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Sample records for identify chemical compounds

  1. 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 (60–70%). 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

  2. Automated microwave double resonance spectroscopy: A tool to identify and characterize chemical compounds.

    PubMed

    Martin-Drumel, Marie-Aline; McCarthy, Michael C; Patterson, David; McGuire, Brett A; Crabtree, Kyle N

    2016-03-28

    Owing to its unparalleled structural specificity, rotational spectroscopy is a powerful technique to unambiguously identify and characterize volatile, polar molecules. We present here a new experimental approach, automated microwave double resonance (AMDOR) spectroscopy, to rapidly determine the rotational constants of these compounds without a priori knowledge of elemental composition or molecular structure. This task is achieved by rapidly acquiring the classical (frequency vs. intensity) broadband spectrum of a molecule using chirped-pulse Fourier transform microwave (FTMW) spectroscopy and subsequently analyzing it in near real-time using complementary cavity FTMW detection and double resonance. AMDOR measurements provide a unique "barcode" for each compound from which rotational constants can be extracted. To illustrate the power of this approach, AMDOR spectra of three aroma compounds - trans-cinnamaldehyde, α-, and β-ionone - have been recorded and analyzed. The prospects to extend this approach to mixture characterization and purity assessment are described. PMID:27036441

  3. Automated microwave double resonance spectroscopy: A tool to identify and characterize chemical compounds

    NASA Astrophysics Data System (ADS)

    Martin-Drumel, Marie-Aline; McCarthy, Michael C.; Patterson, David; McGuire, Brett A.; Crabtree, Kyle N.

    2016-03-01

    Owing to its unparalleled structural specificity, rotational spectroscopy is a powerful technique to unambiguously identify and characterize volatile, polar molecules. We present here a new experimental approach, automated microwave double resonance (AMDOR) spectroscopy, to rapidly determine the rotational constants of these compounds without a priori knowledge of elemental composition or molecular structure. This task is achieved by rapidly acquiring the classical (frequency vs. intensity) broadband spectrum of a molecule using chirped-pulse Fourier transform microwave (FTMW) spectroscopy and subsequently analyzing it in near real-time using complementary cavity FTMW detection and double resonance. AMDOR measurements provide a unique "barcode" for each compound from which rotational constants can be extracted. To illustrate the power of this approach, AMDOR spectra of three aroma compounds — trans-cinnamaldehyde, α-, and β-ionone — have been recorded and analyzed. The prospects to extend this approach to mixture characterization and purity assessment are described.

  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 Tox

  6. A yeast chemical genetics approach identifies the compound 3,4,5-trimethoxybenzyl isothiocyanate as a calcineurin inhibitor.

    PubMed

    Prescott, Thomas A K; Panaretou, Barry; Veitch, Nigel C; Simmonds, Monique S J

    2014-01-31

    The phosphatase enzyme calcineurin controls gene expression in a variety of biological contexts however few potent inhibitors are currently available. A screen of 360 plant extracts for inhibition of calcineurin-dependent gene expression in the model organism Saccharomyces cerevisiae identified the compound 3,4,5-trimethoxybenzyl isothiocyanate as an inhibitor. The compound was subsequently shown to inhibit human calcineurin via a mixed inhibition mechanism. To gain further mechanistic insight a yeast haploinsufficiency screen of 1152 deletion strains was carried out using a novel liquid medium screening method. The resulting haploinsufficiency profile is similar to that reported for the known calcineurin inhibitor FK506. PMID:24374339

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

    SciTech Connect

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

    2015-04-15

    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 was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

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

    PubMed

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

    2015-04-15

    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 was 71-88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. PMID:25560674

  9. 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

  10. Devices for collecting chemical compounds

    DOEpatents

    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.

  11. Heuristics for chemical compound matching.

    PubMed

    Hattori, Masahiro; Okuno, Yasushi; Goto, Susumu; Kanehisa, Minoru

    2003-01-01

    We have developed an efficient algorithm for comparing two chemical compounds, where the chemical structure is treated as a 2D graph consisting of atoms as vertices and covalent bonds as edges. Based on the concept of functional groups in chemistry, 68 atom types (vertex types) are defined for carbon, nitrogen, oxygen, and other atomic species with different environments, which has enabled detection of biochemically meaningful features. Maximal common subgraphs of two graphs can be found by searching for maximal cliques in the association graph, and we have introduced heuristics to accelerate the clique finding. Our heuristic procedure is controlled by some adjustable parameters. Here we applied our procedure to the latest KEGG/LIGAND database with different sets of parameters, and demonstrated the correlation of parameters in our algorithm with the distribution of similarity scores and/or the execution time. Finally, we showed the effectiveness of our heuristics for compound pairs along metabolic pathways. PMID:15706529

  12. Indexing molecules with chemical graph identifiers.

    PubMed

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

    2011-09-01

    Fast and robust algorithms for indexing molecules have been historically considered strategic tools for the management and storage of large chemical libraries. This work introduces a modified and further extended version of the molecular equivalence number naming adaptation of the Morgan algorithm (J Chem Inf Comput Sci 2001, 41, 181-185) for the generation of a chemical graph identifier (CGI). This new version corrects for the collisions recognized in the original adaptation and includes the ability to deal with graph canonicalization, ensembles (salts), and isomerism (tautomerism, regioisomerism, optical isomerism, and geometrical isomerism) in a flexible manner. Validation of the current CGI implementation was performed on the open NCI database and the drug-like subset of the ZINC database containing 260,071 and 5,348,089 structures, respectively. The results were compared with those obtained with some of the most widely used indexing codes, such as the CACTVS hash code and the new InChIKey. The analyses emphasize the fact that compound management activities, like duplicate analysis of chemical libraries, are sensitive to the exact definition of compound uniqueness and thus still depend, to a minor extent, on the type and flexibility of the molecular index being used. PMID:21647928

  13. 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...

  14. 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

  15. [Studies on chemical compounds of Chlorella sorokiniana].

    PubMed

    Zhang, Ling; Liu, Ping-huai; Wu, Jiao-na; Yang, Guo-fu; Suo, Yang-yang; Luo, Ning; Chen, Chen

    2015-04-01

    Chemical constituents of Chlorella sorokiniana were isolated and purified by repeated column chromatographies, over silicagel and Sephadex LH-20. Their structures were identified on the basis of physicochemical properties and spectroscopic data analysis. Five compounds were obtained from the petroleum ether extract of Chlorella sorokiniana, and their structures were identified as (22E, 24R)-5alpha, 3beta-epidioxiergosta-6, 22-dien-3beta-ol(1),(24S)-ergosta-7-en-3beta-ol(2), loliolide(3), stigmasta-7,22-dien-3beta,5alpha,6alpha-triol(4), and 3beta-hydroxy-5alpha,6alpha-epoxy-7-megastigmen-9-one(5). The main liposoluble fractions from Chlorella sorokiniana maiuly contain fatty acids, alkyl acids and olefine acids. Components 1-5 were isolated from the genus Chlorella for the first time. PMID:26281556

  16. Identifying chemicals that are planetary boundary threats.

    PubMed

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

    2014-10-01

    Rockström 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

  17. 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...

  18. 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 ...

  19. Novel compound for identifying Escherichia coli.

    PubMed Central

    Watkins, W D; Rippey, S R; Clavet, C R; Kelley-Reitz, D J; Burkhardt, W

    1988-01-01

    A new chromogenic compound, 5-bromo-4-chloro-3-indoxyl-beta-D-glucuronide, was found to be useful for the rapid, specific, differential identification of Escherichia coli in the sanitary analysis of shellfish and wastewater. Of 1,025 presumptively positive colonies (blue) and 583 presumptively negative colonies (nonblue), only 1% false-negative and 5% false-positive results were found. PMID:3046494

  20. 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

  1. Identifying interactions between chemical entities in biomedical text.

    PubMed

    Lamurias, Andre; Ferreira, João 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

  2. 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...

  3. Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds.

    PubMed

    Bruni, Giancarlo; Rennekamp, Andrew J; Velenich, Andrea; McCarroll, Matthew; Gendelev, Leo; Fertsch, Ethan; Taylor, Jack; Lakhani, Parth; Lensen, Dennis; Evron, Tama; Lorello, Paul J; Huang, Xi-Ping; Kolczewski, Sabine; Carey, Galen; Caldarone, Barbara J; Prinssen, Eric; Roth, Bryan L; Keiser, Michael J; Peterson, Randall T; Kokel, David

    2016-07-01

    Many psychiatric drugs act on multiple targets and therefore require screening assays that encompass a wide target space. With sufficiently rich phenotyping and a large sampling of compounds, it should be possible to identify compounds with desired mechanisms of action on the basis of behavioral profiles alone. Although zebrafish (Danio rerio) behavior has been used to rapidly identify neuroactive compounds, it is not clear what types of behavioral assays would be necessary to identify multitarget compounds such as antipsychotics. Here we developed a battery of behavioral assays in larval zebrafish to determine whether behavioral profiles can provide sufficient phenotypic resolution to identify and classify psychiatric drugs. Using the antipsychotic drug haloperidol as a test case, we found that behavioral profiles of haloperidol-treated zebrafish could be used to identify previously uncharacterized compounds with desired antipsychotic-like activities and multitarget mechanisms of action. PMID:27239787

  4. 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.

  5. 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...

  6. Assimilating chemical compound with a regional chemical model

    NASA Astrophysics Data System (ADS)

    Chang, C.; Yang, S.; Liang, M.; Hsu, S.; Tseng, Y.

    2012-12-01

    To constrain the source and sink of the chemical compounds at surface during model simulation, chemical compound assimilation with Local Ensemble Transform Kalman Filter (LETKF) has been implemented for the WRF-ChemT model. In this study, a two-tier system is applied to assimilating the meteorological and chemical variables in an OSSE framework. The unobserved surface flux is estimated according to the observations in the chemical component. A long-term nature run with total constant emission of 5.3×108 g/s is assumed to be the truth state in the OSSE. The simulated observations are obtained from the truth state by adding random errors. In order to generate the initial CO2 ensembles with similar spatial distribution as truth state without other prior information, the initial perturbation fields of CO2 are randomly chosen from three long-term runs with different emissions. The results indicate that in the constant emission case, the system can successfully estimate the unobserved chemical forcing and improve the distribution of the chemical compound. Under the scenario of diurnal forcing induced by human activities, the problem in estimating surface flux becomes more complex and difficult. A set of experiments with different initial chemical states suggest that the estimation of flux is sensitive to the quality of initial CO2 and CO2 surface flux. Strategies are designed to retrieve the time-varying information. The results show that with time-varying information and reliable initial ensembles, the estimation of surface flux have been significantly improved. Couple assimilation with meteorological and chemical components Surface flux estimation

  7. 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.

  8. Chemical effect on diffusion in intermetallic compounds

    NASA Astrophysics Data System (ADS)

    Chen, Yi-Ting

    With the trend of big data and the Internet of things, we live in a world full of personal electronic devices and small electronic devices. In order to make the devices more powerful, advanced electronic packaging such as wafer level packaging or 3D IC packaging play an important role. Furthermore, ?-bumps, which connect silicon dies together with dimension less than 10 ?m, are crucial parts in advanced packaging. Owing to the dimension of ?-bumps, they transform into intermetallic compound from tin based solder after the liquid state bonding process. Moreover, many new reliability issues will occur in electronic packaging when the bonding materials change; in this case, we no longer have tin based solder joint, instead, we have intermetallic compound ?-bumps. Most of the potential reliability issues in intermetallic compounds are caused by the chemical reactions driven by atomic diffusion in the material; thus, to know the diffusivities of atoms inside a material is significant and can help us to further analyze the reliability issues. However, we are lacking these kinds of data in intermetallic compound because there are some problems if used traditional Darken's analysis. Therefore, we considered Wagner diffusivity in our system to solve the problems and applied the concept of chemical effect on diffusion by taking the advantage that large amount of energy will release when compounds formed. Moreover, by inventing the holes markers made by Focus ion beam (FIB), we can conduct the diffusion experiment and obtain the tracer diffusivities of atoms inside the intermetallic compound. We applied the technique on Ni3Sn4 and Cu3Sn, which are two of the most common materials in electronic packaging, and the tracer diffusivities are measured under several different temperatures; moreover, microstructure of the intermetallic compounds are investigated to ensure the diffusion environment. Additionally, the detail diffusion mechanism was also discussed in aspect of diffusion

  9. Antitumor activity of chemical modified natural compounds.

    PubMed

    de Oliveira, M M

    1991-01-01

    Search of new activity substances starting from chemotherapeutic agents, continuously appears in international literature. Perhaps this search has been done more frequently in the field of antitumor chemotherapy on account of the unsuccess in saving advanced stage patients. The new point in this matter during the last decade was computer aid in planning more rational drugs. In near future "the accessibility of super computers and emergence of computer net systems, will open new avenues to rational drug design" (Portoghese, P. S., J. Med. Chem. 1989, 32, 1). Unknown pharmacological active compounds synthetized by plants can be found even without this electronic devices, as traditional medicine has pointed out in many countries, and give rise to a new drug. These compounds used as found in nature or after chemical modifications have produced successful experimental medicaments as FAA, "flavone acetic acid" with good results as inhibitors of slow growing animal tumors currently in preclinical evaluation for human treatment. In this lecture some international contributions in the field of chemical modified compounds as antineoplastic drugs will be examined, particularly those done by Brazilian researches. PMID:1842015

  10. Identifying Novel Cancer Therapies Using Chemical Genetics and Zebrafish.

    PubMed

    Dang, Michelle; Fogley, Rachel; Zon, Leonard I

    2016-01-01

    Chemical genetics is the use of small molecules to perturb biological pathways. This technique is a powerful tool for implicating genes and pathways in developmental programs and disease, and simultaneously provides a platform for the discovery of novel therapeutics. The zebrafish is an advantageous model for in vivo high-throughput small molecule screening due to translational appeal, high fecundity, and a unique set of developmental characteristics that support genetic manipulation, chemical treatment, and phenotype detection. Chemical genetic screens in zebrafish can identify hit compounds that target oncogenic processes-including cancer initiation and maintenance, metastasis, and angiogenesis-and may serve as cancer therapies. Notably, by combining drug discovery and animal testing, in vivo screening of small molecules in zebrafish has enabled rapid translation of hit anti-cancer compounds to the clinic, especially through the repurposing of FDA-approved drugs. Future technological advancements in automation and high-powered imaging, as well as the development and characterization of new mutant and transgenic lines, will expand the scope of chemical genetics in zebrafish. PMID:27165351

  11. High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult Schistosoma mansoni.

    PubMed

    Mansour, Nuha R; Paveley, Ross; Gardner, J Mark F; Bell, Andrew S; Parkinson, Tanya; Bickle, Quentin

    2016-04-01

    An estimated 600 million people are affected by the helminth disease schistosomiasis caused by parasites of the genus Schistosoma. There is currently only one drug recommended for treating schistosomiasis, praziquantel (PZQ), which is effective against adult worms but not against the juvenile stage. In an attempt to identify improved drugs for treating the disease, we have carried out high throughput screening of a number of small molecule libraries with the aim of identifying lead compounds with balanced activity against all life stages of Schistosoma. A total of almost 300,000 compounds were screened using a high throughput assay based on motility of worm larvae and image analysis of assay plates. Hits were screened against juvenile and adult worms to identify broadly active compounds and against a mammalian cell line to assess cytotoxicity. A number of compounds were identified as promising leads for further chemical optimization. PMID:27128493

  12. High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult Schistosoma mansoni

    PubMed Central

    Gardner, J. Mark F.; Bell, Andrew S.; Parkinson, Tanya; Bickle, Quentin

    2016-01-01

    An estimated 600 million people are affected by the helminth disease schistosomiasis caused by parasites of the genus Schistosoma. There is currently only one drug recommended for treating schistosomiasis, praziquantel (PZQ), which is effective against adult worms but not against the juvenile stage. In an attempt to identify improved drugs for treating the disease, we have carried out high throughput screening of a number of small molecule libraries with the aim of identifying lead compounds with balanced activity against all life stages of Schistosoma. A total of almost 300,000 compounds were screened using a high throughput assay based on motility of worm larvae and image analysis of assay plates. Hits were screened against juvenile and adult worms to identify broadly active compounds and against a mammalian cell line to assess cytotoxicity. A number of compounds were identified as promising leads for further chemical optimization. PMID:27128493

  13. 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

  14. Primary Polymer Aging Processes Identified from Weapon Headspace Chemicals

    SciTech Connect

    Chambers, D M; Bazan, J M; Ithaca, J G

    2002-03-25

    A current focus of our weapon headspace sampling work is the interpretation of the volatile chemical signatures that we are collecting. To help validate our interpretation we have been developing a laboratory-based material aging capability to simulate material decomposition chemistries identified. Key to establishing this capability has been the development of an automated approach to process, analyze, and quantify arrays of material combinations as a function of time and temperature. Our initial approach involves monitoring the formation and migration of volatile compounds produced when a material decomposes. This approach is advantageous in that it is nondestructive and provides a direct comparison with our weapon headspace surveillance initiative. Nevertheless, this approach requires us to identify volatile material residue and decomposition byproducts that are not typically monitored and reported in material aging studies. Similar to our weapon monitoring method, our principle laboratory-based method involves static headspace collection by solid phase microextraction (SPME) followed by gas chromatography/mass spectrometry (GC/MS). SPME is a sorbent collection technique that is ideally suited for preconcentration and delivery of trace gas-phase compounds for analysis by GC. When combined with MS, detection limits are routinely in the low- and sub-ppb ranges, even for semivolatile and polar compounds. To automate this process we incorporated a robotic sample processor configured for SPME collection. The completed system will thermally process, sample, and analyze a material sample. Quantification of the instrument response is another process that has been integrated into the system. The current system screens low-milligram quantities of material for the formation or outgas of small compounds as initial indicators of chemical decomposition. This emerging capability offers us a new approach to identify and non-intrusively monitor decomposition mechanisms that are

  15. 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...

