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1

Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay  

Microsoft Academic Search

There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans

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

2007-01-01

2

Chemical proteomics to identify molecular targets of small compounds.  

PubMed

Most drug targets are cellular proteins that selectively interact with chemicals administered to treat diseases. Chemical proteomics, as an interdisciplinary technology that integrates synthetic and analytic chemistry, biochemistry and cell biology, has recently emerged as a powerful platform to specifically enrich and comprehensively profile drug-binding proteins, and thus has been extensively applied in the identification of drug targets. In addition, chemical proteomics can also provide information for researchers to understand the poly-pharmacological activities of the pharmaceutical compounds, and thus help in maximizing the efficacy and minimizing the side effects of the drugs. In this manuscript, we summarized several popular approaches of chemical proteomics by illustrating their essential features in drug target-fishing through specific profiling of drug-protein interaction. Alternative technologies for target identification were also discussed. PMID:23826922

Sun, B; He, Q-Y

2013-08-01

3

Pharmacological and chemical study to identify wound-healing active compounds in Ageratina pichinchensis.  

PubMed

The aerial parts of Ageratina pichinchensis are used in Mexican traditional medicine for the treatment of skin wounds. Recently, it was demonstrated that the aqueous extract of this plant reduced the time required to cicatrize a wound induced in the rat. The same extract showed a capability to induce overgrowth in normal fetal lung cells (MRC-5). The objective of the present study was isolating and identifying the active compounds in A. pichinchensis that are capable of inducing cellular overgrowth, as well as performing a preliminary evaluation of their anti-inflammatory and toxic effects. By means of bioguided chemical separation of an aqueous extract of A. pichinchensis, the most active compound capable of inducing cellular overgrowth was identified as 7-O-(?-D-glucopyranosyl)-galactin. In vivo inflammation induced with carrageenan in mice was significantly reduced by the aqueous extract of A. pichinchensis, reaching a decrease of up to 60.6 %. Acute (2 g/kg) and subchronic (1 g/kg for 28 days) oral administration of the aqueous extract of this plant did not affect hepatic function (through alanine aminotransferase and aspartate aminotransferase activity evaluation), while no alterations of the histologic samples of liver and kidney were evidenced. PMID:23599006

Romero-Cerecero, Ofelia; Zamilpa, Alejandro; González-Cortazar, Manasés; Alonso-Cortés, Daniel; Jiménez-Ferrer, Enrique; Nicasio-Torres, Pilar; Aguilar-Santamaría, Lucía; Tortoriello, Jaime

2013-05-01

4

Forward chemical genetic screens in Arabidopsis identify genes that influence sensitivity to the phytotoxic compound sulfamethoxazole  

PubMed Central

Background The sulfanilamide family comprises a clinically important group of antimicrobial compounds which also display bioactivity in plants. While there is evidence that sulfanilamides inhibit folate biosynthesis in both bacteria and plants, the complete network of plant responses to these compounds remains to be characterized. As such, we initiated two forward genetic screens in Arabidopsis in order to identify mutants that exhibit altered sensitivity to sulfanilamide compounds. These screens were based on the growth phenotype of seedlings germinated in the presence of the compound sulfamethoxazole (Smex). Results We identified a mutant with reduced sensitivity to Smex, and subsequent mapping indicated that a gene encoding 5-oxoprolinase was responsible for this phenotype. A mutation causing enhanced sensitivity to Smex was mapped to a gene lacking any functional annotation. Conclusions The genes identified through our forward genetic screens represent novel mediators of Arabidopsis responses to sulfanilamides and suggest that these responses extend beyond the perturbation of folate biosynthesis.

2012-01-01

5

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...

6

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

PubMed

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

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

2014-01-31

7

Devices for collecting chemical compounds  

DOEpatents

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.

Scott, Jill R; Groenewold, Gary S

2013-12-24

8

Novel Plant Immune-Priming Compounds Identified via High-Throughput Chemical Screening Target Salicylic Acid Glucosyltransferases in Arabidopsis[W][OA  

PubMed Central

Plant activators are compounds, such as analogs of the defense hormone salicylic acid (SA), that protect plants from pathogens by activating the plant immune system. Although some plant activators have been widely used in agriculture, the molecular mechanisms of immune induction are largely unknown. Using a newly established high-throughput screening procedure that screens for compounds that specifically potentiate pathogen-activated cell death in Arabidopsis thaliana cultured suspension cells, we identified five compounds that prime the immune response. These compounds enhanced disease resistance against pathogenic Pseudomonas bacteria in Arabidopsis plants. Pretreatments increased the accumulation of endogenous SA, but reduced its metabolite, SA-O-?-d-glucoside. Inducing compounds inhibited two SA glucosyltransferases (SAGTs) in vitro. Double knockout plants that lack both SAGTs consistently exhibited enhanced disease resistance. Our results demonstrate that manipulation of the active free SA pool via SA-inactivating enzymes can be a useful strategy for fortifying plant disease resistance and may identify useful crop protectants.

Noutoshi, Yoshiteru; Okazaki, Masateru; Kida, Tatsuya; Nishina, Yuta; Morishita, Yoshihiko; Ogawa, Takumi; Suzuki, Hideyuki; Shibata, Daisuke; Jikumaru, Yusuke; Hanada, Atsushi; Kamiya, Yuji

2012-01-01

9

Identifying new volatile compounds in toasted oak.  

PubMed

Toasting wood to be used in barrels for aging wine produces a great number of volatile and odiferous compounds. Three new volatile odorous compounds in toasted oak were identified. Analysis by high-performance gas chromatography of toasted oak extracts, combined with olfactory detection, enabled various chromatographic peaks with these specific aromas to be isolated. These same odors were simultaneously studied by heating glucose both with and without proline and phenylalanine. Aromatic compounds of interest were identified thanks to a combination of gas chromatography and both mass and infrared spectrometry. An analysis RMN was also used. Hydroxymaltol, 2,5-furanedicarbaldehyde, and furylhydroxymethyl ketone have been detected in extract of toasted oak wood. These molecules may be formed by direct pyrolysis of sugar or Maillard reactions. The acetylformoine was not detected in extract of toasted oak wood, whereas it was detected in heated extracts of various sugars and sugars mixtures with amino acids. PMID:10564035

Cutzach, I; Chatonnet, P; Henry, R; Dubourdieu, D

1999-04-01

10

Automated compound classification using a chemical ontology  

PubMed Central

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

2012-01-01

11

Chemicals identified in human biological media  

SciTech Connect

Sources of data for Chemicals Identified in Human Biological Media are from the world literature, retrospective to 1974. Information from approximately 1500 documents is in the data base at the present time. The data base contains information on 750 chemicals. Approximately 250 of these were added since this time last year. Approximately 10% of the total documents in the file concerned pesticides; 30%, drugs; and 40%, metals. The remaining 20% were about other substances, including industrial chemicals and organics which are of interest to NCI and EPA.

Cone, M.V.; Stroup, C.

1981-01-01

12

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...

13

Lifetime of a Chemically Bound Helium Compound  

NASA Technical Reports Server (NTRS)

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.

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

2001-01-01

14

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

SciTech Connect

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.

Hauschild, Veronique [U.S. Army Public Health Command] [U.S. Army Public Health Command; Watson, Annetta Paule [ORNL] [ORNL

2013-01-01

15

Identifying producers of antibacterial compounds by screening for antibiotic resistance.  

PubMed

Microbially derived natural products are major sources of antibiotics and other medicines, but discovering new antibiotic scaffolds and increasing the chemical diversity of existing ones are formidable challenges. We have designed a screen to exploit the self-protection mechanism of antibiotic producers to enrich microbial libraries for producers of selected antibiotic scaffolds. Using resistance as a discriminating criterion we increased the discovery rate of producers of both glycopeptide and ansamycin antibacterial compounds by several orders of magnitude in comparison with historical hit rates. Applying a phylogeny-based screening filter for biosynthetic genes enabled the binning of producers of distinct scaffolds and resulted in the discovery of a glycopeptide antibacterial compound, pekiskomycin, with an unusual peptide scaffold. This strategy provides a means to readily sample the chemical diversity available in microbes and offers an efficient strategy for rapid discovery of microbial natural products and their associated biosynthetic enzymes. PMID:24056948

Thaker, Maulik N; Wang, Wenliang; Spanogiannopoulos, Peter; Waglechner, Nicholas; King, Andrew M; Medina, Ricardo; Wright, Gerard D

2013-10-01

16

A novel system for rapidly identifying toxic chemicals.  

PubMed

First-responders have a critical need to rapidly identify toxic chemicals during emergencies. However, current systems such as WISER require a large number of inputs before a chemical can be identified. Here we present a novel system which significantly reduces the number of inputs required to identify a toxic chemical. PMID:18999084

Bhavnani, Suresh K; Ganesan, Arun; Scott, Clayton; Weber, Chris; Saxman, Paul

2008-01-01

17

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...

18

A Quantitative High Throughput Assay for Identifying Gametocytocidal Compounds  

PubMed Central

Current antimalarial drug treatment does not effectively kill mature Plasmodium falciparum gametocytes, the parasite stage responsible for malaria transmission from human to human via a mosquito. Consequently, following standard therapy malaria can still be transmitted for over a week after the clearance of asexual parasites. A new generation of malaria drugs with gametocytocidal properties, or a gametocytocidal drug that could be used in combinational therapy with currently available antimalarials, is needed to control the spread of the disease and facilitate eradication efforts. We have developed a 1,536-well gametocyte viability assay for the high throughput screening of large compound collections to identify novel compounds with gametocytocidal activity. The signal-to-basal ratio and Z?-factor for this assay were 3.2-fold and 0.68, respectively. The IC50 value of epoxomicin, the positive control compound, was 1.42 ± 0.09 nM that is comparable to previously reported values. This miniaturized assay significantly reduces the number of gametocytes required for the alamarBlue viability assay, and enables high throughput screening for lead discovery efforts. Additionally, the screen does not require a specialized parasite line, gametocytes from any strain, including field isolates, can be tested. A pilot screen utilizing the commercially available LOPAC library, consisting of 1,280 known compounds, revealed two selective gametocytocidal compounds having 54 and 7.8-fold gametocytocidal selectivity in comparison to their cell cytotoxicity effect against the mammalian SH-SY5Y cell line.

Tanaka, Takeshi Q.; Dehdashti, Seameen J.; Nguyen, Dac-Trung; McKew, John C.; Zheng, Wei; Williamson, Kim C.

2013-01-01

19

Phenyl-Adenine, Identified in a LIGHT-DEPENDENT SHORT HYPOCOTYLS4-Assisted Chemical Screen, Is a Potent Compound for Shoot Regeneration through the Inhibition of CYTOKININ OXIDASE/DEHYDROGENASE Activity1[W][OA  

PubMed Central

In vitro shoot regeneration is implemented in basic plant research and commercial plant production, but for some plant species, it is still difficult to achieve by means of the currently available cytokinins and auxins. To identify novel compounds that promote shoot regeneration, we screened a library of 10,000 small molecules. The bioassay consisted of a two-step regeneration protocol adjusted and optimized for high-throughput manipulations of root explants of Arabidopsis (Arabidopsis thaliana) carrying the shoot regeneration marker LIGHT-DEPENDENT SHORT HYPOCOTYLS4. The screen revealed a single compound, the cytokinin-like phenyl-adenine (Phe-Ade), as a potent inducer of adventitious shoots. Although Phe-Ade triggered diverse cytokinin-dependent phenotypical responses, it did not inhibit shoot growth and was not cytotoxic at high concentrations. Transcript profiling of cytokinin-related genes revealed that Phe-Ade treatment established a typical cytokinin response. Moreover, Phe-Ade activated the cytokinin receptors ARABIDOPSIS HISTIDINE KINASE3 and ARABIDOPSIS HISTIDINE KINASE4 in a bacterial receptor assay, albeit at relatively high concentrations, illustrating that it exerts genuine but weak cytokinin activity. In addition, we demonstrated that Phe-Ade is a strong competitive inhibitor of CYTOKININ OXIDASE/DEHYDROGENASE enzymes, leading to an accumulation of endogenous cytokinins. Collectively, Phe-Ade exhibits a dual mode of action that results in a strong shoot-inducing activity.

Motte, Hans; Galuszka, Petr; Spichal, Lukas; Tarkowski, Petr; Plihal, Ondrej; Smehilova, Maria; Jaworek, Pavel; Vereecke, Danny; Werbrouck, Stefaan; Geelen, Danny

2013-01-01

20

Using Properties to Identify Ionic and Molecular Compounds  

NSDL National Science Digital Library

An inquiry activity for students to test physical properties of several compounds to analyze data and determine if the compound is ionic or covalent. This is ideal for an introduction to ionic and molecular compound nomenclature.

Tamara Ellsworth, Parkers Prairie High School, Parkers Prairie, MN, based on a lab for pre-ap chemistry at the westlake high school website.

21

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

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.

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, Mylene; English, Ann M.; Thomas, David Y.; Titorenko, Vladimir I.

2010-01-01

22

Device for collecting chemical compounds and related methods  

DOEpatents

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.

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

2013-01-01

23

High content screening of diverse compound libraries identifies potent modulators of tubulin dynamics.  

PubMed

Tubulin modulating agents such as the taxanes are among the most effective antimitotic cancer drugs, although resistance and toxicity present significant problems in their clinical use. However, most tubulin modulators are derived from complex natural products, which can make modification of their structure to address these problems difficult. Here, we report the discovery of new antimitotic compounds with simple structures that can be rapidly synthesized, through the phenotypic screening of a diverse compound library for the induction of mitotic arrest. We first identified a compound, which induced mitotic arrest in human cells at submicromolar concentrations. Its simple structure enabled rapid exploration of activity, defining a biphenylacetamide moiety required for activity, A family of analogues was synthesized, yielding optimized compounds that caused mitotic arrest and cell death in the low nanomolar range, comparable to clinically used antimitotic agents. These compounds can be synthesized in 1-3 steps and good yields. We show that one such compound targets tubulin, partially inhibiting colchicine but not vinblastine binding, suggesting that it acts allosterically to the known colchicine-binding site. Thus, our results exemplify the use of phenotypic screening to identify novel antimitotic compounds from diverse chemical libraries and characterize a family of biphenylacetamides (biphenabulins) that show promise for further development. PMID:24900887

Laraia, Luca; Stokes, Jamie; Emery, Amy; McKenzie, Grahame J; Venkitaraman, Ashok R; Spring, David R

2014-05-01

24

Identifying organic nitrogen compounds in Rocky Mountain National Park aerosols  

NASA Astrophysics Data System (ADS)

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

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

2010-12-01

25

A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase  

PubMed Central

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.

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

2013-01-01

26

APPLICATION OF AN ANALYSIS PROTOCOL TO IDENTIFY ORGANIC COMPOUNDS NOT IDENTIFIED BY SPECTRUM MATCHING. PART 1: TEXT  

EPA Science Inventory

Industrial wastewater survey samples were analyzed for organic compounds not identified by spectrum matching. Analysis of the samples proceeded from an initial packed column GC/MS analysis for Priority Pollutants, through computerized spectrum matching for other compounds, to the...

27

APPLICATION OF AN ANALYSIS PROTOCOL TO IDENTIFY ORGANIC COMPOUNDS NOT IDENTIFIED BY SPECTRUM MATCHING. PART 2: APPENDICES  

EPA Science Inventory

Industrial wastewater survey samples were analyzed for organic compounds not identified by spectrum matching. Analysis of the samples proceeded from an initial packed column GC/MS analysis for Priority Pollutants, through computerized spectrum matching for other compounds, to the...

28

Water maze testing to identify compounds for cognitive enhancement.  

PubMed

The water maze task is widely used to evaluate spatial learning and memory in rodents. The basic paradigm requires an animal to swim in a pool until it finds a hidden escape platform. The animals learn to find the platform using extra-maze cues and, after several training trials, are able to swim directly to it from any starting location. Memory for the platform location is assessed by examining swimming behavior with the platform removed from the maze, while sensory, motor and motivational aspects of the task can be examined by making the platform visible to the animals. Described in this unit is the use of the water maze to identify rats with age-related spatial learning and memory impairments. The efficacy of potential pharmacological treatments for alleviating these deficits is then evaluated. This assay provides a means for studying the neurobiology of spatial learning and memory, and to identify potential pharmacotherapies for treating memory-impaired humans. While the use of aged rats is described in this unit, the protocol can also be employed for compound screening with other rodent models that have spatial learning and memory impairments, such as transgenic mouse models of Alzheimer's disease. PMID:23258600

Rose, Gregory M; Rowe, Wayne B

2012-12-01

29

Potential Military Chemical/Biological Agents and Compounds.  

National Technical Information Service (NTIS)

This document provides commanders and staffs with general information and technical data concerning chemical/biological (CB) agents and other compounds of military interest such as toxic industrial chemicals (TIC). It explains the use; classification; and...

