and in a comprehensive prospective application, we identified a multitarget-modulating profile of de novo designed molecules. These results demonstrate that SPiDER may be used to identify innovative compounds in chemical biology and in the early stages of drug discovery, and help investigate the potential side effects of drugs and their repurposing options. PMID:24591595

  1. Sources of toxicity and exposure information for identifying chemicals of high concern to children

    SciTech Connect

    Stone, Alex; Delistraty, Damon

    2010-11-15

    Due to the large number of chemicals in commerce without adequate toxicity characterization data, coupled with an ineffective federal policy for chemical management in the United States, many states are grappling with the challenge to identify toxic chemicals that may pose a risk to human health and the environment. Specific populations (e.g., children, elderly) are particularly sensitive to these toxic chemicals. In 2008, the Children's Safe Product Act (CSPA) was passed in Washington State. The CSPA included specific requirements to identify High Priority Chemicals (HPCs) and Chemicals of High Concern to Children (CHCCs). To implement this legislation, a methodology was developed to identify HPCs from authoritative scientific and regulatory sources on the basis of toxicity criteria. Another set of chemicals of concern was then identified from authoritative sources, based on their potential exposure to children. Exposure potential was evaluated by identifying chemicals detected in biomonitoring studies (i.e., human tissues), as well as those present in residential exposure media (e.g., indoor air, house dust, drinking water, consumer products). Accordingly, CHCCs were defined as HPCs that also appear in biomonitoring studies or relevant exposure media. For chemicals with unique Chemical Abstracts Service (CAS) numbers, we identified 2044 HPCs and 2219 chemicals with potential exposure to children, resulting in 476 CHCCs. The process of chemical identification is dynamic, so that chemicals may be added or subtracted as new information becomes available. Although beyond the scope of this paper, the 476 CHCCs will be prioritized in a more detailed assessment, based on the strength and weight of evidence of toxicity and exposure data. Our approach was developed to be flexible which allows the addition or removal of specific sources of toxicity or exposure information, as well as transparent to allow clear identification of inputs. Although the methodology was constrained by specific requirements in the CSPA, the intent of this work was to identify HPCs and CHCCs that might guide future regulatory actions and inform chemical management policies, aimed at protecting children's health.

  2. Chemical properties and methods of analysis of refractory compounds

    NASA Technical Reports Server (NTRS)

    Samsonov, G. V. (Editor); Frantsevich, I. N. (Editor); Yeremenko, V. N. (Editor); Nazarchuk, T. N. (Editor); Popova, O. I. (Editor)

    1978-01-01

    Reactions involving refractory metals and the alloys based on them are discussed. Chemical, electrochemical, photometric, spectrophotometric, and X-ray analysis are among the methods described for analyzing the results of the reactions and for determining the chemical properties of these materials.

  3. LOW VOLATILE ORGANIC COMPOUND (VOC) CHEMICAL AGENT RESISTANT COATING (CARC)

    EPA Science Inventory

    Chemical warfare causes many problems on the battlefield, among which is decontamination of exposed equipment. Because of this threat, the US Army ahs required the use of a Chemical Agent Resistant Coating (CARC) system on its equipment, beginning in FY 85. The equipment covere...

  4. Process for preparing a chemical compound enriched in isotope content. [nitrogen 15-enriched nitric acid

    DOEpatents

    Michaels, E.D.

    1981-02-25

    A process to prepare a chemical enriched in isotope content includes: a chemical exchange reaction between a first and second compound which yields an isotopically enriched first compound and an isotopically depleted second compound; the removal of a portion of the first compound as product and the removal of a portion of the second compound as spent material; the conversion of the remainder of the first compound to the second compound for reflux at the product end of the chemical exchange reaction region; the conversion of the remainder of the second compound to the first compound for reflux at the spent material end of the chemical exchange region; and the cycling of the additional chemicals produced by one conversion reaction to the other conversion reaction, for consumption therein. One of the conversion reactions is an oxidation reaction, and the energy that it yields is used to drive the other conversion reaction, a reduction. The reduction reaction is carried out in a solid polymer electrolyte electrolytic reactor. The overall process is energy efficient and yields no waste by-products. A particular embodiment of the process in the production of nitrogen-15-enriched nitric acid.

  5. Analogue Experiments Identify Possible Precursor Compounds for Chlorohydrocarbons Detected in SAM

    NASA Astrophysics Data System (ADS)

    Miller, K.; Summons, R. E.; Eigenbrode, J. L.; Freissinet, C.; Glavin, D. P.; Martin, M. G.; Team, M.

    2013-12-01

    Since landing at Gale Crater on August 6, 2012, the Sample Analysis at Mars (SAM) instrument suite, aboard the Curiosity Rover, has conducted multiple analyses of scooped and drilled samples and has identified a suite of chlorohydrocarbons including chloromethane, dichloromethane, trichloromethane, chloromethylpropene, and chlorobenzene (Glavin et al., 2013; Leshin et al., 2013). These compounds were identified after samples were pyrolysed at temperatures up to ~835C through a combination of Evolved Gas Analysis (EGA) and Gas Chromatography Mass Spectrometry (GCMS). Since these chlorinated species were well above the background levels determined by empty cup blanks analyzed prior to solid sample analyses, thermal degradation of oxychlorine phases, such as perchlorate, present in the Martian soil, are the most likely source of chlorine needed to generate these chlorohydrocarbons. Laboratory analogue experiments show that terrestrial organics internal to SAM, such as N-methyl-N(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), a derivatization agent, can react with perchlorates to produce all of the chlorohydrocarbons detected by SAM. However, in pyrolysis-trap-GCMS laboratory experiments with MTBSTFA, C4 compounds are the predominant chlorohydrocarbon observed, whereas on SAM the C1 chlorohydrocarbons dominate (Glavin et al., 2013). This, in addition to the previous identification of chloromethane and dichloromethane by the 1976 Viking missions (Biemann et al., 1977), suggest that there could be another, possibly Martian, source of organic carbon contributing to the formation of the C1 chlorohydrocarbons, or other components of the solid samples analyzed by SAM are having a catalytic effect on chlorohydrocarbon generation. Laboratory analogue experiments investigated a suite of organic compounds that have the potential to accumulate on Mars (Benner et al., 2000) and thus serve as sources of carbon for the formation of chlorohydrocarbons detected by the SAM and Viking GCMS instruments. Experiments were conducted under SAM-like conditions using a commercial pyroprobe equipped with a SAM-like hydrocarbon trap and coupled to a GCMS. In general, when pyrolyzed with 1 wt.% calcium perchlorate, the C1 organic compounds (e.g. methanol, formic acid, and formaldehyde) produced only C1 chlorinated compounds while propanol and butyric acid formed only C3 chlorinated compounds. All of the pyrolysis experiments produced chlorobenzene, suggesting that it forms from chlorine, released during calcium perchlorate decomposition, reacting with benzene and toluene, released from the Tenax component of the hydrocarbon trap. Pyrolysis of phthalic acid however, produces a higher abundance of chlorobenzene than could be attributed to the Tenax alone and also forms C1 chlorohydrocarbons. Additional analogue experiments to identify potential precursor compounds for the chlorohydrocarbons detected by SAM are ongoing. Benner et al., 2000, PNAS, 97(6), 2425-2430 Biemann et al., 1977, JGR, 82(28), 4641-4658 Glavin et al., 2013, JGR-Planets, accepted for publication Leshin et al., 2013, Science, in press

  6. [Assessment of the relationship of properties of chemical compounds and their toxicity to a unified hygienic standardization for chemicals].

    PubMed

    Trushkov, V F; Perminov, K A; Sapozhnikova, V V; Ignatova, O L

    2013-01-01

    The connection of thermodynamic properties and parameters of toxicity of chemical substances was determined. Obtained data are used for the evaluation of toxicity and hygienic rate setting of chemical compounds. The relationship between enthalpy and toxicity of chemical compounds has been established. Orthogonal planning of the experiment was carried out in the course of the investigations. Equation of unified hygienic rate setting in combined, complex, conjunct influence on the organism is presented. Prospects of determination of toxicity and methodology of unified hygienic rate setting in combined, complex, conjunct influence on the organism are presented PMID:24003710

  7. A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions.

    PubMed

    Kraft, Robert; Kahn, Allon; Medina-Franco, Jos L; Orlowski, Mikayla L; Baynes, Cayla; Lpez-Vallejo, Fabian; Barnard, Kobus; Maggiora, Gerald M; Restifo, Linda L

    2013-01-01

    The actin-bundling protein fascin is a key mediator of tumor invasion and metastasis and its activity drives filopodia formation, cell-shape changes and cell migration. Small-molecule inhibitors of fascin block tumor metastasis in animal models. Conversely, fascin deficiency might underlie the pathogenesis of some developmental brain disorders. To identify fascin-pathway modulators we devised a cell-based assay for fascin function and used it in a bidirectional drug screen. The screen utilized cultured fascin-deficient mutant Drosophila neurons, whose neurite arbors manifest the 'filagree' phenotype. Taking a repurposing approach, we screened a library of 1040 known compounds, many of them FDA-approved drugs, for filagree modifiers. Based on scaffold distribution, molecular-fingerprint similarities, and chemical-space distribution, this library has high structural diversity, supporting its utility as a screening tool. We identified 34 fascin-pathway blockers (with potential anti-metastasis activity) and 48 fascin-pathway enhancers (with potential cognitive-enhancer activity). The structural diversity of the active compounds suggests multiple molecular targets. Comparisons of active and inactive compounds provided preliminary structure-activity relationship information. The screen also revealed diverse neurotoxic effects of other drugs, notably the 'beads-on-a-string' defect, which is induced solely by statins. Statin-induced neurotoxicity is enhanced by fascin deficiency. In summary, we provide evidence that primary neuron culture using a genetic model organism can be valuable for early-stage drug discovery and developmental neurotoxicity testing. Furthermore, we propose that, given an appropriate assay for target-pathway function, bidirectional screening for brain-development disorders and invasive cancers represents an efficient, multipurpose strategy for drug discovery. PMID:22917928

  8. A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions

    PubMed Central

    Kraft, Robert; Kahn, Allon; Medina-Franco, Jos L.; Orlowski, Mikayla L.; Baynes, Cayla; Lpez-Vallejo, Fabian; Barnard, Kobus; Maggiora, Gerald M.; Restifo, Linda L.

    2013-01-01

    SUMMARY The actin-bundling protein fascin is a key mediator of tumor invasion and metastasis and its activity drives filopodia formation, cell-shape changes and cell migration. Small-molecule inhibitors of fascin block tumor metastasis in animal models. Conversely, fascin deficiency might underlie the pathogenesis of some developmental brain disorders. To identify fascin-pathway modulators we devised a cell-based assay for fascin function and used it in a bidirectional drug screen. The screen utilized cultured fascin-deficient mutant Drosophila neurons, whose neurite arbors manifest the filagree phenotype. Taking a repurposing approach, we screened a library of 1040 known compounds, many of them FDA-approved drugs, for filagree modifiers. Based on scaffold distribution, molecular-fingerprint similarities, and chemical-space distribution, this library has high structural diversity, supporting its utility as a screening tool. We identified 34 fascin-pathway blockers (with potential anti-metastasis activity) and 48 fascin-pathway enhancers (with potential cognitive-enhancer activity). The structural diversity of the active compounds suggests multiple molecular targets. Comparisons of active and inactive compounds provided preliminary structure-activity relationship information. The screen also revealed diverse neurotoxic effects of other drugs, notably the beads-on-a-string defect, which is induced solely by statins. Statin-induced neurotoxicity is enhanced by fascin deficiency. In summary, we provide evidence that primary neuron culture using a genetic model organism can be valuable for early-stage drug discovery and developmental neurotoxicity testing. Furthermore, we propose that, given an appropriate assay for target-pathway function, bidirectional screening for brain-development disorders and invasive cancers represents an efficient, multipurpose strategy for drug discovery. PMID:22917928

  9. Quantum chemical calculations for polymers and organic compounds

    NASA Technical Reports Server (NTRS)

    Lopez, J.; Yang, C.

    1982-01-01

    The relativistic effects of the orbiting electrons on a model compound were calculated. The computational method used was based on 'Modified Neglect of Differential Overlap' (MNDO). The compound tetracyanoplatinate was used since empirical measurement and calculations along "classical" lines had yielded many known properties. The purpose was to show that for large molecules relativity effects could not be ignored and that these effects could be calculated and yield data in closer agreement to empirical measurements. Both the energy band structure and molecular orbitals are depicted.

  10. Yeast-Based High-Throughput Screens to Identify Novel Compounds Active against Brugia malayi

    PubMed Central

    Bilsland, Elizabeth; Bean, Daniel M.; Devaney, Eileen; Oliver, Stephen G.

    2016-01-01

    Background Lymphatic filariasis is caused by the parasitic worms Wuchereria bancrofti, Brugia malayi or B. timori, which are transmitted via the bites from infected mosquitoes. Once in the human body, the parasites develop into adult worms in the lymphatic vessels, causing severe damage and swelling of the affected tissues. According to the World Health Organization, over 1.2 billion people in 58 countries are at risk of contracting lymphatic filariasis. Very few drugs are available to treat patients infected with these parasites, and these have low efficacy against the adult stages of the worms, which can live for 7–15 years in the human body. The requirement for annual treatment increases the risk of drug-resistant worms emerging, making it imperative to develop new drugs against these devastating diseases. Methodology/Principal Findings We have developed a yeast-based, high-throughput screening system whereby essential yeast genes are replaced with their filarial or human counterparts. These strains are labeled with different fluorescent proteins to allow the simultaneous monitoring of strains with parasite or human genes in competition, and hence the identification of compounds that inhibit the parasite target without affecting its human ortholog. We constructed yeast strains expressing eight different Brugia malayi drug targets (as well as seven of their human counterparts), and performed medium-throughput drug screens for compounds that specifically inhibit the parasite enzymes. Using the Malaria Box collection (400 compounds), we identified nine filarial specific inhibitors and confirmed the antifilarial activity of five of these using in vitro assays against Brugia pahangi. Conclusions/Significance We were able to functionally complement yeast deletions with eight different Brugia malayi enzymes that represent potential drug targets. We demonstrated that our yeast-based screening platform is efficient in identifying compounds that can discriminate between human and filarial enzymes. Hence, we are confident that we can extend our efforts to the construction of strains with further filarial targets (in particular for those species that cannot be cultivated in the laboratory), and perform high-throughput drug screens to identify specific inhibitors of the parasite enzymes. By establishing synergistic collaborations with researchers working directly on different parasitic worms, we aim to aid antihelmintic drug development for both human and veterinary infections. PMID:26812604

  11. Use of dermal equivalent and skin equivalent models for identifying phototoxic compounds in vitro.

    PubMed

    Augustin, C; Collombel, C; Damour, O

    1997-01-01

    Phototoxicity inducing in vivo photoirritation, a reversible inflammatory reaction of the skin after chemical contact and UVA radiation exposure, is increasingly observed as a side effect associated with the use of both cosmetics and systemic drugs. In order to systematically screen for the phototoxic potential of new compounds, we propose two three-dimensional models suitable for in vitro testing: a dermal equivalent (DE) and a skin equivalent (SE) model. The DE model includes a collagen-glycosaminoglycans-chitosan porous matrix populated by normal human fibroblasts. The SE model is made by seeding normal human keratinocytes onto the DE, leading to a fully differentiated epidermis. The objectives of this pilot study are: 1) to compare the deleterious effects of UVA radiation on the two models and 2) to evaluate to what extent the in vitro results can predict the in vivo phototoxicity caused by well-known photoirritant compounds, included in the COLIPA validation phototoxicity reference chemical list. Dilutions of thiourea, sulisobenzone, promethazine, chlorpromazine and tetracycline were applied (20 microliters) onto DEs and SEs (n = 6) and incubated for 1 h (or 15 h) at 37 degrees C. Irradiated samples received 3 J/cm2 UVA. The 24 h post-irradiation residual cellular viability was measured using the MTT test on treated and untreated tissues and IL-1 alpha release measurement in collected SE culture media. A concordance in terms of photoirritant/non-photoirritant was obtained between the in vivo data and the in vitro results, suggesting that the DE and the SE models could be integrated, after a complete validation study, into a protocol for in vitro testing of the photoirritant potential of new molecules. PMID:9361126

  12. Compounds identified in-flight by ROSETTA-COSIMA before the comet encounter

    NASA Astrophysics Data System (ADS)

    Hilchenbach, M.; Fischer, H.; Krger, H.; Thirkell, L.; Ryn, J.

    2013-09-01

    Secondary ion mass spectrometry (SIMS) is a laboratory surface analyzing technique and, with the COSIMA instrument onboard ROSETTA, it will be applied for the first time to in-situ measurements of cometary grains, once ROSETTA encounters its target comet, 67P/Churyumov-Gerasimenko, in the September 2014. The COmetary Secondary Ion Mass analyzer (COSIMA) onboard ROSETTA will expose metal targets, collect cometary dust grains in the inner coma and analyze these with an optical microscope as well as secondary ion mass spectrometry [1]. The COSIMA instrument has been operated in-flight for commissioning in the first months after launch in March 2004 and on a regular basis during the passive and active spacecraft check-out time intervals up to ROSETTA hibernation from June 2011 onwards. The secondary ion mass spectra background and /or contamination level of the COSIMA metal targets has been identified prior to launch and these had been selected accordingly to avoid masking of single elements or compounds by carrying different metal targets for cometary grain collection. The main compounds identified in-flight are silicon polymers and hydrocarbons. We will discuss the surface analysis results with COSIMA, carried out far off any comet or asteroid in interplanetary space, their time evolution and their potential sources within ROSETTA.

  13. Microtubule inhibitors: structure-activity analyses suggest rational models to identify potentially active compounds.

    PubMed Central

    Callahan, H L; Kelley, C; Pereira, T; Grogl, M

    1996-01-01

    Trifluralin, a dinitroaniline microtubule inhibitor currently in use as an herbicide, has been shown to inhibit the proliferation of Plasmodium falciparum, Trypanosoma brucei, and several species of Leishmania, in vitro. As a topical formulation, trifluralin is also effective in vivo (in BALB/c mice) against Leishmania major and Leishmania mexicana. Although trifluralin and other dinitroaniline herbicides show significant activity as antiparasitic compounds, disputed indications of potential carcinogenicity will probably limit advanced development of these substances. However, researchers have suggested that the activity of trifluralin is due to an impurity or contaminant, not to trifluralin itself. We have pursued this lead and identified the structure of the active impurity. This compound, chloralin, is 100 times more active than trifluralin. On the basis of its structure, we developed a rational structure-activity model for chloralin. Using this model, we have successfully predicted and tested active analogs in a Leishmania promastigote assay; thus, we have identified the putative mechanism of action of this class of drugs in Leishmania species. Potentially, this will allow the design of noncarcinogenic, active drugs. PMID:8849257

  14. Apatite Formation: Why It May Not Work as Planned, and How to Conclusively Identify Apatite Compounds

    PubMed Central

    2013-01-01

    Calcium phosphate apatites are inorganic compounds encountered in many different mineralized tissues. Bone mineral, for example, is constituted of nanocrystalline nonstoichiometric apatite, and the production of “analogs” through a variety of methods is frequently reported. In another context, the ability of solid surfaces to favor the nucleation and growth of “bone-like” apatite upon immersion in supersaturated fluids such as SFB is commonly used as one evaluation index of the “bioactivity” of such surfaces. Yet, the compounds or deposits obtained are not always thoroughly characterized, and their apatitic nature is sometimes not firmly assessed by appropriate physicochemical analyses. Of particular importance are the “actual” conditions in which the precipitation takes place. The precipitation of a white solid does not automatically indicate the formation of a “bone-like carbonate apatite layer” as is sometimes too hastily concluded: “all that glitters is not gold.” The identification of an apatite phase should be carefully demonstrated by appropriate characterization, preferably using complementary techniques. This review considers the fundamentals of calcium phosphate apatite characterization discussing several techniques: electron microscopy/EDX, XRD, FTIR/Raman spectroscopies, chemical analyses, and solid state NMR. It also underlines frequent problems that should be kept in mind when making “bone-like apatites.” PMID:23984373

  15. Apatite formation: why it may not work as planned, and how to conclusively identify apatite compounds.

    PubMed

    Drouet, Christophe

    2013-01-01

    Calcium phosphate apatites are inorganic compounds encountered in many different mineralized tissues. Bone mineral, for example, is constituted of nanocrystalline nonstoichiometric apatite, and the production of "analogs" through a variety of methods is frequently reported. In another context, the ability of solid surfaces to favor the nucleation and growth of "bone-like" apatite upon immersion in supersaturated fluids such as SFB is commonly used as one evaluation index of the "bioactivity" of such surfaces. Yet, the compounds or deposits obtained are not always thoroughly characterized, and their apatitic nature is sometimes not firmly assessed by appropriate physicochemical analyses. Of particular importance are the "actual" conditions in which the precipitation takes place. The precipitation of a white solid does not automatically indicate the formation of a "bone-like carbonate apatite layer" as is sometimes too hastily concluded: "all that glitters is not gold." The identification of an apatite phase should be carefully demonstrated by appropriate characterization, preferably using complementary techniques. This review considers the fundamentals of calcium phosphate apatite characterization discussing several techniques: electron microscopy/EDX, XRD, FTIR/Raman spectroscopies, chemical analyses, and solid state NMR. It also underlines frequent problems that should be kept in mind when making "bone-like apatites." PMID:23984373

  16. Effects-driven chemical fractionation of heavy fuel oil to isolate compounds toxic to trout embryos.

    PubMed

    Bornstein, Jason M; Adams, Julie; Hollebone, Bruce; King, Thomas; Hodson, Peter V; Brown, R Stephen

    2014-04-01

    Heavy fuel oil (HFO) spills account for approximately 60% of ship-source oil spills and are up to 50 times more toxic than medium and light crude oils. Heavy fuel oils contain elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and alkyl-PAHs, known to be toxic to fish; however, little direct characterization of HFO toxicity has been reported. An effects-driven chemical fractionation was conducted on HFO 7102 to separate compounds with similar chemical and physical properties, including toxicity, to isolate the groups of compounds most toxic to trout embryos. After each separation, toxicity tests directed the next phase of fractionation, and gas chromatography-mass spectrometry analysis correlated composition with toxicity, with a focus on PAHs. Low-temperature vacuum distillation permitted the separation of HFO into 3 fractions based on boiling point ranges. The most toxic of these fractions underwent wax precipitation to remove long-chain n-alkanes. The remaining PAH-rich extract was further separated using open column chromatography, which provided distinct fractions that were grouped according to increasing aromatic ring count. The most toxic of these fractions was richest in PAHs and alkyl-PAHs. The results of the present study were consistent with previous crude oil studies that identified PAH-rich fractions as the most toxic. PMID:24375845

  17. Atmospheric pressure chemical ionization source. 1. Ionization of compounds in the gas phase.

    PubMed

    Andrade, Francisco J; Shelley, Jacob T; Wetzel, William C; Webb, Michael R; Gamez, Gerardo; Ray, Steven J; Hieftje, Gary M

    2008-04-15

    A novel chemical ionization source for organic mass spectrometry is introduced. This new source uses a glow discharge in the flowing afterglow mode for the generation of excited species and ions. The direct-current gas discharge is operated in helium at atmospheric pressure; typical operating voltages and currents are around 500 V and 25 mA, respectively. The species generated by this atmospheric pressure glow discharge are mixed with ambient air to generate reagent ions (mostly ionized water clusters and NO+), which are then used for the ionization of gaseous organic compounds. A wide variety of substances, both polar and nonpolar, can be ionized. The resulting mass spectra generally show the parent molecular ion (M+ or MH+) with little or no fragmentation. Proton transfer from ionized water clusters has been identified as the main ionization pathway. However, the presence of radical molecular ions (M+) for some compounds indicates that other ionization mechanisms are also involved. The analytical capabilities of this source were evaluated with a time-of-flight mass spectrometer, and preliminary characterization shows very good stability, linearity, and sensitivity. Limits of detection in the single to tens of femtomole range are reported for selected compounds. PMID:18345693

  18. CARBON-13 CHEMICAL SHIFTS IN SOLID METAL SANDWICH COMPOUNDS

    SciTech Connect

    Wemmer, D.E.; Pines, A.

    1980-08-01

    C!wmical shielding parameters are reported for the metallocenes of Fe, Ru, Mg; biscyclopentadionyl complexes Cp{sub 2}TiCl{sub 2}, (CpMe{sub 5}){sub 2}CoCl, and (CpMe{sub 5}){sub 2}Fe and bisbenzene chromium. The shielding tensor anisotropy seems to reflect the character of bonding. Motion detected in many of these compounds and has been used in some cases to assign the shielding tensor principle directions.

  19. Radiation induced chemical changes of phenolic compounds in strawberries

    NASA Astrophysics Data System (ADS)

    Breitfellner, F.; Solar, S.; Sontag, G.

    2003-06-01

    In unirradiated strawberries four phenolic acids (gallic acid, p-coumaric acid, caffeic acid and 4-hydroxybenzoic acid), the flavonoids (+)-catechin, (-)-epicatechin and glycosides from kaempferol and quercetin were determined by reversed phase chromatography with diode array detection. Characteristic linear dose/concentration relationships were found for 4-hydroxybenzoic acid and two unidentified compounds. One of them may be usable as marker to prove an irradiation treatment.

  20. Chemical evolution and the preservation of organic compounds on Mars

    NASA Technical Reports Server (NTRS)

    Kanavarioti, Anastassia; Mancinelli, Rocco L.

    1989-01-01

    Several lines of evidence suggest that the environment on early Mars and early Earth were very similar. Since life is abundant on Earth, it seems likely that conditions on early Earth were conducive to chemical evolution and the origin of life. The similarity between early Mars and early Earth encourages the hypothesis that chemical evolution might have also occurred on Mars, but that decreasing temperatures and the loss of its atmosphere brought the evolution to a halt. The possibility of finding on Mars remnants of organic material dating back to this early clement period is addressed.

  1. Cyanobacterium sp. host cell and vector for production of chemical compounds in cyanobacterial cultures

    DOEpatents

    Piven, Irina; Friedrich, Alexandra; Duhring, Ulf; Uliczka, Frank; Baier, Kerstin; Inaba, Masami; Shi, Tuo; Wang, Kui; Enke, Heike; Kramer, Dan

    2014-09-30

    A cyanobacterial host cell, Cyanobacterium sp., that harbors at least one recombinant gene for the production of a chemical compounds is provided, as well as vectors derived from an endogenous plasmid isolated from the cell.

  2. PREDICTION OF CHEMICAL REACTIVITY PARAMETERS AND PHYSICAL PROPERTIES OF ORGANIC COMPOUNDS FROM MOLECULAR STRUCTURE USING SPARC

    EPA Science Inventory

    The computer program SPARC (SPARC Performs Automated Reasoning in Chemistry) has been under development for several years to estimate physical properties and chemical reactivity parameters of organic compounds strictly from molecular structure. SPARC uses computational algorithms...

  3. ESTIMATION OF PHYSICAL PROPERTIES AND CHEMICAL REACTIVITY PARAMETERS OF ORGANIC COMPOUNDS

    EPA Science Inventory

    The computer program SPARC (Sparc Performs Automated Reasoning in Chemistry)has been under development for several years to estimate physical properties and chemical reactivity parameters of organic compounds strictly from molecular structure. SPARC uses computational algorithms ...

  4. EVALUATION USING AN ORGANOPHILIC CLAY TO CHEMICALLY STABILIZE WASTE CONTAINING ORGANIC COMPOUNDS

    EPA Science Inventory

    A modified clay (organophilic) was utilized to evaluate the potential for chemically stabilizing a waste containing organic compounds. hemical bonding between the binder and the contaminants was indicated. eachate testing also indicated strong binding. Copy available at NTIS as ...

  5. Inhibition of the compound action potentials of frog sciatic nerves by aroma oil compounds having various chemical structures.

    PubMed

    Ohtsubo, Sena; Fujita, Tsugumi; Matsushita, Akitomo; Kumamoto, Eiichi

    2015-03-01

    Plant-derived chemicals including aroma oil compounds have an ability to inhibit nerve conduction and modulate transient receptor potential (TRP) channels. Although applying aroma oils to the skin produces a local anesthetic effect, this has not been yet examined throughly. The aim of the present study was to know how nerve conduction inhibitions by aroma oil compounds are related to their chemical structures and whether these activities are mediated by TRP activation. Compound action potentials (CAPs) were recorded from the frog sciatic nerve by using the air-gap method. Citral (aldehyde), which activates various types of TRP channels, attenuated the peak amplitude of CAP with the half-maximal inhibitory concentration (IC50) value of 0.46mmol/L. Another aldehyde (citronellal), alcohol (citronellol, geraniol, ()-linalool, (-)-linalool, (+)-borneol, (-)-borneol, ?-terpineol), ester (geranyl acetate, linalyl acetate, bornyl acetate), and oxide (rose oxide) compounds also reduced CAP peak amplitudes (IC50: 0.50, 0.35, 0.53, 1.7, 2.0, 1.5, 2.3, 2.7, 0.51, 0.71, 0.44, and 2.6mmol/L, respectively). On the other hand, the amplitudes were reduced by a small extent by hydrocarbons (myrcene and p-cymene) and ketone (camphor) at high concentrations (2-5mmol/L). The activities of citral and other TRP agonists ((+)-borneol and camphor) were resistant to TRP antagonist ruthenium red. An efficacy sequence for the CAP inhibitions was generally aldehydes ? esters ? alcohols > oxides > hydrocarbons. The CAP inhibition by the aroma oil compound was not related to its octanol-water partition coefficient. It is suggested that aroma oil compounds inhibit nerve conduction in a manner specific to their chemical structures without TRP activation. PMID:26038703

  6. Inhibition of the compound action potentials of frog sciatic nerves by aroma oil compounds having various chemical structures

    PubMed Central

    Ohtsubo, Sena; Fujita, Tsugumi; Matsushita, Akitomo; Kumamoto, Eiichi

    2015-01-01

    Plant-derived chemicals including aroma oil compounds have an ability to inhibit nerve conduction and modulate transient receptor potential (TRP) channels. Although applying aroma oils to the skin produces a local anesthetic effect, this has not been yet examined throughly. The aim of the present study was to know how nerve conduction inhibitions by aroma oil compounds are related to their chemical structures and whether these activities are mediated by TRP activation. Compound action potentials (CAPs) were recorded from the frog sciatic nerve by using the air-gap method. Citral (aldehyde), which activates various types of TRP channels, attenuated the peak amplitude of CAP with the half-maximal inhibitory concentration (IC50) value of 0.46mmol/L. Another aldehyde (citronellal), alcohol (citronellol, geraniol, ()-linalool, (?)-linalool, (+)-borneol, (?)-borneol, ?-terpineol), ester (geranyl acetate, linalyl acetate, bornyl acetate), and oxide (rose oxide) compounds also reduced CAP peak amplitudes (IC50: 0.50, 0.35, 0.53, 1.7, 2.0, 1.5, 2.3, 2.7, 0.51, 0.71, 0.44, and 2.6mmol/L, respectively). On the other hand, the amplitudes were reduced by a small extent by hydrocarbons (myrcene and p-cymene) and ketone (camphor) at high concentrations (25mmol/L). The activities of citral and other TRP agonists ((+)-borneol and camphor) were resistant to TRP antagonist ruthenium red. An efficacy sequence for the CAP inhibitions was generally aldehydes ? esters ? alcohols > oxides >> hydrocarbons. The CAP inhibition by the aroma oil compound was not related to its octanolwater partition coefficient. It is suggested that aroma oil compounds inhibit nerve conduction in a manner specific to their chemical structures without TRP activation. PMID:26038703

  7. CHEMICAL SPECIATION OF INORGANIC COMPOUNDS UNDER HYDROTHERMAL CONDITIONS

    EPA Science Inventory

    This research will utilize the high-intensity x-rays available at the Advance Photon Source (APS) to study the inorganic chemistry occurring during the hydrothermal oxidation of tank waste and the chemistry associated with tank waste vitrification. Although the chemical conversio...

  8. 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.

  9. Chloracne in seven organic chemists exposed to novel polycyclic halogenated chemical compounds (triazoloquinoxalines).

    PubMed

    Gawkrodger, D J; Harris, G; Bojar, R A

    2009-10-01

    Chloracne is an acneiform eruption caused though poisoning by aromatic compounds (usually halogenated) showing a specific molecular configuration. We describe an outbreak of chloracne among seven discovery chemists who synthesized novel polycyclic halogenated chemical compounds which were classified as triazoloquinoxalines, not known to be chloracnegenic. The diagnosis of chloracne, made clinically, elicited a thorough risk assessment and monitoring programme by the occupational health department. The chemists were investigated by serum excretion rates, skin sampling for Propionibacterium acnes, skin biopsy and laboratory blood investigations. Sebum excretion was normal in five cases, raised in one case and severely reduced in another. Skin levels of P. acnes were normal in all patients except for the one subject who had low sebum excretion, in whom they were undetectable. One subject had a slightly raised serum level of alanine aminotransferase. There were no other signs of systemic toxicity. Two subjects were treated with an oral antibiotic, two received topical therapy only and three required no treatment at all. The patients have had thorough health surveillance at 6-monthly and yearly intervals. In each case the chloracne mostly resolved within 18-24 months although on examination about 3 years later, five of the seven still showed minor changes of chloracne. This outbreak emphasizes the need for vigilance in discovery science. The triazoloquinoxalines were not previously recognized as being chloracnegens although their chemical characteristics were subsequently identified as being in keeping with other chemicals that can cause chloracne. Chloracne can be a difficult diagnosis to make when it occurs in a novel setting: occupational physicians and dermatologists need to be vigilant when dealing with unusual eruptions in discovery chemists. PMID:19558551

  10. Revealing of Biological Activity in Crude Extracts, Seperated Fractions, Groups of Chemical Substance and Individual Compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crude extracts, separated fractions, groups of chemical substances, and individual compounds from natural sources are all evaluated stepwise while performing purifications in in-house bioassays. In a stepwise fashion proceeding from crude extracts to fractions and on to pure compounds, decisions ar...

  11. Chemical process for the catalytic oxidation of formaldehyde and other organic compounds

    SciTech Connect

    Murphy, A.P.

    1991-01-01

    The invention discusses a chemical process for the catalytic oxidation of formaldehyde and other organic compounds contained in a dilute aqueous solution, particularly waste water. The inventive feature resides in the use of a cobalt catalyst to increase the rate of oxidation of the organic compounds when hypochlorous acid is the oxidant. The latter may be provided by a chlorine compound, such as sodium hypochlorite, calcium hypochlorite or chlorine gas dissolved in water.

  12. Combined rational design and a high throughput screening platform for identifying chemical inhibitors of a Ras-activating enzyme.

    PubMed

    Evelyn, Chris R; Biesiada, Jacek; Duan, Xin; Tang, Hong; Shang, Xun; Papoian, Ruben; Seibel, William L; Nelson, Sandra; Meller, Jaroslaw; Zheng, Yi

    2015-05-15

    The Ras family small GTPases regulate multiple cellular processes, including cell growth, survival, movement, and gene expression, and are intimately involved in cancer pathogenesis. Activation of these small GTPases is catalyzed by a special class of enzymes, termed guanine nucleotide exchange factors (GEFs). Herein, we developed a small molecule screening platform for identifying lead hits targeting a Ras GEF enzyme, SOS1. We employed an ensemble structure-based virtual screening approach in combination with a multiple tier high throughput experimental screen utilizing two complementary fluorescent guanine nucleotide exchange assays to identify small molecule inhibitors of GEF catalytic activity toward Ras. From a library of 350,000 compounds, we selected a set of 418 candidate compounds predicted to disrupt the GEF-Ras interaction, of which dual wavelength GDP dissociation and GTP-loading experimental screening identified two chemically distinct small molecule inhibitors. Subsequent biochemical validations indicate that they are capable of dose-dependently inhibiting GEF catalytic activity, binding to SOS1 with micromolar affinity, and disrupting GEF-Ras interaction. Mutagenesis studies in conjunction with structure-activity relationship studies mapped both compounds to different sites in the catalytic pocket, and both inhibited Ras signaling in cells. The unique screening platform established here for targeting Ras GEF enzymes could be broadly useful for identifying lead inhibitors for a variety of small GTPase-activating GEF reactions. PMID:25825487

  13. Chemical pneumonitis due to exposure to bromine compounds

    SciTech Connect

    Kraut, A.; Lilis, R.

    1988-07-01

    A 60-year-old laboratory technician developed pulmonary infiltrates consistent with chemical pneumonitis following accidental exposure to a mixture of hydrogen bromide and phosphorus tribromide. A protracted clinical course ensued consistent with bronchiolitis obliterans. These problems may have been avoided if the potential for subsequent damage had been realized at the time of the initial exposure. Health personnel must be aware of the potentially delayed effects of accidental exposures to respiratory irritants.

  14. Chemical genomic profiling via barcode sequencing to predict compound mode of action

    PubMed Central

    Piotrowski, Jeff S.; Simpkins, Scott W.; Li, Sheena C.; Deshpande, Raamesh; McIlwain, Sean; Ong, Irene; Myers, Chad L.; Boone, Charlie; Andersen, Raymond J.

    2015-01-01

    Summary Chemical genomics is an unbiased, whole-cell approach to characterizing novel compounds to determine mode of action and cellular target. Our version of this technique is built upon barcoded deletion mutants of Saccharomyces cerevisiae and has been adapted to a high-throughput methodology using next-generation sequencing. Here we describe the steps to generate a chemical genomic profile from a compound of interest, and how to use this information to predict molecular mechanism and targets of bioactive compounds. PMID:25618354

  15. Enhancement of the chemical semantic web through the use of InChI identifiers.

    PubMed

    Coles, Simon J; Day, Nick E; Murray-Rust, Peter; Rzepa, Henry S; Zhang, Yong

    2005-05-21

    Molecules, as defined by connectivity specified via the International Chemical Identifier (InChI), are precisely indexed by major web search engines so that Internet tools can be transparently used for unique structure searches. PMID:15889163

  16. 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

  17. 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…

  18. Photochemical ozone creation potentials for organic compounds in northwest Europe calculated with a master chemical mechanism

    NASA Astrophysics Data System (ADS)

    Derwent, Richard G.; Jenkin, Michael E.; Saunders, Sandra M.; Pilling, Michael J.

    Master Chemical Mechanism containing over 2400 chemical species and over 7100 chemical reactions is employed here to describe the atmospheric degradation of 120 organic compounds and the associated regional scale ozone and PAN formation under conditions appropriate to the polluted boundary layer over northwest Europe. Photochemical ozone and PAN creation potentials (POCP and PPCP) are derived for each organic compound from their propensities to form ozone and PAN relative to ethylene and propylene, respectively. The robustness of these POCP values to changes in the NO x emission densities across Europe is tested and the values are compared with previous studies. The POCP values are reviewed and rationalised against the background of our current understanding of the intrinsic properties of each organic compound, their atmospheric degradation pathways and other mechanistic data. These POCPs should assist policy-makers in defining realistic and robust pollution control strategies which focus on those organic compounds which contribute most to regional scale ozone formation across northwest Europe.

  19. Gametocytocidal Screen Identifies Novel Chemical Classes with Plasmodium falciparum Transmission Blocking Activity

    PubMed Central

    Sanders, Natalie G.; Sullivan, David J.; Mlambo, Godfree; Dimopoulos, George; Tripathi, Abhai K.

    2014-01-01

    Discovery of transmission blocking compounds is an important intervention strategy necessary to eliminate and eradicate malaria. To date only a small number of drugs that inhibit gametocyte development and thereby transmission from the mosquito to the human host exist. This limitation is largely due to a lack of screening assays easily adaptable to high throughput because of multiple incubation steps or the requirement for high gametocytemia. Here we report the discovery of new compounds with gametocytocidal activity using a simple and robust SYBR Green I- based DNA assay. Our assay utilizes the exflagellation step in male gametocytes and a background suppressor, which masks the staining of dead cells to achieve healthy signal to noise ratio by increasing signal of viable parasites and subtracting signal from dead parasites. By determining the contribution of exflagellation to fluorescent signal and using appropriate cutoff values, we were able to screen for gametocytocidal compounds. After assay validation and optimization, we screened an FDA approved drug library of approximately 1500 compounds, as well as the 400 compound MMV malaria box and identified 44 gametocytocidal compounds with sub to low micromolar IC50s. Major classes of compounds with gametocytocidal activity included quaternary ammonium compounds with structural similarity to choline, acridine-like compounds similar to quinacrine and pyronaridine, as well as antidepressant, antineoplastic, and anthelminthic compounds. Top drug candidates showed near complete transmission blocking in membrane feeding assays. This assay is simple, reproducible and demonstrated robust Z-factor values at low gametocytemia levels, making it amenable to HTS for identification of novel and potent gametocytocidal compounds. PMID:25157792

  20. STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS

    PubMed Central

    Macher, Egon; Chase, Merrill W.

    1969-01-01

    In light of knowledge of the rate and route of dispersal of allergenic chemicals from ear sites (0.25 g of picryl chloride, or 2:4 dinitrochlorobenzene in 0.25 g and 5.0 g amounts), dispersal was interrupted at selected times by ear excision. The animals exposed in this manner to different, tiny amounts of allergen were tested for development of contact type hypersensitivity. Both of these allergenic chemicals left the local ear site in about three phases of successively lengthening "half-lives." In the first phase, the escape rate was high. The principal pathway of escape was not via the lymphatics but via the blood vessels. Ear excisions made at 24 hr after injection of 0.25 g of picryl chloride (PCl) or at 12 hr after injection of 5.0 g of dinitrochlorobenzene (DNCB) essentially blocked onset of delayed type hypersensitivity, hence the first fraction to escape (80% of PCl, 98% of DNCB) was not used for sensitization. This large fraction serves rather to set up a state of specific tolerance, for these individuals showed extensive deficits in their ability to respond to a later sensitizing course. Also the ability to form hapten-specific antibody appeared nearly completely suppressed. Injections of allergen into the blood stream or directly in auricular nodes, in an amount approximating that which escaped early from the ear, also led to the same degrees of unresponsivenesssometimes full, sometimes partial tolerance. The same types of specific tolerance were secured also by injecting subsensitizing doses into the ear, without excision, or into the flank and by contact tests applied to the flank. The allergen remaining in the ear after the early outflow, particularly between 1224 hr and 34 days, appeared to constitute the sensitizing depot. The longer this depot was available to the animals the greater the immunological "information" for sensitization was picked up until the depot had served its full function around the 4th day. "Peripheral sensitization" was clearly demonstrable. The eventual degree of sensitivity attained by the animals was a resultant of two immunologic processes which occurred independentlytolerogenic effects of escaped chemical on the one hand and on the other the sensitizing effect of the local sensitizing depot of allergen bound in the ear tissue. PMID:5782765

  1. Toxicological and chemical assessment of ordnance compounds in marine sediments and porewaters

    USGS Publications Warehouse

    Nipper, M.; Carr, R.S.; Biedenbach, J.M.; Hooten, R.L.; Miller, K.

    2002-01-01

    Toxicological and chemical studies were performed with a silty and a sandy marine sediment spiked with 2,6-dinitrotoluene (2,6-DNT), 2,4,6-trinitrophenylmethylnitramine (tetryl), or 2,4,6-trinitrophenol (picric acid). Whole sediment toxicity was analyzed by the 10-day survival test with the amphipod Ampelisca abdita, and porewater toxicity tests assessed macro-algae (Ulva fasciata) zoospore germination and germling growth, sea urchin (Arbacia punctulata) embryological development, and polychaete (Dinophilus gyrociliatus) survival and reproduction. Whole sediments spiked with 2,6-DNT were not toxic to amphipods. The fine-grained sediment spiked with tetryl was also not acutely toxic. The tetryl and picric acid LC50 values in the sandy sediment were 3.24 and 144 mg/kg dry weight, respectively. The fine-grained sediment spiked with picric acid generated a U-shaped concentration-response curve in the amphipod test, with increased survival both in the lowest and highest concentration. Grain-size distribution and organic carbon content strongly influenced the behavior of ordnance compounds in spiked sediments. Very low concentrations were measured in some of the treatments and irreversible binding and biodegradation are suggested as the processes responsible for the low measurements. Porewater toxicity varied with its sedimentary origin and with ordnance compound. The sea urchin embryological development test tended to be the least sensitive. Tetryl was the most toxic chemical in all porewater tests, and picric acid the least toxic. Samples spiked with 2,6-DNT contained a degradation product identified as 2-methyl-3-nitroaniline (also known as 2-amino-6-nitrotoluene), and unidentified peaks, possibly degradation products, were also seen in some of the picric acid- and tetryl-spiked samples. Degradation products may have played a role in observed toxicity. ?? 2002 Elsevier Science Ltd. All rights reserved.

  2. Toxicological and chemical assessment of ordinance compounds in marine sediments and porewaters.

    PubMed

    Nipper, M; Carr, R S; Biedenbach, J M; Hooten, R L; Miller, K

    2002-08-01

    Toxicological and chemical studies were performed with a silty and a sandy marine sediment spiked with 2,6-dinitrotoluene (2,6-DNT), 2,4,6-trinitrophenylmethylnitramine (tetryl), or 2,4,6-trinitrophenol (picric acid). Whole sediment toxicity was analyzed by the 10-day survival test with the amphipod Ampelisca abdita, and porewater toxicity tests assessed macro-algae (Ulva fasciata) zoospore germination and germling growth, sea urchin (Arbacia punctulata) embryological development, and polychaete (Dinophilus gyrociliatus) survival and reproduction. Whole sediments spiked with 2,6-DNT were not toxic to amphipods. The fine-grained sediment spiked with tetryl was also not acutely toxic. The tetryl and picric acid LC50 values in the sandy sediment were 3.24 and 144 mg/kg dry weight, respectively. The fine-grained sediment spiked with picric acid generated a U-shaped concentration-response curve in the amphipod test, with increased survival both in the lowest and highest concentration. Grain-size distribution and organic carbon content strongly influenced the behavior of ordnance compounds in spiked sediments. Very low concentrations were measured in some of the treatments and irreversible binding and biodegradation are suggested as the processes responsible for the low measurements. Porewater toxicity varied with its sedimentary origin and with ordnance compound. The sea urchin embryological development test tended to be the least sensitive. Tetryl was the most toxic chemical in all porewater tests, and picric acid the least toxic. Samples spiked with 2,6-DNT contained a degradation product identified as 2-methyl-3-nitroaniline (also known as 2-amino-6-nitrotoluene), and unidentified peaks, possibly degradation products, were also seen in some of the picric acid- and tetryl-spiked samples. Degradation products may have played a role in observed toxicity. PMID:12269482

  3. Anti-trypanosomal activities and structural chemical properties of selected compound classes.

    PubMed

    Ponte-Sucre, Alicia; Bruhn, Heike; Schirmeister, Tanja; Cecil, Alexander; Albert, Christian R; Buechold, Christian; Tischer, Maximilian; Schlesinger, Susanne; Goebel, Tim; Fu, Antje; Mathein, Daniela; Merget, Benjamin; Sotriffer, Christoph A; Stich, August; Krohne, Georg; Engstler, Markus; Bringmann, Gerhard; Holzgrabe, Ulrike

    2015-02-01

    Potent compounds do not necessarily make the best drugs in the market. Consequently, with the aim to describe tools that may be fundamental for refining the screening of candidates for animal and preclinical studies and further development, molecules of different structural classes synthesized within the frame of a broad screening platform were evaluated for their trypanocidal activities, cytotoxicities against murine macrophages J774.1 and selectivity indices, as well as for their ligand efficiencies and structural chemical properties. To advance into their modes of action, we also describe the morphological and ultrastructural changes exerted by selected members of each compound class on the parasite Trypanosoma brucei. Our data suggest that the potential organelles targeted are either the flagellar pocket (compound 77, N-Arylpyridinium salt; 15, amino acid derivative with piperazine moieties), the endoplasmic reticulum membrane systems (37, bisquaternary bisnaphthalimide; 77, N-Arylpyridinium salt; 68, piperidine derivative), or mitochondria and kinetoplasts (88, N-Arylpyridinium salt; 68, piperidine derivative). Amino acid derivatives with fumaric acid and piperazine moieties (4, 15) weakly inhibiting cysteine proteases seem to preferentially target acidic compartments. Our results suggest that ligand efficiency indices may be helpful to learn about the relationship between potency and chemical characteristics of the compounds. Interestingly, the correlations found between the physico-chemical parameters of the selected compounds and those of commercial molecules that target specific organelles indicate that our rationale might be helpful to drive compound design toward high activities and acceptable pharmacokinetic properties for all compound families. PMID:25416330

  4. A chemical biology approach identified PI3K as a potential therapeutic target for neurofibromatosis type 2

    PubMed Central

    Petrilli, Alejandra M; Fuse, Marisa A; Donnan, Mathew S; Bott, Marga; Sparrow, Nicklaus A; Tondera, Daniel; Huffziger, Julia; Frenzel, Corina; Malany, C Siobhan; Echeverri, Christophe J; Smith, Layton; Fernández-Valle, Cristina

    2014-01-01

    Mutations in the merlin tumor suppressor gene cause Neurofibromatosis type 2 (NF2), which is a disease characterized by development of multiple benign tumors in the nervous system. The current standard of care for NF2 calls for surgical resection of the characteristic tumors, often with devastating neurological consequences. There are currently no approved non-surgical therapies for NF2. In an attempt to identify much needed targets and therapeutically active compounds for NF2 treatment, we employed a chemical biology approach using ultra-high-throughput screening. To support this goal, we created a merlin-null mouse Schwann cell (MSC) line to screen for compounds that selectively decrease their viability and proliferation. We optimized conditions for 384-well plate assays and executed a proof-of-concept screen of the Library of Pharmacologically Active Compounds. Further confirmatory and selectivity assays identified phosphatidylinositol 3-kinase (PI3K) as a potential NF2 drug target. Notably, loss of merlin function is associated with activation of the PI3K/Akt pathway in human schwannomas. We report that AS605240, a PI3K inhibitor, decreased merlin-null MSC viability in a dose-dependent manner without significantly decreasing viability of control Schwann cells. AS605240 exerted its action on merlin-null MSCs by promoting caspase-dependent apoptosis and inducing autophagy. Additional PI3K inhibitors tested also decreased viability of merlin-null MSCs in a dose-dependent manner. In summary, our chemical genomic screen and subsequent hit validation studies have identified PI3K as potential target for NF2 therapy. PMID:25360213

  5. Chemical modifier screen identifies HDAC inhibitors as suppressors of PKD models.

    PubMed

    Cao, Ying; Semanchik, Nicole; Lee, Seung Hun; Somlo, Stefan; Barbano, Paolo Emilio; Coifman, Ronald; Sun, Zhaoxia

    2009-12-22

    Polycystic kidney disease (PKD) is a common human genetic disease with severe medical consequences. Although it is appreciated that the cilium plays a central role in PKD, the underlying mechanism for PKD remains poorly understood and no effective treatment is available. In zebrafish, kidney cyst formation is closely associated with laterality defects and body curvature. To discover potential drug candidates and dissect signaling pathways that interact with ciliary signals, we performed a chemical modifier screen for the two phenotypes using zebrafish pkd2(hi4166) and ift172(hi2211) models. pkd2 is a causal gene for autosomal dominant PKD and ift172 is essential for building and maintaining the cilium. We identified trichostatin A (TSA), a pan-HDAC (histone deacetylase) inhibitor, as a compound that affected both body curvature and laterality. Further analysis verified that TSA inhibited cyst formation in pkd2 knockdown animals. Moreover, we demonstrated that inhibiting class I HDACs, either by valproic acid (VPA), a class I specific HDAC inhibitor structurally unrelated to TSA, or by knocking down hdac1, suppressed kidney cyst formation and body curvature caused by pkd2 deficiency. Finally, we show that VPA was able to reduce the progression of cyst formation and slow the decline of kidney function in a mouse ADPKD model. Together, these data suggest body curvature may be used as a surrogate marker for kidney cyst formation in large-scale high-throughput screens in zebrafish. More importantly, our results also reveal a critical role for HDACs in PKD pathogenesis and point to HDAC inhibitors as drug candidates for PKD treatment. PMID:19966229

  6. High-throughput chemical screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression and urine concentration

    PubMed Central

    Nomura, Naohiro; Nunes, Paula; Bouley, Richard; Nair, Anil V.; Shaw, Stanley; Ueda, Erica; Pathomthongtaweechai, Nutthapoom; Lu, Hua A. Jenny

    2014-01-01

    A reduction or loss of plasma membrane aquaporin 2 (AQP2) in kidney principal cells due to defective vasopressin (VP) signaling through the VP receptor causes excessive urine production, i.e., diabetes insipidus. The amount of AQP2 on the plasma membrane is regulated by a balance of exocytosis and endocytosis and is the rate limiting step for water reabsorption in the collecting duct. We describe here a systematic approach using high-throughput screening (HTS) followed by in vitro and in vivo assays to discover novel compounds that enhance vasopressin-independent AQP2 membrane expression. We performed initial chemical library screening with a high-throughput exocytosis fluorescence assay using LLC-PK1 cells expressing soluble secreted yellow fluorescent protein and AQP2. Thirty-six candidate exocytosis enhancers were identified. These compounds were then rescreened in AQP2-expressing cells to determine their ability to increase AQP2 membrane accumulation. Effective drugs were then applied to kidney slices in vitro. Three compounds, AG-490, ?-lapachone, and HA14-1 increased AQP2 membrane accumulation in LLC-PK1 cells, and both AG-490 and ?-lapachone were also effective in MDCK cells and principal cells in rat kidney slices. Finally, one compound, AG-490 (an EGF receptor and JAK-2 kinase inhibitor), decreased urine volume and increased urine osmolality significantly in the first 24 h after a single injection into VP-deficient Brattleboro rats. In conclusion, we have developed a systematic procedure for identifying new compounds that modulate AQP2 trafficking using initial HTS followed by in vitro assays in cells and kidney slices, and concluding with in vivo testing in an animal model. PMID:24944200

  7. Toxics release inventory: Guidance for reporting toxic chemicals within the polycyclic aromatic compounds category

    SciTech Connect

    1995-02-01

    Section 313 of the Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA) requires certain facilities manufacturing, processing, or otherwise using listed toxic chemicals to report their environmental releases of such chemicals annually. On November 30, 1994 the U.S. Environmental Protection Agency (EPA) added 286 chemicals and chemical categories, At the time of the addition, EPA indicated that the Agency would develop, as appropriate, interpretations and guidance that the Agency determines are necessary to facilitate accurate reporting for these categories. This document constitutes such guidance for the polycyclic aromatic compounds category.