  16. 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.

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

    PubMed Central

    Schön, 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

  18. 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

  19. 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...

  20. 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

  1. 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 π-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.

  2. Identification of anti-cancer chemical compounds using Xenopus embryos.

    PubMed

    Tanaka, Masamitsu; Kuriyama, Sei; Itoh, Go; Kohyama, Aki; Iwabuchi, Yoshiharu; Shibata, Hiroyuki; Yashiro, Masakazu; Aiba, Namiko

    2016-06-01

    Cancer tissues have biological characteristics similar to those observed in embryos during development. Many types of cancer cells acquire pro-invasive ability through epithelial-mesenchymal transition (EMT). Similar processes (gastrulation and migration of cranial neural crest cells [CNCC]) are observed in the early stages of embryonic development in Xenopus during which cells that originate from epithelial sheets through EMT migrate to their final destinations. The present study examined Xenopus embryonic tissues to identify anti-cancer compounds that prevent cancer invasion. From the initial test of known anti-cancer drugs, AMD3100 (an inhibitor of CXCR4) and paclitaxel (a cytoskeletal drug targeting microtubules) effectively prevented migration during gastrulation or CNCC development. Blind-screening of 100 synthesized chemical compounds was performed, and nine candidates that inhibited migration of these embryonic tissues without embryonic lethality were selected. Of these, C-157 (an analog of podophyllotoxin) and D-572 (which is an indole alkaroid) prevented cancer cell invasion through disruption of interphase microtubules. In addition, these compounds affected progression of mitotic phase and induced apoptosis of SAS oral cancer cells. SAS tumors were reduced in size after intratumoral injection of C-157, and peritoneal dissemination of melanoma cells and intracranial invasion of glioma cells were inhibited by C-157 and D-572. When the other analogues of these chemicals were compared, those with subtle effect on embryos were not tumor suppressive. These results suggest that a novel chemical-screening approach based on Xenopus embryos is an effective method for isolating anti-cancer drugs and, in particular, targeting cancer cell invasion and proliferation. PMID:27019404

  3. 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

  4. Process for preparing a chemical compound enriched in isotope content

    DOEpatents

    Michaels, Edward D.

    1982-01-01

    A process to prepare a chemical enriched in isotope content which includes: (a) A chemical exchange reaction between a first and second compound which yields an isotopically enriched first compound and an isotopically depleted second compound; (b) the removal of a portion of the first compound as product and the removal of a portion of the second compound as spent material; (c) 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; (d) 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.

  5. 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

  6. 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

  7. 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

  8. 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)

  9. Chemical compounds of the foraging recruitment pheromone in bumblebees

    NASA Astrophysics Data System (ADS)

    Granero, Angeles Mena; Sanz, José M. Guerra; Gonzalez, Francisco J. Egea; Vidal, José L. Martinez; Dornhaus, Anna; Ghani, Junaid; Serrano, Ana Roldán; Chittka, Lars

    2005-08-01

    When the frenzied and irregular food-recruitment dances of bumblebees were first discovered, it was thought that they might represent an evolutionary prototype to the honeybee waggle dance. It later emerged that the primary function of the bumblebee dance was the distribution of an alerting pheromone. Here, we identify the chemical compounds of the bumblebee recruitment pheromone and their behaviour effects. The presence of two monoterpenes and one sesquiterpene (eucalyptol, ocimene and farnesol) in the nest airspace and in the tergal glands increases strongly during foraging. Of these, eucalyptol has the strongest recruitment effect when a bee nest is experimentally exposed to it. Since honeybees use terpenes for marking food sources rather than recruiting foragers inside the nest, this suggests independent evolutionary roots of food recruitment in these two groups of bees.

  10. 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.

  11. Zebrafish screen identifies novel compound with selective toxicity against leukemia

    PubMed Central

    Ridges, Suzanne; Heaton, Will L.; Joshi, Deepa; Choi, Henry; Eiring, Anna; Batchelor, Lance; Choudhry, Priya; Manos, Elizabeth J.; Sofla, Hossein; Sanati, Ali; Welborn, Seth; Agarwal, Archana; Spangrude, Gerald J.; Miles, Rodney R.; Cox, James E.; Frazer, J. Kimble; Deininger, Michael; Balan, Kaveri; Sigman, Matthew; Müschen, Markus; Perova, Tatiana; Johnson, Radia; Montpellier, Bertrand; Guidos, Cynthia J.; Jones, David A.

    2012-01-01

    To detect targeted antileukemia agents we have designed a novel, high-content in vivo screen using genetically engineered, T-cell reporting zebrafish. We exploited the developmental similarities between normal and malignant T lymphoblasts to screen a small molecule library for activity against immature T cells with a simple visual readout in zebrafish larvae. After screening 26 400 molecules, we identified Lenaldekar (LDK), a compound that eliminates immature T cells in developing zebrafish without affecting the cell cycle in other cell types. LDK is well tolerated in vertebrates and induces long-term remission in adult zebrafish with cMYC-induced T-cell acute lymphoblastic leukemia (T-ALL). LDK causes dephosphorylation of members of the PI3 kinase/AKT/mTOR pathway and delays sensitive cells in late mitosis. Among human cancers, LDK selectively affects survival of hematopoietic malignancy lines and primary leukemias, including therapy-refractory B-ALL and chronic myelogenous leukemia samples, and inhibits growth of human T-ALL xenografts. This work demonstrates the utility of our method using zebrafish for antineoplastic candidate drug identification and suggests a new approach for targeted leukemia therapy. Although our efforts focused on leukemia therapy, this screening approach has broad implications as it can be translated to other cancer types involving malignant degeneration of developmentally arrested cells. PMID:22490804

  12. Chemical compounds isolated from Talinum triangulare (Portulacaceae).

    PubMed

    de Oliveira Amorim, Ana Paula; de Carvalho, Almir Ribeiro; Lopes, Norberto Peporine; Castro, Rosane Nora; de Oliveira, Marcia Cristina Campos; de Carvalho, Mário Geraldo

    2014-10-01

    This first phytochemical study of Talinum triangulare Leach (Portulacaceae), also known as 'cariru', which is a commonly consumed food in Northern Brazil, allowed the isolation and structural determination of four new compounds: one acrylamide, 3-N-(acryloyl, N-pentadecanoyl) propanoic acid (5), and three new phaeophytins named (15(1)S, 17R, 18R)-Ficuschlorin D acid (3(1),3(2)-didehydro-7-oxo-17(3)-O-phytyl-rhodochlorin-15-acetic acid), (13), Talichorin A (17R, 18R)-phaeophytin b-15(1)-hidroxy, 15(2),15(3)-acetyl-13(1)-carboxilic acid (14), and (15(1)S, 17R, 18R)-phaeophytin b peroxylactone or (15(1)S, 17R, 18R)-hydroperoxy-ficuschlorin D (16), together with twelve known compounds, including four phaeophytins (11,12, 15 and 17). The structures of the compounds were established on the basis of 1D and 2D NMR, IR, HRESI-MS spectra, including GC-MS, and HPLC-UV analysis, as well as comparisons with the literature data. The CD spectra data analysis were used to define the absolute configuration of phaeophytins 12 (13(2)R, 17R, 18R)-13(2)-hydroxyphaeophytin a, 13 and 16, 15 (15(1)S, 17R, 18R)-3(1),3(2)-didehydro-15(1)-hydroxyrhodochlorin-15-acetic acid δ-lactone-15(2)-methyl-17(3)-phytyl ester and 17 (17R, 18R)-purpurin 18-phytyl ester. PMID:24799228

  13. 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

  14. 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 ...

  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. 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

  17. 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

  18. 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 ...

  19. 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

  20. 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 Brönsted or Lewis acidity of clay minerals. PMID:2533556

  1. 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…

  2. 30 CFR 47.21 - Identifying hazardous chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... standards in 30 CFR chapter I. (3) Occupational Safety and Health Administration (OSHA), 29 CFR part 1910... TRAINING HAZARD COMMUNICATION (HazCom) Hazard Determination § 47.21 Identifying hazardous chemicals. The... Human Services, National Toxicology Program (NTP), Ninth Annual Report on Carcinogens, January 2001....

  3. Chemical bath deposition of II-VI compound thin films

    NASA Astrophysics Data System (ADS)

    Oladeji, Isaiah Olatunde

    II-VI compounds are direct bandgap semiconductors with great potentials in optoelectronic applications. Solar cells, where these materials are in greater demand, require a low cost production technology that will make the final product more affordable. Chemical bath deposition (CBD) a low cost growth technique capable of producing good quality thin film semiconductors over large area and at low temperature then becomes a suitable technology of choice. Heterogeneous reaction in a basic aqueous solution that is responsible for the II-VI compound film growth in CBD requires a metal complex. We have identified the stability constant (k) of the metal complex compatible with CBD growth mechanism to be about 106.9. This value is low enough to ensure that the substrate adsorbed complex relax for subsequent reaction with the chalcogen precursor to take place. It is also high enough to minimize the metal ion concentration in the bath participating in the precipitation of the bulk compounds. Homogeneous reaction that leads to precipitation in the reaction bath takes place because the solubility products of bulk II-VI compounds are very low. This reaction quickly depletes the bath of reactants, limit the film thickness, and degrade the film quality. While ZnS thin films are still hard to grow by CBD because of lack of suitable complexing agent, the homogeneous reaction still limits quality and thickness of both US and ZnS thin films. In this study, the zinc tetraammine complex ([Zn(NH3) 4]2+) with k = 108.9 has been forced to acquire its unsaturated form [Zn(NH3)3]2+ with a moderate k = 106.6 using hydrazine and nitrilotriacetate ion as complementary complexing agents and we have successfully grown ZnS thin films. We have also, minimized or eliminated the homogeneous reaction by using ammonium salt as a buffer and chemical bath with low reactant concentrations. These have allowed us to increase the saturation thickness of ZnS thin film by about 400% and raise that of US film

  4. Screening of antitubercular compound library identifies novel shikimate kinase inhibitors of Mycobacterium tuberculosis.

    PubMed

    Rajput, Vikrant S; Mehra, Rukmankesh; Kumar, Sanjay; Nargotra, Amit; Singh, Parvinder Pal; Khan, Inshad Ali

    2016-06-01

    Shikimate kinase of Mycobacterium tuberculosis is involved in the biosynthesis of aromatic amino acids through shikimate pathway. The enzyme is essential for the survival of M. tuberculosis and is absent from mammals, thus providing an excellent opportunity for identifying new chemical entities to combat tuberculosis with a novel mechanism of action. In this study, an antitubercular library of 1000 compounds was screened against M. tuberculosis shikimate kinase (MtSK). This effort led to the identification of 20 inhibitors, among which five promising leads exhibited half maximal inhibitory concentration (IC50) values below 10 μM. The most potent inhibitor ("5631296") showed an IC50 value of 5.10 μM ± 0.6. The leads were further evaluated for the activity against multidrug-resistant (MDR)-TB, Gram-positive and Gram-negative bacterial strains, mode of action, docking simulations, and combinatorial study with three frontline anti-TB drugs. Compound "5491210" displayed a nearly synergistic activity with rifampicin, isoniazid, and ethambutol while compound "5631296" was synergistic with rifampicin. In vitro cytotoxicity against HepG2 cell line was evaluated and barring one compound; all were found to be non-toxic (SI > 10). In order to rule out mitochondrial toxicity, the promising inhibitors were also evaluated for cell cytotoxicity using galactose medium where compounds "5631296" and "5122752" appeared non-toxic. Upon comprehensive analysis, compound "5631296" was found to be the most promising MtSK inhibitor that was safe, synergistic with rifampicin, and bactericidal against M. tuberculosis. PMID:26887318

  5. Novel Anti-Campylobacter Compounds Identified Using High Throughput Screening of a Pre-selected Enriched Small Molecules Library

    PubMed Central

    Kumar, Anand; Drozd, Mary; Pina-Mimbela, Ruby; Xu, Xiulan; Helmy, Yosra A.; Antwi, Janet; Fuchs, James R.; Nislow, Corey; Templeton, Jillian; Blackall, Patrick J.; Rajashekara, Gireesh

    2016-01-01

    Campylobacter is a leading cause of foodborne bacterial gastroenteritis worldwide and infections can be fatal. The emergence of antibiotic-resistant Campylobacter spp. necessitates the development of new antimicrobials. We identified novel anti-Campylobacter small molecule inhibitors using a high throughput growth inhibition assay. To expedite screening, we made use of a “bioactive” library of 4182 compounds that we have previously shown to be active against diverse microbes. Screening for growth inhibition of Campylobacter jejuni, identified 781 compounds that were either bactericidal or bacteriostatic at a concentration of 200 μM. Seventy nine of the bactericidal compounds were prioritized for secondary screening based on their physico-chemical properties. Based on the minimum inhibitory concentration against a diverse range of C. jejuni and a lack of effect on gut microbes, we selected 12 compounds. No resistance was observed to any of these 12 lead compounds when C. jejuni was cultured with lethal or sub-lethal concentrations suggesting that C. jejuni is less likely to develop resistance to these compounds. Top 12 compounds also possessed low cytotoxicity to human intestinal epithelial cells (Caco-2 cells) and no hemolytic activity against sheep red blood cells. Next, these 12 compounds were evaluated for ability to clear C. jejuni in vitro. A total of 10 compounds had an anti-C. jejuni effect in Caco-2 cells with some effective even at 25 μM concentrations. These novel 12 compounds belong to five established antimicrobial chemical classes; piperazines, aryl amines, piperidines, sulfonamide, and pyridazinone. Exploitation of analogs of these chemical classes may provide Campylobacter specific drugs that can be applied in both human and animal medicine. PMID:27092106

  6. Chemicals from coal. Utilization of coal-derived phenolic compounds

    SciTech Connect

    Song, C.; Schobert, H.H.

    1999-07-01

    This article provides an overview for possible utilization of coal-derived phenolic compounds. Phenolic compounds are abundant in coal-derived liquids. Coal-derived phenolic compounds include phenol, cresol, catechol, methylcatechol, naphthol, and their derivatives. Liquids from coal liquefaction, pyrolysis, gasification, and carbonization are potential sources of phenolic chemicals, although certain processing and separation are needed. There are opportunities for coal-based phenolic chemicals, because there are existing industrial applications and potential new applications. Currently the petrochemical industry produces phenol in multi-step processes, and new research and development has resulted in a one-step process. Selective methylation of phenol can produce a precursor for aromatic engineering plastics. Catalytic oxidation of phenol has been commercialized recently for catechol production. There are potential new uses of phenol that could replace large-volume multi-step chemical processes that are based on benzene as the starting material. New chemical research on coal and coal-derived liquids can pave the way for their non-fuel uses for making chemicals and materials.

  7. Semantic Similarity for Automatic Classification of Chemical Compounds

    PubMed Central

    Ferreira, João D.; Couto, Francisco M.