2005-01-01

30

Estrogen-like effect and cytotoxicity of chemical compounds.  

PubMed

Luciferase assay, cytotoxicity test and protein quantitative analysis were performed after the exposure of chemical compounds to MVLN cells that are utilized to detect the endocrine disrupting activity. These consequences indicate that the concentration is different between the estrogen receptor mediated proliferation of breast cancer cells and the estrogen receptor mediated transcription by chemical compounds. PMID:12523779

Katori, Y; Ksu, Y; Utsumi, H

2002-01-01

31

Chemical Genetics: Elucidating Biological Systems with Small-Molecule Compounds  

Microsoft Academic Search

Chemical genetics employs diverse small-molecule compounds to elucidate biological processes in a manner analogous to the mutagenesis strategies at the core of classical genetics. Screening small-molecule libraries for compounds that induce a phenotype of interest represents the forward chemical genetic approach, whereas the reverse approach involves small molecules targeting a single protein. Here, we review key differences between the goals

Masaoki Kawasumi; Paul Nghiem

2007-01-01

32

Comparison of descriptor spaces for chemical compound retrieval and classification  

Microsoft Academic Search

In recent years the development of computational techniques that build models to correctly assign chemical compounds to various classes or to retrieve po- tential drug-like compounds has been an active area of research. Many of the best- performing techniques for these tasks utilize a descriptor-based representation of the compound that captures various aspects of the underlying molecular graph's topology. In

Nikil Wale; Ian A. Watson; George Karypis

2008-01-01

33

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

PubMed

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

Shah, Falgun; Greene, Nigel

2014-01-21

34

Environmental Chamber Test Protocol for Measuring Chemical Emissions, Including Sulfur Compounds from Drywall with Preliminary Results  

Microsoft Academic Search

Recently, drywall produced in China has been implicated as the cause of health complaints and corrosion of metal components in houses, with sulfur compounds as the potential source. Federal and state agencies are interested in determining if sulfur containing chemicals are being released from this drywall and identifying the compounds. To assist these agencies, as well as product manufacturers and

Stephany I. Mason; Tony Worthan

35

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 ...

36

Process for preparing a chemical compound enriched in isotope content  

DOEpatents

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.

Michaels, Edward D. (Spring Valley, OH)

1982-01-01

37

Finding Frequent Substructures in Chemical Compounds  

Microsoft Academic Search

The discovery of the relationships between chemical structure and biological function is central to biologi- cal science and medicine. In this paper we apply data mining to the problem of predicting chemical carcino- genicity. This toxicology application was launched at IJCAI'97 as a research challenge for artificial intelli- gence. Our approach to the problem is descriptive rather than based on

Luc Dehaspe; Hannu Toivonen; Ross D. King

1998-01-01

38

Development of the Chemical Compound Registry System.  

National Technical Information Service (NTIS)

The report describes in detail the work performed and the present status of a task whose objectives are the registration of chemical substances. The programs and achievements described constitute the first significant efforts to develop a user-oriented, c...

1967-01-01

39

Chemical bonding in titanium-metalloid compounds  

Microsoft Academic Search

First-principles molecular-orbital calculations for titanium-metalloid compounds TiB, TiB2, TiC, Ti2N, TiN, TiO, TiO2, TiSi, TiSi2, TiP, TiS, and TiS2 have been made by the use of discrete-variational Xalpha method with model clusters composed of about 100 atoms. In order to compare the covalent bonding quantitatively among these compounds with different crystal structures, we used covalent bond density in which both

Masataka Mizuno; Isao Tanaka; Hirohiko Adachi

1999-01-01

40

Chemistry and Synthesis of Multifunctional Chemical Compounds.  

National Technical Information Service (NTIS)

A study of the chemistry and synthesis of certain multifunctional aromatic and heterocyclic intermediates for polymer synthesis was carried out. Compounds supplied to Air Force Materials Laboratory include biphenyl-2,2',6,6'-tetracarboxylic acid, 2,2',6,6...

E. S. Blake R. E. DeBrunner J. A. Webster

1967-01-01

41

Chemical compounds of the foraging recruitment pheromone in bumblebees  

NASA Astrophysics Data System (ADS)

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.

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

42

Directing the immune system with chemical compounds.  

PubMed

Agonists of immune cell receptors direct innate and adaptive immunity. These agonists range in size and complexity from small molecules to large macromolecules. Here, agonists of a class of immune cell receptors known as the Toll-like receptors (TLRs) are highlighted focusing on the distinctive molecular moieties that pertain to receptor binding and activation. How the structure and combined chemical signals translate into a variety of immune responses remain major questions in the field. In this structure-focused review, we outline potential areas where the tools of chemical biology could help decipher the emerging molecular codes that direct immune stimulation. PMID:24690004

Mancini, Rock J; Stutts, Lalisa; Ryu, Keun Ah; Tom, Janine K; Esser-Kahn, Aaron P

2014-05-16

43

Chemical compounds isolated from Talinum triangulare (Portulacaceae).  

PubMed

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 ?-lactone-15(2)-methyl-17(3)-phytyl ester and 17 (17R, 18R)-purpurin 18-phytyl ester. PMID:24799228

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

44

Target Fishing for Chemical Compounds using Target-Ligand Activity data and Ranking based Methods  

PubMed Central

In recent years the development of computational techniques that identify all the likely targets for a given chemical compound, also termed as the problem of Target Fishing, has been an active area of research. Identification of likely targets of a chemical compound helps to understand problems such as toxicity, lack of efficacy in humans, and poor physical properties associated with that compound in the early stages of drug discovery. In this paper we present a set of techniques whose goal is to rank or prioritize targets in the context of a given chemical compound such that most targets that this compound may show activity against appear higher in the ranked list. These methods are based on our extensions to the SVM and Ranking Perceptron algorithms for this problem. Our extensive experimental study shows that the methods developed in this work outperform previous approaches by 2% to 60% under different evaluation criterions.

Wale, Nikil; Karypis, George

2009-01-01

45

LIGAND: Database of Chemical Compounds and Reactions in Biological Pathways  

NSDL National Science Digital Library

The Institute for Chemical Research at Kyoto University provides this frequently updated and well-documented database of enzyme reactions. With more than 9,300 entries, the LIGAND Chemical Database includes over 3,700 entries for enzymes (the Enzyme Reaction Database) and 5,600 entries for compounds (Chemical Compound Database). The database is searchable by keyword using DBGET (which supports numerous other databases and gene catalogs as well) and is accompanied by clear instructions. The LIGAND database, updated weekly, may be downloaded via anonymous FTP.

46

Cyclopropyl Carboxamides, a Chemically Novel Class of Antimalarial Agents Identified in a Phenotypic Screen ?  

PubMed Central

Malaria is one of the deadliest infectious diseases in the world, with the eukaryotic parasite Plasmodium falciparum causing the most severe form of the disease. Discovery of new classes of antimalarial drugs has become an urgent task to counteract the increasing problem of drug resistance. Screening directly for compounds able to inhibit parasite growth in vitro is one of the main approaches the malaria research community is now pursuing for the identification of novel antimalarial drug leads. Very recently, thousands of compounds with potent activity against the parasite P. falciparum have been identified and information about their molecular descriptors, antiplasmodial potency, and cytotoxicity is publicly available. Now the challenges are how to identify the most promising chemotypes for further development and how best to progress these compounds through a lead optimization program to generate antimalarial drug candidates. We report here the first chemical series to be characterized from one of those screenings, a completely novel chemical class with the generic name cyclopropyl carboxamides that has never before been described as having antimalarial or other pharmacological activities. Cyclopropyl carboxamides are potent inhibitors of drug-sensitive and -resistant strains of P. falciparum in vitro and show in vivo oral efficacy in malaria mouse models. In the present work, we describe the biological characterization of this chemical family, showing that inhibition of their still unknown target has very favorable pharmacological consequences but the compounds themselves seem to select for resistance at a high frequency.

Sanz, Laura M.; Jimenez-Diaz, M. Belen; Crespo, Benigno; De-Cozar, Cristina; Almela, M. Jesus; Angulo-Barturen, Inigo; Castaneda, Pablo; Ibanez, Javier; Fernandez, Esther Pilar; Ferrer, Santiago; Herreros, Esperanza; Lozano, Sonia; Martinez, Maria Santos; Rueda, Lourdes; Burrows, Jeremy N.; Garcia-Bustos, Jose F.; Gamo, Francisco-Javier

2011-01-01

47

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

NASA Technical Reports Server (NTRS)

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.

Misra, Ajay K.

1993-01-01

48

Effect of chemical degradation on fluxes of reactive compounds  

NASA Astrophysics Data System (ADS)

In the analyses of VOC fluxes measured above plant canopies, one usually assumes the flux above canopy to equal the emission at the surface. Thus one assumes the chemical degradation to be much slower than the turbulent transport. We used a stochastic Lagrangian transport model in which the chemical degradation was described as first order decay in order to study the effect of the chemical degradation on above canopy fluxes of chemically reactive species. With the model we explored the sensitivity of the ratio of the above canopy flux to the surface emission on several parameters such as chemical lifetime of the compound, friction velocity, stability, and canopy density. Our results show that friction velocity and chemical lifetime affected the loss during transport the most. The canopy density had a significant effect if the chemically reactive compound was emitted from the forest floor. We used the results of the simulations together with oxidant data measured during HUMPPA-COPEC-2010 campaign at a Scots pine site to estimate the effect of the chemistry on fluxes of three typical biogenic VOCs, isoprene, ?-pinene, and ?-caryophyllene. Of these, the chemical degradation had a~major effect on the fluxes of the most reactive species ?-caryophyllene, while the fluxes of ?-pinene were affected during nighttime. For these two compounds representing the mono- and sesquiterpenes groups, the effect of chemical degradation had also a significant diurnal cycle with the highest chemical loss at night. The different day and night time loss terms need to be accounted for, when measured fluxes of reactive compounds are used to reveal relations between primary emission and environmental parameters.

Rinne, J.; Markkanen, T.; Ruuskanen, T. M.; Petäjä, T.; Keronen, P.; Tang, M. J.; Crowley, J. N.; Rannik, Ü.; Vesala, T.

2011-12-01

49

Neuron-Semiconductor Chip with Chemical Synapse between Identified Neurons  

NASA Astrophysics Data System (ADS)

Noninvasive electrical stimulation and recording of neuronal networks from semiconductor chips is a prerequisite for the development of neuroelectronic devices. In a proof-of-principle experiment, we implemented the fundamental element of such future hybrids by joining a silicon chip with an excitatory chemical synapse between a pair of identified neurons from the pond snail. We stimulated the presynaptic cell (VD4) with a chip capacitor and recorded the activity of the postsynaptic cell (LPeD1) with a transistor. We enhanced the strength of the soma-soma synapse by repetitive capacitor stimulation, establishing a neuronal memory on the silicon chip.

Kaul, R. Alexander; Syed, Naweed I.; Fromherz, Peter

2004-01-01

50

Sensitivity, robustness, and identifiability in stochastic chemical kinetics models  

PubMed Central

We present a novel and simple method to numerically calculate Fisher information matrices for stochastic chemical kinetics models. The linear noise approximation is used to derive model equations and a likelihood function that leads to an efficient computational algorithm. Our approach reduces the problem of calculating the Fisher information matrix to solving a set of ordinary differential equations. This is the first method to compute Fisher information for stochastic chemical kinetics models without the need for Monte Carlo simulations. This methodology is then used to study sensitivity, robustness, and parameter identifiability in stochastic chemical kinetics models. We show that significant differences exist between stochastic and deterministic models as well as between stochastic models with time-series and time-point measurements. We demonstrate that these discrepancies arise from the variability in molecule numbers, correlations between species, and temporal correlations and show how this approach can be used in the analysis and design of experiments probing stochastic processes at the cellular level. The algorithm has been implemented as a Matlab package and is available from the authors upon request.

Komorowski, Michal; Costa, Maria J.; Rand, David A.; Stumpf, Michael P. H.

2011-01-01

51

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

PubMed

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

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

2011-06-01

52

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

PubMed Central

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.

2014-01-01

53

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

SciTech Connect

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.

Sinha, D.N.; Springer, K.; Han, W.; Lizon, D.; Kogan, S. [Los Alamos National Lab., NM (United States). Electronic Materials and Devices Group

1997-12-01

54

Monitoring FoxO1 localization in Chemically Identified Neurons  

PubMed Central

The PI3K-Akt-FoxO1 pathway contributes to the actions of insulin and leptin in several cell types, including neurons in the central nervous system. However, identifying these actions in chemically identified neurons has proven difficult. To address this problem, we have developed a reporter mouse for monitoring PI3K-Akt signaling in specific populations of neurons, based on FoxO1 nucleocytoplasmic shuttling. The reporter, FoxO1 fused to GFP (FoxO1GFP), is expressed under the control of a ubiquitous promoter that is silenced by a loxP flanked transcriptional blocker. Thus, the expression of the reporter in selected cells is dependent on the action Cre-recombinase. Using this model, we found that insulin treatment resulted in the nuclear exclusion of FoxO1GFP within POMC and AgRP neurons in a dose- and time-dependent manner. FoxO1GFP nuclear exclusion was also observed in POMC neurons following in vivo administration of insulin. In addition, leptin induced transient nuclear export of FoxO1GFP in POMC neurons in a dose dependent fashion. Finally, insulin-induced nuclear export was impaired in POMC neurons by pretreatment with free fatty acids, a paradigm known to induce insulin resistance in peripheral insulin target tissues. Thus, our FoxO1GFP mouse provides a tool for monitoring the status of PI3K-Akt signaling in a cell-specific manner under physiological and pathophysiological conditions.

Fukuda, Makoto; Jones, Juli E.; Olson, David; Hill, Jennifer; Lee, Charlotte E.; Gautron, Laurent; Choi, Michelle; Zigman, Jeffrey M.; Lowell, Bradford B.; Elmquist, Joel K.

2009-01-01

55

Antifoaming effect of chemical compounds in manure biogas reactors.  

PubMed

A precise and efficient antifoaming control strategy in bioprocesses is a challenging task as foaming is a very complex phenomenon. Nevertheless, foam control is necessary, as foam is a major operational problem in biogas reactors. In the present study, the effect of 14 chemical compounds on foam reduction was evaluated at concentration of 0.05%, 0.1% and 0.5% v/v(sample), in raw and digested manure. Moreover, two antifoam injection methods were compared for foam reduction efficiency. Natural oils (rapeseed and sunflower oil), fatty acids (oleic, octanoic and derivative of natural fatty acids), siloxanes (polydimethylsiloxane) and ester (tributylphosphate) were found to be the most efficient compounds to suppress foam. The efficiency of antifoamers was dependant on their physicochemical properties and greatly correlated to their chemical characteristics for dissolving foam. The antifoamers were more efficient in reducing foam when added directly into the liquid phase rather than added in the headspace of the reactor. PMID:23972674

Kougias, P G; Tsapekos, P; Boe, K; Angelidaki, I

2013-10-15

56

Quantitative chemical proteomics for identifying candidate drug targets.  

PubMed

We have developed a systematic strategy for drug target identification. This consists of the following sequential steps: (1) enrichment of total binding proteins using two differential affinity matrixes upon which are immobilized positive and negative chemical structures for drug activity, respectively; (2) covalent labeling of the proteins with a new cleavable isotope-coded affinity tag (ICAT) reagent, followed by proteolysis of the combined proteins; (3) isolation, identification, and relative quantification of the tagged peptides by liquid chromatography-mass spectrometry; (4) array-based transcription profiling to select candidate proteins; and (5) confirmation of direct interaction between the activity-associated structure and the selected proteins by using surface plasmon resonance. We present a typical application to identify the primary binding protein of a novel class of anticancer agents exemplified by E7070. Our results suggest that this approach provides a new aspect of quantitative proteomics to find specific binding proteins from protein mixture and should be applicable to a wide variety of biologically active small molecules with unidentified target proteins. PMID:12720356

Oda, Yoshiya; Owa, Takashi; Sato, Toshitaka; Boucher, Brian; Daniels, Scott; Yamanaka, Hidenori; Shinohara, Yasuhiro; Yokoi, Akira; Kuromitsu, Junro; Nagasu, Takeshi

2003-05-01

57

ElectroChemical Treeing in Ethylene-Propylene Rubber Compounds  

Microsoft Academic Search

A series of Ethylene-Propylene Diene (EPDM) compounds, designed to be transparent or translucent in nature, were formulated for the purpose of studying electro-chemical treeing, Systems were tested in sheet form for evaluation of physical properties and crosslinking behavior, and extruded under laboratory conditions over 14 AWG bare copper wire into thin wall mini-cables. Cables were then subjected to the Phelps

B. S. Bernstein; N. Srinivas; J. D. Hogan; C. Katz

1975-01-01

58

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

SciTech Connect

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

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

1994-09-01

59

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

PubMed Central

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

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

2011-01-01

60

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

PubMed

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

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

2014-06-30

61

Chemical metabolism of medicinal compounds from natural botanicals.  