  8. Prediction of the rodent carcinogenicity of organic compounds from their chemical structures using the FALS method.

    PubMed Central

    Moriguchi, I; Hirano, H; Hirono, S

    1996-01-01

    Fuzzy adaptive least-squares (FALS), a pattern recognition method recently developed in our laboratory for correlating structure with activity rating, was used to generate quantitative structure-activity relationship (QSAR) models on the carcinogenicity of organic compounds of several chemical classes. Using the predictive models obtained from the chemical class-based FALS QSAR approach, the rodent carcinogenicity or noncarcinogenicity of a group of organic chemicals currently being tested by the U.S. National Toxicology Program was estimated from their chemical structures. PMID:8933054

  9. Pharmacophore modeling, molecular docking, and molecular dynamics simulation approaches for identifying new lead compounds for inhibiting aldose reductase 2.

    PubMed

    Sakkiah, Sugunadevi; Thangapandian, Sundarapandian; Lee, Keun Woo

    2012-07-01

    Aldose reductase 2 (ALR2), which catalyzes the reduction of glucose to sorbitol using NADP as a cofactor, has been implicated in the etiology of secondary complications of diabetes. A pharmacophore model, Hypo1, was built based on 26 compounds with known ALR2-inhibiting activity values. Hypo1 contains important chemical features required for an ALR2 inhibitor, and demonstrates good predictive ability by having a high correlation coefficient (0.95) as well as the highest cost difference (128.44) and the lowest RMS deviation (1.02) among the ten pharmacophore models examined. Hypo1 was further validated by Fisher's randomization method (95%), test set (r = 0.91), and the decoy set shows the goodness of fit (0.70). Furthermore, during virtual screening, Hypo1 was used as a 3D query to screen the NCI database, and the hit leads were sorted by applying Lipinski's rule of five and ADME properties. The best-fitting leads were subjected to docking to identify a suitable orientation at the ALR2 active site. The molecule that showed the strongest interactions with the critical amino acids was used in molecular dynamics simulations to calculate its binding affinity to the candidate molecules. Thus, Hypo1 describes the key structure-activity relationship along with the estimated activities of ALR2 inhibitors. The hit molecules were searched against PubChem to find similar molecules with new scaffolds. Finally, four molecules were found to satisfy all of the chemical features and the geometric constraints of Hypo1, as well as to show good dock scores, PLPs and PMFs. Thus, we believe that Hypo1 facilitates the selection of novel scaffolds for ALR2, allowing new classes of ALR2 inhibitors to be designed. PMID:22249747

  10. Targeting apoptosis pathways by natural compounds in cancer: marine compounds as lead structures and chemical tools for cancer therapy.

    PubMed

    von Schwarzenberg, Karin; Vollmar, Angelika M

    2013-05-28

    Natural compounds derived from marine organisms have shown a wide variety of anti-tumor effects and a lot of attention has been drawn to further development of the isolated compounds. A vast quantity of individual chemical structures from different organisms has shown a variety of apoptosis inducing mechanisms in a variety of tumor cells. The bis-steroidal cephalostatin 1 for example, induces apoptosis via activation of caspases whereas the polyketide discodermolide inhibits cell growth by binding to and stabilizing microtubule and salisporamide A, the product of an actinobacterial strain, is an inhibitor of the proteasome. This great variety of mechanisms of action can help to overcome the multitude of resistances exhibited by different tumor specimens. Products from marine organisms and their synthetic derivates are therefore an important source for new therapeutics for single agent or combined therapy with other chemotherapeutics to support the struggle against cancer. PMID:20673697

  11. A small organic compound enhances the religation reaction of human topoisomerase I and identifies crucial elements for the religation mechanism

    PubMed Central

    Arn, Barbara; Coletta, Andrea; Tesauro, Cinzia; Zuccaro, Laura; Fiorani, Paola; Lentini, Sara; Galloni, Pierluca; Conte, Valeria; Floris, Barbara; Desideri, Alessandro

    2013-01-01

    The different steps of the human Top1 (topoisomerase I) catalytic cycle have been analysed in the presence of a pentacyclic-diquinoid synthetic compound. The experiments indicate that it efficiently inhibits the cleavage step of the enzyme reaction, fitting well into the catalytic site. Surprisingly the compound, when incubated with the binary topoisomeraseDNA cleaved complex, helps the enzyme to remove itself from the cleaved DNA and close the DNA gap, increasing the religation rate. The compound also induces the religation of the stalled enzymeCPT (camptothecin)DNA ternary complex. Analysis of the molecule docked over the binary complex, together with its chemical properties, suggests that the religation enhancement is due to the presence on the compound of two oxygen atoms that act as hydrogen acceptors. This property facilitates the deprotonation of the 5? DNA end, suggesting that this is the limiting step in the topoisomerase religation mechanism. PMID:23368812

  12. Ion beam thermography analysis of chemical compounds using ion beam techniques

    NASA Astrophysics Data System (ADS)

    Martinsson, Bengt G.; Hansson, Hans-Christen

    1988-08-01

    The analytical technique of ion beam thermography (IBT) is reported for the first time. IBT is a technique for the determination of chemical compounds. This IBT setup combines the multielemental ion beam technique's particle-induced X-ray emission (PIXE) and particle elastic scattering analysis (PESA) with thermography. A large number of elements are monitored with PIXE ( Z > 14) and PESA (hydrogen, carbon, nitrogen and oxygen). The thermographie treatment results in a thermogram for each element. The chemical compounds are inferred from these thermograms. This work describes the experimental setup. The capability of IBT is demonstrated on NH 4C1, NH 4NO 3 and (NH 4) 2SO 4.

  13. Identifying chemical functionalization on individual carbon nanotubes and graphene by local vibrational fingerprinting.

    PubMed

    Zuccaro, Laura; Kern, Klaus; Balasubramanian, Kannan

    2015-03-24

    Chemical functionalization of carbon nanotubes (CNTs) and graphene allows for fine-tuning their physical and chemical properties to realize fascinating new fundamental phenomena as well as exotic applications. A primary challenge in such endeavors is the need to identify the chemical nature of attached functionalities at a single-nano-object level in a spatially resolved manner. Here we report the vibrational fingerprinting of functional groups that are attached to individual CNTs and graphene flakes. In order to achieve this, we decorate noncovalently functionalized CNTs and graphene with nanoparticles, which leads to the appearance of Raman peaks that can be correlated with the vibrational modes characteristic of the functional groups with diffraction-limited spatial resolution. The presented strategy is generic enough to be extended to other chemical modification routes on a range of nanostructures and hence will allow for rapid characterization of chemical modification of individual (semi)conducting nanostructures. PMID:25731644

  14. Chemical screen to reduce sterol accumulation in Niemann-Pick C disease cells identifies novel lysosomal acid lipase inhibitors.

    PubMed

    Rosenbaum, Anton I; Rujoi, Madalina; Huang, Amy Y; Du, Hong; Grabowski, Gregory A; Maxfield, Frederick R

    2009-12-01

    Niemann-Pick C disease (NPC) is a lysosomal storage disorder causing abnormal accumulation of unesterified free cholesterol in lysosomal storage organelles. High content phenotypic microscopy chemical screens in both human and hamster NPC-deficient cells have identified several compounds that partially revert the NPC phenotype. Cell biological and biochemical studies show that several of these molecules inhibit lysosomal acid lipase, the enzyme that hydrolyzes LDL-derived triacylglycerol and cholesteryl esters. The effects of reduced lysosomal acid lipase activity in lowering cholesterol accumulation in NPC mutant cells were verified by RNAi-mediated knockdown of lysosomal acid lipase in NPC1-deficient human fibroblasts. This work demonstrates the utility of phenotypic cellular screens as a means to identify molecular targets for altering a complex process such as intracellular cholesterol trafficking and metabolism. PMID:19699313

  15. Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators.

    PubMed

    Hieronymus, Haley; Lamb, Justin; Ross, Kenneth N; Peng, Xiao P; Clement, Cristina; Rodina, Anna; Nieto, Maria; Du, Jinyan; Stegmaier, Kimberly; Raj, Srilakshmi M; Maloney, Katherine N; Clardy, Jon; Hahn, William C; Chiosis, Gabriela; Golub, Todd R

    2006-10-01

    Although androgen receptor (AR)-mediated signaling is central to prostate cancer, the ability to modulate AR signaling states is limited. Here we establish a chemical genomic approach for discovery and target prediction of modulators of cancer phenotypes, as exemplified by AR signaling. We first identify AR activation inhibitors, including a group of structurally related compounds comprising celastrol, gedunin, and derivatives. To develop an in silico approach for target pathway identification, we apply a gene expression-based analysis that classifies HSP90 inhibitors as having similar activity to celastrol and gedunin. Validating this prediction, we demonstrate that celastrol and gedunin inhibit HSP90 activity and HSP90 clients, including AR. Broadly, this work identifies new modes of HSP90 modulation through a gene expression-based strategy. PMID:17010675

  16. Identifying biologically active compound classes using phenotypic screening data and sampling statistics.

    PubMed

    Klekota, Justin; Brauner, Erik; Schreiber, Stuart L

    2005-01-01

    Scoring the activity of compounds in phenotypic high-throughput assays presents a unique challenge because of the limited resolution and inherent measurement error of these assays. Techniques that leverage the structural similarity of compounds within an assay can be used to improve the hit-recovery rate from screening data. A technique is presented that uses clustering and sampling statistics to predict likely compound activity by scoring entire structural classes. A set of phenotypic assays performed against a commercially available compound library was used as a test set. Using the class-scoring technique, the resultant activity prediction scores were more reproducible than individual assay measurements, and class scoring recovered known active compounds more efficiently than individual assay measurements because class scoring had fewer false positives. Known biologically active compounds were recovered 87% of the time using class scores, suggesting a low false-negative rate that compared well to individual assay measurements. In addition, many weak and potentially novel classes of active compounds, overlooked by individual assay measurements, were suggested. PMID:16309290

  17. 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 cm30 cm45 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 -patchoulene, -guaiene, -patchoulene, -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 proportional to the pupal mortality. Conclusion These results suggest that the P. cablin chemical compositions have the potential to be used as an ideal eco-friendly approach for the control of mosquitoes. This is the first report on the mosquito repellent and pupicidal activities of the reported P. cablin chemical compositions.

  18. Identification and quantitative analysis of chemical compounds based on multiscale linear fitting of terahertz spectra

    NASA Astrophysics Data System (ADS)

    Qiao, Lingbo; Wang, Yingxin; Zhao, Ziran; Chen, Zhiqiang

    2014-07-01

    Terahertz (THz) time-domain spectroscopy is considered as an attractive tool for the analysis of chemical composition. The traditional methods for identification and quantitative analysis of chemical compounds by THz spectroscopy are all based on full-spectrum data. However, intrinsic features of the THz spectrum only lie in absorption peaks due to existence of disturbances, such as unexpected components, scattering effects, and barrier materials. We propose a strategy that utilizes Lorentzian parameters of THz absorption peaks, extracted by a multiscale linear fitting method, for both identification of pure chemicals and quantitative analysis of mixtures. The multiscale linear fitting method can automatically remove background content and accurately determine Lorentzian parameters of the absorption peaks. The high recognition rate for 16 pure chemical compounds and the accurate predicted concentrations for theophylline-lactose mixtures demonstrate the practicability of our approach.

  19. A field-portable ion trap for the detection of chemical weapons compounds

    SciTech Connect

    Palausky, M.A.; Lammert, S.A.; Merriweather, R.

    1995-12-31

    The pending ratification of the Chemical Weapons Convention Treaty imposes the almost immediate requirement of on-site inspections of chemical facilities worldwide. In support of this activity, the Defense Nuclear Agency has tasked Edgewood Research Development and Engineering Center (ERDEC) to develop a small, field portable mass spectrometer (the {open_quotes}Generic Detector{close_quotes}) which is capable of unambiguous detection of chemical warfare agents and their associated precursors and by-products. Concerns by the chemical industry as to the disclosure of proprietary information necessitates the development of instruments which are specific only to the targeted compounds while remaining blind to proprietary compounds not covered by the treaty. Ion trap MS/MS, with its combination of high sensitivity and selectivity is uniquely suited for this role.

  20. Relationships between chemical structure and rat repellency: II. compounds screened between 1950 and 1960

    USGS Publications Warehouse

    Bowles, Walter A.; Adomaitis, V.A.; DeWitt, J.B.; Pratt, J.J., Jr.

    1974-01-01

    Over 4,600 compounds, chiefly organic types, were evaluated using both a food acceptance test (Part A) and a barrier penetration bioassay (Part B), to correlate relationships between chemical structure and rodent repellency. These chemicals are indexed and classified according to the functional groups present and to the degree of substitution within their molecular structures. The results of reduction in food consumption for each compound appraised are calculated and their K values listed in Table 1. The repellent activities of the functional groups represented, alone or in combinations, are expressed in Table II by a Functional Group Repellency Index.. A ranking of these indices suggests that acyclic and heteroyclic compounds containing tri- or pentavalent nitrogen would be a parent compound of choice for synthesizing novel repellents. Other molecular arrangements, spatial configurations and combinations of functional groups are compared. There were 123 active, interesting or promising compounds included in the 699 having K values of 85 or greater, which were selected for the barrier appraisal study. These chemicals were formulated in selective solvents at several concentrations and applied to burlap. Small food bags were fashioned using the fabric impregnated with the candidate formulation, and exposed to rodent attack following storage periods of varying intervals. The results of these tests are listed in Table III. Again, those compounds containing nitrogen in the functional groupings indicated a high order of effectiveness. Several commercial patents covering rodent repellents were issued using the data from the food acceptance and barrier studies. Organizations and cooperators which supplied samples for the program are listed in Appendix I. The Wiswesser cipher for compounds in Table I is used in Appendix II to facilitate location of chemicals by sample code number as they appear under the index headings, and for computer storage and analysis.

  1. Relationships between chemical structure and rat repellency. II. Compounds screened between 1950 and 1960

    USGS Publications Warehouse

    Bowles, W.A.; Adomaitis, V.A.; DeWitt, J.B.; Pratt, J.J., Jr.

    1974-01-01

    Over 4,600 compounds, chiefly organic types, were evaluated using both a food acceptance test (Part A) and a barrier penetration bioassay (Part B), to correlate relationships between chemical structure and rodent repellency.These chemicals are indexed and classified according to the functional groups present and to the degree of substitution within their molecular structures. The results of reduction in foot consumption for each compound appraised are calculated and their K values listed in Table I.The repellent activities of the functional groups represented, alone or in combinations, are expressed in Table II by a Functional Group Repellency Index. A ranking of these indices suggests that acyclic and heteroyclic compounds containing tri- or pentavalent nitrogen would be a parent compound of choice for synthesizing novel repellents. Other molecular arrangements, spatial configurations and combinations of functional groups are compared.There were 123 active, interesting or promising compounds included in the 699 having K values of 85 or greater, which were selected for the barrier appraisal study. These chemicals were formulated in selective solvents at several concentrations and applied to burlap. Small foot bags were fashioned using the fabric impregnated with the candidate formulation, and exposed to rodent attack following storage periods of varying intervals. The results of these tests are listed in Table III. Again, those compounds containing nitrogen in the functional groupings indicated a high order of effectiveness. Several commercial patents covering rodent repellents were issued using the data from the food acceptance and barrier studies.Organizations and cooperators which supplied samples for the program are listed in Appendix I. The Wiswesser cipher for compounds in Table I is used in Appendix II to facilitate location of chemicals by sample code number as they appear under the index headings, and for computer storage and analysis.

  2. Managing, profiling and analyzing a library of 2.6 million compounds gathered from 32 chemical providers.

    PubMed

    Monge, Aurlien; Arrault, Alban; Marot, Christophe; Morin-Allory, Luc

    2006-08-01

    The data for 3.8 million compounds from structural databases of 32 providers were gathered and stored in a single chemical database. Duplicates are removed using the IUPAC International Chemical Identifier. After this, 2.6 million compounds remain. Each database and the final one were studied in term of uniqueness, diversity, frameworks, 'drug-like' and 'lead-like' properties. This study also shows that there are more than 87 000 frameworks in the database. It contains 2.1 million 'drug-like' molecules among which, more than one million are 'lead-like'. This study has been carried out using 'ScreeningAssistant', a software dedicated to chemical databases management and screening sets generation. Compounds are stored in a MySQL database and all the operations on this database are carried out by Java code. The druglikeness and leadlikeness are estimated with 'in-house' scores using functions to estimate convenience to properties; unicity using the InChI code and diversity using molecular frameworks and fingerprints. The software has been conceived in order to facilitate the update of the database. 'ScreeningAssistant' is freely available under the GPL license. PMID:17031540

  3. Identifying new small molecule anti-invasive compounds for glioma treatment

    PubMed Central

    Munson, Jennifer; Bonner, Michael; Fried, Levi; Hofmekler, Jonathan; Arbiser, Jack; Bellamkonda, Ravi

    2013-01-01

    Glioblastoma is a disease with poor survival rates after diagnosis. Treatment of the disease involves debulking of the tumor, which is limited by the degree of invasiveness of the disease. Therefore, a treatment to halt the invasion of glioma is desirable for clinical implementation. There have been several candidate compounds targeting specific aspects of invasion, including cell adhesions, matrix degradation, and cytoskeletal rearrangement, but they have failed clinically for a variety of reasons. New targets against glioma invasion include upstream mediators of these classical targets in an effort to better inhibit invasion with more specificity for cancer. Included in these treatments is a new class of compounds inhibiting the generation of reactive oxygen species by targeting the NADPH oxidases. These compounds stand to inhibit multiple pathways, including nuclear factor kappa B and Akt. By conducting a screen of compounds thought to inhibit these pathways, a new compound to halt invasion was found that may have a beneficial effect against glioma, based on recent publications. Further, there are still limitations to the treatment of glioblastoma regardless of the discovery of new targets and compounds that should be addressed to better the therapies against this deadly cancer. PMID:24067366

  4. Combining non selective gas sensors on a mobile robot for identification and mapping of multiple chemical compounds.

    PubMed

    Bennetts, Victor Hernandez; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J; Marco, Santiago; Trincavelli, Marco

    2014-01-01

    In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources. PMID:25232911

  5. Combining Non Selective Gas Sensors on a Mobile Robot for Identification and Mapping of Multiple Chemical Compounds

    PubMed Central

    Victor Hernandez, Bennetts; Schaffernicht, Erik; Pomareda, Victor; Lilienthal, Achim J.; Marco, Santiago; Trincavelli, Marco

    2014-01-01

    In this paper, we address the task of gas distribution modeling in scenarios where multiple heterogeneous compounds are present. Gas distribution modeling is particularly useful in emission monitoring applications where spatial representations of the gaseous patches can be used to identify emission hot spots. In realistic environments, the presence of multiple chemicals is expected and therefore, gas discrimination has to be incorporated in the modeling process. The approach presented in this work addresses the task of gas distribution modeling by combining different non selective gas sensors. Gas discrimination is addressed with an open sampling system, composed by an array of metal oxide sensors and a probabilistic algorithm tailored to uncontrolled environments. For each of the identified compounds, the mapping algorithm generates a calibrated gas distribution model using the classification uncertainty and the concentration readings acquired with a photo ionization detector. The meta parameters of the proposed modeling algorithm are automatically learned from the data. The approach was validated with a gas sensitive robot patrolling outdoor and indoor scenarios, where two different chemicals were released simultaneously. The experimental results show that the generated multi compound maps can be used to accurately predict the location of emitting gas sources. PMID:25232911

  6. Chemical mutagenesis testing in Drosophila. VII. Results of 22 coded compounds tested in larval feeding experiments

    SciTech Connect

    Zimmering, S.; Mason, J.M.; Valencia, R. )

    1989-01-01

    Twenty-two chemicals were tested for mutagenicity in the sex-linked recessive lethal (SLRL) mutation assay after being fed to Drosophila melanogaster larvae. One compound, maleic hydrazide, was found to be mutagenic. It was tested for the ability to produce reciprocal translocations (RTs) and was positive in that assay as well.

  7. Characterization of Spatial Repellent, Contact Irritant and Toxicant Chemical Actions of Standard Vector Control Compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A previously described modular high-throughput screening system (HITTS) was used to characterize the spatial repellent, contact irritant and toxicant chemical actions of 14 compounds with a history of use in vector control. The response of F1-F4 Aedes aegypti to various concentrations of four organo...

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

    PubMed

    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

  9. 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

  10. 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...

  11. Antibacterial activity of coffee extracts and selected coffee chemical compounds against enterobacteria.

    PubMed

    Almeida, Ana Amlia P; Farah, Adriana; Silva, Daniela A M; Nunan, Elzria A; Glria, M Beatriz A

    2006-11-15

    The in vitro antimicrobial activity of commercial coffee extracts and chemical compounds was investigated on nine strains of enterobacteria. The antimicrobial activity investigated by the disc diffusion method was observed in both the extracts and tested chemical compounds. Even though pH, color, and the contents of trigonelline, caffeine, and chlorogenic acids differed significantly among the coffee extracts, no significant differences were observed in their antimicrobial activity. Caffeic acid and trigonelline showed similar inhibitory effect against the growth of the microorganisms. Caffeine, chlorogenic acid, and protocatechuic acid showed particularly strong effect against Serratia marcescens and Enterobacter cloacae. The IC(50) and IC(90) for the compounds determined by the microtiter plate method indicated that trigonelline, caffeine, and protocatechuic acids are potential natural antimicrobial agents against Salmonella enterica. The concentrations of caffeine found in coffee extracts are enough to warrant 50% of the antimicrobial effect against S. enterica, which is relevant to human safety. PMID:17090115

  12. Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

    PubMed Central

    Essack, Magbubah; Alzubaidy, Hanin S.; Bajic, Vladimir B.; Archer, John A. C.

    2014-01-01

    In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review. PMID:25356733

  13. Chemical Genetics Reveals an RGS/G-Protein Role in the Action of a Compound

    PubMed Central

    Fitzgerald, Kevin; Tertyshnikova, Svetlana; Moore, Lisa; Bjerke, Lynn; Burley, Ben; Cao, Jian; Carroll, Pamela; Choy, Robert; Doberstein, Steve; Dubaquie, Yves; Franke, Yvonne; Kopczynski, Jenny; Korswagen, Hendrik; Krystek, Stanley R; Lodge, Nicholas J; Plasterk, Ronald; Starrett, John; Stouch, Terry; Thalody, George; Wayne, Honey; van der Linden, Alexander; Zhang, Yongmei; Walker, Stephen G; Cockett, Mark; Wardwell-Swanson, Judi; Ross-Macdonald, Petra; Kindt, Rachel M

    2006-01-01

    We report here on a chemical genetic screen designed to address the mechanism of action of a small molecule. Small molecules that were active in models of urinary incontinence were tested on the nematode Caenorhabditis elegans, and the resulting phenotypes were used as readouts in a genetic screen to identify possible molecular targets. The mutations giving resistance to compound were found to affect members of the RGS protein/G-protein complex. Studies in mammalian systems confirmed that the small molecules inhibit muscarinic G-protein coupled receptor (GPCR) signaling involving G-?q (G-protein alpha subunit). Our studies suggest that the small molecules act at the level of the RGS/G-?q signaling complex, and define new mutations in both RGS and G-?q, including a unique hypo-adapation allele of G-?q. These findings suggest that therapeutics targeted to downstream components of GPCR signaling may be effective for treatment of diseases involving inappropriate receptor activation. PMID:16683034

  14. Parallelization of enumerating tree-like chemical compounds by breadth-first search order

    PubMed Central

    2015-01-01

    Enumeration of chemical compounds greatly assists designing and finding new drugs, and determining chemical structures from mass spectrometry. In our previous study, we developed efficient algorithms, BfsSimEnum and BfsMulEnum for enumerating tree-like chemical compounds without and with multiple bonds, respectively. For many instances, our previously proposed algorithms were able to enumerate chemical structures faster than other existing methods. Latest processors consist of multiple processing cores, and are able to execute many tasks at the same time. In this paper, we develop three parallelized algorithms BfsEnumP1-3 by modifying BfsSimEnum in simple manners to further reduce execution time. BfsSimEnum constructs a family tree in which each vertex denotes a molecular tree. BfsEnumP1-3 divide a set of vertices with some given depth of the family tree into several subsets, each of which is assigned to each processor. For evaluation, we perform experiments for several instances with varying the division depth and the number of processors, and show that BfsEnumP1-3 are useful to reduce the execution time for enumeration of tree-like chemical compounds. In addition, we show that BfsEnumP3 achieves more than 80% parallelization efficiency using up to 11 processors, and reduce the execution time using 12 processors to about 1/10 of that by BfsSimEnum. PMID:26044861

  15. Genetic and environmental factors affecting host response to drugs and other chemical compounds in our environment.

    PubMed Central

    Vesell, E S; Passananti, G T

    1977-01-01

    Compared to laboratory animals, humans are extremely heterogenous with respect to the many factors that can influence the distribution and biological effects of toxic chemicals. This heterogeneity can prevent an accurate assessment of the impact of a particular toxic compound on the health of an individual subject. Some of the factors that can significantly modify the host response to certain drugs, which serve in this review as a model for environmental chemicals, are enumerated and discussed. Although the mechanisms by which many of these factors modify the biological effects of certain environmental chemicals and drugs have been determined in some cases, better definition of the nature of interactions between these factors and environmental chemicals in a particular individual is required at a biochemical and molecular level. Recommendations are offered for the further development of our knowledge concerning interactions between environmental chemicals and such factors in a particular individual. PMID:598349

  16. Survey of Chemical Compounds Tested In Vitro against Rumen Protozoa for Possible Control of Bloat

    PubMed Central

    Willard, F. L.; Kodras, Rudolph

    1967-01-01

    Over 170 chemical agents were screened for antiprotozoal action in bovine ruminal fluid. Compounds were tested at 0.1 and 0.05% concentrations. Tested compounds included inorganic compounds, antibiotics, biocides, neuromuscular agents, arsenicals, plant and animal hormones, antimalarials, surface-active agents, anthelmintics, and many others. The most active compounds were cupric sulfate, nickel sulfate, nitrofurazone, hydrogen peroxide, dodecyl sodium sulfate, pelargonic acid, iodoacetic acid, 1-diethylaminoethylamino-4-methylthiaxanthrone, sodium arsanilate, sodium arsenate, bismuth glycolyl arsanilate, 1-?-hydroxyethyl-2-methyl-5-nitroimidazole, and p-nitroaniline. Copper ion was not particularly effective against entodinia; nickel ion had no effect on holotrichs. Hydrogen peroxide and iodoacetic acid were effective at a concentration of 0.005%. Anionic surface-active agents were very effective, especially long-chain sulfates and phosphates. These antiprotozoal agents warrant further in vivo studies for possible use in treating or curing bloat in ruminants. PMID:6077407

  17. Cdc25B Dual-Specificity Phosphatase Inhibitors Identified in a High-Throughput Screen of the NIH Compound Library

    PubMed Central

    Foster, Caleb A.; Tierno, Marni Brisson; Shun, Tong Ying; Shinde, Sunita N.; Paquette, William D.; Brummond, Kay M.; Wipf, Peter; Lazo, John S.

    2009-01-01

    Abstract The University of Pittsburgh Molecular Library Screening Center (Pittsburgh, PA) conducted a screen with the National Institutes of Health compound library for inhibitors of in vitro cell division cycle 25 protein (Cdc25) B activity during the pilot phase of the Molecular Library Screening Center Network. Seventy-nine (0.12%) of the 65,239 compounds screened at 10 μM met the active criterion of ≥50% inhibition of Cdc25B activity, and 25 (31.6%) of these were confirmed as Cdc25B inhibitors with 50% inhibitory concentration (IC50) values <50 μM. Thirteen of the Cdc25B inhibitors were represented by singleton chemical structures, and 12 were divided among four clusters of related structures. Thirteen (52%) of the Cdc25B inhibitor hits were quinone-based structures. The Cdc25B inhibitors were further characterized in a series of in vitro secondary assays to confirm their activity, to determine their phosphatase selectivity against two other dual-specificity phosphatases, mitogen-activated protein kinase phosphatase (MKP)-1 and MKP-3, and to examine if the mechanism of Cdc25B inhibition involved oxidation and inactivation. Nine Cdc25B inhibitors did not appear to affect Cdc25B through a mechanism involving oxidation because they did not generate detectable amounts of H2O2 in the presence of dithiothreitol, and their Cdc25B IC50 values were not significantly affected by exchanging the dithiothreitol for β-mercaptoethanol or reduced glutathione or by adding catalase to the assay. Six of the nonoxidative hits were selective for Cdc25B inhibition versus MKP-1 and MKP-3, but only the two bisfuran-containing hits, PubChem substance identifiers 4258795 and 4260465, significantly inhibited the growth of human MBA-MD-435 breast and PC-3 prostate cancer cell lines. To confirm the structure and biological activity of 4260465, the compound was resynthesized along with two analogs. Neither of the substitutions to the two analogs was tolerated, and only the resynthesized hit 26683752 inhibited Cdc25B activity in vitro (IC50 = 13.83 ± 1.0 μM) and significantly inhibited the growth of the MBA-MD-435 breast and PC-3 prostate cancer cell lines (IC50 = 20.16 ± 2.0 μM and 24.87 ± 2.25 μM, respectively). The two bis-furan-containing hits identified in the screen represent novel nonoxidative Cdc25B inhibitor chemotypes that block tumor cell proliferation. The availability of non-redox active Cdc25B inhibitors should provide valuable tools to explore the inhibition of the Cdc25 phosphatases as potential mono- or combination therapies for cancer. PMID:19530895

  18. Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds.

    PubMed

    Sawamura, Seishiro; Hatano, Masahiko; Takada, Yoshinori; Hino, Kyosuke; Kawamura, Tetsuya; Tanikawa, Jun; Nakagawa, Hiroshi; Hase, Hideharu; Nakao, Akito; Hirano, Mitsuru; Rotrattanadumrong, Rachapun; Kiyonaka, Shigeki; Mori, Masayuki X; Nishida, Motohiro; Hu, Yaopeng; Inoue, Ryuji; Nagata, Ryu; Mori, Yasuo

    2016-03-01

    Transient receptor potential canonical (TRPC) proteins form Ca(2+)-permeable cation channels activated upon stimulation of metabotropic receptors coupled to phospholipase C. Among the TRPC subfamily, TRPC3 and TRPC6 channels activated directly by diacylglycerol (DAG) play important roles in brain-derived neurotrophic factor (BDNF) signaling, promoting neuronal development and survival. In various disease models, BDNF restores neurologic deficits, but its therapeutic potential is limited by its poor pharmacokinetic profile. Elucidation of a framework for designing small molecules, which elicit BDNF-like activity via TRPC3 and TRPC6, establishes a solid basis to overcome this limitation. We discovered, through library screening, a group of piperazine-derived compounds that activate DAG-activated TRPC3/TRPC6/TRPC7 channels. The compounds [4-(5-chloro-2-methylphenyl)piperazin-1-yl](3-fluorophenyl)methanone (PPZ1) and 2-[4-(2,3-dimethylphenyl)piperazin-1-yl]-N-(2-ethoxyphenyl)acetamide (PPZ2) activated, in a dose-dependent manner, recombinant TRPC3/TRPC6/TRPC7 channels, but not other TRPCs, in human embryonic kidney cells. PPZ2 activated native TRPC6-like channels in smooth muscle cells isolated from rabbit portal vein. Also, PPZ2 evoked cation currents and Ca(2+) influx in rat cultured central neurons. Strikingly, both compounds induced BDNF-like neurite growth and neuroprotection, which were abolished by a knockdown or inhibition of TRPC3/TRPC6/TRPC7 in cultured neurons. Inhibitors of Ca(2+) signaling pathways, except calcineurin, impaired neurite outgrowth promotion induced by PPZ compounds. PPZ2 increased activation of the Ca(2+)-dependent transcription factor, cAMP response element-binding protein. These findings suggest that Ca(2+) signaling mediated by activation of DAG-activated TRPC channels underlies neurotrophic effects of PPZ compounds. Thus, piperazine-derived activators of DAG-activated TRPC channels provide important insights for future development of a new class of synthetic neurotrophic drugs. PMID:26733543

  19. 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. PMID:15865202

  20. Chemical constituents of peppers (Piper spp.) and application to food preservation: naturally occurring antioxidative compounds.

    PubMed

    Nakatani, N; Inatani, R; Ohta, H; Nishioka, A

    1986-08-01

    In a structure analysis of the compounds of the genus Piper (Family Piperaceae), we identified five phenolic amides from Piper nigrum, seven compounds from P. retrofractum, and two compounds from P. baccatum. All the phenolic amides possess significant antioxidant activities that are more effective than the naturally occurring antioxidant, alpha-tocopherol. One amide, feruperine, has antioxidant activity as high as the synthetic antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). Naturally occurring antioxidants, therefore, may surpass BHA and BHT in their ability to inactivate mutagens in food. PMID:3757949

  1. Chemical compounds in the remote Pacific troposphere: Comparison between MLOPEX measurements and chemical transport model calculations

    NASA Astrophysics Data System (ADS)

    Brasseur, G. P.; Hauglustaine, D. A.; Walters, S.

    1996-06-01

    A global three-dimensional chemical transport model, called MOZART (Model of OZone And Related species in the Troposphere), is used to compare calculated abundances of chemical species and their seasonal evolution in the remote Pacific troposphere near Hawaii with values observed during the Mauna Loa Observatory Photochemistry Experiments (MLOPEX 1 and 2). MOZART is a fully diurnal model which calculates the time evolution of about 30 chemical species from the surface to the upper stratosphere. It accounts for surface emissions of source gases, wet and dry depositions, photochemical transformations and transport processes. The dynamical variables are provided by the National Center for Atmospheric Research (NCAR) Community Climate Model (CCM2) at T42 resolution (2.8 2.8) and 18 levels in the vertical. Simulated abundances of 222Rn reveal an underestimate of the transport of continental emissions to the remote Pacific troposphere, more particularly during winter and summer. Calculated concentrations of chemical species are generally in fair agreement with observations. However, the abundances of soluble species are overestimated, leading, for example, to concentrations of nitric acid (HNO3) and hydrogen peroxide (H2O2) which are overpredicted by a factor of 3-8, depending on the season. This feature is attributed to insufficient washout by clouds and precipitation in the model. MOZART succesfully reproduces the development of high-NOx episodes at Mauna Loa Observatory (MLO) associated with anticyclonic conditions to the north of Hawaii and breakdown of the polar jet which tends to deflect to the central Pacific the flow of NOx transported from eastern Asia (China, Japan). During high NOx episodes, the calculated NOx mixing ratio in the vicinity of the MLO increases by about a factor of 3 over its background level (reaching 90-100 pptv) within 3-5 days.

  2. Crystal chemical and quantum chemical studies of Ba(Sr)-Nb oxide compounds

    NASA Technical Reports Server (NTRS)

    Zubkov, V. G.; Turzhevsky, S. A.; Pereliaev, V. A.; Liechtenstein, A. I.; Gubanov, V. A.

    1990-01-01

    The information available on the BaO(SrO)-NbO-NbO2 system with the niobium atom in the lower oxidation degree is very limited. Very few compounds have been found previously in this system. They are BaNbO3, SrxNbO3(0,7=x=1), Ba2Nb2O9, SrNb8O14; and some suggestions on the BaNb8O14 existence have been made also. At the same time Nb-based oxide compounds could be quite interesting in the search of new noncopper high T(sub c) superconductors Researchers studied Ba(Sr) NbxO2x-2 and Ba2(Sr2)-NbxO2x-1 compositions in the phase diagram of BaO(SrO)-NbO-NbO2 system. The synthesis of the materials was carried out in vacuum at the temperatures of 1000 to 1500 C. Barium carbonate and niobium pentoxide were used as initial components. X-ray analysis was carried out.

  3. Crystal chemical and quantum chemical studies of Ba(Sr)-Nb oxide compounds

    NASA Astrophysics Data System (ADS)

    Zubkov, V. G.; Turzhevsky, S. A.; Pereliaev, V. A.; Liechtenstein, A. I.; Gubanov, V. A.

    1990-04-01

    The information available on the BaO(SrO)-NbO-NbO2 system with the niobium atom in the lower oxidation degree is very limited. Very few compounds have been found previously in this system. They are BaNbO3, SrxNbO3(0,7=x=1), Ba2Nb2O9, SrNb8O14; and some suggestions on the BaNb8O14 existence have been made also. At the same time Nb-based oxide compounds could be quite interesting in the search of new noncopper high T(sub c) superconductors Researchers studied Ba(Sr) NbxO2x-2 and Ba2(Sr2)-NbxO2x-1 compositions in the phase diagram of BaO(SrO)-NbO-NbO2 system. The synthesis of the materials was carried out in vacuum at the temperatures of 1000 to 1500 C. Barium carbonate and niobium pentoxide were used as initial components. X-ray analysis was carried out.

  4. Recombinogenic activity of 10 chemical compounds in male germ cells of Drosophila melanogaster.

    PubMed

    Pontecorvo, Giovanni; Fantaccione, Stefania

    2006-09-01

    The Drosophila melanogaster male germ cells are sensitive to the recombinogenic activity of chemical compounds. In our experiments, we have employed four recessive markers located on the 2nd chromosome: dumpy (dp, 13.0), black (b, 48.5), cinnabar (cn, 57.5), and brown (bw, 104.5); b and cn flank the centromere. Three-day-old larvae, heterozygous for these markers, were treated chronically by oral administration with the test compounds. The chemicals already shown to be positive or negative in the assay systems to test chemical agents in D. melanogaster are three carcinogens (4-nitroquinoline N-oxide, hydroxylamine HCl, and acrylamide), four herbicides (maleic hydrazide, alachlor, trifluralin, and amitrol), and three insecticides (endrin, piperonyl butoxide, and allethrin). In our study, some compounds induced recombinogenic effects in Drosophila premeiotic male germ cells, and comparison of our results with those reported in the literature with the Drosophila wing somatic mutation and recombination assay showed that the somatic cells and the germinal cells have a differential response to the defined compounds. PMID:16043220

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

    SciTech Connect

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.

    2012-05-01

    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 working 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 antigestagenic activity. ► SULT1E1 is a significant marker for endometrial antiprogestin effects. ► Ishikawa cells are a tissue-specific approach for characterization of SPRMs. ► Chemicals acting as progesterone receptor antagonists may exert antifertility effects.

  6. Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening

    PubMed Central

    Wolff, Brian; Snedecor, June; Lim, Kee-Chong; Xu, Fengyun; Renslo, Adam R.; Williams, Janice; McKerrow, James H.; Caffrey, Conor R.

    2009-01-01

    Background Praziquantel (PZQ) is the only widely available drug to treat schistosomiasis. Given the potential for drug resistance, it is prudent to search for novel therapeutics. Identification of anti-schistosomal chemicals has traditionally relied on phenotypic (whole organism) screening with adult worms in vitro and/or animal models of diseasetools that limit automation and throughput with modern microtiter plate-formatted compound libraries. Methods A partially automated, three-component phenotypic screen workflow is presented that utilizes at its apex the schistosomular stage of the parasite adapted to a 96-well plate format with a throughput of 640 compounds per month. Hits that arise are subsequently screened in vitro against adult parasites and finally for efficacy in a murine model of disease. Two GO/NO GO criteria filters in the workflow prioritize hit compounds for tests in the animal disease model in accordance with a target drug profile that demands short-course oral therapy. The screen workflow was inaugurated with 2,160 chemically diverse natural and synthetic compounds, of which 821 are drugs already approved for human use. This affords a unique starting point to reposition (re-profile) drugs as anti-schistosomals with potential savings in development timelines and costs. Findings Multiple and dynamic phenotypes could be categorized for schistosomula and adults in vitro, and a diverse set of hit drugs and chemistries were identified, including anti-schistosomals, anthelmintics, antibiotics, and neuromodulators. Of those hits prioritized for tests in the animal disease model, a number of leads were identified, one of which compares reasonably well with PZQ in significantly decreasing worm and egg burdens, and disease-associated pathology. Data arising from the three components of the screen are posted online as a community resource. Conclusions To accelerate the identification of novel anti-schistosomals, we have developed a partially automated screen workflow that interfaces schistosomula with microtiter plate-formatted compound libraries. The workflow has identified various compounds and drugs as hits in vitro and leads, with the prescribed oral efficacy, in vivo. Efforts to improve throughput, automation, and rigor of the screening workflow are ongoing. PMID:19597541

  7. Chemical characterisation of bioactive compounds in Medicago sativa growing in the desert of Oman.

    PubMed

    Hanif, Muhammad Asif; Al-Maskari, Ahmed Yahya; Al-Sabahi, Jamal Nasser; Al-Hdhrami, Ibtisam; Khan, Muhammad Mumtaz; Al-Azkawi, Ahlam; Hussain, Abdullah Ijaz

    2015-12-01

    Medicago sativa Linn growing in Omani desert were chemically characterised using flame photometry, inductively coupled plasma, gas chromatography-mass spectrometry and high performance liquid chromatographic (HPLC) analysis. HPLC analyses were performed to determine the phenolics and flavonoids present in M. sativa. The major compounds detected in M. sativa leaves were protchaechenic acid (3.22%), hydroxyl benzoic acid (1.05%), ?-Phenyl caffate (0.97%) and kaempherol (0.89%). Pterostilbene, a cholesterol-lowering compound, was detected in M. sativa. PMID:25674815

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

    SciTech Connect

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

    1981-12-01

    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 that 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.

  9. Development of a Fundamental Understanding of Chemical Bonding and Electronic Structure in Spinel Compounds

    SciTech Connect

    Sickafus, K.E.; Wills, J.M.; Chen, S.-P.; Terry, J.H., Jr.; Hartmann, T.; Sheldon, R.I.

    1999-06-03

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Hundreds of ceramic compounds possess the spinel crystal structure and exhibit a remarkable variety of properties, ranging from compounds that are electrical insulators to compounds that are superconducting, or from compounds with ferri- and antiferromagnetic behavior to materials with colossal magnetoresistive characteristics. The unique crystal structure of spinel compounds is in many ways responsible for the widely varying physical properties of spinels. The objective of this project is to investigate the nature of chemical bonding, point defects, and electronic structure in compounds with the spinel crystal structure. Our goal is to understand and predict the stability of the spinel structure as a function of chemical composition, stoichiometry, and cation disorder. The consequences of cation disorder in spinel materials can be profound . The ferromagnetic characteristics of magnesioferrite, for instance, are entirely attributable to disorder on the cation sublattices. Our studies provide insight into the mechanisms of point defect formation and cation disorder and their effects on the electronic band structure and crystal structure of spinel-structure materials. Our ultimate objective is to develop a more substantive knowledge of the spinel crystal structure and to promote new and novel uses for spinel compounds. The technical approach to achieve our goals is to combine first-principles calculations with experimental measurements. The structural and electronic properties of spinel samples were experimentally determined primarily with X-ray and neutron scattering, optical and X-ray absorption, and electron energy-loss spectroscopy. Total energy electronic structure calculations were performed to determine structural stability, band structure, density of states, and electron distribution. We also used shell-model total -energy calculations to assess point-defect formation and migration energies in magnesio-aluminate spinel.

  10. Development of a Fundamental Understanding of Chemical Bonding and Electronic Structure in Spinel Compounds

    SciTech Connect

    Sickafus, K.E.; Wills, J.M.; Chen, S.-P.; Terry, J.H., Jr.; Hartmann, T.; Sheldon, R.I.

    1999-05-14

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos national Laboratory (LANL). Hundreds of ceramic compounds possess the spinel crystal structure and exhibit a remarkable variety of properties, ranging from compounds that are electrical insulators to compounds that are superconducting, or from compounds with ferri- and antiferromagnetic behavior to materials with colossal magnetoresistive characteristics. The unique crystal structure of spinel compounds is in many ways responsible for the widely varying physical properties of spinels. The objective of this project is to investigate the nature of chemical bonding, point defects, and electronic structure in compounds with the spinel crystal structure. Our goal is to understand and predict the stability of the spinel structure as a function of chemical composition, stoichiometry, and cation disorder. The consequences of cation disorder in spinel materials can be profound . The ferromagnetic characteristics of magnesioferrite, for instance, are entirely attributable to disorder on the cation sublattices. Our studies provide insight into the mechanisms of point defect formation and cation disorder and their effects on the electronic band structure and crystal structure of spinel-structure materials. our ultimate objective is to develop a more substantive knowledge of the spinel crystal structure and to promote new and novel uses for spinel compounds. The technical approach to achieve our goals is to combine first-principles calculations with experimental measurements. The structural and electronic properties of spinel samples were experimentally determined primarily with X-ray and neutron scattering, optical and X-ray absorption, and electron energy-loss spectroscopy. Total energy electronic structure calculations were performed to determine structural stability, band structure, density of states, and electron distribution. We also used shell-model total -energy calculations to assess point-defect formation and migration energies in magnesio-aluminate spinel.

  11. Identifying Bottled Water: A Problem-Solving Exercise in Chemical Identification

    NASA Astrophysics Data System (ADS)

    Myers, Richard L.

    1998-12-01

    The availability of a variety of bottled waters from a number of sources provides a readily available resource for problem-solving exercises in chemical analysis. Students are challenged to identify water samples using the known chemical analyses of bottled waters. Several common water quality measurements such as hardness, alkalinity, and ion analysis can be used by students to identify the unknown water. This exercise develops problem-solving skills as students become familiar with basic lab techniques, quality control, data interpretation, and standard methods. Throughout the activity students become more conscious of both their data and data obtained from references. Students learn that data reported from a source are not absolute values, and develop varying degrees of confidence in data sources.