    2010-01-01

    With the increasing amount of data made available in the chemical field, there is a strong need for systems capable of comparing and classifying chemical compounds in an efficient and effective way. The best approaches existing today are based on the structure-activity relationship premise, which states that biological activity of a molecule is strongly related to its structural or physicochemical properties. This work presents a novel approach to the automatic classification of chemical compounds by integrating semantic similarity with existing structural comparison methods. Our approach was assessed based on the Matthews Correlation Coefficient for the prediction, and achieved values of 0.810 when used as a prediction of blood-brain barrier permeability, 0.694 for P-glycoprotein substrate, and 0.673 for estrogen receptor binding activity. These results expose a significant improvement over the currently existing methods, whose best performances were 0.628, 0.591, and 0.647 respectively. It was demonstrated that the integration of semantic similarity is a feasible and effective way to improve existing chemical compound classification systems. Among other possible uses, this tool helps the study of the evolution of metabolic pathways, the study of the correlation of metabolic networks with properties of those networks, or the improvement of ontologies that represent chemical information. PMID:20885779

  8. An Unbiased Oncology Compound Screen to Identify Novel Combination Strategies.

    PubMed

    O'Neil, Jennifer; Benita, Yair; Feldman, Igor; Chenard, Melissa; Roberts, Brian; Liu, Yaping; Li, Jing; Kral, Astrid; Lejnine, Serguei; Loboda, Andrey; Arthur, William; Cristescu, Razvan; Haines, Brian B; Winter, Christopher; Zhang, Theresa; Bloecher, Andrew; Shumway, Stuart D

    2016-06-01

    Combination drug therapy is a widely used paradigm for managing numerous human malignancies. In cancer treatment, additive and/or synergistic drug combinations can convert weakly efficacious monotherapies into regimens that produce robust antitumor activity. This can be explained in part through pathway interdependencies that are critical for cancer cell proliferation and survival. However, identification of the various interdependencies is difficult due to the complex molecular circuitry that underlies tumor development and progression. Here, we present a high-throughput platform that allows for an unbiased identification of synergistic and efficacious drug combinations. In a screen of 22,737 experiments of 583 doublet combinations in 39 diverse cancer cell lines using a 4 by 4 dosing regimen, both well-known and novel synergistic and efficacious combinations were identified. Here, we present an example of one such novel combination, a Wee1 inhibitor (AZD1775) and an mTOR inhibitor (ridaforolimus), and demonstrate that the combination potently and synergistically inhibits cancer cell growth in vitro and in vivo This approach has identified novel combinations that would be difficult to reliably predict based purely on our current understanding of cancer cell biology. Mol Cancer Ther; 15(6); 1155-62. ©2016 AACR. PMID:26983881

  9. Accurate ab initio energy gradients in chemical compound space.

    PubMed

    Anatole von Lilienfeld, O

    2009-10-28

    Analytical potential energy derivatives, based on the Hellmann-Feynman theorem, are presented for any pair of isoelectronic compounds. Since energies are not necessarily monotonic functions between compounds, these derivatives can fail to predict the right trends of the effect of alchemical mutation. However, quantitative estimates without additional self-consistency calculations can be made when the Hellmann-Feynman derivative is multiplied with a linearization coefficient that is obtained from a reference pair of compounds. These results suggest that accurate predictions can be made regarding any molecule's energetic properties as long as energies and gradients of three other molecules have been provided. The linearization coefficent can be interpreted as a quantitative measure of chemical similarity. Presented numerical evidence includes predictions of electronic eigenvalues of saturated and aromatic molecular hydrocarbons. PMID:19894922

  10. 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

  11. 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.

  12. Chemical Compounds and Extraction Methods of “Maollahm”

    PubMed Central

    Sadeghpoor, Omid; Dayeni, Manijeh; Razi, Samane

    2016-01-01

    Background: Maollahm or meat juice, a by-product of meat, is a traditional remedy in Persian medicine. This product was used as a nourishment or treatment substance for sick people. According to the ancient Persian medicine, animal meat has more affinity with the human body and the body easily absorbs its nutrition. Therefore, one could resort to maollahm for patients requiring urgent nourishment to boost and strengthen their body. Methods: In this work, different ways of preparing maollahm from poultry, goat, cow, and sheep meat are studied. Most of these methods are based on distillation or barbecue before distillation, as prescribed by traditional medicine books. The reactions, chemical processes, and volatile compounds related to different types of cooked meat are also compared with the outcome of recent research studies. Results: The difference between various types of meat is related to their compounds. Different cooking processes such as barbecuing, roasting, cooking, and boiling have an effect on the taste, smell and the chemical constituents of maollahm. Additionally, the type of meat, animal feed, as well as using or removing the fat during the cooking process, have an effect on the produced volatile compounds. Conclusion: Cooking process and the type of meat have a direct effect on the compounds of maollahm. Possible reactions in the preparation process of maollahm are investigated and presented according to the new research studies. PMID:27516659

  13. 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 (ΔfH298°), 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

  14. 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.

  15. International chemical identifier for reactions (RInChI)

    PubMed Central

    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

  16. 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

  17. Chemical degradation of fluorosulfonamide fuel cell membrane polymer model compounds

    NASA Astrophysics Data System (ADS)

    Alsheheri, Jamela M.; Ghassemi, Hossein; Schiraldi, David A.

    2014-12-01

    The durability of a polymer electrolyte fuel cell membrane, along with high proton conductivity and mechanical performance is critical to the success of these energy conversion devices. Extending our work in perfluorinated membrane stability, aromatic trifluoromethyl sulfonamide model compounds were prepared, and their oxidative degradation was examined. The chemical structures for the models were based on mono-, di- and tri-perfluorinated sulfonamide modified phenyl rings. Durability of the model compounds was evaluated by exposure to hydroxyl radicals generated using Fenton reagent and UV irradiation of hydrogen peroxide. LC-MS results for the mono-substituted model compound indicate greater stability to radical oxidation than the di-substituted species; loss of perfluorinated fonamide side chains appears to be an important pathway, along with dimerization and aromatic ring hydroxylation. The tri-substituted model compound also shows loss of side chains, with the mono-substituted compound being a major oxidation product, along with a limited amount of hydroxylation and dimerization of the starting material.

  18. Mapping the chemical chromatin reactivation landscape identifies BRD4-TAF1 cross-talk.

    PubMed

    Sdelci, Sara; Lardeau, Charles-Hugues; Tallant, Cynthia; Klepsch, Freya; Klaiber, Björn; Bennett, James; Rathert, Philipp; Schuster, Michael; Penz, Thomas; Fedorov, Oleg; Superti-Furga, Giulio; Bock, Christoph; Zuber, Johannes; Huber, Kilian V M; Knapp, Stefan; Müller, Susanne; Kubicek, Stefan

    2016-07-01

    Bromodomain-containing proteins of the BET family recognize histone lysine acetylation and mediate transcriptional activation of target genes such as the MYC oncogene. Pharmacological inhibitors of BET domains promise therapeutic benefits in a variety of cancers. We performed a high-diversity chemical compound screen for agents capable of modulating BRD4-dependent heterochromatization of a generic reporter in human cells. In addition to known and new compounds targeting BRD4, we identified small molecules that mimic BRD4 inhibition without direct engagement. One such compound was a potent inhibitor of the second bromodomain of TAF1. Using this inhibitor, we discovered that TAF1 synergizes with BRD4 to control proliferation of cancer cells, making TAF1 an attractive epigenetic target in cancers driven by MYC. PMID:27159579

  19. 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

  20. 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

  1. An overview of NMR-based metabolomics to identify secondary plant compounds involved in host plant resistance.

    PubMed

    Leiss, Kirsten A; Choi, Young H; Verpoorte, Robert; Klinkhamer, Peter G L

    2011-06-01

    Secondary metabolites provide a potential source for the generation of host plant resistance and development of biopesticides. This is especially important in view of the rapid and vast spread of agricultural and horticultural pests worldwide. Multiple pests control tactics in the framework of an integrated pest management (IPM) programme are necessary. One important strategy of IPM is the use of chemical host plant resistance. Up to now the study of chemical host plant resistance has, for technical reasons, been restricted to the identification of single compounds applying specific chemical analyses adapted to the compound in question. In biological processes however, usually more than one compound is involved. Metabolomics allows the simultaneous detection of a wide range of compounds, providing an immediate image of the metabolome of a plant. One of the most universally used metabolomic approaches comprises nuclear magnetic resonance spectroscopy (NMR). It has been NMR which has been applied as a proof of principle to show that metabolomics can constitute a major advancement in the study of host plant resistance. Here we give an overview on the application of NMR to identify candidate compounds for host plant resistance. We focus on host plant resistance to western flower thrips (Frankliniella occidentalis) which has been used as a model for different plant species. PMID:21765818

  2. Analysis of chlorocarbon compounds identified in the SAM Investigation of the Mars Science Laboratory mission

    NASA Astrophysics Data System (ADS)

    Freissinet, Caroline; Mahaffy, P.; Glavin, D.; Buch, A.; Brunner, A.; Eigenbrode, J.; Martin, M.; Miller, K.; Steele, A.; Szopa, C.; SAM; MSL science Team

    2013-10-01

    The gas chromatograph mass spectrometer (GCMS) mode of the Sample Analysis at Mars (SAM) experiment was designed for the separation and identification of the chemical components of the gases released from a solid sample or trapped from the atmosphere. Gases from solid samples are either produced by heating a cell from ambient to >800-1100oC (EGA mode) or by wet chemistry extraction and reactions (not yet employed on Mars). Prior to EGA analysis of portions of the first 3 solid samples (Rocknest, John Klein and Cumberland) collected by MSL and delivered to SAM, an internal SAM blank run was carried out with an empty quartz cup. These blank analyses are required to understand the background signal intrinsic to the GCMS and its gas manifolds and traps. Several peaks have been identified as part of SAM background, some of them below the nmol level, which attests of the sensitivity of the instrument and as-designed performance of the GCMS. The origin of each peak has been investigated, and two major contributors are revealed; residual vapor from one of the chemicals used for SAM wet chemistry experiment: N-methyl-N-tert-butyldimethylsilyl-trifluoroacetamide (MTBSTFA), and the Tenax from the hydrocarbon trap. Supporting lab experiments are in progress to understand the reaction pathways of the molecules identified in the SAM background. These experiments help elucidate which molecules may be interpreted as indigenous to Mars. Of the three solid samples analyzed on 11 runs, it was possible to detect and identify several chlorinated compounds including several chlorohydrocarbons. The chlorine is likely derived from the decomposition of martian perchlorates or other indigenous Cl-containing species while the origin of the carbon is presently under investigation for each detected molecule. To date, a subset these molecules have been identified in lab studies and a terrestrial contribution to the observed products are more easily explained. The combined results from SAM and

  3. Electrolytic photodissociation of chemical compounds by iron oxide electrodes

    DOEpatents

    Somorjai, Gabor A.; Leygraf, Christofer H.

    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.

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

    DOEpatents

    Somorjai, Gabor A.; Leygraf, Christofer H.

    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.

  5. 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

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

    PubMed

    Wang, H; Volarath, P; Harrison, R

    2005-01-01

    A searching or identifying of chemical compounds is an important process in drug design and in chemistry research. An efficient search engine involves a close coupling of the search algorithm and database implementation. The database must process chemical structures, which demands the approaches to represent, store, and retrieve structures in a database system. In this paper, a general database framework for working as a chemical compound search engine in Oracle database is described. The framework is devoted to eliminate data type constrains for potential search algorithms, which is a crucial step toward building a domain specific query language on top of SQL. A search engine implementation based on the database framework is also demonstrated. The convenience of the implementation emphasizes the efficiency and simplicity of the framework. PMID:17282834

  7. 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

  8. 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

  9. The Privileged Chemical Space Predictor (PCSP): A computer program that identifies privileged chemical space from screens of modularly assembled chemical libraries

    PubMed Central

    Seedhouse, Steven J.; Labuda, Lucas P.; Disney, Matthew D.

    2010-01-01

    Modularly assembled combinatorial libraries are often used to identify ligands that bind to and modulate the function of a protein or a nucleic acid. Much of the data from screening these compounds, however, is not efficiently utilized to define structure-activity relationships (SAR). If SAR data are accurately constructed, it can enable the design of more potent binders. Herein, we describe a computer program called Privileged Chemical Space Predictor (PCSP) that statistically determines SAR from high-throughput screening (HTS) data and then identifies features in small molecules that predispose them for binding a target. Features are scored for statistical significance and can be utilized to design improved second generation compounds or more target-focused libraries. The program’s utility is demonstrated through analysis of a modularly assembled peptoid library that was screened for binding to and inhibiting a group I intron RNA from the fungal pathogen Candida albicans. PMID:20097562

  10. Quantitative high-throughput screening: A titration-based approach that efficiently identifies biological activities in large chemical libraries

    PubMed Central

    Inglese, James; Auld, Douglas S.; Jadhav, Ajit; Johnson, Ronald L.; Simeonov, Anton; Yasgar, Adam; Zheng, Wei; Austin, Christopher P.

    2006-01-01

    High-throughput screening (HTS) of chemical compounds to identify modulators of molecular targets is a mainstay of pharmaceutical development. Increasingly, HTS is being used to identify chemical probes of gene, pathway, and cell functions, with the ultimate goal of comprehensively delineating relationships between chemical structures and biological activities. Achieving this goal will require methodologies that efficiently generate pharmacological data from the primary screen and reliably profile the range of biological activities associated with large chemical libraries. Traditional HTS, which tests compounds at a single concentration, is not suited to this task, because HTS is burdened by frequent false positives and false negatives and requires extensive follow-up testing. We have developed a paradigm, quantitative HTS (qHTS), tested with the enzyme pyruvate kinase, to generate concentration–response curves for >60,000 compounds in a single experiment. We show that this method is precise, refractory to variations in sample preparation, and identifies compounds with a wide range of activities. Concentration–response curves were classified to rapidly identify pyruvate kinase activators and inhibitors with a variety of potencies and efficacies and elucidate structure–activity relationships directly from the primary screen. Comparison of qHTS with traditional single-concentration HTS revealed a high prevalence of false negatives in the single-point screen. This study demonstrates the feasibility of qHTS for accurately profiling every compound in large chemical libraries (>105 compounds). qHTS produces rich data sets that can be immediately mined for reliable biological activities, thereby providing a platform for chemical genomics and accelerating the identification of leads for drug discovery. PMID:16864780

  11. 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

  12. A chemical rescue screen identifies a Plasmodium falciparum apicoplast inhibitor targeting MEP isoprenoid precursor biosynthesis.

    PubMed

    Wu, Wesley; Herrera, Zachary; Ebert, Danny; Baska, Katie; Cho, Seok H; DeRisi, Joseph L; Yeh, Ellen

    2015-01-01

    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

  13. Transcriptional Inhibitors Identified in a 160,000-Compound Small-Molecule DUX4 Viability Screen.

    PubMed

    Choi, Si Ho; Bosnakovski, Darko; Strasser, Jessica M; Toso, Erik A; Walters, Michael A; Kyba, Michael

    2016-08-01

    Facioscapulohumeral muscular dystrophy is a genetically dominant, currently untreatable muscular dystrophy. It is caused by mutations that enable expression of the normally silent DUX4 gene, which encodes a pathogenic transcription factor. A screen based on Tet-on DUX4-induced mouse myoblast death previously uncovered compounds from a 44,000-compound library that protect against DUX4 toxicity. Many of those compounds acted downstream of DUX4 in an oxidative stress pathway. Here, we extend this screen to an additional 160,000 compounds and, using greater stringency, identify a new set of DUX4-protective compounds. From 640 hits, we performed secondary screens, repurchased 46 of the most desirable, confirmed activity, and tested each for activity against other cell death-inducing insults. The majority of these compounds also protected against oxidative stress. Of the 100 repurchased compounds identified through both screens, only SHC40, 75, and 98 inhibited DUX4 target genes, but they also inhibited dox-mediated DUX4 expression. Using a target gene readout on the 640-compound hit set, we discovered three overlooked compounds, SHC351, 540, and 572, that inhibit DUX4 target gene upregulation without nonspecific effects on the Tet-on system. These novel inhibitors of DUX4 transcriptional activity may thus act on pathways or cofactors needed by DUX4 for transcriptional activation in these cells. PMID:27245141

  14. A chemical screen to identify inducers of the mitochondrial unfolded protein response in C. elegans

    PubMed Central

    Rauthan, Manish; Pilon, Marc

    2015-01-01

    We previously showed that inhibition of the mevalonate pathway in C. elegans causes inhibition of protein prenylation, developmental arrest and lethality. We also showed that constitutive activation of the mitochondrial unfolded protein response, UPRmt, is an effective way for C. elegans to become resistant to the negative effects of mevalonate pathway inhibition. This was an important finding since statins, a drug class prescribed to lower cholesterol levels in patients, act by inhibiting the mevalonate pathway, and it is therefore possible that some of their undesirable side effects could be alleviated by activating the UPRmt. Here, we screened a chemical library and identified 4 compounds that specifically activated the UPRmt. One of these compounds, methacycline hydrochloride (a tetracycline antibiotic) also protected C. elegans and mammalian cells from statin toxicity. Methacycline hydrochloride and ethidium bromide, a known UPRmt activator, were also tested in mice: only ethidium bromide significantly activate the UPRmt in skeletal muscles. PMID:27123370

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

    PubMed Central

    Gergely, Szabolcs; Hegedűs, Csaba; Lakatos, Petra; Kovács, Katalin; Gáspár, Renáta; Csont, Tamás; Virág, László

    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

  16. New effective chemically synthesized anti-smallpox compound NIOCH-14.

    PubMed

    Mazurkov, Oleg Yu; Kabanov, Alexey S; Shishkina, Larisa N; Sergeev, Alexander A; Skarnovich, Maksim O; Bormotov, Nikolay I; Skarnovich, Maria A; Ovchinnikova, Alena S; Titova, Ksenya A; Galahova, Darya O; Bulychev, Leonid E; Sergeev, Artemiy A; Taranov, Oleg S; Selivanov, Boris A; Tikhonov, Alexey Ya; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2016-05-01

    Antiviral activity of the new chemically synthesized compound NIOCH-14 (a derivative of tricyclodicarboxylic acid) in comparison with ST-246 (the condensed derivative of pyrroledione) was observed in experiments in vitro and in vivo using orthopoxviruses including highly pathogenic ones. After oral administration of NIOCH-14 to outbred ICR mice infected intranasally with 100 % lethal dose of ectromelia virus, it was shown that 50 % effective doses of NIOCH-14 and ST-246 did not significantly differ. The 'therapeutic window' varied from 1 day before infection to 6 days post-infection (p.i.) to achieve 100-60 % survival rate. The administration of NIOCH-14 and ST-246 to mice resulted in a significant reduction of ectromelia virus titres in organs examined as compared with the control and also reduced pathological changes in the lungs 6 days p.i. Oral administration of NIOCH-14 and ST-246 to ICR mice and marmots challenged with monkeypox virus as compared with the control resulted in a significant reduction of virus production in the lungs and the proportion of infected mice 7 days p.i. as well as the absence of disease in marmots. Significantly lower proportions of infected mice and virus production levels in the lungs as compared with the control were demonstrated in experiments after oral administration of NIOCH-14 and ST-246 to ICR mice and immunodeficient SCID mice challenged with variola virus 3 and 4 days p.i., respectively. The results obtained suggest good prospects for further study of the chemical compound NIOCH-14 to create a new smallpox drug on its basis. PMID:26861777

  17. 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

  18. 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

  19. 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

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

    PubMed

    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

  1. 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

  2. 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. DSF–Cu 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

  3. 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

  4. 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.