PubMed

Traditional Chinese medicine (TCM) and its natural products are complex mixtures containing hundreds of chemically different constituents but only a few components are responsible for the pharmacological effects and bioactivities. In order to clarify the functional mechanism of active compounds, the studies on metabolism are of great significance and necessity. Previously, research mainly focused on the aspect of pharmacokinetics, however in recent years, chemical metabolism of active compounds has drawn increasing attention. Researches on the chemical metabolism of single phytochemicals help to understand the transformation process in vivo and mechanism of action, also contribute to pharmacodynamics and toxicology studies and new drug development. In the present paper, the chemical metabolism of nine categories of phytochemicals was reviewed. This review focused on pharmacological action, metabolic characteristics, metabolic pathways, metabolites and assay method of alkaloids, flavonoids, saponins, terpenoids, stilbenes, phenols, quinones, lignans and esters. The parent drugs, perhaps the metabolites, or they together play a role in pharmacological effects. And different routes of administration may lead to different results of transformation pathways and metabolites. Moreover, high-tech assay methods, particularly the combined use of modern instrument analytical techniques, are beneficial to the research of drug metabolism. PMID:22414089

Lu, Q; Jiang, J-G

2012-01-01

62

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

PubMed Central

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

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

2012-01-01

63

Autotaxin inhibition: development and application of computational tools to identify site-selective lead compounds.  

PubMed

Autotaxin (ATX) catalyzes the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA). Both ATX and LPA have been linked to pathophysiologies ranging from cancer to neuropathic pain. Inhibition of LPA production by ATX is therefore of therapeutic interest. Here we report the application of previously-developed, subsite-targeted pharmacophore models in a screening workflow that involves either docking or binary QSAR as secondary filters to identify ATX inhibitors from previously unreported structural types, four of which have sub-micromolar inhibition constants. Cell-based assays demonstrate that ATX inhibition and cytotoxicity structure-activity-relationships (SAR) exhibit selectivity cliffs, characterized by structurally similar compounds exhibiting similar biological activities with respect to ATX inhibition but very different biological activities with respect to cytotoxicity. Thus, general cytotoxicity should not be used as an early filter to eliminate candidate ATX inhibitor scaffolds from further SAR studies. Assays using two substrates of vastly different sizes demonstrate that the tools developed to identify compounds binding outside the central core of the active site did identify compounds acting at an allosteric site. In contrast, tools developed to identify active-site directed compounds did not identify active-site directed compounds. The stronger volume overlap imposed when selecting screening candidates expected to bind outside the active site is likely responsible for the stronger match between intended and actual target site. PMID:23816044

Norman, Derek D; Ibezim, Ayolah; Scott, Whitney E; White, Stanley; Parrill, Abby L; Baker, Daniel L

2013-09-01

64

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

Microsoft Academic Search

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,

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

1997-01-01

65

Application of Micro Arrayed Compound Screening (pcARCS) to Identify Inhibitors of Caspase3  

Microsoft Academic Search

Micro Arrayed Compound Screening (pARCS) is a miniaturized ultra-high-throughput screening platform developed at Abbott Laboratories. In this format, 8640 discrete compounds are spotted and dried onto a polystyrene sheet, which has the same footprint as a 96-well plate. A homogeneous time-resolved fluorescence assay format (LANCE) was applied to identify the inhibitors of caspase-3 using a peptide substrate labeled with a

Sujatha M. Gopalakrishnan; Jarkko Karvinen; James L. Kofron; David J. Burns; Usha Warrior

2002-01-01

66

Indoor Volatile Organic Compounds and Chemical Sensitivity Reactions  

PubMed Central

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.

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

2013-01-01

67

Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach  

PubMed Central

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.

2014-01-01

68

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

PubMed

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

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

2013-11-21

69

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

PubMed

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

Bankova, Vassya; Popova, Milena; Trusheva, Boryana

2014-01-01

70

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

PubMed

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

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

2012-10-01

71

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

PubMed

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

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

2014-06-01

72

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

PubMed Central

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

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

2012-01-01

73

Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds  

PubMed Central

Aims: To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships. Methods: A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model. Results: Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%. Conclusions: Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard.

Jarvis, J; Seed, M; Elton, R; Sawyer, L; Agius, R

2005-01-01

74

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

PubMed

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

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

2012-11-15

75

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

PubMed Central

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

2013-01-01

76

Criteria for identifying endogenous compounds as digoxin-like immunoreactive factors in humans.  

PubMed

Endogenous digoxin-like immunoreactive factors (DLIF) are factors in plasma that interact with anti-digoxin antibodies. In this report we propose specific empirical criteria that must be satisfied by any group of endogenous compounds purported to account for DLIF activity in human plasma. These criteria include immunoreactive potency relative to existing physiologic concentrations as well as the biochemical and protein binding properties of these compounds. Recent studies have identified several congeners of fatty acids and phospholipids, hydrocortisone, and dehydroepiandrosterone-sulfate as compounds likely to account for DLIF activity in plasma. Using the above criteria we demonstrate that the highest reported plasma concentrations of these compounds combined account for less than 25% of DLIF reported in healthy adult subjects, less than 11% in newborns, less than 27% in pregnant women, and less than 39% in patients with renal failure. Human serum albumin at a concentration of 40 g/l completely abolished any detectable interaction of these compounds with both anti-digoxin antibodies or canine kidney Na/K-ATPase. The immunoreactive and physical properties of these compounds are also not consistent with those reported for DLIF. We conclude that these compounds do not account for the plasma DLIF concentrations measured in human subjects nor are they likely to play a role as specific endogenous regulators of Na/K-ATPase. PMID:2844442

Lau, B W; Valdes, R

1988-06-30

77

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...

78

Activation of the TCR complex by small chemical compounds.  

PubMed

Small chemical compounds and certain metal ions can activate T cells, resulting in drug hypersensitivity reactions that are a main problem in pharmacology. Mostly, the drugs generate new antigenic epitopes on peptide-major histocompatibility complex (MHC) molecules that are recognized by the T-cell antigen receptor (TCR). In this review we discuss the molecular mechanisms of how the drugs alter self-peptide-MHC, so that neo-antigens are produced. This includes (1) haptens covalently bound to peptides presented by MHC, (2) metal ions and drugs that non-covalently bridge self-pMHC to the TCR, and (3) drugs that allow self-peptides to be presented by MHCs that otherwise are not presented. We also briefly discuss how a second signal-next to the TCR-that naïve T cells require to become activated is generated in the drug hypersensitivity reactions. PMID:24214616

Louis-Dit-Sully, Christine; Schamel, Wolfgang W A

2014-01-01

79

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

PubMed

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

Torres, Alexia

2012-12-01

80

Yeast as a biosensor of detoxification: a tool for identifying new compounds that revert multidrug resistance.  

PubMed

During tumour progression, cells accumulate secondary mutations and/or chromosomal aberrations that generate genetic diversity within the tumour cell population. This may result in the acquisition of new properties that increase tumour malignancy, such as invasiveness or resistance to chemotherapy. One of the important mechanisms of chemotherapy resistance is overexpression or biochemical activation of ABC family transporters. ABC transporters remove anti tumour drugs from the cell, reducing their intracellular concentration and producing resistance against a wide range of chemically unrelated drugs, known as multidrug resistant phenotype (MDR). During recent decades, much effort has been devoted to the isolation of compounds able to inhibit the activity of these transporters. However, few such compounds have reached clinical practice and MDR remains a serious complication in cancer therapy. In an innovative approach to finding new ABC inhibitors, we propose using fission yeast Schizosaccharomyces pombe as a biosensor of detoxification that would enable cost-efficient screening of natural compounds and chemical libraries for molecules that revert the MDR phenotype. Existing fission yeast tools provide genetic, biochemical and cell biological analysis, thereby facilitating identification of drug targets. Putative inhibitors and modulators of ABC transporters could be used in combination with chemotherapeutic drugs for the treatment of multidrug resistant tumours. PMID:23614676

Martín-Cordero, Carmen; Sanchez-Pico, Angeles; Leon-Gonzalez, Antonio J; Perez-Pulido, Antonio J; Daga, Rafael R

2013-08-01

81

Systems biology approaches in identifying the targets of natural compounds for cancer therapy.  

PubMed

Natural compounds have been known to exert inhibitory effects on the development and progression of human cancers. However, the targets of these naturally occurring agents are largely elusive. Recently, systems biology approaches based on high-throughput technologies such as DNA microarrays have begun to be utilized for investigating the targets of drugs including natural compounds. Therefore, in this review article, we will briefly introduce the several systems biology approaches, and will discuss the application of these new technologies for identifying the therapeutic targets of natural compounds for supporting their roles in the prevention and/or treatment of human cancers. Furthermore, identification of the novel targets will be useful for designing more effective and targeted therapeutic strategies for achieving better treatment outcome in patients diagnosed with cancers. PMID:23237676

Tan, Yi; Wu, Qiong; Xia, Jun; Miele, Lucio; Sarkar, Fazlul H; Wang, Zhiwei

2013-06-01

82

A Chemical Screen to Identify Novel Inhibitors of Fin Regeneration in Zebrafish  

PubMed Central

Abstract We performed a chemical screen to look for novel inhibitors of zebrafish caudal fin regeneration. In a pilot screen, 520 compounds were tested. Two compounds, budesonide and AGN192403, abrogated fin regeneration. One compound in particular, AGN192403, targets the imidazoline receptor, a pathway not previously linked to fin regeneration. In addition to inhibiting regeneration of the adult fin, AGN192403 also blocked regeneration of the larval fin fold. Finally, the inhibitory effect of AGN192403 on fin regeneration persisted after removal of the drug. These studies demonstrate that chemical screening is feasible in adult zebrafish and that it is a reasonable strategy to use for exploring the biology of regeneration.

Oppedal, Douglas

2010-01-01

83

A chemical screen to identify novel inhibitors of fin regeneration in zebrafish.  

PubMed

We performed a chemical screen to look for novel inhibitors of zebrafish caudal fin regeneration. In a pilot screen, 520 compounds were tested. Two compounds, budesonide and AGN192403, abrogated fin regeneration. One compound in particular, AGN192403, targets the imidazoline receptor, a pathway not previously linked to fin regeneration. In addition to inhibiting regeneration of the adult fin, AGN192403 also blocked regeneration of the larval fin fold. Finally, the inhibitory effect of AGN192403 on fin regeneration persisted after removal of the drug. These studies demonstrate that chemical screening is feasible in adult zebrafish and that it is a reasonable strategy to use for exploring the biology of regeneration. PMID:20384483

Oppedal, Douglas; Goldsmith, Matthew I

2010-03-01

84

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

SciTech Connect

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.

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

2001-12-13

85

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

PubMed Central

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

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

2014-01-01

86

The Use of Functional Chemical-Protein Associations to Identify Multi-Pathway Renoprotectants  

PubMed Central

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

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

2014-01-01

87

A Screen for Kinetochore-Microtubule Interaction Inhibitors Identifies Novel Antitubulin Compounds  

Microsoft Academic Search

BackgroundProtein assemblies named kinetochores bind sister chromatids to the mitotic spindle and orchestrate sister chromatid segregation. Interference with kinetochore activity triggers a spindle checkpoint mediated arrest in mitosis, which frequently ends in cell death. We set out to identify small compounds that inhibit kinetochore-microtubule binding for use in kinetochore-spindle interaction studies and to develop them into novel anticancer drugs.Methodology\\/Principal FindingsA

Emanuela Screpanti; Stefano Santaguida; Tam Nguyen; Romano Silvestri; Rick Gussio; Andrea Musacchio; Ernest Hamel; Peter de Wulf; Daniela Cimini

2010-01-01

88

Volatile chemicals identified in extracts from newly hybrid citrus, dekopon (Shiranuhi mandarin Suppl. J.).  

PubMed

Extracts from the peel and flesh of a citrus fruit, dekopon (Shiranuhi mandarin Suppl. J.), were obtained under reduced pressure followed by dichloromethane extraction. A total of 127 volatile chemicals were identified in the extracts using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). They included 11 monoterpenes, 32 monoterpenoids, 9 sesquiterpenes, 5 sesquiterpenoids, 20 aliphatic alcohols, 14 aliphatic esters, 15 aliphatic aldehydes and ketones, 7 aliphatic acids, and 10 miscellaneous compounds. The major volatile constituents of the extract from the peel were d-limonene (2380.33 mg/kg), myrcene (36.54 mg/kg), bisabolene (30.03 mg/kg), sabinene (21.12 mg/kg), trans-beta-ocimene (16.96 mg/kg), valencene (12.84 mg/kg), decanal (8.14 mg/kg), beta-phellandrene (4.53 mg/kg), citronellol (4.51 mg/kg), 4-terpineol (4.50 mg/kg), linalool (4.13 mg/kg), and citronellyl acetate (3.63 mg/kg). The major volatile constituents of the extract from the flesh were ethyl acetate (21.54 mg/kg), acetoin (7.23 mg/kg), 3-methylbutanol (2.79 mg/kg), p-mentha-cis-2,8-dien-1-ol (1.01 mg/kg), 3-methylbutanoic acid (0.95 mg/kg), isobutanol (0.59 mg/kg), trans-isopiperitenol (0.58 mg/kg), p-mentha-trans-2,8-dien-1-ol, and trans-carveol (0.44 mg/kg). Compositions of volatile chemicals in peel and flesh extract were considerably different: the peel extract was rich in terpenes, whereas the flesh extract was rich in aliphatic compounds. PMID:12207474

Umano, Katumi; Hagi, Yukio; Shibamoto, Takayuki

2002-09-11

89

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

SciTech Connect

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

Stone, Alex, E-mail: alst461@ecy.wa.go [Washington State Department of Ecology, P.O. Box 47600, Olympia, WA 98504-7600 (United States); Delistraty, Damon, E-mail: ddel461@ecy.wa.go [Washington State Department of Ecology, Spokane, WA 99205-1295 (United States)

2010-11-15

90

Chemical modification of the multitarget neuroprotective compound fisetin.  

PubMed

Many factors are implicated in age-related central nervous system (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 EC(50) in cell based assays, low lipophilicity, high topological polar surface area (tPSA), and poor bioavailability suggest that there is room for medicinal chemical improvement. Here we describe a multitiered 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

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

2012-01-12

91

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

PubMed

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

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

2014-03-18

92

Chemical environment and Ce valence: Global trends in transition-metal compounds  

SciTech Connect

Results of L/sub III/ absorption spectroscopy measurements on a wide range of Ce--transition-metal (T) compounds are presented and Ce valence-state estimates are made. We are able to identify extremely regular trends in the response of the Ce valence and Ce-T hybridization strength to systematic variations in the solid-state chemical environment. Our work facilitates identification of the specific elements in the T-metal electronic structure which drive the Ce valence-state change.

Neifeld, R.A.; Croft, M.; Mihalisin, T.; Segre, C.U.; Madigan, M.; Torikachvili, M.S.; Maple, M.B.; DeLong, L.E.

1985-11-15

93

Machine learning of molecular electronic properties in chemical compound space  

NASA Astrophysics Data System (ADS)

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.

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

2013-09-01

94

Chemicals identified in human biological media, a data base. Second annual report, October 1980  

SciTech Connect

A comprehensive data base of chemicals identified in human biological media (tissues and body fluids) has been established. This two-part volume is the second annual publication of the data base. Part 2 contains the data base in tabular format and arranged alphabetically by Chemical Abstracts Service (CAS) preferred chemical name. The chemical is given along with its CAS registry number, formula, atomic weight, melting point, boiling point, and vapor pressure. Tissues are listed alphabetically in with the record number.

Cone, M.V.; Baldauf, M.F.; Martin, F.M.; Ensminger, T. (comps.)

1981-01-01

95

Alarm responses caused by newly identified compounds derived from the honeybee sting.  

PubMed

Twelve compounds identified from honeybee,Apis mellifera L., sting extracts were evaluated in a standardized laboratory test for their effectiveness in eliciting an alarm response from caged worker honeybees. Two-1-decanol and phenol-were judged ineffective as alarm pheromones. The other ten-1-butanol, isopentyl acetate, isopentyl alcohol, 1-hexanol, 2-heptyl acetate, 2-heptanol, 1-octanol, 1-acetoxy-2-octene, 2-nonyl acetate, and 1-acetoxy-2-nonene-produced alarm responses of similar speed and intensity. Three non-sting-derived compounds-?-ionone, methyl benzoate, andtrans-cinnamaldehyde-caused weak or no responses, indicating that the responses were not simply a reaction to concentrated odoriferous substances. PMID:24408619

Collins, A M; Blum, M S

1983-01-01

96

Chemical reactivity and biological activity of chalcones and other ?,?-unsaturated carbonyl compounds.  