  12. FAF-Drugs3: a web server for compound property calculation and chemical library design.

    PubMed

    Lagorce, David; Sperandio, Olivier; Baell, Jonathan B; Miteva, Maria A; Villoutreix, Bruno O

    2015-07-01

    Drug attrition late in preclinical or clinical development is a serious economic problem in the field of drug discovery. These problems can be linked, in part, to the quality of the compound collections used during the hit generation stage and to the selection of compounds undergoing optimization. Here, we present FAF-Drugs3, a web server that can be used for drug discovery and chemical biology projects to help in preparing compound libraries and to assist decision-making during the hit selection/lead optimization phase. Since it was first described in 2006, FAF-Drugs has been significantly modified. The tool now applies an enhanced structure curation procedure, can filter or analyze molecules with user-defined or eight predefined physicochemical filters as well as with several simple ADMET (absorption, distribution, metabolism, excretion and toxicity) rules. In addition, compounds can be filtered using an updated list of 154 hand-curated structural alerts while Pan Assay Interference compounds (PAINS) and other, generally unwanted groups are also investigated. FAF-Drugs3 offers access to user-friendly html result pages and the possibility to download all computed data. The server requires as input an SDF file of the compounds; it is open to all users and can be accessed without registration at http://fafdrugs3.mti.univ-paris-diderot.fr. PMID:25883137

  13. FAF-Drugs3: a web server for compound property calculation and chemical library design

    PubMed Central

    Lagorce, David; Sperandio, Olivier; Baell, Jonathan B.; Miteva, Maria A.; Villoutreix, Bruno O.

    2015-01-01

    Drug attrition late in preclinical or clinical development is a serious economic problem in the field of drug discovery. These problems can be linked, in part, to the quality of the compound collections used during the hit generation stage and to the selection of compounds undergoing optimization. Here, we present FAF-Drugs3, a web server that can be used for drug discovery and chemical biology projects to help in preparing compound libraries and to assist decision-making during the hit selection/lead optimization phase. Since it was first described in 2006, FAF-Drugs has been significantly modified. The tool now applies an enhanced structure curation procedure, can filter or analyze molecules with user-defined or eight predefined physicochemical filters as well as with several simple ADMET (absorption, distribution, metabolism, excretion and toxicity) rules. In addition, compounds can be filtered using an updated list of 154 hand-curated structural alerts while Pan Assay Interference compounds (PAINS) and other, generally unwanted groups are also investigated. FAF-Drugs3 offers access to user-friendly html result pages and the possibility to download all computed data. The server requires as input an SDF file of the compounds; it is open to all users and can be accessed without registration at http://fafdrugs3.mti.univ-paris-diderot.fr. PMID:25883137

  14. National body-burden database. Chemicals identified in human biological media, 1984. Volume VII, Part 3

    SciTech Connect

    Cone, M.V.; Ferguson, M.; Powers, C.D.; Hammons, A.S.

    1986-01-01

    The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposure to environmental contaminants and the assessment of the significance of such exposure. Data included are obtained through routine manual searches of selected scientific journals, augmented by computer searches. The database, which includes the separately published files, Chemicals Identified in Human Biological Media and Chemicals Identified in Feral and Food Animals, contains information on more than 1600 chemicals. The database is used in exposure, hazard and risk assessment; identifying potential human and environmental health problems including sources of contamination; planning research and comparing results; and in teaching at medical and public health schools. The database is under the aegis of the Interagency Collaborative Group on Environmental Carcinogenesis, National Cancer Institute (NCI) and is maintained by the Health and Environmental Information Section, Science Applications International Corporation under the direction of the Exposure Evaluation Division, US Environmental Protection Agency (EPA). Funding is provided through interagency agreements involving NCI, EPA, and the US Department of Energy.

  15. National body-burden database. Chemicals identified in human biological media, 1984. Volume VII, Part 2

    SciTech Connect

    Cone, M.V.; Ferguson, M.; Powers, C.D.; Hammons, A.S.

    1986-01-01

    The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposure to environmental contaminants and the assessment of the significance of such exposure. Data included are obtained through routine manual searches of selected scientific journals, augmented by computer searches. The database, which includes the separately published files, Chemicals Identified in Human Biological Media and Chemicals Identified in Feral and Food Animals, contains information on more than 1600 chemicals. The database is used in exposure, hazard and risk assessment; identifying potential human and environmental health problems including sources of contamination; planning research and comparing results; and in teaching at medical and public health schools. The database is under the aegis of the Interagency Collaborative Group on Environmental Carcinogenesis, National Cancer Institute (NCI) and is maintained by the Health and Environmental Information Section, Science Applications International Corporation under the direction of the Exposure Evaluation Division, US Environmental Protection Agency (EPA). Funding is provided through interagency agreements involving NCI, EPA, and the US Department of Energy.

  16. National body-burden database. Chemicals identified in human biological media, 1984. Volume VII, Part 1

    SciTech Connect

    Cone, M.V.; Ferguson, M.; Powers, C.D.; Hammons, A.S.

    1986-01-01

    The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposure to environmental contaminants and the assessment of the significance of such exposure. Data included are obtained through routine manual searches of selected scientific journals, augmented by computer searches. The database, which includes the separately published files, Chemicals Identified in Human Biological Media and Chemicals Identified in Feral and Food Animals, contains information on more than 1600 chemicals. The database is used in exposure, hazard and risk assessment; identifying potential human and environmental health problems including sources of contamination; planning research and comparing results; and in teaching at medical and public health schools. The database is under the aegis of the Interagency Collaborative Group on Environmental Carcinogenesis, National Cancer Institute (NCI) and is maintained by the Health and Environmental Information Section, Science Applications International Corporation under the direction of the Exposure Evaluation Division, US Environmental Protection Agency (EPA). Funding is provided through interagency agreements involving NCI, EPA, and the US Department of Energy.

  17. Extended Functional Groups (EFG): An Efficient Set for Chemical Characterization and Structure-Activity Relationship Studies of Chemical Compounds.

    PubMed

    Salmina, Elena S; Haider, Norbert; Tetko, Igor V

    2015-01-01

    The article describes a classification system termed "extended functional groups" (EFG), which are an extension of a set previously used by the CheckMol software, that covers in addition heterocyclic compound classes and periodic table groups. The functional groups are defined as SMARTS patterns and are available as part of the ToxAlerts tool (http://ochem.eu/alerts) of the On-line CHEmical database and Modeling (OCHEM) environment platform. The article describes the motivation and the main ideas behind this extension and demonstrates that EFG can be efficiently used to develop and interpret structure-activity relationship models. PMID:26703557

  18. Micro- and Nanostructured Metal Oxide Chemical Sensors for Volatile Organic Compounds

    NASA Technical Reports Server (NTRS)

    Alim, M. A.; Penn, B. G.; Currie, J. R., Jr.; Batra, A. K.; Aggarwal, M. D.

    2008-01-01

    Aeronautic and space applications warrant the development of chemical sensors which operate in a variety of environments. This technical memorandum incorporates various kinds of chemical sensors and ways to improve their performance. The results of exploratory investigation of the binary composite polycrystalline thick-films such as SnO2-WO3, SnO2-In2O3, SnO2-ZnO for the detection of volatile organic compound (isopropanol) are reported. A short review of the present status of the new types of nanostructured sensors such as nanobelts, nanorods, nanotube, etc. based on metal oxides is presented.

  19. Thin-layer Chromatographic (TLC) Separations and Bioassays of Plant Extracts to Identify Antimicrobial Compounds

    PubMed Central

    Kagan, Isabelle A.; Flythe, Michael D.

    2014-01-01

    A common screen for plant antimicrobial compounds consists of separating plant extracts by paper or thin-layer chromatography (PC or TLC), exposing the chromatograms to microbial suspensions (e.g. fungi or bacteria in broth or agar), allowing time for the microbes to grow in a humid environment, and visualizing zones with no microbial growth. The effectiveness of this screening method, known as bioautography, depends on both the quality of the chromatographic separation and the care taken with microbial culture conditions. This paper describes standard protocols for TLC and contact bioautography with a novel application to amino acid-fermenting bacteria. The extract is separated on flexible (aluminum-backed) silica TLC plates, and bands are visualized under ultraviolet (UV) light. Zones are cut out and incubated face down onto agar inoculated with the test microorganism. Inhibitory bands are visualized by staining the agar plates with tetrazolium red. The method is applied to the separation of red clover (Trifolium pratense cv. Kenland) phenolic compounds and their screening for activity against Clostridium sticklandii, a hyper ammonia-producing bacterium (HAB) that is native to the bovine rumen. The TLC methods apply to many types of plant extracts and other bacterial species (aerobic or anaerobic), as well as fungi, can be used as test organisms if culture conditions are modified to fit the growth requirements of the species. PMID:24747583

  20. In Vivo Rapid Assessment of Compound Exposure (RACE) for Profiling the Pharmacokinetics of Novel Chemical Probes

    PubMed Central

    McAnally, Danielle; Vicchiarelli, Michael; Siddiquee, Khandaker

    2013-01-01

    The RACE assay is an easy and efficient method for estimating the exposure of novel chemical probe compounds in mice. RACE is a truncated and compressed version of a traditional comprehensive in vivo pharmacokinetics study. The method uses a single standard formulation, dose, route of administration, and a small cohort of mice (n=4). Standardized protocols and an abbreviated sample collection scheme reduce the labor needed to perform both the in life and bioanalytical phases of the study. The procedure reduces the complexity of data analysis by eliminating all but one calculated pharmacokinetic parameter; estimated exposure (eAUC20-120), a parameter that is sufficient to rank order compounds based on exposure, but is also easily determined by most software using the simple trapezoidal rule. The RACE assay protocol is readily applicable to early/exploratory studies of most compounds, and is intended to be employed by laboratories with limited expertise in pharmacology and pharmacokinetics. PMID:23788556

  1. Real-time monitoring of volatile organic compounds using chemical ionization mass spectrometry

    DOEpatents

    Mowry, Curtis Dale (Albuquerque, NM); Thornberg, Steven Michael (Peralta, NM)

    1999-01-01

    A system for on-line quantitative monitoring of volatile organic compounds (VOCs) includes pressure reduction means for carrying a gaseous sample from a first location to a measuring input location maintained at a low pressure, the system utilizing active feedback to keep both the vapor flow and pressure to a chemical ionization mode mass spectrometer constant. A multiple input manifold for VOC and gas distribution permits a combination of calibration gases or samples to be applied to the spectrometer.

  2. Metal organic chemical vapor deposition of 111-v compounds on silicon

    DOEpatents

    Vernon, Stanley M. (Wellesley, MA)

    1986-01-01

    Expitaxial composite comprising thin films of a Group III-V compound semiconductor such as gallium arsenide (GaAs) or gallium aluminum arsenide (GaAlAs) on single crystal silicon substrates are disclosed. Also disclosed is a process for manufacturing, by chemical deposition from the vapor phase, epitaxial composites as above described, and to semiconductor devices based on such epitaxial composites. The composites have particular utility for use in making light sensitive solid state solar cells.

  3. Identifying key non-volatile compounds in ready-to-drink green tea and their impact on taste profile.

    PubMed

    Yu, Peigen; Yeo, Angelin Soo-Lee; Low, Mei-Yin; Zhou, Weibiao

    2014-07-15

    Thirty-nine non-volatile compounds in seven ready-to-drink (RTD) green tea samples were analysed and quantified using liquid chromatography. Taste reconstruction experiments using thirteen selected compounds were conducted to identify the key non-volatile tastants. Taste profiles of the reconstructed samples did not differ significantly from the RTD tea samples. To investigate the taste contribution and significance of individual compounds, omission experiments were carried out by removing individual or a group of compounds. Sensory evaluation revealed that the astringent- and bitter-tasting (-)-epigallocatechin gallate, bitter-tasting caffeine, and the umami-tasting l-glutamic acid were the main contributors to the taste of RTD green tea. Subsequently, the taste profile of the reduced recombinant, comprising of a combination of these three compounds and l-theanine, was found to not differ significantly from the sample recombinant and RTD tea sample. Lastly, regression models were developed to objectively predict and assess the intensities of bitterness and astringency in RTD green teas. PMID:24594147

  4. Selenium status in workers handling aromatic nitro-amino compounds in a chemical factory

    SciTech Connect

    Yoshida, M.; Sunaga, M.; Hara, I. )

    1990-09-01

    The selenium status of workers handling aromatic nitro-amino (ANA) compounds was evaluated by measurement of their blood and urinary selenium concentrations and blood glutathione peroxidase (GSH-Px) activities. Forty-seven healthy Japanese male workers (42.7 +/- 12.1 yr) handling ANA compounds routinely in a chemical factory were studied as exposed workers, and 107 nonindustrial healthy Japanese males (39.3 +/- 10.0 yr) in the same region served as a control group. Urinary diazoreaction-positive metabolites and methemoglobin, both of which have been used as indices of exposure to ANA compounds, were significantly elevated in the exposed workers. Both plasma and erythrocyte selenium in the exposed workers showed 20% lower values compared to the control group. GSH-Px activities in plasma and erythrocytes were also significantly decreased in the exposed workers, but urinary selenium excretions were similar between the two groups. Questionnaire information obtained from each subject regarding intake habits of selenium-rich foods (bread, eggs, meat, and fish) indicated that the average dietary selenium intake was similar for the control group and the exposed workers. These results indicate that (1) the workers handling ANA compounds were surely exposed to these chemicals; (2) their selenium status was lower than that of the nonindustrial controls; and (3) the low selenium status was not associated with any dietary factor.

  5. Chemical Shifts to Metabolic Pathways: Identifying Metabolic Pathways Directly from a Single 2D NMR Spectrum.

    PubMed

    Dubey, Abhinav; Rangarajan, Annapoorni; Pal, Debnath; Atreya, Hanudatta S

    2015-12-15

    Identifying cellular processes in terms of metabolic pathways is one of the avowed goals of metabolomics studies. Currently, this is done after relevant metabolites are identified to allow their mapping onto specific pathways. This task is daunting due to the complex nature of cellular processes and the difficulty in establishing the identity of individual metabolites. We propose here a new method: ChemSMP (Chemical Shifts to Metabolic Pathways), which facilitates rapid analysis by identifying the active metabolic pathways directly from chemical shifts obtained from a single two-dimensional (2D) [(13)C-(1)H] correlation NMR spectrum without the need for identification and assignment of individual metabolites. ChemSMP uses a novel indexing and scoring system comprised of a "uniqueness score" and a "coverage score". Our method is demonstrated on metabolic pathways data from the Small Molecule Pathway Database (SMPDB) and chemical shifts from the Human Metabolome Database (HMDB). Benchmarks show that ChemSMP has a positive prediction rate of >90% in the presence of decluttered data and can sustain the same at 60-70% even in the presence of noise, such as deletions of peaks and chemical shift deviations. The method tested on NMR data acquired for a mixture of 20 amino acids shows a success rate of 93% in correct recovery of pathways. When used on data obtained from the cell lysate of an unexplored oncogenic cell line, it revealed active metabolic pathways responsible for regulating energy homeostasis of cancer cells. Our unique tool is thus expected to significantly enhance analysis of NMR-based metabolomics data by reducing existing impediments. PMID:26556218

  6. Miniaturized sequential injection analyzer for the monitoring and quantitation of chemical weapons degradation compounds

    NASA Astrophysics Data System (ADS)

    Lancaster, Herbert L., III; Postlethwaite, Timothy A.; Zhang, Peng; Sorrells, Richard

    2002-06-01

    The ability to monitor and detect chemical warfare agents and their degradation compounds continues to be of utmost importance. Remote on-site field analysis of these compounds is also extremely important as it relates to treaty verification for the Chemical Weapons Convention, as well as the minimization and elimination of human exposure. A portable instrument has been developed and miniaturized that allows for the detection of these compounds in the field with better quantitative results and higher reproducibility than traditional field test kits. All sample and reagent manipulations are conducted in a completely automated fashion. Quantitative results may be determined colorimetrically using the molybdenum blue reaction for the final degradation product of phosphonic acid based chemical warfare agents with a detection limit of 0.05 ppm. The instrument is based on the flow analysis technique of sequential injection analysis (SIA). The benefits of this approach are that the method provides rapid response, high reproducibility of results, high sensitivity and minimal waste production.

  7. Solvent Extraction of Chemical Attribution Signature Compounds from Painted Wall Board: Final Report

    SciTech Connect

    Wahl, Jon H.; Colburn, Heather A.

    2009-10-29

    This report summarizes work that developed a robust solvent extraction procedure for recovery of chemical attribution signature (CAS) compound dimethyl methyl phosphonate (DMMP) (as well as diethyl methyl phosphonate (DEMP), diethyl methyl phosphonothioate (DEMPT), and diisopropyl methyl phosphonate (DIMP)) from painted wall board (PWB), which was selected previously as the exposed media by the chemical attribution scientific working group (CASWG). An accelerated solvent extraction approach was examined to determine the most effective method of extraction from PWB. Three different solvent systems were examined, which varied in solvent strength and polarity (i.e., 1:1 dichloromethane : acetone,100% methanol, and 1% isopropanol in pentane) with a 1:1 methylene chloride : acetone mixture having the most robust and consistent extraction for four original target organophosphorus compounds. The optimum extraction solvent was determined based on the extraction efficiency of the target analytes from spiked painted wallboard as determined by gas chromatography x gas chromatography mass spectrometry (GCxGC-MS) analysis of the extract. An average extraction efficiency of approximately 60% was obtained for these four compounds. The extraction approach was further demonstrated by extracting and detecting the chemical impurities present in neat DMMP that was vapor-deposited onto painted wallboard tickets.

  8. Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women

    PubMed Central

    Pinkerton, JoAnn V.; Santoro, Nanette

    2015-01-01

    Abstract Objective: Two surveys (Harris and Rose surveys) were conducted to quantify the use of compounded hormone therapy (CHT; or bioidentical hormone therapy) among perimenopausal and postmenopausal women in the United States, to assess women's knowledge of CHT versus Food and Drug Administration (FDA)–approved hormone therapy, and to gather information on menopausal experience. Methods: The Harris survey was administered to 801 women aged 45 to 60 years who had experienced at least one menopausal symptom. The Rose survey was administered to 2,044 women aged 40 years or older who were ever users of hormone therapy. Women were queried about menopausal symptoms, hormone therapy use, and knowledge of CHT. Findings from the Rose survey were extrapolated using US Census Bureau data and prescription claims for FDA-approved hormone therapy to estimate the prevalence of CHT use. Results: According to extrapolations using Rose data, up to 2.5 million US women aged 40 years or older may use CHT annually, accounting for 28% to 68% of hormone therapy prescriptions. Harris data showed that 86% of women surveyed were unaware that CHT products are not FDA-approved. The Rose survey asked a subset of 1,771 women whether their hormone therapy had been personalized based on hormone levels; 21% (378) answered “yes” whereas 27% (476) did not know. In both surveys, most hormone therapy users stated that their physician had recommended the treatment. Conclusions: We estimate that 1 million to 2.5 million US women aged 40 years or older use CHT. The data suggest that many women are unaware that compounded hormones have not been evaluated or approved by the FDA. Providers have an educational opportunity to ensure that women considering hormone therapy understand the risks and benefits of inadequately regulated CHT. PMID:25692877

  9. Tankyrase 1 Inhibitors with Drug-like Properties Identified by Screening a DNA-Encoded Chemical Library.

    PubMed

    Samain, Florent; Ekblad, Torun; Mikutis, Gediminas; Zhong, Nan; Zimmermann, Mauro; Nauer, Angela; Bajic, Davor; Decurtins, Willy; Scheuermann, Jrg; Brown, Peter J; Hall, Jonathan; Grslund, Susanne; Schler, Herwig; Neri, Dario; Franzini, Raphael M

    2015-06-25

    We describe the synthesis and screening of a DNA-encoded chemical library containing 76230 compounds. In this library, sets of amines and carboxylic acids are directly linked producing encoded compounds with compact structures and drug-like properties. Affinity screening of this library yielded inhibitors of the potential pharmaceutical target tankyrase 1, a poly(ADP-ribose) polymerase. These compounds have drug-like characteristics, and the most potent hit compound (X066/Y469) inhibited tankyrase 1 with an IC50 value of 250 nM. PMID:26061013

  10. Estrogenic activity assessment of environmental chemicals using in vitro assays: identification of two new estrogenic compounds.

    PubMed Central

    Lascombe, I; Beffa, D; Regg, U; Tarradellas, J; Wahli, W

    2000-01-01

    Environmental chemicals with estrogenic activities have been suggested to be associated with deleterious effects in animals and humans. To characterize estrogenic chemicals and their mechanisms of action, we established in vitro and cell culture assays that detect human estrogen receptor [alpha] (hER[alpha])-mediated estrogenicity. First, we assayed chemicals to determine their ability to modulate direct interaction between the hER[alpha] and the steroid receptor coactivator-1 (SRC-1) and in a competition binding assay to displace 17ss-estradiol (E(2)). Second, we tested the chemicals for estrogen-associated transcriptional activity in the yeast estrogen screen and in the estrogen-responsive MCF-7 human breast cancer cell line. The chemicals investigated in this study were o,p'-DDT (racemic mixture and enantiomers), nonylphenol mixture (NPm), and two poorly analyzed compounds in the environment, namely, tris-4-(chlorophenyl)methane (Tris-H) and tris-4-(chlorophenyl)methanol (Tris-OH). In both yeast and MCF-7 cells, we determined estrogenic activity via the estrogen receptor (ER) for o,p'-DDT, NPm, and for the very first time, Tris-H and Tris-OH. However, unlike estrogens, none of these xenobiotics seemed to be able to induce ER/SRC-1 interactions, most likely because the conformation of the activated receptor would not allow direct contacts with this coactivator. However, these compounds were able to inhibit [(3)H]-E(2) binding to hER, which reveals a direct interaction with the receptor. In conclusion, the test compounds are estrogen mimics, but their molecular mechanism of action appears to be different from that of the natural hormone as revealed by the receptor/coactivator interaction analysis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:10903615

  11. Development of a screening assay to identify teratogenic and embryotoxic chemicals using the zebrafish embryo.

    PubMed

    Selderslaghs, Ingrid W T; Van Rompay, An R; De Coen, Wim; Witters, Hilda E

    2009-11-01

    We developed and optimized a screening procedure, in which zebrafish embryos were explored as a model for the evaluation of the specific embryotoxic and teratogenic potential of chemicals. A selection of known positive (retinoic acid, valproic acid, caffeine, lithium chloride) and negative (glucose, saccharin) compounds for developmental toxicity were used to evaluate this method. We exposed embryos and evaluated embryotoxicity and morphological characteristics of the embryos at 24, 48, 72 and 144 h post fertilization. After evaluation of the induced effects, concentration-response curves were created for both embryotoxicity and teratogenic effects. Values for teratogenic indices (TI) were calculated as the ratio LC(50)/EC(50). The results obtained were compared to existing data from studies with laboratory animals and humans. We demonstrated that our classification of the compounds, based on TI values, allows to distinguish teratogens from non-teratogens and supports the application of zebrafish embryos as an alternative method for developmental toxicity studies to predict effects in mammals. PMID:19447169

  12. Source and plume investigation of chlorinated compounds in groundwater at a chemical plant

    SciTech Connect

    Trahan, D.B.

    1995-10-01

    A site assessment was conducted to determine the distribution of chlorinated compounds in soil and groundwater at a chemical plant in Geismar, Louisiana. The assessment first included an investigation of the source(S) of the contaminants using aerial photos, interviews and plant records. Next, the stratigraphic framework of the site was defined with a hydrogeological investigation using historic borin logs and cone penetrometer testing (CPT). Finally, a plume investigation was performed to determine the horizontal and vertical extent of the contamination using direct-push methods for sampling of soil and groundwater. It was determined that chlorinated compounds originated from leaking drums and cleaning operations prior to 1975. Downward migration of these compounds may have been promoted by the installation of uncased 50-foot wooden pillings. The contamination is limited both vertical and horizontally, to three hydrogeologic zones: (1) the first water-bearing silt zone; (2) an intermediate zone consisting of interlayered silt and clay; and (3) the second water-bearing silt zone. The concentration of chlorinated compounds are greatest in the intermediate zone. There is some evidence of natural degradation of the chlorinated compounds, particularly in the first water-bearing zone.

  13. Volatile Organic Compounds Identified in Post-Flight Air Analysis of the Multipurpose Logistics Module from International Space Station

    NASA Astrophysics Data System (ADS)

    Peterson, B.; Wheeler, R.

    Bioregenerative systems involve storing and processing waste along with atmospheric management. The MPLM, Multipurpose Logistics Module, is a reusable logistics carrier and primary delivery system used to resupply the International Space Station (ISS) and return Station cargo that requires a pressurized environment. The cylindrical module is approximately 6.4 meters long, 4.6 meters in diameter, and weighs almost 4,082kg. The module provides storage and additional workspace for up to two astronauts when docked to the ISS. It can carry up to 9,072 kg of supplies, science experiments, spare parts and other logistical components for ISS. There is concern for a potentially hazardous condition caused by contamination of the atmosphere in the MPLM upon return from orbit. This would be largely due to unforeseen spills or container leakage. This has led to the need for special care in handling the returned module prior to processing the module for its next flight. Prior to opening the MPLM, atmospheric samples are analyzed for trace volatile organic compounds, VOC's. It is noted that our analyses also reflect the atmosphere in the ISS on that day of closure. With the re turn of STS-108, 12th ISS Flight (UF1), the analysis showed 24 PPM of methane. This corresponds to the high levels on space station during a time period when the air filtration system was shut off. Chemical characterization of atmospheres on the ISS and MPLM provide useful information for concerns with plant growth experiments on ISS. Work with closed plant growth chambers show potential for VOC's to accumulate to toxic levels for plants. The ethylene levels for 4 MPLM analyses over the course on one year were measured at, 0.070, 0.017, 0.012 and 0.007 PPM. Phytochemical such as ethylene are detected with natural plant physiological events such as flowering and as a result of plant damage or from decaying food. A build up of VOC's may contribute to phytotoxic effects for the plant growth experiments or health problems for humans. Other identified components from the MPLM are quite similar to those found from off gassing of construction material and laboratory reagents characterized in ground based studies with closed plant growth chambers.

  14. Clinical breath analysis: discriminating between human endogenous compounds and exogenous (environmental) chemical confounders.

    PubMed

    Pleil, Joachim D; Stiegel, Matthew A; Risby, Terence H

    2013-03-01

    Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic (anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous have been proposed to be useful as preclinical biomarkers of various undiagnosed diseases including lung cancer, breast cancer, and cardio-pulmonary disease. The usual approach is to develop difference algorithms comparing VOC profiles from nominally healthy controls to cohorts of patients presenting with a documented disease, and then to apply the resulting rules to breath profiles of subjects with unknown disease status. This approach to diagnosis has a progression of sophistication; at the most rudimentary level, all measurable VOCs are included in the model. The next level corrects exhaled VOC concentrations for current inspired air concentrations. At the highest level, VOCs exhibiting discriminatory value also require a plausible biochemical pathway for their production before inclusion. Although these approaches have all shown some level of success, there is concern that pattern recognition is prone to error from environmental contamination and between-subject variance. In this paper, we explore the underlying assumptions for the interpretation and assignment of endogenous compounds with probative value for assessing changes. Specifically, we investigate the influence of previous exposures, elimination mechanisms and partitioning of exogenous compounds as confounders of true endogenous compounds. We provide specific examples based on a simple classical pharmacokinetic approach to identify potential misinterpretations of breath data and propose some remedies. PMID:23445880

  15. Mutations in a translation initiation factor identify target of a memory-enhancing compound

    PubMed Central

    Sekine, Yusuke; Zyryanova, Alisa; Crespillo-Casado, Ana; Fischer, Peter M.; Harding, Heather P.; Ron, David

    2015-01-01

    The integrated stress response (ISR) modulates mRNA translation to regulate the mammalian unfolded protein response (UPR), immunity and memory formation. A chemical ISR inhibitor, ISRIB, enhances cognitive function and modulates the UPR in vivo. To explore mechanisms involved in ISRIB action we screened cultured mammalian cells for somatic mutations that reversed its effect on the ISR. Clustered missense mutations were found at the N-terminal portion of the delta subunit of guanine nucleotide exchange factor (GEF) eIF2B. When reintroduced by CRISPR-Cas9 gene editing of wildtype cells, these mutations reversed both ISRIB-mediated inhibition of the ISR and its stimulatory effect on eIF2B GEF activity towards its substrate, eIF2, in vitro. Thus ISRIB targets an interaction between eIF2 and eIF2B that lies at the core of the ISR. PMID:25858979

  16. A Substrate Pharmacophore for the Human Organic Cation/Carnitine Transporter Identifies Compounds Associated with Rhabdomyolysis

    PubMed Central

    Ekins, Sean; Diao, Lei; Polli, James E.

    2012-01-01

    The human Organic Cation/Carnitine Transporter (hOCTN2), is a high affinity cation/carnitine transporter expressed widely in human tissues and is physiologically important for the homeostasis of L-carnitine. The objective of this study was to elucidate the substrate requirements of this transporter via computational modelling based on published in vitro data. Nine published substrates of hOCTN2 were used to create a common features pharmacophore that was validated by mapping other known OCTN2 substrates. The pharmacophore was used to search a drug database and retrieved molecules that were then used as search queries in PubMed for instances of a side effect (rhabdomyolysis) associated with interference with L-carnitine transport. The substrate pharmacophore was comprised of two hydrogen bond acceptors, a positive ionizable feature and ten excluded volumes. The substrate pharmacophore also mapped 6 out of 7 known substrate molecules used as a test set. After searching a database of ~800 known drugs, thirty drugs were predicted to map to the substrate pharmacophore with L-carnitine shape restriction. At least 16 of these molecules had case reports documenting an association with rhabdomyolysis and represent a set for prioritizing for future testing as OCTN2 substrates or inhibitors. This computational OCTN2 substrate pharmacophore derived from published data partially overlaps a previous OCTN2 inhibitor pharmacophore and is also able to select compounds that demonstrate rhabdomyolysis, further confirming the possible linkage between this side effect and hOCTN2. PMID:22339151

  17. An In Silico Approach for Identification of Potential Anti-Mycobacterial Targets of Vasicine and Related Chemical Compounds.

    PubMed

    Chaliha, Amrita Kashyap; Gogoi, Dhrubajyoti; Chetia, Pankaj; Sarma, Diganta; Buragohain, Alak Kumar

    2016-01-01

    Tuberculosis (TB) is known to mankind as one of the most pervasive and persistent of diseases since the early days of civilization. The growing resistance of the causative pathogen Mycobacterium tuberculosis to the standard drug regimen for TB poses further difficulty in its treatment and control. Screening of novel plant-derived compounds with promising anti-tubercular activity has been cited as a prospective route for new anti-tubercular drug discovery and design. Justicia adhatoda L. is a perennial evergreen shrub which is widely mentioned in scientific literature on account of its potent anti-mycobacterial properties. In the present study, we have employed a series of computational methodologies to reveal the probable molecular interactions of vasicine, the principal alkaloid of Justicia adhatoda L., and two of its close natural derivatives- vasicinone and deoxyvasicine, with certain biological targets in M. tuberculosis. Targets were identified from literature and through a reverse Pharmacophore-based approach. Subsequent comparative molecular docking to identify the best ligand-target interactions revealed Antigen 85C of M. tuberculosis as the most potent biological target of vasicine on the basis of optimum molecular docking values. A chemogenomics approach was also employed to validate the molecular interactions between the same class of chemical compounds as vasicine and Antigen 85C. Further, a library of structural analogs of vasicine was created by bioiosterism-based drug design to identify structural analogs with better inhibitory potential against Antigen 85C. PMID:26632438

  18. On the chemical bonding features in boron containing compounds: a combined QTAIM/ELF topological analysis.

    PubMed

    Alikhani, M Esmal

    2013-08-14

    The nature of chemical bonding in four classes of boron-containing compounds has been investigated using two topological approaches: the "quantum theory of atoms in molecules (QTAIM)" and "electron localization function (ELF)". It has been shown that the bonding in these compounds could be described in terms of familiar schemes (covalent single, double or triple bonds, dative bond, etc.) and be rationalized from the QTAIM tools. The ELF analysis is the bridge between two worlds: classical donor-acceptor and delocalization in the one hand, and the quantum chemical concepts obtained from the charge and its Laplacian topology. Particularly, we have shown that: (1) in the case of boron-boron bonding, although the V(B,B) basins are similar to the V(C,C) ones, but the V(B,B) population is always smaller than the corresponding V(C,C). (2) In the planar tetracoordinate boron species, each boron atom is characterized by three chemical bonds despite four neighboring atoms. (3). In the [RuH2(?(2):?(2)-H2BMes)(PCy3)2] compound, the B-Ru bonding belongs to the closed-shell interaction, and there is no BCP between the hydrogen bridge atoms (H(B)) and the ruthenium center despite the close contact of the atoms. (4) In the case of the XHMHX hydrogen bonding, we found a complex bonding mode involving not only the two hydrogen atoms, but also the two boron atoms. The presence of an RCP in the center of the B-H-Cr-H-B five-membered cycle confers to the compound the potential to evolve under perturbation. PMID:23812504

  19. Laboratory Infrared Spectroscopy to Identify New Compounds on Icy Moon Surfaces

    NASA Astrophysics Data System (ADS)

    Wray, James J.; Young, Cindy L.; Hand, Kevin P.; Poston, Michael J.; Carlson, Robert W.; Clark, Roger N.; Spencer, John R.; Jennings, Donald E.

    2014-11-01

    We are exploring the value of mid-infrared spectroscopy for identifying non-H2O constituents of icy moon surfaces. Recently we reported evidence for a new emissivity feature identified on Iapetus using Cassini’s Composite Infrared Spectrometer [1]. This 11.7 μm feature is consistent with emissivity minima (transparency features) of very fine-grained silicates. Its position and shape may be diagnostic of silicate type, but most lab data at these wavelengths have been acquired using coarser grains and/or at Earth surface pressures and temperatures. Infrared spectra can change substantially under low-temperature, vacuum conditions [e.g., 2,3].We prepared sieved (<0.4 mm) and very fine-grained (few μm) powders of six different silicates and measured their VNIR (0.35-2.5 μm) reflectance spectra under ambient air, and mid-IR (1.2-20 μm) spectra in a purged N2 glovebox. All silicates exhibited mid-IR transparency features (and loss of other features) in micronized form that were not observed for the coarser grain sizes. Muscovite, a phyllosilicate mineral possibly similar to those tentatively identified on Europa [4], provided the closest match to Iapetus in the mid-IR--although clear VNIR features of muscovite have not been identified on Iapetus [5]--and therefore we measured muscovite across the same wavelength range under Iapetus-like conditions (T=125 K, P<3x10^-8 torr). We will report on our ongoing analysis and plans for additional future measurements in JPL’s Icy Worlds Simulation Lab. [1] Young, C.L., et al. (2014), Workshop on the Habitability of Icy Worlds, Abstract #4038.[2] Logan, L.M., et al. (1973), J. Geophys. Res., 78(23), 4983-5003.[3] Donaldson Hanna, K.L., et al. (2012), J. Geophys. Res., 117, E00H05.[4] Shirley, J.H., et al. (2013), AGU Fall Meeting, Abstract #P54A-07.[5] Clark, R.N., et al. (2012), Icarus, 218, 831-860.

  20. Spectral library validation to identify ingredients of compound feedingstuffs by near infrared reflectance microscopy.

    PubMed

    Fernndez-Ibez, V; Fearn, T; Soldado, A; de la Roza-Delgado, B

    2009-11-15

    To guarantee feed quality and safety the development and improvement of analytical methods for feed authentication and detection of contaminants is fundamental. Near infrared reflectance microscopy (NIRM) has been investigated as an alternative method to contribute to control systems for feed materials. The major task is the need to build NIRM reference spectral libraries that must represent the variability in feed ingredients. The aim of the present work was to evaluate the performance of a NIRM reference spectral library on animal feed, with external samples of animal feed ingredients and possible contaminants such as processed animal proteins, and in particular to assess its ability to identify ingredients in mixtures. Three external sample sets were used: (A) artificial mixtures, (B) synthetic mixtures and (C) synthetic binary mixtures. The prediction and repeatability results for set A, in which the spectra are from pure ingredients, were very good for both animal and vegetable ingredients and confirm that the spectral library is very good at identifying spectra from pure ingredients. For sets B and C, in which the spectra were measured on mixtures, the prediction results were very disappointing compared with the artificial samples. This means that a strategy that tries to match the spectra taken from a mixture with those of pure ingredients is unlikely to meet with much success. It is possible that an interpolation between pure ingredients for suitably chosen spectral ranges may provide a way to extend this system to mixtures, including mixtures of several ingredients. PMID:19782192

  1. FP Tethering: a screening technique to rapidly identify compounds that disrupt protein-protein interactions

    PubMed Central

    Lodge, Jean M.; Rettenmaier, T. Justin; Wells, James A.; Pomerantz, William C.; Mapp, Anna K.

    2014-01-01

    Tethering is a screening technique for discovering small-molecule fragments that bind to pre-determined sites via formation of a disulphide bond. Tethering screens traditionally rely upon mass spectrometry to detect disulphide bind formation, which requires a time-consuming liquid chromatography step. Here we show that Tethering can be performed rapidly and inexpensively using a homogenous fluorescence polarization (FP) assay that detects displacement of a peptide ligand from the protein target as an indirect readout of disulphide formation. We apply this method, termed FP Tethering, to identify fragments that disrupt the protein-protein interaction between the KIX domain of the transcriptional coactivator CBP and the transcriptional activator peptide pKID. PMID:24795804

  2. High-resolution transcriptional profiling of chemical-stimulated dendritic cells identifies immunogenic contact allergens, but not prohaptens.

    PubMed

    Ott, H; Wiederholt, T; Bergstrm, M Andresen; Heise, R; Skazik, C; Czaja, K; Marquardt, Y; Karlberg, A-T; Merk, H-F; Baron, J M

    2010-01-01

    Allergic contact dermatitis is a complex syndrome and knowledge about the in vitro detection of small-molecular-weight compounds, particularly prohaptens, is limited. Therefore, we investigated chemical-induced gene expression changes in human antigen-presenting cells upon stimulation with immunogenic contact allergens, prohaptens and irritants. Monocyte-derived dendritic cells (moDCs) and THP-1 cells were stimulated with the prohapten cinnamic alcohol (CAlc), the hapten cinnamic aldehyde (CAld), an irritant and an obligatory sensitizer in vitro. Whole-genome screening and consecutive PCR analysis of differential gene expression in moDCs stimulated with either CAld or the obligatory sensitizer revealed coregulation of 11 marker genes which were related to immunological reactions (IL-8, CD1e, CD200R1, PLA2G5, TNFRSF11A), oxidative or metabolic stress responses (AKR1C3, SLC7A11, GCLM) or other processes (DPYLS3, TFPI, TRIM16). In contrast, the prohapten CAlc and the irritant did not change marker gene expression. In THP-1 cells, CAld and the positive control elicited similar expression changes in only 4 of the previously identified genes (IL-8, TRIM16, CD200R1, GCLM). In conclusion, we provide important insights into the pathophysiological basis of allergic contact dermatitis, identify marker genes suitable for skin hazard assessment and demonstrate that contact-allergenic prohaptens escape in in vitro detection if their skin metabolism is not taken into account. PMID:20431333

  3. Identifying and characterizing chemical skin sensitizers without animal testing: Colipa's research and method development program.

    PubMed

    Aeby, P; Ashikaga, T; Bessou-Touya, S; Schepky, A; Gerberick, F; Kern, P; Marrec-Fairley, M; Maxwell, G; Ovigne, J-M; Sakaguchi, H; Reisinger, K; Tailhardat, M; Martinozzi-Teissier, S; Winkler, P

    2010-09-01

    The sensitizing potential of chemicals is usually identified and characterized using one of the available animal test methods, such as the mouse local lymph node assay. Due to the increasing public and political concerns regarding the use of animals for the screening of new chemicals, the Colipa Skin Tolerance Task Force collaborates with and/or funds research groups to increase and apply our understanding of the events occurring during the acquisition of skin sensitization. Knowledge gained from this research is used to support the development and evaluation of novel alternative approaches for the identification and characterization of skin sensitizing chemicals. At present one in chemico (direct peptide reactivity assay (DPRA)) and two in vitro test methods (cell based assays (MUSST and h-CLAT)) have been evaluated within Colipa inter-laboratory ring trials and accepted by the European Centre for the Validation of Alternative Methods (ECVAM) for pre-validation. Data from all three test methods will be used to support the development of testing strategy approaches for skin sensitizer potency prediction. The replacement of the need for animal testing for skin sensitization risk assessment is viewed as ultimately achievable and the next couple of years should set the timeline for this milestone. PMID:20624454

  4. Review physical and chemical aspects of stabilization of compounds in silk.

    PubMed

    Pritchard, Eleanor M; Dennis, Patrick B; Omenetto, Fiorenzo; Naik, Rajesh R; Kaplan, David L

    2012-06-01

    The challenge of stabilization of small molecules and proteins has received considerable interest. The biological activity of small molecules can be lost as a consequence of chemical modifications, while protein activity may be lost due to chemical or structural degradation, such as a change in macromolecular conformation or aggregation. In these cases, stabilization is required to preserve therapeutic and bioactivity efficacy and safety. In addition to use in therapeutic applications, strategies to stabilize small molecules and proteins also have applications in industrial processes, diagnostics, and consumer products like food and cosmetics. Traditionally, therapeutic drug formulation efforts have focused on maintaining stability during product preparation and storage. However, with growing interest in the fields of encapsulation, tissue engineering, and controlled release drug delivery systems, new stabilization challenges are being addressed; the compounds or protein of interest must be stabilized during: (1) fabrication of the protein or small molecule-loaded carrier, (2) device storage, and (3) for the duration of intended release needs in vitro or in vivo. We review common mechanisms of compound degradation for small molecules and proteins during biomaterial preparation (including tissue engineering scaffolds and drug delivery systems), storage, and in vivo implantation. We also review the physical and chemical aspects of polymer-based stabilization approaches, with a particular focus on the stabilizing properties of silk fibroin biomaterials. PMID:22270942

  5. Revisiting benzene cluster cations for the chemical ionization of dimethyl sulfide and select volatile organic compounds

    NASA Astrophysics Data System (ADS)

    Kim, M. J.; Zoerb, M. C.; Campbell, N. R.; Zimmermann, K. J.; Blomquist, B. W.; Huebert, B. J.; Bertram, T. H.

    2015-10-01

    Benzene cluster cations were revisited as a sensitive and selective reagent ion for the chemical ionization of dimethyl sulfide (DMS) and a select group of volatile organic compounds (VOCs). Laboratory characterization was performed using both a new set of compounds (i.e. DMS, β-caryophyllene) as well as previously studied VOCs (i.e., isoprene, α-pinene). Using a field deployable chemical ionization time-of-flight mass spectrometer (CI-ToFMS), benzene cluster cations demonstrated high sensitivity (> 1 ncps ppt-1) to DMS, isoprene, and α-pinene standards. Parallel measurements conducted using a chemical-ionization quadrupole mass spectrometer, with a weaker electric field, demonstrated that ion-molecule reactions likely proceed through a combination of ligand-switching and direct charge transfer mechanisms. Laboratory tests suggest that benzene cluster cations may be suitable for the selective ionization of sesquiterpenes, where minimal fragmentation (< 25 %) was observed for the detection of β-caryophyllene, a bicyclic sesquiterpene. The field stability of benzene cluster cations using CI-ToFMS was examined in the marine boundary layer during the High Wind Gas Exchange Study (HiWinGS). The use of benzene cluster cation chemistry for the selective detection of DMS was validated against an atmospheric pressure ionization mass spectrometer. Measurements from the two instruments were highly correlated (R2=0.80) over a wide range of sampling conditions.

  6. Real-time monitoring of volatile organic compounds using chemical ionization mass spectroscopy: Final report

    SciTech Connect

    Thornberg, S.M.; Mowry, C.D.; Keenan, M.R.; Bender, S.F.A.; Owen, T.

    1997-04-01

    Volatile organic compound (VOC) emission to the atmosphere is of great concern to semiconductor manufacturing industries, research laboratories, the public, and regulatory agencies. Some industries are seeking ways to reduce emissions by reducing VOCs at the point of use (or generation). This paper discusses the requirements, design, calibration, and use of a sampling inlet/quadrupole mass spectrometer system for monitoring VOCs in a semiconductor manufacturing production line. The system uses chemical ionization to monitor compounds typically found in the lithography processes used to manufacture semiconductor devices (e.g., acetone, photoresist). The system was designed to be transportable from tool to tool in the production line and to give the operator real-time feedback so the process(es) can be adjusted to minimize VOC emissions. Detection limits ranging from the high ppb range for acetone to the low ppm range fore other lithography chemicals were achieved using chemical ionization mass spectroscopy at a data acquisition rate of approximately 1 mass spectral scan (30 to 200 daltons) per second. A demonstration of exhaust VOC monitoring was performed at a working semiconductor fabrication facility during actual wafer processing.

  7. Symbolic, neural, and Bayesian machine learning models for predicting carcinogenicity of chemical compounds.

    PubMed

    Bahler, D; Stone, B; Wellington, C; Bristol, D W

    2000-01-01

    Experimental programs have been underway for several years to determine the environmental effects of chemical compounds, mixtures, and the like. Among these programs is the National Toxicology Program (NTP) on rodent carcinogenicity. Because these experiments are costly and time-consuming, the rate at which test articles (i.e., chemicals) can be tested is limited. The ability to predict the outcome of the analysis at various points in the process would facilitate informed decisions about the allocation of testing resources. To assist human experts in organizing an empirical testing regime, and to try to shed light on mechanisms of toxicity, we constructed toxicity models using various machine learning and data mining methods, both existing and those of our own devising. These models took the form of decision trees, rule sets, neural networks, rules extracted from trained neural networks, and Bayesian classifiers. As a training set, we used recent results from rodent carcinogenicity bioassays conducted by the NTP on 226 test articles. We performed 10-way cross-validation on each of our models to approximate their expected error rates on unseen data. The data set consists of physical-chemical parameters of test articles, alerting chemical substructures, salmonella mutagenicity assay results, subchronic histopathology data, and information on route, strain, and sex/species for 744 individual experiments. These results contribute to the ongoing process of evaluating and interpreting the data collected from chemical toxicity studies. PMID:10955517

  8. 93Nb and 17O NMR chemical shifts of niobiophosphate compounds.

    PubMed

    Flambard, A; Montagne, L; Delevoye, L; Steuernagel, S

    2007-10-01

    Niobiophosphate compounds with a large range of niobium and oxygen environments were studied with (93)Nb and (17)O solid-state NMR. (93)Nb isotropic chemical shift of pure niobate Nb(ONb)(6), pure phosphate Nb(OP)(6) and mixed phosphate-niobate Nb(OP)(x)(ONb)((6-x)) (1chemical shifts were found to be sensitive to the variation of local charge on Nb, but not to the local bond geometry (i.e. crystallographic site and edge or corner connectivity). A systematic shift to high field of the (93)Nb chemical shift is measured when x increases. Then, (17)O NMR spectra of a series of enriched samples provided the chemical shift and quadrupolar parameters for 4 types of oxygen environment (P-O-P, P-O-Na, P-O-Nb and Nb-O-Nb). Finally, Nb-O-Nb sites were characterized by a large (17)O chemical shift anisotropy. PMID:17728114

  9. Identifying chemical carcinogens and assessing potential risk in short-term bioassays using transgenic mouse models.

    PubMed Central

    Tennant, R W; French, J E; Spalding, J W

    1995-01-01

    Cancer is a worldwide public health concern. Identifying carcinogens and limiting their exposure is one approach to the problem of reducing risk. Currently, epidemiology and rodent bioassays are the means by which putative human carcinogens are identified. Both methods have intrinsic limitations: they are slow and expensive processes with many uncertainties. The development of methods to modify specific genes in the mammalian genome has provided promising new tools for identifying carcinogens and characterizing risk. Transgenic mice may provide advantages in shortening the time required for bioassays and improving the accuracy of carcinogen identification; transgenic mice might now be included in the testing armamentarium without abandoning the two-year bioassay, the current standard. We show that mutagenic carcinogens can be identified with increased sensitivity and specificity using hemizygous p53 mice in which one allele of the p53 gene has been inactivated. Furthermore, the TG.AC transgenic model, carrying a v-Ha-ras construct, has developed papillomas and malignant tumors in response to a number of mutagenic and nonmutagenic carcinogens and tumor promoters, but not to noncarcinogens. We present a decision-tree approach that permits, at modest extra cost, the testing of more chemicals with improved ability to extrapolate from rodents to humans. Images Figure 1. Figure 2. Figure 3. PMID:8529591

  10. In vivo interactions between ionizing radiation, inflammation and chemical carcinogens identified by increased DNA damage responses.

    PubMed

    McAllister, K A; Lorimore, S A; Wright, E G; Coates, P J

    2012-05-01

    Exposure to ionizing radiation or a variety of chemical agents is known to increase the risk of developing malignancy and many tumors have been linked to inflammatory processes. In most studies, the potentially harmful effects of ionizing radiation or other agents are considered in isolation, mainly due to the large number of experiments required to assess the effects of mixed exposures with different doses and different schedules, and the length of time and expense of studies using disease as the measure of outcome. Here, we have used short-term DNA damage responses to identify interactive effects of mixed exposures. The data demonstrate that exposure to ionizing radiation on two separate occasions ten days apart leads to an increase in the percentage of cells with a sub-G(0) DNA content compared to cells exposed only once, and this is a greater than additive effect. Short-term measurements of p53 stabilization, induction of p21/Cdkn1a and of apoptosis also identify these interactive effects. We also demonstrate similar interactive effects of radiation with the mutagenic chemical methyl-nitrosourea and with a nonspecific pro-inflammatory agent, lipopolysaccharide. The magnitude of the interactive effects is greater in cells taken from mice first exposed as juveniles compared to adults. These data indicate that short-term measurements of DNA damage and response to damage are useful for the identification of interactions between ionizing radiation and other agents. PMID:22463680

  11. Phenotypic assays to identify agents that induce reactive gliosis: a counter-screen to prioritize compounds for preclinical animal studies.