  5. Anti-tubercular drug development: computational strategies to identify potential compounds.

    PubMed

    Rajkhowa, Sanchaita; Jha, Anupam Nath; Deka, Ramesh Chandra

    2015-11-01

    InhA is an attractive target to combat tuberculosis (TB), which is targeted by many pro-drugs (isoniazid, etc.) and drugs such as triclosan. However, triclosan is less useful as an antitubercular drug due to its low bioavailability and therefore, in order to overcome this difficulty, many derivatives of triclosan were prepared. Here, we have combined various computational techniques to virtually screen out four potential triclosan derivatives. Molecular docking methods have been employed to screen out 32 out of 62 triclosan derivatives considering the mode of binding and the top re-rank scores. A comparative study on the chemical properties of triclosan and some of its derivatives has been performed using density functional theory (DFT) calculations. DFT based global reactivity descriptors (GRD), such as hardness, chemical potential, chemical softness, electrophilicity index, Fukui function, and local philicity calculated at the optimized geometries were used to investigate the usefulness of these descriptors for understanding the reactive nature and sites of the molecules. QSAR equations were built using these descriptors considering these 32 compounds. Four common compounds showing the best correlation and the best docking scores were considered for the ADMET property calculations and their dynamical movements have been studied using molecular dynamics simulations. Our results showed that these four compounds are chemically more active than triclosan and have the potential to inhibit the Mycobacterium tuberculosis enoyl acyl carrier protein reductase. This work shows that combination of different computational techniques may help to screen out potential drug candidates from a list of possible ones. PMID:26386453

  6. Detailed Chemical Kinetic Reaction Mechanisms for Incineration of Organophosphorus and Fluoro-Organophosphorus Compounds

    SciTech Connect

    Glaude, P A; Melius, C; Pitz, W J; Westbrook, C K

    2001-12-13

    A detailed chemical kinetic reaction mechanism is developed to describe incineration of the chemical warfare nerve agent sarin (GB), based on commonly used principles of bond additivity and hierarchical reaction mechanisms. The mechanism is based on previous kinetic models of organophosphorus compounds such as TMP, DMMP and DIMP that are often used as surrogates to predict incineration of GB. Kinetic models of the three surrogates and GB are then used to predict their consumption in a perfectly stirred reactor fueled by natural gas to simulate incineration of these chemicals. Computed results indicate that DIMP is the only one of these surrogates that adequately describes combustion of GB under comparable conditions. The kinetic pathways responsible for these differences in reactivity are identified and discussed. The most important reaction in GB and DIMP that makes them more reactive than TMP or DMMP is found to be a six-center molecular elimination reaction producing propene.

  7. 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

  8. 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.

  9. Chemical Modification of the Multi-Target Neuroprotective Compound Fisetin

    PubMed Central

    Chiruta, Chandramouli; Schubert, David; Dargusch, Richard; Maher, Pamela

    2012-01-01

    Many factors are implicated in age-related CNS disorders making it unlikely that modulating only a single factor will provide effective treatment. Perhaps a better approach is to identify small molecules that have multiple biological activities relevant to the maintenance of brain function. Recently, we identified an orally active, neuroprotective and cognition-enhancing molecule, the flavonoid fisetin, that is effective in several animal models of CNS disorders. Fisetin has direct antioxidant activity and can also increase the intracellular levels of glutathione (GSH), the major endogenous antioxidant. In addition, fisetin has both neurotrophic and anti-inflammatory activity. However, its relatively high EC50 in cell based assays, low lipophilicity, high tPSA and poor bioavailability suggest that there is room for medicinal chemical improvement. Here we describe a multi-tiered approach to screening that has allowed us to identify fisetin derivatives with significantly enhanced activity in an in vitro neuroprotection model while at the same time maintaining other key activities. PMID:22192055

  10. Identifying and designing chemicals with minimal acute aquatic toxicity

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. 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...

  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. 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, Jürgen 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

  15. High-Throughput Yeast-Based Reporter Assay to Identify Compounds with Anti-inflammatory Potential.

    PubMed

    Garcia, G; Santos, C Nunes do; Menezes, R

    2016-01-01

    The association between altered proteostasis and inflammatory responses has been increasingly recognized, therefore the identification and characterization of novel compounds with anti-inflammatory potential will certainly have a great impact in the therapeutics of protein-misfolding diseases such as degenerative disorders. Although cell-based screens are powerful approaches to identify potential therapeutic compounds, establishing robust inflammation models amenable to high-throughput screening remains a challenge. To bridge this gap, we have exploited the use of yeasts as a platform to identify lead compounds with anti-inflammatory properties. The yeast cell model described here relies on the high-degree homology between mammalian and yeast Ca(2+)/calcineurin pathways converging into the activation of NFAT and Crz1 orthologous proteins, respectively. It consists of a recombinant yeast strain encoding the lacZ gene under the control of Crz1-recongition elements to facilitate the identification of compounds interfering with Crz1 activation through the easy monitoring of β-galactosidase activity. Here, we describe in detail a protocol optimized for high-throughput screening of compounds with potential anti-inflammatory activity as well as a protocol to validate the positive hits using an alternative β-galactosidase substrate. PMID:27613055

  16. LigandBox: A database for 3D structures of chemical compounds

    PubMed Central

    Kawabata, Takeshi; Sugihara, Yusuke; Fukunishi, Yoshifumi; Nakamura, Haruki

    2013-01-01

    A database for the 3D structures of available compounds is essential for the virtual screening by molecular docking. We have developed the LigandBox database (http://ligandbox.protein.osaka-u.ac.jp/ligandbox/) containing four million available compounds, collected from the catalogues of 37 commercial suppliers, and approved drugs and biochemical compounds taken from KEGG_DRUG, KEGG_COMPOUND and PDB databases. Each chemical compound in the database has several 3D conformers with hydrogen atoms and atomic charges, which are ready to be docked into receptors using docking programs. The 3D conformations were generated using our molecular simulation program package, myPresto. Various physical properties, such as aqueous solubility (LogS) and carcinogenicity have also been calculated to characterize the ADME-Tox properties of the compounds. The Web database provides two services for compound searches: a property/chemical ID search and a chemical structure search. The chemical structure search is performed by a descriptor search and a maximum common substructure (MCS) search combination, using our program kcombu. By specifying a query chemical structure, users can find similar compounds among the millions of compounds in the database within a few minutes. Our database is expected to assist a wide range of researchers, in the fields of medical science, chemical biology, and biochemistry, who are seeking to discover active chemical compounds by the virtual screening. PMID:27493549

  17. Environmental Fate of Organophosphorus Compounds Related to Chemical Weapons

    SciTech Connect

    Davisson, M L; Love, A H; Vance, A; Reynolds, J G

    2005-02-08

    Man-made organophosphorus compounds have been widely distributed throughout our environment as pesticides since their development during and after WWII. Many important studies have documented their relative persistence and toxicity. Development and use of some organophosphorus compounds as nerve agents gave rise to a separate but parallel effort to understand environmental persistence. In this latter case, the experiments have focused mainly on evaporation rates and first-order reaction kinetics. However, because organophosphorus compounds are easily polarized, the ionic content of a surrounding media directly factors into these reaction rates, but limited work in this regard has been done under environmentally relevant conditions. Furthermore, limited experiments investigating persistence of these agents on soil has resulted in widely varying degradation rates. Not surprisingly, no studies have investigated affinities of organophosphorus nerve agents to mineral or organic matter typically found in soil. As a result, we initiated laboratory experiments on dilute concentrations of nerve agent O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX) to quantify persistence in simulated environmental aqueous conditions. A quantitative analytical method was developed for VX and its degradation products using High Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (HPLC-ESI-MS). VX hydrolysis rate is known to have a pH-dependency, however, the type of buffer and the relative proportion of different nucleophiles in solution significantly affect the overall rate and mechanism of degradation. For example, dissolved carbonate, a weak nucleophile dominating natural water, yielded pseudo-first order rate constants of {approx} 8 x 10{sup -3}/hr at pH 5 and 2 x 10{sup -2}/hr at pH 11. This small pH-dependent variation departs significantly from widely accepted rates at this pH range (4 x 10{sup -4}/hr to 8 x 10{sup -2}/hr) that were based on

  18. MBROLE 2.0—functional enrichment of chemical compounds

    PubMed Central

    López-Ibáñez, Javier; Pazos, Florencio; Chagoyen, Mónica

    2016-01-01

    Metabolites Biological Role (MBROLE) is a server that performs functional enrichment analysis of a list of chemical compounds derived from a metabolomics experiment, which allows this list to be interpreted in biological terms. Since its release in 2011, MBROLE has been used by different groups worldwide to analyse metabolomics experiments from a variety of organisms. Here we present the latest version of the system, MBROLE2, accessible at http://csbg.cnb.csic.es/mbrole2. MBROLE2 has been supplemented with 10 databases not available in the previous version, which allow analysis over a larger, richer set of vocabularies including metabolite–protein and drug–protein interactions. This new version performs automatic conversion of compound identifiers from different databases, thus simplifying usage. In addition, the user interface has been redesigned to generate an interactive, more intuitive representation of the results. PMID:27084944

  19. 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

  20. Drug Repurposing Screening Identifies Novel Compounds That Effectively Inhibit Toxoplasma gondii Growth

    PubMed Central

    Dittmar, Ashley J.; Drozda, Allison A.

    2016-01-01

    ABSTRACT The urgent need to develop new antimicrobial therapies has spawned the development of repurposing screens in which well-studied drugs and other types of compounds are tested for potential off-label uses. As a proof-of-principle screen to identify compounds effective against Toxoplasma gondii, we screened a collection of 1,120 compounds for the ability to significantly reduce Toxoplasma replication. A total of 94 compounds blocked parasite replication with 50% inhibitory concentrations of <5 µM. A significant number of these compounds are established inhibitors of dopamine or estrogen signaling. Follow-up experiments with the dopamine receptor inhibitor pimozide revealed that the drug impacted both parasite invasion and replication but did so independently of inhibition of dopamine or other neurotransmitter receptor signaling. Tamoxifen, which is an established inhibitor of the estrogen receptor, also reduced parasite invasion and replication. Even though Toxoplasma can activate the estrogen receptor, tamoxifen inhibits parasite growth independently of this transcription factor. Tamoxifen is also a potent inducer of autophagy, and we find that the drug stimulates recruitment of the autophagy marker light chain 3-green fluorescent protein onto the membrane of the vacuolar compartment in which the parasite resides and replicates. In contrast to other antiparasitic drugs, including pimozide, tamoxifen treatment of infected cells leads to a time-dependent elimination of intracellular parasites. Taken together, these data suggest that tamoxifen restricts Toxoplasma growth by inducing xenophagy or autophagic destruction of this obligate intracellular parasite. IMPORTANCE There is an urgent need to develop new therapies to treat microbial infections, and the repurposing of well-characterized compounds is emerging as one approach to achieving this goal. Using the protozoan parasite Toxoplasma gondii, we screened a library of 1,120 compounds and identified several

  1. Drug Repurposing Screening Identifies Novel Compounds That Effectively Inhibit Toxoplasma gondii Growth.

    PubMed

    Dittmar, Ashley J; Drozda, Allison A; Blader, Ira J

    2016-01-01

    The urgent need to develop new antimicrobial therapies has spawned the development of repurposing screens in which well-studied drugs and other types of compounds are tested for potential off-label uses. As a proof-of-principle screen to identify compounds effective against Toxoplasma gondii, we screened a collection of 1,120 compounds for the ability to significantly reduce Toxoplasma replication. A total of 94 compounds blocked parasite replication with 50% inhibitory concentrations of <5 µM. A significant number of these compounds are established inhibitors of dopamine or estrogen signaling. Follow-up experiments with the dopamine receptor inhibitor pimozide revealed that the drug impacted both parasite invasion and replication but did so independently of inhibition of dopamine or other neurotransmitter receptor signaling. Tamoxifen, which is an established inhibitor of the estrogen receptor, also reduced parasite invasion and replication. Even though Toxoplasma can activate the estrogen receptor, tamoxifen inhibits parasite growth independently of this transcription factor. Tamoxifen is also a potent inducer of autophagy, and we find that the drug stimulates recruitment of the autophagy marker light chain 3-green fluorescent protein onto the membrane of the vacuolar compartment in which the parasite resides and replicates. In contrast to other antiparasitic drugs, including pimozide, tamoxifen treatment of infected cells leads to a time-dependent elimination of intracellular parasites. Taken together, these data suggest that tamoxifen restricts Toxoplasma growth by inducing xenophagy or autophagic destruction of this obligate intracellular parasite. IMPORTANCE There is an urgent need to develop new therapies to treat microbial infections, and the repurposing of well-characterized compounds is emerging as one approach to achieving this goal. Using the protozoan parasite Toxoplasma gondii, we screened a library of 1,120 compounds and identified several

  2. 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 ...

  3. 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

  4. Identifying antimalarial compounds targeting dihydrofolate reductase-thymidylate synthase (DHFR-TS) by chemogenomic profiling.

    PubMed

    Aroonsri, Aiyada; Akinola, Olugbenga; Posayapisit, Navaporn; Songsungthong, Warangkhana; Uthaipibull, Chairat; Kamchonwongpaisan, Sumalee; Gbotosho, Grace O; Yuthavong, Yongyuth; Shaw, Philip J

    2016-07-01

    The mode of action of many antimalarial drugs is unknown. Chemogenomic profiling is a powerful method to address this issue. This experimental approach entails disruption of gene function and phenotypic screening for changes in sensitivity to bioactive compounds. Here, we describe the application of reverse genetics for chemogenomic profiling in Plasmodium. Plasmodium falciparum parasites harbouring a transgenic insertion of the glmS ribozyme downstream of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene were used for chemogenomic profiling of antimalarial compounds to identify those which target DHFR-TS. DHFR-TS expression can be attenuated by exposing parasites to glucosamine. Parasites with attenuated DHFR-TS expression were significantly more sensitive to antifolate drugs known to target DHFR-TS. In contrast, no change in sensitivity to other antimalarial drugs with different modes of action was observed. Chemogenomic profiling was performed using the Medicines for Malaria Venture (Switzerland) Malaria Box compound library, and two compounds were identified as novel DHFR-TS inhibitors. We also tested the glmS ribozyme in Plasmodium berghei, a rodent malaria parasite. The expression of reporter genes with downstream glmS ribozyme could be attenuated in transgenic parasites comparable with that obtained in P. falciparum. The chemogenomic profiling method was applied in a P. berghei line expressing a pyrimethamine-resistant Toxoplasma gondii DHFR-TS reporter gene under glmS ribozyme control. Parasites with attenuated expression of this gene were significantly sensitised to antifolates targeting DHFR-TS, but not other drugs with different modes of action. In conclusion, these data show that the glmS ribozyme reverse genetic tool can be applied for identifying primary targets of antimalarial compounds in human and rodent malaria parasites. PMID:27150044

  5. 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

  6. 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.