PubMed

Abstract 1. Chalcones are structural analogues of benzalacetophenone (BAP). Several derivatives have been identified in plants and anticarcinogenic and anti-inflammatory properties were attributed to the compounds, probably related to their direct antioxidant activity or stimulatory effects on the expression of endogenous defence enzymes like hemeoxygenase-1 (HO-1). HO-1 expression is triggered by the Nrf2-Keap1 signalling pathway, initiated by the addition of chalcones to thiol groups of Keap1 via Michael-type reaction. 2. The present study used a model system estimating the reactivity of different synthetic chalcones and other ?,?-unsaturated carbonyl compounds with thiols and compared the chemical reactivity with the biological activity, measured by HO-1 expression in human dermal fibroblasts. 3. Chemical reactivity with the thiol group of N-acetylcysteine was determined with 5,5'-dithiobis-(2-nitrobenzoic acid) and followed chemical principles of structure-reactivity relationship. Most reactive were sulforaphane, dimethylfumarate, chalcone 3 ((2E)-1-phenyl-3-pyrimidin-2-ylprop-2-en-1-one) and chalcone 7 (1,3-diphenylprop-2-yn-1-one). This result demonstrates that ?,?-unsaturated carbonyl derivatives react with thiols differently. All compounds were also biologically active; however, expression of HO-1 was not only related to the chemical reactivity but also to the lipophilicity of the molecules which likely affected transmembrane uptake. Most efficient inducers of HO-1 expression were BAP, 4-hydroxynonenal and chalcone 1 (4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]benzonitrile), chalcone 5 ((2E)-1-phenyl-3-[4-(trifluoromethyl)-phenyl]prop-2-en-1-one) and chalcone 7. PMID:23339572

Maydt, Daniela; De Spirt, Silke; Muschelknautz, Christian; Stahl, Wilhelm; Müller, Thomas J J

2013-08-01

97

Study on the chemical evolution of low molecular weight compounds in a highly oxidized atmosphere using electric discharges.  

PubMed

The molecular basis for the chemical evolution of low molecular compounds was studied using electric discharges on a highly oxidized atmosphere comprised of CO2, N2 and H2O. In the gas phase, O2 and CO were formed by the decomposition of CO2 and their yields were enhanced by the addition of N2 to the gas mixture. It was demonstrated that H2O suppressed the reduction of CO2 while H2O also had a role in producing organic compounds such as formic acid and formaldehyde. Infrared analysis of the water soluble products and the inner surface of the reaction vessel indicated the production of compounds more complex than formic acid and formaldehyde. These compounds contained the chemical bonds which were identified to be OH, CO, CN and/or CC. PMID:6815608

Kawamoto, K; Akaboshi, M

1982-06-01

98

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

PubMed

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

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

99

[Chemical discrimination of compounds possessing an amino group].  

PubMed

Cyclic 1,3-amino alcohols have been successfully resolved via lipase-catalysed O-acylation of their Z derivatives, using vinyl butyrate as acyl donor in different ether solvents. A direct HPLC method was developed for the monitoring of the resolutions. Most of the screened lipases preferred the S enantiomer. Both alcohol and ester enantiomers were obtained in ee > 90% after gram-scale resolutions. A new isothiocyanato-type CDA, (1S,2S)- or (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propyl isothiocyanate [(R,R)- or (S,S)-DANI], was designed for the indirect HPLC enantioseparation of primary and secondary amino compounds. The new reagent can be readily synthetized in optically pure form (> or = 99.5%) after a straightforward two-step synthesis. It is stable chemically and stereochemically both in the solid and in the solution phase. It is available in both enantiomeric forms, allowing the appropriate selection of the elution sequence. The kinetics of derivatization was studied in detail for alpha-amino acids and for beta-blockers. The quantitativeness of reactions was ensured by optimization of reaction conditions (pH, reagent excess, temperature). As concerns the HPLC analyses of the thiourea derivatives formed, significant differences were found between selectivities of the organic modifiers applied; in most cases, MeOH proved much more effective than MeCN with respect to both retention times and resolutions. In conclusion, the new CDA was capable of the resolution of most of the investigated analytes. PMID:12498041

Péter, Mária

2002-01-01

100

A gold coordination compound as a chemical probe to unravel aquaporin-7 function.  

PubMed

Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many physiological functions. Aquaporin-based modulators are predicted to have potential utility in the treatment of several diseases, as well as chemical tools to assess AQPs function in biological systems. We recently reported gold(III) compounds as human AQP3 inhibitors, with Auphen as the most potent of the series. In this work, we assessed the modulation of aquaporin-7 (AQP7) expressed in an adipocyte cell model and show that Auphen significantly inhibits mouse and human AQP7. By homology modeling and molecular docking it was possible to identify the thioether groups of methionine residues, in particular Met47, as likely candidates for binding to the gold(III) complex. Our data point to Auphen as a useful chemical tool to detect AQP7 function. It might constitute a basis to develop inhibitors with improved affinity towards different aquaglyceroporin isoforms. PMID:24891084

Madeira, Ana; de Almeida, Andreia; de Graaf, Chris; Camps, Marta; Zorzano, Antonio; Moura, Teresa F; Casini, Angela; Soveral, Graça

2014-07-01

101

A 1536-well quantitative high-throughput screen to identify compounds targeting cancer stem cells.  

PubMed

Tumor cell subpopulations called cancer stem cells (CSCs) or tumor-initiating cells (TICs) have self-renewal potential and are thought to drive metastasis and tumor formation. Data suggest that these cells are resistant to current chemotherapy and radiation therapy treatments, leading to cancer recurrence. Therefore, finding new drugs and/or drug combinations that cause death of both the differentiated tumor cells as well as CSC populations is a critical unmet medical need. Here, we describe how cancer-derived CSCs are generated from cancer cell lines using stem cell growth media and nonadherent conditions in quantities that enable high-throughput screening (HTS). A cell growth assay in a 1536-well microplate format was developed with these CSCs and used to screen a focused collection of oncology drugs and clinical candidates to find compounds that are cytotoxic against these highly aggressive cells. A hit selection process that included potency and efficacy measurements during the primary screen allowed us to efficiently identify compounds with potent cytotoxic effects against spheroid-derived CSCs. Overall, this research demonstrates one of the first miniaturized HTS assays using CSCs. The procedures described here should enable further testing of the effect of compounds on CSCs and help determine which pathways need to be targeted to kill them. PMID:22927676

Mathews, Lesley A; Keller, Jonathan M; Goodwin, Bonnie L; Guha, Rajarshi; Shinn, Paul; Mull, Rebecca; Thomas, Craig J; de Kluyver, Rachel L; Sayers, Thomas J; Ferrer, Marc

2012-10-01

102

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

PubMed

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

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

2003-01-01

103

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

NASA Technical Reports Server (NTRS)

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.

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

2005-01-01

104

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

PubMed Central

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.

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

2013-01-01

105

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

PubMed

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

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

106

Graph kernels for chemical compounds using topological and three-dimensional local atom pair environments  

Microsoft Academic Search

Approaches that can predict the biological activity or properties of a chemical compound are an important application of machine learning. In this paper, we introduce a new kernel function for measuring the similarity between chemical compounds and for learning their related properties and activities. The method is based on local atom pair environments which can be rapidly computed by using

Georg Hinselmann; Nikolas Fechner; Andreas Jahn; Matthias Eckert; Andreas Zell

2010-01-01

107

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

PubMed Central

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.”

2013-01-01

108

Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease  

PubMed Central

The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a unique bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease.

Bradner, James E.; Mak, Raymond; Tanguturi, Shyam K.; Mazitschek, Ralph; Haggarty, Stephen J.; Ross, Kenneth; Chang, Cindy Y.; Bosco, Jocelyn; West, Nathan; Morse, Elizabeth; Shen, John Paul; Kwiatkowski, Nicholas P.; Gheldof, Nele; Dekker, Job; DeAngelo, Daniel J.; Carr, Steven A.; Schreiber, Stuart L.; Golub, Todd R.; Ebert, Benjamin L.

2010-01-01

109

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

DOEpatents

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.

Grindstaff, Quirinus G. (Oak Ridge, TN)

1992-01-01

110

Metabolism of fluoroorganic compounds in microorganisms: impacts for the environment and the production of fine chemicals  

Microsoft Academic Search

Incorporation of fluorine into an organic compound can favourably alter its physicochemical properties with respect to biological\\u000a activity, stability and lipophilicity. Accordingly, this element is found in many pharmaceutical and industrial chemicals.\\u000a Organofluorine compounds are accepted as substrates by many enzymes, and the interactions of microorganisms with these compounds\\u000a are of relevance to the environment and the fine chemicals industry.

Cormac D. Murphy; Benjamin R. Clark; Jessica Amadio

2009-01-01

111

Environmental Fate of Organophosphorus Compounds Related to Chemical Weapons  

Microsoft Academic Search

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

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

2005-01-01

112

Organic--Inorganic Layer Compounds: Physical Properties and Chemical Reactions  

Microsoft Academic Search

In contrast with intercalation compounds, which can exist both with and without organic molecules between the planes of inorganic material, `molecular composite' compounds have organic groups covalently or ionically bound to inorganic layers. In such crystals the aim is to combine magnetic or optical properties characteristic of the inorganic solid state, like magnetism and luminescence, with properties found in the

P. Day

1985-01-01

113

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)

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.

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

2001-08-01

114

Identifying the nonpoint source of perfluorinated compounds using a geographic information system based approach.  

PubMed

Perfluorinated compounds (PFCs) have been detected in a wide range of places. They have also been reported to come from nonpoint sources, but the origin of these sources has not been identified. In the present study, we attempted to characterize the nonpoint source of PFCs in the Hayabuchi River, Japan, which runs through an urban area, using a geographic information system (GIS) and statistical analysis. We also estimated annual PFC loads from nonpoint sources in Japan as a whole, determining a magnitude comparable to that from sewage treatment plants (STPs); the range was a few tons per year for each PFC. Perfluorinated compound pollution in river water was found to increase when the river received drainage from an area with a high proportion of commercial and/or transportation land use. It was also found that more PFCs were discharged from the watersheds where train stations are located. This result could be interpreted as the use of land for commercial and transportation purposes is prevalent in close proximity to train stations, and that the effluents from those areas contain high concentrations of PFCs. These findings suggested that train stations could be indicators of nonpoint sources of PFCs. PMID:19159126

Zushi, Yasuyuki; Masunaga, Shigeki

2009-04-01

115

Chemical Carcinogenesis: Azo Dyes, Aryl Amines, and Related Compounds.  

National Technical Information Service (NTIS)

This agent-oriented Cancergram deals with carcinogenicity of fluorene derivatives, azo compounds, naphthylamines, nitroguinoline oxides, and other related specific substances (including hair dyes). The scope includes carcinogenicity and modification of ca...

1982-01-01

116

Identification of IAA transport inhibitors including compounds affecting cellular PIN trafficking by two chemical screening approaches using maize coleoptile systems.  

PubMed

The monocot coleoptile tip region has been generally supposed to be the source of IAA to supply IAA to basal parts by the polar IAA transport system, which results in gravi- and phototropic curvature of coleoptiles. Based on this IAA transport system and gravitropism of maize coleoptiles, we have developed two screening methods to identify small molecules from a large chemical library that inhibit IAA transport. The methods detect molecules that affect (i) gravitropic curvature of coleoptiles; and (ii) the amount of IAA transported from the tip. From 10,000 chemicals, eight compounds were identified and categorized into two groups. Four chemicals in group A decreased IAA transport from the tip, and increased endogenous IAA levels in the tip. The structures of two compounds resembled that of 1-N-naphthylphthalamic acid (NPA), but those of the other two differed from structures of known IAA transport inhibitors. Four chemicals in group B strongly inhibited IAA transport from the tip, but IAA levels at the tip were only slightly affected. At higher concentrations, group B compounds inhibited germination of Arabidopsis, similarly to brefeldin A (BFA). Analysis of the cellular distribution of PIN2-green fluorescent protein (GFP) and PIN1-GFP in Arabidopsis revealed that one of the four chemicals in group B induced internalization of PIN1 and PIN2 proteins into vesicles smaller than BFA bodies, suggesting that this compound affects cellular vesicle trafficking systems related to PIN trafficking. The eight chemicals identified here will be a useful tool for understanding the mechanisms of IAA transport in plants. PMID:22875609

Nishimura, Takeshi; Matano, Naoyuki; Morishima, Taichi; Kakinuma, Chieko; Hayashi, Ken-Ichiro; Komano, Teruya; Kubo, Minoru; Hasebe, Mitsuyasu; Kasahara, Hiroyuki; Kamiya, Yuji; Koshiba, Tomokazu

2012-10-01

117

Microscopic physical and chemical properties of graphite intercalation compounds  

SciTech Connect

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.

Eklund, P.C.

1992-08-24

118

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

DOEpatents

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.

Michaels, E.D.

1981-02-25

119

Chemical properties and methods of analysis of refractory compounds  

NASA Technical Reports Server (NTRS)

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.

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

1978-01-01

120

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...

121

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

PubMed

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

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

2013-01-01

122

Virtual Screening for LPA2-Specific Agonists Identifies a Nonlipid Compound with Antiapoptotic ActionsS?  

PubMed Central

Lysophosphatidic acid (LPA) is a highly potent endogenous lipid mediator that protects and rescues cells from programmed cell death. Earlier work identified the LPA2 G protein-coupled receptor subtype as an important molecular target of LPA mediating antiapoptotic signaling. Here we describe the results of a virtual screen using single-reference similarity searching that yielded compounds 2-((9-oxo-9H-fluoren-2-yl)carbamoyl)benzoic acid (NSC12404), 2-((3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)thio)benzoic acid (GRI977143), 4,5-dichloro-2-((9-oxo-9H-fluoren-2-yl)carbamoyl)benzoic acid (H2L5547924), and 2-((9,10-dioxo-9,10-dihydroanthracen-2-yl)carbamoyl) benzoic acid (H2L5828102), novel nonlipid and drug-like compounds that are specific for the LPA2 receptor subtype. We characterized the antiapoptotic action of one of these compounds, GRI977143, which was effective in reducing activation of caspases 3, 7, 8, and 9 and inhibited poly(ADP-ribose)polymerase 1 cleavage and DNA fragmentation in different extrinsic and intrinsic models of apoptosis in vitro. Furthermore, GRI977143 promoted carcinoma cell invasion of human umbilical vein endothelial cell monolayers and fibroblast proliferation. The antiapoptotic cellular signaling responses were present selectively in mouse embryonic fibroblast cells derived from LPA1&2 double-knockout mice reconstituted with the LPA2 receptor and were absent in vector-transduced control cells. GRI977143 was an effective stimulator of extracellular signal-regulated kinase 1/2 activation and promoted the assembly of a macromolecular signaling complex consisting of LPA2, Na+-H+ exchange regulatory factor 2, and thyroid receptor interacting protein 6, which has been shown previously to be a required step in LPA-induced antiapoptotic signaling. The present findings indicate that nonlipid LPA2-specific agonists represent an excellent starting point for development of lead compounds with potential therapeutic utility for preventing the programmed cell death involved in many types of degenerative and inflammatory diseases.

Kiss, Gyongyi N.; Fells, James I.; Gupte, Renuka; Lee, Sue-Chin; Liu, Jianxiong; Nusser, Nora; Lim, Keng G.; Ray, Ramesh M.; Lin, Fang-Tsyr; Parrill, Abby L.; Sumegi, Balazs; Miller, Duane D.

2012-01-01

123

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

PubMed

Heavy fuel oil (HFO) spills account for approximately 60% of ship-source oil spills and are up to 50 times more toxic than medium and light crude oils. Heavy fuel oils contain elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and alkyl-PAHs, known to be toxic to fish; however, little direct characterization of HFO toxicity has been reported. An effects-driven chemical fractionation was conducted on HFO 7102 to separate compounds with similar chemical and physical properties, including toxicity, to isolate the groups of compounds most toxic to trout embryos. After each separation, toxicity tests directed the next phase of fractionation, and gas chromatography-mass spectrometry analysis correlated composition with toxicity, with a focus on PAHs. Low-temperature vacuum distillation permitted the separation of HFO into 3 fractions based on boiling point ranges. The most toxic of these fractions underwent wax precipitation to remove long-chain n-alkanes. The remaining PAH-rich extract was further separated using open column chromatography, which provided distinct fractions that were grouped according to increasing aromatic ring count. The most toxic of these fractions was richest in PAHs and alkyl-PAHs. The results of the present study were consistent with previous crude oil studies that identified PAH-rich fractions as the most toxic. Environ Toxicol Chem 2014;33:814-824. © 2013 SETAC. PMID:24375845

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

2014-04-01

124

Characterization of traditional Istrian dry-cured ham by means of physical and chemical analyses and volatile compounds.  