    PubMed

    Beckerman, Samuel R; Jimenez, Joaquin E; Shi, Yan; Al-Ali, Hassan; Bixby, John L; Lemmon, Vance P

    2015-09-01

    Astrocyte phenotypes change in a process called reactive gliosis after traumatic central nervous system (CNS) injury. Astrogliosis is characterized by expansion of the glial fibrillary acidic protein (GFAP) cytoskeleton, adoption of stellate morphologies, and differential expression of some extracellular matrix molecules. The astrocytic response immediately after injury is beneficial, but in the chronic injury phase, reactive astrocytes produce inhibitory factors (i.e., chondroitin sulfate proteoglycans [CSPGs]) that limit the regrowth of injured axons. There are no drugs that promote axon regeneration or functional recovery after CNS trauma in humans. To develop novel therapeutics for the injured CNS, we screened various libraries in a phenotypic assay to identify compounds that promote neurite outgrowth. However, the effects these compounds have on astrocytes are unknown. Specifically, we were interested in whether compounds could alter astrocytes in a manner that mimics the glial reaction to injury. To test this hypothesis, we developed cell-based phenotypic bioassays to measure changes in (1) GFAP morphology/localization and (2) CSPG expression/immunoreactivity from primary astrocyte cultures. These assays were optimized for six-point dose-response experiments in 96-well plates. The GFAP morphology assay is suitable for counter-screening with a Z-factor of 0.44±0.03 (mean±standard error of the mean; N=3 biological replicates). The CSPG assay is reproducible and informative, but does not satisfy common metrics for a "screenable" assay. As proof of principle, we tested a small set of hit compounds from our neurite outgrowth bioassay and identified one that can enhance axon growth without exacerbating the deleterious characteristics of reactive gliosis. PMID:26230074

  12. Effect of chemical pretreatment on anaerobic biodegradation of refractory organic compounds

    SciTech Connect

    Wang, Y.T. )

    1992-08-01

    The potential for using chemical oxidation to enhance anaerobic biodegradability and reduce toxicity of two model phenolic compounds (o-cresol and 2,4-DNP) was evaluated. Batch bioassays were performed on the model compounds and their oxidation samples to determine biodegradability and toxicity in batch methanogenic cultures. Ozone, hydrogen peroxide, and potassium permanganate were the three oxidants examined in this study. A dose of approximately 5 moles hydrogen peroxide, in the presence of a ferrous iron catalyst (Fenton's reagent), 7 moles permanganate, or 25 moles of ozone per mole of o-cresol was needed to significantly enhance anaerobic biodegradability of oxidation samples. Approximately 2.5-4.5 moles of hydrogen peroxide or 7 moles of ozone per mole of 2,4-DNP reduced methanogenic toxicity by 50%. 25 refs., 6 figs., 3 tabs.

  13. Quantitative detection of chemical compounds in human hair with coherent anti-Stokes Raman scattering microscopy

    PubMed Central

    Zimmerley, Maxwell; Lin, Chia-Yu; Oertel, David C.; Marsh, Jennifer M.; Ward, Jimmie L.; Potma, Eric Olaf

    2010-01-01

    Coherent anti-Stokes Raman scattering (CARS) microscopy is used to determine the distribution and concentration of selected compounds in intact human hair. By generating images based on ratiometric CARS contrast, quantitative concentration maps of both water and externally applied d-glycine are produced in the cortex of human hair fibers. Both water and d-glycine are found to homogeneously distribute throughout the cortical regions of the hair. The ability to selectively detect molecular agents in hair fibers is of direct relevance to understanding the chemical and physical mechanisms that underlie the performance of hair-care products. PMID:19725730

  14. Influence of chemical bonding on X-ray spectra of different aluminium compounds

    NASA Astrophysics Data System (ADS)

    Bonetto, Rita; Trincavelli, Jorge; Vasconcellos, Marcos

    2005-11-01

    Five minerals containing aluminium in different crystal configurations are studied. The different kinds of chemical bonding between aluminium and oxygen originate molecular orbitals with energy levels and transition probabilities varying from one compound to another. This effect appears as shifts and changes in relative intensities of K? emission lines and as modifications of the K? characteristic spectrum. In the present work, the aluminium K characteristic spectra obtained by means of an electron microprobe with a wavelength dispersive system are compared for topaz, albite, spodumene, biotite and corundum.

  15. A general mathematical model for chemical-enhanced flushing of soil contaminated by organic compounds

    NASA Astrophysics Data System (ADS)

    Ji, Wei; Brusseau, Mark L.

    The use of chemical agents to enhance the in situ removal of hydrophobic organic compounds (HOCs) from porous media is an emerging remediation technology. Whereas surfactants and cosolvents are the primary agents examined to date, others, such as natural organic matter and complexing agents, have also been examined for their ability to enhance the solubilization of HOCs. While the mode of action of each type of enhanced-solubilization agent may be different, they all induce similar responses. In this paper, a general mathematical model is developed to simulate the enhanced-solubilization process for various chemical agents, including cosolvents, surfactants, natural organic matter, and complexing agents. This model is developed using a master-equation approach that incorporates the solubilization mechanisms associated with each type of agent. A limited evaluation of the model is conducted by comparing simulations to the results of two laboratory experiments. A sensitivity analysis is performed to illustrate the influence of various factors on contaminant removal.

  16. Determination of the bioactive compounds, antioxidant activity and chemical composition of Brazilian blackberry, red raspberry, strawberry, blueberry and sweet cherry fruits.

    PubMed

    de Souza, Vanessa Rios; Pereira, Patrcia Aparecida Pimenta; da Silva, Thais Lomnaco Teodoro; de Oliveira Lima, Luiz Carlos; Pio, Rafael; Queiroz, Fabiana

    2014-08-01

    This study aimed to evaluate the chemical composition, identify the bioactive compounds and measure the antioxidant activity present in blackberry, red raspberry, strawberry, sweet cherry and blueberry fruits produced in the subtropical areas of Brazil and to verify that the chemical properties of these fruit are similar when compared to the temperate production zones. Compared with berries and cherries grown in temperate climates, the centesimal composition and physical chemical characteristics found in the Brazilian berries and cherries are in agreement with data from the literature. For the mineral composition, the analyzed fruits presented lower concentrations of P, K, Ca, Mg and Zn and higher levels of Fe. The values found for the bioactive compounds generally fit the ranges reported in the literature with minor differences. The greatest difference was found in relation to ascorbic acid, as all fruits analyzed showed levels well above those found in the literature. PMID:24629981

  17. Chemical characterization of dissolved organic compounds from coastal sea surface microlayers (Baltic Sea, Germany).

    PubMed

    van Pinxteren, Manuela; Mller, Conny; Iinuma, Yoshiteru; Stolle, Christian; Herrmann, Hartmut

    2012-10-01

    The physicochemical properties of the sea surface microlayer (SML), i.e. the boundary layer between the air and the sea, and its impact on air-sea exchange processes have been investigated for decades. However, a detailed description about these processes remains incomplete. In order to obtain a better chemical characterization of the SML, in a case study three pairs of SML and corresponding bulk water samples were taken in the southern Baltic Sea. The samples were analyzed for dissolved organic carbon and dissolved total nitrogen, as well as for several organic nitrogen containing compounds and carbohydrates, namely aliphatic amines, dissolved free amino acids, dissolved free monosaccharides, sugar alcohols, and monosaccharide anhydrates. Therefore, reasonable analytical procedures with respect to desalting and enrichment were established. All aliphatic amines and the majority of the investigated amino acids (11 out of 18) were found in the samples with average concentrations between 53 ng L(-1) and 1574 ng L(-1). The concentrations of carbohydrates were slightly higher, averaging 2900 ng L(-1). Calculation of the enrichment factor (EF) between the sea surface microlayer and the bulk water showed that dissolved total nitrogen was more enriched (EF: 1.1 and 1.2) in the SML than dissolved organic carbon (EF: 1.0 and 1.1). The nitrogen containing organic compounds were generally found to be enriched in the SML (EF: 1.9-9.2), whereas dissolved carbohydrates were not enriched or even depleted (EF: 0.7-1.2). Although the investigated compounds contributed on average only 0.3% to the dissolved organic carbon and 0.4% to the total dissolved nitrogen fraction, these results underline the importance of single compound analysis to determine SML structure, function, and its potential for a transfer of compounds into the atmosphere. PMID:22475414

  18. Modeling the Detection of Organic and Inorganic Compounds Using Iodide-Based Chemical Ionization.

    PubMed

    Iyer, Siddharth; Lopez-Hilfiker, Felipe; Lee, Ben H; Thornton, Joel A; Kurtn, Theo

    2016-02-01

    Iodide-based chemical ionization mass spectrometry (CIMS) has been used to detect and measure concentrations of several atmospherically relevant organic and inorganic compounds. The significant electronegativity of iodide and the strong acidity of hydroiodic acid makes electron transfer and proton abstraction essentially negligible, and the soft nature of the adduct formation ionization technique reduces the chances of sample fragmentation. In addition, iodide has a large negative mass defect, which, when combined with the high resolving power of a high resolution time-of-flight chemical ionization mass spectrometer (HR-ToF-CIMS), provides good selectivity. In this work, we use quantum chemical methods to calculate the binding energies, enthalpies and free energies for clusters of an iodide ion with a number of atmospherically relevant organic and inorganic compounds. Systematic configurational sampling of the free molecules and clusters was carried out at the B3LYP/6-31G* level, followed by subsequent calculations at the PBE/SDD and DLPNO-CCSD(T)/def2-QZVPP//PBE/aug-cc-pVTZ-PP levels. The binding energies, enthalpies, and free energies thus obtained were then compared to the iodide-based University of Washington HR-ToF-CIMS (UW-CIMS) instrument sensitivities for these molecules. We observed a reasonably linear relationship between the cluster binding enthalpies and logarithmic instrument sensitivities already at the PBE/SDD level, which indicates that relatively simple quantum chemical methods can predict the sensitivity of an iodide-based CIMS instrument toward most molecules. However, higher level calculations were needed to treat some outlier molecules, most notably oxalic acid and methylerythritol. Our calculations also corroborated the recent experimental findings that the molecules that the UW-CIMS detects at maximum sensitivity usually have binding enthalpies to iodide which are higher than about 26 kcal/mol, depending slightly on the level of theory. PMID:26736021

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

    DOEpatents

    Yu, Conrad M. (Antioch, CA); Koo, Jackson C. (San Ramon, CA)

    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.

  20. A novel 3D high-content assay identifies compounds that prevent fibroblast invasion into tissue surrogates.

    PubMed

    Wenzel, Carsten; Otto, Saskia; Prechtl, Stefan; Parczyk, Karsten; Steigemann, Patrick

    2015-11-15

    Invasion processes underlie or accompany several pathological processes but only a limited number of high-throughput capable phenotypic models exist to test anti-invasive compounds in vitro. We here evaluated 3D co-cultures as a high-content phenotypic screening system for fibrotic invasive processes. 3D multicellular spheroids were used as living tissue surrogates in co-culture with fluorescently labeled lung fibroblasts to monitor invasion processes by automated microscopy. This setup was used to screen a compound library containing 480 known bioactive substances. Identified hits prevented fibroblast invasion and could be subdivided into two hit classes. First, Prostaglandins were shown to prevent fibroblast invasion, most likely mediated by the prostaglandin EP2 receptor and generation of cAMP. Additionally, Rho-associated protein kinase (ROCK) inhibitors prevented fibroblast invasion, possibly by inactivation of myosin II. Importantly, both Prostaglandins and ROCK inhibitors are potential treatment options shown to be effective in in vitro and in vivo models of fibrotic diseases. This validates the presented novel phenotypic screening approach for the evaluation of potential inhibitors and the identification of novel compounds with activity in diseases that are associated with fibroblast invasion. PMID:26475730

  1. Chemical compound of a snow cover in taiga zone territory of the European northeast of Russia

    NASA Astrophysics Data System (ADS)

    Mariya, Vasilevich

    2013-04-01

    Receipt of substances from atmosphere plays an important role in geochemical balance of ecosystems. Atmosphere participates participate in an exchange and substance redistribution for the Earth, and its chemical compound gives the objective information on quality of the air environment. The snow cover acts as the effective store of substances which remain in it in an invariable condition within winter. Chemical compound of snow reflects the valid size of dry both damp losses and quantitative parametres of pollution of ecosystems. Sensitivity of a snow cover to change of industrial conditions in region allows to estimate a state of environment objectively. Distinction of areas on natural receipt macro- and microcomponents from atmosphere causes of an estimation of their background receipt on spreading surface. The purpose of the present work is studying of a chemical compound of a snow cover and spatial distribution of macrocomponents to a taiga zone territories of the European northeast (Republic Komi). It is established that average value of a mineralization of thawed snow, has made 2.8 mg/dm3 and tends to reduction with width increase. Our results have shown that thawed snow water in a taiga zone is characterised by subacidic reaction. Average value ?? has made 4.7 0.1. The oxidation of snow cover is observed from the north on the south. Formation of acidity of a snow cover estimated through the relation of the sum of concentration anions (A = [SO42-] + [N?3-] + [?l-]) to the sum of cations concentration (K = [NH4+] + [Ca2+] + [Mg2+] + [Na+] + [K+]). The received data follows that thawed snow of a taiga zone is characterised by values ?/? <1 at increase in the given relation from the south on the north from 0.42 till (average value equally 0.58). Thus, the acid-base properties of a taiga zone snow cover are defined by deficiency of neutralised connections and prevalence in thawed snow of ions of hydrogen that corresponds to the general situation in the European territory of Russia. Differentiation in distribution macro- and microcomponents in snow from the south on the north is observed statistically authentic latitude: the total maintenance of cations increases in and reduction of anions. The raised receipt of substances is characteristic for southwest and east borders of the investigated territory. Atmospheric precipitation plays an important role in receipt of the basic biogenic substances on a taiga zone territory. Accumulation of organic carbon makes 20 % from the general module of substances. Share reduction of carbon and the general nitrogen in a snow cover from the south on the north is noted. Formation of a snow cover chemical compound of a taiga zone background territories occurs, mainly, at the expense of soluble connections of elements. Factors of enrichment by elements of soluble fraction much more, than for fraction fixed connections also are close to values of accumulation factors of atmospheric aerosol. Chemical compound of snow cover of a taiga zone background territories is formed mainly at the expense of distant carryings over, influence of local sources is slightly. The cartographical basis of spatial distribution of chemical components in a snow cover is created.

  2. Stereoregularity of poly (lactic acid) and their model compounds as studied by NMR and quantum chemical calculations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to understand the origin of the tacticity splitting in the NMR spectrum of poly(lactic acid), monomer model compound and dimer model compounds (both isotactic and syndiotactic) were synthesized and their 1H and 13C NMR chemical shifts observed. Two energetically stable conformations were o...

  3. DETERMINATION OF CHEMICAL CLASSES FROM MASS SPECTRA OF TOXIC ORGANIC COMPOUNDS BY SIMCA PATTERN RECOGNITION AND INFORMATION THEORY

    EPA Science Inventory

    The low resolution mass spectra of a set of 78 toxic volatile organic compounds were examined for information concerning chemical classes. These compounds were predominately chloro- and/or bromoaromatics, -alkanes, or -alkenes, which are routinely sought at trace levels in ambien...

  4. Identifying the causes of differences in ozone production from the CB05 and CBMIV chemical mechanisms

    NASA Astrophysics Data System (ADS)

    Saylor, R. D.; Stein, A. F.

    2011-10-01

    An investigation was conducted to identify the mechanistic differences between two versions of the carbon bond gas-phase chemical mechanism (CB05 and CBMIV) which consistently lead to larger ground-level ozone concentrations being produced in the CB05 version of the National Air Quality Forecasting Capability (NAQFC) modeling system even though the two parallel forecast systems utilize the same meteorology and base emissions and similar initial and boundary conditions. Box models of each of the mechanisms as they are implemented in the NAQFC were created and a set of 12 sensitivity simulations was designed. The sensitivity simulations independently probed the conceptual mechanistic differences between CB05 and CBMIV and were exercised over a 45-scenario simulation suite designed to emulate the wide range of chemical regimes encountered in a continental-scale atmospheric chemistry model. Results of the sensitivity simulations indicate that two sets of reactions that were included in the CB05 mechanism, but which were absent from the CBMIV mechanism, are the primary causes of the greater ozone production in the CB05 version of the NAQFC. One set of reactions recycles the higher organic peroxide species of CB05 (ROOH), resulting in additional photochemically reactive products that act to produce additional ozone in some chemical regimes. The other set of reactions recycles reactive nitrogen from less reactive forms back to NO2, increasing the effective NOx concentration of the system. In particular, the organic nitrate species (NTR), which was a terminal product for reactive nitrogen in the CBMIV mechanism, acts as a reservoir species in CB05 to redistribute NOx from major source areas to potentially NOx-sensitive areas where additional ozone may be produced in areas remote from direct NOx sources.

  5. Identifying the causes of differences in ozone production from the CB05 and CBMIV chemical mechanisms

    NASA Astrophysics Data System (ADS)

    Saylor, R. D.; Stein, A. F.

    2012-02-01

    An investigation was conducted to identify the mechanistic differences between two versions of the carbon bond gas-phase chemical mechanism (CB05 and CBMIV) which consistently lead to larger ground-level ozone concentrations being produced in the CB05 version of the National Air Quality Forecasting Capability (NAQFC) modeling system even though the two parallel forecast systems utilize the same meteorology and base emissions and similar initial and boundary conditions. Box models of each of the mechanisms as they are implemented in the NAQFC were created and a set of 12 sensitivity simulations was designed. The sensitivity simulations independently probed the conceptual mechanistic differences between CB05 and CBMIV and were exercised over a 45-scenario simulation suite designed to emulate the wide range of chemical regimes encountered in a continental-scale atmospheric chemistry model. Results of the sensitivity simulations indicate that two sets of reactions that were included in the CB05 mechanism, but which were absent from the CBMIV mechanism, are the primary causes of the greater ozone production in the CB05 version of the NAQFC. One set of reactions recycles the higher organic peroxide species of CB05 (ROOH), resulting in additional photochemically reactive products that act to produce additional ozone in some chemical regimes. The other set of reactions recycles reactive nitrogen from less reactive forms back to NO2, increasing the effective NOx concentration of the system. In particular, the organic nitrate species (NTR), which was a terminal product for reactive nitrogen in the CBMIV mechanism, acts as a reservoir species in CB05 to redistribute NOx from major source areas to potentially NOx-sensitive areas where additional ozone may be produced in areas remote from direct NOx sources.

  6. 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.

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

    PubMed

    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 (DAGL?) and -beta (DAGL?) to neurons and microglia, respectively. Disruption of DAGL? 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. PMID:26779719

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

    DOEpatents

    Holzrichter, John F. (Berkeley, CA); Siekhaus, Wigbert J. (Berkeley, CA)

    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.

  9. A chemical screen identifies class A G-protein coupled receptors as regulators of cilia

    PubMed Central

    Avasthi, Prachee; Marley, Aaron; Lin, Henry; Gregori-Puigjane, Elisabet; Shoichet, Brian K.; von Zastrow, Mark; Marshall, Wallace F.

    2012-01-01

    Normal cilia length and motility are critical for proper cellular function. Prior studies of the regulation of ciliary structure and length have primarily focused on the intraflagellar transport machinery and motor proteins required for ciliary assembly and disassembly. However, several mutants with abnormal length flagella highlight the importance of signaling proteins as well. In this study, an unbiased chemical screen was performed to uncover signaling pathways that are critical for ciliogenesis and length regulation using flagella of the green alga Chlamydomonas reinhardtii as a model. The annotated Sigma LOPAC1280 chemical library was screened for effects on flagellar length, motility and severing as well as cell viability. Assay data were clustered to identify pathways regulating flagella. The most frequently target found to be involved in flagellar length regulation was the family of dopamine binding G-protein coupled receptors (GPCRs). In mammalian cells, cilium length could indeed be altered with expression of the dopamine D1 receptor. Our screen thus reveals signaling pathways that are potentially critical for ciliary formation, resorption, and length maintenance, which represent candidate targets for therapeutic intervention of disorders involving ciliary malformation and malfunction. PMID:22375814

  10. [Source profile and chemical reactivity of volatile organic compounds from vehicle exhaust].

    PubMed

    Qiao, Yue-Zhen; Wang, Hong-Li; Huang, Cheng; Chen, Chang-Hong; Su, Lei-Yan; Zhou, Min; Xu, Hua; Zhang, Gang-Feng; Chen, Yi-Ran; Li, Li; Chen, Ming-Hua; Huang, Hai-Ying

    2012-04-01

    Light-duty gasoline taxis (LDGT) and passenger cars (LDGV), heavy-duty diesel buses (HDDB) and trucks (HDDT), gasoline motorcycles (MC) and LPG scooters (LPGS), were selected for tailpipe volatile organic compounds (VOCs) samplings by using transient dynamometer and on road test combined with SUMMA canisters technology. The samples were tested by GC-MS to analyze the concentration and species composition of VOCs. The results indicate that light-duty gasoline automobiles have higher fractions of aromatic hydrocarbons, which account for 43.38%-44.45% of the total VOCs, the main aromatic hydrocarbons are toluene and xylenes. Heavy-duty diesel vehicles have higher fractions of alkanes, which constitute 46.86%-48.57% of the total VOCs, the main alkanes are propane, n-dodecane and n-undecane. In addition, oxy-organics account for 13.28%-15.01% of the VOCs, the main oxy-organics is acetone. The major compound from MC and LPGS exhaust is acetylene, it accounts for 39.75% and 76.67% of the total VOCs, respectively. VOCs exhaust from gasoline motorcycles and light-duty gasoline automobiles has a significantly higher chemical reactivity than those from heavy-duty diesel vehicles, which contribute 55% and 44% to the atmospheric chemical reactivity in Shanghai. The gasoline motorcycles and light-duty gasoline automobiles are the key pollution sources affecting city and region ambient oxidation, and the key active species of toluene, xylenes, propylene, and styrene make the greatest contribution. PMID:22720548

  11. Chemical kinetic study of the oxidation of toluene and related cyclic compounds

    SciTech Connect

    Mehl, M; Frassoldati, A; Fietzek, R; Faravelli, T; Pitz, W; Ranzi, E

    2009-10-01

    Chemical kinetic models of hydrocarbons found in transportation fuels are needed to simulate combustion in engines and to improve engine performance. The study of the combustion of practical fuels, however, has to deal with their complex compositions, which generally involve hundreds of compounds. To provide a simplified approach for practical fuels, surrogate fuels including few relevant components are used instead of including all components. Among those components, toluene, the simplest of the alkyl benzenes, is one of the most prevalent aromatic compounds in gasoline in the U.S. (up to 30%) and is a promising candidate for formulating gasoline surrogates. Unfortunately, even though the combustion of aromatics been studied for a long time, the oxidation processes relevant to this class of compounds are still matter of discussion. In this work, the combustion of toluene is systematically approached through the analysis of the kinetics of some important intermediates contained in its kinetic submechanism. After discussing the combustion chemistry of cyclopentadiene, benzene, phenol and, finally, of toluene, the model is validated against literature experimental data over a wide range of operating conditions.

  12. Element and chemical compounds transfer in bio-crude from hydrothermal liquefaction of microalgae.

    PubMed

    Tang, Xiaohan; Zhang, Chao; Li, Zeyu; Yang, Xiaoyi

    2016-02-01

    In this study, hydrothermal liquefaction (HTL) experiments of Nannochloropsis and Spirulina were carried out at different temperatures (220-300°C) to explore the effects of temperature on bio-crude yield and properties. The optimal temperature for bio-crude yield was around 260-280°C. Transfers of element and chemical compounds in bio-crude were discussed in detail to deduce the reaction mechanism. The hydrogen and carbon recoveries were consistent with the results of bio-crude yields at every temperature point. The relative percentage of fatty acid in bio-crude decreased and the amine and amide increased for both microalgae with temperature rising. The N-heterocyclic compounds in bio-crude increased with temperature rising for Nannochloropsis, while decreased when temperature increased from 220°C to 280°C for Spirulina. Bio-crude gained at higher temperature or from microalgae with high protein content may contain high heteroatom compounds. PMID:26700753

  13. Passive Sampling in Regulatory Chemical Monitoring of Nonpolar Organic Compounds in the Aquatic Environment.

    PubMed

    Booij, Kees; Robinson, Craig D; Burgess, Robert M; Mayer, Philipp; Roberts, Cindy A; Ahrens, Lutz; Allan, Ian J; Brant, Jan; Jones, Lisa; Kraus, Uta R; Larsen, Martin M; Lepom, Peter; Petersen, Jördis; Pröfrock, Daniel; Roose, Patrick; Schäfer, Sabine; Smedes, Foppe; Tixier, Céline; Vorkamp, Katrin; Whitehouse, Paul

    2016-01-01

    We reviewed compliance monitoring requirements in the European Union, the United States, and the Oslo-Paris Convention for the protection of the marine environment of the North-East Atlantic, and evaluated if these are met by passive sampling methods for nonpolar compounds. The strengths and shortcomings of passive sampling are assessed for water, sediments, and biota. Passive water sampling is a suitable technique for measuring concentrations of freely dissolved compounds. This method yields results that are incompatible with the EU's quality standard definition in terms of total concentrations in water, but this definition has little scientific basis. Insufficient quality control is a present weakness of passive sampling in water. Laboratory performance studies and the development of standardized methods are needed to improve data quality and to encourage the use of passive sampling by commercial laboratories and monitoring agencies. Successful prediction of bioaccumulation based on passive sampling is well documented for organisms at the lower trophic levels, but requires more research for higher levels. Despite the existence of several knowledge gaps, passive sampling presently is the best available technology for chemical monitoring of nonpolar organic compounds. Key issues to be addressed by scientists and environmental managers are outlined. PMID:26619247

  14. Big Data in Chemical Toxicity Research: The Use of High-Throughput Screening Assays To Identify Potential Toxicants

    PubMed Central

    2015-01-01

    High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compounds ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described. PMID:25195622

  15. Quinones and Aromatic Chemical Compounds in Particulate Matter Induce Mitochondrial Dysfunction: Implications for Ultrafine Particle Toxicity

    PubMed Central

    Xia, Tian; Korge, Paavo; Weiss, James N.; Li, Ning; Venkatesen, M. Indira; Sioutas, Constantinos; Nel, Andre

    2004-01-01

    Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)enriched aromatic fraction in O2? generation, decrease of membrane potential (??m), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on ??m at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in ??m at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and ??m are mediated by adsorbed chemicals rather than the particles themselves. PMID:15471724

  16. Advances in SXFA-coated SAW chemical sensors for organophosphorous compound detection.

    PubMed

    Wang, Wen; He, Shitang; Li, Shunzhou; Liu, Minghua; Pan, Yong

    2011-01-01

    A polymer-coated surface acoustic wave (SAW)-based chemical sensor for organophosphorous compound sensing at extremely low concentrations was developed, in which a dual-delay-line oscillator coated with fluoroalcoholpolysiloxane (SXFA) acted as the sensor element. Response mechanism analysis was performed on the SXFA-coated chemical sensor, resulting in the optimal design parameters. The shear modulus of the SXFA, which is the key parameter for theoretical simulation, was extracted experimentally. New designs were done on the SAW devices to decrease the insertion loss. Referring to the new phase modulation approach, superior short-term frequency stability (2 Hz in seconds) was achieved from the SAW oscillator using the fabricated 300 MHz delay line as the feedback element. In the sensor experiment on dimethylmethylphosphonate (DMMP) detection, the fabricated SXFA-coated chemical sensor exhibited an excellent threshold detection limit up to 0.004 mg/m(3) (0.7 ppb) and good sensitivity (?485 Hz/mg/m(3) for a DMMP concentration of 2?14 mg/m(3)). PMID:22319366

  17. Advances in SXFA-Coated SAW Chemical Sensors for Organophosphorous Compound Detection

    PubMed Central

    Wang, Wen; He, Shitang; Li, Shunzhou; Liu, Minghua; Pan, Yong

    2011-01-01

    A polymer-coated surface acoustic wave (SAW)-based chemical sensor for organophosphorous compound sensing at extremely low concentrations was developed, in which a dual-delay-line oscillator coated with fluoroalcoholpolysiloxane (SXFA) acted as the sensor element. Response mechanism analysis was performed on the SXFA-coated chemical sensor, resulting in the optimal design parameters. The shear modulus of the SXFA, which is the key parameter for theoretical simulation, was extracted experimentally. New designs were done on the SAW devices to decrease the insertion loss. Referring to the new phase modulation approach, superior short-term frequency stability (2 Hz in seconds) was achieved from the SAW oscillator using the fabricated 300 MHz delay line as the feedback element. In the sensor experiment on dimethylmethylphosphonate (DMMP) detection, the fabricated SXFA-coated chemical sensor exhibited an excellent threshold detection limit up to 0.004 mg/m3 (0.7 ppb) and good sensitivity (?485 Hz/mg/m3 for a DMMP concentration of 2?14 mg/m3). PMID:22319366

  18. Influences of biomass burning during the Transport and Chemical Evolution Over the Pacific (TRACE-P) experiment identified by the regional chemical transport model

    NASA Astrophysics Data System (ADS)

    Tang, Youhua; Carmichael, Gregory R.; Woo, Jung-Hun; Thongboonchoo, Narisara; Kurata, Gakuji; Uno, Itsushi; Streets, David G.; Blake, Donald R.; Weber, Rodney J.; Talbot, Robert W.; Kondo, Yutaka; Singh, Hanwant B.; Wang, Tao

    2003-11-01

    Using a regional chemical transport model, STEM 2K1, and the emission inventory for the Transport and Chemical Evolution Over the Pacific (TRACE-P) period [Woo et al., , this issue], we successfully simulated important features of the biomass burning (BB) CO outflow. Simulated results agree well with the TRACE-P aircraft measurements and Thailand surface observations. On the basis of sensitivity studies with and without biomass emissions, we identified nine flight segments that are affected by biomass plumes during the TRACE-P period and compared the characteristics of the BB air masses with the other air masses. The BB air masses emitted from Southeast Asia contain relatively high HCN (ΔHCN/ΔCO ˜ 0.0015) and potassium (ΔK+/ΔCO ˜ 0.0038) but very low NOy (ΔNOy/ΔCO ˜ 0.005) mixing ratios, which may be associated with the special burning condition in this region. The biomass burning air masses have high ozone production efficiency. The observed ΔO3/ΔNOz values were ˜17 in biomass events and 1.7 in other events. The BB influence on the trace gas distributions can be divided into two categories: the influence through direct reactions and the influence caused by BB aerosols changing J values. These two influences are discussed for the BB-affected TRACE-P flights and for east Asia. The BB influences on chemical species are not only determined by the BB plume intensity but also by the ambient environment caused by other emissions. In Southeast Asia, where the biogenic emissions are very strong, the OH background concentration is low, and the BB gas-phase compounds mainly contribute to OH production. Arranged in the sensitivity to the J value change caused by BB aerosols, we have OH > HO2 > HCHO > O3 when evaluated on a regional average. Averaged over March, the biomass burning net influence is as high as 50% for OH, 40% for HO2, 60% for HCHO, and 10 ppbv for O3 for the layers below 1 km.

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

    PubMed Central

    Yuan, Fei; Zhou, You; Wang, Meng; Yang, Jing; Wu, Kai; Lu, Changhong; Kong, Xiangyin; Cai, Yu-Dong

    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

  20. Big data in chemical toxicity research: the use of high-throughput screening assays to identify potential toxicants.

    PubMed

    Zhu, Hao; Zhang, Jun; Kim, Marlene T; Boison, Abena; Sedykh, Alexander; Moran, Kimberlee

    2014-10-20

    High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound's ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described. PMID:25195622

  1. Relativistic DFT Calculation of (119)Sn Chemical Shifts and Coupling Constants in Tin Compounds.

    PubMed

    Bagno, Alessandro; Casella, Girolamo; Saielli, Giacomo

    2006-01-01

    The nuclear shielding and spin-spin coupling constants of (119)Sn in stannane, tetramethylstannane, methyltin halides Me4-nSnXn (X = Cl, Br, I; n = 1-3), tin halides, and some stannyl cations have been investigated computationally by DFT methods and Slater all-electron basis sets, including relativistic effects by means of the zeroth order regular approximation (ZORA) method up to spin-orbit coupling. Calculated (119)Sn chemical shifts generally correlate well with experimental values, except when several heavy halogen atoms, especially iodine, are bound to tin. In such cases, calculated chemical shifts are almost constant at the scalar (spin-free) ZORA level; only at the spin-orbit level is a good correlation, which holds for all compounds examined, attained. A remarkable "heavy-atom effect", analogous to that observed for analogous alkyl halides, is evident. The chemical shift of the putative stannyl cation (SnH3(+)) has also been examined, and it is concluded that the spectrum of the species obtained in superacids is inconsistent with a simple SnH3(+) structure; strong coordination to even weak nucleophiles such as FSO3H leads to a very satisfactory agreement. On the contrary, the calculated (119)Sn chemical shift of the trimesitylstannyl cation is in very good agreement with the experimental value. Coupling constants between (119)Sn and halogen nuclei are also well-modeled in general (taking into account the large uncertainties in the experimental values); relativistic spin-orbit effects are again quite evident. Couplings to (13)C and (1)H also fall, on the average, on the same correlation line, but individual values show a significant deviation from the expected unit slope. PMID:26626377

  2. 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.

  3. IDENTIFYING CHEMICALS FOR CUMULATIVE RISK ASSESSMENT USING COMMON MECHANISMS OF ACTION AND TOXICITY

    EPA Science Inventory

    Traditionally, potential health risk assessments from exposure to contaminated food, drinking water, or environmental media have been conducted on individual pesticides or chemicals in each medium of concern. However, humans are generally exposed to multiple chemicals and stress...

  4. Can Coffee Chemical Compounds and Insecticidal Plants Be Harnessed for Control of Major Coffee Pests?

    PubMed

    Green, Paul W C; Davis, Aaron P; Cossé, Allard A; Vega, Fernando E

    2015-11-01

    Pests and pathogens threaten coffee production worldwide and are difficult to control using conventional methods, such as insecticides. We review the literature on the chemistry of coffee, concentrating on compounds most commonly reported from Coffea arabica and Coffea canephora. Differences in chemistry can distinguish coffee species and varieties, and plants grown under different biogeographic conditions exhibit different chemotypes. A number of chemical groups, such as alkaloids and caffeoylquinic acids, are known to be insecticidal, but most studies have investigated their effects on coffee quality and flavor. More research is required to bridge this gap in knowledge, so that coffee can be bred to be more resistant to pests. Furthermore, we report on some pesticidal plants that have been used for control of coffee pests. Locally sourced pesticidal plants have been underutilized and offer a sustainable alternative to conventional insecticides and could be used to augment breeding for resilience of coffee plants. PMID:26458882

  5. A yeast-based chemical screen identifies a PDE inhibitor that elevates steroidogenesis in mouse Leydig cells via PDE8 and PDE4 inhibition.

    PubMed

    Demirbas, Didem; Wyman, Arlene R; Shimizu-Albergine, Masami; Cakici, Ozgur; Beavo, Joseph A; Hoffman, Charles S

    2013-01-01

    A cell-based high-throughput screen (HTS) was developed to detect phosphodiesterase 8 (PDE8) and PDE4/8 combination inhibitors. By replacing the Schizosaccharomyces pombe PDE gene with the murine PDE8A1 gene in strains lacking adenylyl cyclase, we generated strains whose protein kinase A (PKA)-stimulated growth in 5-fluoro orotic acid (5FOA) medium reflects PDE8 activity. From our previously-identified PDE4 and PDE7 inhibitors, we identified a PDE4/8 inhibitor that allowed us to optimize screening conditions. Of 222,711 compounds screened, ?0.2% displayed composite Z scores of >20. Additional yeast-based assays using the most effective 367 compounds identified 30 candidates for further characterization. Among these, compound BC8-15 displayed the lowest IC?? value for both PDE4 and PDE8 inhibition in in vitro enzyme assays. This compound also displays significant activity against PDE10A and PDE11A. BC8-15 elevates steroidogenesis in mouse Leydig cells as a single pharmacological agent. Assays using BC8-15 and two structural derivatives support a model in which PDE8 is a primary regulator of testosterone production by Leydig cells, with an additional role for PDE4 in this process. BC8-15, BC8-15A, and BC8-15C, which are commercially available compounds, display distinct patterns of activity against PDE4, PDE8, PDE10A, and PDE11A, representing a chemical toolkit that could be used to examine the biological roles of these enzymes in cell culture systems. PMID:23967182

  6. 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...

  7. [A comparative study of the antiviral activity of chemical compounds concerning the orthopoxviruses experiments in vivo].

    PubMed

    Kabanov, A S; Sergeev, Al A; Shishkina, L N; Bulychev, L E; Skarnovich, M O; Sergeev, Ar A; Bormotov, N I; P'iankov, O V; Serova, O A; Bodnev, S A; Selivanov, B A; Tikhonov, A Ia; Agafonov, A P; Sergeev, A N

    2013-01-01

    In the experiments using intranasal (i/n) infection of mice with the ectromelia virus (EV) in a dose 10 LD50/head (10 x 50% lethal doselhead) or with the monkaypox virus (MPXV) in a dose 10 ID50/head (10 x 50% infective dose/ head) it was demonstrated that the antiviral efficiency of chemical compounds - the condensed derivatives of pyrrolidin-2,5-dion, as well as their predecessors and the nearest analogues, synthesized in Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences (NIOCH SB RAS) was observed. As a positive control we used the antipoxvirus chemical preparation ST-246 available from SIGA Technologies Inc. (USA), synthesized in NIOCH SB RAS by the technique suggested by the authors. It was demonstrated that the compound NIOCH-14 (7-[N'-(4-Trifluoromethylbenzoil)-hydrazidecarbonil]-tricyclo[3.2.2.02,4]non-8-en-6-carbonic acid) possessed comparable with ST-246 antiviral activity concerning EV and MPXV on all indicators used. Therefore, at infection of mice with EV (strain K-1) and peroral administration of NIOCH-14 and ST-246 in a dose 50 mkg/g of mouse weight (12-14 g) within 10 days the survival rate and average life expectancy of mice authentically exceeded the control levels. EV titers in lungs through 6 days after infection in the same groups were lower than in the control. In addition to that, after 7 days of infection of mice with MPXV (strain V79-1-005) and daily peroral administration of NIOCH-14 and ST-246 in a dose 60 mkg/g of mouse weight (9-11 g) authentic decrease in a part of infected animals and MPXV titers in lungs was observed. PMID:24354064

  8. 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 (DAGL?) and beta (DAGL?) to neurons and microglia, respectively. Disruption of DAGL? 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

  9. Engineering nanoparticles surface for biosensing: "Chemical noses" to detect and identify proteins, bacteria and cancerous cells

    NASA Astrophysics Data System (ADS)

    Miranda-Sanchez, Oscar Ramon

    Rapid and sensitive detection of biomolecules is an important issue in nanomedicine. Many disorders are manifested by changes in protein levels of serum and other biofluids. Rapid and effective differentiation between normal and cancerous cells is an important challenge for the diagnosis and treatment of tumor. Likewise, rapid and effective identification of pathogens is a key target in both biomedical and environmental monitoring. Most biological recognition processes occur via specific interactions. Gold nanoparticles (AuNP s) feature sizes commensurate with biomacromolecules, coupled with useful physical and optical properties. A key issue in the use of nanomaterials is controlling the interfacial interactions of these complex systems. Modulation of these physicochemical properties can be readily achieved by engineering nanoparticles surface. Inspired by the idea of mimicking nature, a convenient, precise and rapid method for sensing proteins, cancerous cells and bacteria has been developed by overtaking the superb performance of biological olfactory systems in odor detection, identification, tracking, and location. On the fundamental side, an array-based/'chemical nose' sensor composed of cationic functionalized AuNPs as receptors and anionic fluorescent conjugated polymers or green fluorescent proteins or enzyme/substrates as transducers that can properly detect and identify proteins, bacteria, and cancerous cells has been successfully fabricated.

  10. Catalytic Conversion of Carbon-Containing Compounds into Valuable Chemicals and Fuels

    NASA Astrophysics Data System (ADS)

    Cheng, Zhuo

    Conversion of carbon-containing compounds, especially C1 compounds such as carbon dioxide and methane, to valuable chemicals and fuels will hopefully address concerns over decreasing supplies of fossil fuels and mitigate the eects of greenhouse gas emissions on global climate change. Many challenges, however, remain to be addressed before these technologies may be adopted on an industrial scale. Chiefly, catalysts must be developed to activate carbon-containing compounds from their thermodynamically stable ground states, using hydrogen, electrons, or heat as energy sources. We chose as model catalytic systems: 1) Metathesis of ethene and 2-butene; 2) Methane dehydrogenation and carbon dioxide hydrogenation. We developed three computational methodologies to study these processes across a range of length and time scales. First, we investigated how electronic structure affects the properties and reactivity of these catalyst systems; by computing the partial electronic density of states, electronic localization function, and excess spin density, we showed how redox supports, such as ceria, promote electron transfer reactions. We applied this to the studies of methane activation and carbon dioxide activation. Second, we developed a non-equilibrium thermodynamics approach to calculate energies of activation at nite temperatures, based on the Bronsted-Evans-Polanyi principle and the Nudged Elastic Band method. Third, we developed an approach to numerically compute heat capacities and other thermodynamic properties on extended catalytic systems that are comparable in accuracy and precision to methods that have been well-developed for gas-phase molecules. We applied these to the studies of metathesis propagation and carbon dioxide hydrogenation. We gained mechanistic, thermodynamic, and kinetic insight into the elementary steps that comprise larger reaction networks of interest to the broader catalysis community. Ultimately, these theoretical and computational predictions can be used to guide experimental design, synthesis, and characterization of new catalyst systems.

  11. DESI-MS/MS of Chemical Warfare Agents and Related Compounds

    NASA Astrophysics Data System (ADS)

    D'Agostino, Paul A.

    Solid phase microextraction (SPME) fibers were used to headspace ­sample chemical warfare agents and their hydrolysis products from glass vials and glass vials containing spiked media, including Dacron swabs, office carpet, paper and fabric. The interface of the Z-spray source was modified to permit safe introduction of the SPME fibers for desorption electrospray ionization mass spectrometric (DESI-MS) analysis. A "dip and shoot" method was also developed for the rapid sampling and DESI-MS analysis of chemical warfare agents and their hydrolysis products in liquid samples. Sampling was performed by simply dipping fused silica, stainless steel or SPME tips into the organic or aqueous samples. Replicate analyses were completed within several minutes under ambient conditions with no sample pre-treatment, resulting in a significant increase in sample throughput. The developed sample handling and analysis method was applied to the determination of chemical warfare agent content in samples containing unknown chemical and/or biological warfare agents. Ottawa sand was spiked with sulfur mustard, extracted with water and autoclaved to ensure sterility. Sulfur mustard was completely hydrolysed during the extraction/autoclave step and thiodiglycol was identified by DESI-MS, with analyses generally being completed within 1 min using the "dip and shoot" method.

  12. An Automated High-Throughput Cell-Based Multiplexed Flow Cytometry Assay to Identify Novel Compounds to Target Candida albicans Virulence-Related Proteins

    PubMed Central

    Bernardo, Stella M.; Allen, Christopher P.; Waller, Anna; Young, Susan M.; Oprea, Tudor; Sklar, Larry A.; Lee, Samuel A.

    2014-01-01

    Although three major classes of systemic antifungal agents are clinically available, each is characterized by important limitations. Thus, there has been considerable ongoing effort to develop novel and repurposed agents for the therapy of invasive fungal infections. In an effort to address these needs, we developed a novel high-throughput, multiplexed screening method that utilizes small molecules to probe candidate drug targets in the opportunistic fungal pathogen Candida albicans. This method is amenable to high-throughput automated screening and is based upon detection of changes in GFP levels of individually tagged target proteins. We first selected four GFP-tagged membrane-bound proteins associated with virulence or antifungal drug resistance in C. albicans. We demonstrated proof-of-principle that modulation of fluorescence intensity can be used to assay the expression of specific GFP-tagged target proteins to inhibitors (and inducers), and this change is measurable within the HyperCyt automated flow cytometry sampling system. Next, we generated a multiplex of differentially color-coded C. albicans strains bearing C-terminal GFP-tags of each gene encoding candidate drug targets incubated in the presence of small molecules from the Prestwick Chemical Library in 384-well microtiter plate format. Following incubation, cells were sampled through the HyperCyt system and modulation of protein levels, as indicated by changes in GFP-levels of each strain, was used to identify compounds of interest. The hit rate for both inducers and inhibitors identified in the primary screen did not exceed 1% of the total number of compounds in the small-molecule library that was probed, as would be expected from a robust target-specific, high-throughput screening campaign. Secondary assays for virulence characteristics based on null mutant strains were then used to further validate specificity. In all, this study presents a method for the identification and verification of new antifungal drugs targeted to fungal virulence proteins using C. albicans as a model fungal pathogen. PMID:25350399

  13. Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

    EPA Science Inventory

    Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

  14. A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds.

    PubMed

    Lucantoni, Leonardo; Silvestrini, Francesco; Signore, Michele; Siciliano, Giulia; Eldering, Maarten; Dechering, Koen J; Avery, Vicky M; Alano, Pietro

    2015-01-01

    Plasmodium falciparum gametocytes, specifically the mature stages, are the only malaria parasite stage in humans transmissible to the mosquito vector. Anti-malarial drugs capable of killing these forms are considered essential for the eradication of malaria and tools allowing the screening of large compound libraries with high predictive power are needed to identify new candidates. As gametocytes are not a replicative stage it is difficult to apply the same drug screening methods used for asexual stages. Here we propose an assay, based on high content imaging, combining "classic" gametocyte viability readout based on gametocyte counts with a functional viability readout, based on gametocyte activation and the discrimination of the typical gamete spherical morphology. This simple and rapid assay has been miniaturized to a 384-well format using acridine orange staining of wild type P. falciparum 3D7A sexual forms, and was validated by screening reference antimalarial drugs and the MMV Malaria Box. The assay demonstrated excellent robustness and ability to identify quality hits with high likelihood of confirmation of transmission reducing activity in subsequent mosquito membrane feeding assays. PMID:26553647

  15. A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds

    PubMed Central

    Lucantoni, Leonardo; Silvestrini, Francesco; Signore, Michele; Siciliano, Giulia; Eldering, Maarten; Dechering, Koen J.; Avery, Vicky M.; Alano, Pietro

    2015-01-01

    Plasmodium falciparum gametocytes, specifically the mature stages, are the only malaria parasite stage in humans transmissible to the mosquito vector. Anti-malarial drugs capable of killing these forms are considered essential for the eradication of malaria and tools allowing the screening of large compound libraries with high predictive power are needed to identify new candidates. As gametocytes are not a replicative stage it is difficult to apply the same drug screening methods used for asexual stages. Here we propose an assay, based on high content imaging, combining “classic” gametocyte viability readout based on gametocyte counts with a functional viability readout, based on gametocyte activation and the discrimination of the typical gamete spherical morphology. This simple and rapid assay has been miniaturized to a 384-well format using acridine orange staining of wild type P. falciparum 3D7A sexual forms, and was validated by screening reference antimalarial drugs and the MMV Malaria Box. The assay demonstrated excellent robustness and ability to identify quality hits with high likelihood of confirmation of transmission reducing activity in subsequent mosquito membrane feeding assays. PMID:26553647

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

    SciTech Connect

    Kleinstreuer, N.C.; Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R.; Weir-Hauptman, A.M.; Palmer, J.A.; Knudsen, T.B.; Dix, D.J.; Donley, E.L.R.; Cezar, G.G.; University of Wisconsin-Madison, Madison, WI 53706

    2011-11-15

    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 Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal development and pregnancy. Black-Right-Pointing-Pointer Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.

  17. Characterization of Sources and Chemical Transformations of Volatile Organic Compounds (Invited)

    NASA Astrophysics Data System (ADS)

    Emmons, L. K.; Apel, E. C.; Hornbrook, R. S.; Blake, N. J.; Blake, D. R.; Guenther, A. B.; Kaser, L.; Yuan, B.; De Gouw, J. A.

    2013-12-01

    Volatile organic compounds (VOCs) are directly emitted from natural and anthropogenic sources, as well as chemically produced in the atmosphere. The emission rates of VOCs are not as well understood as other gases (e.g., CO, NOx), but play an important role in determining ozone production rates and formation of secondary organic aerosols (SOA). Many recent field experiments have included comprehensive measurements of VOCs in a variety of environments. This study will focus on observations from the Deep Convective Cloud and Chemistry (DC3) experiment (May-June 2012), which included sampling of air influenced by emissions from vegetation, oil and gas extraction and wildfires from the NSF GV and NASA DC-8 aircraft. Observations from aircraft during other experiments will also be used, such as the NASA DC-8 during the ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites) experiment (Spring and Summer 2008), and the NSF C-130 during the NOMADSS (Nitrogen, Oxidants, Mercury and Aerosol Distributions, Sources and Sinks) experiment (June-July 2013). These observations are used to evaluate model simulations from the Community Atmosphere Model with Chemistry (CAM-chem), a component of the NCAR Community Earth System Model. Through comparison of VOC/CO ratios between observations and models near source regions, the emission inventories are evaluated. The chemical evolution of VOCs, in particular the formation of oxidized species such as formaldehyde, acetaldehyde and acetone, are studied.