  7. Yeast-based automated high-throughput screens to identify anti-parasitic lead compounds.

    PubMed

    Bilsland, Elizabeth; Sparkes, Andrew; Williams, Kevin; Moss, Harry J; de Clare, Michaela; Pir, Pinar; Rowland, Jem; Aubrey, Wayne; Pateman, Ron; Young, Mike; Carrington, Mark; King, Ross D; Oliver, Stephen G

    2013-02-01

    We have developed a robust, fully automated anti-parasitic drug-screening method that selects compounds specifically targeting parasite enzymes and not their host counterparts, thus allowing the early elimination of compounds with potential side effects. Our yeast system permits multiple parasite targets to be assayed in parallel owing to the strains' expression of different fluorescent proteins. A strain expressing the human target is included in the multiplexed screen to exclude compounds that do not discriminate between host and parasite enzymes. This form of assay has the advantages of using known targets and not requiring the in vitro culture of parasites. We performed automated screens for inhibitors of parasite dihydrofolate reductases, N-myristoyltransferases and phosphoglycerate kinases, finding specific inhibitors of parasite targets. We found that our 'hits' have significant structural similarities to compounds with in vitro anti-parasitic activity, validating our screens and suggesting targets for hits identified in parasite-based assays. Finally, we demonstrate a 60 per cent success rate for our hit compounds in killing or severely inhibiting the growth of Trypanosoma brucei, the causative agent of African sleeping sickness. PMID:23446112

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

    DOEpatents

    Grindstaff, Quirinus G.

    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.

  9. Identification of a novel Vpr-binding compound that inhibits HIV-1 multiplication in macrophages by chemical array.

    PubMed

    Hagiwara, Kyoji; Murakami, Tomoyuki; Xue, Guangai; Shimizu, Yasuo; Takeda, Eri; Hashimoto, Yoshie; Honda, Kaori; Kondoh, Yasumitsu; Osada, Hiroyuki; Tsunetsugu-Yokota, Yasuko; Aida, Yoko

    2010-12-01

    Although HIV-1 replication can be controlled by highly active anti-retroviral therapy (HAART) using protease and reverse transcriptase inhibitors, the development of multidrug-resistant viruses compromises the efficacy of HAART. Thus, it is necessary to develop new drugs with novel targets. To identify new anti-HIV-1 compounds, recombinant Vpr was purified from transfected COS-7 cells and used to screen compounds by chemical array to identify those that bound Vpr. From this screen, 108 compounds were selected as positive for Vpr binding. Among these, one structurally similar group of four compounds showed anti-HIV activity in macrophages. In particular, compound SIP-1 had high inhibition activity and reduced the levels of p24 by more than 98% in macrophages after 8 or 12 days of infection. SIP-1 had no cytotoxic effects and did not disrupt cell cycle progression or induce apoptosis of Molt-4 and HeLa cell lines as measured by MTT assay, flow-cytometry analysis, and a caspase-3 assay. In addition, SIP-1 specifically bound to Vpr as assessed by photo-cross-linked small-molecule affinity beads. These results suggest that Vpr is a good target for the development of compounds that could potentially inhibit HIV-1 replication. Collectively, our results strongly suggest that chemical array is a useful method for screening anti-viral compounds. PMID:21036153

  10. Advanced exact structure searching in large databases of chemical compounds.

    PubMed

    Trepalin, Sergey V; Skorenko, Andrey V; Balakin, Konstantin V; Nasonov, Anatoly F; Lang, Stanley A; Ivashchenko, Andrey A; Savchuk, Nikolay P

    2003-01-01

    Efficient recognition of tautomeric compound forms in large corporate or commercially available compound databases is a difficult and labor intensive task. Our data indicate that up to 0.5% of commercially available compound collections for bioscreening contain tautomers. Though in the large registry databases, such as Beilstein and CAS, the tautomers are found in an automated fashion using high-performance computational technologies, their real-time recognition in the nonregistry corporate databases, as a rule, remains problematic. We have developed an effective algorithm for tautomer searching based on the proprietary chemoinformatics platform. This algorithm reduces the compound to a canonical structure. This feature enables rapid, automated computer searching of most of the known tautomeric transformations that occur in databases of organic compounds. Another useful extension of this methodology is related to the ability to effectively search for different forms of compounds that contain ionic and semipolar bonds. The computations are performed in the Windows environment on a standard personal computer, a very useful feature. The practical application of the proposed methodology is illustrated by several examples of successful recovery of tautomers and different forms of ionic compounds from real commercially available nonregistry databases. PMID:12767143

  11. 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

  12. A chemical screen to identify inducers of the mitochondrial unfolded protein response in C. elegans.

    PubMed

    Rauthan, Manish; Pilon, Marc

    2015-01-01

    We previously showed that inhibition of the mevalonate pathway in C. elegans causes inhibition of protein prenylation, developmental arrest and lethality. We also showed that constitutive activation of the mitochondrial unfolded protein response, UPR(mt), is an effective way for C. elegans to become resistant to the negative effects of mevalonate pathway inhibition. This was an important finding since statins, a drug class prescribed to lower cholesterol levels in patients, act by inhibiting the mevalonate pathway, and it is therefore possible that some of their undesirable side effects could be alleviated by activating the UPR(mt). Here, we screened a chemical library and identified 4 compounds that specifically activated the UPR(mt). One of these compounds, methacycline hydrochloride (a tetracycline antibiotic) also protected C. elegans and mammalian cells from statin toxicity. Methacycline hydrochloride and ethidium bromide, a known UPR(mt) activator, were also tested in mice: only ethidium bromide significantly activate the UPR(mt) in skeletal muscles. PMID:27123370

  13. Sexual Differences in Chemical Composition and Aroma-active Compounds of Essential Oil from Flower Buds of Eurya japonica.

    PubMed

    Miyazawa, Mitsuo; Usami, Atsushi; Tanaka, Takio; Tsuji, Kaoru; Takehara, Manami; Hori, Yuki

    2016-04-01

    This study was conducted to determine the composition of essential oil from buds of male and female Eurya japonica flowers and to determine the aroma-active compounds of this plant by gas chromatography-mass spectrometry (GC-MS), sensory evaluation, and odor activity values (OAV). The oils contained eighty-five compounds. We identified for the first time forty-four compounds in E. japonica. Through sensory evaluation, nineteen aroma-active compounds were identified by gas chromatography-olfactometry (GC-O). Because the chemical composition can affect the interaction between plants and herbivorous insects, our results suggest that essential oils from male and female flower buds of E. japonica differently affect herbivores. Sexual differences in essential oils deserve further investigations in this plant-insect system. PMID:26972466

  14. Histone markers identify the mode of action for compounds positive in the TK6 micronucleus assay.

    PubMed

    Cheung, Jennifer R; Dickinson, Donna A; Moss, Jocelyn; Schuler, Maik J; Spellman, Richard A; Heard, Pamela L

    2015-01-01

    The in vitro micronucleus assay with TK6 cells is frequently used as part of the genotoxicity testing battery for pharmaceuticals. Consequently, follow-up testing strategies are needed for positive compounds to determine their mode of action, which would then allow for deployment of appropriate in vivo follow-up strategies. We have chosen 3 micronucleus positive compounds, the clastogen etoposide, the aneugen noscapine and the cytotoxicant tunicamycin to evaluate different approaches to determine their aneugenic or clastogenic properties. Each of the three compounds were evaluated following 4 and 24h of continuous treatment by flow cytometry for micronucleus induction, the aneugenicity markers phosphorylated-histone 3 (p-H3) and polyploidy, the clastogenicity marker γH2AX and the apoptosis marker cleaved caspase 3. They were further evaluated by Western blot for mono-ubiquitinated and γH2AX. Results show that the clastogen etoposide produced a dose related increase in γH2AX and mono-ubiquitinated H2AX and a dose related decrease in p-H3 positive mitotic cells. Conversely, the aneugen produced increases in p-H3 and polyploidy with no significant increases seen in mono-ubiquitinated H2AX or γH2AX. Lastly, the cytotoxicant tunicamycin induced neither an increase in p-H3 nor γH2AX. All three compounds produced dose-related increases in cleaved caspase 3. The results from this study provide evidence that adding clastogenicity and aneugenicity markers to the in vitro micronucleus assay in TK6 cells could help to identify the mode of action of positive compounds. The combination of endpoints suggested here needs to be further evaluated by a broader set of test compounds. PMID:25726170

  15. 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.

  16. Acute oral toxicity test of chemical compounds in silkworms.

    PubMed

    Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

    2016-02-01

    This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals. PMID:26971557

  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. Identification and quantification of individual chemical compounds in biogenic secondary organic aerosols using GCxGC-VUV/EI-HRTOFMS

    NASA Astrophysics Data System (ADS)

    Decker, M.; Worton, D. R.; Isaacman, G. A.; Chan, A. W.; Ruehl, C.; Zhao, Y.; Wilson, K. R.; Goldstein, A. H.

    2012-12-01

    Atmospheric aerosols have adverse effects on human health and air quality and affect radiative forcing and thus climate. While the organic fraction of aerosols is substantial, the sources and chemistry leading to the formation of secondary organic aerosols are very poorly understood. Characterizing individual compounds present in organic aerosol provides insights into the sources, formation mechanisms and oxidative transformations that have taken place. Fifteen aerosol samples collected over a 5 day period at the Blodgett Forest Research Station in the Sierra Nevada Mountains, part of the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX) in July 2009, were analyzed using comprehensive two dimensional gas chromatography with high resolution time of flight mass spectrometry (GCxGC-HRTOFMS). Approximately 600 compounds were observed in each sample as significant peaks in the chromatogram. Of these, around a third were identified by matching the unique electron ionization (EI) mass spectrum of each compound to the NIST library of characteristic fragmentation patterns. One filter sample was also analyzed using vacuum ultraviolet ionization (VUV) instead of EI. This 'soft' ionization technique results in much less fragmentation yielding the molecular ion of each compound, from which the exact mass was determined. If the formula of the EI library matched compound equaled the high mass resolution VUV molecular weight within a certain tolerance (< 30 ppm), then the library match was considered confirmed; 226 compounds were identified in this way. Using the VUV technique 234 additional compounds that were not in the EI mass spectral database were assigned chemical formulas based on the observed molecular weights. The chemical formulas in conjunction with the location of the compound in the GCxGC chromatogram were used to provide further classification of these compounds based on their likely functionalization. The broad array of observed oxygenated

  19. 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...

  20. 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.

  1. 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

  2. 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.

  3. GPM: A Graph Pattern Matching Kernel with Diffusion for Chemical Compound Classification

    PubMed Central

    Smalter, Aaron; Huan, Jun; Lushington, Gerald

    2010-01-01

    Classifying chemical compounds is an active topic in drug design and other cheminformatics applications. Graphs are general tools for organizing information from heterogenous sources and have been applied in modelling many kinds of biological data. With the fast accumulation of chemical structure data, building highly accurate predictive models for chemical graphs emerges as a new challenge. In this paper, we demonstrate a novel technique called Graph Pattern Matching kernel (GPM). Our idea is to leverage existing frequent pattern discovery methods and explore their application to kernel classifiers (e.g. support vector machine) for graph classification. In our method, we first identify all frequent patterns from a graph database. We then map subgraphs to graphs in the database and use a diffusion process to label nodes in the graphs. Finally the kernel is computed using a set matching algorithm. We performed experiments on 16 chemical structure data sets and have compared our methods to other major graph kernels. The experimental results demonstrate excellent performance of our method. PMID:20428463

  4. 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

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

    PubMed

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

    2014-03-18

    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

  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. 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

  8. Chemical weapons: documented use and compounds on the horizon.

    PubMed

    Bismuth, Chantal; Borron, Stephen W; Baud, Frederic J; Barriot, Patrick

    2004-04-01

    Man's inhumanity to man is expressed through a plethora of tools of modern warfare and terror. The use of chemical and biological weapons with the goals of assault, demoralisation and lethality has been documented in recent history, both on the battlefield and in urban terror against civilians. A general review of a few of the currently employed chemical weapons and biological toxins, along with a look at potential chemical weapons and tools of counter-terrorism, follows. While these weapons are fearsome elements, the dangers should be viewed in the context of the widespread availability and efficacy of conventional weapons. PMID:15093243

  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. New clues on carcinogenicity-related substructures derived from mining two large datasets of chemical compounds.

    PubMed

    Golbamaki, Azadi; Benfenati, Emilio; Golbamaki, Nazanin; Manganaro, Alberto; Merdivan, Erinc; Roncaglioni, Alessandra; Gini, Giuseppina

    2016-04-01

    In this study, new molecular fragments associated with genotoxic and nongenotoxic carcinogens are introduced to estimate the carcinogenic potential of compounds. Two rule-based carcinogenesis models were developed with the aid of SARpy: model R (from rodents' experimental data) and model E (from human carcinogenicity data). Structural alert extraction method of SARpy uses a completely automated and unbiased manner with statistical significance. The carcinogenicity models developed in this study are collections of carcinogenic potential fragments that were extracted from two carcinogenicity databases: the ANTARES carcinogenicity dataset with information from bioassay on rats and the combination of ISSCAN and CGX datasets, which take into accounts human-based assessment. The performance of these two models was evaluated in terms of cross-validation and external validation using a 258 compound case study dataset. Combining R and H predictions and scoring a positive or negative result when both models are concordant on a prediction, increased accuracy to 72% and specificity to 79% on the external test set. The carcinogenic fragments present in the two models were compared and analyzed from the point of view of chemical class. The results of this study show that the developed rule sets will be a useful tool to identify some new structural alerts of carcinogenicity and provide effective information on the molecular structures of carcinogenic chemicals. PMID:26986491

  11. Prediction of Bioactive Compounds Using Computed NMR Chemical Shifts.

    PubMed

    Karthikeyan, Muthukumarasamy; Rajamohanan, Pattuparambil Ramanpillai; Vyas, Renu

    2015-01-01

    NMR based chemical shifts are an important diagnostic parameter for structure elucidation as they capture rich information related to conformational, electronic and stereochemical arrangement of functional groups in a molecule which is responsible for its activity towards any biological target. The present work discusses the importance of computing NMR chemical shifts from molecular structures. The NMR chemical shift data (experimental or computed) was used to generate fingerprints in binary formats for mapping molecular fragments (as descriptors) and correlating with the bioactivity classes. For this study, chemical shift data derived binary fingerprints were computed for 149 classes and 4800 bioactive molecules. The sensitivity and selectivity of fingerprints in discriminating molecules belonging to different therapeutic categories was assessed using a LibSVM based classifier. An accuracy of 82% for proton and 94% for carbon NMR fingerprints were obtained for anti-psoriatic and anti-psychotic molecules demonstrating the effectiveness of this approach for virtual screening. PMID:26138568

  12. Lead selection and characterization of antitubercular compounds using the Nested Chemical Library.

    PubMed

    Sipos, Anna; Pató, János; Székely, Rita; Hartkoorn, Ruben C; Kékesi, László; Őrfi, László; Szántai-Kis, Csaba; Mikušová, Katarína; Svetlíková, Zuzana; Korduláková, Jana; Nagaraja, Valakunja; Godbole, Adwait Anand; Bush, Natassja; Collin, Frédéric; Maxwell, Anthony; Cole, Stewart T; Kéri, György

    2015-06-01

    Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based approaches against several validated mycobacterial enzymes and phenotypic screens. We screened more than 17,000 compounds from Vichem's Nested Chemical Library™ using an integrated strategy involving whole cell-based assays with Corynebacterium glutamicum and Mycobacterium tuberculosis, and target-based assays with protein kinases PknA, PknB and PknG as well as other targets such as PimA and bacterial topoisomerases simultaneously. With the help of the target-based approach we have found very potent hits inhibiting the selected target enzymes, but good minimal inhibitory concentrations (MIC) against M. tuberculosis were not achieved. Focussing on the whole cell-based approach several potent hits were found which displayed minimal inhibitory concentrations (MIC) against M. tuberculosis below 10 μM and were non-mutagenic, non-cytotoxic and the targets of some of the hits were also identified. The most active hits represented various scaffolds. Medicinal chemistry-based lead optimization was performed applying various strategies and, as a consequence, a series of novel potent compounds were synthesized. These efforts resulted in some effective potential antitubercular lead compounds which were confirmed in phenotypic assays. PMID:25801335

  13. 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

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

    PubMed Central

    Kraft, Robert; Kahn, Allon; Medina-Franco, José L.; Orlowski, Mikayla L.; Baynes, Cayla; López-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

  15. A small molecule screen identifies a novel compound that induces a homeotic transformation in Hydra.

    PubMed

    Glauber, Kristine M; Dana, Catherine E; Park, Steve S; Colby, David A; Noro, Yukihiko; Fujisawa, Toshitaka; Chamberlin, A Richard; Steele, Robert E

    2013-12-01

    Developmental processes such as morphogenesis, patterning and differentiation are continuously active in the adult Hydra polyp. We carried out a small molecule screen to identify compounds that affect patterning in Hydra. We identified a novel molecule, DAC-2-25, that causes a homeotic transformation of body column into tentacle zone. This transformation occurs in a progressive and polar fashion, beginning at the oral end of the animal. We have identified several strains that respond to DAC-2-25 and one that does not, and we used chimeras from these strains to identify the ectoderm as the target tissue for DAC-2-25. Using transgenic Hydra that express green fluorescent protein under the control of relevant promoters, we examined how DAC-2-25 affects tentacle patterning. Genes whose expression is associated with the tentacle zone are ectopically expressed upon exposure to DAC-2-25, whereas those associated with body column tissue are turned off as the tentacle zone expands. The expression patterns of the organizer-associated gene HyWnt3 and the hypostome-specific gene HyBra2 are unchanged. Structure-activity relationship studies have identified features of DAC-2-25 that are required for activity and potency. This study shows that small molecule screens in Hydra can be used to dissect patterning processes. PMID:24255098

  16. A small molecule screen identifies a novel compound that induces a homeotic transformation in Hydra

    PubMed Central

    Glauber, Kristine M.; Dana, Catherine E.; Park, Steve S.; Colby, David A.; Noro, Yukihiko; Fujisawa, Toshitaka; Chamberlin, A. Richard; Steele, Robert E.