PubMed

The aroma-active compounds of Istrian dry-cured ham were investigated by using headspace-solid phase microextraction and gas chromatography-mass spectrometry (GC-MS). Samples of biceps femoris were also evaluated by measuring physical and chemical characteristics: moisture, protein, fat, ash and NaCl content, a(w) value; colour: L*, a*, b* and oxidation of fat: TBARS test. About 50 volatile compounds were identified and quantified which belonged to several classes of chemical: 5 alcohols, 8 aldehydes, 7 alkanes, 1 ketone, 2 esters, 9 monoterpenes and 15 sesquiterpenes. Except volatile compounds derived from lipolysis and proteolysis the most abundant constituents were terpenes (62.97; 41.43%) that originate from spices added in the salting phase of the production process. PMID:21435796

Maruši?, Nives; Petrovi?, Marinko; Vida?ek, Sanja; Petrak, Tomislav; Medi?, Helga

2011-08-01

125

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

SciTech Connect

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 17?-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ? We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ? 4-Nonylphenol, bisphenol A and apigenin exert weak antigestagenic activity. ? SULT1E1 is a significant marker for endometrial antiprogestin effects. ? Ishikawa cells are a tissue-specific approach for characterization of SPRMs. ? Chemicals acting as progesterone receptor antagonists may exert antifertility effects.

Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)] [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany)] [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany)] [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)] [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

2012-05-01

126

STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS  

PubMed Central

Sensitization of guinea pigs to picric acid was obtained by application of oil solutions to the skin, preferably on inflamed sites or by treatment with a compound of picric acid with n-butyl-p-aminobenzoate. The lesions obtained in sensitive animals on superficial administration bore resemblance to human eczema. It seems probable that picric acid sensitization is an instance where a substance does not sensitize directly but after conversion into a more reactive compound, a principle which should be of wider application to instances where the original substance does not readily form conjugates.

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

1940-01-01

127

Mutagenicity of Polycyclic Aromatic Compounds (PAC), Identified in Source Emissions and Ambient Air.  

National Technical Information Service (NTIS)

Several polycyclic aromatic compounds including nitrated and oxygenated derivatives of polycyclic aromatic hydrocarbons were tested for mutagenic activity in the Salmonella/ microsome assay. Among the compounds tested the isomer mix of nitro-1-hydroxypyre...

M. Moeller I. Hagen T. Randahl

1985-01-01

128

Chemical and biological characterisation of nutraceutical compounds of broccoli  

Microsoft Academic Search

People's diet offers a greater and more diverse group of plant bioactives than do drugs, and they often do not realise that many drugs are derived from the compounds originally discovered in plant foods.Numerous epidemiological studies indicate that Brassica vegetables in general, and broccoli in particular, protect humans against cancer since they are rich sources of glucosinolates as well as

D. A. Moreno; M. Carvajal; C. López-Berenguer; C. García-Viguera

2006-01-01

129

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...

130

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 ...

131

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 ...

132

Prediction of Chemical Reactivity Parameters and Physical Properties of Organic Compounds from Molecular Structure Using Sparc.  

National Technical Information Service (NTIS)

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...

S. H. Hilal S. W. Karickhoff L. A. Carreira

2003-01-01

133

Chemical evolution and the preservation of organic compounds on Mars  

NASA Technical Reports Server (NTRS)

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.

Kanavarioti, Anastassia; Mancinelli, Rocco L.

1989-01-01

134

Reagents and methods for using human embryonic stem cells to evaluate toxicity of pharmaceutical compounds and other chemicals  

US Patent & Trademark Office Database

The invention provides biomarker profiles of cellular metabolites and methods for screening chemical compounds including pharmaceutical agents, lead and candidate drug compounds and other chemicals using human embryonic stem cells (hESC) or lineage-specific cells produced therefrom. The inventive methods are useful for testing toxicity, particularly developmental toxicity and detecting teratogenic effects of such chemical compounds.

2014-04-22

135

Spiperone, identified through compound screening, activates calcium-dependent chloride secretion in the airway  

PubMed Central

Cystic fibrosis (CF) is caused by mutations in the gene producing the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR functions as a Cl? channel. Its dysfunction limits Cl? secretion and enhances Na+ absorption, leading to viscous mucus in the airway. Ca2+-activated Cl? channels (CaCCs) are coexpressed with CFTR in the airway surface epithelia. Increases in cytosolic Ca2+ activate the epithelial CaCCs, which provides an alternative Cl? secretory pathway in CF. We developed a screening assay and screened a library for compounds that could enhance cytoplasmic Ca2+, activate the CaCC, and increase Cl? secretion. We found that spiperone, a known antipsychotic drug, is a potent intracellular Ca2+ enhancer and demonstrated that it stimulates intracellular Ca2+, not by acting in its well-known role as an antagonist of serotonin 5-HT2 or dopamine D2 receptors, but through a protein tyrosine kinase-coupled phospholipase C-dependent pathway. Spiperone activates CaCCs, which stimulates Cl? secretion in polarized human non-CF and CF airway epithelial cell monolayers in vitro and in CFTR-knockout mice in vivo. In conclusion, we have identified spiperone as a new therapeutic platform for correction of defective Cl? secretion in CF via a pathway independent of CFTR.

Liang, Lihua; MacDonald, Kelvin; Schwiebert, Erik M.; Zeitlin, Pamela L.; Guggino, William B.

2009-01-01

136

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...

137

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

SciTech Connect

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.

Murphy, A.P.

1991-01-01

138

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

SciTech Connect

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.

Buchanan, D.H.; Amin, M.; Cunningham, R.; Galyen, J. [Eastern Illinois Univ., Charleston, IL (United States)

1994-06-01

139

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

Microsoft Academic Search

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

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

2001-01-01

140

Chemical assessment of the electric arc furnace slag as construction material: Expansive compounds  

Microsoft Academic Search

To carry out a correct management of electric arc furnace slags (EAS) requires a detailed knowledge of their properties. From a chemical point of view, the EAS are surrounded by some chemical problems related to its volume instability when they are used as construction materials, due to the presence of potentially expansive compounds such as free lime and mainly free

Moisés Fr??as Rojas; M. I. Sánchez de Rojas

2004-01-01

141

ToxAlerts: a Web server of structural alerts for toxic chemicals and compounds with potential adverse reactions.  

PubMed

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 growing. PMID:22876798

Sushko, Iurii; Salmina, Elena; Potemkin, Vladimir A; Poda, Gennadiy; Tetko, Igor V

2012-08-27

142

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

PubMed Central

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 growing.

2012-01-01

143

Investigating the Effect of Emetic Compounds on Chemotaxis in Dictyostelium Identifies a Non-Sentient Model for Bitter and Hot Tastant Research  

PubMed Central

Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion/food avoidance in sentient animals. We have used a range of compounds with known emetic /aversive properties to examine the possibility of using the social amoeba, Dictyostelium discoideum, for research into identifying and understanding emetic liability, and hence reduce adverse animal experimentation in this area. Twenty eight emetic or taste aversive compounds were employed to investigate the acute (10 min) effect of compounds on Dictyostelium cell behaviour (shape, speed and direction of movement) in a shallow chemotaxic gradient (Dunn chamber). Compound concentrations were chosen based on those previously reported to be emetic or aversive in in vivo studies and results were recorded and quantified by automated image analysis. Dictyostelium cell motility was rapidly and strongly inhibited by four structurally distinct tastants (three bitter tasting compounds - denatonium benzoate, quinine hydrochloride, phenylthiourea, and the pungent constituent of chilli peppers - capsaicin). In addition, stomach irritants (copper chloride and copper sulphate), and a phosphodiesterase IV inhibitor also rapidly blocked movement. A concentration-dependant relationship was established for five of these compounds, showing potency of inhibition as capsaicin (IC50?=?11.9±4.0 µM) > quinine hydrochloride (IC50?=?44.3±6.8 µM) > denatonium benzoate (IC50?=?129±4 µM) > phenylthiourea (IC50?=?366±5 µM) > copper sulphate (IC50?=?1433±3 µM). In contrast, 21 compounds within the cytotoxic and receptor agonist/antagonist classes did not affect cell behaviour. Further analysis of bitter and pungent compounds showed that the effect on cell behaviour was reversible and not cytotoxic, suggesting an uncharacterised molecular mechanism of action for these compounds. These results therefore demonstrate that Dictyostelium has potential as a non-sentient model in the analysis of the molecular effects of tastants, although it has limited utility in identification of emetic agents in general.

Robery, Steven; Mukanowa, Janina; Percie du Sert, Nathalie; Andrews, Paul L. R.; Williams, Robin S. B.

2011-01-01

144

Prediction of individual compounds forming activity cliffs using emerging chemical patterns.  

PubMed

Activity cliffs are formed by structurally similar or analogous compounds having large potency differences. In medicinal chemistry, pairs or groups of compounds forming activity cliffs are of interest for structure-activity relationship (SAR) analysis and compound optimization. Thus far, activity cliff assessment has mostly been descriptive, i.e., compound data sets and activity landscape representations have been searched for activity cliffs in the context of SAR analysis. Only recently, first attempts have also been made to depart from descriptive analysis and predict activity cliffs. This has been done by building computational models that distinguish compound pairs forming activity cliffs from non-cliff pairs. However, it is principally more challenging to predict single compounds that participate in activity cliffs. Here, we show that individual compounds having high or low potency can be accurately predicted to form activity cliffs on the basis of emerging chemical patterns. PMID:24304008

Namasivayam, Vigneshwaran; Iyer, Preeti; Bajorath, Jürgen

2013-12-23

145

Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure.  

PubMed

Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate (p = 4.4 × 10(-5), q = 0.013), tryptophan (p = 7.0 × 10(-4), q = 0.035) and 2-hydroxyglutarate (p = 1.1 × 10(-4), q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate (p = 3.8 × 10(-7)). Associations specific to repeated (5 day) MA exposure included phosphocholine (p = 4.0 × 10(-4), q = 0.087) and ergothioneine (p = 3.0 × 10(-4), q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects. PMID:23554582

McClay, Joseph L; Adkins, Daniel E; Vunck, Sarah A; Batman, Angela M; Vann, Robert E; Clark, Shaunna L; Beardsley, Patrick M; van den Oord, Edwin J C G

2013-04-01

146

Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure  

PubMed Central

Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate (p = 4.4 × 10?5, q = 0.013), tryptophan (p = 7.0 × 10?4, q = 0.035) and 2-hydroxyglutarate (p = 1.1 × 10?4, q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate (p = 3.8 × 10?7). Associations specific to repeated (5 day) MA exposure included phosphocholine (p = 4.0 × 10?4, q = 0.087) and ergothioneine (p = 3.0 × 10?4, q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects.

Adkins, Daniel E.; Vunck, Sarah A.; Batman, Angela M.; Vann, Robert E.; Clark, Shaunna L.; Beardsley, Patrick M.; van den Oord, Edwin J. C. G.

2012-01-01

147

Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis.  

PubMed

Articular cartilage, which is mainly composed of collagen II, enables smooth skeletal movement. Degeneration of collagen II can be caused by various events, such as injury, but degeneration especially increases over the course of normal aging. Unfortunately, the body does not fully repair itself from this type of degeneration, resulting in impaired movement. Microfracture, an articular cartilage repair surgical technique, has been commonly used in the clinic to induce the repair of tissue at damage sites. Mesenchymal stem cells (MSC) have also been used as cell therapy to repair degenerated cartilage. However, the therapeutic outcomes of all these techniques vary in different patients depending on their age, health, lesion size and the extent of damage to the cartilage. The repairing tissues either form fibrocartilage or go into a hypertrophic stage, both of which do not reproduce the equivalent functionality of endogenous hyaline cartilage. One of the reasons for this is inefficient chondrogenesis by endogenous and exogenous MSC. Drugs that promote chondrogenesis could be used to induce self-repair of damaged cartilage as a non-invasive approach alone, or combined with other techniques to greatly assist the therapeutic outcomes. The recent development of human induced pluripotent stem cell (iPSCs), which are able to self-renew and differentiate into multiple cell types, provides a potentially valuable cell resource for drug screening in a "more relevant" cell type. Here we report a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis. PMID:23161332

Yang, Sheng-Lian; Harnish, Erica; Leeuw, Thomas; Dietz, Uwe; Batchelder, Erika; Wright, Paul S; Peppard, Jane; August, Paul; Volle-Challier, Cecile; Bono, Francoise; Herbert, Jean-Marc; Izpisua Belmonte, Juan Carlos

2012-12-01

148

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

PubMed

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 17?-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. PMID:22414680

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

149

Hydroxynaphthoic acids identified in a high throughput screening potently ameliorate endoplasmic reticulum stress as novel chemical chaperones.  

PubMed

Folding of newly synthesized protein occurs in endoplasmic reticulum (ER) and is assisted by chaperone molecules. In ER stress conditions, misfolded proteins are enriched in a lumen of ER perturbing its normal function, which triggers cellular self-defense mechanism, the unfolded protein response (UPR). It was reported that tunicamycin-induced ER stress can be modulated with high concentration of chemicals such as 4-phenylbutyric acid and salicylate. In search of assay systems to identify such compounds, we have developed a cell-based reporter assay where renilla luciferase activity is driven by glucose-regulated protein 78 (GRP78) promoter. Using our reporter assay, we have screened chemical libraries and found that hydroxynaphthoic acids, especially 1-, 3-, and 6-hydroxy-2-naphthoic acids, potently decrease the ER stress signal, showing an order of magnitude better activity than salicylate. UPR markers such as GRP78, C/EBP homology protein (CHOP) and phosphorylated protein kinase RNA-activated (PKR)-like ER kinase (PERK) were significantly down-regulated with hydroxynaphthoic acids in western blot. Among the analogues, 1-hydroxy-2-naphthoic acid was the most potent in down-regulating those UPR markers. Further, both phosphorylated inositol-requiring enzyme 1? (IRE1?) and spliced form of X-box binding protein 1 (XBP1) were decreased in the protein and the mRNA level, implying both PERK and IRE1? branches in UPR mechanism are controlled with hydroxynaphthoic acids. Taken together, it was suggested that hydroxynaphthoic acids exert their ER stress-reducing activity prior to the UPR activation as chemical chaperones do. In summary, we report a cell-based assay system for the screening of ER stress-reducing compounds and hydroxynaphthoic acids as novel series of chemical chaperones. PMID:23812398

Jeong, Kwi-wan; Ku, Jin-mo; Park, Myung-whan; Park, Sun-mi; Yang, Jung-eun; Nam, Tae-gyu

2013-01-01

150

An isogenic cell panel identifies compounds that inhibit proliferation of mTOR-pathway addicted cells by different mechanisms.  

PubMed

The mTOR pathway is a critical integrator of nutrient and growth factor signaling. Once activated, mTOR promotes cell growth and proliferation. Several components of the mTOR pathway are frequently deregulated in tumors, leading to constitutive activation of the pathway and thus contribute to uncontrolled cell growth. We performed a high-throughput screen with an isogenic cell line system to identify compounds specifically inhibiting proliferation of PTEN/mTOR-pathway addicted cells. We show here the characterization and mode of action of two such compound classes. One compound class inhibits components of the PTEN/mTOR signaling pathway, such as S6 ribosomal protein phosphorylation, and leads to cyclin D3 downregulation. These compounds are not adenosine triphosphate competitive inhibitors for kinases in the pathway, nor do they require FKBP12 for activity like rapamycin. The other compound class turned out to be a farnesylation inhibitor, blocking the activity of GTPases, as well as an inducer of oxidative stress. Our results demonstrate that an isogenic cell system with few specific mutations in oncogenes and tumor suppressor genes can identify different classes of compounds selectively inhibiting proliferation of PTEN/mTOR pathway-addicted isogenic clones. The identified mechanisms are in line with the known cellular signaling networks activated by the altered oncogenes and suppressor genes in the isogenic system. PMID:23954931

Wyder Peters, Lorenza; Molle, Klaus D; Thiemeyer, Anke; Knopf, Agnes; Goxe, Marie; Guerry, Philippe; Brodbeck, Daniela; Colombi, Marco; Hall, Michael N; Moroni, Christoph; Regenass, Urs

2014-01-01

151

Deducing the mechanism of action of compounds identified in phenotypic screens by integrating their multiparametric profiles with a reference genetic screen.  

PubMed

Cell-based high-content screens are increasingly used to discover bioactive small molecules. However, identifying the mechanism of action of the selected compounds is a major bottleneck. Here we describe a protocol consisting of experimental and computational steps to identify the cellular pathways modulated by chemicals, and their mechanism of action. The multiparametric profiles from a 'query' chemical screen are used as constraints to select genes with similar profiles from a 'reference' genetic screen. In our case, the query screen is the intracellular survival of mycobacteria and the reference is a genome-wide RNAi screen of endocytosis. The two disparate screens are bridged by an 'intermediate' chemical screen of endocytosis, so that the similarity in the multiparametric profiles between the chemical and the genetic perturbations can generate a testable hypothesis of the cellular pathways modulated by the chemicals. This approach is not assay specific, but it can be broadly applied to various quantitative, multiparametric data sets. Generation of the query system takes 3-6 weeks, and data analysis and integration with the reference data set takes an 3 additional weeks. PMID:24481274

Sundaramurthy, Varadharajan; Barsacchi, Rico; Chernykh, Mikhail; Stöter, Martin; Tomschke, Nadine; Bickle, Marc; Kalaidzidis, Yannis; Zerial, Marino

2014-02-01

152

Web server to identify similarity of amino acid motifs to compounds (SAAMCO).  