  18. Development of a Wireless and Passive SAW-Based Chemical Sensor for Organophosphorous Compound Detection.

    PubMed

    Xu, Fang-Qian; Wang, Wen; Xue, Xu-Feng; Hu, Hao-Liang; Liu, Xin-Lu; Pan, Yong

    2015-01-01

    A new wireless and passive surface acoustic wave (SAW)-based chemical sensor for organophosphorous compound (OC) detection is presented. A 434 MHz reflective delay line configuration composed by single phase unidirectional transducers (SPUDTs) and three shorted reflectors was fabricated on YZ LiNbO? piezoelectric substrate as the sensor element. A thin fluoroalcoholpolysiloxane (SXFA) film acted as the sensitive interface deposited onto the SAW propagation path between the second and last reflectors of the SAW device. The first reflector was used for the temperature compensation utilizing the difference method. The adsorption between the SXFA and OC molecules modulates the SAW propagation, especially for the time delay of the SAW, hence, the phase shifts of the reflection peaks from the corresponding reflectors can be used to characterize the target OC. Prior to the sensor fabrication, the coupling of modes (COM) and perturbation theory were utilized to predict the SAW device performance and the gas adsorption. Referring to a frequency-modulated continuous wave (FMCW)-based reader unit, the developed SAW chemical sensor was wirelessly characterized in gas exposure experiments for dimethylmethylphosphonate (DMMP) detection. Sensor performance parameters such as phase sensitivity, repeatability, linearity, and temperature compensation were evaluated experimentally. PMID:26633419

  19. Development of a Wireless and Passive SAW-Based Chemical Sensor for Organophosphorous Compound Detection

    PubMed Central

    Xu, Fang-Qian; Wang, Wen; Xue, Xu-Feng; Hu, Hao-Liang; Liu, Xin-Lu; Pan, Yong

    2015-01-01

    A new wireless and passive surface acoustic wave (SAW)-based chemical sensor for organophosphorous compound (OC) detection is presented. A 434 MHz reflective delay line configuration composed by single phase unidirectional transducers (SPUDTs) and three shorted reflectors was fabricated on YZ LiNbO3 piezoelectric substrate as the sensor element. A thin fluoroalcoholpolysiloxane (SXFA) film acted as the sensitive interface deposited onto the SAW propagation path between the second and last reflectors of the SAW device. The first reflector was used for the temperature compensation utilizing the difference method. The adsorption between the SXFA and OC molecules modulates the SAW propagation, especially for the time delay of the SAW, hence, the phase shifts of the reflection peaks from the corresponding reflectors can be used to characterize the target OC. Prior to the sensor fabrication, the coupling of modes (COM) and perturbation theory were utilized to predict the SAW device performance and the gas adsorption. Referring to a frequency-modulated continuous wave (FMCW)-based reader unit, the developed SAW chemical sensor was wirelessly characterized in gas exposure experiments for dimethylmethylphosphonate (DMMP) detection. Sensor performance parameters such as phase sensitivity, repeatability, linearity, and temperature compensation were evaluated experimentally. PMID:26633419

  20. Safety in the Chemical Laboratory: Nitric Acid, Nitrates, and Nitro Compounds.

    ERIC Educational Resources Information Center

    Bretherick, Leslie

    1989-01-01

    Discussed are the potential hazards associated with nitric acid, inorganic and organic nitrate salts, alkyl nitrates, acyl nitrates, aliphatic nitro compounds, aromatic nitro compounds, and nitration reactions. (CW)

  1. Chemical evolution of volatile organic compounds in the outflow of the Mexico City Metropolitan area

    SciTech Connect

    Apel, E.; Springston, S.; Karl, T.; Emmons, L.; Flocke, F.; Hills, A. J.; Madronich, S.; Lee-Taylor, J.; Fried, A.; Weibring, P.; Walega, J.; Richter, D., Tie, X.; Mauldin, L.; Campos, T.; Sive, B.; Kleinman, L.; Springston, S., Zaveri, R.; deGouw, J.; Zheng, J.; Zhang, R.; Rudolph, J.; Junkermann, W.; Riemer, D. D.

    2009-11-01

    The volatile organic compound (VOC) distribution in the Mexico City Metropolitan Area (MCMA) and its evolution as it is uplifted and transported out of the MCMA basin was studied during the 2006 MILAGRO/MIRAGE-Mex field campaign. The results show that in the morning hours in the city center, the VOC distribution is dominated by non-methane hydrocarbons (NMHCs) but with a substantial contribution from oxygenated volatile organic compounds (OVOCs), predominantly from primary emissions. Alkanes account for a large part of the NMHC distribution in terms of mixing ratios. In terms of reactivity, NMHCs also dominate overall, especially in the morning hours. However, in the afternoon, as the boundary layer lifts and air is mixed and aged within the basin, the distribution changes as secondary products are formed. The WRF-Chem (Weather Research and Forecasting with Chemistry) model and MOZART (Model for Ozone and Related chemical Tracers) were able to reproduce the general features of the daytime cycle of the VOC OH reactivity distribution showing that NMHCs dominate the distribution except in the afternoon hours and that the VOC OH reactivity peaks in the early morning due to high morning emissions from the city into a shallow boundary layer. The WRF-Chem and MOZART models showed higher reactivity than the experimental data during the nighttime cycle, perhaps indicating problems with the modeled nighttime boundary layer height. In addition, a plume was studied in which air was advected out of the MCMA and intercepted downwind with the DOE G1 on 18 March and the NCAR C130 one day later on 19 March. A number of identical species measured aboard each aircraft gave insight into the chemical evolution of the plume as it aged and was transported as far as 1000 km downwind. Ozone and many OVOCs were photochemically produced in the plume. The WRF-Chem and MOZART models were used to examine the spatial and temporal extent of the 19 March plume and to help interpret the OH reactivity in the downwind plume. The model results generally showed good agreement with experimental results for the total VOC OH reactivity downwind and gave insight into the distributions of VOC chemical classes downwind. A box model with detailed gas phase chemistry (NCAR Master Mechanism), initialized with concentrations observed at one of the ground sites in the MCMA, was used to examine the expected evolution of specific VOCs over a 1-2 day period. The models clearly supported the experimental evidence for NMHC oxidation leading to the formation of OVOCs downwind, which then become the primary fuel for ozone production far away from the MCMA.

  2. Chemical evolution of volatile organic compounds in the outflow of the Mexico City Metropolitan area

    SciTech Connect

    Apel, Eric; Emmons, L.; Karl, Thomas G.; Flocke, Frank M.; Hills, A. J.; Madronich, Sasha; Lee-Taylor, J.; Fried, Alan; Weibring, P.; Walega, J.; Richter, Dirk; Tie, X.; Mauldin, L.; Campos, Teresa; Weinheimer, Andrew J.; Knapp, David; Sive, B.; Kleinman, Lawrence I.; Springston, S.; Zaveri, Rahul A.; Ortega, John V.; Voss, Paul B.; Blake, D. R.; Baker, Angela K.; Warneke, Carsten; Welsh-Bon, Daniel; de Gouw, Joost A.; Zheng, J.; Zhang, Renyi; Rudolph, Jochen; Junkermann, W.; Riemer, D.

    2010-01-01

    The volatile organic compound (VOC) distribution in the Mexico City Metropolitan Area (MCMA) and its evolution as it is uplifted and transported out of the MCMA basin was studied during the 2006 MILAGRO/MIRAGE-Mex field campaign. The results show that in the morning hours in the city center, the VOC distribution is dominated by non-methane hydrocarbons (NMHCs) but with a substantial contribution from oxygenated volatile organic compounds (OVOCs), predominantly from primary emissions. Alkanes account for a large part of the NMHC distribution in terms of mixing ratios. In terms of reactivity, NMHCs also dominate overall, especially in the morning hours. However, in the afternoon, as the boundary layer lifts and air is mixed and aged within the basin, the distribution changes as secondary products are formed. The WRF-Chem (Weather Research and Forecasting with Chemistry) model and MOZART (Model for Ozone and Related chemical Tracers) were able to reproduce the general features of the daytime cycle of the VOC OH reactivity distribution showing that NMHCs dominate the distribution except in the afternoon hours and that the VOC OH reactivity peaks in the early morning due to high morning emissions from the city into a shallow boundary layer. The WRF-Chem and MOZART models showed higher reactivity than the experimental data during the nighttime cycle, perhaps indicating problems with the modeled nighttime boundary layer height. In addition, a plume was studied in which air was advected out of the MCMA and intercepted downwind with the DOE G1 on March 18 and the NCAR C130 one day later on March 19. A number of identical species measured aboard each aircraft gave insight into the chemical evolution of the plume as it aged and was transported as far as 1000 km downwind. Ozone and many OVOCs were photochemically produced in the plume. The WRF-Chem and MOZART models were used to examine the spatial and temporal extent of the March 19 plume and to help interpret the OH reactivity in the downwind plume. The model results generally showed good agreement with experimental results for the total VOC OH reactivity downwind and gave insight into the distributions of VOC chemical classes downwind. A box model with detailed gas phase chemistry (NCAR Master Mechanism), initialized with concentrations observed at one of the ground sites in the MCMA, was used to examine the expected evolution of specific VOCs over a 1-2 day period. The models clearly supported the experimental evidence for NMHC oxidation leading to the formation of OVOCs downwind, which then become the primary fuel for ozone production far away from the MCMA.

  3. The nematode Caenorhabditis elegans as a tool to predict chemical activity on mammalian development and identify mechanisms influencing toxicological outcome

    PubMed Central

    Harlow, Philippa H.; Perry, Simon J.; Widdison, Stephanie; Daniels, Shannon; Bondo, Eddie; Lamberth, Clemens; Currie, Richard A.; Flemming, Anthony J.

    2016-01-01

    To determine whether a C. elegans bioassay could predict mammalian developmental activity, we selected diverse compounds known and known not to elicit such activity and measured their effect on C. elegans egg viability. 89% of compounds that reduced C. elegans egg viability also had mammalian developmental activity. Conversely only 25% of compounds found not to reduce egg viability in C. elegans were also inactive in mammals. We conclude that the C. elegans egg viability assay is an accurate positive predictor, but an inaccurate negative predictor, of mammalian developmental activity. We then evaluated C. elegans as a tool to identify mechanisms affecting toxicological outcomes among related compounds. The difference in developmental activity of structurally related fungicides in C. elegans correlated with their rate of metabolism. Knockdown of the cytochrome P450s cyp-35A3 and cyp-35A4 increased the toxicity to C. elegans of the least developmentally active compounds to the level of the most developmentally active. This indicated that these P450s were involved in the greater rate of metabolism of the less toxic of these compounds. We conclude that C. elegans based approaches can predict mammalian developmental activity and can yield plausible hypotheses for factors affecting the biological potency of compounds in mammals. PMID:26987796

  4. The nematode Caenorhabditis elegans as a tool to predict chemical activity on mammalian development and identify mechanisms influencing toxicological outcome.

    PubMed

    Harlow, Philippa H; Perry, Simon J; Widdison, Stephanie; Daniels, Shannon; Bondo, Eddie; Lamberth, Clemens; Currie, Richard A; Flemming, Anthony J

    2016-01-01

    To determine whether a C. elegans bioassay could predict mammalian developmental activity, we selected diverse compounds known and known not to elicit such activity and measured their effect on C. elegans egg viability. 89% of compounds that reduced C. elegans egg viability also had mammalian developmental activity. Conversely only 25% of compounds found not to reduce egg viability in C. elegans were also inactive in mammals. We conclude that the C. elegans egg viability assay is an accurate positive predictor, but an inaccurate negative predictor, of mammalian developmental activity. We then evaluated C. elegans as a tool to identify mechanisms affecting toxicological outcomes among related compounds. The difference in developmental activity of structurally related fungicides in C. elegans correlated with their rate of metabolism. Knockdown of the cytochrome P450s cyp-35A3 and cyp-35A4 increased the toxicity to C. elegans of the least developmentally active compounds to the level of the most developmentally active. This indicated that these P450s were involved in the greater rate of metabolism of the less toxic of these compounds. We conclude that C. elegans based approaches can predict mammalian developmental activity and can yield plausible hypotheses for factors affecting the biological potency of compounds in mammals. PMID:26987796

  5. ION COMPOSITION ELUCIDATION (ICE): A HIGH RESOLUTION MASS SPECTROMETRIC TOOL FOR IDENTIFYING ORGANIC COMPOUNDS IN COMPLEX EXTRACTS OF ENVIRONMENTAL SAMPLES

    EPA Science Inventory


    Unidentified Organic Compounds. For target analytes, standards are purchased, extraction and clean-up procedures are optimized, and mass spectra and retention times for the chromatographic separation are obtained for comparison to the target compounds in environmental sample ...

  6. Characterization of Pellicle Inhibition in Gluconacetobacter xylinus 53582 by a Small Molecule, Pellicin, Identified by a Chemical Genetics Screen

    PubMed Central

    Strap, Janice L.; Latos, Andrew; Shim, Isaac; Bonetta, Dario T.

    2011-01-01

    Pellicin ([2E]-3-phenyl-1-[2,3,4,5-tetrahydro-1,6-benzodioxocin-8-yl]prop-2-en-1-one) was identified in a chemical genetics screen of 10,000 small molecules for its ability to completely abolish pellicle production in Gluconacetobacter xylinus. Cells grown in the presence of pellicin grew 1.5 times faster than untreated cells. Interestingly, growth in pellicin also caused G. xylinus cells to elongate. Measurement of cellulose synthesis in vitro showed that cellulose synthase activity was not directly inhibited by pellicin. Rather, when cellulose synthase activity was measured in cells that were pre-treated with the compound, the rate of cellulose synthesis increased eight-fold over that observed for untreated cells. This phenomenon was also apparent in the rapid production of cellulose when cells grown in the presence of pellicin were washed and transferred to media lacking the inhibitor. The rate at which cellulose was produced could not be accounted for by growth of the organism. Pellicin was not detected when intracellular contents were analyzed. Furthermore, it was found that pellicin exerts its effect extracellularly by interfering with the crystallization of pre-cellulosic tactoidal aggregates. This interference of the crystallization process resulted in enhanced production of cellulose II as evidenced by the ratio of acid insoluble to acid soluble product in in vitro assays and confirmed in vivo by scanning electron microscopy and powder X-ray diffraction. The relative crystallinity index, RCI, of pellicle produced by untreated G. xylinus cultures was 70% while pellicin-grown cultures had RCI of 38%. Mercerized pellicle of untreated cells had RCI of 42%, which further confirms the mechanism of action of pellicin as an inhibitor of the cellulose I crystallization process. Pellicin is a useful tool for the study of cellulose biosynthesis in G. xylinus. PMID:22174763

  7. Chemical oxidation of a malodorous compound, indole, using iron entrapped in calcium alginate beads.

    PubMed

    Ben Hammouda, Samia; Adhoum, Nafaâ; Monser, Lotfi

    2016-01-15

    Iron-alginate beads (Fe-ABs) were successfully prepared by the ion-gelation method, and applied as heterogeneous Fenton catalysts for the removal of a malodorous compound 'indole'. Similarly, copper-enriched alginate beads (Cu-ABs) were synthesized and tested as like-Fenton catalyst, however, their application proved not to be effective for this purpose. Fe-ABs catalysts were characterized by FTIR, SEM, EDS and AAS spectroscopy. Results pointed out that the parameters affecting Fenton catalysis must be carefully chosen to avoid excessive iron release. Under optimal conditions, complete indole removal and considerably high reduction of TOC, without significant leaching was achieved. Indole decay followed a pseudo-first-order kinetics. The absolute rate constant for indole hydroxylation was 3.59×10(9) M(-1) s(-1), as determined by the competition kinetics method. Four reaction intermediates (Isatin, Dioxindole, Oxindole and Anthralinic acid) were identified by ULC/MS/MS analysis. Short-chain aliphatic carboxylic acids like formic, acetic, oxalic, maleic, oxamic and pyruvic acids were identified by ion exclusion chromatography and as end-products. Based on the identified by-products, a plausible mineralization pathway was proposed. Moreover, the catalyst was recovered quantitatively by simple filtration and reused for several times without significant loss of activity. PMID:26384996

  8. 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…

  9. 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...

  10. Electrocatalytic processing of renewable biomass-derived compounds for production of chemicals, fuels and electricity

    NASA Astrophysics Data System (ADS)

    Xin, Le

    The dual problems of sustaining the fast growth of human society and preserving the environment for future generations urge us to shift our focus from exploiting fossil oils to researching and developing more affordable, reliable and clean energy sources. Human beings had a long history that depended on meeting our energy demands with plant biomass, and the modern biorefinery technologies realize the effective conversion of biomass to production of transportation fuels, bulk and fine chemicals so to alleviate our reliance on fossil fuel resources of declining supply. With the aim of replacing as much non-renewable carbon from fossil oils with renewable carbon from biomass as possible, innovative R&D activities must strive to enhance the current biorefinery process and secure our energy future. Much of my Ph.D. research effort is centered on the study of electrocatalytic conversion of biomass-derived compounds to produce value-added chemicals, biofuels and electrical energy on model electrocatalysts in AEM/PEM-based continuous flow electrolysis cell and fuel cell reactors. High electricity generation performance was obtained when glycerol or crude glycerol was employed as fuels in AEMFCs. The study on selective electrocatalytic oxidation of glycerol shows an electrode potential-regulated product distribution where tartronate and mesoxalate can be selectively produced with electrode potential switch. This finding then led to the development of AEMFCs with selective production of valuable tartronate or mesoxalate with high selectivity and yield and cogeneration of electricity. Reaction mechanisms of electrocatalytic oxidation of ethylene glycol and 1,2-propanediol were further elucidated by means of an on-line sample collection technique and DFT modeling. Besides electro-oxidation of biorenewable alcohols to chemicals and electricity, electrocatalytic reduction of keto acids (e.g. levulinic acid) was also studied for upgrading biomass-based feedstock to biofuels while achieving renewable electricity storage. Meanwhile, ORR that is often coupled in AEMFCs on the cathode was investigated on non-PGM electrocatalyst with comparable activity to commercial Pt/C. The electro-biorefinery process could be coupled with traditional biorefinery operation and will play a significant role in our energy and chemical landscape.

  11. Acute toxicity of Daphnia pulex to six classes of chemical compounds potentially hazardous to Great Lakes aquatic biota

    USGS Publications Warehouse

    Smith, Stephen B.; Savino, Jacqueline F.; Blouin, Marc A.

    1988-01-01

    Of the six classes of chemicals potentially hazardous to Great Lakes aquatic biota, derivatives of polyaromatic hydrocarbons (PAHs) were the most acutely toxic (48-h EC 50) to Daphnia pulex. The other classes, listed in order of decreasing toxicity were alkyl halides, nitrogen-containing compounds, cyclic alkanes, heterocyclic nitrogen compounds, silicon-containing compounds. O f the 41 compounds representing the six chemical classes, 6 were extremely toxic (> 0.01 - 0.1 mg/L), 11 highly toxic (> 01. - 1.0 mg/L), 20 moderately toxic (> 1.0 - 10.0 mg/L), and 4 slightly toxic (>10 - 100 mg/L). The reference compound, p, p'DDT, was super toxic (< 0.01 mg/L). Based on toxicity and relative abundance (hazard ranking) of the 21 compounds that were detected in tissue of Great Lakes fishes, the classes of compounds that present the greatest threat to Great Lakes aquatic biota are PAH derivatives, alkyl halides, and cyclic aklanes.

  12. Acute toxicity to Daphnia pulex of six classes of chemical compounds potentially hazardous to Great Lakes aquatic biota

    SciTech Connect

    Smith, S.B.; Savino, J.F.; Blouin, M.A. )

    1988-01-01

    Of the six classes of chemicals potentially hazardous to Great Lakes aquatic biota, derivatives of polyaromatic hydrocarbons (PAHs) were the most acutely toxic (48-h EC 50) to Daphnia pulex. The other classes, listed in order of decreasing toxicity, were alkyl halides, nitrogen-containing compounds, cyclic alkanes, heterocyclic nitrogen compounds, silicon-containing compounds. Of the 41 compounds representing the six chemical classes, 6 were extremely toxic (> 0.01-0.1 mg/L), 11 highly toxic (> 0.1 {minus} 1.0 mg/L), 20 moderately toxic (> 1.0 {minus} 10.0 mg/L), and 4 slightly toxic (> 10 {minus} 100 mg/L). The reference compound, p, p'DDT, was super toxic (< 0.01 mg/L). Based on toxicity and relative abundance (hazard ranking) of the 21 compounds that were detected in tissue of Great Lakes fishes, the classes of compounds that present the greatest threat to Great Lakes aquatic biota are PAH derivatives, alkyl halides, and cyclic alkanes.

  13. The correlation between photocatalytic oxidation performance and chemical/physical properties of indoor volatile organic compounds

    NASA Astrophysics Data System (ADS)

    Yu, Kuo-Pin; Lee, Grace W. M.; Huang, Wei-Ming; Wu, Chihcheng; Yang, Shinhao

    In this study, six species of volatile organic compounds (VOCs), n-hexane, iso-butanol, toluene, p-xylene, m-xylene, and mesitylene, were selected as the target pollutants to investigate how the photocatalytic oxidation (PCO) performance is related to their physical/chemical properties. The PCO kinetics were well fit by a Langmuir-Hinshelwood (L-H) model for bimolecular surface reaction and competitive adsorption at gas flow rate above 1000 mL min -1 (reaction-controlling region), where the gas-phase mass transfer effect was negligible. The rate constants of PCO for toluene, p-xylene, m-xylene, and mesitylene ranged from 1.22 to 4.00 ?mol m -2 s -1, and were proportional to VOC-hydroxyl radical rate constant ( kOH). The Langmuir adsorption constants of the four aromatic VOCs investigated and water ranged from 0.95 to 1.35 ppm -1 and from 5.6110 -3 to 1.4410 -3 ppm -1, respectively. A strongly linear positive relationship was found between the reciprocal of the Langmuir adsorption constants of the four aromatic VOCs investigated and Henry's Law constants. Conversely, the reciprocal of Langmuir adsorption constants of water showed a strong negative relationship with Henry's Law constants (in units kPa m 3 mol -1) of the four aromatic VOCs investigated. The relationships noted above were not found between different classes of VOCs ( n-hexane, iso-butanol, and aromatic VOCs investigated). The percentage of residual intermediates (partially oxidized and incompletely mineralized organic compound from the primary VOCs) decreased as the inlet VOCs concentration decreased.

  14. Chemical Characterization of Secondary Organic Aerosol Formed from Atmospheric Aqueous-phase Reactions of Phenolic Compounds

    NASA Astrophysics Data System (ADS)

    Yu, L.; Smith, J.; Anastasio, C.; Zhang, Q.

    2012-12-01

    Phenolic compounds, which are released in significant amounts from biomass burning, may undergo fast aqueous-phase reactions to form secondary organic aerosol (SOA) in the atmosphere. Understanding the aqueous-phase reaction mechanisms of these compounds and the composition of their reaction products is thus important for constraining SOA sources and predicting organic aerosol properties in models. In this study, we investigate the aqueous-phase reactions of three phenols (phenol, guaiacol and syringol) with two oxidants - excited triplet states (3C*) of non-phenolic aromatic carbonyls and hydroxyl radical (OH). By employing four analytical methods including high-resolution aerosol mass spectrometry, total organic carbon analysis, ion chromatography, and liquid chromatography-mass spectrometry, we thoroughly characterize the chemical compositions of the low volatility reaction products of phenols and propose formation mechanisms based on this information. Our results indicate that phenolic SOA is highly oxygenated, with O/C ratios in the range of 0.83-1.03, and that the SOA of phenol is usually more oxidized than those of guaiacol and syringol. Among the three precursors, syringol generates the largest fraction of higher molecular weight (MW) products. For the same precursor, the SOA formed via reaction with 3C* is less oxidized than that formed via reaction with OH. In addition, oxidation by 3C* enhances the formation of higher MW species, including phenolic dimers, higher oligomers and hydroxylated products, compared to reactions initiated by OH, which appear to favor the formation of organic acids. However, our results indicate that the yields of small organic acids (e.g., formate, acetate, oxalate, and malate) are low for both reaction pathways, together accounting for less than 5% of total SOA mass.

  15. Theoretical Study of Indium Compounds of Interest for Organometallic Chemical Vapor Deposition

    NASA Technical Reports Server (NTRS)

    Cardelino, B. H.; Moore, C. E.; Cardelino, C. A.; Frazier, D. O.; Backmann, K. J.

    2000-01-01

    The structural. electronic and therinochemical properties of indium compounds which are of interest in halide transport and organometallic chemical vapor deposition processes have been studied by ab initio and statistical mechanics methods. The compounds reported include: indium halides and hydrides (InF, InCl, InCl3, InH, InH2, InH3); indium clusters (In2, In3); methylindium, dimethylindium, and their hydrogen derivatives [In(CH3), In(CH3)H, In(CH3)H2, In(CH3)2, In(CH3)2H]; dimethyl-indium dimer [In2(CH3)4], trimethyl-indium [In(CH3)3]; dehydrogenated methyl, dimethyl and trimethylindium [In(CH3)2CH2, In(CH3)CH2, In(CH2)], trimethylindium adducts with ammonia, trimethylamine and hydrazine [(CH3)3In:NH3, (CH3)3In:N(CH3)3, (CH3)3In:N(H2)N(H2)]; dimethylamino-indium and methylimino-indium [In(CH3)2(NH2), In(CH3)(NH)]; indium nitride and indium nitride dimer (InN, In2N2), indium phosphide, arsenide and antimonide ([InP, InAs, InSb). The predicted electronic properties are based on density functional theory calculations; the calculated thermodynamic properties are reported following the format of the JANAF (Joint Army, Navy, NASA, Air Force) Tables. Equilibrium compositions at two temperatures (298 and 1000 K) have been analyzed for groups of competing simultaneous reactions.

  16. 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 paradigm shift: Individual ice nucleating particle composition indicates that IN are similar to the majority of particles in the population and not exceptional. This suggests that composition alone may not be a determinant for IN identification. Furthermore, the results suggest that particle abundance may be a crucial parameter for IN efficiency when predicting cloud glaciation processes. These findings would have important consequences for cloud modeling, laboratory ice nucleation experiments, and field measurements.

  17. Effects of Chemical Speciation on the Mineralization of Organic Compounds by Microorganisms

    PubMed Central

    Madsen, E. L.; Alexander, Martin

    1985-01-01

    The mineralization of 1.0 to 100 ng each of four complexing compounds—oxalate, citrate, nitrilotriacetate (NTA), and EDTA—per ml was tested in media prepared in accordance with equilibrium calculations by a computer program so that the H, Ca, Mg, Fe, or Al complex (chemical species) was predominant. Sewage microorganisms mineralized calcium citrate more rapidly than iron, aluminum, or hydrogen citrate, and magnesium citrate was degraded slowest. Aluminum, hydrogen, and iron oxalates were mineralized more rapidly than calcium oxalate, and magnesium oxalate was decomposed slowest. Sewage microorganisms mineralized calcium NTA but not aluminum, magnesium, hydrogen, or iron NTA or any of the EDTA complexes. Pseudomonas sp. mineralized calcium and iron citrates but had no activity on hydrogen, aluminum, or magnesium citrate. Pseudomonas pseudoalcaligenes mineralized calcium, iron, hydrogen, and aluminum citrates but had little activity on magnesium citrate. Pseudomonas alcaligenes used calcium, iron, hydrogen, and aluminum oxalates readily, but it used magnesium oxalate at a slower rate. Listeria sp. destroyed calcium NTA but had no effect on hydrogen, iron, or magnesium NTA. Increasing the Ca concentration in the medium enhanced the breakdown of NTA by Listeria sp. The different activities of the bacterial isolates were not a result of the toxicity of the complexes or the lack of availability of a nutrient element. NTA mineralization was not enhanced by the addition of Ca to Beebe Lake water, but it was enhanced when Ca and an NTA-degrading inoculum were added to water from an oligotrophic lake. The data show that chemical speciation influences the mineralization of organic compounds by naturally occurring microbial communities and by individual bacterial populations. PMID:16346854

  18. Adverse Outcome Pathways for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptor

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  19. 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...

  20. Chemical and thermal freeze-out of identified hadrons at the LHC

    NASA Astrophysics Data System (ADS)

    Zhu, Xiangrong; Song, Huichao

    2016-01-01

    This proceedings contribution briefly summarizes our recent VISHNU hybrid model investigations on the chemical and thermal freeze-out of various hadrons species in 2.76 A TeV Pb+Pb collisions. Detailed analysis on the evolution of particle yields and the last elastic collisions distributions during the hadronic evolution reveals that the two multi-strange hadrons, Ξ and Ω, experience early chemical and thermal freeze-out when compared with other hadron species.

  1. Using Cs-137, C-14 and biomarker compounds to identify reasons for C and N losses in resampled profiles

    NASA Astrophysics Data System (ADS)

    Baisden, W. T.; Parfitt, R. L.; Schipper, L. A.; Filley, T. R.; Ross, C.

    2008-12-01

    A New Zealand data set of archived and resampled pasture soil profiles has identified a systematic pattern large soil C and N losses and gains that appear to be related to land-use intensity. We use isotope and organic geochemistry techniques in selected archived and resampled soil horizons to identify reasons for the observed large soil C and N losses and gains in intensive flat non-allophanic pasture and hill country soil profiles, respectively. These techniques allow us to examine 3 of the ~10 hypotheses proposed to explain the large losses initially observed in intensive pasture soils. These three hypotheses are: (1) soil C and N changes may be due to erosion and deposition; (2) pre-European forest-derived organic matter is being lost; and (3) changes in litter quality are reducing the amount of plant C and N stabilized in soil. To test hypothesis (1), we use 137Cs, accumulated in the soil clay fraction from nuclear fallout between 1945 and 1965. Measurements comparing archived (post-1965) and resampled horizons show losses or gains of 137Cs, which we interpret as erosion and deposition, respectively. Apparent wind erosion of up to ~6 cm of surface soil explains large surface soil C losses in 2 flat profiles, while apparent deposition explains soil C gains in two hill country profiles. Measurements of 14C assist in the evaluation of hypothesis (2) by suggesting that, after accounting for 137Cs-estimated erosion or deposition, surface soils are mainly losing C fixed since bomb 14C was injected into the atmosphere (post-1950). In contrast, soil C losses below 40 cm depth are dominated by C derived from pre-European forests. Biomarker compounds, particularly lignin-derivatives, allow us to evaluate hypotheses (2) and (3). Results to date suggest that failure to stabilize grass-derived C is more important than losses of forest-derived C in explaining soil C losses in the upper 30 cm. More broadly, biomarker and 137Cs measurements suggest that steady-state assumptions must be carefully applied in models of C and N in New Zealand pasture soils, and will be inappropriate in some circumstances. Based on these studies of 3-5 selected profiles, we examine approaches to broaden the use of these techniques to identify reasons for C and N losses and gains as the resampling of archived New Zealand soil profiles continues.

  2. Chemical composition and biological activity of four salvia essential oils and individual compounds against two species of mosquitoes.

    PubMed

    Ali, Abbas; Tabanca, Nurhayat; Demirci, Betul; Blythe, Eugene K; Ali, Zulfiqar; Baser, K Husnu Can; Khan, Ikhlas A

    2015-01-21

    The chemical compositions of essential oils obtained from four species of genus Salvia were analyzed by gas chromatography with a flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The main compounds identified from Salvia species essential oils were as follows: 1,8-cineole (71.7%), ?-pinene (5.1%), camphor (4.4%), and ?-pinene (3.8%) in Salvia apiana; borneol (17.4%), ?-eudesmol (10.4%), bornyl acetate (5%), and guaiol (4.8%) in Salvia elegans; bornyl acetate (11.4%), ?-caryophyllene (6.5%), caryophyllene oxide (13.5%), and spathulenol (7.0%) in Salvia leucantha; ?-thujene (25.8%), viridiflorol (20.4%), ?-thujene (5.7%), and camphor (6.4%) in Salvia officinalis. In biting-deterrent bioassays, essential oils of S. leucantha and S. elegans at 10 ?g/cm(2) showed activity similar to that of DEET (97%, N, N-diethyl-m-toluamide) in two species of mosquitoes, whereas the activities of S. officinalis and S. apiana essential oils were lower than those of the other oils or DEET. Pure compounds ?-eudesmol and guaiol showed biting-deterrent activity similar to DEET at 25 nmol/cm(2), whereas the activity of 13-epi-manool, caryophyllene oxide, borneol, bornyl acetate, and ?-caryophyllene was significantly lower than that of ?-eudesmol, guaiol, or DEET. All essential oils showed larvicidal activity except that of S. apiana, which was inactive at the highest dose of 125 ppm against both mosquito species. On the basis of 95% CIs, all of the essential oils showed higher toxicity in Anopheles quadrimaculatus than in Aedes aegypti. The essential oil of S. leucantha with an LC50 value of 6.2 ppm showed highest toxicity in An. quadrimaculatus. PMID:25531412

  3. Nature of the chemical bond and prediction of radiation tolerance in pyrochlore and defect fluorite compounds

    SciTech Connect

    Lumpkin, Gregory R. Pruneda, Miguel; Rios, Susana; Smith, Katherine L.; Trachenko, Kostya; Whittle, Karl R.; Zaluzec, Nestor J.

    2007-04-15

    The radiation tolerance of synthetic pyrochlore and defect fluorite compounds has been studied using ion irradiation. We show that the results can be quantified in terms of the critical temperature for amorphization, structural parameters, classical Pauling electronegativity difference, and disorder energies. Our results demonstrate that radiation tolerance is correlated with a change in the structure from pyrochlore to defect fluorite, a smaller unit cell dimension, and lower cation-anion disorder energy. Radiation tolerance is promoted by an increase in the Pauling cation-anion electronegativity difference or, in other words, an increase in the ionicity of the chemical bonds. A further analysis of the data indicates that, of the two possible cation sites in ideal pyrochlore, the smaller B-site cation appears to play the major role in bonding. This result is supported by ab initio calculations of the structure and bonding, showing a correlation between the Mulliken overlap populations of the B-site cation and the critical temperature. - Graphical abstract: Three-dimensional representation of the predicted critical amorphization temperature in pyrochlores.

  4. Immunological mechanisms of adaptation to the low-weight chemical compounds in ontogenesis.

    PubMed

    Glushkov, A N

    2003-09-01

    It is postulated that adaptation to the low-weight chemical compounds includes six consistent ontogenetic periods: the reciprocal selection of the marriage partners; the maturation of the gametes; the formation of the zygote; the development of the fetus; the birth and nursing of the child; and the sexual maturation of a human being. The main immunological parts of adaptation are: the antibodies to the low-weight xeno- and endobiotics; the reciprocal immune-like recognition of the maternal and paternal gametes; and the maternal immune reaction on the paternal histocompatibility antigens of the fetus. The main immunological mechanisms of adaptation are: the promotion of the selectivity in the smell recognition of the marriage partners by the antibodies to the xeno- and endobiotics expanding the individual spectrum of their metabolites; the inhibition of the xenobiotic genotoxic action on the gametes, fetus and child by the antibodies; the prevention of the development of gene-damaged gametes and fetus by antibodies to the sexual hormones; and the immune preservation (elimination) of the heterozygote (homozygote) fetus. PMID:12944111

  5. Two-dimensional carbon compounds derived from graphyne with chemical properties superior to those of graphene.

    PubMed

    Zheng, Jia-Jia; Zhao, Xiang; Zhao, Yuliang; Gao, Xingfa

    2013-01-01

    Computational studies considering both thermodynamic and kinetic aspects revealed that graphyne, a carbon material that has recently been of increasing interest, favours unprecedented homogeneous "in-plane" addition reactions. The addition of dichlorocarbene to the C(sp)-C(sp) bond, a site with outstanding regioselectivity in graphyne, proceeds via a stepwise mechanism. Due to their homogeneous nature, additions occurring at C(sp)-C(sp) bonds yield structurally ordered two-dimensional carbon compounds (2DCCs). 2DCCs have electronic band structures near the Fermi level that are similar to those of graphene and are either electrically semi-conductive or metallic depending on whether the reactions break the hexagonal symmetry. Notably, 2DCCs can be further functionalised through substitution reactions with little damage to the extended ?-electron conjugation system. These results suggest that 2DCCs derived from graphyne have physical properties comparable to those of graphene and chemical properties superior to those of graphene. Therefore, 2DCCs are expected to be better suited to practical applications. PMID:23429350

  6. Phenotypic Screening of Primary Human Cell Culture Systems to Identify Potential for Compound Toxicity (CHI Phenotypic Screening)

    EPA Science Inventory

    Addressing safety aspects of drugs and environmental chemicals has historically been undertaken through animal testing. However, the quantity of chemicals needing assessment and the challenge of species extrapolation require development of alternative approaches. Assessing phenot...

  7. CFam: a chemical families database based on iterative selection of functional seeds and seed-directed compound clustering

    PubMed Central

    Zhang, Cheng; Tao, Lin; Qin, Chu; Zhang, Peng; Chen, Shangying; Zeng, Xian; Xu, Feng; Chen, Zhe; Yang, Sheng Yong; Chen, YuZong

    2015-01-01

    Similarity-based clustering and classification of compounds enable the search of drug leads and the structural and chemogenomic studies for facilitating chemical, biomedical, agricultural, material and other industrial applications. A database that organizes compounds into similarity-based as well as scaffold-based and property-based families is useful for facilitating these tasks. CFam Chemical Family database http://bidd2.cse.nus.edu.sg/cfam was developed to hierarchically cluster drugs, bioactive molecules, human metabolites, natural products, patented agents and other molecules into functional families, superfamilies and classes of structurally similar compounds based on the literature-reported high, intermediate and remote similarity measures. The compounds were represented by molecular fingerprint and molecular similarity was measured by Tanimoto coefficient. The functional seeds of CFam families were from hierarchically clustered drugs, bioactive molecules, human metabolites, natural products, patented agents, respectively, which were used to characterize families and cluster compounds into families, superfamilies and classes. CFam currently contains 11 643 classes, 34 880 superfamilies and 87 136 families of 490 279 compounds (1691 approved drugs, 1228 clinical trial drugs, 12 386 investigative drugs, 262 881 highly active molecules, 15 055 human metabolites, 80 255 ZINC-processed natural products and 116 783 patented agents). Efforts will be made to further expand CFam database and add more functional categories and families based on other types of molecular representations. PMID:25414339

  8. Framework for identifying chemicals with structural features associated with the potential to act as developmental or reproductive toxicants.

    PubMed

    Wu, Shengde; Fisher, Joan; Naciff, Jorge; Laufersweiler, Michael; Lester, Cathy; Daston, George; Blackburn, Karen

    2013-12-16

    Developmental and reproductive toxicity (DART) end points are important hazard end points that need to be addressed in the risk assessment of chemicals to determine whether or not they are the critical effects in the overall risk assessment. These hazard end points are difficult to predict using current in silico tools because of the diversity of mechanisms of action that elicit DART effects and the potential for narrow windows of vulnerability. DART end points have been projected to consume the majority of animals used for compliance with REACH; thus, additional nonanimal predictive tools are urgently needed. This article presents an empirically based decision tree for determining whether or not a chemical has receptor-binding properties and structural features that are consistent with chemical structures known to have toxicity for DART end points. The decision tree is based on a detailed review of 716 chemicals (664 positive, 16 negative, and 36 with insufficient data) that have DART end-point data and are grouped into defined receptor binding and chemical domains. When tested against a group of chemicals not included in the training set, the decision tree is shown to identify a high percentage of chemicals with known DART effects. It is proposed that this decision tree could be used both as a component of a screening system to identify chemicals of potential concern and as a component of weight-of-evidence decisions based on structure-activity relationships (SAR) to fill data gaps without generating additional test data. In addition, the chemical groupings generated could be used as a starting point for the development of hypotheses for in vitro testing to elucidate mode of action and ultimately in the development of refined SAR principles for DART that incorporate mode of action (adverse outcome pathways). PMID:24206190

  9. Identification of chlorinated solvents degradation zones in clay till by high resolution chemical, microbial and compound specific isotope analysis

    NASA Astrophysics Data System (ADS)

    Damgaard, Ida; Bjerg, Poul L.; Blum, Jacob; Scheutz, Charlotte; Hunkeler, Daniel; Jacobsen, Carsten S.; Tuxen, Nina; Broholm, Mette M.

    2013-03-01

    The degradation of chlorinated ethenes and ethanes in clay till was investigated at a contaminated site (Vadsby, Denmark) by high resolution sampling of intact cores combined with groundwater sampling. Over decades of contamination, bioactive zones with degradation of trichloroethene (TCE) and 1,1,1-trichloroethane (1,1,1-TCA) to 1,2-cis-dichloroethene (cis-DCE) and 1,1-dichloroethane, respectively, had developed in most of the clay till matrix. Dehalobacter dominated over Dehalococcoides (Dhc) in the clay till matrix corresponding with stagnation of sequential dechlorination at cis-DCE. Sporadically distributed bioactive zones with partial degradation to ethene were identified in the clay till matrix (thickness from 0.10 to 0.22 m). In one sub-section profile the presence of Dhc with the vcrA gene supported the occurrence of degradation of cis-DCE and VC, and in another enriched ?13C for TCE, cis-DCE and VC documented degradation. Highly enriched ?13C for 1,1,1-TCA (25) and cis-DCE (- 4) suggested the occurrence of abiotic degradation in a third sub-section profile. Due to fine scale heterogeneity the identification of active degradation zones in the clay till matrix depended on high resolution subsampling of the clay till cores. The study demonstrates that an integrated approach combining chemical analysis, molecular microbial tools and compound specific isotope analysis (CSIA) was required in order to document biotic and abiotic degradations in the clay till system.

  10. Identification of chlorinated solvents degradation zones in clay till by high resolution chemical, microbial and compound specific isotope analysis.

    PubMed

    Damgaard, Ida; Bjerg, Poul L; Blum, Jacob; Scheutz, Charlotte; Hunkeler, Daniel; Jacobsen, Carsten S; Tuxen, Nina; Broholm, Mette M

    2013-03-01

    The degradation of chlorinated ethenes and ethanes in clay till was investigated at a contaminated site (Vadsby, Denmark) by high resolution sampling of intact cores combined with groundwater sampling. Over decades of contamination, bioactive zones with degradation of trichloroethene (TCE) and 1,1,1-trichloroethane (1,1,1-TCA) to 1,2-cis-dichloroethene (cis-DCE) and 1,1-dichloroethane, respectively, had developed in most of the clay till matrix. Dehalobacter dominated over Dehalococcoides (Dhc) in the clay till matrix corresponding with stagnation of sequential dechlorination at cis-DCE. Sporadically distributed bioactive zones with partial degradation to ethene were identified in the clay till matrix (thickness from 0.10 to 0.22 m). In one sub-section profile the presence of Dhc with the vcrA gene supported the occurrence of degradation of cis-DCE and VC, and in another enriched ?(13)C for TCE, cis-DCE and VC documented degradation. Highly enriched ?(13)C for 1,1,1-TCA (25) and cis-DCE (-4) suggested the occurrence of abiotic degradation in a third sub-section profile. Due to fine scale heterogeneity the identification of active degradation zones in the clay till matrix depended on high resolution subsampling of the clay till cores. The study demonstrates that an integrated approach combining chemical analysis, molecular microbial tools and compound specific isotope analysis (CSIA) was required in order to document biotic and abiotic degradations in the clay till system. PMID:23357226

  11. 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...

  12. Identify Beta-Hairpin Motifs with Quadratic Discriminant Algorithm Based on the Chemical Shifts

    PubMed Central

    YongE, Feng; GaoShan, Kou

    2015-01-01

    Successful prediction of the beta-hairpin motif will be helpful for understanding the of the fold recognition. Some algorithms have been proposed for the prediction of beta-hairpin motifs. However, the parameters used by these methods were primarily based on the amino acid sequences. Here, we proposed a novel model for predicting beta-hairpin structure based on the chemical shift. Firstly, we analyzed the statistical distribution of chemical shifts of six nuclei in not beta-hairpin and beta-hairpin motifs. Secondly, we used these chemical shifts as features combined with three algorithms to predict beta-hairpin structure. Finally, we achieved the best prediction, namely sensitivity of 92%, the specificity of 94% with 0.85 of Mathews correlation coefficient using quadratic discriminant analysis algorithm, which is clearly superior to the same method for the prediction of beta-hairpin structure from 20 amino acid compositions in the three-fold cross-validation. Our finding showed that the chemical shift is an effective parameter for beta-hairpin prediction, suggesting the quadratic discriminant analysis is a powerful algorithm for the prediction of beta-hairpin. PMID:26422468

  13. Identifying unknown minerals and compounds from X-ray diffraction patterns using the Johnson and Vand FORTRAN 4 computer program

    NASA Technical Reports Server (NTRS)

    Kyte, F. T.

    1976-01-01

    Automated computer identification of minerals and compounds from unknown samples is provided along with detailed instructions and worked examples for use in graduate level courses in mineralogy and X-ray analysis applications.

  14. Inhibitory effects of opioids on compound action potentials in frog sciatic nerves and their chemical structures.

    PubMed

    Mizuta, Kotaro; Fujita, Tsugumi; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2008-08-01

    An opioid tramadol more effectively inhibits compound action potentials (CAPs) than its metabolite mono-O-demethyl-tramadol (M1). To address further this issue, we examined the effects of opioids (morphine, codeine, ethylmorphine and dihydrocodeine) and cocaine on CAPs by applying the air-gap method to the frog sciatic nerve. All of the opioids at concentrations less than 10 mM reduced the peak amplitude of the CAP in a reversible and dose-dependent manner. The sequence of the CAP peak amplitude reductions was ethylmorphine>codeine>dihydrocodeine> or = morphine; the effective concentration for half-maximal inhibition (IC(50)) of ethylmorphine was 4.6 mM. All of the CAP inhibitions by opioids were resistant to a non-specific opioid-receptor antagonist naloxone. The CAP peak amplitude reductions produced by morphine, codeine and ethylmorphine were related to their chemical structures in such that this extent enhanced with an increase in the number of -CH(2) in a benzene ring, as seen in the inhibitory actions of tramadol and M1. Cocaine reduced CAP peak amplitudes with an IC(50) value of 0.80 mM. It is concluded that opioids reduce CAP peak amplitudes in a manner being independent of opioid-receptor activation and with an efficacy being much less than that of cocaine. It is suggested that the substituted groups of -OH bound to the benzene ring of morphine, codeine and ethylmorphine as well as of tramadol and M1, the structures of which are quite different from those of the opioids, may play an important role in producing nerve conduction block. PMID:18593589

  15. Chemical characterization of volatile organic compounds near the World Trade Center: Ambient concentrations and source apportionment

    NASA Astrophysics Data System (ADS)

    Olson, David A.; Norris, Gary A.; Seila, Robert L.; Landis, Matthew S.; Vette, Alan F.

    Concentrations of 53 volatile organic compounds (VOCs) are reported from four locations near the World Trade Center (WTC) (New York, USA) complex for canister samples collected from September 2001 through January 2002. Across the four sampling sites, mean concentrations ranged from 94.5 to 219?gm-3 for total VOCs. The highest mean concentrations for individual VOCs at any site were for ethane (18.7?gm-3), isopentane (17.1?gm-3), and m,p-xylenes (17.0?gm-3). VOC concentrations were generally highest for samples collected north and west of the WTC complex. Concentrations of total VOCs (and most individual VOCs) decreased from the period when fires were present at the WTC complex (before 19 December 2001) to the period after fires. The EPA Unmix Version 5.0 receptor model was used to assess the impact of WTC fires and recovery efforts on ambient VOC concentrations. Four factors were identified: burning of building debris, a mixed recovery/heating source, motor vehicle exhaust, and a mixed gasoline source.

  16. Chemical characterization of oak heartwood from Spanish forests of Quercus pyrenaica (Wild.). Ellagitannins, low molecular weight phenolic, and volatile compounds.

    PubMed

    Fernandez de Simn, Brgida; Sanz, Miriam; Cadaha, Estrella; Poveda, Pilar; Broto, Miguel

    2006-10-18

    The need for new sources of quality wood supply for cooperage has led to looking into the possibility of utilizing Quercus pyrenaica Wild. oak, a species native to the Iberian peninsula, as an alternative to other European (Quercus robur and Qurecus petraea) and American (Quercus alba) oaks. The low molecular weight phenolic composition, ellagitannins, and volatile compounds (including a wide range of compound families such as volatile phenols, furanic compounds, lactones, phenyl ketones, other lignin-derived compounds, and volatile compounds related to off-flavors) of green heartwood from Spanish forest regions were studied by HPLC and GC, in order to know its enological characteristics. The chemical composition of Q. pyrenaica is similar to that of other species commonly used in cooperage to make barrels, showing only quantitative differences that were more significant with respect to American than to French species. The four provenance regions studied showed similar chemical composition, with high variability among individuals, often higher than the variability among regions of provenance, but in line with that described in other European and American oak woods. Therefore, this species must be considered to be suitable for aging wine. PMID:17032045

  17. Evaluation of the protective effect of chemical additives in the oxidation of phenolic compounds catalysed by peroxidase.

    PubMed

    Torres, Juliana Arriel; Chagas, Pricila Maria Batista; Silva, Maria Cristina; Dos Santos, Custódio Donizete; Corrêa, Angelita Duarte

    2016-05-01

    The use of oxidoredutive enzymes in removing organic pollutants has been the subject of much research. The oxidation of phenolic compounds in the presence of chemical additives has been the focus of this study. In this investigation, the influence of the additives polyethylene glycol and Triton X-100 was evaluated in the phenol oxidation, caffeic acid, chlorogenic acid and total phenolic compounds present in coffee processing wastewater (CPW) at different pH values, performed by turnip peroxidase and peroxidase extracted from soybean seed hulls. The influence of these additives was observed only in the oxidation of phenol and caffeic acid. In the oxidation of other studied phenolic compounds, the percentage of oxidation remained unchanged in the presence of these chemical additives. In the oxidation of CPW in the presence of additives, no change in the oxidation of phenolic compounds was observed. Although several studies show the importance of evaluating the influence of additives on the behaviour of enzymes, this study found a positive response from the economic point of view for the treatment of real wastewater, since the addition of these substances showed no influence on the oxidation of phenolic compounds, which makes the process less costly. PMID:26502790

  18. The chemical processing of gas-phase carbonyl compounds by sulfuric acid aerosols: 2,4-pentanedione

    NASA Astrophysics Data System (ADS)

    Nozire, Barbara; Riemer, Daniel D.