    2013-01-01

    Developmental processes such as morphogenesis, patterning and differentiation are continuously active in the adult Hydra polyp. We carried out a small molecule screen to identify compounds that affect patterning in Hydra. We identified a novel molecule, DAC-2-25, that causes a homeotic transformation of body column into tentacle zone. This transformation occurs in a progressive and polar fashion, beginning at the oral end of the animal. We have identified several strains that respond to DAC-2-25 and one that does not, and we used chimeras from these strains to identify the ectoderm as the target tissue for DAC-2-25. Using transgenic Hydra that express green fluorescent protein under the control of relevant promoters, we examined how DAC-2-25 affects tentacle patterning. Genes whose expression is associated with the tentacle zone are ectopically expressed upon exposure to DAC-2-25, whereas those associated with body column tissue are turned off as the tentacle zone expands. The expression patterns of the organizer-associated gene HyWnt3 and the hypostome-specific gene HyBra2 are unchanged. Structure-activity relationship studies have identified features of DAC-2-25 that are required for activity and potency. This study shows that small molecule screens in Hydra can be used to dissect patterning processes. PMID:24255098

  17. 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 ~835°C 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

  18. Using fragmentation trees and mass spectral trees for identifying unknown compounds in metabolomics

    PubMed Central

    Vaniya, Arpana

    2015-01-01

    Identification of unknown metabolites is the bottleneck in advancing metabolomics, leaving interpretation of metabolomics results ambiguous. The chemical diversity of metabolism is vast, making structure identification arduous and time consuming. Currently, comprehensive analysis of mass spectra in metabolomics is limited to library matching, but tandem mass spectral libraries are small compared to the large number of compounds found in the biosphere, including xenobiotics. Resolving this bottleneck requires richer data acquisition and better computational tools. Multi-stage mass spectrometry (MSn) trees show promise to aid in this regard. Fragmentation trees explore the fragmentation process, generate fragmentation rules and aid in sub-structure identification, while mass spectral trees delineate the dependencies in multi-stage MS of collision-induced dissociations. This review covers advancements over the past 10 years as a tool for metabolite identification, including algorithms, software and databases used to build and to implement fragmentation trees and mass spectral annotations. PMID:26213431

  19. Grape Seed Oil Compounds: Biological and Chemical Actions for Health

    PubMed Central

    Garavaglia, Juliano; Markoski, Melissa M.; Oliveira, Aline; Marcadenti, Aline

    2016-01-01

    Grape seed oil is rich in phenolic compounds, fatty acids, and vitamins, with economic importance to pharmaceutical, cosmetic, and food industry. Its use as an edible oil has also been suggested, especially due to its pleasant sensory characteristics. Grape seed oil has beneficial properties for health that are mainly detected by in vitro studies, such as anti-inflammatory, cardioprotective, antimicrobial, and anticancer properties, and may interact with cellular and molecular pathways. These effects have been related to grape seed oil constituents, mainly tocopherol, linolenic acid, resveratrol, quercetin, procyanidins, carotenoids, and phytosterols. The aim of this article was to briefly review the composition and nutritional aspects of grape seed oil, the interactions of its compounds with molecular and cellular pathways, and its possible beneficial effects on health. PMID:27559299

  20. Grape Seed Oil Compounds: Biological and Chemical Actions for Health.

    PubMed

    Garavaglia, Juliano; Markoski, Melissa M; Oliveira, Aline; Marcadenti, Aline

    2016-01-01

    Grape seed oil is rich in phenolic compounds, fatty acids, and vitamins, with economic importance to pharmaceutical, cosmetic, and food industry. Its use as an edible oil has also been suggested, especially due to its pleasant sensory characteristics. Grape seed oil has beneficial properties for health that are mainly detected by in vitro studies, such as anti-inflammatory, cardioprotective, antimicrobial, and anticancer properties, and may interact with cellular and molecular pathways. These effects have been related to grape seed oil constituents, mainly tocopherol, linolenic acid, resveratrol, quercetin, procyanidins, carotenoids, and phytosterols. The aim of this article was to briefly review the composition and nutritional aspects of grape seed oil, the interactions of its compounds with molecular and cellular pathways, and its possible beneficial effects on health. PMID:27559299

  1. 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.

  2. Chemical profiles and identification of key compound caffeine in marine-derived traditional Chinese medicine Ostreae concha.

    PubMed

    Yang, Xue; Zhou, Shi-Lu; Ma, Ai-Cui; Xu, Hai-Tao; Guan, Hua-Shi; Liu, Hong-Bing

    2012-05-01

    To compare the chemical differences between the medicinal and cultured oyster shells, their chemical profiles were investigated. Using the ultra performance liquid chromatography-electron spraying ionization-mass spectrometry (UPLC-ESI-MS), combined with principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA), the discrimination of the chemical characteristics among the medicinal and cultured oyster shells was established. Moreover, the chemometric analysis revealed some potential key compounds. After a large-scale extraction and isolation, one target key compound was unambiguously identified as caffeine based on extensive spectroscopic data analysis (1D and 2D NMR, MS, and UV) and comparison with literature data. PMID:22822365

  3. Chemical Profiles and Identification of Key Compound Caffeine in Marine-Derived Traditional Chinese Medicine Ostreae concha

    PubMed Central

    Yang, Xue; Zhou, Shi-Lu; Ma, Ai-Cui; Xu, Hai-Tao; Guan, Hua-Shi; Liu, Hong-Bing

    2012-01-01

    To compare the chemical differences between the medicinal and cultured oyster shells, their chemical profiles were investigated. Using the ultra performance liquid chromatography-electron spraying ionization-mass spectrometry (UPLC-ESI-MS), combined with principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA), the discrimination of the chemical characteristics among the medicinal and cultured oyster shells was established. Moreover, the chemometric analysis revealed some potential key compounds. After a large-scale extraction and isolation, one target key compound was unambiguously identified as caffeine (1) based on extensive spectroscopic data analysis (1D and 2D NMR, MS, and UV) and comparison with literature data. PMID:22822365

  4. 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.

  5. 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 ...

  6. 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...

  7. 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.

  8. 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

    2016-04-19

    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.

  9. 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 ...

  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

  11. 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

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

    NASA Astrophysics Data System (ADS)

    Hilchenbach, M.; Fischer, H.; Krüger, H.; Thirkell, L.; Rynö, 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. E-prescribing errors identified in a compounding pharmacy: a quality-improvement project.

    PubMed

    Reed-Kane, Dana; Kittell, Katrina; Adkins, Jacquelyn; Flocks, Sarah; Nguyen, Thu

    2014-01-01

    Errors during the prescribing process can cause problems for patients. When the pharmacist intercepts a prescribing error, it can cause a delay, as the patient may not receive the medication until the problem is resolved. Electronic prescriptions are purported to reduce prescribing errors. However, studies have shown that electronic prescriptions can be prone to certain types of errors. Compounding pharmacies may present an additional obstacle for e-prescribing, as the prescribed medications are not commercially available and may not be listed in the e-prescribing software. The objectives of this study were to estimate the electronic prescription error rate in a compounding pharmacy, determine the most common error types, list the most common interventions pharmacists made, and estimate how long it took to resolve these errors. The study design was quality improvement with descriptive data. During the four weeks of data collection, the pharmacists were trained to complete a standardized data collection form when they identified an electronic prescription error. Percentages were calculated for new prescriptions, electronic prescriptions with errors, error types, and error resolution methods. In the four-week period of the study, there were 982 new prescriptions, 111 of which were electronic prescriptions. Of those 111 electronic prescriptions, 70 had errors. The electronic prescriptions error rate was 63%. The most common type of error was wrong entry field (70.3%). For this project, wrong entry field was defined to mean that the drug name was in the wrong field (81%) or that multiple entries were in the wrong field (7%). Pharmacists usually used their own judgment to resolve an error (67%). Many e-prescription errors were identified in this compounding pharmacy. When prescription errors happen, workflow and patient care are disrupted. Our goal is to discuss these findings with Surescripts and e-prescribing software companies to seek systems-based solutions. PMID

  14. 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...

  15. 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 0.46 mmol/L. Another aldehyde (citronellal), alcohol (citronellol, geraniol, (±)-linalool, (−)-linalool, (+)-borneol, (−)-borneol, α-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 2.6 mmol/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 (2–5 mmol/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

  16. 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...

  17. 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.

  18. Chemical Screens Identify Drugs that Enhance or Mitigate Cellular Responses to Antibody-Toxin Fusion Proteins

    PubMed Central

    Guha, Rajarshi; Simon, Nathan; Pasetto, Matteo; Keller, Jonathan; Huang, Manjie; Angelus, Evan; Pastan, Ira; Ferrer, Marc; FitzGerald, David J.; Thomas, Craig J.

    2016-01-01

    The intersection of small molecular weight drugs and antibody-based therapeutics is rarely studied in large scale. Both types of agents are currently part of the cancer armamentarium. However, very little is known about how to combine them in optimal ways. Immunotoxins are antibody-toxin gene fusion proteins engineered to target cancer cells via antibody binding to surface antigens. For fusion proteins derived from Pseudomonas exotoxin (PE), potency relies on the enzymatic domain of the toxin which catalyzes the ADP-ribosylation of EF2 causing inhibition of protein synthesis leading to cell death. Candidate immunotoxins have demonstrated clear value in clinical trials but generally have not been curative as single agents. Therefore we undertook three screens to discover effective combinations that could act synergistically. From the MIPE-3 library of compounds we identified various enhancers of immunotoxin action and at least one major class of inhibitor. Follow-up experiments confirmed the screening data and suggested that immunotoxins when administered with everolimus or nilotinib exhibit favorable combinatory activity and would be candidates for preclinical development. Mechanistic studies revealed that everolimus-immunotoxin combinations acted synergistically on elements of the protein synthetic machinery, including S61 kinase and 4E-BP1 of the mTORC1 pathway. Conversely, PARP inhibitors antagonized immunotoxins and also blocked the toxicity due to native ADP-ribosylating toxins. Thus, our goal of investigating a chemical library was justified based on the identification of several approved compounds that could be developed preclinically as ‘enhancers’ and at least one class of mitigator to be avoided. PMID:27556570

  19. 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.

  20. Potent Plasmodium falciparum gametocytocidal activity of diaminonaphthoquinones, lead antimalarial chemotypes identified in an antimalarial compound screen.

    PubMed

    Tanaka, Takeshi Q; Guiguemde, W Armand; Barnett, David S; Maron, Maxim I; Min, Jaeki; Connelly, Michele C; Suryadevara, Praveen Kumar; Guy, R Kiplin; Williamson, Kim C

    2015-03-01

    Forty percent of the world's population is threatened by malaria, which is caused by Plasmodium parasites and results in an estimated 200 million clinical cases and 650,000 deaths each year. Drug resistance has been reported for all commonly used antimalarials and has prompted screens to identify new drug candidates. However, many of these new candidates have not been evaluated against the parasite stage responsible for transmission, gametocytes. If Plasmodium falciparum gametocytes are not eliminated, patients continue to spread malaria for weeks after asexual parasite clearance. Asymptomatic individuals can also harbor gametocyte burdens sufficient for transmission, and a safe, effective gametocytocidal agent could also be used in community-wide malaria control programs. Here, we identify 15 small molecules with nanomolar activity against late-stage gametocytes. Fourteen are diaminonaphthoquinones (DANQs), and one is a 2-imino-benzo[d]imidazole (IBI). One of the DANQs identified, SJ000030570, is a lead antimalarial candidate. In contrast, 94% of the 650 compounds tested are inactive against late-stage gametocytes. Consistent with the ineffectiveness of most approved antimalarials against gametocytes, of the 19 novel compounds with activity against known anti-asexual-stage targets, only 3 had any strong effect on gametocyte viability. These data demonstrate the distinct biology of the transmission stages and emphasize the importance of screening for gametocytocidal activity. The potent gametocytocidal activity of DANQ and IBI coupled with their efficacy against asexual parasites provides leads for the development of antimalarials with the potential to prevent both the symptoms and the spread of malaria. PMID:25512421

  1. Potent Plasmodium falciparum Gametocytocidal Activity of Diaminonaphthoquinones, Lead Antimalarial Chemotypes Identified in an Antimalarial Compound Screen

    PubMed Central

    Tanaka, Takeshi Q; Guiguemde, W. Armand; Barnett, David S.; Maron, Maxim I.; Min, Jaeki; Connelly, Michele C.; Suryadevara, Praveen Kumar; Guy, R. Kiplin

    2014-01-01

    Forty percent of the world's population is threatened by malaria, which is caused by Plasmodium parasites and results in an estimated 200 million clinical cases and 650,000 deaths each year. Drug resistance has been reported for all commonly used antimalarials and has prompted screens to identify new drug candidates. However, many of these new candidates have not been evaluated against the parasite stage responsible for transmission, gametocytes. If Plasmodium falciparum gametocytes are not eliminated, patients continue to spread malaria for weeks after asexual parasite clearance. Asymptomatic individuals can also harbor gametocyte burdens sufficient for transmission, and a safe, effective gametocytocidal agent could also be used in community-wide malaria control programs. Here, we identify 15 small molecules with nanomolar activity against late-stage gametocytes. Fourteen are diaminonaphthoquinones (DANQs), and one is a 2-imino-benzo[d]imidazole (IBI). One of the DANQs identified, SJ000030570, is a lead antimalarial candidate. In contrast, 94% of the 650 compounds tested are inactive against late-stage gametocytes. Consistent with the ineffectiveness of most approved antimalarials against gametocytes, of the 19 novel compounds with activity against known anti-asexual-stage targets, only 3 had any strong effect on gametocyte viability. These data demonstrate the distinct biology of the transmission stages and emphasize the importance of screening for gametocytocidal activity. The potent gametocytocidal activity of DANQ and IBI coupled with their efficacy against asexual parasites provides leads for the development of antimalarials with the potential to prevent both the symptoms and the spread of malaria. PMID:25512421

  2. Combined Rational Design and a High Throughput Screening Platform for Identifying Chemical Inhibitors of a Ras-activating Enzyme*

    PubMed Central

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

    2015-01-01

    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

  3. Reactivity of target compounds for chemical coal desulfurization. Technical report, 1 December 1993--28 February 1994

    SciTech Connect

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

    1994-06-01

    This project seeks to identify representative organosulfur compounds which are removed by coal desulfurization reactions. Demineralized coals from the Illinois Basin Coal Sample Program are solvent extracted and the extracts fractionated to separate and concentrate organosulfur compounds for analysis by Gas Chromatography/Mass Spectroscopy. After sulfur compounds are characterized, the parent extracts will be subjected to reactions previously shown to reduce the organic sulfur content of Illinois coals, fractionated and again analyzed for organosulfur content to determine which compounds reacted during the chemical treatment. The original coal 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. During this quarter, work continued on developing efficient methods to isolate and analyze sulfur-rich coal extract fractions by GC/MS. Since only relatively non-polar compounds can be analyzed, pyridine extracts must be fractionated. Direct extraction of several coals with toluene is quicker but did not give as much toluene soluble material as fractionation of pyridine extracts and is thus not suitable for preparation of representative analytical samples. The authors observe that most IBC sample program coals contain elemental sulfur due to oxidation of pyrite. There is less elemental sulfur in IBC-101 than in other Herrin coals. This coal was washed in a preparation plant to reduce pyrite concentration. Since elemental sulfur slowly reacts to produce organosulfur compounds in coal during storage or handling, this suggests that early removal of pyrite can reduce formation of these hard to remove compounds.