PubMed

Protein-protein interactions are fundamental in mediating biological processes including metabolism, cell growth, and signaling. To be able to selectively inhibit or induce protein activity or complex formation is a key feature in controlling disease. For those situations in which protein-protein interactions derive substantial affinity from short linear peptide sequences, or motifs, we can develop search algorithms for peptidomimetic compounds that resemble the short peptide's structure but are not compromised by poor pharmacological properties. SAAMCO is a Web service ( http://bioware.ucd.ie/ approximately saamco) that facilitates the screening of motifs with known structures against bioactive compound databases. It is built on an algorithm that defines compound similarity based on the presence of appropriate amino acid side chain fragments and a favorable Root Mean Squared Deviation (RMSD) between compound and motif structure. The methodology is efficient as the available compound databases are preprocessed and fast regular expression searches filter potential matches before time-intensive 3D superposition is performed. The required input information is minimal, and the compound databases have been selected to maximize the availability of information on biological activity. "Hits" are accompanied with a visualization window and links to source database entries. Motif matching can be defined on partial or full similarity which will increase or reduce respectively the number of potential mimetic compounds. The Web server provides the functionality for rapid screening of known or putative interaction motifs against prepared compound libraries using a novel search algorithm. The tabulated results can be analyzed by linking to appropriate databases and by visualization. PMID:18570372

Casey, Fergal P; Davey, Norman E; Baran, Ivan; Varekova, Radka Svobodova; Shields, Denis C

2008-07-01

153

Studies identify problems and strengths of collector seals and sealing compounds  

SciTech Connect

Results of an extensive literature search and accelerated testing of elastomers used for preformed seals and sealing compounds in solar collectors are summarized. Data include compression set thermal aging data, sealant outgassing test results, and the effect of glaze deposits on relative light transmittance. The preformd seals and sealing compounds recommended are fluorocarbons for high temperature, and silicones, acrylics, acrylic copolymers and EPDMs for intermediate temperature. (LEW)

Not Available

1981-08-01

154

Chemicals identified in human biological media, a data base. Second annual report, October 1980  

SciTech Connect

A comprehensive data base of chemicals identified in human biological media (tissues and body fluids) has been established. Data were obtained primarily from the open literature through manual searches (retrospective to 1974) of the journals listed in Appendix A. The data base now contains information on over 500 different substances. Chemicals are listed by Chemical Abstracts Service (CAS) registry numbers and preferred names in Appendix B. For the user's convenience, cross-referenced chemical lists of CAS names are provided in Appendix C. The human tissues and body fluids found to be contaminated by these chemicals are listed in Appendix D. The data base is published annually in two parts. Part 1 contains introductory materials, references, appendices, indices, and a chemical directory. Information in Part 1 is cumulative, thus allowing the user access to information in the previous edition of Part 2. Data from more than one-third of the over 3000 body-burden documents collected to date have been entered in the data base as of October 1980. The emphasis on inputting recent literature and significant research documents has resulted in a chronological mix of articles from 1974 to the present in the first two publications of the data base.

Cone, M.V.; Baldauf, M.F.; Martin, F.M.; Ensminger, J.T. (comps.)

1981-01-01

155

Compound  

NASA Astrophysics Data System (ADS)

Recently, Cu-based chalcogenides such as Cu3SbSe4, Cu2Se, and Cu2SnSe3 have attracted much attention because of their high thermoelectric performance and their common feature of very low thermal conductivity. However, for practical use, materials without toxic elements such as selenium are preferable. In this paper, we report Se-free Cu3SbS4 thermoelectric material and improvement of its figure of merit ( ZT) by chemical substitutions. Substitutions of 3 at.% Ag for Cu and 2 at.% Ge for Sb lead to significant reductions in the thermal conductivity by 37% and 22%, respectively. These substitutions do not sacrifice the power factor, thus resulting in enhancement of the ZT value. The sensitivity of the thermal conductivity to chemical substitutions in these compounds is discussed in terms of the calculated phonon dispersion and previously proposed models for Cu-based chalcogenides. To improve the power factor, we optimize the hole carrier concentration by substitution of Ge for Sb, achieving a power factor of 16 ?W/cm K2 at 573 K, which is better than the best reported for Se-based Cu3SbSe4 compounds.

Suzumura, Akitoshi; Watanabe, Masaki; Nagasako, Naoyuki; Asahi, Ryoji

2014-06-01

156

Indirect Similarity Based Methods for Effective Scaffold-Hopping in Chemical Compounds  

PubMed Central

Methods that can screen large databases to retrieve a structurally diverse set of compounds with desirable bioactivity properties are critical in the drug discovery and development process. This paper presents a set of such methods that are designed to find compounds that are structurally different to a certain query compound while retaining its bioactivity properties (scaffold hops). These methods utilize various indirect ways of measuring the similarity between the query and a compound that take into account additional information beyond their structure-based similarities. The set of techniques that are presented capture these indirect similarities using approaches based on analyzing the similarity network formed by the query and the database compounds. Experimental evaluation shows that most of these methods substantially outperform previously developed approaches both in terms of their ability to identify structurally diverse active compounds as well as active compounds in general.

Wale, Nikil; Watson, Ian A.; Karypis, George

2008-01-01

157

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

PubMed Central

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.

Moriguchi, I; Hirano, H; Hirono, S

1996-01-01

158

Chemicals identified in human biological media: a data base. Fourth annual report, October 1982  

SciTech Connect

A comprehensive data base of chemicals identified in human biological media (tissues and body fluids) has been established. This two-part volume is the annual publication of the data base for 1982. Data were obtained primarily from the open literature through manual searches (retrospective to 1974. The data base now contains information on over 1000 different substances, all of which are listed by Chemical Abstracts Service (CAS) preferred names. The data base is published annually in tabular format with indices and chemical listings that allow specific searching. The purpose of the data base is to provide a centralized resource of body-burden data, and in no way is it intended to obviate the need for the user to ultimately refer to the original literature or data source.

Cone, M.V.; Baldauf, M.F.; Opresko, D.M.; Uziel, M.S. (comps.)

1982-12-01

159

Chemicals identified in human biological media: a data base. Fourth annual report  

SciTech Connect

A comprehensive data base of chemicals identified in human biological media (tissues and body fluids) has been established. This two-part volume is the annual publication of the data base for 1982. Data were obtained primarily from the open literature through manual searches (retrospective to 1974). The data base now contains information on over 1000 different substances, all of which are listed by Chemical Abstracts Service (CAS) preferred names. The data base is published annually in tabular format with indices and chemical listings that allow specific searching. The purpose of the data base is to provide a centralized resource of body-burden data, and in no way is it intended to obviate the need for the user to ultimately refer to the original literature or data source.

Cone, M.V.; Baldauf, M.F.; Opresko, D.M.; Uziel, M.S. (comps.)

1982-10-01

160

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

SciTech Connect

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.

Cone, M.V.; Baldauf, M.F.; Martin, F.M. (comps.) [comps.

1981-12-01

161

Nondestructive detection of hidden chemical compounds with laser Compton-scattering gamma rays  

NASA Astrophysics Data System (ADS)

A nondestructive assay method for measuring a shielded chemical compound has been proposed. The chemical compound is measured by using a nuclear resonance fluorescence (NRF) measurement technique with an energy tunable laser Compton-scattering (LCS) ?-ray source. This method has an advantage that hidden materials can be detected through heavy shields such as iron plates of a thickness of several centimeters. A detection of a chemical compound of melamine, C3H6N6, shielded by 15-mm-thick iron and 4-mm-thick lead plates is demonstrated. The NRF ?-rays of 12C and 14N of the melamine are measured by using the LCS ?-rays of the energies of up to 5.0 MeV. The observed ratio (12C/14N)exp=0.39+/-0.12 is consistent with (C/N)melamine=0.5.

Hayakawa, Takehito; Ohgaki, Hideaki; Shizuma, Toshiyuki; Hajima, Ryoichi; Kikuzawa, Nobuhiro; Minehara, Eisuke; Kii, Toshiteru; Toyokawa, Hiroyuki

2009-04-01

162

Nondestructive detection of hidden chemical compounds with laser Compton-scattering gamma rays.  

PubMed

A nondestructive assay method for measuring a shielded chemical compound has been proposed. The chemical compound is measured by using a nuclear resonance fluorescence (NRF) measurement technique with an energy tunable laser Compton-scattering (LCS) gamma-ray source. This method has an advantage that hidden materials can be detected through heavy shields such as iron plates of a thickness of several centimeters. A detection of a chemical compound of melamine, C(3)H(6)N(6), shielded by 15-mm-thick iron and 4-mm-thick lead plates is demonstrated. The NRF gamma-rays of (12)C and (14)N of the melamine are measured by using the LCS gamma-rays of the energies of up to 5.0 MeV. The observed ratio ((12)C/(14)N)(exp)=0.39+/-0.12 is consistent with (C/N)(melamine)=0.5. PMID:19405694

Hayakawa, Takehito; Ohgaki, Hideaki; Shizuma, Toshiyuki; Hajima, Ryoichi; Kikuzawa, Nobuhiro; Minehara, Eisuke; Kii, Toshiteru; Toyokawa, Hiroyuki

2009-04-01

163

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

SciTech Connect

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

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

1986-01-01

164

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

SciTech Connect

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

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

1986-01-01

165

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

SciTech Connect

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

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

1986-01-01

166

A chemical biology approach identifies AMPK as a modulator of melanoma oncogene MITF.  

PubMed

The microphthalmia-associated transcription factor (MITF) is indispensable for the viability of melanocytic cells, is an oncogene in melanoma and has a cell type-specific expression pattern. As the modulation of MITF activity by direct chemical targeting remains a challenge, we assessed a panel of drugs for their ability to downregulate MITF expression or activity by targeting its upstream modulators. We found that the multi-kinase inhibitors midostaurin and sunitinib downregulate MITF protein levels. To identify the target molecules shared by both the drugs in melanocytic cells, a chemical proteomic approach was applied and AMP-activated kinase (AMPK) was identified as the relevant target for the observed phenotype. RNA interference and chemical inhibition of AMPK led to a decrease in MITF protein levels. Reduction of MITF protein levels was the result of proteasomal degradation, which was preceded by enhanced phosphorylation of MITF mediated by ERK. As expected, downregulation of MITF protein levels by AMPK inhibition was associated with decreased viability. Together, these results identify AMPK as an important regulator for the maintenance of MITF protein levels in melanocytic cells. PMID:23728343

Borgdorff, V; Rix, U; Winter, G E; Gridling, M; Müller, A C; Breitwieser, F P; Wagner, C; Colinge, J; Bennett, K L; Superti-Furga, G; Wagner, S N

2014-05-01

167

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

PubMed Central

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

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

2013-01-01

168

STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS  

PubMed Central

The fate of 14C-labeled allergens injected intradermally into guinea pigs, namely picryl chloride (PCl*) and 2:4 dinitrochlorobenzene (DNCB*), was followed during the induction period of delayed hypersensitivity. Both chemicals were applied in a single injection into one ear in amounts that approached their minimal sensitizing doses (PCl, 0.25 µg; DNCB, 5.0 µg). Radioactivity in the various tissues was determined by liquid scintillation counting after combustion of tissues to CO2 and H2O. The injected allergens seemed to leave the injection site in three phases. A large proportion of allergen escaped rapidly from the ear, about 50% within 3 hr in the case of PCl, within 15 min for DNCB, the difference probably reflecting their unequal reaction constants. Initially there was a "half-life" escape in 2.5 hr with injected dosage of 0.25 µg PCl and in 18 hr for 5.0 µg DNCB. This escape occurred via the regional veins and not via the lymphatics. Radioactive decomposition products of the allergens were already present in the urine within 3–4 hr. After 6–8 hr, the half-life time of escape lengthened to approximately 28 hr for both allergens used in their respective initial dosages, holding up to 2 days after which there occurred still further slowing; between 2 and 4 days the time was about 43 hr for PCl, much longer (72–88 hr?) for DNCB, apparently reflecting different physicochemical properties of this second fraction. Sensitization seemed to be connected with the portion that was present between 12 hr and 4 days of the induction period. It is not known how far the escape of radioactivity during this period may represent gradual hydrolysis of attached picryl and dinitrophenyl groupings, respectively, to form picric acid and dinitrophenol. Gradual accumulation of the second fraction in the regional lymph nodes could definitely be excluded. It was noted that no hypersensitivity arose and essentially no depot of radioactivity existed between 12 hr and 4 days when DNCB was injected in a dose of 0.25 µg, owing to its ready escape from the ear; but 20 times as much DNCB caused sensitization and provided about the same fixed depot as 0.25 µg of picryl chloride. After delayed hypersensitivity had been established, traces of radioactivity were still measurable at the site. This third fraction, probably representing a different coupling product, escaped at a very low rate and was traceable up through several weeks. No demonstrable radioactivity could be detected in thymus, spleen, and mesenteric nodes when examined at short intervals between ½ min and 17 days. In analogy with findings on transplantation "immunity" and with studies reported in the following paper, the induction of delayed hypersensitivity can be explained by encounters between lymphoid cells and the hapten complex which is found present in the local site for 4 days, in agreement with Medawar's concept of peripheral sensitization.

Macher, Egon; Chase, Merrill W.

1969-01-01

169

Chemicals identified in human biological media, a data base. Interim report, May 1982 Volume IV  

SciTech Connect

A comprehensive data base of chemicals identified in human biological media has been established under the direction of the Exposure Evaluation Division in the US Environmental Protection Agency's Office of Toxic Substances. This centralized resource of body-burden information has grown out of the concern of government scientists over continuing reports of toxic chemicals in human tissues and body fluids. Body burden is a reflection of exposures to food, air, and water contaminants, as well as administration of pharmaceuticals. The systematic acquisition of body-burden data will facilitate a more relevant assessment of human exposure to xenobiotics than was previously possible using environmental contamination levels. Data were obtained primarily from the open literature (retrospective to 1974), and contains information on over 950 different substances. For the user's convenience, cross-referenced chemical lists of CAS preferred names and common names are provided. The human tissues and body fluids found to be contaminated by these chemicals are also listed. The data base is published annually in tabular format with indices and chemical listings that allow specific searching. The file is now available online in the US Department of Energy's RECON and is being prepared for Lockheed's DIALOG. The purpose of the data base is to provide a centralized resource of body-burden data.

Cone, M.V.; Baldauf, M.F.; Opresko, D.M.; Uziel, M.S. (comps.)

1982-05-01

170

Solubility of single chemical compounds from an atmospheric aerosol in pure water  

NASA Astrophysics Data System (ADS)

The water-solubility differentiates atmospheric particles into cloud condensation nuclei (CCN) and interstitial aerosol. This interaction between aerosol and cloud influences the climate in different known and hypothetical ways [Hansson et al. (1994) In Proceedings of EUROTRAC Symposium' 94, (edited by Borrell P. M.), p. 984. SPB Academic Publishing, The Hague; Schwartz et al. (1995) In Aerosol Forcing of Climate (edited by Charlson R. J. and Heintzanberg J.), p. 251. Wiley, London]. Some authors studied the fraction of water-soluble amounts with particle size [Mészáros (1968) Tellus20, 443; Winkler (1974) Meteorol. Rdsch.27, 129; Fuzzi et al. (1988) Journal of geophysics Research93, 11141; Svenningsson et al. (1992) Tellus44B, 556; (1994) Journal of Atmospheric Chemistry19, 129). As the water-solubility (or hygroscopicity) is a property of chemical compounds it is of great interest to identify the chemical composition of aerosols and of the dissolved fraction. Using an optimal combination of analytical methods, the elemental and species concentrations were determined in the original aerosol as well as in the resulting solutions. The fraction of soluble species were calculated from the measured values and three groups were found: with high (50-73%), medium (20-26%), and low (2%) dissolved fraction. In a further series of experiments the rate constants of dissolution of various species were determined. These can be arranged in the order of decreasing rate of dissolution: the alkaline and alkaline earth elements K + ? Mg 2+ > NH 4+ > Na + > Ca 2+ the anions NO 3- ? SO 42- Cl -, and for the iron oxidation states Fe 3+ ? Fe 2+. A photolytic reduction of Fe 3+ to Fe 2+ was also observed. For Mg 2+, Ca 2+, and SO 42- a dependance of the rate constants for dissolution on time was discovered. This can be explained by the presence of different chemical compounds in the aerosol. The discussion of the results with regard to the time scale of the formation of cloud or fog droplets shows that the slightly soluble inventory of a solid aerosol of the alkaline and alkaline earth elements, as well as of the anions, is dissolved into the aqueous phase in a relatively short time interval of 10-700s. On the other hand, Fe 3+ is dissolved in a time period of 3000-4500s, whereas Fe 2+ appears in the solution in a time period of up to 7000s.