    This work investigates the interactions between gas-phase carbonyl compounds and sulfuric acid aerosols. It focuses on understanding the chemical processes, giving a first estimate of their importance in the atmosphere, and suggesting directions for further investigations. The solubility and reactivity of a compound with a large enolization constant, 2,4-pentanedione, in water/sulfuric acid solutions 0-96 wt% have been investigated at room temperature using the bubble column/GC-FID technique. 2,4-pentanedione was found to undergo aldol condensation at acidities as low as 20 wt% H 2SO 4, that is, well in the tropospheric range of aerosol composition. In agreement with well-established organic chemical knowledge, this reaction resulted in changes of color of the solutions of potential importance for the optical properties of the aerosols. 2,4-pentanedione was also found to undergo retroaldol reaction, specific to dicarbonyl compounds, producing acetone and acetaldehyde. The Henry's law coefficient for 2,4-pentanedione was found to be a factor 5 larger than the one of acetone over the whole range of acidity, with a value in water of H (297 K)=(15527) M atm -1. A chemical system is proposed to describe the transformations of carbonyl compounds in sulfuric acid aerosols. Aldol condensation is likely to be the most common reaction for these compounds, probably involving a large number of the ones present in the atmosphere and a wide range of aerosol compositions. The enolization constant contributes as a proportional factor to the rate constant for aldol condensation, and is shown in this work to contribute as an additive constant to the Henry's law coefficient. In addition to the many important aspects of these reactions illustrated in this work, the rate of aldol condensation was estimated to be potentially fast enough for the losses of some compounds in acidic aerosols to compete with their gas-phase chemistry in the atmosphere.

  19. Comparison of predicted and derived measures of volatile organic compounds inside four relocatable classrooms due to identified interior finish sources

    SciTech Connect

    Hodgson, Alfred T.; Shendell, Derek G.; Fisk, William J.; Apte, Michael G.

    2003-06-01

    Indoor exposures to toxic and odorous volatile organic compounds (VOCs) are of general concern. Recently, VOCs in portable or relocatable classrooms (RCs) have received particular attention. However, very little was known about indoor environmental quality (IEQ) and the sources, composition, and indoor concentrations of VOCs in RCs. This project task focused on developing and demonstrating a process for selecting interior finish materials for RCs that have relatively low impacts with respect to their emissions of toxic and odorous VOCs. This task was part of a larger project to demonstrate the potential for simultaneous improvements in IEQ and energy efficiency in four new RCs equipped both with a continuously ventilating advanced heating, ventilating, and air conditioning system (HVAC) and a standard HVAC system. These HVACs were operated on alternate weeks. One RC per pair was constructed with standard interior finish materials, and the other included alternate interior materials identified in our prior laboratory study to have low VOC emissions. The RCs were sited in side-by-side pairs at two elementary schools in distinct northern California climate zones. Classroom VOC emission rates (mg hr{sup -1}) and concentrations were predicted based on VOC emission factors ({micro}g m{sup -2} hr{sup -1}) measured for individual materials in the laboratory, the quantities of installed materials and design ventilation rates. Predicted emission rates were compared to values derived from classroom measurements of VOC concentrations and ventilation rates made at pre-occupancy, eight weeks, and 27 weeks. Predicted concentrations were compared to measured integrated VOC indoor minus outdoor concentrations during school hours in the fall cooling season with the advanced HVAC operated. These measured concentrations also were compared between standard and material-modified RCs. Our combined laboratory and field process proved effective by correctly predicting that IEQ impacts of material VOC emissions would be minor when RCs were ventilated at or above code-minimum requirements. Assuming code-minimum ventilation rates are maintained, the benefits attributable to the use of alternate interior finish materials in RC's constructed by the manufacturer associated with this study are small, implying that it is not imperative to use such alternative finishing materials. However, it is essential to avoid materials that can degrade IEQ, and the results of this study demonstrate that laboratory-based material testing combined with modeling and field validation can help to achieve that aim.

  20. Application of yeast-two hybrid assay to chemical genomic screens: a high-throughput system to identify novel molecules modulating plant hormone receptor complexes.

    PubMed

    Chini, Andrea

    2014-01-01

    Phytohormones are endogenous signalling molecules that regulate plant development, adaptation to the environment, and survival. Upon internal or external stimuli, hormones are quickly accumulated and perceived, which in turn activates specific signalling cascades regulating the appropriate physiological responses. In the last decade, great advances in understanding plant hormone perception mechanisms have been achieved. Among different methodological approaches, yeast-two hybrid (Y2H) assays played a pivotal role in the identification and analysis of plant hormone perception complexes. The Y2H assay is a rapid and straightforward technique that can be easily employed to identify small molecules directly modulating plant hormone perception complexes in a high-throughput manner. However, an Y2H chemical screen tends to isolate false positive molecules, and therefore a secondary in planta screen is required to confirm the genuine bioactivity of putative positive hits. This two-step screening approach can substantially save time and manual labor. This chapter focuses on the prospects of Y2H-based chemical genomic high-throughput screens applied to plant hormone perception complexes. Specifically, the method employed to carry out a chemical genomic screen to identify agonist and antagonist molecules of the phytohormone jasmonic acid in its conjugated form jasmonic acid-isoleucine (JA-Ile) is described. An easy in planta confirmation assay is also illustrated. However, this methodology can be easily extended to detect novel chemical compounds perturbing additional plant hormone receptor complexes. Finally, the high-throughput approach described here can also be implemented for the identification of molecules interfering with protein-protein interaction of plant complexes other than hormone receptors. PMID:24306860

  1. Data mining the NCI cancer cell line compound GI(50) values: identifying quinone subtypes effective against melanoma and leukemia cell classes.

    PubMed

    Marx, Kenneth A; O'Neil, Philip; Hoffman, Patrick; Ujwal, M L

    2003-01-01

    Using data mining techniques, we have studied a subset (1400) of compounds from the large public National Cancer Institute (NCI) compounds data repository. We first carried out a functional class identity assignment for the 60 NCI cancer testing cell lines via hierarchical clustering of gene expression data. Comprised of nine clinical tissue types, the 60 cell lines were placed into six classes-melanoma, leukemia, renal, lung, and colorectal, and the sixth class was comprised of mixed tissue cell lines not found in any of the other five classes. We then carried out supervised machine learning, using the GI(50) values tested on a panel of 60 NCI cancer cell lines. For separate 3-class and 2-class problem clustering, we successfully carried out clear cell line class separation at high stringency, p < 0.01 (Bonferroni corrected t-statistic), using feature reduction clustering algorithms embedded in RadViz, an integrated high dimensional analytic and visualization tool. We started with the 1400 compound GI(50) values as input and selected only those compounds, or features, significant in carrying out the classification. With this approach, we identified two small sets of compounds that were most effective in carrying out complete class separation of the melanoma, non-melanoma classes and leukemia, non-leukemia classes. To validate these results, we showed that these two compound sets' GI(50) values were highly accurate classifiers using five standard analytical algorithms. One compound set was most effective against the melanoma class cell lines (14 compounds), and the other set was most effective against the leukemia class cell lines (30 compounds). The two compound classes were both significantly enriched in two different types of substituted p-quinones. The melanoma cell line class of 14 compounds was comprised of 11 compounds that were internal substituted p-quinones, and the leukemia cell line class of 30 compounds was comprised of 6 compounds that were external substituted p-quinones. Attempts to subclassify melanoma or leukemia cell lines based upon their clinical cancer subtype met with limited success. For example, using GI(50) values for the 30 compounds we identified as effective against all leukemia cell lines, we could subclassify acute lymphoblastic leukemia (ALL) origin cell lines from non-ALL leukemia origin cell lines without significant overlap from non-leukemia cell lines. Based upon clustering using GI(50) values for the 60 cancer cell lines laid out by the RadViz algorithm, these two compound subsets did not overlap with clusters containing any of the NCI's 92 compounds of known mechanism of action, a few of which are quinones. Given their structural patterns, the two p-quinone subtypes we identified would clearly be expected to possess different redox potentials/substrate specificities for enzymatic reduction in vivo. These two p-quinone subtypes represent valuable information that may be used in the elucidation of pharmacophores for the design of compounds to treat these two cancer tissue types in the clinic. PMID:14502500

  2. Detection of semi-volatile organic compounds (SVOCs) in surface water, soil, and groundwater in a chemical industrial park in Eastern China.

    PubMed

    Liu, Benhua; Li, Yuehua; Ma, Jianfeng; Huang, Linxian; Chen, Liang

    2016-01-01

    China is suffering from serious water and soil pollution, especially in the North China Plain. This work investigated semi-volatile organic compounds (SVOCs) in surface water, groundwater and soil within a chemical industrial park in Eastern China, for which the volatile organic compound (VOC) results have been previously reported. A total of 20 samples were collected from the field, and analyzed in the laboratory. A 100% detection frequency of SVOCs in samples from this chemical industrial park was observed (same as VOCs). Moreover, the detection frequency of 113 SVOCs in each sample reached 15.93, 12.39 and 20.35% for surface water, groundwater and soil, respectively. The most detected SVOCs in the park included N-containing SVOCs, polycyclic aromatic hydrocarbons, phthalates, organic pesticides and polychlorodiphenyls. The elevated detecting frequencies and concentration levels of SVOCs identified in the groundwater were attributed to the intensive chemical production activities in the park. In addition, the agricultural activities in the area might also have contributed to the SVOCs to the groundwater. The results of VOCs and SVOCs from this and previous studies suggest that the groundwater in this industrial park has been severely contaminated, and the contamination likely spreads beyond the park. Imminent hydrogeological assessments and remedial actions are warranted to eliminate the source and mitigate the potential plume expansion beyond the park boundary. PMID:26942541

  3. The UV-filter benzophenone-1 inhibits 17beta-hydroxysteroid dehydrogenase type 3: Virtual screening as a strategy to identify potential endocrine disrupting chemicals.

    PubMed

    Nashev, Lyubomir G; Schuster, Daniela; Laggner, Christian; Sodha, Seloni; Langer, Thierry; Wolber, Gerhard; Odermatt, Alex

    2010-04-15

    The prevalence of male reproductive disorders and testicular cancer is steadily increasing. Because the exposure to chemicals disrupting natural hormone action has been associated with these diseases, it is important to identify endocrine disrupting chemicals (EDCs) and their targets of action. Here, a 3D-structural database that can be applied for virtual screening approaches to facilitate the identification of EDCs was constructed. The database was screened using pharmacophores of 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3), which catalyzes the last step of testosterone synthesis in testicular Leydig cells and plays an essential role during male sexual development. Among other chemicals, benzophenone (BP) UV-filters were predicted as potential 17beta-HSD3 inhibitors. Biological analyses revealed (2,4-dihydroxyphenyl)-phenylmethanone (also known as benzophenone-1, BP-1) as an inhibitor of human 17beta-HSD3 (IC(50) 1.05microM). BP-1 also efficiently blocked conversion of androstenedione to testosterone by mouse and rat 17beta-HSD3 in whole-organ enzyme assays. Moreover, BP-1 antagonized the testosterone-dependent activation of androgen receptors (IC(50) 5.7microM), suggesting synergistic anti-androgenic effects of BP-1 by preventing testosterone formation and blocking receptor activation. In addition, analyses of several commonly used UV-filters on estrogen- and androgen-metabolizing 17beta-HSD enzymes revealed 3-benzylidene camphor (3-BC) and 4-methylbenzylidene camphor (4-MBC) as low micromolar 17beta-HSD2 inhibitors. In conclusion, screening of virtual chemical structure libraries can facilitate the identification of compounds interfering with hormone action. The potential disruption of 17beta-HSD enzyme function by the UV-filters BP-1, 3-BC and 4-MBC requires further investigation and should be considered for safety assessment of these chemicals. PMID:20005209

  4. Extraction, chemical characterization and biological activity determination of broccoli health promoting compounds.

    PubMed

    Ares, Ana M; Nozal, Mara J; Bernal, Jos

    2013-10-25

    Broccoli (Brassica oleracea L. var. Italica) contains substantial amount of health-promoting compounds such as vitamins, glucosinolates, phenolic compounds, and dietary essential minerals; thus, it benefits health beyond providing just basic nutrition, and consumption of broccoli has been increasing over the years. This review gives an overview on the extraction and separation techniques, as well as the biological activity of some of the above mentioned compounds which have been published in the period January 2008 to January 2013. The work has been distributed according to the different families of health promoting compounds discussing the extraction procedures and the analytical techniques employed for their characterization. Finally, information about the different biological activities of these compounds has been also provided. PMID:23899380

  5. A Quantum Chemical and Statistical Study of Cytotoxic Activity of Compounds Isolated from Curcuma zedoaria

    PubMed Central

    Hamdi, Omer Abdalla Ahmed; Anouar, El Hassane; Shilpi, Jamil A.; Trabolsy, Zuhra Bashir Khalifa Al; Zain, Sharifuddin Bin Md; Zakaria, Nur Shahidatul Shida; Zulkefeli, Mohd; Weber, Jean-Frdric F.; Malek, Sri Nurestri A.; Rahman, Syarifah Nur Syed Abdul; Awang, Khalijah

    2015-01-01

    A series of 21 compounds isolated from Curcuma zedoaria was subjected to cytotoxicity test against MCF7; Ca Ski; PC3 and HT-29 cancer cell lines; and a normal HUVEC cell line. To rationalize the structureactivity relationships of the isolated compounds; a set of electronic; steric and hydrophobic descriptors were calculated using density functional theory (DFT) method. Statistical analyses were carried out using simple and multiple linear regressions (SLR; MLR); principal component analysis (PCA); and hierarchical cluster analysis (HCA). SLR analyses showed that the cytotoxicity of the isolated compounds against a given cell line depend on certain descriptors; and the corresponding correlation coefficients (R2) vary from 0%55%. MLR results revealed that the best models can be achieved with a limited number of specific descriptors applicable for compounds having a similar basic skeleton. Based on PCA; HCA and MLR analyses; active compounds were classified into subgroups; which was in agreement with the cell based cytotoxicity assay. PMID:25923077

  6. The radiolysis of aqueous acetonitrile - Compounds of interest to chemical evolution studies

    SciTech Connect

    Draganic, I.G.; Jovanovic, S.

    1980-07-01

    Oxygen free aqueous solutions of CH3CN (0.1 M, pH 6) were exposed to gamma rays from a Co-60 source, the mixtures of nonvolatile radiolytic products was fractionated and the fractions were analysed. Succinic, maleic, fumaric, malonic and pyruvic acids were identified. Glycol aldehyde, glucose and probably ribose were observed in the hydrolysate of fractionated material. It has been suggested that an oligomer is formed which has a fragment with the polyhydroxy structure and on hydrolysis releases the carbohydrates. Radiolytic products which release amino acids on hydrolysis were found in several fractions. The amino acid contents of the hydrolysates were up to about 2.8% of the fraction mass. The presence of several protein and nonprotein amino acids suggests that their origin should be in a peptidic structure, which is probably a fragment of an oligomer radiolytically produced. A direct analysis of the irradiated solution shows the presence of acetaldehyde, propionaldehyde, glyoxal and of biacetyl. Experimental findings are discussed and a free-radical mechanism is proposed to account for the chemical changes observed.

  7. Hot wire chemical vapor deposition chemistry in the gas phase and on the catalyst surface with organosilicon compounds.

    PubMed

    Shi, Yujun

    2015-02-17

    CONSPECTUS: Hot wire chemical vapor deposition (HWCVD), also referred to as catalytic CVD (Cat-CVD), has been used to produce Si-containing thin films, nanomaterials, and functional polymer coatings that have found wide applications in microelectronic and photovoltaic devices, in automobiles, and in biotechnology. The success of HWCVD is largely due to its various advantages, including high deposition rate, low substrate temperatures, lack of plasma-induced damage, and large-area uniformity. Film growth in HWCVD is induced by reactive species generated from primary decomposition on the metal wire or from secondary reactions in the gas phase. In order to achieve a rational and efficient optimization of the process, it is essential to identify the reactive species and to understand the chemical kinetics that govern the production of these precursor species for film growth. In this Account, we report recent progress in unraveling the complex gas-phase reaction chemistry in the HWCVD growth of silicon carbide thin films using organosilicon compounds as single-source precursors. We have demonstrated that laser ionization mass spectrometry is a powerful diagnostic tool for studying the gas-phase reaction chemistry when combined with the methods of isotope labeling and chemical trapping. The four methyl-substituted silane molecules, belonging to open-chain alkylsilanes, dissociatively adsorb on W and Ta filaments to produce methyl radical and H2 molecule. Under the typical deposition pressures, with increasing number of methyl substitution, the dominant chemistry occurring in the gas phase switches from silylene/silene reactions to free-radical short chain reactions. This change in dominant reaction intermediates from silylene/silene to methyl radicals explains the observation from thin film deposition that silicon carbide films become more C-rich with a decreasing number of Si-H bonds in the four precursor molecules. In the case of cyclic monosilacyclobutanes, we have shown that ring-opening reactions play a vital role in characterizing the reaction chemistry. On the other hand, exocyclic Si-H(CH3) bond cleavages are more important in the less-puckered disilacyclobutane molecules. Metal filaments are essential in HWCVD since they serve as catalysts to decompose precursor gases to reactive species, which initiate gas-phase reaction chemistry and thin film growth. We discuss the structural changes in metal filaments when exposed to various precursor gases. Depending on the nature of the radical intermediates formed from the hot-wire decomposition and subsequent gas-phase reactions, metal silicides and carbides can be formed. Overall, study of the gas-phase reaction chemistry in HWCVD provides important knowledge of the chemical species produced prior to their deposition on a substrate surface. This helps in identifying the major contributor to alloy formation on the filament itself and the film growth, and consequently, in determining the properties of the deposited films. An integrated knowledge of the gas-phase reaction chemistry, filament alloy formation, and thin film deposition is required for an efficient deposition of high-quality thin films and nanomaterials. PMID:25586211

  8. Eryngial (trans-2-dodecenal), a bioactive compound from Eryngium foetidum: its identification, chemical isolation, characterization and comparison with ivermectin in vitro.

    PubMed

    Forbes, W M; Gallimore, W A; Mansingh, A; Reese, P B; Robinson, R D

    2014-02-01

    Methanol-water (4:1, v/v) crude extracts (50 mg mL(-1)) of 25 Jamaican medicinal plants were screened in vitro for anthelmintic activity using infective third-stage larvae of Strongyloides stercoralis. The most effective extract was further chemically scrutinized to isolate and identify the source of the bioactivity, and the efficacy of this compound was compared with ivermectin. Eosin exclusion (0.1 mg mL(-1)) served as the indicator of mortality in all bioassays. A crude extract of Eryngium foetidum (Apiaceae) was significantly (Probit Analysis, P<0.05) more potent than the other plant extracts, taking 18.9 h to kill 50% (LT50) of the larvae. Further, the petrol extract of E. foetidum was significantly more effective (Probit Analysis, P<0.05) at killing the larvae (LT50, 4.7 h) than either its methanol-water or dichloromethane extract. The latter two effected less than 1% larval mortality after 120 h. With bioassay-driven column chromatography of the petrol extract, trans-2-dodecenal (eryngial) was identified and chemically isolated as the main anthelmintic compound in E. foetidum. There was a significant difference between the 24 h LD50 values (mm) of trans-2-dodecenal (0.461) and ivermectin (2.251) but there was none between the 48 h LD50 values (mm): trans-2-dodecenal (0.411) and ivermectin (0.499) in vitro. PMID:24139239

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

    SciTech Connect

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

    1981-12-01

    Part 2 contains the data base in tabular format. There are two sections, the first with records on nondrug substances, and the second with records on drugs. Chemicals in each section are arranged alphabetically by CAS preferred name, CAS registry number, formula, atomic weight, melting point, boiling point, and vapor pressure. Tissues are listed alphabetically with exposure route, analytical method, number of cases, range, and mean - when available in the source document. A variety of information may also be included that is pertinent to the range and mean as well as experimental design, demography, health effects, pathology, morphology, and toxicity. Review articles are included in the data base; however, no data have been extracted from such documents because the original research articles are included.

  10. Antioxidant and Anti-Inflammatory Activity Determination of One Hundred Kinds of Pure Chemical Compounds Using Offline and Online Screening HPLC Assay

    PubMed Central

    Lee, Kwang Jin; Oh, You Chang; Cho, Won Kyung; Ma, Jin Yeul

    2015-01-01

    This study investigated the antioxidant activity of one hundred kinds of pure chemical compounds found within a number of natural substances and oriental medicinal herbs (OMH). Three different methods were used to evaluate the antioxidant activity of DPPH radical-scavenging activity, ABTS radical-scavenging activity, and online screening HPLC-ABTS assays. The results indicated that 17 compounds exhibited better inhibitory activity against ABTS radical than DPPH radical. The IC50 rate of a more practical substance is determined, and the ABTS assay IC50 values of gallic acid hydrate, (+)-catechin hydrate, caffeic acid, rutin hydrate, hyperoside, quercetin, and kaempferol compounds were 1.03 ± 0.25, 3.12 ± 0.51, 1.59 ± 0.06, 4.68 ± 1.24, 3.54 ± 0.39, 1.89 ± 0.33, and 3.70 ± 0.15 μg/mL, respectively. The ABTS assay is more sensitive to identifying the antioxidant activity since it has faster reaction kinetics and a heightened response to antioxidants. In addition, there was a very small margin of error between the results of the offline-ABTS assay and those of the online screening HPLC-ABTS assay. We also evaluated the effects of 17 compounds on the NO secretion in LPS-stimulated RAW 264.7 cells and also investigated the cytotoxicity of 17 compounds using a cell counting kit (CCK) in order to determine the optimal concentration that would provide an effective anti-inflammatory action with minimum toxicity. These results will be compiled into a database, and this method can be a powerful preselection tool for compounds intended to be studied for their potential bioactivity and antioxidant activity related to their radical-scavenging capacity. PMID:26504472

  11. Using fewer animals to identify chemical eye hazards: revised criteria necessary to maintain equivalent hazard classification.

    PubMed

    Haseman, Joseph K; Allen, David G; Lipscomb, Elizabeth A; Truax, James F; Stokes, William S

    2011-10-01

    U.S. Federal Hazardous Substances Act (FHSA) regulations specify eye safety testing procedures and hazard classification criteria for substances regulated by the U.S. Consumer Product Safety Commission (CPSC). Current regulations require up to three sequential 6-animal tests. Testing consistent with the Organisation for Economic Co-operation and Development (OECD) test guideline for eye irritation/corrosion, which specifies 3 animals, can also be submitted to US agencies. However, current FHSA regulations do not provide criteria to classify results from 3-animal tests. An analysis was conducted to determine criteria using results from 3-animal tests that would provide equivalent labeling to FHSA regulations. The frequency that FHSA requirements identify substances as ocular irritants was compared with the frequency that a criterion of either ? 1/3 or ? 2/3 positive animals would identify these substances. A database of rabbit eye tests was also used to estimate over- and underprediction rates for each criterion. In each instance, a criterion of ? 1/3 positive animals more closely matched the expected outcome based on FHSA requirements, while a criterion of ? 2/3 positive animals identified far fewer irritants. Using a classification criterion of ? 1/3 positive animals provided equivalent or greater eye hazard labeling as current FHSA requirements, while using 50-83% fewer animals. PMID:21745525

  12. Callicarpenal and Intermedeol: Two Natural Arthropod Feeding Deterrent and Repellent Compounds Identified from the Southern Folk Remedy Plant, Callicarpa americana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In previous studies on the American beautyberry (Callicarpa americana), it was demonstrated that callicarpenal and intermedeol were responsible for the arthropod repellent and feeding deterrent activity of this folk remedy. Both compounds showed significant bite-deterring activity against Aedes aeg...

  13. Data on pigments and long-chain fatty compounds identified in Dietzia sp. A14101 grown on simple and complex hydrocarbons

    PubMed Central

    Hvidsten, Ina; Mjs, Svein Are; Bdtker, Gunhild; Barth, Tanja

    2015-01-01

    This data article provides: 1. An overview of tentatively identified long chain compounds in Dietzia sp. A14101 grown on simple and complex hydrocarbons; 2. Preliminary Identification of pigments in bacterial material obtained from incubation with a hydrocarbon (dodecane, n-C12) as the only carbon and energy source; 3. Some pictures to illustrate the cell surface charge test. PMID:26442286

  14. A novel energy-efficient plasma chemical process for the destruction of volatile toxic compounds. 1998 annual progress report

    SciTech Connect

    Pinnaduwage, L.A.

    1998-06-01

    'Removal of low-concentrations (below several percent) of volatile toxic compounds (VTCs) from contaminated air streams is encountered at DOE waste sites in two instances: (1) off-gases resulting from air-stripping of contaminated soils; and (2) effluent from the incineration of highly-concentrated combustible hazardous wastes The objective of the research program is to develop a novel plasma chemical process for the destruction of VTC''s in low-concentration waste streams.'

  15. Heteroepitaxial growth of 3-5 semiconductor compounds by metal-organic chemical vapor deposition for device applications

    NASA Technical Reports Server (NTRS)

    Collis, Ward J.; Abul-Fadl, Ali

    1988-01-01

    The purpose of this research is to design, install and operate a metal-organic chemical vapor deposition system which is to be used for the epitaxial growth of 3-5 semiconductor binary compounds, and ternary and quaternary alloys. The long-term goal is to utilize this vapor phase deposition in conjunction with existing current controlled liquid phase epitaxy facilities to perform hybrid growth sequences for fabricating integrated optoelectronic devices.

  16. Model for the Vaporization of Mixed Organometallic Compounds in the Metalorganic Chemical Vapor Deposition of High Temperature Superconducting Films

    NASA Technical Reports Server (NTRS)

    Meng, Guangyao; Zhou, Gang; Schneider, Roger L.; Sarma, Bimal K.; Levy, Moises

    1993-01-01

    A model of the vaporization and mass transport of mixed organometallics from a single source for thin film metalorganic chemical vapor deposition is presented. A stoichiometric gas phase can be obtained from a mixture of the organometallics in the desired mole ratios, in spite of differences in the volatilities of the individual compounds. Proper film composition and growth rates are obtained by controlling the velocity of a carriage containing the organometallics through the heating zone of a vaporizer.

  17. Identifying multiple eruption phases from a compound tephra blanket: an example of the AD1256 Al-Madinah eruption, Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Kawabata, E.; Cronin, S. J.; Bebbington, M. S.; Moufti, M. R. H.; El-Masry, N.; Wang, T.

    2015-01-01

    Complex eruption episodes commonly produce several phases of tephra fall and/or concurrent falls from multiple vents. Phases of eruption are challenging to reconstruct from the geological record, especially where there is a lack of distinct physical or chemical variations during an eruption episode. A statistical method is proposed for identifying the most likely combination of multiple fall lobes for composite tephra deposits, using a new high-resolution tephra fall map from the basaltic AD1256 Harrat Al-Madinah fissure eruption in Saudi Arabia. This dominantly effusive eruption episode lasted 52 days periodically producing tephra from several vents along the fissure. Most tephra was produced from high Hawaiian fountains and dispersed under differing wind conditions. The widest-dispersed tephra occurred under phases of the highest fountains, at least 500 m high and probably closer to 1000 m. These high fountains produced pyroclasts with a broad range of vesicularity. Similar total versus lobe-specific grain size determinations showed little systematic variation of maximum fountain-height phases. Individual tephra lobe properties (vesicle form, density, particle shape and particle-size distribution) in different sectors around the volcano varied only subtly. From the statistical distribution of spot fall-thickness measurements, a semi-empirical tephra fallout model, modified to account for weathering, wind remobilisation and settling, was fitted using maximum likelihood estimation. A range of likely eruption-event scenarios were evaluated, concluding that the AD1256 eruption most likely comprised three separate fall-producing eruptions from its northern vent under differing wind conditions. The first of these occurred concurrently with high-fountaining events from two other major vents southward along the fissure, producing overlapping fall lobes. Applying this method to other similar compound tephra deposits will help elucidate more realistic eruption scenarios and event reconstructions from the geological record.

  18. A model explaining and predicting lamb flavour from the aroma-active chemical compounds released upon grilling light lamb loins.

    PubMed

    Bueno, Mónica; Campo, M Mar; Cacho, Juan; Ferreira, Vicente; Escudero, Ana

    2014-12-01

    The objective of the work is to understand the role of the different aroma compounds in the perception of the local "lamb flavour" concept. For this, a set of 70 loins (Longissimus dorsi) from approximately seventy day-old Rasa Aragonesa male lambs were grilled and the aroma-active chemicals released during the grilling process were trapped and analyzed. Carbonyl compounds were derivatizated and determined by GC-NCI-MS, whereas other aromatic compounds were directly analyzed by GC-GC-MS. Odour activity values (OAVs) were calculated using their odour threshold values in air. Lamb flavour could be satisfactory explained by a partial least-squares model (74% explained variance in cross-validation) built by the OAVs of 32 aroma-active chemical compounds. The model demonstrates that the lamb flavour concept is the result of a complex balance. Its intensity critically and positively depends to the levels of volatile fatty acids and several dimethylpyrazines while is negatively influenced by the different alkenals and alkadienals. (E,E)-2,4-decadienal and (E)-2-nonenal showed top OAVs. PMID:25089786

  19. Gas chromatography plasma-assisted reaction chemical ionization mass spectrometry for quantitative detection of bromine in organic compounds.

    PubMed

    Lin, Ninghang; Wang, Haopeng; Kahen, Kaveh; Badiei, Hamid; Jorabchi, Kaveh

    2014-08-01

    We have recently introduced plasma-assisted reaction chemical ionization mass spectrometry (PARCI-MS) for elemental analysis of halogens in organic compounds. Here, we utilize gas chromatography (GC) coupled to PARCI-MS to investigate the mechanism of Br(-) ion generation from organobromines and to evaluate analytical performance of PARCI for organobromine analysis. Bromine atoms in compounds eluting from GC are converted to HBr in a low-pressure microwave induced helium plasma with trace amounts of hydrogen added as a reaction gas. Ionization is achieved by introducing nitrogen into the afterglow region of the plasma, liberating electrons via penning ionization and leading to formation of negative ions. We demonstrate that N2 largely affects the ionization process, whereas H2 affects both the ionization process and in-plasma reactions. Our investigations also suggest that dissociative electron capture is the main ionization route for formation of Br(-) ions. Importantly, GC-PARCI-MS shows a uniform response factor for bromine across brominated compounds of drastically different chemical structures, confirming PARCI's ability to quantify organobromines in the absence of compound-specific standards. Over 3 orders of magnitude linear dynamic range is demonstrated for bromine quantification. We report a detection limit of 29 fg of bromine on-column, ~4-fold better than inductively coupled plasma-MS. PMID:25003497

  20. National body-burden database. Chemicals identified in feral and food animals, 1984. Volume IV, Part 2

    SciTech Connect

    Cone, M.V.; Ferguson, M.; Powers, C.D.; Hammons, A.S.

    1986-01-01

    The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposure to environmental contaminants and the assessment of the significance of such exposure. Data included are obtained through routine manual searches of selected scientific journals, augmented by computer searches. The database, which includes the separately published files, Chemicals Identified in Human Biological Media and Chemicals Identified in Feral and Food Animals, contains information on more than 1600 chemicals. The database is used in exposure, hazard and risk assessment; identifying potential human and environmental health problems including sources of contamination; planning research and comparing results; and in teaching at medical and public health schools. The database is under the aegis of the Interagency Collaborative Group on Environmental Carcinogenesis, National Cancer Institute (NCI), and is maintained by the Health and Environmental Information Section, Science Applications International Corporation under the direction of the Exposure Evaluation Division, US Environmental Protection Agency (EPA). Funding is provided through interagency agreements involving NCI, EPA, and the US Department of Energy.

  1. National body-burden database: chemicals identified in feral and food animals, 1984. Volume IV, Part 1

    SciTech Connect

    Cone, M.V.; Ferguson, M.; Powers, C.D.; Hammons, A.S.

    1986-01-01

    The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposure to environmental contaminants and the assessment of the significance of such exposure. Data included are obtained through routine manual searches of selected scientific journals, augmented by computer searches. The database, which includes the separately published files, Chemicals Identified in Human Biological Media and Chemicals Identified in Feral and Food Animals, contains information on more than 1600 chemicals. The database is used in exposure, hazard and risk assessment; identifying potential human and environmental health problems including sources of contamination; planning research and comparing results; and in teaching at medical and public health schools. The database is under the aegis of the Interagency Collaborative Group on Environmental Carcinogenesis, National Cancer Institute (NCI), and is maintained by the Health and Environmental Information Section, Science Applications International Corporation under the direction of the Exposure Evaluation Division, US Environmental Protection Agency (EPA). Funding is provided through interagency agreements involving NCI, EPA, and the US Department of Energy.

  2. Catalytic decomposition of diazomethane as a general method for the methylenation of chemical compounds

    NASA Astrophysics Data System (ADS)

    Tomilov, Yury V.; Dokitchev, V. A.; Dzhemilev, Usein M.; Nefedov, Oleg M.

    1993-09-01

    The principal advances and trends in the application of diazomethane as a methylenating agent in synthetic chemistry using transition and non-transition metal compounds as catalysts are surveyed and analysed. The catalytic reactions of diazomethane with olefins, acethylenes, aromatic compounds, ketones, alcohols and amines are examined. A systematic account is given of data concerning the influence of the structure of the initial substrates and of the nature of the catalyst components on the regio- and stereo-selectivity of the reactions considered. The possibilities of the catalytic conversion by diazomethane (generated in situ) of unsaturated compounds into cyclopropane derivatives are considered. The bibliography includes 284 references.

  3. Thymine vanadyl(II) compound as a diabetic drug model: Chemical spectroscopic and antimicrobial assessments

    NASA Astrophysics Data System (ADS)

    El-Sayed, Mohamed Y.; Refat, Moamen S.

    2014-09-01

    The aim of this study was to synthesize a novel bifunctionalized thymine vanadyl(II) compound. The solid vanadyl(II) compound has been characterized by elemental analyses (CHN), Raman laser, infrared spectra, molar conductivity, electronic spectra, thermogravimetric analyses (TGA), scanning electron microscopy (SEM) and X-ray powder diffraction (XRD) studies. Electronic and magnetic measurements have confirmed that the speculated geometry of vanadyl(II) compound is square pyramidal geometry. The microbial test was performed for the vanadyl complex against some kinds of bacteria and fungi. The results suggested that [VO(Thy)2] adduct has an anti-diabetic profile.

  4. Enhancing of chemical compound and drug name recognition using representative tag scheme and fine-grained tokenization

    PubMed Central

    2015-01-01

    Background The functions of chemical compounds and drugs that affect biological processes and their particular effect on the onset and treatment of diseases have attracted increasing interest with the advancement of research in the life sciences. To extract knowledge from the extensive literatures on such compounds and drugs, the organizers of BioCreative IV administered the CHEMical Compound and Drug Named Entity Recognition (CHEMDNER) task to establish a standard dataset for evaluating state-of-the-art chemical entity recognition methods. Methods This study introduces the approach of our CHEMDNER system. Instead of emphasizing the development of novel feature sets for machine learning, this study investigates the effect of various tag schemes on the recognition of the names of chemicals and drugs by using conditional random fields. Experiments were conducted using combinations of different tokenization strategies and tag schemes to investigate the effects of tag set selection and tokenization method on the CHEMDNER task. Results This study presents the performance of CHEMDNER of three more representative tag schemes-IOBE, IOBES, and IOB12E-when applied to a widely utilized IOB tag set and combined with the coarse-/fine-grained tokenization methods. The experimental results thus reveal that the fine-grained tokenization strategy performance best in terms of precision, recall and F-scores when the IOBES tag set was utilized. The IOBES model with fine-grained tokenization yielded the best-F-scores in the six chemical entity categories other than the "Multiple" entity category. Nonetheless, no significant improvement was observed when a more representative tag schemes was used with the coarse or fine-grained tokenization rules. The best F-scores that were achieved using the developed system on the test dataset of the CHEMDNER task were 0.833 and 0.815 for the chemical documents indexing and the chemical entity mention recognition tasks, respectively. Conclusions The results herein highlight the importance of tag set selection and the use of different tokenization strategies. Fine-grained tokenization combined with the tag set IOBES most effectively recognizes chemical and drug names. To the best of the authors' knowledge, this investigation is the first comprehensive investigation use of various tag set schemes combined with different tokenization strategies for the recognition of chemical entities. PMID:25810771

  5. Toward Relatively General and Accurate Quantum Chemical Predictions of Solid-State (17)O NMR Chemical Shifts in Various Biologically Relevant Oxygen-Containing Compounds.

    PubMed

    Rorick, Amber; Michael, Matthew A; Yang, Liu; Zhang, Yong

    2015-09-01

    Oxygen is an important element in most biologically significant molecules, and experimental solid-state (17)O NMR studies have provided numerous useful structural probes to study these systems. However, computational predictions of solid-state (17)O NMR chemical shift tensor properties are still challenging in many cases, and in particular, each of the prior computational works is basically limited to one type of oxygen-containing system. This work provides the first systematic study of the effects of geometry refinement, method, and basis sets for metal and nonmetal elements in both geometry optimization and NMR property calculations of some biologically relevant oxygen-containing compounds with a good variety of XO bonding groups (X = H, C, N, P, and metal). The experimental range studied is of 1455 ppm, a major part of the reported (17)O NMR chemical shifts in organic and organometallic compounds. A number of computational factors toward relatively general and accurate predictions of (17)O NMR chemical shifts were studied to provide helpful and detailed suggestions for future work. For the studied kinds of oxygen-containing compounds, the best computational approach results in a theory-versus-experiment correlation coefficient (R(2)) value of 0.9880 and a mean absolute deviation of 13 ppm (1.9% of the experimental range) for isotropic NMR shifts and an R(2) value of 0.9926 for all shift-tensor properties. These results shall facilitate future computational studies of (17)O NMR chemical shifts in many biologically relevant systems, and the high accuracy may also help the refinement and determination of active-site structures of some oxygen-containing substrate-bound proteins. PMID:26274812

  6. Chemical decomposition of iron in Spanish coal pyrolysis identified by Moessbauer spectroscopy at different temperatures

    SciTech Connect

    Ahmed, M.A.; Blesa, M.J.; Moliner, R.

    2007-07-01

    Three chars from lignite (Se), sub bituminous (AA6), bituminous (BCA) Spanish coals produced at 673 K, 773 K, and 873 K were analyzed by Moessbauer spectroscopy at room temperature, and 80 K, except BCA char produced at 873 K, its analysis was extended down to 10 K. Least square fit analysis for the spectra of Se chars showed that, jarosite/Fe{sup 3+} was hydrolyzed into rozenite/Fe2+ at 873 K. Pyrite was reduced to troilite (FeS) at 773 K. Both jarosite and very broad doublet were observed at T = 673 K. The hyperfine parameters of this phase gave close values to microcrystalline iron in either Fe (II) or Fe (III) states. On the other hand, the spectral analysis of AA6 chars ascertained that rozenite was hydrolyzed to goethite (FeOOH) in the range of 773 K-873 K, whereas pyrite was reduced to pyrrohotite (Fe{sub 1-x}S). However, no chemical changes were observed for jarosite in all AA6-chars. Likewise, siderite was changed into magnetite in the BCA chars produced at 673 K and 773 K. Spectrum performed at 10 K for char produced at 873 K proved the presence of ferrihydrite (H = 489.2 kOe), troilite (H = 355.3 kOe) and a broad paramagnetic doublet belonging to an organic iron. These phases and still remaining siderite inferred also that such transformations are incomplete.

  7. Scalarane and homoscalarane compounds from the nudibranchs Glossodoris sedna and Glossodoris dalli: chemical and biological properties.

    TOXLINE Toxicology Bibliographic Information

    Fontana A; Mollo E; Ortea J; Gavagnin M; Cimino G

    2000-04-01

    A series of homoscalarane and scalarane compounds (2-7) have been isolated from two distinct species of Pacific Glossodoris nudibranchs. The structure and elucidation of the relative stereochemistry of the new metabolites 2 and 3 were obtained by spectroscopic methods. Compound 2 was ichthyotoxic at 0.1 ppm against Gambusia affinis and showed moderate activity (IC(50) 18 microM) to inhibit mammalian phospholipase A(2).

  8. Scalarane and homoscalarane compounds from the nudibranchs Glossodoris sedna and Glossodoris dalli: chemical and biological properties.

    PubMed

    Fontana, A; Mollo, E; Ortea, J; Gavagnin, M; Cimino, G

    2000-04-01

    A series of homoscalarane and scalarane compounds (2-7) have been isolated from two distinct species of Pacific Glossodoris nudibranchs. The structure and elucidation of the relative stereochemistry of the new metabolites 2 and 3 were obtained by spectroscopic methods. Compound 2 was ichthyotoxic at 0.1 ppm against Gambusia affinis and showed moderate activity (IC(50) 18 microM) to inhibit mammalian phospholipase A(2). PMID:10785432

  9. Cytotoxic Activity and Chemical Composition of the Root Extract from the Mexican Species Linum scabrellum: Mechanism of Action of the Active Compound 6-Methoxypodophyllotoxin.

    PubMed

    Alejandre-García, Ivonne; Álvarez, Laura; Cardoso-Taketa, Alexandre; González-Maya, Leticia; Antúnez, Mayra; Salas-Vidal, Enrique; Díaz, J Fernando; Marquina-Bahena, Silvia; Villarreal, María Luisa

    2015-01-01

    The cytotoxic activity and the chemical composition of the dichloromethane/methanol root extract of Linum scabrellum Planchon (Linaceae) were analyzed. Using NMR spectra and mass spectrometry analyses of the extract we identified eight main constituents: oleic acid (1), octadecenoic acid (2), stigmasterol (3), α-amyrin (4), pinoresinol (5), 6 methoxypodophyllotoxin (6), coniferin (7), and 6-methoxypodophyllotoxin-7-O-β-D-glucopyranoside (8). By using the sulforhodamine B assay, an important cytotoxic activity against four human cancer cell lines, HF6 colon (IC50 = 0.57 μg/mL), MCF7 breast (IC50 = 0.56 μg/mL), PC3 prostate (IC50 = 1.60 μg/mL), and SiHa cervical (IC50 = 1.54 μg/mL), as well as toward the normal fibroblasts line HFS-30 IC50 = 1.02 μg/mL was demonstrated. Compound 6 (6-methoxypodophyllotoxin) was responsible for the cytotoxic activity exhibiting an IC50 value range of 0.0632 to 2.7433 µg/mL against the tested cell lines. Cell cycle studies with compound 6 exhibited a cell arrest in G2/M of the prostate PC3 cancer cell line. Microtubule disruption studies demonstrated that compound 6 inhibited the polymerization of tubulin through its binding to the colchicine site (binding constant K b = 7.6 × 10(6) M(-1)). A dose-response apoptotic effect was also observed. This work constitutes the first investigation reporting the chemical composition of L. scabrellum and the first study determining the mechanism of action of compound 6. PMID:26246833

  10. Cytotoxic Activity and Chemical Composition of the Root Extract from the Mexican Species Linum scabrellum: Mechanism of Action of the Active Compound 6-Methoxypodophyllotoxin

    PubMed Central

    Alejandre-García, Ivonne; Álvarez, Laura; Cardoso-Taketa, Alexandre; González-Maya, Leticia; Antúnez, Mayra; Salas-Vidal, Enrique; Díaz, J. Fernando; Marquina-Bahena, Silvia; Villarreal, María Luisa

    2015-01-01

    The cytotoxic activity and the chemical composition of the dichloromethane/methanol root extract of Linum scabrellum Planchon (Linaceae) were analyzed. Using NMR spectra and mass spectrometry analyses of the extract we identified eight main constituents: oleic acid (1), octadecenoic acid (2), stigmasterol (3), α-amyrin (4), pinoresinol (5), 6 methoxypodophyllotoxin (6), coniferin (7), and 6-methoxypodophyllotoxin-7-O-β-D-glucopyranoside (8). By using the sulforhodamine B assay, an important cytotoxic activity against four human cancer cell lines, HF6 colon (IC50 = 0.57 μg/mL), MCF7 breast (IC50 = 0.56 μg/mL), PC3 prostate (IC50 = 1.60 μg/mL), and SiHa cervical (IC50 = 1.54 μg/mL), as well as toward the normal fibroblasts line HFS-30 IC50 = 1.02 μg/mL was demonstrated. Compound 6 (6-methoxypodophyllotoxin) was responsible for the cytotoxic activity exhibiting an IC50 value range of 0.0632 to 2.7433 µg/mL against the tested cell lines. Cell cycle studies with compound 6 exhibited a cell arrest in G2/M of the prostate PC3 cancer cell line. Microtubule disruption studies demonstrated that compound 6 inhibited the polymerization of tubulin through its binding to the colchicine site (binding constant Kb = 7.6 × 106 M−1). A dose-response apoptotic effect was also observed. This work constitutes the first investigation reporting the chemical composition of L. scabrellum and the first study determining the mechanism of action of compound 6. PMID:26246833

  11. Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease

    PubMed Central

    Khare, Shilpi; Roach, Steven L.; Barnes, S. Whitney; Hoepfner, Dominic; Walker, John R.; Chatterjee, Arnab K.; Neitz, R. Jeffrey; Arkin, Michelle R.; McNamara, Case W.; Ballard, Jaime; Lai, Yin; Fu, Yue; Molteni, Valentina; Yeh, Vince; McKerrow, James H.; Glynne, Richard J.; Supek, Frantisek

    2015-01-01

    Unbiased phenotypic screens enable identification of small molecules that inhibit pathogen growth by unanticipated mechanisms. These small molecules can be used as starting points for drug discovery programs that target such mechanisms. A major challenge of the approach is the identification of the cellular targets. Here we report GNF7686, a small molecule inhibitor of Trypanosoma cruzi, the causative agent of Chagas disease, and identification of cytochrome b as its target. Following discovery of GNF7686 in a parasite growth inhibition high throughput screen, we were able to evolve a GNF7686-resistant culture of T. cruzi epimastigotes. Clones from this culture bore a mutation coding for a substitution of leucine by phenylalanine at amino acid position 197 in cytochrome b. Cytochrome b is a component of complex III (cytochrome bc1) in the mitochondrial electron transport chain and catalyzes the transfer of electrons from ubiquinol to cytochrome c by a mechanism that utilizes two distinct catalytic sites, QN and QP. The L197F mutation is located in the QN site and confers resistance to GNF7686 in both parasite cell growth and biochemical cytochrome b assays. Additionally, the mutant cytochrome b confers resistance to antimycin A, another QN site inhibitor, but not to strobilurin or myxothiazol, which target the QP site. GNF7686 represents a promising starting point for Chagas disease drug discovery as it potently inhibits growth of intracellular T. cruzi amastigotes with a half maximal effective concentration (EC50) of 0.15 µM, and is highly specific for T. cruzi cytochrome b. No effect on the mammalian respiratory chain or mammalian cell proliferation was observed with up to 25 µM of GNF7686. Our approach, which combines T. cruzi chemical genetics with biochemical target validation, can be broadly applied to the discovery of additional novel drug targets and drug leads for Chagas disease. PMID:26186534

  12. Influence of chemical doping and hydrostatic pressure on the magnetic properties of Mn1 -xFexAs magnetocaloric compounds

    NASA Astrophysics Data System (ADS)

    Rocco, D. L.; de Campos, A.; Carvalho, A. Magnus G.; dos Santos, A. O.; da Silva, L. M.; Gama, S.; da Luz, M. S.; von Ranke, P.; de Oliveira, N. A.; Coelho, A. A.; Cardoso, L. P.; Souza, J. A.

    2016-02-01

    This paper presents the results of an investigation of the magnetic and structural properties of Mn1-xFexAs compounds under hydrostatic pressure and chemical doping. The chemical doping was performed by using low Fe doping levels (x =0 , 0.003, 0.006, 0.010, 0.015, and 0.018), which emulates the negative pressure effect on the crystal structure. The results of this approach were compared with the physical pressure effect (hydrostatic pressure from 0 to 2.2 kbar) on the Mn0.997Fe0.003As . Both approaches exhibit the same magnetic behaviors: the TC and saturation magnetization decrease as the pressure increases; for the highest pressure studied, an orthorhombic antiferromagnetic phase occurs below the critical temperature and coexists with the ferromagnetic hexagonal phase. The equivalence between hydrostatic pressure and chemical doping indicates that the Fe doping only causes structural deformation. In addition, we performed magnetic measurements at high temperature (up to 520 K) on the samples with x =0 and 0.003 in order to investigate the magnetic behavior above TC=310 K. These results, along with structural characterization, clearly show that between TC and Tt the system is a weak antiferromagnet with short-range order confined only in the a b plane. Finally, using the low- and high-temperature data, the magnetic phase diagrams of the compound under hydrostatic pressure and chemical doping were redrawn.

  13. Antirheumatoid Arthritis Activities and Chemical Compositions of Phenolic Compounds-Rich Fraction from Urtica atrichocaulis, an Endemic Plant to China

    PubMed Central

    Wang, Mengyue; Li, Ke; Nie, Yuxiao; Wei, Yingfang; Li, Xiaobo

    2012-01-01

    Urtica atrichocaulis, an endemic plant to China, is commonly used to treat rheumatoid arthritis even though its pharmaceutical activities and chemical constituents were not studied. Herein, we reported our investigations on the chemical compositions of the phenolic compounds-rich fraction from U. atrichocaulis (TFUA) and their antirheumatoid arthritis activities. We found that the TFUA significantly inhibited the adjuvant-induced rats arthritis, carrageenin-induced rats paw edema, cotton pellet-induced mice granuloma, and the acetic acid-induced mice writhing response. Our phytochemical investigations on the TFUA resulted in the first-time isolation and identification of 17 phenolic constituents and a bis (5-formylfurfuryl) ether. The extensive HPLC analysis also revealed the chemical compositions of TFUA. Our further biological evaluation of the main phenolic components, individually and collectively, indicated that the antirheumatoid arthritis activities of TFUA were the combined effect of multiple phenolic constituents. PMID:21904564

  14. Stochastic voyages into uncharted chemical space produce a representative library of all possible drug-like compounds.