  4. 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

  5. A Chemical Genetic Screen for Modulators of Exocytic Transport Identifies Inhibitors of a Transport Mechanism Linked to GTR2 Function▿

    PubMed Central

    Zhang, Lisha; Huang, Min; Harsay, Edina

    2010-01-01

    Membrane and protein traffic to the cell surface is mediated by partially redundant pathways that are difficult to perturb in ways that yield a strong phenotype. Such robustness is expected in a fine-tuned process, regulated by environmental cues, that is required for controlled cell surface growth and cell proliferation. Synthetic genetic interaction screens are especially valuable for investigating complex processes involving partially redundant pathways or mechanisms. In a previous study, we used a triple-synthetic-lethal yeast mutant screen to identify a novel component of the late exocytic transport machinery, Avl9. In a chemical-genetic version of the successful mutant screen, we have now identified small molecules that cause a rapid (within 15 min) accumulation of secretory cargo and abnormal Golgi compartment-like membranes at low concentration (<2 μM), indicating that the compounds likely target the exocytic transport machinery at the Golgi. We screened for genes that, when overexpressed, suppress the drug effects, and found that the Ras-like small GTPase, Gtr2, but not its homolog and binding partner, Gtr1, efficiently suppresses the toxic effects of the compounds. Furthermore, assays for suppression of the secretory defect caused by the compounds suggest that Gtr proteins can regulate a pathway that is perturbed by the compounds. Because avl9Δ and gtr mutants share some phenotypes, our results indicate that the small molecules identified by our chemical-genetic strategy are promising tools for understanding Avl9 function and the mechanisms that control late exocytic transport. PMID:19897736

  6. Characterization of the reactivities of volatile organic compounds using a master chemical mechanism.

    PubMed

    Derwent, R G; Jenkin, M E; Saunders, S M; Pilling, M J

    2001-05-01

    A comprehensive description of the ozone-forming potentials of 101 organic compounds has been constructed under North American urban "averaged conditions" using a detailed master chemical mechanism and a simple air parcel trajectory model. This chemical mechanism describes the reactions of 3603 chemical species taking part in more than 10,500 chemical reactions. An index value has been calculated for each organic compound, which describes the increment in ozone concentrations found downwind of an urban area following the emission of a fixed increment in the mass emission of each organic compound. These indices, termed photochemical ozone creation potentials (POCPs), have been expressed on a scale relative to ethylene (ethene) = 100, and, a reactivity scale has been generated for alkanes, alkenes, and oxygenated and halogenated organic compounds. A high degree of correlation (R2 = 0.9) was found between these POCP values and the most widely accepted urban reactivity scale. While the reactivities of most of the 86 organic compounds compared fell within a consistent range, significant discrepancies were found for only 5 compounds. Single-day or multiday conditions appear to be important in establishing quantitative reactivity scales for the less reactive organic compounds. PMID:11355457

  7. 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

  8. ToxAlerts: A Web Server of Structural Alerts for Toxic Chemicals and Compounds with Potential Adverse Reactions

    PubMed Central

    2012-01-01

    The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at http://ochem.eu/alerts, and it is constantly

  9. 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…

  10. 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

  11. Spectral imaging of chemical compounds using multivariate optically enhanced filters integrated with InGaAs VGA cameras

    NASA Astrophysics Data System (ADS)

    Priore, Ryan J.; Jacksen, Niels

    2016-05-01

    Infrared hyperspectral imagers (HSI) have been fielded for the detection of hazardous chemical and biological compounds, tag detection (friend versus foe detection) and other defense critical sensing missions over the last two decades. Low Size/Weight/Power/Cost (SWaPc) methods of identification of chemical compounds spectroscopy has been a long term goal for hand held applications. We describe a new HSI concept for low cost / high performance InGaAs SWIR camera chemical identification for military, security, industrial and commercial end user applications. Multivariate Optical Elements (MOEs) are thin-film devices that encode a broadband, spectroscopic pattern allowing a simple broadband detector to generate a highly sensitive and specific detection for a target analyte. MOEs can be matched 1:1 to a discrete analyte or class prediction. Additionally, MOE filter sets are capable of sensing an orthogonal projection of the original sparse spectroscopic space enabling a small set of MOEs to discriminate a multitude of target analytes. This paper identifies algorithms and broadband optical filter designs that have been demonstrated to identify chemical compounds using high performance InGaAs VGA detectors. It shows how some of the initial models have been reduced to simple spectral designs and tested to produce positive identification of such chemicals. We also are developing pixilated MOE compressed detection sensors for the detection of a multitude of chemical targets in challenging backgrounds/environments for both commercial and defense/security applications. This MOE based, real-time HSI sensor will exhibit superior sensitivity and specificity as compared to currently fielded HSI systems.

  12. Organohelium compounds: structures, stabilities and chemical bonding analyses.

    PubMed

    Fourré, Isabelle; Alvarez, Elsa; Chaquin, Patrick

    2014-02-24

    This paper deals with the possibility of forming short and relatively strong carbon-helium bonds in small typical organic molecules through substitution of one or several H atoms by He(+). A structural and energetics study (based on high-level calculations) of this unusual bonding, as well as a topological characterization of the resulting cations, is undertaken. Stable species generally requires substitution of about half of the hydrogen atoms for formation. Under these conditions, the number of such species appears to be potentially unlimited. "True" C-He bonds exhibit equilibrium distances ranging from 1.327 (C2H2He2(2+)) to 1.129 Å (He2CO(2+)). The energies of neutral He releasing range from approximately 5 kcal mol(-1) [He2CO(2+), (Z)-C2H2He2(2+)] to 25 kcal mol(-1) (C2HHe3(3+)), but remain most frequently around 10 kcal mol(-1). However, most of He(+)-substituted hydrocarbons are metastable with respect to C-C cleavage, except derivatives of ethene. Atoms in molecules (AIM) and electron localization function (ELF) topological descriptors classify the C-He bond as a weak charge-shift interaction [S. Shaik, D. Danovich, B. Silvi, D. L. Lauvergnat, P. C. Hiberty, Chem. Eur. J. 2005, 11, 6358-6371] in agreement with a recent publication by Rzepa [S. H. Rzepa, Nat. Chem. 2010, 2, 390-393]. He2CO(2+) is the only investigated compound that presents a C-He bonding ELF basin, which indicates a non-negligible covalent contribution to the bond. Other modifications in the electronic structure, such as the breaking of the triple bond in ethyne derivatives or the loss of aromaticity in C6H3He3(3+), are also nicely revealed by the ELF topology. PMID:24488791

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  17. 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

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

    PubMed Central

    Kochanek, Jitka; Flematti, Gavin R.

    2016-01-01

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

  19. [Recent advances in the study of antifungal lead compounds with new chemical scaffolds].

    PubMed

    Shao, Lü-cheng; Sheng, Chun-quan; Zhang, Wan-nian

    2007-11-01

    In recent years, the incidence of infections caused by invasive fungal pathogens has increased dramatically. However, most antifungal agents used in clinic have many drawbacks and cannot meet the demand of the clinical use. Therefore, for the development of new generation of antifungal agents, it is of great significance to find antifungal lead compounds with novel chemical scaffolds and new mode of action. Novel antifungal lead compounds reported in recent years are reviewed. Their chemical structures, antifungal activity and structure-activity relationship are discussed in detail, and current problems and trends in future research are also emphasized. PMID:18300466

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

    PubMed Central

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

    2013-01-01

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

  1. 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.

  2. 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

  3. Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections.

    PubMed

    Don, Rob; Ioset, Jean-Robert

    2014-01-01

    The Drugs for Neglected Diseases initiative (DNDi) has defined and implemented an early discovery strategy over the last few years, in fitting with its virtual R&D business model. This strategy relies on a medium- to high-throughput phenotypic assay platform to expedite the screening of compound libraries accessed through its collaborations with partners from the pharmaceutical industry. We review the pragmatic approaches used to select compound libraries for screening against kinetoplastids, taking into account screening capacity. The advantages, limitations and current achievements in identifying new quality series for further development into preclinical candidates are critically discussed, together with attractive new approaches currently under investigation. PMID:23985066

  4. 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.

  5. 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.

  6. 3D numerical simulation of the transport of chemical signature compounds from buried landmines

    NASA Astrophysics Data System (ADS)

    Irrazabal, Maik; Borrero, Ernesto; Briano, Julio G.; Castro, Miguel; Hernandez, Samuel P.

    2005-06-01

    The transport of the chemical signature compounds from buried landmines in a three-dimensional (3D) array has been numerically modeled using the finite-volume technique. Compounds such as trinitrotoluene, dinitrotoluene, and their degradation products, are semi volatile and somewhat soluble in water. Furthermore, they can strongly adsorb to the soil and undergo chemical and biological degradation. Consequently, the spatial and temporal concentration distributions of such chemicals depend on the mobility of the water and gaseous phases, their molecular and mechanical diffusion, adsorption characteristics, soil water content, compaction, and environmental factors. A 3D framework is required since two-dimensional (2D) symmetry may easily fade due to terrain topography: non-flat surfaces, soil heterogeneity, or underground fractures. The spatial and temporal distribution of the chemical-signature-compounds, in an inclined grid has been obtained. The fact that the chemicals may migrate horizontally, giving higher surface concentrations at positions not directly on top of the objects, emphasizes the need for understanding the transport mechanism when a chemical detector is used. Deformation in the concentration contours after rainfall is observed in the inclined surface and is attributed to both: the advective flux, and to the water flux at the surface caused by the slope. The analysis of the displacements in the position of the maximum concentrations at the surface, respect to the actual location of the mine, in an inclined system, is presented.

  7. 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

  8. 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

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

    PubMed

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

    2016-04-01

    The epithelial-to-mesenchymal transition (EMT) is a highly conserved morphogenetic program essential for embryogenesis, regeneration and cancer metastasis. In cancer cells, EMT also triggers cellular reprogramming and chemoresistance, which underlie disease relapse and decreased survival. Hence, identifying compounds that block EMT is essential to prevent or eradicate disseminated tumor cells. Here, we establish a whole-animal-based EMT reporter in zebrafish for rapid drug screening, calledTg(snai1b:GFP), which labels epithelial cells undergoing EMT to producesox10-positive neural crest (NC) cells. Time-lapse and lineage analysis ofTg(snai1b:GFP)embryos reveal that cranial NC cells delaminate from two regions: an early population delaminates adjacent to the neural plate, whereas a later population delaminates from within the dorsal neural tube. TreatingTg(snai1b:GFP)embryos with candidate small-molecule EMT-inhibiting compounds identified TP-0903, a multi-kinase inhibitor that blocked cranial NC cell delamination in both the lateral and medial populations. RNA sequencing (RNA-Seq) analysis and chemical rescue experiments show that TP-0903 acts through stimulating retinoic acid (RA) biosynthesis and RA-dependent transcription. These studies identify TP-0903 as a new therapeutic for activating RAin vivoand raise the possibility that RA-dependent inhibition of EMT contributes to its prior success in eliminating disseminated cancer cells. PMID:26794130

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

    PubMed Central

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

    2016-01-01

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

  11. 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...

  12. 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.

  13. Chemical compounds toxic to invertebrates isolated from marine cyanobacteria of potential relevance to the agricultural industry.

    PubMed

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

    2014-11-01

    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

  14. 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

  15. Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes.

    PubMed

    Coimbra, Maria; Isacchi, Benedetta; van Bloois, Louis; Torano, Javier Sastre; Ket, Aldo; Wu, Xiaojie; Broere, Femke; Metselaar, Josbert M; Rijcken, Cristianne J F; Storm, Gert; Bilia, Rita; Schiffelers, Raymond M

    2011-09-20

    Natural bioactive compounds have been studied for a long time for their chemopreventive and therapeutic potential in several chronic inflammatory diseases, including cancer. However, their physicochemical properties generally result in poor chemical stability and lack of in vivo bioavailability. Very few human clinical trials have addressed absorption, distribution, metabolism, and excretion of these compounds in relation to efficacy. This limits the use of these valuable natural compounds in the clinic. In this study, we examined caffeic acid (derivatives), carvacrol (derivatives), thymol, pterostilbene (derivatives), and N-(3-oxo-dodecanoyl)-l-homoserine lactone. These are natural compounds with strong anti-inflammatory properties derived from plants and bacteria. However, these compounds have poor water solubility or are chemically unstable. To overcome these limitations we have prepared liposomal formulations. Our results show that lipophilic 3-oxo-C(12)-homoserine lactone and stilbene derivatives can be loaded into liposomal lipid bilayer with efficiencies of 50-70%. Thereby, the liposomes solubilize these compounds, allowing intravenous administration without use of solvents. When compounds could not be loaded into the lipid bilayer (carvacrol and thymol) or are rapidly extracted from the liposomes in the presence of serum albumin (3-oxo-C(12)-homoserine lactone and pterostilbene derivatives), derivatization of the compound into a water-soluble prodrug was shown to improve loading efficiency and encapsulation stability. The phosphate forms of carvacrol and pterostilbene were loaded into the aqueous interior of the liposomes and encapsulation was unaffected by the presence of serum albumin. Chemical instability of resveratrol was improved by liposome-encapsulation, preventing inactivating cis-trans isomerization. For caffeic acid, liposomal encapsulation did not prevent oxidation into a variety of products. Still, by derivatization into a phenyl ester, the

  16. Chemical indicators of sulfate sensitivity to nitrogen oxides and volatile organic compounds

    NASA Astrophysics Data System (ADS)

    Stein, Ariel F.; Lamb, Dennis

    2002-10-01

    The formation of aerosol sulfate (SO42-) in eastern North America is chemically linked to the emissions of nitrogen oxides (NOx) and volatile organic compounds (VOC) through oxidation of the gaseous precursor, sulfur dioxide (SO2). The response of sulfate production to controls in NOx and VOC emissions depends, in part, on the resulting changes in oxidant levels and the competition that naturally exists between the gas- and aqueous-phase pathways for SO2 oxidation. We propose the use of a combination of concentrations of nitric acid, particulate nitrate, hydrogen peroxide, and ambient sulfate as a nondimensional indicator of the effectiveness of VOC or NOx controls in decreasing SO42- abundance. The concentrations of these indicator species were calculated from a series of photochemical model simulations with varying rates of NOx and VOC emissions using a three-dimensional Eulerian model (MODELS-3) that covers the northeastern United States. This study shows that ambient sulfate concentrations are likely to decrease more effectively as VOC emissions are reduced, when the nondimensional indicator is less than a certain threshold. However, a higher value of the indicator identifies a regime in which NOx emissions reductions are more effective for reducing sulfate than are VOC emissions. In addition, a description of the sulfate-formation pathways, along with a theoretical analysis of the transition between NOx- and VOC-sensitive regimes, provides a strong rationale for the use of the sulfate sensitivity indicator.

  17. 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

  18. 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

  19. 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...

  20. Experimental Evaluation of the UV Raman Lidar Sensitivity in Detection of Traces of Chemical Compounds

    NASA Astrophysics Data System (ADS)

    Bobrovnikov, Sergey; Gorlov, Evgeny; Zharkov, Viktor

    2016-06-01

    Experimental results are presented on the remote detection of traces of some chemical compounds on the surface with the help of Raman lidar built on the basis of an excimer KrF laser with a narrow line emission and multi-channel spectrum analyzer based on the diffraction spectrograph and a time gated ICCD camera. The sensitivity of the system is evaluated for the sensing range of 10 m. At the accumulation of the signal over 1000 laser pulses, the detection threshold of the nitrogencontaining chemical compounds of about of units of μg/cm2 has been reached. The effect of the substrate material on the sensitivity of the Ramanlidar method for detecting traces of chemicals on the surface is analyzed.

  1. 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

  2. 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-β-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

  3. Chemical, physical, and biological properties of compounds present at hazardous-waste sites. Final report

    SciTech Connect

    Not Available

    1985-09-27

    The chemical profiles are intended to serve as a concise reference with information on the physicochemical properties, transport and fate, toxicity, and regulatory standards for individual chemicals identified by the EPA Office of Waste Program Enforcement at hazardous-waste sites. The profiles can be used in conjunction with the Toxicology and Endangerment Assessment Handbooks.

  4. Prediction of compounds in different local structure-activity relationship environments using emerging chemical patterns.