Hoffmann, P.; Dedik, A. N.; Deutsch, F.; Sinner, T.; Weber, S.; Eichler, R.; Sterkel, S.; Sastri, C. S.; Ortner, H. M.

171

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

PubMed Central

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.

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

2008-01-01

172

The Periodic Table as a Part of the Periodic Table of Chemical Compounds  

Microsoft Academic Search

The numbers of natural chemical elements, minerals, inorganic and organic chemical compounds are determined by 1, 2, 3 and 4-combinations of a set 95 and are respectively equal to 95, 4,465, 138,415 and 3,183,545. To explain these relations it is suggested the concept of information coefficient of proportionality as mathematical generalization of the proportionality coefficient for any set of positive

Mikhail M. Labushev

2011-01-01

173

Waterborne chemical compounds in tropical macroalgae: positive and negative cues for larval settlement  

Microsoft Academic Search

Settlement sites of marine invertebrate larvae are frequently influenced by positive or negative cues, many of which are chemical in nature. Following from the observation that many shallow-water, Hawai'ian marine macroalgae are free of fouling by sessile invertebrates, we predicted that the algae are chemically protected and dependent on either surface-bound or continuously released soluble compounds to deter settling invertebrate

L. J. Walters; M. G. Hadfield; C. M. Smith

1996-01-01

174

Determination of Chemical Classes from Mass Spectra of Toxic Organic Compounds by SIMCA Pattern Recognition and Information Theory.  

National Technical Information Service (NTIS)

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

D. R. Scott

1986-01-01

175

Unbiased compound screening identifies unexpected drug sensitivities and novel treatment options for gastrointestinal stromal tumors.  

PubMed

Most gastrointestinal stromal tumors (GIST) are caused by oncogenic KIT or platelet-derived growth factor receptor activation, and the small molecule kinase inhibitor imatinib mesylate is an effective first-line therapy for metastatic or unresectable GIST. However, complete remissions are rare and most patients ultimately develop resistance, mostly because of secondary mutations in the driver oncogenic kinase. Hence, there is a need for novel treatment options to delay failure of primary treatment and restore tumor control in patients who progress under therapy with targeted agents. Historic data suggest that GISTs do not respond to classical chemotherapy, but systematic unbiased screening has not been performed. In screening a compound library enriched for U.S. Food and Drug Administration (FDA)-approved chemotherapeutic agents (NCI Approved Oncology Drugs Set II), we discovered that GIST cells display high sensitivity to transcriptional inhibitors and topoisomerase II inhibitors. Mechanistically, these compounds exploited the cells' dependency on continuous KIT expression and/or intrinsic DNA damage response defects, explaining their activity in GIST. Mithramycin A, an indirect inhibitor of the SP1 transcription factor, and mitoxantrone, a topoisomerase II inhibitor, exerted significant antitumor effects in mouse xenograft models of human GIST. Moreover, these compounds were active in patient-derived imatinib-resistant primary GIST cells, achieving efficacy at clinically relevant concentrations. Taken together, our findings reveal that GIST cells have an unexpectedly high and specific sensitivity to certain types of FDA-approved chemotherapeutic agents, with immediate implications for encouraging their clinical exploration. PMID:24385214

Boichuk, Sergei; Lee, Derek J; Mehalek, Keith R; Makielski, Kathleen R; Wozniak, Agnieszka; Seneviratne, Danushka S; Korzeniewski, Nina; Cuevas, Rolando; Parry, Joshua A; Brown, Matthew F; Zewe, James; Taguchi, Takahiro; Kuan, Shin-Fan; Schöffski, Patrick; Debiec-Rychter, Maria; Duensing, Anette

2014-02-15

176

Chemical loss of volatile organic compounds and its impact on the source analysis through a two-year continuous measurement  

NASA Astrophysics Data System (ADS)

Chemical loss of volatile organic compounds (VOCs) is more important than the observed VOCs, which is the real actor of the chemical process in the atmosphere. The chemical loss of VOCs might impact on the identification of VOCs sources in ambient. For this reason, VOCs with 56 species were continuously measured in the urban area of Shanghai from 2009 to 2010, and based on the measurement the chemical loss of VOCs was calculated. According to the result, the initial VOCs in Shanghai urban was (34.8 ± 20.7) ppbv, higher than the observed one by ˜35%, including alkanes (˜38%), aromatics (˜36%), alkenes (˜17%), and acetylene (˜8%). The chemical reactivity of VOCs would be underestimated by ˜60% if the chemical loss were ignored. The chemical loss of VOCs showed a good agreement with Ox (O3 + NO2). C7-C8 aromatics and C3-C5 alkenes contributed ˜60% of consumed VOCs. Seven sources were identified and quantified from positive matrix factorization (PMF) analysis. Vehicular emissions were the largest anthropogenic source of VOCs in Shanghai urban, accounting for 27.6% of VOCs, followed by solvent usage (19.4%), chemical industry (13.2%), petrochemical industry (9.1%), and coal burning (˜5%). The contribution of biogenic emissions to total VOCs was 5.8%. Besides the five local anthropogenic sources and one biogenic source, the regional transportation was identified as one important source, contributing about 20% of VOCs in Shanghai urban. Sources apportionment results from PMF analysis based on the initial VOCs showed some differences from those based on observed data and might be more appropriate to be applied into the formulation of air pollution control measures.

Wang, H. L.; Chen, C. H.; Wang, Q.; Huang, C.; Su, L. Y.; Huang, H. Y.; Lou, S. R.; Zhou, M.; Li, L.; Qiao, L. P.; Wang, Y. H.

2013-12-01

177

IAP Binding Peptides and Assay for Identifying Compounds that Bind IAP.  

National Technical Information Service (NTIS)

The present invention relates to the field of drug design and development for prevention and treatment of cell proliferative disease. Specifically, the invention features an assay for identifying peptides and peptidomimetics for promoting apotosis in cell...

G. McLendon R. A. Kipp M. Case Y. Shi

2002-01-01

178

Development of a piezoelectric chemical sensor using metalloporphyrins compounds as a coating material  

Microsoft Academic Search

The piezoelectric quartz crystal chemical sensor was developed for volatile organic compounds (VOCs) detection. The sensing sensitivity of the devices was measured based on the small change in mass of quartz crystal. The addition of mass causes changes its natural frequency when exposing the thin film towards vapor molecules. The system sensor was used with metalloporphyrin thin films as a

Ruziana Mohamed; Muhamad Mat Salleh; Muhammad Yahaya

2012-01-01

179

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

SciTech Connect

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.

Zimmering, S.; Mason, J.M.; Valencia, R. (Brown Univ., Providence, RI (USA))

1989-01-01

180

A structure-motivated hybrid machine for prediction of biological activity of chemical compounds  

Microsoft Academic Search

In this work we propose a hybrid learning machine, combining artificial neural networks (ANNs) and binary decision trees, to predict quantitative structure activity relationships (QSARs). This approach directly uses the structural cues from chemical compounds and has been validated for the two significant prediction problems, viz. regression and classification. For regression analysis we show the utility of the algorithm in

Amit Kumar Mishra; O. P. Patri

2010-01-01

181

A Quantum Chemical Study of Bismuth Compounds Thermodynamic Properties and Configuration of Pentacoordinated Organobismuth Molecules  

Microsoft Academic Search

By the PM3 method, standard values of entropy, heats, and free energies of formation have been computed for a series of inorganic and organic bismuth compounds. Linear dependences P exper = b P theor (where P is any of the mentioned properties) have been stated, allowing a priori evaluation of thermodynamic characteristics of Bi-containing substances. A quantum chemical calculation reproduces

Alexei N. Pankratov; Inna M. Uchaeva

2002-01-01

182

Survey for N-Nitroso Compounds at Onyx Chemical Company, Jersey City, NJ.  

National Technical Information Service (NTIS)

An environmental survey was conducted on April 16, 1980, to determine whether N-nitroso compounds were present or formed in cationic surfactants produced at the Onyx Chemical Company (SIC-2841), in Jersey City, New Jersey. Area air samples were collected ...

D. Rounbehler J. Reisch J. Coombs

1980-01-01

183

Determining the chemical activity of hydrophobic organic compounds in soil using polymer coated vials  

Microsoft Academic Search

BACKGROUND: In soils contaminated by hydrophobic organic compounds, the concentrations are less indicative of potential exposure and distribution than are the associated chemical activities, fugacities and freely dissolved concentrations. The latter can be measured by diffusive sampling into thin layers of polymer, as in, for example, solid phase micro-extraction. Such measurements require equilibrium partitioning of analytes into the polymer while

Fredrik Reichenberg; Foppe Smedes; Jan-Åke Jönsson; Philipp Mayer

2008-01-01

184

Importance of molding compound chemical shrinkage in the stress and warpage analysis of PQFPs  

Microsoft Academic Search

This paper addresses the use of finite element (FE) techniques to predict residual warpage in plastic quad flat packs (PQFPs) after encapsulation. Experimental measurements of package warpage are used to validate FE models of the packages. Failure to incorporate mold compound chemical shrinkage into the FE analysis leads to erroneous predictions of package warpage. The warpage sensitivity of different packages

G. Kelly; C. Lyden; W. Lawton; J. Barrett; A. Saboui; H. Pape; H. J. B. Peters

1996-01-01

185

Controlled Chemical and Drug Delivery via the Internal and External Surfaces of Layered Compounds  

Microsoft Academic Search

We demonstrate, and review the very small, but growing body of literature regarding a recently discovered application of layered compounds, which involves the ability of layered materials to sequester and later release molecules of chemical and biological significance. The application relies upon intercalation chemistry; a reversible process whereby atoms, molecules, macromolecules, and polymers may be inserted into the interstices of

Joseph F. Bringley; Nancy B. Liebert

2003-01-01

186

Parallel Chemical Genetic and Genome-Wide RNAi Screens Identify Cytokinesis Inhibitors and Targets  

PubMed Central

Cytokinesis involves temporally and spatially coordinated action of the cell cycle and cytoskeletal and membrane systems to achieve separation of daughter cells. To dissect cytokinesis mechanisms it would be useful to have a complete catalog of the proteins involved, and small molecule tools for specifically inhibiting them with tight temporal control. Finding active small molecules by cell-based screening entails the difficult step of identifying their targets. We performed parallel chemical genetic and genome-wide RNA interference screens in Drosophila cells, identifying 50 small molecule inhibitors of cytokinesis and 214 genes important for cytokinesis, including a new protein in the Aurora B pathway (Borr). By comparing small molecule and RNAi phenotypes, we identified a small molecule that inhibits the Aurora B kinase pathway. Our protein list provides a starting point for systematic dissection of cytokinesis, a direction that will be greatly facilitated by also having diverse small molecule inhibitors, which we have identified. Dissection of the Aurora B pathway, where we found a new gene and a specific small molecule inhibitor, should benefit particularly. Our study shows that parallel RNA interference and small molecule screening is a generally useful approach to identifying active small molecules and their target pathways.

2004-01-01

187

Chemical fate and biological effects of several endocrine disrupters compounds in two echinoderm species.  

PubMed

Two echinoderm species, the sea urchin Paracentrotus lividus and the feather star Antedon mediterranea, were exposed for 28 days to several EDCs: three putative androgenic compounds, triphenyltin (TPT), fenarimol (FEN), methyltestosterone (MET), and two putative antiandrogenic compounds, p,p'-DDE (DDE) and cyproterone acetate (CPA). The exposure nominal concentrations were from 10 to 3000 ng L(-1), depending on the compound. This paper is an attempt to join three different aspects coming from our ecotoxicological tests: (1) the chemical behaviour inside the experimental system; (2) the measured toxicological endpoints; (3) the biochemical responses, to which the measured endpoints may depend. The chemical fate of the different compounds was enquired by a modelling approach throughout the application of the 'Aquarium model'. An estimation of the day-to-day concentration levels in water and biota were obtained together with the amount assumed each day by each animal (uptake in microg animal(-1) d(-1) or ng g-wet weight(-1) d(-1)). The toxicological endpoints investigated deal with the reproductive potential (gonad maturation stage, gonad index and oocyte diameter) and with the regenerative potential (growth and histology). Almost all the compounds exerted some kind of effect at the tested concentrations, however TPT was the most effective in altering both reproductive and regenerative parameters (also at the concentration of few ng L(-1)). The biochemical analyses of testosterone (T) and 17beta-estradiol (E(2)) also showed the ability of the selected compounds to significantly alter endogenous steroid concentrations. PMID:19937112

Sugni, Michela; Tremolada, Paolo; Porte, Cinta; Barbaglio, Alice; Bonasoro, Francesco; Carnevali, M Daniela Candia

2010-03-01

188

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

PubMed Central

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.

Vesell, E S; Passananti, G T

1977-01-01

189

Thin-layer chromatographic (TLC) separations and bioassays of plant extracts to identify antimicrobial compounds.  

PubMed

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

Kagan, Isabelle A; Flythe, Michael D

2014-01-01

190

Targeting the Wnt pathway in zebrafish as a screening method to identify novel therapeutic compounds.  

PubMed

Activating mutations in the Wnt signaling pathway account for the initiation of greater than 90% of all colorectal cancers and this pathway has been implicated in numerous other diseases. Therefore, identifying small molecule inhibitors of this pathway is of critical importance towards identifying clinically relevant drugs. Numerous screens have been employed to identify therapeutic reagents, but none have made it to advanced clinical trials, suggesting that traditional screening methods are ineffective at identifying clinically relevant targets. Here, we describe a novel in vivo screen to identify small molecule inhibitors of the Wnt pathway. Specifically, treatment of zebrafish embryos with LiCl inhibits GSK3 kinase function, resulting in hyperactivation of the signaling pathway and an eyeless phenotype at 1 day post fertilization. Using the small molecule XAV939, a known inhibitor of Wnt signaling, we rescued the LiCl induced eyeless phenotype, confirming efficacy of the screen. We next tested our assay with 400 known small molecule kinase inhibitors, none of which should inhibit Wnt signaling below the level of GSK3 based on their known targets. Accordingly, none of these small molecules rescued the eyeless phenotype, which demonstrates the stringency of the assay. However, several of these small molecule kinase inhibitors did generate a non-Wnt phenotype in accordance with the kinase they targeted. Therefore, combining the efficacy, sensitivity, and stringency of this preliminary screen, this model will provide an alternative to the traditional in vitro screen, generating potentially clinical relevant drugs in a rapid and cost-effective way. PMID:24414478

Robertson, Joshua K; Danzmann, Kestral; Charles, Sherise; Blake, Katherine; Olivares, Annia; Bamikole, Solape; Olson, Meghan; Van Raay, Terence J

2014-02-01

191

Unbiased probing of the entire hepatitis C virus life cycle identifies clinical compounds that target multiple aspects of the infection  

PubMed Central

Over 170 million people are chronically infected by the hepatitis C virus (HCV) and at risk for dying from liver cirrhosis and hepatocellular carcinoma. Current therapy is expensive, associated with significant side effects, and often ineffective. Discovery of antiviral compounds against HCV traditionally involves a priori target identification followed by biochemical screening and confirmation in cell-based replicon assays. Typically, this results in the discovery of compounds that address a few predetermined targets and are prone to select for escape variants. To attempt to identify antiviral compounds with broad target specificity, we developed an unbiased cell-based screening system involving multiple rounds of infection in a 96-well format. Analysis of a publicly available library of 446 clinically approved drugs identified 33 compounds that targeted both known and previously unexplored aspects of HCV infection, including entry, replication, and assembly. Discovery of novel viral and cellular targets in this manner will broaden the therapeutic armamentarium against this virus, allowing for the development of drug mixtures that should reduce the likelihood of mutational escape.

Gastaminza, Pablo; Whitten-Bauer, Christina; Chisari, Francis V.

2009-01-01

192

Unbiased probing of the entire hepatitis C virus life cycle identifies clinical compounds that target multiple aspects of the infection.  