    PubMed

    Virshup, Aaron M; Contreras-Garca, Julia; Wipf, Peter; Yang, Weitao; Beratan, David N

    2013-05-15

    The "small molecule universe" (SMU), the set of all synthetically feasible organic molecules of 500 Da molecular weight or less, is estimated to contain over 10(60) structures, making exhaustive searches for structures of interest impractical. Here, we describe the construction of a "representative universal library" spanning the SMU that samples the full extent of feasible small molecule chemistries. This library was generated using the newly developed Algorithm for Chemical Space Exploration with Stochastic Search (ACSESS). ACSESS makes two important contributions to chemical space exploration: it allows the systematic search of the unexplored regions of the small molecule universe, and it facilitates the mining of chemical libraries that do not yet exist, providing a near-infinite source of diverse novel compounds. PMID:23548177

  15. Stochastic voyages into uncharted chemical space produce a representative library of all possible drug-like compounds

    PubMed Central

    Virshup, Aaron M.; Contreras-Garca, Julia; Wipf, Peter; Yang, Weitao; Beratan, David N.

    2013-01-01

    The small molecule universe (SMU), the set of all synthetically feasible organic molecules of 500 Daltons molecular weight or less, is estimated to contain over 1060 structures, making exhaustive searches for structures of interest impractical. Here, we describe the construction of a representative universal library spanning the SMU that samples the full extent of feasible small molecule chemistries. This library was generated using the newly developed Algorithm for Chemical Space Exploration with Stochastic Search (ACSESS). ACSESS makes two important contributions to chemical space exploration: it allows the systematic search of the unexplored regions of the small molecule universe, and it facilitates the mining of chemical libraries that do not yet exist, providing a near-infinite source of diverse novel compounds. PMID:23548177

  16. A High-Resolution Genetic Map of Yellow Monkeyflower Identifies Chemical Defense QTLs and Recombination Rate Variation

    PubMed Central

    Holeski, Liza M.; Monnahan, Patrick; Koseva, Boryana; McCool, Nick; Lindroth, Richard L.; Kelly, John K.

    2014-01-01

    Genotyping-by-sequencing methods have vastly improved the resolution and accuracy of genetic linkage maps by increasing both the number of marker loci as well as the number of individuals genotyped at these loci. Using restriction-associated DNA sequencing, we construct a dense linkage map for a panel of recombinant inbred lines derived from a cross between divergent ecotypes of Mimulus guttatus. We used this map to estimate recombination rate across the genome and to identify quantitative trait loci for the production of several secondary compounds (PPGs) of the phenylpropanoid pathway implicated in defense against herbivores. Levels of different PPGs are correlated across recombinant inbred lines suggesting joint regulation of the phenylpropanoid pathway. However, the three quantitative trait loci identified in this study each act on a distinct PPG. Finally, we map three putative genomic inversions differentiating the two parental populations, including a previously characterized inversion that contributes to life-history differences between the annual/perennial ecotypes. PMID:24626287

  17. High Throughput Screening for Compounds That Alter Muscle Cell Glycosylation Identifies New Role for N-Glycans in Regulating Sarcolemmal Protein Abundance and Laminin Binding*

    PubMed Central

    Cabrera, Paula V.; Pang, Mabel; Marshall, Jamie L.; Kung, Raymond; Nelson, Stanley F.; Stalnaker, Stephanie H.; Wells, Lance; Crosbie-Watson, Rachelle H.; Baum, Linda G.

    2012-01-01

    Duchenne muscular dystrophy is an X-linked disorder characterized by loss of dystrophin, a cytoskeletal protein that connects the actin cytoskeleton in skeletal muscle cells to extracellular matrix. Dystrophin binds to the cytoplasmic domain of the transmembrane glycoprotein ?-dystroglycan (?-DG), which associates with cell surface ?-dystroglycan (?-DG) that binds laminin in the extracellular matrix. ?-DG can also associate with utrophin, and this differential association correlates with specific glycosylation changes on ?-DG. Genetic modification of ?-DG glycosylation can promote utrophin binding and rescue dystrophic phenotypes in mouse dystrophy models. We used high throughput screening with the plant lectin Wisteria floribunda agglutinin (WFA) to identify compounds that altered muscle cell surface glycosylation, with the goal of finding compounds that increase abundance of ?-DG and associated sarcolemmal glycoproteins, increase utrophin usage, and increase laminin binding. We identified one compound, lobeline, from the Prestwick library of Food and Drug Administration-approved compounds that fulfilled these criteria, increasing WFA binding to C2C12 cells and to primary muscle cells from wild type and mdx mice. WFA binding and enhancement by lobeline required complex N-glycans but not O-mannose glycans that bind laminin. However, inhibiting complex N-glycan processing reduced laminin binding to muscle cell glycoproteins, although O-mannosylation was intact. Glycan analysis demonstrated a general increase in N-glycans on lobeline-treated cells rather than specific alterations in cell surface glycosylation, consistent with increased abundance of multiple sarcolemmal glycoproteins. This demonstrates the feasibility of high throughput screening with plant lectins to identify compounds that alter muscle cell glycosylation and identifies a novel role for N-glycans in regulating muscle cell function. PMID:22570487

  18. Students' Predictions about the Sensory Properties of Chemical Compounds: Additive versus Emergent Frameworks

    ERIC Educational Resources Information Center

    Talanquer, Vicente

    2008-01-01

    We investigated general chemistry students' intuitive ideas about the expected properties of the products of a chemical reaction. In particular, we analyzed college chemistry students' predictions about the color, smell, and taste of the products of chemical reactions represented at the molecular level. The study was designed to explore the extent

  19. Surface chemical reaction of polymer film with reactive intermediates produced by laser ablation of azido compound

    NASA Astrophysics Data System (ADS)

    Niino, Hiroyuki; Yabe, Akira

    1996-04-01

    The surface of poly(ethylene terephthalate) film was chemically modified with the fragments produced by ablation of pentafluorophenylazide at 90 K upon KrF excimer laser radiation. When the surface was exposed to the fragments in a vacuum, the photolyzed phenylazide was immobilized onto the surface through the chemical bond.

  20. Identification of chemical compounds present in different fractions of Annona reticulata L. leaf by using GC-MS.

    PubMed

    Rout, Soumya P; Kar, Durga M

    2014-01-01

    GC-MS analysis of fractions prepared from hydro-alcoholic extract of Annona reticulata Linn (Family Annonaceae) leaf revealed the presence of 9,10-dimethyltricyclo[4.2.1.1(2,5)]decane-9,10-diol; 4-(1,5-dihydroxy-2,6,6-trimethylcyclohex-2-enyl)but-3-en-2-one; 3,7-dimethyl-6-nonen-1-ol acetate; 9-octadecenamide,(Z)-; glycerine; D-glucose,6-O-?-D-galactopyranosyl-; desulphosinigrin and ?-methyl-D-mannopyranoside as few of the major compounds in different fractions. The presence of these compounds in the plant has been identified for the first time. PMID:25050939

  1. Screening of novel chemical compounds as possible inhibitors of carbonic anhydrase and photosynthetic activity of photosystem II.

    PubMed

    Karacan, Mehmet Sayım; Zharmukhamedov, Sergei K; Mamaş, Serhat; Kupriyanova, Elena V; Shitov, Alexandr V; Klimov, Vyacheslav V; Özbek, Neslihan; Özmen, Ümmühan; Gündüzalp, Ayla; Schmitt, Franz-Josef; Karacan, Nurcan; Friedrich, Thomas; Los, Dmitry A; Carpentier, Robert; Allakhverdiev, Suleyman I

    2014-08-01

    Thirty novel chemical compounds were designed and synthesized expecting that they would be possible inhibitors. From this number eleven were organic bases, twenty-four were their organic derivatives and fourteen were metal complexes. Screening of these chemicals by their action on photosynthetic electron transfer (PET) and carbonic anhydrase (CA) activity (CAA) of photosystem II (PSII), α-CA, as well as β-CA was done. Several groups were revealed among them. Some of them are capable to suppress either one, two, three, or even all of the measured activities. As example, one of the Cu(II)-phenyl sulfonylhydrazone complexes (compound 25) suppresses CAA of α-CA by 88%, CAA of β-CA by 100% inhibition; CAA of PSII by 100% and the PSII photosynthetic activity by 66.2%. The Schiff base compounds (12, 15) and Cu(II)-phenyl sulfonylhydrazone complexes (25, 26) inhibited the CAA and PET of PSII significantly. The obtained data indicate that the PSII donor side is a target of the inhibitory action of these agents. Some physico- or electrochemical properties such as diffusion coefficient, number of transferred electrons, peak potential and heterogeneous standard rate constants of the compounds were determined in nonaqueous media. pKa values were also determined in nonaqueous and aqueous media. Availability in the studied group of novel chemical agents possessing different inhibitory activity allow in future to isolate the "active part" in the structure of the inhibitors responsible for different inhibitory mechanisms, as well as to determine the influence of side substituters on its inhibitory efficiency. PMID:24418071

  2. Chemical compounds and toxicological assessments of drinking water stored in polyethylene terephthalate (PET) bottles: A source of controversy reviewed.

    PubMed

    Bach, Cristina; Dauchy, Xavier; Chagnon, Marie-Christine; Etienne, Serge

    2012-03-01

    A declaration of conformity according to European regulation No. 10/2011 is required to ensure the safety of plastic materials in contact with foodstuffs. This regulation established a positive list of substances that are authorized for use in plastic materials. Some compounds are subject to restrictions and/or specifications according to their toxicological data. Despite this, the analysis of PET reveals some non-intentionally added substances (NIAS) produced by authorized initial reactants and additives. Genotoxic and estrogenic activities in PET-bottled water have been reported. Chemical mixtures in bottled water have been suggested as the source of these toxicological effects. Furthermore, sample preparation techniques, such as solid-phase extraction (SPE), to extract estrogen-like compounds in bottled water are controversial. It has been suggested that inappropriate extraction methods and sample treatment may result in false-negative or positive responses when testing water extracts in bioassays. There is therefore a need to combine chemical analysis with bioassays to carry out hazard assessments. Formaldehyde, acetaldehyde and antimony are clearly related to migration from PET into water. However, several studies have shown other theoretically unexpected substances in bottled water. The origin of these compounds has not been clearly established (PET container, cap-sealing resins, background contamination, water processing steps, NIAS, recycled PET, etc.). Here, we surveyed toxicological studies on PET-bottled water and chemical compounds that may be present therein. Our literature review shows that contradictory results for PET-bottled water have been reported, and differences can be explained by the wide variety of analytical methods, bioassays and exposure conditions employed. PMID:22196043

  3. Identification of Three Classes of Heteroaromatic Compounds with Activity against Intracellular Trypanosoma cruzi by Chemical Library Screening

    PubMed Central

    Bettiol, Esther; Samanovic, Marie; Murkin, Andrew S.; Raper, Jayne; Buckner, Frederick; Rodriguez, Ana

    2009-01-01

    The development of new drugs against Chagas disease is a priority since the currently available medicines have toxic effects, partial efficacy and are targeted against the acute phase of disease. At present, there is no drug to treat the chronic stage. In this study, we have optimized a whole cell-based assay for high throughput screening of compounds that inhibit infection of mammalian cells by Trypanosoma cruzi trypomastigotes. A 2000-compound chemical library was screened using a recombinant T. cruzi (Tulahuen strain) expressing ?-galactosidase. Three hits were selected for their high activity against T. cruzi and low toxicity to host cells in vitro: PCH1, NT1 and CX1 (IC50: 54, 190 and 23 nM, respectively). Each of these three compounds presents a different mechanism of action on intracellular proliferation of T. cruzi amastigotes. CX1 shows strong trypanocidal activity, an essential characteristic for the development of drugs against the chronic stage of Chagas disease where parasites are found intracellular in a quiescent stage. NT1 has a trypanostatic effect, while PCH1 affects parasite division. The three compounds also show high activity against intracellular T. cruzi from the Y strain and against the related kinetoplastid species Leishmania major and L. amazonensis. Characterization of the antiT. cruzi activity of molecules chemically related to the three library hits allowed the selection of two compounds with IC50 values of 2 nM (PCH6 and CX2). These values are approximately 100 times lower than those of the medicines used in patients against T. cruzi. These results provide new candidate molecules for the development of treatments against Chagas disease and leishmaniasis. PMID:19238193

  4. Gaseous chemical compounds in indoor and outdoor air of 602 houses throughout Japan in winter and summer.

    PubMed

    Uchiyama, Shigehisa; Tomizawa, Takuya; Tokoro, Asumo; Aoki, Manami; Hishiki, Mayu; Yamada, Tomomi; Tanaka, Reiko; Sakamoto, Hironari; Yoshida, Tsutomu; Bekki, Kanae; Inaba, Yohei; Nakagome, Hideki; Kunugita, Naoki

    2015-02-01

    A nationwide survey of indoor air quality in Japan was conducted using four types of diffusive samplers. Gaseous chemical compounds such as carbonyls, volatile organic compounds (VOC), acid gases, basic gases, and ozone were measured in indoor and outdoor air of 602 houses throughout Japan in winter and summer. Four kinds of diffusive samplers were used in this study: DSD-BPE/DNPH packed with 2,4-dinitrophenyl hydrazine and trans-1,2-bis(2-pyridyl)ethylene coated silica for ozone and carbonyls; VOC-SD packed with Carboxen 564 particles for volatile organic compounds; DSD-TEA packed with triethanolamine impregnated silica for acid gases; and DSD-NH3 packed with phosphoric acid impregnated silica for basic gases. These samplers are small and lightweight and do not require a power source, hence, it was possible to obtain a large number of air samples via mail from throughout Japan. Almost all compounds in indoor air were present at higher levels in summer than in winter. In particular, formaldehyde, toluene, and ammonia were strongly dependent on temperature, and their levels increased with temperature. The nitrogen dioxide concentration in indoor air particularly increased only during winter and was well correlated with the formic acid concentration (correlation coefficient=0.959). Ozone concentrations in indoor air were extremely low compared with the outdoor concentrations. Ozone flowing from outdoor air may be decomposed quickly by chemical compounds in indoor air; therefore, it is suggested that the indoor/outdoor ratio of ozone represents the ventilation of the indoor environment. PMID:25601740

  5. Identifying rhodamine dye plume sources in near-shore oceanic environments by integration of chemical and visual sensors.

    PubMed

    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

  6. 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

  7. Activation of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPAR?1) by Semi-Volatile Compounds (SVOCs) and Chemical Mixtures in Indoor Dust.

    PubMed

    Fang, Mingliang; Webster, Thomas F; Stapleton, Heather M

    2015-08-18

    Recently, we reported that several semi-volatile compounds (SVOCs) were competitive ligands for human peroxisome proliferator-activated nuclear receptor gamma (PPAR?1). We also observed significant binding from chemicals extracted from house dust at a concentration of 3 mg dust/mL in the dosing medium. To follow up on this study, a commercially available reporter gene assay (GeneBLAzer PPAR?1 non-DA Assay, Invitrogen) was used to investigate the PPAR?1 activation by 30 common SVOCs (e.g., brominated flame retardants, organophosphates, and phthalates) and in house dust extracts. Twenty-eight SVOCs or their metabolites were either confirmed or for the first time were found to be weak or moderate PPAR?1 agonists. We also observed activation in 15 of 25 dust extracts examined. In some cases, activation was as high as 50% of the activation of the positive control (rosiglitazone). Furthermore, there was a significant and positive correlation (r = 0.7, p < 0.003) between data collected from this reporter assay and our previous ligand binding assay tested on the same dust extracts. Our results suggest that many SVOCs ubiquitous in house dust, or their metabolites, are possible PPAR?1 agonists. Also, chemical mixtures present in house dust at environmentally relevant levels can activate human PPAR?1 in a transfected cell culture system, and further research is needed to identify the primary chemical(s) driving this activity. PMID:26172262

  8. Deduction of the chemical state and the electronic structure of Nd{sub 2}Fe{sub 14}B compound from X-ray photoelectron spectroscopy core-level and valence-band spectra

    SciTech Connect

    Wang, Jing; Liang, Le; Zhang, Lanting E-mail: lmsun@sjtu.edu.cn; Sun, Limin E-mail: lmsun@sjtu.edu.cn; Hirano, Shinichi

    2014-10-28

    Characterization of chemical state and electronic structure of the technologically important Nd{sub 2}Fe{sub 14}B compound is attractive for understanding the physical nature of its excellent magnetic properties. X-ray photoelectron spectroscopy (XPS) study of such rare-earth compound is important and also challenging due to the easy oxidation of surface and small photoelectron cross-sections of rare-earth 4f electrons and B 2p electrons, etc. Here, we reported an investigation based on XPS spectra of Nd{sub 2}Fe{sub 14}B compound as a function of Ar ion sputtering time. The chemical state of Fe and that of B in Nd{sub 2}Fe{sub 14}B compound can be clearly determined to be 0 and −3, respectively. The Nd in Nd{sub 2}Fe{sub 14}B compound is found to have the chemical state of close to +3 instead of +3 as compared with the Nd in Nd{sub 2}O{sub 3}. In addition, by comparing the valence-band spectrum of Nd{sub 2}Fe{sub 14}B compound to that of the pure Fe, the contributions from Nd, Fe, and B to the valence-band structure of Nd{sub 2}Fe{sub 14}B compound is made more clear. The B 2p states and B 2s states are identified to be at ∼11.2 eV and ∼24.6 eV, respectively, which is reported for the first time. The contribution from Nd 4f states can be identified both in XPS core-level spectrum and XPS valence-band spectrum. Although Nd 4f states partially hybridize with Fe 3d states, Nd 4f states are mainly localized in Nd{sub 2}Fe{sub 14}B compound.

  9. Chemicals with weak skin sensitizing properties can be identified using low-density microarrays on immature dendritic cells.

    PubMed

    Cluzel-Tailhardat, M; Bonnet-Duquennoy, M; de Queral, D Pelle; Vocanson, M; Kurfrst, R; Courtellemont, P; Le Varlet, B; Nicolas, J-F

    2007-11-01

    A critical step in the induction of allergic contact dermatitis is the interaction of haptens with immature dendritic cells (iDC) leading to their activation. Therefore iDC appear as suitable targets for the evaluation of the sensitizing properties of haptens with the aim of developing in vitro toxicologic methods. Here, using a low-density cDNA-array, we analyzed the expression of 165 genes related to dendritic cell biology in human iDC following a 24h incubation with four haptens representative of strong (DNBS), moderate (isoeugenol) and weak (eugenol, hydroxycitronellal) contact sensitizers and with one irritant sodium dodecyl sulphate (SDS). Results show that 21/165 iDC genes were significantly modulated by hapten treatment. Some genes were preferentially modulated by a given chemical. Thus, DNBS, isoeugenol, eugenol and hydroxycitronellal consistently modulated CCR5, CCL27, CCL2 and CCR7, respectively, whereas the CXCL10 gene was regulated by SDS. When subjected to principal component analysis, the 21 target genes fell into four groups associated with a particular type of chemical endowed with distinct sensitizing or irritant properties. Thus, gene profiling of iDC using low-density microarray allows, for screening of chemicals, the indentification of weak haptens with potential skin sensitizing properties. These results suggest that gene profiling of iDC using low-density microarrays may be useful to identify chemicals with weak skin sensitizing properties. PMID:17936526

  10. A comparison of {sup 252}Cf and 14-MeV neutron excitation to identify chemical warfare agents by PGNAA

    SciTech Connect

    Caffrey, A.J.; Harlow, B.D.; Edwards, A.J.; Krebs, K.M.; Jones, J.L.; Yoon, W.; Zabriskie, J.M.; Dougan, A.D.

    2000-07-01

    Since 1992, Idaho National Engineering and Environmental Laboratory's portable isotopic neutron spectrometry (PINS) system has been widely used for the nondestructive assessment of munitions suspected to contain chemical warfare agents, such as the nerve agent sarin. PINS is a {sup 252}Cf-based prompt gamma-ray neutron activation analysis (PGNAA) system. The standard PINS system employs a partially moderated 5-{micro}g {sup 252}Cf source emitting 10{sup 7} n/s to excite the atomic nuclei inside the item under test. The chemical elements inside the item are revealed by their characteristic gamma-ray spectrum, measured by a high-resolution high-purity germanium gamma-ray spectrometer. The system computer then infers the fill compound or mixture from the elemental data extracted from the gamma-ray spectrum. Reliable PINS assessments can be completed in as little as 100 s for favorable cases such as white phosphorus smoke munitions, but normally, a 1000 to 3000 live-second counting interval is required. To improve PINS throughput when hundreds or more munitions must be assessed, they are evaluating the possible advantages of 14-MeV neutron excitation over their current radioisotopic source.

  11. Isolation and Chemical Structural Characterisation of a Compound with Antioxidant Activity from the Roots of Senna italica

    PubMed Central

    Mokgotho, Matlou Phineas; Gololo, Stanley Sechene; Masoko, Peter; Shai, Leshwene Jeremiah; Bagla, Victor Patrick; Eloff, Jacobus Nicolaas

    2013-01-01

    Senna italica, a member of the Fabaceae family (subfamily Caesalpiniaceae), is widely used in South African traditional medicine to treat a number of disease conditions. Aqueous extracts of the plant are mainly used to treat sexually transmitted infections and intestinal complications. The roots of S. italica were ground to a fine powder and sequentially extracted with n-hexane, dichloromethane, acetone, and methanol using serial exhaustive extraction (SEE) method. Thin layer chromatography was used to analyse the phytochemical composition of the extracts and DPPH radical scavenging method to detect the presence of antioxidant compounds. The bioassay guided fractionation of the acetone fraction afforded an antioxidant compound with free radical scavenging activity. The isolated compound was subsequently identified as 3,4?,5-trihydroxystilbene (resveratrol). This study represents the first report of the stilbene resveratrol in S. italica. PMID:23843877

  12. Isolation and Chemical Structural Characterisation of a Compound with Antioxidant Activity from the Roots of Senna italica.

    PubMed

    Mokgotho, Matlou Phineas; Gololo, Stanley Sechene; Masoko, Peter; Mdee, Ladislaus Kakore; Mbazima, Vusi; Shai, Leshwene Jeremiah; Bagla, Victor Patrick; Eloff, Jacobus Nicolaas; Mampuru, Leseilane

    2013-01-01

    Senna italica, a member of the Fabaceae family (subfamily Caesalpiniaceae), is widely used in South African traditional medicine to treat a number of disease conditions. Aqueous extracts of the plant are mainly used to treat sexually transmitted infections and intestinal complications. The roots of S. italica were ground to a fine powder and sequentially extracted with n-hexane, dichloromethane, acetone, and methanol using serial exhaustive extraction (SEE) method. Thin layer chromatography was used to analyse the phytochemical composition of the extracts and DPPH radical scavenging method to detect the presence of antioxidant compounds. The bioassay guided fractionation of the acetone fraction afforded an antioxidant compound with free radical scavenging activity. The isolated compound was subsequently identified as 3,4',5-trihydroxystilbene (resveratrol). This study represents the first report of the stilbene resveratrol in S. italica. PMID:23843877

  13. 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. PMID:26092703

  14. Estimation of Physical Properties and Chemical Reactivity Parameters of Organic Compounds for Environmental Modeling by SPARC

    EPA Science Inventory

    Mathematical models for predicting the transport and fate of pollutants in the environment require reactivity parameter values that is value of the physical and chemical constants that govern reactivity. Although empirical structure activity relationships have been developed th...

  15. EXPOSURE-DOSE-EFFECT LINKAGES FOR CHEMICALLY REACTIVE AIR TOXIC COMPOUNDS

    EPA Science Inventory

    This project represents a multidisciplinary collaboration to develop and test methods for more precisely predicting human exposure-dose-response relationships of respiratory tract irritants. These irritants have the unique property of reacting chemically with proteins and lipids ...

  16. Using the chemical equilibrium partitioning space to explore factors influencing the phase distribution of compounds involved in secondary organic aerosol formation

    NASA Astrophysics Data System (ADS)

    Wania, F.; Lei, Y. D.; Wang, C.; Abbatt, J. P. D.; Goss, K.-U.

    2015-03-01

    Many atmospheric and chemical variables influence the partitioning equilibrium between gas phase and condensed phases of compounds implicated in the formation of secondary organic aerosol (SOA). The large number of factors and their interaction makes it often difficult to assess their relative importance and concerted impact. Here we introduce a two-dimensional space which maps regions of dominant atmospheric phase distribution within a coordinate system defined by equilibrium partition coefficients between the gas phase, an aqueous phase and a water-insoluble organic matter (WIOM) phase. Placing compounds formed from the oxidation of n-alkanes, terpenes and mono-aromatic hydrocarbons on the maps based on their predicted partitioning properties allows for a simple graphical assessment of their equilibrium phase distribution behaviour. Specifically, it allows for the simultaneous visualisation and quantitative comparison of the impact on phase distribution of changes in atmospheric parameters (such as temperature, salinity, WIOM-phase polarity, organic aerosol load, and liquid water content) and chemical properties (such as oxidation state, molecular size, functionalisation, and dimerisation). The graphical analysis reveals that the addition of hydroxyl, carbonyl and carboxyl groups increases the affinity of aliphatic, alicyclic and aromatic hydrocarbons for the aqueous phase more rapidly than their affinity for WIOM, suggesting that the aqueous phase may often be relevant even for substances that are considerably larger than the C2 and C3 compounds that are typically believed to be associated with aqueous SOA. In particular, the maps identify some compounds that contribute to SOA formation if partitioning to both WIOM and aqueous phase is considered but would remain in the gas phase if either condensed phase were neglected. For example, many semi-volatile α-pinene oxidation products will contribute to aqueous SOA under the conditions of high liquid water content encountered in clouds but would remain vapours in wet aerosol. It is conceivable to develop parameterisations of "partitioning basis sets" that group compounds with comparable partitioning properties, which - when combined with data on the abundance of those groups of compounds - could serve in the simulation of SOA formation.

  17. Using the chemical equilibrium partitioning space to explore factors influencing the phase distribution of compounds involved in secondary organic aerosol formation

    NASA Astrophysics Data System (ADS)

    Wania, F.; Lei, Y. D.; Wang, C.; Abbatt, J. P. D.; Goss, K.-U.

    2014-10-01

    Many atmospheric and chemical variables influence the partitioning equilibrium between gas phase and condensed phases of compounds implicated in the formation of secondary organic aerosol (SOA). The large number of factors and their interaction makes it often difficult to assess their relative importance and concerted impact. Here we introduce a two-dimensional space, which maps regions of dominant atmospheric phase distribution within a coordinate system defined by equilibrium partitioning coefficients between the gas phase, an aqueous phase and a water insoluble organic matter (WIOM) phase. Placing compounds formed from the oxidation of n-alkanes, terpenes and mono-aromatic hydrocarbons on the maps based on their predicted partitioning properties allows for a simple graphical assessment of their equilibrium phase distribution behaviour. Specifically, it allows for the simultaneous visualization and quantitative comparison of the impact on phase distribution of changes in atmospheric parameters (such as temperature, salinity, WIOM phase polarity, organic aerosol load, and liquid water content), and chemical properties (such as oxidation state, molecular size, functionalization, and dimerisation). The graphical analysis reveals that the addition of hydroxyl, carbonyl and carboxyl groups increases the affinity of aliphatic, alicyclic and aromatic hydrocarbons for the aqueous phase more rapidly than their affinity for WIOM, suggesting that the aqueous phase may often be relevant even for substances that are considerably larger than the C2 and C3 compounds that are typically believed to be associated with aqueous SOA. In particular, the maps identify some compounds that contribute to SOA formation if partitioning to both WIOM and aqueous phase is considered, but would remain in the gas phase if either condensed phase were neglected. For example, many semi-volatile ?-pinene oxidation products will contribute to aqueous SOA under the high liquid water content conditions encountered in clouds, but would remain vapours in wet aerosol. It is conceivable to develop parameterizations of "partitioning basis sets" that group compounds with comparable partitioning properties, which - when combined with data on the abundance of those groups of compounds - could serve in the simulation of SOA formation.

  18. ISOTOPIC (14C) AND CHEMICAL COMPOSITION OF ATMOSPHERIC VOLATILE ORGANIC COMPOUND FRACTIONS - PRECURSORS TO OZONE FORMATION

    EPA Science Inventory

    Atmospheric volatile organic compounds (VOCs) are an important factor in the production of ozone near ground level [3]. Many hydrocarbons originate from auto exhaust. However, a number of VOCs, e.g., isoprene, are known to be natural in origin. To develop reliable models for un...

  19. Potassium Tris (Oxalato) Ferrate (III): A Versatile Compound to Illustrate the Principles of Chemical Equilibria

    ERIC Educational Resources Information Center

    Gonzalez, Gabriel; Seco, Miquel

    2004-01-01

    The potassium salt is an easy product to synthesize in an introductory course on inorganic chemistry and the students are required to prepare this product in order to improve their laboratory skills and as an introduction to the synthesis of coordination compounds. The complex potassium tris (oxalato) ferrate (III) is used to illustrate the

  20. Recent efforts in engineering microbial cells to produce new chemical compounds.

    PubMed

    de Boer, Arjo L; Schmidt-Dannert, Claudia

    2003-04-01

    In the process of evolution, variation and combination of basic building blocks has led to an astonishing wealth of secondary metabolites. Recently, the same evolutionary tools have been used to create novel compounds that have not been found in nature. PMID:12714061

  1. ANALYSIS OF AMBIENT POLAR VOLATILE ORGANIC COMPOUNDS USING CHEMICAL IONIZATION -- ION TRAP DETECTOR

    EPA Science Inventory

    The current approach to measuring trace levels of volatile organic compounds (VOCs) in ambient air requires cryogenic trapping of the analytes, followed by thermal desorption and low-temperature refocussing onto a column for analysis by capillary gas chromatography/mass spectrome...

  2. A NOVEL ENERGY-EFFICIENT PLASMA CHEMICAL PROCESS FOR THE DESTRUCTION OF VOLATILE TOXIC COMPOUNDS

    EPA Science Inventory

    Removal of low-concentrations (below several percent) of toxic volatile compounds from contaminated air streams is encountered at DOE waste sites in two instances:(i) off-gases resulting from air-stripping of contaminated soils and (ii) effluent from the incineration of highly-co...

  3. Chemical characterization of bioactive compounds from the endophytic fungus Diaporthe helianthi isolated from Luehea divaricata.

    PubMed

    Specian, Vnia; Sarragiotto, Maria Helena; Pamphile, Joo Alencar; Clemente, Edmar

    2012-07-01

    Endophytic microorganisms, defined as fungi or bacteria that colonize the interior of plants without causing any immediate negative effects or damages, have reciprocal relationships with host plants. In some cases their presence is beneficial to the host due to the synthesis of bioactive compounds, among which several alcohols, esters, ketones and others that may react with other compounds and may be lethal to pathogenic microorganisms. Diaporthe helianthi (Phomopsis helianthi in its anamorphic phase) is available worldwide, especially in Europe, Asia and America. Isolated in Europe as an agent of the sunflower stem cancer, it has also been endophytically isolated from tropical and temperate plants. A D. helianthi strain isolated from Luehea divaricata has been employed in current research. An investigation of the secondary metabolite from D. helianthi by CC and NMR of (1)H and (13)C yielded the separation of 10 fractions and the identification of the phenolic compound 2(-4 hydroxyphenyl)-ethanol (Tyrosol). Its antimicrobial reaction was tested and the ensuing antagonistic effects on the human pathogenic bacteria Enterococcus hirae, Escherichia coli, Micrococcus luteus, Salmonella typhi, Staphylococcus aureus, phytopathogenic Xanthomonas asc. phaseoli and phytopathogenic fungi were demonstrated. Results show that bioactive compounds and Tyrosol produced by D. helianthi have a biotechnological potential. PMID:24031942

  4. Potassium Tris (Oxalato) Ferrate (III): A Versatile Compound to Illustrate the Principles of Chemical Equilibria

    ERIC Educational Resources Information Center

    Gonzalez, Gabriel; Seco, Miquel

    2004-01-01

    The potassium salt is an easy product to synthesize in an introductory course on inorganic chemistry and the students are required to prepare this product in order to improve their laboratory skills and as an introduction to the synthesis of coordination compounds. The complex potassium tris (oxalato) ferrate (III) is used to illustrate the…

  5. EFFECTS OF CHEMICAL SPECIATION ON THE MINERALIZATION OF ORGANIC COMPOUNDS BY MICROORGANISMS

    EPA Science Inventory

    The mineralization of 1.0 to 100 ng/ml of four complexing compounds--oxalate, citrate, nitrilotriacetate (NTA), and ethylene diaminetetraacetate (EDTA)--was tested in media prepared according to equilibrium calculations by a computer program so that the H, Ca, Mg, Fe, or Al compl...

  6. Chemical characterization of bioactive compounds from the endophytic fungus Diaporthe helianthi isolated from Luehea divaricata

    PubMed Central

    Specian, Vânia; Sarragiotto, Maria Helena; Pamphile, João Alencar; Clemente, Edmar

    2012-01-01

    Endophytic microorganisms, defined as fungi or bacteria that colonize the interior of plants without causing any immediate negative effects or damages, have reciprocal relationships with host plants. In some cases their presence is beneficial to the host due to the synthesis of bioactive compounds, among which several alcohols, esters, ketones and others that may react with other compounds and may be lethal to pathogenic microorganisms. Diaporthe helianthi (Phomopsis helianthi in its anamorphic phase) is available worldwide, especially in Europe, Asia and America. Isolated in Europe as an agent of the sunflower stem cancer, it has also been endophytically isolated from tropical and temperate plants. A D. helianthi strain isolated from Luehea divaricata has been employed in current research. An investigation of the secondary metabolite from D. helianthi by CC and NMR of 1H and 13C yielded the separation of 10 fractions and the identification of the phenolic compound 2(-4 hydroxyphenyl)-ethanol (Tyrosol). Its antimicrobial reaction was tested and the ensuing antagonistic effects on the human pathogenic bacteria Enterococcus hirae, Escherichia coli, Micrococcus luteus, Salmonella typhi, Staphylococcus aureus, phytopathogenic Xanthomonas asc. phaseoli and phytopathogenic fungi were demonstrated. Results show that bioactive compounds and Tyrosol produced by D. helianthi have a biotechnological potential. PMID:24031942

  7. Multipurpose indicator in cells using intramolecular FRET between GFP and chemical compounds

    NASA Astrophysics Data System (ADS)

    Suzuki, Miho; Ito, Yoichiro; Savage, Hannah E.; Husimi, Yuzuru; Douglas, Kenneth T.

    2003-07-01

    Specific, surface cysteine sites have been introduced into Green Fluorescent Protein (GFP) to allow site-specific chemical modification by thiol-directed reagents. These sites have been labelled using BODIPY/eosin/rhodamine reagents as chemical FRET partners for the native GFP chromophore. When they were excited at 488 nm these engineered GFP: conjugated-fluorophore constructs, showed quenching of the native GFP fluorophore emission at 511 nm. New emission bands appeared correponding to each chemical fluorophore emission. Thus the new GFP chimeras exhibited strong intramolecular FRET. GFP mutants were then engineered with trypsin-sensitive sequences located close to the chemical fluorophore-bearing cysteine site. Trypsinolysis caused major changes in the FRET fluorescence spectra. On trypsinolysis the FRET was destroyed, as the FRET partners were now on separate molecules in the cleaved products. T Consequently, the emission wavelength altered from that of the chemically conjugated FRET partner back to that of the native fluorophore of the GFP (511 nm). This provides the possibility of efficient, ratio-based detection. Thus, protein re-engineering has led to novel probes capable of enzymatic triggering based on intramolecular FRET between GFP and specifically sited chemical labels.

  8. Transport of chemical and microbial compounds from known wastewater discharges: Potential for use as indicators of human fecal contamination

    USGS Publications Warehouse

    Glassmeyer, S.T.; Furlong, E.T.; Kolpin, D.W.; Cahill, J.D.; Zaugg, S.D.; Werner, S.L.; Meyer, M.T.; Kryak, D.D.

    2005-01-01

    The quality of drinking and recreational water is currently (2005) determined using indicator bacteria. However, the culture tests used to analyze for these bacteria require a long time to complete and do not discriminate between human and animal fecal material sources. One complementary approach is to use chemicals found in human wastewater, which would have the advantages of (1) potentially shorter analysis times than the bacterial culture tests and (2) being selected for human-source specificity. At 10 locations, water samples were collected upstream and at two successive points downstream from a wastewaster treatment plant (WWTP); a treated effluent sample was also collected at each WWTP. This sampling plan was used to determine the persistence of a chemically diverse suite of emerging contaminants in streams. Samples were also collected at two reference locations assumed to have minimal human impacts. Of the 110 chemical analytes investigated in this project, 78 were detected at least once. The number of compounds in a given sample ranged from 3 at a reference location to 50 in a WWTP effluent sample. The total analyte load at each location varied from 0.018 ?g/L at the reference location to 97.7 ?g/L in a separate WWTP effluent sample. Although most of the compound concentrations were in the range of 0.01?1.0 ?g/L, in some samples, individual concentrations were in the range of 5?38 ?g/L. The concentrations of the majority of the chemicals present in the samples generally followed the expected trend:? they were either nonexistent or at trace levels in the upstream samples, had their maximum concentrations in the WWTP effluent samples, and then declined in the two downstream samples. This research suggests that selected chemicals are useful as tracers of human wastewater discharge.

  9. Transport of chemical and microbial compounds from known wastewater discharges: potential for use as indicators of human fecal contamination.

    PubMed

    Glassmeyer, Susan T; Furlong, Edward T; Kolpin, Dana W; Cahill, Jeffery D; Zaugg, Steven D; Werner, Stephen L; Meyer, Michael T; Kryak, David D

    2005-07-15

    The quality of drinking and recreational water is currently (2005) determined using indicator bacteria. However, the culture tests used to analyze forthese bacteria require a long time to complete and do not discriminate between human and animal fecal material sources. One complementary approach is to use chemicals found in human wastewater, which would have the advantages of (1) potentially shorter analysis times than the bacterial culture tests and (2) being selected for human-source specificity. At 10 locations, water samples were collected upstream and at two successive points downstream from a wastewaster treatment plant (WWTP); a treated effluent sample was also collected at each WWTP. This sampling plan was used to determine the persistence of a chemically diverse suite of emerging contaminants in streams. Samples were also collected at two reference locations assumed to have minimal human impacts. Of the 110 chemical analytes investigated in this project, 78 were detected at least once. The number of compounds in a given sample ranged from 3 at a reference location to 50 in a WWTP effluent sample. The total analyte load at each location varied from 0.018 microg/L at the reference location to 97.7 microg/L in a separate WWTP effluent sample. Although most of the compound concentrations were in the range of 0.01-1.0 microg/L, in some samples, individual concentrations were in the range of 5-38 microg/L. The concentrations of the majority of the chemicals present in the samples generally followed the expected trend: they were either nonexistent or at trace levels in the upstream samples, had their maximum concentrations in the WWTP effluent samples, and then declined in the two downstream samples. This research suggests that selected chemicals are useful as tracers of human wastewater discharge. PMID:16082943

  10. Phenocopy – A Strategy to Qualify Chemical Compounds during Hit-to-Lead and/or Lead Optimization

    PubMed Central

    Ittrich, Carina; Rust, Werner; Fundel-Clemens, Katrin; Siewert, Susanne; Baur, Martin; Mara, Lisa; Gruenbaum, Lore; Heckel, Armin; Eils, Roland; Kontermann, Roland E.; Roth, Gerald J.; Gantner, Florian; Schnapp, Andreas; Park, John E.; Weith, Andreas; Quast, Karsten; Mennerich, Detlev

    2010-01-01

    A phenocopy is defined as an environmentally induced phenotype of one individual which is identical to the genotype-determined phenotype of another individual. The phenocopy phenomenon has been translated to the drug discovery process as phenotypes produced by the treatment of biological systems with new chemical entities (NCE) may resemble environmentally induced phenotypic modifications. Various new chemical entities exerting inhibition of the kinase activity of Transforming Growth Factor β Receptor I (TGF-βR1) were qualified by high-throughput RNA expression profiling. This chemical genomics approach resulted in a precise time-dependent insight to the TGF-β biology and allowed furthermore a comprehensive analysis of each NCE's off-target effects. The evaluation of off-target effects by the phenocopy approach allows a more accurate and integrated view on optimized compounds, supplementing classical biological evaluation parameters such as potency and selectivity. It has therefore the potential to become a novel method for ranking compounds during various drug discovery phases. PMID:21170314

  11. Changes on physico-chemical properties, lipid oxidation and volatile compounds during the manufacture of celta dry-cured loin.

    PubMed

    Pateiro, M; Franco, D; Carril, J A; Lorenzo, J M

    2015-08-01

    The present study deals with the changes on the main technological characteristics and volatile compounds profile of a traditional Spanish dry-ripened loin from Celta pig breed. The evolution of physicochemical properties, colour, texture, free fatty acid profile and volatile compounds were assessed throughout the process seasoning, post-seasoning and after 30 and 60days of dry-ripening. As it was expected, pH, moisture and activity water were significantly (P?compounds were identified during the manufacture of Celta dry-cured loin. At the end of process, volatile compounds from microbial activity were the most abundant followed by volatile compounds from lipid oxidation. PMID:26243901

  12. JV Task 86 - Identifying the Source of Benzene in Indoor Air Using Different Compound Classes from TO-15 Data

    SciTech Connect

    Steven B. Hawthorne

    2007-04-15

    Volatile organic compound (VOC) data that had already been collected using EPA method TO-15 at four different sites under regulatory scrutiny (a school, strip mall, apartment complex, and business/residential neighborhood) were evaluated to determine whether the source of indoor air benzene was outdoor air or vapor intrusion from contaminated soil. Both the use of tracer organics characteristic of different sources and principal component statistical analysis demonstrated that the source of indoor air at virtually all indoor sampling locations was a result of outdoor air, and not contaminated soil in and near the indoor air-sampling locations. These results show that proposed remediation activities to remove benzene-contaminated soil are highly unlikely to reduce indoor air benzene concentrations. A manuscript describing these results is presently being prepared for submission to a peer-reviewed journal.

  13. Anti-Prion Activity of a Panel of Aromatic Chemical Compounds: In Vitro and In Silico Approaches

    PubMed Central

    Ferreira, Natalia C.; Marques, Icaro A.; Conceio, Wesley A.; Macedo, Bruno; Machado, Clarice S.; Mascarello, Alessandra; Chiaradia-Delatorre, Louise Domeneghini; Yunes, Rosendo Augusto; Nunes, Ricardo Jos; Hughson, Andrew G.; Raymond, Lynne D.; Pascutti, Pedro G.; Caughey, Byron; Cordeiro, Yraima

    2014-01-01

    The prion protein (PrP) is implicated in the Transmissible Spongiform Encephalopathies (TSEs), which comprise a group of fatal neurodegenerative diseases affecting humans and other mammals. Conversion of cellular PrP (PrPC) into the scrapie form (PrPSc) is the hallmark of TSEs. Once formed, PrPSc aggregates and catalyzes PrPC misfolding into new PrPSc molecules. Although many compounds have been shown to inhibit the conversion process, so far there is no effective therapy for TSEs. Besides, most of the previously evaluated compounds failed in vivo due to poor pharmacokinetic profiles. In this work we propose a combined in vitro/in silico approach to screen for active anti-prion compounds presenting acceptable drugability and pharmacokinetic parameters. A diverse panel of aromatic compounds was screened in neuroblastoma cells persistently infected with PrPSc (ScN2a) for their ability to inhibit PK-resistant PrP (PrPRes) accumulation. From ?200 compounds, 47 were effective in decreasing the accumulation of PrPRes in ScN2a cells. Pharmacokinetic and physicochemical properties were predicted in silico, allowing us to obtain estimates of relative blood brain barrier permeation and mutagenicity. MTT reduction assays showed that most of the active compounds were non cytotoxic. Compounds that cleared PrPRes from ScN2a cells, were non-toxic in the MTT assay, and presented a good pharmacokinetic profile were investigated for their ability to inhibit aggregation of an amyloidogenic PrP peptide fragment (PrP109149). Molecular docking results provided structural models and binding affinities for the interaction between PrP and the most promising compounds. In summary, using this combined in vitro/in silico approach we have identified new small organic anti-scrapie compounds that decrease the accumulation of PrPRes in ScN2a cells, inhibit the aggregation of a PrP peptide, and possess pharmacokinetic characteristics that support their drugability. These compounds are attractive candidates for prion disease therapy. PMID:24400098

  14. The Arctic seasonal snow pack as a transfer mechanism and a reactor for lower atmosphere chemical compounds (Invited)

    NASA Astrophysics Data System (ADS)

    Douglas, T. A.

    2013-12-01

    The Polar Regions are snow covered for two thirds of the year (or longer) and in many locations there are few melt events during the winter. As a consequence, the late winter snow pack presents a spatial and temporal archive of the previous winter's precipitation, snow-atmosphere exchange, and within snow pack physical and chemical processes. However, to use the snow pack as a 'sensor' we have to understand the physical and chemical exchange processes between atmospheric compounds and snow and ice surfaces. Of equal importance is knowledge of the reactions that occur in and on snow and ice particle surfaces. Recent research has provided insights on the pathways individual compounds take from the lower atmosphere to snow and on the physical and chemical processes occurring within the snow pack at a variety of scales. Snow on or near sea ice has markedly higher major ion concentrations than snow on the terrestrial snow pack, most notably for chloride and bromide. This difference in chemical composition can be dramatic even in coastal regions where the land is only hundreds of meters away. As a consequence, we have to treat chemical cycling processes in/on snow on sea ice and snow on land differently. Since these halogens, particularly bromine, play critical roles in the spring time photochemical reactions that oxidize ozone and mercury their presence and fate on the sea ice snow pack is of particular interest. A future Arctic is expected to have a thinner, more dynamic sea ice cover that will arrive later and melt earlier. The areal extent of young ice production will likely increase markedly. This would lead to a different snow depositional and chemical regime on sea ice with potential ramifications for chemical exchange with the lower atmosphere. The roles of clear sky precipitation ('diamond dust') and surface hoar deposition in providing a unique lower atmospheric 'reactor' and potential source of water equivalence have been largely overlooked. This despite the fact that the highest mercury concentrations measured in surface snow or ice precipitation have been from diamond dust. Yet diamond dust has extremely low concentrations of major ions. This discrepancy may yield clues into how reactive aerosol particles sorb to falling ice crystals or how reactive aerosols provide a nucleation site around which ice accumulates. This presentation will cover recent field measurements addressing these topics with an eye toward how snow physical and chemical processes may be altered as a result of a projected warmer Arctic. Team Environment Canada and Team Desert Research Institute working on the sea ice north of Barrow, Alaska during the BROMEX 2012 field campaign.

  15. Changes in physico-chemical properties and volatile compounds throughout the manufacturing process of dry-cured foal loin.

    PubMed

    Lorenzo, Jos M; Carballo, J

    2015-01-01

    Physico-chemical, textural, lipolytic and volatile compound changes that occur during the manufacture of dry-cured foal loin were studied. Hardness and chewiness increased significantly (P<0.001) from 1.67 kg and 0.48 kg ? mm to 18.33 kg and 5.01 kg?mm, respectively during ripening process. The total average content of free fatty acid increased significantly (P<0.001), from 768.8 mg/100g of fat in the loins immediately after the seasoning period to 1271.1mg/100g of fat at the end of the drying-ripening period. In the final product, aldehydes became the dominant volatile compounds. PMID:25280362

  16. Characterizing the Smell of Marijuana by Odor Impact of Volatile Compounds: An Application of Simultaneous Chemical and Sensory Analysis

    PubMed Central

    2015-01-01

    Recent US legislation permitting recreational use of marijuana in certain states brings the use of marijuana odor as probable cause for search and seizure to the forefront of forensic science, once again. This study showed the use of solid-phase microextraction with multidimensional gas chromatography—mass spectrometry and simultaneous human olfaction to characterize the total aroma of marijuana. The application of odor activity analysis offers an explanation as to why high volatile chemical concentration does not equate to most potent odor impact of a certain compound. This suggests that more attention should be focused on highly odorous compounds typically present in low concentrations, such as nonanal, decanol, o-cymene, benzaldehyde, which have more potent odor impact than previously reported marijuana headspace volatiles. PMID:26657499

  17. An in vivo chemical genetic screen identifies phosphodiesterase 4 as a pharmacological target for hedgehog signaling inhibition.

    PubMed

    Williams, Charles H; Hempel, Jonathan E; Hao, Jijun; Frist, Audrey Y; Williams, Michelle M; Fleming, Jonathan T; Sulikowski, Gary A; Cooper, Michael K; Chiang, Chin; Hong, Charles C

    2015-04-01

    Hedgehog (Hh) signaling plays an integral role in vertebrate development, and its dysregulation has been accepted widely as a driver of numerous malignancies. While a variety of small molecules target Smoothened (Smo) as a strategy for Hh inhibition, Smo gain-of-function mutations have limited their clinical implementation. Modulation of targets downstream of Smo could define a paradigm for treatment of Hh-dependent cancers. Here, we describe eggmanone, a small molecule identified from a chemical genetic zebrafish screen, which induced an Hh-null phenotype. Eggmanone exerts its Hh-inhibitory effects through selective antagonism of phosphodiesterase 4 (PDE4), leading to protein kinase A activation and subsequent Hh blockade. Our study implicates PDE4 as a target for Hh inhibition, suggests an improved strategy for Hh-dependent cancer therapy, and identifies a unique probe of downstream-of-Smo Hh modulation. PMID:25818300

  18. Stimulation of Ideas through Compound-Based Bibliometrics: Counting and Mapping Chemical Compounds for Analyzing Research Topics in Chemistry, Physics, and Materials Science

    PubMed Central

    Barth, Andreas; Marx, Werner

    2012-01-01

    Counting compounds (rather than papers or citations) offers a new perspective for quantitative analyses of research activities. First of all, we can precisely define (compound-related) research topics and access the corresponding publications (scientific papers as well as patents) as a measure of research activity. We can also establish the time evolution of the publications dealing with specific compounds or compound classes. Moreover, the mapping of compounds by establishing compound-based landscapes has some potential to visualize the compound basis of research topics for further research activities. We have analyzed the rare earth compounds to give an example of a broad compound class. We present the number of the currently existing compounds and of the corresponding publications as well as the time evolution of the papers and patents. Furthermore, we have analyzed the rare earth cuprates (copper oxides) as an example of a narrower compound class to demonstrate the potential of mapping compounds by compound-based landscapes. We have quantified the various element combinations of the existing compounds and revealed all element combinations not yet realized in the synthesis within this compound class. Finally, we have analyzed the quasicrystal compound category as an example of a compound class that is not defined by a specific element combination or a molecular structure. PMID:24551517

  19. Analysis of gaseous toxic industrial compounds and chemical warfare agent simulants by atmospheric pressure ionization mass spectrometry.