    PubMed

    Namasivayam, Vigneshwaran; Gupta-Ostermann, Disha; Balfer, Jenny; Heikamp, Kathrin; Bajorath, Jürgen

    2014-05-27

    Active compounds can participate in different local structure-activity relationship (SAR) environments and introduce different degrees of local SAR discontinuity, depending on their structural and potency relationships in data sets. Such SAR features have thus far mostly been analyzed using descriptive approaches, in particular, on the basis of activity landscape modeling. However, compounds in different local SAR environments have not yet been predicted. Herein, we adapt the emerging chemical patterns (ECP) method, a machine learning approach for compound classification, to systematically predict compounds with different local SAR characteristics. ECP analysis is shown to accurately assign many compounds to different local SAR environments across a variety of activity classes covering the entire range of observed local SARs. Control calculations using random forests and multiclass support vector machines were carried out and a variety of statistical performance measures were applied. In all instances, ECP calculations yielded comparable or better performance than controls. The approach presented herein can be applied to predict compounds that complement local SARs or prioritize compounds with different SAR characteristics. PMID:24803014

  5. 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

  6. 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.

  7. Chemical aspects of coumarin compounds for the prevention of hepatocellular carcinomas.

    PubMed

    Okamoto, Toshihiro; Kobayashi, Tadashi; Yoshida, Shinichi

    2005-01-01

    The normalization of plasma alanine aminotransferase (ALT) has been proved to be a strategy for preventing the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infection. Glycyrrhizin, a plant medicine, normalizes plasma ALT and prevents HCC. However, glycyrrhizin is administered intravenously and thereby chemical which is effective on oral administration is required. Coumarin compounds are active components of herbs used for the treatment of various diseases. The ability of coumarin compounds to lower plasma ALT were examined using mice concanavalin A-induced hepatitis and mice anti-Fas antibody-induced hepatitis. Furanocoumarins pd-Ia, pd-II and pd-III lower plasma ALT, but they are large molecules that are hardly absorbed on oral administration. Furocoumarin effectively lowers plasma ALT, but the safety range between the effective and toxic dosages is narrow. In contrast, osthole, a simple coumarin, causes strong reduction of plasma ALT and also inhibits caspase-3 activation. Furthermore, this chemical is quite safe upon large dose administration. In the structure of osthole, the methoxy group at position-7 and the 3-methyl-2-butenyl group at position-8 were elucidated to be essential for the beneficial effect of this chemical. We conclude that osthole will become a leading chemical for synthesizing a compound which prevents HCC on oral administration. PMID:15720260

  8. Changes on physico-chemical, textural, lipolysis and volatile compounds during the manufacture of dry-cured foal "cecina".

    PubMed

    Lorenzo, José M

    2014-01-01

    The changes in the physico-chemical and textural properties, lipolysis and volatile compounds during the manufacture of dry-cured foal "cecina" were studied. The pH increased during the last stages of processing but gradually declined over the curing period. TBARS values, hardness and chewiness increased with processing time from 0.14, 2.74 and 0.83 to 3.49 mg malonaldehyde/kg, 20.33 kg and 5.05 kg∗mm, respectively. Ripening time also affected the colour parameters: lightness (L*), redness (a*) and yellowness (b*) (P<0.001). The total average content of free fatty acid (FFA) increased significantly from 433.7 mg/100 g of fat in the raw pieces to 2655.5 mg/100 g of fat at the end of the drying-ripening stage. The main FFA at the end of the manufacturing process was palmitic acid (C16:0), followed by oleic (C18:1cis9), stearic (C18:0) and linoleic (C18:2n-6). A total of fifty five volatile compounds were identified during the manufacture of dry-cured foal "cecina", including esters, aldehydes, aliphatic hydrocarbons, branched hydrocarbons, alcohols, aromatic hydrocarbons, furans, ketones. Aldehydes reached their maximum level at the end of the post-salting stage. In the final product, esters became the dominant chemical compounds. PMID:23916960

  9. 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

  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

  11. 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

  12. 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

  13. Identifying the structural requirements for chromosomal aberration by incorporating molecular flexibility and metabolic activation of chemicals.

    PubMed

    Mekenyan, Ovanes; Todorov, Milen; Serafimova, Rossitsa; Stoeva, Stoyanka; Aptula, Aynur; Finking, Robert; Jacob, Elard

    2007-12-01

    Modeling the potential of chemicals to induce chromosomal damage has been hampered by the diversity of mechanisms which condition this biological effect. The direct binding of a chemical to DNA is one of the underlying mechanisms that is also responsible for bacterial mutagenicity. Disturbance of DNA synthesis due to inhibition of topoisomerases and interaction of chemicals with nuclear proteins associated with DNA (e.g., histone proteins) were identified as additional mechanisms leading to chromosomal aberrations (CA). A comparative analysis of in vitro genotoxic data for a large number of chemicals revealed that more than 80% of chemicals that elicit bacterial mutagenicity (as indicated by the Ames test) also induce CA; alternatively, only 60% of chemicals that induce CA have been found to be active in the Ames test. In agreement with this relationship, a battery of models is developed for modeling CA. It combines the Ames model for bacterial mutagenicity, which has already been derived and integrated into the Optimized Approach Based on Structural Indices Set (OASIS) tissue metabolic simulator (TIMES) platform, and a newly derived model accounting for additional mechanisms leading to CA. Both models are based on the classical concept of reactive alerts. Some of the specified alerts interact directly with DNA or nuclear proteins, whereas others are applied in a combination of two- or three-dimensional quantitative structure-activity relationship models assessing the degree of activation of the alerts from the rest of the molecules. The use of each of the alerts has been justified by a mechanistic interpretation of the interaction. In combination with a rat liver S9 metabolism simulator, the model explained the CA induced by metabolically activated chemicals that do not elicit activity in the parent form. The model can be applied in two ways: with and without metabolic activation of chemicals. PMID:18052113

  14. EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen.

    PubMed

    Scheipl, Susanne; Barnard, Michelle; Cottone, Lucia; Jorgensen, Mette; Drewry, David H; Zuercher, William J; Turlais, Fabrice; Ye, Hongtao; Leite, Ana P; Smith, James A; Leithner, Andreas; Möller, Peter; Brüderlein, Silke; Guppy, Naomi; Amary, Fernanda; Tirabosco, Roberto; Strauss, Sandra J; Pillay, Nischalan; Flanagan, Adrienne M

    2016-07-01

    Chordoma is a rare malignant bone tumour with a poor prognosis and limited therapeutic options. We undertook a focused compound screen (FCS) against 1097 compounds on three well-characterized chordoma cell lines; 154 compounds were selected from the single concentration screen (1 µm), based on their growth-inhibitory effect. Their half-maximal effective concentration (EC50 ) values were determined in chordoma cells and normal fibroblasts. Twenty-seven of these compounds displayed chordoma selective cell kill and 21/27 (78%) were found to be EGFR/ERBB family inhibitors. EGFR inhibitors in clinical development were then studied on an extended cell line panel of seven chordoma cell lines, four of which were sensitive to EGFR inhibition. Sapitinib (AstraZeneca) emerged as the lead compound, followed by gefitinib (AstraZeneca) and erlotinib (Roche/Genentech). The compounds were shown to induce apoptosis in the sensitive cell lines and suppressed phospho-EGFR and its downstream pathways in a dose-dependent manner. Analysis of substituent patterns suggested that EGFR-inhibitors with small aniline substituents in the 4-position of the quinazoline ring were more effective than inhibitors with large substituents in that position. Sapitinib showed significantly reduced tumour growth in two xenograft mouse models (U-CH1 xenograft and a patient-derived xenograft, SF8894). One of the resistant cell lines (U-CH2) was shown to express high levels of phospho-MET, a known bypass signalling pathway to EGFR. Neither amplifications (EGFR, ERBB2, MET) nor mutations in EGFR, ERBB2, ERBB4, PIK3CA, BRAF, NRAS, KRAS, PTEN, MET or other cancer gene hotspots were detected in the cell lines. Our findings are consistent with the reported (p-)EGFR expression in the majority of clinical samples, and provide evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. © 2016

  15. 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

  16. 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

  17. Thin film synthesis of superconducting chemical compounds. Final report 1 January 1981-30 December 1983

    SciTech Connect

    Sienko, M.J.; Hoffmann, R.; Newman, J.A.; Burlitch, J.M.

    1984-05-31

    The objective of this research was to define the chemical factors that affect onset of superconductivity in ternary compounds: to determine how small changes in stoichiometry and microstructure influence critical temperature, how the number and placing of magnetic ions act to quench superconductivity, and how the crystal structure can be modified to enhance superconductivity. The approach was to synthesize, from ultrapure starting elements, ternary borides, silicides, sulfides and selenides of the second and third row transition elements, to characterize the new compounds for x-ray structure, electric and magnetic behavior, and then compare them with doped materials. Four kinds of compounds were investigated: rare earth diosmium disilicides, rare earth osmium-iridium borides, layered structure transition metal dichalcogenides, and Chevrel type molybdenum ternaries. Both the rare earth osmium-iridium borides and rare earth diosmium disilicides were synthesized by arc melting. The crystal structures were refined and magnetic susceptibility studies revealed conventional Hund's rule behavior in the disilicides while the (Pr, Nd) (Os, Ir) 4B4 compounds are characterized by Van Vleck paramagnetism of closely spaced multiplets. Only LaOs/sub 2/Si/sub 2/ and LuOs/sub 2/Si/sub 2/ compounds are superconducting with Tc's in the 2-4K range. In the layered compounds, lithium intercalated ZrS/sub 2/, ZrSe/sub 2/, NbS/sub 2/, and NbSe/sub 2/ were studied.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Transcriptome Sequencing of Chemically Induced Aquilaria sinensis to Identify Genes Related to Agarwood Formation

    PubMed Central

    Ye, Wei; Wu, Hongqing; He, Xin; Wang, Lei; Zhang, Weimin; Li, Haohua; Fan, Yunfei; Tan, Guohui; Liu, Taomei; Gao, Xiaoxia

    2016-01-01

    Background Agarwood is a traditional Chinese medicine used as a clinical sedative, carminative, and antiemetic drug. Agarwood is formed in Aquilaria sinensis when A. sinensis trees are threatened by external physical, chemical injury or endophytic fungal irritation. However, the mechanism of agarwood formation via chemical induction remains unclear. In this study, we characterized the transcriptome of different parts of a chemically induced A. sinensis trunk sample with agarwood. The Illumina sequencing platform was used to identify the genes involved in agarwood formation. Methodology/Principal Findings A five-year-old Aquilaria sinensis treated by formic acid was selected. The white wood part (B1 sample), the transition part between agarwood and white wood (W2 sample), the agarwood part (J3 sample), and the rotten wood part (F5 sample) were collected for transcriptome sequencing. Accordingly, 54,685,634 clean reads, which were assembled into 83,467 unigenes, were obtained with a Q20 value of 97.5%. A total of 50,565 unigenes were annotated using the Nr, Nt, SWISS-PROT, KEGG, COG, and GO databases. In particular, 171,331,352 unigenes were annotated by various pathways, including the sesquiterpenoid (ko00909) and plant–pathogen interaction (ko03040) pathways. These pathways were related to sesquiterpenoid biosynthesis and defensive responses to chemical stimulation. Conclusions/Significance The transcriptome data of the different parts of the chemically induced A. sinensis trunk provide a rich source of materials for discovering and identifying the genes involved in sesquiterpenoid production and in defensive responses to chemical stimulation. This study is the first to use de novo sequencing and transcriptome assembly for different parts of chemically induced A. sinensis. Results demonstrate that the sesquiterpenoid biosynthesis pathway and WRKY transcription factor play important roles in agarwood formation via chemical induction. The comparative analysis of

  3. Chemical characterization of brominated flame retardants and identification of structurally representative compounds.

    PubMed

    Andersson, Patrik L; Oberg, Kjell; Orn, Ulrika

    2006-05-01

    Three training sets were selected, each consisting of 10 structurally diverse compounds representative of brominated flame retardants (BFRs) that are either in use or have been used. Just three compounds account for nearly all the total production volume of BFRs. In the present study, however, the physicochemical characteristics of a far more structurally diverse set of 65 BFRs was explored using 15 molecular descriptors (including log P, constitutional counts, and semiempirical quantum mechanical parameters) and principal component analysis (PCA). The PCA generated an overview of the structural variation among BFRs, and certain compounds with unique physicochemical properties and specific clusters of compounds with distinct properties were identified. The training-set compounds were selected by applying the condensed information obtained from the PCA and statistical experimental design. The three training sets, which were designated as optimal, practical, and alternative, were selected either to maximize the structural variation (optimal) or to combine structural variation with practical advantages, such as ease of experimental handling and commercial availability (practical and alternative). Inclusion of the suggested compounds in assessments of the persistence, bioaccumulation, and toxicity properties of BFRs and related programs should help to increase our understanding of the effects and environmental fate of these compounds. PMID:16704058

  4. Kinetics of gas-phase reactions relevant to the chemical vapor deposition of indium compounds

    SciTech Connect

    Allendorf, M.D.; McDaniel, A.H.

    1998-03-01

    Compounds containing indium are of interest for electronic and optical applications. These compounds include III-V semiconductors such as InP and InAs used in both electronic devices and solar cells, and indium tin oxide, which can be used for optical memory and antireflection coatings. Chemical vapor deposition (CVD) techniques can be used to deposit these materials on a variety of substrates. At the temperatures typically employed (550--900 K), gas-phase chemical reactions involving the indium-containing precursor can occur. The kinetics of trimethylindium pyrolysis are investigated in a flow reactor equipped with a molecular-beam mass-spectrometric sampling system. Data are analyzed using a new computational approach that accounts for heat and mass transport in the reactor. The measured activation energy, 46.2 kcal/mol, is in good agreement with previously reported values.

  5. The relationship between the chemical structure and neurotoxicity of alkyl organophosphorus compounds

    PubMed Central

    Davies, D. R.; Holland, P.; Rumens, M. J.

    1960-01-01

    Thirty-six alkyl organophosphorus compounds have been tested for neurotoxicity in the chicken. The individual compounds were chosen to enable the importance of each portion of the molecule to be assessed in relation to the property of neurotoxicity. Seventeen substances were found to be neurotoxic, fifteen for the first time. All of these contained fluorine. On the basis of the results reported, certain predictions have been made about the chemical structure of compounds which would be expected to be neurotoxic. The importance of fluorine suggests that it plays a direct role in the development of the biochemical lesion, and this may occur as the result of its being carried by the molecule as a whole to specific areas in the nervous system. By the action of cholinesterase, the P-F bond may be ruptured and ionic fluorine liberated where it blocks some metabolic cycle. PMID:13814387

  6. Electronic properties and chemical bondings of Csbnd Hsbnd Nsbnd O compounds

    NASA Astrophysics Data System (ADS)

    Qin, Han; Liu, Qi-Jun; Chai, Rui-Qing; Liu, Fu-Sheng; Liu, Zheng-Tang

    2016-07-01

    We have performed the density functional theory (DFT) calculations within generalized gradient approximation (GGA) plus TS scheme to calculate the structural and electronic properties of Csbnd Hsbnd Nsbnd O compounds. Due to the insufficient description of intermolecular interactions within the GGA calculations, the GGA plus TS dispersion correction have been used to optimize the structural parameters. The calculated results based on the GGA + TS calculations are in agreement with the experimental data, indicating that the introduction of TS dispersion correction can effectively obtain the structural properties of Csbnd Hsbnd Nsbnd O compounds. The electronic properties of nineteen Csbnd Hsbnd Nsbnd O compounds including density of states, Mulliken charges, bond populations and band structures have been obtained and analyzed. According to these calculated data, the electron distributions and charge transfers have been investigated, which are conducive to clarify the chemical bonding characters and further help to future research of understanding the initial chemistry within the detonating energetic materials.

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

    DOEpatents

    Mowry, Curtis Dale; Thornberg, Steven Michael

    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.

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

    DOEpatents

    Vernon, Stanley M.

    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.

  9. Optical methods for creating delivery systems of chemical compounds to plant roots

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Pavel E.; Rogacheva, Svetlana M.; Arefeva, Oksana A.; Minin, Dmitryi V.; Tolmachev, Sergey A.; Kupadze, Machammad S.

    2004-08-01

    Spectrophotometric and fluorescence methods have been used for creation and investigation of various systems of target delivery of chemical compounds to roots of plants. The possibility of using liposomes, incrusted by polysaccharides of the external surface of nitrogen-fixing rizospheric bacteria Azospirillum brasilense SP 245, and nanoparticles incrusted by polysaccharides of wheat roots, as the named systems has been shown. The important role of polysaccharide-polysaccharide interaction in the adsorption processes of bacteria on wheat roots has been demonstrated.

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

    PubMed Central

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

    2008-01-01

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