    PubMed

    Cotte-Rodrguez, Ismael; Justes, Dina R; Nanita, Sergio C; Noll, Robert J; Mulligan, Christopher C; Sanders, Nathaniel L; Cooks, R Graham

    2006-04-01

    The suitability of atmospheric pressure chemical ionization mass spectrometry as sensing instrumentation for the real-time monitoring of low levels of toxic compounds is assessed, especially with respect to public safety applications. Gaseous samples of nine toxic industrial compounds, NH3, H2S, Cl2, CS2, SO2, C2H4O, HBr, C6H6 and AsH3, and two chemical warfare agent simulants, dimethyl methylphosphonate (DMMP) and methyl salicylate (MeS), were studied. API-MS proves highly suited to this application, with speedy analysis times (<30 seconds), high sensitivity, high selectivity towards analytes, good precision, dynamic range and accuracy. Tandem MS methods were implemented in selected cases for improved selectivity, sensitivity, and limits of detection. Limits of detection in the parts-per-billion and parts-per-trillion range were achieved for this set of analytes. In all cases detection limits were well below the compounds' permissible exposure limits (PELs), even in the presence of added complex mixtures of alkanes. Linear responses, up to several orders of magnitude, were obtained over the concentration ranges studied (sub-ppb to ppm), with relative standard deviations less than 3%, regardless of the presence of alkane interferents. Receiver operating characteristic (ROC) curves are presented to show the performance trade-off between sensitivity, probability of correct detection, and false positive rate. A dynamic sample preparation system for the production of gas phase analyte concentrations ranging from 100 pptr to 100 ppm and capable of admixing gaseous matrix compounds and control of relative humidity and temperature is also described. PMID:16568176

  20. Production of Monomeric Aromatic Compounds from Oil Palm Empty Fruit Bunch Fiber Lignin by Chemical and Enzymatic Methods.

    PubMed

    Tang, Pei-Ling; Hassan, Osman; Maskat, Mohamad Yusof; Badri, Khairiah

    2015-01-01

    In this study, oil palm empty fruit bunch (OPEFBF) was pretreated with alkali, and lignin was extracted for further degradation into lower molecular weight phenolic compounds using enzymes and chemical means. Efficiency of monomeric aromatic compounds production from OPEFBF lignin via chemical (nitrobenzene versus oxygen) and enzymatic [cutinase versus manganese peroxidase (MnP)] approaches was investigated. The effects of sodium hydroxide concentration (2, 5, and 10%?wt.) and reaction time (30, 90, and 180 minutes) on the yield of aromatic compounds were studied. The results obtained indicated that nitrobenzene oxidation produced the highest yield (333.17 49.44?ppm hydroxybenzoic acid, 5.67 0.25?ppm p-hydroxybenzaldehyde, 25.57 1.64?ppm vanillic acid, 168.68 23.23?ppm vanillin, 75.44 6.71?ppm syringic acid, 815.26 41.77?ppm syringaldehyde, 15.21 2.19?ppm p-coumaric acid, and 44.75 3.40?ppm ferulic acid), among the tested methods. High sodium hydroxide concentration (10%?wt.) was needed to promote efficient nitrobenzene oxidation. However, less severe oxidation condition was preferred to preserve the hydroxycinnamic acids (p-coumaric acid and ferulic acid). Cutinase-catalyzed hydrolysis was found to be more efficient than MnP-catalyzed oxidation in the production of aromatic compounds. By hydrolyzed 8%?wt. of lignin with 0.625?mL cutinase g(-1) lignin at pH 8 and 55C for 24 hours, about 642.83 14.45?ppm hydroxybenzoic acid, 70.19 3.31?ppm syringaldehyde, 22.80 1.04?ppm vanillin, 27.06 1.20?ppm p-coumaric acid, and 50.19 2.23?ppm ferulic acid were produced. PMID:26798644

  1. Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions.

    PubMed

    Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A; Decker, William; Manjili, Masoud H; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A Ivana; Raju, Jayadev; Hamid, Roslida A; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K; Ryan, Elizabeth P; Brown, Dustin G; Bisson, William H; Lowe, Leroy; Lyerly, H Kim

    2015-06-01

    An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-?, FAK, IGF-1, HIF-1?, IL-6, IL-1?, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. PMID:26002081

  2. Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa.

    PubMed

    de Mello Schier, Alexandre R; de Oliveira Ribeiro, Natalia P; Coutinho, Danielle S; Machado, Sergio; Arias-Carrin, Oscar; Crippa, Jose A; Zuardi, Antonio W; Nardi, Antonio E; Silva, Adriana C

    2014-01-01

    Anxiety and depression are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a constituent non-psychotomimetic of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The aim of this study is to review studies of animal models using CBD as an anxiolytic-like and antidepressant-like compound. Studies involving animal models, performing a variety of experiments on the above-mentioned disorders, such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel conflict test (VCT), suggest that CBD exhibited an anti-anxiety and antidepressant effects in animal models discussed. Experiments with CBD demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor. PMID:24923339

  3. Beyond DP4: an Improved Probability for the Stereochemical Assignment of Isomeric Compounds using Quantum Chemical Calculations of NMR Shifts.

    PubMed

    Grimblat, Nicols; Zanardi, Mara M; Sarotti, Ariel M

    2015-12-18

    The DP4 probability is one of the most sophisticated and popular approaches for the stereochemical assignment of organic molecules using GIAO NMR chemical shift calculations when only one set of experimental data is available. In order to improve the performance of the method, we have developed a modified probability (DP4+), whose main differences from the original DP4 are the inclusion of unscaled data and the use of higher levels of theory for the NMR calculation procedure. With these modifications, a significant improvement in the overall performance was achieved, providing accurate and confident results in establishing the stereochemistry of 48 challenging isomeric compounds. PMID:26580165

  4. Scalar relativistic correction to nucleus-independent chemical shifts of coinage-metal compounds: How does the pseudopotential approximation perform?

    NASA Astrophysics Data System (ADS)

    Corminboeuf, Clmence

    2006-02-01

    The performance of commonly used pseudopotentials for calculations of nucleus-independent chemical shifts (NICS) at the center of coinage-metal rings (M 4Li 2 (D 4h), M = Cu, Ag, Au) is investigated. The scalar relativity, which has a non-negligible effect on NICS, is found to be accurately described by the pseudopotential approximation. Overall, good agreement is obtained with all-electron relativistic methods, however, careful comparisons with these calculations and consideration for large triple- ? basis sets are recommended when aiming to accurately define the relative degree of diatropicity among a series of compounds.

  5. Chemical oxidation of volatile and semi-volatile organic compounds in soil

    SciTech Connect

    Gates, D.D.; Siegrist, R.L.; Cline, S.R.

    1995-06-01

    Subsurface contamination with fuel hydrocarbons or chlorinated hydrocarbons is prevalent throughout the Department of Energy (DOE) complex and in many sites managed by the Environmental Protection Agency (EPA) Superfund program. The most commonly reported chlorinated hydrocarbons (occurring > 50% of DOE contaminated sites) were trichloroethylene (TCE), 1, 1, 1,-trichloroethane (TCA), and tetrachloroethylene (PCE) with concentrations in the range of 0.2 {mu}g/kg to 12,000 mg/kg. The fuel hydrocarbons most frequently reported as being present at DOE sites include aromatic compounds and polyaromatic compounds such as phenanthrene, pyrene, and naphthalene. The primary sources of these semi-volatile organic compounds (SVOCs) are coal waste from coal fired electric power plants used at many of these facilities in the past and gasoline spills and leaks. Dense non-aqueous phase liquids (DNAPLs) can migrate within the subsurface for long periods of time along a variety of pathways including fractures, macropores, and micropores. Diffusion of contaminants in the non-aqueous, aqueous, and vapor phase can occur from the fractures and macropores into the matrix of fine-textured media. As a result of these contamination processes, removal of contaminants from the subsurface and the delivery of treatment agents into and throughout contaminated regions are often hindered, making rapid and extensive remediation difficult.

  6. Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound.

    PubMed

    Sekine, Yusuke; Zyryanova, Alisa; Crespillo-Casado, Ana; Fischer, Peter M; Harding, Heather P; Ron, David

    2015-05-29

    The integrated stress response (ISR) modulates messenger RNA translation to regulate the mammalian unfolded protein response (UPR), immunity, and memory formation. A chemical ISR inhibitor, ISRIB, enhances cognitive function and modulates the UPR in vivo. To explore mechanisms involved in ISRIB action, we screened cultured mammalian cells for somatic mutations that reversed its effect on the ISR. Clustered missense mutations were found at the amino-terminal portion of the delta subunit of guanine nucleotide exchange factor (GEF) eIF2B. When reintroduced by CRISPR-Cas9 gene editing of wild-type cells, these mutations reversed both ISRIB-mediated inhibition of the ISR and its stimulatory effect on eIF2B GEF activity toward its substrate, the translation initiation factor eIF2, in vitro. Thus, ISRIB targets an interaction between eIF2 and eIF2B that lies at the core of the ISR. PMID:25858979

  7. Quantitative chemical proteomics identifies novel targets of the anti-cancer multi-kinase inhibitor E-3810.

    PubMed

    Colzani, Mara; Noberini, Roberta; Romanenghi, Mauro; Colella, Gennaro; Pasi, Maurizio; Fancelli, Daniele; Varasi, Mario; Minucci, Saverio; Bonaldi, Tiziana

    2014-06-01

    Novel drugs are designed against specific molecular targets, but almost unavoidably they bind non-targets, which can cause additional biological effects that may result in increased activity or, more frequently, undesired toxicity. Chemical proteomics is an ideal approach for the systematic identification of drug targets and off-targets, allowing unbiased screening of candidate interactors in their natural context (tissue or cell extracts). E-3810 is a novel multi-kinase inhibitor currently in clinical trials for its anti-angiogenic and anti-tumor activity. In biochemical assays, E-3810 targets primarily vascular endothelial growth factor and fibroblast growth factor receptors. Interestingly, E-3810 appears to inhibit the growth of tumor cells with low to undetectable levels of these proteins in vitro, suggesting that additional relevant targets exist. We applied chemical proteomics to screen for E-3810 targets by immobilizing the drug on a resin and exploiting stable isotope labeling by amino acids in cell culture to design experiments that allowed the detection of novel interactors and the quantification of their dissociation constant (Kd imm) for the immobilized drug. In addition to the known target FGFR2 and PDGFR?, which has been described as a secondary E-3810 target based on in vitro assays, we identified six novel candidate kinase targets (DDR2, YES, LYN, CARDIAK, EPHA2, and CSBP). These kinases were validated in a biochemical assay and-in the case of the cell-surface receptor DDR2, for which activating mutations have been recently discovered in lung cancer-cellular assays. Taken together, the success of our strategy-which integrates large-scale target identification and quality-controlled target affinity measurements using quantitative mass spectrometry-in identifying novel E-3810 targets further supports the use of chemical proteomics to dissect the mechanism of action of novel drugs. PMID:24696502

  8. Quantitative Chemical Proteomics Identifies Novel Targets of the Anti-cancer Multi-kinase Inhibitor E-3810*

    PubMed Central

    Colzani, Mara; Noberini, Roberta; Romanenghi, Mauro; Colella, Gennaro; Pasi, Maurizio; Fancelli, Daniele; Varasi, Mario; Minucci, Saverio; Bonaldi, Tiziana

    2014-01-01

    Novel drugs are designed against specific molecular targets, but almost unavoidably they bind non-targets, which can cause additional biological effects that may result in increased activity or, more frequently, undesired toxicity. Chemical proteomics is an ideal approach for the systematic identification of drug targets and off-targets, allowing unbiased screening of candidate interactors in their natural context (tissue or cell extracts). E-3810 is a novel multi-kinase inhibitor currently in clinical trials for its anti-angiogenic and anti-tumor activity. In biochemical assays, E-3810 targets primarily vascular endothelial growth factor and fibroblast growth factor receptors. Interestingly, E-3810 appears to inhibit the growth of tumor cells with low to undetectable levels of these proteins in vitro, suggesting that additional relevant targets exist. We applied chemical proteomics to screen for E-3810 targets by immobilizing the drug on a resin and exploiting stable isotope labeling by amino acids in cell culture to design experiments that allowed the detection of novel interactors and the quantification of their dissociation constant (Kd imm) for the immobilized drug. In addition to the known target FGFR2 and PDGFR?, which has been described as a secondary E-3810 target based on in vitro assays, we identified six novel candidate kinase targets (DDR2, YES, LYN, CARDIAK, EPHA2, and CSBP). These kinases were validated in a biochemical assay andin the case of the cell-surface receptor DDR2, for which activating mutations have been recently discovered in lung cancercellular assays. Taken together, the success of our strategywhich integrates large-scale target identification and quality-controlled target affinity measurements using quantitative mass spectrometryin identifying novel E-3810 targets further supports the use of chemical proteomics to dissect the mechanism of action of novel drugs. PMID:24696502

  9. Biomarker responses and chemical analyses in fish indicate leakage of polycyclic aromatic hydrocarbons and other compounds from car tire rubber.

    PubMed

    Stephensen, Eirkur; Adolfsson-Erici, Margaretha; Celander, Malin; Hulander, Mats; Parkkonen, Jari; Hegelund, Tove; Sturve, Joachim; Hasselberg, Linda; Bengtsson, Madeleine; Frlin, Lars

    2003-12-01

    Rubber tire material contains toxic compounds including oils rich in polycyclic aromatic hydrocarbons (PAH), so-called highly aromatic (HA) oils, as well as other reactive additives used as antioxidants, antiozonants, and vulcanization accelerators. The toxicity of rubber tire leachates to aquatic organisms has been demonstrated before. However, previous studies have focused on lethal rather than sublethal effects. We kept rainbow trout (Oncorhynchus mykiss) in tanks with two types of tires: a tire containing HA oils in the tread or a tire free of HA oils in the tread. After 1 d of exposure, an induction of cytochrome P4501A1 (CYP1A1) was evident in both exposed groups, measured as elevated ethoxyresorufin-O-deethylase (EROD) activity and increased CYP1A1 mRNA levels. After two weeks of exposure, EROD activity and CYP1A1 mRNA were still high in fish exposed to leachate from HA oil-containing tire, whereas the effect was somewhat lower in fish exposed to leachate from HA oil-free tread tire. Compounds in the tire leachates also affected antioxidant parameters. Total glutathione concentration in liver as well as hepatic glutathione reductase, glutathione S-transferase, and glucose-6-phosphate dehydrogenase activities were markedly elevated after two weeks of exposure in both groups. The responses were greater in the group exposed to leachate from HA oil-free tread tire. Vitellogenin measurements did not indicate leakage of estrogenic compounds from the tires. Chemical analyses of bile from exposed fish revealed the presence of hydroxylated PAH as well as aromatic nitrogen compounds indicating uptake of these compounds by the fish. PMID:14713032

  10. Evaluation of performance reference compounds (PRCs) to monitor emerging polar contaminants by polar organic chemical integrative samplers (POCIS) in rivers.

    PubMed

    Carpinteiro, Inmaculada; Schopfer, Adrien; Estoppey, Nicolas; Fong, Camille; Grandjean, Dominique; de Alencastro, Luiz F

    2016-02-01

    In this work, a method combining polar organic chemical integrative samplers (POCIS) and ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was assessed for the determination of two corrosion inhibitors (benzotriazole and methylbenzotriazole), seven pesticides (atrazine, diuron, isoproturon, linuron, metolachlor, penconazole, terbuthylazine), and four pharmaceuticals (carbamazepine, diclofenac, metformin, sulfamethoxazole) in river water. As a first step, two POCIS sorbents, hydrophilic-lipophilic balance (HLB) and Strata X-CW, were compared. The comparison of the uptake profiles of the studied compounds showed that the HLB sorbent provides better uptake (higher sampled amount and better linearity) than Strata X-CW except for the basic compound metformin. Since the sampling rate (R s) of POCIS depends on environmental factors, seven compounds were evaluated as potential performance reference compounds (PRCs) through kinetic experiments. Deisopropylatrazine-d5 (DIA-d5) and, as far as we know, for the first time 4-methylbenzotriazole-d3 showed suitable desorption. The efficiency of both compounds to correct for the effect of water velocity was shown using a channel system in which POCIS were exposed to 2 and 50 cm s(-1). Finally, POCIS were deployed upstream and downstream of agricultural wine-growing and tree-growing areas in the Lienne River and the Uvrier Canal (Switzerland). The impact of the studied areas on both streams could be demonstrated. Graphical Abstract Photos of POCIS in the channel system (left, top), a POCIS in the cage (left, middle) and in the channel (left, bottom) and desorption kinetics (right, top) of PRCs (DIA-d5 and 4-methylbenzotriazol-d3) and estimated concentrations for methylbenzotriazol in the real river using DIA-d5 or 4-methylbenzotriazold3 as PRC (right, bottom). PMID:26637214

  11. Predicting physical properties of emerging compounds with limited physical and chemical data: QSAR model uncertainty and applicability to military munitions.

    PubMed

    Bennett, Erin R; Clausen, Jay; Linkov, Eugene; Linkov, Igor

    2009-11-01

    Reliable, up-front information on physical and biological properties of emerging materials is essential before making a decision and investment to formulate, synthesize, scale-up, test, and manufacture a new material for use in both military and civilian applications. Multiple quantitative structure-activity relationships (QSARs) software tools are available for predicting a material's physical/chemical properties and environmental effects. Even though information on emerging materials is often limited, QSAR software output is treated without sufficient uncertainty analysis. We hypothesize that uncertainty and variability in material properties and uncertainty in model prediction can be too large to provide meaningful results. To test this hypothesis, we predicted octanol water partitioning coefficients (logP) for multiple, similar compounds with limited physical-chemical properties using six different commercial logP calculators (KOWWIN, MarvinSketch, ACD/Labs, ALogP, CLogP, SPARC). Analysis was done for materials with largely uncertain properties that were similar, based on molecular formula, to military compounds (RDX, BTTN, TNT) and pharmaceuticals (Carbamazepine, Gemfibrizol). We have also compared QSAR modeling results for a well-studied pesticide and pesticide breakdown product (Atrazine, DDE). Our analysis shows variability due to structural variations of the emerging chemicals may be several orders of magnitude. The model uncertainty across six software packages was very high (10 orders of magnitude) for emerging materials while it was low for traditional chemicals (e.g. Atrazine). Thus the use of QSAR models for emerging materials screening requires extensive model validation and coupling QSAR output with available empirical data and other relevant information. PMID:19793608

  12. Chemical characterization and mutagenic properties of polycyclic aromatic compounds in sediment from tributaries of the Great Lakes

    USGS Publications Warehouse

    Fabacher, David L.; Schmitt, Christopher J.; Besser, John M.; Mac, Michael J.

    1988-01-01

    Sediments from four inshore industrial sites and a reference site in the Great Lakes were extracted with solvents and characterized chemically for polycyclic aromatic compounds (PACs). An aqueous phase and a crude organic extract were obtained. The crude organic extract was further resolved into fractions A-2 (polycyclic aromatic hydrocarbons) and A-3 (nitrogen-containing polycyclic aromatic compounds), which were analyzed for PACs by gas chromatography and gas chromatography-mass spectrometry. The extracts and fractions were tested for mutagenicity in three assays: Ames, rat hepatocyte unscheduled DNA synthesis, and Chinese hamster ovary hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT). Sediments from the industrial sites contained 27 to 363 μg/g total PACs; the reference site, less than 1 μg/g. Qualitative differences in the residue profiles among the sites were attributable to the probable sources of the PACs (petroleum versus combustion). Only one industrial site yielded measurable (0.1 μg/g or more) concentrations of individual nitrogen-containing PACs. In the Ames assay, only the highest doses of the A-2 fractions from two sites approached positive results. Conversely, the crude organic extract and A-2 and A-3 fractions from all sites induced unscheduled DNA synthesis. Crude organic extracts and the A-2 and A-3 fractions from all industrial sites gave well-defined dose-response relations in the CHO/HGPRT assay. We established the presence of chemical mutagens in sediment that could be correlated with neoplasms in fish from many of the sites; however, the mutagenicity of the sediment extracts was not completely related to the degree of contamination by PACs. We also discuss the utility of mutagenicity assays in the evaluation of complex chemical mixtures and recommend the use of a CHO/HGPRT-type assay in which cells are not required to proliferate in the presence of potential interfering chemicals.

  13. Comment on the reference compound for chemical shift and Knight shift determination of (209)Bi nuclei.

    PubMed

    Nowak, Bogdan

    2015-01-01

    Several groups exploring the (209)Bi NMR in solids, including usual insulators, metallic and magnetic materials and recently diamagnetic topological materials, use different standards (usually old and invalid) for chemical shift (Knight shift) determination, ignoring IUPAC recommendations. As a consequence the published shift values exhibit considerable differences (up to 17,500 ppm). PMID:25534279

  14. Pharmacophore modeling and molecular dynamics simulation to identify the critical chemical features against human sirtuin 2 inhibitors

    NASA Astrophysics Data System (ADS)

    Sakkiah, Sugunadevi; Baek, Ayoung; Lee, Keun Woo

    2012-03-01

    Sirtuin 2 (SIRT2) is one of the emerging targets in chemotherapy field and mainly associated with many diseases such as cancer and Parkinson's. Hence, quantitative hypothesis was developed using Discovery Studio v2.5. Top ten resultant hypotheses were generated, among them Hypo1 was selected as a best hypothesis based on the statistical parameters like high cost difference (52), lowest RMS (0.71), and good correlation coefficient (0.96). Hypo1 has been validated by using well known methodologies such as Fischer's randomization method (95% confidence level), test set which has shown the correlation coefficient of 0.93 as well as the goodness of hit (0.65), and enrichment factor (8.80). All the above statistical validations confirm that the chemical features in Hypo1 (1 hydrogen bond acceptor, 1 hydrophobic, and 2 ring aromatic features) was able to inhibit the function of SIRT2. Hence, Hypo1 was used as a query in virtual screening to find a novel scaffolds by screening the various chemical databases. The screened molecules from the databases were checked for the ADMET as well as the drug-like properties. Due to the lack of SIRT2-ligand complex structure in PDB, molecular docking and molecular dynamics (MD) simulation was carried out to find the suitable orientation of ligand in the active site. The representative structure from MD simulations was used as a receptor to dock the molecules which passed the drug-like properties from the virtual screening. Finally, 29 compounds were selected as a potent candidate leads based on the interactions with the active site residues of SIRT2. Thus, the resultant pharmacophore can be used to discover and design the SIRT2 inhibitors with desired biological activity.

  15. Isolation of an unknown compound, from both blood of Bhopal aerosol disaster victims and residue of tank E-610 of Union Carbide India Limited--chemical characterization of the structure.

    PubMed

    Chandra, H; Saraf, A K; Jadhav, R K; Rao, G J; Sharma, V K; Sriramachari, S; Vairamani, M

    1994-04-01

    A total of more than 28 chemical entities/reaction products in the form of gases, vapour and particulate matter were reported from the tank E-610 of methyl isocyanate (MIC) storage tank of Union Carbide India Limited on the night of 2/3 December 1984 in Bhopal. In earlier studies, methyl isocyanate and its trimer, with a few other compounds, were reported in the human victims preserved in deep freeze. Randomly selected samples were analysed by gas chromatograph coupled with mass spectrometer (ITD-800, Finnigan MAT, UK). Four of the cases showed the peaks and fragmentation pattern identified with one of the unidentified compound of molecular weight 269 amu in the Tank Residue, which constituted about 0.2 area per cent on GC-ITD. After isolation by column chromatography and being exposed to characterization, it was identified as a Spiro compound. It was possibly formed by the polymerization of five molecules of methyl isocyanate. PMID:8054074

  16. Correlations between chemical reactivity and mutagenic activity against S. typhimurium TA100 for alpha-dicarbonyl compounds as a proof of the mutagenic mechanism.

    PubMed

    Rodrguez Mellado, J M; Ruiz Montoya, M

    1994-01-16

    The mutagenic activities in the Ames test against S. typhimurium TA100 for a series of alpha-dicarbonyl compounds are examined together with the formation constants of the adducts formed between such compounds and guanine and guanosine. Correlations between the equilibrium constants, the apparent reaction enthalpies, and the mutagenic activity are presented. These correlations imply that the mutagenic activity is related to the chemical reactivity of the dicarbonyl compounds with the puric bases. PMID:7506369

  17. A High-content screen identifies compounds promoting the neuronal differentiation and the midbrain dopamine neuron specification of human neural progenitor cells

    PubMed Central

    Rhim, Ji heon; Luo, Xiangjian; Xu, Xiaoyun; Gao, Dongbing; Zhou, Tieling; Li, Fuhai; Qin, Lidong; Wang, Ping; Xia, Xiaofeng; Wong, Stephen T. C.

    2015-01-01

    Small molecule compounds promoting the neuronal differentiation of stem/progenitor cells are of pivotal importance to regenerative medicine. We carried out a high-content screen to systematically characterize known bioactive compounds, on their effects on the neuronal differentiation and the midbrain dopamine (mDA) neuron specification of neural progenitor cells (NPCs) derived from the ventral mesencephalon of human fetal brain. Among the promoting compounds three major pharmacological classes were identified including the statins, TGF-βRI inhibitors, and GSK-3 inhibitors. The function of each class was also shown to be distinct, either to promote both the neuronal differentiation and mDA neuron specification, or selectively the latter, or promote the former but suppress the latter. We then carried out initial investigation on the possible mechanisms underlying, and demonstrated their applications on NPCs derived from human pluripotent stem cells (PSCs). Our study revealed the potential of several small molecule compounds for use in the directed differentiation of human NPCs. The screening result also provided insight into the signaling network regulating the differentiation of human NPCs. PMID:26542303

  18. 40 CFR 721.9668 - Organotin lithium compound.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Organotin lithium compound. 721.9668... Substances § 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN...

  19. 40 CFR 721.9668 - Organotin lithium compound.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Organotin lithium compound. 721.9668... Substances § 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN...

  20. 40 CFR 721.9668 - Organotin lithium compound.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Organotin lithium compound. 721.9668... Substances 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN...

  1. 40 CFR 721.9668 - Organotin lithium compound.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Organotin lithium compound. 721.9668... Substances 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN...

  2. 40 CFR 721.9668 - Organotin lithium compound.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Organotin lithium compound. 721.9668... Substances 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN...

  3. Identifying vacancy complexes in compound semiconductors with positron annihilation spectroscopy: A case study of InN

    NASA Astrophysics Data System (ADS)

    Rauch, Christian; Makkonen, Ilja; Tuomisto, Filip

    2011-09-01

    We present a comprehensive study of vacancy and vacancy-impurity complexes in InN combining positron annihilation spectroscopy and ab initio calculations. Positron densities and annihilation characteristics of common vacancy-type defects are calculated using density functional theory, and the feasibility of their experimental detection and distinction with positron annihilation methods is discussed. The computational results are compared to positron lifetime and conventional as well as coincidence Doppler broadening measurements of several representative InN samples. The particular dominant vacancy-type positron traps are identified and their characteristic positron lifetimes, Doppler ratio curves, and line-shape parameters determined. We find that indium vacancies (VIn) and their complexes with nitrogen vacancies (VN) or impurities act as efficient positron traps, inducing distinct changes in the annihilation parameters compared to the InN lattice. Neutral or positively charged VN and pure VN complexes, on the other hand, do not trap positrons. The predominantly introduced positron trap in irradiated InN is identified as the isolated VIn, while in as-grown InN layers VIn do not occur isolated but complexed with one or more VN. The number of VN per VIn in these complexes is found to increase from the near-surface region toward the layer-substrate interface.

  4. Attomole detection of isotope-labeled compounds in chemical defense research

    SciTech Connect

    Vogel, J.S.; Buchholz, B.A.; Pawley, N.H.; Mauthe, R.E.; Dingley, K.; Turteltaub, K.

    1996-11-01

    AMS detects 14C at zeptomole to femtomole sensitivities. We detected the effect of ChE-blocking pyridostigmine bromide on the CNS uptake of a pyrethroid insecticide at scaled human-equivalent exposures in rats. Significant blood to brain protection from permethrin dosed at 5mg/kg is seen in the CNS of rats receiving pyridostigmine bromide pretreatments in chow at 2mg/kg/day. The synergy of these compounds was suggested as a precursor to some symptoms of `Gulf War Syndrome`.

  5. A non-archimedean theory of interaction of chemical compounds with membranes.

    PubMed

    Iordache, O; Isopescu, R; Isopescu, A; Frangopol, P T

    1990-01-01

    The permeability of procaine across axon membranes and the effect of formaldehyde (FA), crotonic aldehyde (CA) and glutaraldehyde (GA) on the compound action potential of frog sciatic nerve was studied by utilizing a non-archimedean (NA) model of the relaxation process. Such models allow a characterization of biosystems exhibiting more than one time scale. Expansions using Laguerre polynomials have been obtained for relaxation functions. The new approach is tested by fitting the model to the experimental data of other authors, and then applying to extract molecular level information from macroscopic data. PMID:2123408

  6. Screening Compounds with a Novel High-Throughput ABCB1-Mediated Efflux Assay Identifies Drugs with Known Therapeutic Targets at Risk for Multidrug Resistance Interference

    PubMed Central

    Ansbro, Megan R.; Shukla, Suneet; Ambudkar, Suresh V.; Yuspa, Stuart H.; Li, Luowei

    2013-01-01

    ABCB1, also known as P-glycoprotein (P-gp) or multidrug resistance protein 1 (MDR1), is a membrane-associated multidrug transporter of the ATP-binding cassette (ABC) transporter family. It is one of the most widely studied transporters that enable cancer cells to develop drug resistance. Reliable high-throughput assays that can identify compounds that interact with ABCB1 are crucial for developing new therapeutic drugs. A high-throughput assay for measuring ABCB1-mediated calcein AM efflux was developed using a fluorescent and phase-contrast live cell imaging system. This assay demonstrated the time- and dose-dependent accumulation of fluorescent calcein in ABCB1-overexpressing KB-V1 cells. Validation of the assay was performed with known ABCB1 inhibitors, XR9576, verapamil, and cyclosporin A, all of which displayed dose-dependent inhibition of ABCB1-mediated calcein AM efflux in this assay. Phase-contrast and fluorescent images taken by the imaging system provided additional opportunities for evaluating compounds that are cytotoxic or produce false positive signals. Compounds with known therapeutic targets and a kinase inhibitor library were screened. The assay identified multiple agents as inhibitors of ABCB1-mediated efflux and is highly reproducible. Among compounds identified as ABCB1 inhibitors, BEZ235, BI 2536, IKK 16, and ispinesib were further evaluated. The four compounds inhibited calcein AM efflux in a dose-dependent manner and were also active in the flow cytometry-based calcein AM efflux assay. BEZ235, BI 2536, and IKK 16 also successfully inhibited the labeling of ABCB1 with radiolabeled photoaffinity substrate [125I]iodoarylazidoprazosin. Inhibition of ABCB1 with XR9576 and cyclosporin A enhanced the cytotoxicity of BI 2536 to ABCB1-overexpressing cancer cells, HCT-15-Pgp, and decreased the IC50 value of BI 2536 by several orders of magnitude. This efficient, reliable, and simple high-throughput assay has identified ABCB1 substrates/inhibitors that may influence drug potency or drug-drug interactions and predict multidrug resistance in clinical treatment. PMID:23593196

  7. Effect of ultrasound-assisted freezing on the physico-chemical properties and volatile compounds of red radish.

    PubMed

    Xu, Bao-guo; Zhang, Min; Bhandari, Bhesh; Cheng, Xin-feng; Islam, Md Nahidul

    2015-11-01

    Power ultrasound, which can enhance nucleation rate and crystal growth rate, can also affect the physico-chemical properties of immersion frozen products. In this study, the influence of slow freezing (SF), immersion freezing (IF) and ultrasound-assisted freezing (UAF) on physico-chemical properties and volatile compounds of red radish was investigated. Results showed that ultrasound application significantly improved the freezing rate; the freezing time of ultrasound application at 0.26 W/cm(2) was shorten by 14% and 90%, compared to IF and SF, respectively. UAF products showed significant (p<0.05) reduction in drip loss and phytonutrients (anthocyanins, vitamin C and phenolics) loss. Compared to SF products, IF and UAF products showed better textural preservation and higher calcium content. The radish tissues exhibited better cellular structures under ultrasonic power intensities of 0.17 and 0.26 W/cm(2) with less cell separation and disruption. Volatile compound data revealed that radish aromatic profile was also affected in the freezing process. PMID:26186850

  8. Development of the performance reference compound approach for the calibration of "polar organic chemical integrative sampler" (POCIS).

    PubMed

    Belles, Angel; Tapie, Nathalie; Pardon, Patrick; Budzinski, Hlne

    2014-02-01

    The purpose of the Water Framework Directive is to ensure the quality of the natural water across Europe. In this context, passive samplers have shown interesting capacities for the monitoring of contaminants in aqueous ecosystems. They allow the measurement of time-weighted average concentrations, overcoming many drawbacks of the spot-sampling techniques known to be expensive and time consuming. However, application of passive samplers such as polar organic chemical integrative samplers (POCIS) for the monitoring of hydrophilic contaminants requires calibration to define compound sampling rates; key parameters to deduce the pollutant water concentrations from the amounts of pollutants accumulated by the device. Unfortunately, sampling rates are influenced by a range of environmental factors; in that respect, a question remains: is it not evident to know to what extent the sampling rates obtained in laboratory experiments can be used in field conditions? The problem can be solved for hydrophobic samplers by using performance reference compounds (PRCs), and an ongoing challenge for POCIS is focused on the improvement of the quantitative aspect of this family of samplers. In this study, potential PRCs have been selected during a specific experiment and their performance was tested in the laboratory under two hydrodynamic conditions. Results revealed a good proportionality between elimination rates of PRCs and sampling rates of chemicals. Afterwards, the application of the approach under environmental conditions was assessed by deploying POCIS in the Arcachon Bay (France) where POCIS-PRC-derived water concentrations appear to be close to the simultaneous grab-sampling results. PMID:23978936

  9. Direct Analysis of Nonvolatile Chemical Compounds on Surfaces Using a Hand-Held Mass Spectrometer with Synchronized Discharge Ionization Function.

    PubMed

    Wang, Xiao; Zhou, Xiaoyu; Ouyang, Zheng

    2016-01-01

    Synchronized discharge ionization (SDI) was previously developed for hand-held mass spectrometers with discontinuous atmospheric pressure interfaces. The function of SDI has been demonstrated for analysis of volatile organic compounds in air at high sensitivity, which is attributed to the fact that ions were produced next to the ion trap mass analyzer inside the vacuum manifold. In this study, a simple sampling device was designed and fitted to a hand-held mass spectrometer to characterize its potential in direct analysis of low-volatility chemicals on surfaces. Nine chemicals of vapor pressures ranging from 10(-4) to 10(-8) Torr (at room temperature), including pesticides, illicit drugs, and explosives, were selected to evaluate and demonstrate the analytical capability of the designed system. Compounds of vapor pressures below 10(-7) Torr, such as tetryl, cocaine, and tetrahydrocannabinol (THC), have been successfully detected. Direct analysis of pesticides from fruit and explosives from a large surface area has also been demonstrated. Tandem mass analysis was performed, which helped to confirm the analyte identity as well as to improve the signal-to-noise ratio (S/N). PMID:26618852

  10. [Experience in the use of chemical compounds for the primary identification and differentiation of enteroviruses].

    PubMed

    Amvros'eva, T V; Votiakov, V I; Andreeva, O T; Kazinets, O N; Bogush, Z F; Sharko, R M; Kvacheva, Z B

    2003-02-01

    Data on the usage of chemical inhibitors nifan and belvtazid, which possess a selective and antienteroviral effect, in the primary identification of enteroviruses and their differentiation into polio- and non-poliomyelytic ones isolated from human clinical materials or the environment by using the cell culture are presented in the article. The method is recommended for the practical use by the virology service in the diagnostics of enteroviral infections and in the identification of cytopathic agents isolated from the enviroment. PMID:12688219

  11. Novel chemical library screen identifies naturally occurring plant products that specifically disrupt glioblastoma-endothelial cell interactions

    PubMed Central

    Marasa, Jayne; Taylor, Sara; Jackson, Erin; Warrington, Nicole M.; Rao, Shyam; Kim, Albert H.; Leonard, Jeffrey R.; Piwnica-Worms, David; Rubin, Joshua B.

    2015-01-01

    Tumor growth is not solely a consequence of autonomous tumor cell properties. Rather, tumor cells act upon and are acted upon by their microenvironment. It is tumor tissue biology that ultimately determines tumor growth. Thus, we developed a compound library screen for agents that could block essential tumor-promoting effects of the glioblastoma (GBM) perivascular stem cell niche (PVN). We modeled the PVN with three-dimensional primary cultures of human brain microvascular endothelial cells in Matrigel. We previously demonstrated stimulated growth of GBM cells in this PVN model and used this to assay PVN function. We screened the Microsource Spectrum Collection library for drugs that specifically blocked PVN function, without any direct effect on GBM cells themselves. Three candidate PVN-disrupting agents, Iridin, Tigogenin and Triacetylresveratrol (TAR), were identified and evaluated in secondary in vitro screens against a panel of primary GBM isolates as well as in two different in vivo intracranial models. Iridin and TAR significantly inhibited intracranial tumor growth and prolonged survival in these mouse models. Together these data identify Iridin and TAR as drugs with novel GBM tissue disrupting effects and validate the importance of preclinical screens designed to address tumor tissue function rather than the mechanisms of autonomous tumor cell growth. PMID:26286961

  12. Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening.

    PubMed

    Orr, Adam L; Ashok, Deepthi; Sarantos, Melissa R; Shi, Tong; Hughes, Robert E; Brand, Martin D

    2013-12-01

    Mitochondrial production of reactive oxygen species is often considered an unavoidable consequence of aerobic metabolism and currently cannot be manipulated without perturbing oxidative phosphorylation. Antioxidants are widely used to suppress effects of reactive oxygen species after formation, but they can never fully prevent immediate effects at the sites of production. To identify site-selective inhibitors of mitochondrial superoxide/H2O2 production that do not interfere with mitochondrial energy metabolism, we developed a robust small-molecule screen and secondary profiling strategy. We describe the discovery and characterization of a compound (N-cyclohexyl-4-(4-nitrophenoxy)benzenesulfonamide; CN-POBS) that selectively inhibits superoxide/H2O2 production from the ubiquinone-binding site of complex I (site I(Q)) with no effects on superoxide/H2O2 production from other sites or on oxidative phosphorylation. Structure/activity studies identified a core structure that is important for potency and selectivity for site I(Q). By employing CN-POBS in mitochondria respiring on NADH-generating substrates, we show that site I(Q) does not produce significant amounts of superoxide/H2O2 during forward electron transport on glutamate plus malate. Our screening platform promises to facilitate further discovery of direct modulators of mitochondrially derived oxidative damage and advance our ability to understand and manipulate mitochondrial reactive oxygen species production under both normal and pathological conditions. PMID:23994103

  13. Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening

    PubMed Central

    Orr, Adam L.; Ashok, Deepthi; Sarantos, Melissa R.; Shi, Tong; Hughes, Robert E.; Brand, Martin D.

    2013-01-01

    Mitochondrial production of reactive oxygen species is often considered an unavoidable consequence of aerobic metabolism and currently cannot be manipulated without perturbing oxidative phosphorylation. Antioxidants are widely used to suppress effects of reactive oxygen species after formation, but they can never fully prevent immediate effects at the sites of production. To identify site-selective inhibitors of mitochondrial superoxide/H2O2 production that do not interfere with mitochondrial energy metabolism, we developed a robust small-molecule screen and secondary profiling strategy. We describe the discovery and characterization of a compound (N-cyclohexyl-4-(4-nitrophenoxy)benzenesulfonamide; CN-POBS) that selectively inhibits superoxide/H2O2 production from the ubiquinone-binding site of complex I (site IQ) with no effects on superoxide/H2O2 production from other sites or on oxidative phosphorylation. Structure/activity studies identified a core structure that is important for potency and selectivity for site IQ. By employing CN-POBS in mitochondria respiring on NADH-generating substrates, we show that site IQ does not produce significant amounts of superoxide/H2O2 during forward electron transport on glutamate plus malate. Our screening platform promises to facilitate further discovery of direct modulators of mitochondrially-derived oxidative damage and advance our ability to understand and manipulate mitochondrial reactive oxygen species production in both normal and pathological conditions. PMID:23994103

  14. Novel chemical library screen identifies naturally occurring plant products that specifically disrupt glioblastoma-endothelial cell interactions.

    PubMed

    Sengupta, Rajarshi; Barone, Amy; Marasa, Jayne; Taylor, Sara; Jackson, Erin; Warrington, Nicole M; Rao, Shyam; Kim, Albert H; Leonard, Jeffrey R; Piwnica-Worms, David; Rubin, Joshua B

    2015-07-30

    Tumor growth is not solely a consequence of autonomous tumor cell properties. Rather, tumor cells act upon and are acted upon by their microenvironment. It is tumor tissue biology that ultimately determines tumor growth. Thus, we developed a compound library screen for agents that could block essential tumor-promoting effects of the glioblastoma (GBM) perivascular stem cell niche (PVN). We modeled the PVN with three-dimensional primary cultures of human brain microvascular endothelial cells in Matrigel. We previously demonstrated stimulated growth of GBM cells in this PVN model and used this to assay PVN function. We screened the Microsource Spectrum Collection library for drugs that specifically blocked PVN function, without any direct effect on GBM cells themselves. Three candidate PVN-disrupting agents, Iridin, Tigogenin and Triacetylresveratrol (TAR), were identified and evaluated in secondary in vitro screens against a panel of primary GBM isolates as well as in two different in vivo intracranial models. Iridin and TAR significantly inhibited intracranial tumor growth and prolonged survival in these mouse models. Together these data identify Iridin and TAR as drugs with novel GBM tissue disrupting effects and validate the importance of preclinical screens designed to address tumor tissue function rather than the mechanisms of autonomous tumor cell growth. PMID:26286961

  15. A Bmp Reporter Transgene Mouse Embryonic Stem Cell Model as a Tool to Identify and Characterize Chemical Teratogens.

    PubMed

    Kugler, Josephine; Tharmann, Julian; Chuva de Sousa Lopes, Susana M; Kemler, Rolf; Luch, Andreas; Oelgeschlger, Michael

    2015-08-01

    Embryonic stem cells (ESCs) were first isolated from mouse embryos more than 30 years ago. They have proven invaluable not only in generating genetically modified mice that allow for analysis of gene function in tissue development and homeostasis but also as models for genetic disease. In addition, ESCs invitro are finding inroads in pharmaceutical and toxicological testing, including the identification of teratogenic compounds. Here, we describe the use of a bone morphogenetic protein (Bmp)-reporter ESC line, isolated from a well-characterized transgenic mouse line, as a new tool for the identification of chemical teratogens. The Bmp-mediated expression of the green fluorescent protein enabled the quantification of dose- and time-dependent effects of valproic acid as well as retinoic acid. Significant effects were detectable at concentrations that were comparable to the ones observed in the classical embryonic stem cell test, despite the fact that the reporter gene is expressed in distinct cell types, including endothelial and endodermal cells. Thus these cells provide a valuable new tool for the identification and characterization of relevant mechanisms of embryonic toxicity. PMID:26001961

  16. Leaf Surface Lipophilic Compounds as One of the Factors of Silver Birch Chemical Defense against Larvae of Gypsy Moth

    PubMed Central

    Martemyanov, Vyacheslav V.; Pavlushin, Sergey V.; Dubovskiy, Ivan M.; Belousova, Irina A.; Yushkova, Yuliya V.; Morosov, Sergey V.; Chernyak, Elena I.; Glupov, Victor V.

    2015-01-01

    Plant chemical defense against herbivores is a complex process which involves a number of secondary compounds. It is known that the concentration of leaf surface lipophilic compounds (SLCs), particularly those of flavonoid aglycones are increased with the defoliation treatment of silver birch Betula pendula. In this study we investigated how the alteration of SLCs concentration in the food affects the fitness and innate immunity of the gypsy moth Lymantria dispar. We found that a low SLCs concentrations in consumed leaves led to a rapid larval development and increased females’ pupae weight (= fecundity) compared to larvae fed with leaves with high SLCs content. Inversely, increasing the compounds concentration in an artificial diet produced the reverse effects: decreases in both larval weight and larval survival. Low SLCs concentrations in tree leaves differently affected larval innate immunity parameters. For both sexes, total hemocytes count in the hemolymph increased, while the activity of plasma phenoloxidase decreased when larvae consume leaves with reduced content of SLCs. Our results clearly demonstrate that the concentration of SLCs in silver birch leaves affects not only gypsy moth fitness but also their innate immune status which might alter the potential resistance of insects against infections and/or parasitoids. PMID:25816371

  17. Development of a Cell-Based Fluorescence Polarization Biosensor Using Preproinsulin to Identify Compounds That Alter Insulin Granule Dynamics.

    PubMed

    Yi, Na Young; He, Qingping; Caligan, Thomas B; Smith, Ginger R; Forsberg, Lawrence J; Brenman, Jay E; Sexton, Jonathan Z

    2015-11-01

    Diabetes currently affects 9.3% of the U.S. population totaling $245 billion annually in U.S. direct and indirect healthcare costs. Current therapies for diabetes are limited in their ability to control blood glucose and/or enhance insulin sensitivity. Therefore, innovative and efficacious therapies for diabetes are urgently needed. Herein we describe a fluorescent insulin reporter system (preproinsulin-mCherry, PPI-mCherry) that tracks live-cell insulin dynamics and secretion in pancreatic ?-cells with utility for high-content assessment of real-time insulin dynamics. Additionally, we report a new modality for sensing insulin granule packaging in conventional high-throughput screening (HTS), using a hybrid cell-based fluorescence polarization (FP)/internal FRET biosensor using the PPI-mCherry reporter system. We observed that bafilomycin, a vacuolar H(+) ATPase inhibitor and inhibitor of insulin granule formation, significantly increased mCherry FP in INS-1 cells with PPI-mCherry. Partial least squares regression analysis demonstrated that an increase of FP by bafilomycin is significantly correlated with a decrease in granularity of PPI-mCherry signal in the cells. The increased FP by bafilomycin is due to inhibition of self-Frster resonant energy transfer (homo-FRET) caused by the increased mCherry intermolecular distance. FP substantially decreases when insulin is tightly packaged in the granules, and the homo-FRET decreases when insulin granule packaging is inhibited, resulting in increased FP. We performed pilot HTS of 1782 FDA-approved small molecules and natural products from Prestwick and Enzo chemical libraries resulting in an overall Z'-factor of 0.52??0.03, indicating the suitability of this biosensor for HTS. This novel biosensor enables live-cell assessment of protein-protein interaction/protein aggregation in live cells and is compatible with conventional FP plate readers. PMID:26505612

  18. The effect of probiotic microorganisms and bioactive compounds on chemically induced carcinogenesis in rats.

    PubMed

    Bertkova, I; Hijova, E; Chmelarova, A; Mojzisova, G; Petrasova, D; Strojny, L; Bomba, A; Zitnan, R

    2010-01-01

    Diet interventions and natural bioactive supplements have now been extensively studied to reduce risks of colon cancer, which is one of the major public health problem throughout the world. The objective of our investigation was to study the effects of probiotic, prebiotic, nutritional plant extract, and plant oil on selected biochemical and immunological parameters in rats with colon cancer induced by N,N dimethylhydrazine (DMH). Male and female Wistar albino rats were were fed by a high-fat (HF) diet (10% fat in the diet) and were divided into 9 groups: Control group; PRO group - HF diet supplemented with probiotic Lactobacillus plantarum to provide 3 x 109 c.f.u. of strain/1 ml of medium; PRE group - HF diet supplemented with inulin enriched with oligofructose (2% of HF diet); HES group - HF diet supplemented with plant extract of Aesculus hippocastanum L. (1% of HF diet); OIL group - HF diet comprised Linioleum virginale (2% of HF diet); and combination of probiotic microorganisms and bioactive compounds in the groups - PRO-PRE, PRO-HES, PRO-OIL, PRE-OIL. Carcinogenesis was initiated with subcutaneous injection of DMH (20 mg/kg) two times at week interval and dietary treatments were continued for the six weeks. Application of probiotic microorganisms and bioactive compounds in all treated groups significantly decreased the activities of bacterial enzymes (p<0.001), the fecal bile acids concentration (p<0.01; p<0.001) and significantly increased serum TNFalpha level (p<0.001) in comparison to the control rats. The number of coliforms was reduced in PRO, PRO-PRE, PRO-OIL and PRE-OIL groups and significantly higher count of lactobacilli (p<0.05) was observed in PRO-PRE, PRO-OIL and PRE-OIL groups in compare with the controls. In conclusion, the results of this study indicate that probiotic microorganisms and bioactive compounds could exert a preventive effect on colon carcinogenesis induced by DMH. PMID:20568896

  19. Determination of chemical warfare agents and related compounds in environmental samples by solid-phase microextraction with gas chromatography.

    PubMed

    Popiel, Stanisław; Sankowska, Monika

    2011-11-25

    Solid phase microextraction (SPME) is an increasingly common method of sample isolation and enhancement. SPME is a convenient and simple sample preparation technique for chromatographic analysis and a useful alternative to liquid-liquid extraction and solid phase extraction. SPME is speed and simply method, which has been widely used in environmental analysis because it is a rather safe method when dealing with highly toxic chemicals. A combination of SPME and gas chromatography (GC) permits both the qualitative and quantitative analysis of toxic industrial compounds, pesticides and chemical warfare agents (CWAs), including their degradation products, in air, water and soil samples. This work presents a combination of SPME and GC