PubMed

Over 170 million people are chronically infected by the hepatitis C virus (HCV) and at risk for dying from liver cirrhosis and hepatocellular carcinoma. Current therapy is expensive, associated with significant side effects, and often ineffective. Discovery of antiviral compounds against HCV traditionally involves a priori target identification followed by biochemical screening and confirmation in cell-based replicon assays. Typically, this results in the discovery of compounds that address a few predetermined targets and are prone to select for escape variants. To attempt to identify antiviral compounds with broad target specificity, we developed an unbiased cell-based screening system involving multiple rounds of infection in a 96-well format. Analysis of a publicly available library of 446 clinically approved drugs identified 33 compounds that targeted both known and previously unexplored aspects of HCV infection, including entry, replication, and assembly. Discovery of novel viral and cellular targets in this manner will broaden the therapeutic armamentarium against this virus, allowing for the development of drug mixtures that should reduce the likelihood of mutational escape. PMID:19995961

Gastaminza, Pablo; Whitten-Bauer, Christina; Chisari, Francis V

2010-01-01

193

Inferring Genetic Networks and Identifying Compound Mode of Action via Expression Profiling  

Microsoft Academic Search

The complexity of cellular gene, protein, and metabolite networks can hinder attempts to elucidate their structure and function. To address this problem, we used systematic transcriptional perturbations to construct a first-order model of regulatory interactions in a nine-gene subnetwork of the SOS pathway in Escherichia coli. The model correctly identified the major regulatory genes and the transcriptional targets of mitomycin

Timothy S. Gardner; Diego di Bernardo; David Lorenz; James J. Collins

2003-01-01

194

Identifying chemicals with potential therapy of HIV based on protein-protein and protein-chemical interaction network.  

PubMed

Acquired immune deficiency syndrome (AIDS) is a severe infectious disease that causes a large number of deaths every year. Traditional anti-AIDS drugs directly targeting the HIV-1 encoded enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) usually suffer from drug resistance after a period of treatment and serious side effects. In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention. In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy. In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying novel anti-HIV drugs. PMID:23762317

Li, Bi-Qing; Niu, Bing; Chen, Lei; Wei, Ze-Jun; Huang, Tao; Jiang, Min; Lu, Jing; Zheng, Ming-Yue; Kong, Xiang-Yin; Cai, Yu-Dong

2013-01-01

195

Identifying Chemicals with Potential Therapy of HIV Based on Protein-Protein and Protein-Chemical Interaction Network  

PubMed Central

Acquired immune deficiency syndrome (AIDS) is a severe infectious disease that causes a large number of deaths every year. Traditional anti-AIDS drugs directly targeting the HIV-1 encoded enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) usually suffer from drug resistance after a period of treatment and serious side effects. In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention. In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy. In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying novel anti-HIV drugs.

Chen, Lei; Wei, Ze-Jun; Huang, Tao; Jiang, Min; Lu, Jing; Zheng, Ming-Yue; Kong, Xiang-Yin; Cai, Yu-Dong

2013-01-01

196

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

PubMed

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

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

2010-09-01

197

An FTIR point sensor for identifying chemical WMD and hazardous materials  

NASA Astrophysics Data System (ADS)

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

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

198

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

PubMed

Metals have been central to the development of human civilisation from the Bronze Age to modern times, although in the past, metal mining and smelting have been the cause of serious environmental pollution with the potential to harm human health. Despite problems from artisanal mining in some developing countries, modern mining to Western standards now uses the best available mining technology combined with environmental monitoring, mitigation and remediation measures to limit emissions to the environment. This paper develops risk screening and prioritisation methods previously used for contaminated land on military and civilian sites and engineering systems for the analysis and prioritisation of chemical risks from modern metal mining operations. It uses hierarchical holographic modelling and multi-criteria decision making to analyse and prioritise the risks from potentially hazardous inorganic chemical substances released by mining operations. A case study of an active platinum group metals mine in South Africa is used to demonstrate the potential of the method. This risk-based methodology for identifying, filtering and ranking mining-related environmental and human health risks can be used to identify exposure media of greatest concern to inform risk management. It also provides a practical decision-making tool for mine acquisition and helps to communicate risk to all members of mining operation teams. PMID:19353294

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

2010-04-01

199

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

NASA Astrophysics Data System (ADS)

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

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

1996-06-01

200

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

PubMed

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

Lorenzo, José M

2014-01-01

201

Chemical degradation of substituted aromatic hydrocarbon compounds in soil/sediment systems: Progress report  

SciTech Connect

This project addresses the fate of organic contaminants in soil and sediment systems. The project is directed towards understanding some of the chemical pathways by which energy-related organic compounds may be oxidized in soils and sediments as a result of redox reaction with oxide minerals. Chemical degradation pathways may be an important mechanism for remediation of contaminated soils/sediments in the absence of microbial degradation. This project complements another research investigation which is investigating microbial degradation of unsubstituted polycyclic aromatic hydrocarbon compounds in different redox environments. The project is studying the chemical reactions of nitrogen-containing aromatic hydrocarbons with iron and manganese oxides. These oxides are likely to be the most prevalent oxidizing agents in soils and sediments in the absence of molecular oxygen and microbial activity. Previous screening studies in this laboratory have shown that unsubstituted PAH (e.g, naphthalene) are non-reactive with respect to redox reactions with manganese oxide, while hydroxy- and nitrogen-substituted aromatic hydrocarbon compounds undergo redox reaction with manganese oxide. The laboratory work for the near future will focus on understanding the reaction mechanisms of nitrogen-substituted aromatic hydrocarbon compounds with manganese oxide. The results of the study are expected to be useful in helping to develop basic knowledge on the fate and transport of aromatic hydrocarbon contaminants in subsurface environments.

Shanmuganantha, S.; Luthy, R.G.

1987-05-01

202

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

NASA Technical Reports Server (NTRS)

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.

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

1990-01-01

203

Chemical transformations of lead compounds under humid conditions: implications for bioaccessibility.  

PubMed

This short communication documents chemical transformations caused by weathering of two Pb compounds that commonly occur in house dust. Chamber experiments were designed to simulate humid indoor environment conditions to determine whether Pb compounds undergo chemical transformations influencing bioaccessibility. Reference compounds of Pb metal (12 % bioaccessibility) and Pb sulfate (14 % bioaccessibility) were subjected to an oxygenated, humidified atmosphere in closed chambers for 4 months. X-ray diffraction (XRD) and X-ray absorption near-edge structure (XANES) spectroscopy were used to characterize the main Pb species, and the change in Pb bioaccessibility was determined using a simulated gastric acid digestion. At the end of the weathering period a small amount of Pb carbonate (9 % of total Pb) appeared in the Pb sulfate sample. Weathering of the Pb metal sample resulted in the formation of two compounds, hydrocerussite (Pb hydroxyl carbonate) and Pb oxide, in significant amounts (each accounted for 26 % of total Pb). The formation of highly bioaccessible Pb carbonate (73 % bioaccessibility), hydrocerussite (76 % bioaccessibility), and Pb oxide (67 % bioaccessibility) during weathering resulted in a measurable increase in the overall Pb bioaccessibility of both samples, which was significant (p = .002) in the case of the Pb metal sample. This study demonstrates that Pb compounds commonly found in indoor dust can 'age' into more bioaccessible forms under humid indoor conditions. PMID:22740126

Maclean, Lachlan C W; Beauchemin, Suzanne; Rasmussen, Pat E

2013-02-01

204

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

PubMed Central

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

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

2012-01-01

205

Chemically engineered extracts as an alternative source of bioactive natural product-like compounds  

PubMed Central

The access to libraries of molecules with interesting biomolecular properties is a limiting step in the drug discovery process. By virtue of a long molecular evolution process, natural products are recognized as biologically validated starting points in structural space for library development. We introduce here a strategy to generate natural product-like libraries. A semisynthetic mixture of compounds was produced by diversification of a natural product extract through the chemical transformation of common chemical functionalities in natural products into chemical functionalities rarely found in nature. The resulting mixture showed antifungal activity against Candida albicans, whereas the starting extract did not show such activity. Bioguided fractionation led to the isolation of a previously undescribed active semisynthetic pyrazole. The result illustrates how biological activity can be generated by designed chemical diversification of a natural product mixture, and represents the proof of principle of an alternative strategy for producing natural product-like libraries from natural products libraries.

Lopez, Silvia N.; Ramallo, I. Ayelen; Sierra, Manuel Gonzalez; Zacchino, Susana A.; Furlan, Ricardo L. E.

2007-01-01

206

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

DOEpatents

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

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

2000-01-01

207

Inclusion compound of vitamin B6 in ?-CD. Physico-chemical and structural investigations  

NASA Astrophysics Data System (ADS)

Structural and physico-chemical characterization of supramolecular assembly of vitamin B6 with ?-cyclodextrin (?-CD) prepared by different methods (kneading, co-precipitation and freeze-drying) has been performed by using several spectroscopic techniques (FTIR, 1H NMR, UV-Vis), powder X-ray diffraction and DSC in order to evidence the inclusion compound formation. An analysis of the chemical shifts observed in the 1H-NMR spectra and of the vibrational frequency shifts led to the tentative conclusion that the vitamin B6 probably enters the cyclodextrin torus when forming the ?-CD-vitamin B6 inclusion complex.

Borodi, Gheorghe; Kacso, Irina; Farca?, Sorin I.; Bratu, Ioan

2009-08-01

208

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

NASA Technical Reports Server (NTRS)

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.

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

2008-01-01

209

Review of volatile organic compound source apportionment by chemical mass balance  

NASA Astrophysics Data System (ADS)

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 in the calculation, the apportionment units, and the source profiles applied. Nevertheless, they show similar results for VOC fractions contributed by different sources. Gasoline vehicle exhaust, liquid gasoline, and gasoline evaporation contribute up to 50% or more of the ambient VOCs in many of these studies. Relative motor vehicle source contributions determined by CMB were similar to or larger than their proportions in emissions inventories. Coatings and solvent contributions from CMB were much lower than the proportions attributed to these sources in current emissions inventories. Several measurement and reporting conventions would facilitate CMB analyses of VOC data sets.

Watson, John G.; Chow, Judith C.; Fujita, Eric M.

210

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

SciTech Connect

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.

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

1998-03-01

211

Triacylglycerols profiling as a chemical tool to identify mushrooms submitted to gamma or electron beam irradiation.  

PubMed

In order to define irradiation treatment as a routine conservation methodology, it is imperative to develop chemometric indicators with the ability to distinguish irradiated from unirradiated foodstuffs. Electron spin resonance, photostimulated luminescence and thermoluminescence methods were employed to monitor radiation-induced markers, as well as different chemical compounds produced from the lipidic fraction of different foodstuffs. Apart from these methods, the specificity of triacylglycerol profiles has previously been detected in mushroom species, as has the effect of irradiation treatment in the triacylglycerol profiles of chestnut. Accordingly, the feasibility of using this as a chemometric indicator of irradiated mushrooms was evaluated. In line with the obtained results in literature, the effects of each type of irradiation were significantly different, as can be concluded from the correlations among discriminant functions and variables within each statistical test. Triacylglycerol profiling proved to be a useful tool to detect irradiated mushrooms, independently of the species or irradiation source, especially for doses above 1 kGy. PMID:24767073

Fernandes, Ângela; Barreira, João C M; Antonio, Amilcar L; Martins, Anabela; Ferreira, Isabel C F R; Oliveira, M Beatriz P P

2014-09-15

212

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

DOEpatents

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

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

1997-04-15

213

A chemical screen identifies class a g-protein coupled receptors as regulators of cilia.  

PubMed

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

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

2012-05-18

214

Quality control of rare earth compounds by multielement analysis without chemical separation  

Microsoft Academic Search

The determination of impurities in the concentration range down to about 0.1 mg\\/kg in rare earth compounds without chemical separation or preconcentration has been investigated by application of various multielement methods suitable for routine analysis. Mass spectrometry with a plasma ion source (ICP-MS) is most favourable for the determination of foreign rare earth elements (REE) and provides very low detection

W. Fey; K. H. Lieser

1993-01-01

215

The development of the concept of the chemical bond from hydrogen to cluster compounds  

NASA Astrophysics Data System (ADS)

The principal types of chemical bond have been analysed, and their ranges of applicability noted. Fields in which the concept of a localised bond is inapplicable have been indicated, and, in particular, the electronic structure of ?-polyhedral clusters has been examined. The principle of isolobal analogy has been discussed, and its unique importance for an understanding of the structure of organometallic compounds has been demonstrated. The bibliography contains 136 references.

Gambaryan, Nina P.; Stankevich, Ivan V.

1989-12-01

216

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

DOEpatents

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.

Vernon, Stanley M. (Wellesley, MA)

1986-01-01

217

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

DOEpatents

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.

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

1999-01-01

218

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

PubMed Central

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

McAnally, Danielle; Vicchiarelli, Michael; Siddiquee, Khandaker

2013-01-01

219

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

NASA Astrophysics Data System (ADS)

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

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

2002-06-01

220

Disputable issues in interpreting the results of chemical extraction of iron compounds from soils  

NASA Astrophysics Data System (ADS)

In Russia, iron is chemically fractionated according to a parallel scheme. Pyrophosphate-soluble iron (Fepyr) is considered to participate in organomineral complexes, oxalate-soluble iron (Feox) is believed to enter amorphous + poorly crystallized compounds, and dithionite-soluble iron (Fedit) is meant to represent the free (nonsilicate) compounds. However, the investigations prove that the commonly used subtraction operations (Feox - Fepyr) and (Fedit - Feox) are invalid because of the nonadditive action of the reagents in the parallel scheme of extraction. The low selectivity of reagents requires a new interpretation of chemically extracted iron compounds. In automorphic soils, the content of oxalate-soluble iron should be interpreted as the amount of Fe(III) capable of complexing with organic ligands; in hydromorphic soils with a stagnant moisture regime, it should be interpreted as the amount of iron (III) capable of being reduced in a short time. The content of dithionite-soluble compounds should be regarded as the amount of iron (III) within both (hydr)oxides and silicates potentially prone to reduction.

Vodyanitskii, Yu. N.; Shoba, S. A.

2014-06-01

221

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

PubMed Central

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

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

2000-01-01

222

Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex  

PubMed Central

Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53+/+ and p53?/? cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53+/+ cells but not in p53?/? cells. Among up-regulated genes in HCT p53+/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53+/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach.

Golubovskaya, Vita M.; Ho, Baotran; Conroy, Jeffrey; Liu, Song; Wang, Dan; Cance, William G.

2014-01-01

223

Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex.  

PubMed

Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53+/+ and p53-/- cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53+/+ cells but not in p53-/- cells. Among up-regulated genes in HCT p53+/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53+/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach. PMID:24452144

Golubovskaya, Vita M; Ho, Baotran; Conroy, Jeffrey; Liu, Song; Wang, Dan; Cance, William G

2014-01-01

224

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

PubMed Central

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

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

2013-01-01

225

Estrogenicity profile and estrogenic compounds determined in river sediments by chemical analysis, ELISA and yeast assays  

Microsoft Academic Search

An effects-directed strategy was applied to bed sediments of a polluted tributary in order to isolate and identify the major estrogenic chemicals it discharges into the River Po, the principal Italian watercourse. Sediment extract was concentrated by solid phase extraction and then fractioned into 10 fractions by reversed phase high performance liquid chromatography (RP-HPLC). Estrogenic activity of whole extract and

Luigi Viganò; Emilio Benfenati; Anne van Cauwenberge; Janne K. Eidem; Claudio Erratico; Anders Goksøyr; Werner Kloas; Silvia Maggioni; Alberta Mandich; Ralph Urbatzka

2008-01-01

226

Photocatalytic and chemical oxidation of organic compounds in supercritical carbon dioxide. 1998 annual progress report  

SciTech Connect

'This report summarizes the results of work done during the first 1.3 years of a three year project. During the first nine months effort focussed on the design, construction and testing of a closed recirculating system that can be used to study photochemistry in supercritical carbon dioxide at pressures up to 5,000 psi and temperatures up to about 50 C. This was followed by a period of work in which the photocatalytic oxidation of benzene and acetone in supercritical, liquid, and gaseous carbon dioxide containing dissolved oxygen was demonstrated. The photocatalyst was titanium dioxide supported on glass spheres. This was the first time it was possible to observe photocatalytic oxidation in a supercritical fluid and to compare reaction in the three fluid phases of a solvent. This also demonstrated that it is possible to purify supercritical and liquid carbon dioxide using photochemical oxidation with no chemical additions other than oxygen. The oxidation of benzene produced no intermediates detectable using on line spectroscopic analysis or by gas chromatographic analysis of samples taken from the flow system. The catalyst surface did darken as the reaction proceeded indicating that oxidation products were accumulating on the surface. This is analogous to the behavior of aromatic compounds in air phase photocatalytic oxidation. The reaction of acetone under similar conditions resulted in the formation of low levels of by-products. Two were identified as products of the reaction of acetone with itself (4-methyl-3-penten-2-one and 4-hydroxy-4-methyl-2-pentanone) using gas chromatography with a mass spectrometer detector. Two other by-products also appear to be from the self-reaction of acetone. By-products of this type had not been observed in prior studies of the gas-phase photocatalytic oxidation of acetone. The by-products that have been observed can also be oxidized under the treatment conditions. The above results establish that photocatalytic oxidation of organic compounds in supercritical carbon dioxide can be achieved. Until recently it was not possible for us to obtain high quality, quantitative kinetic data. The original flow cell used to obtain UV-Visible spectra on the recirculating fluid did not provide quantitative concentration data because the sapphire windows did not have adequate transmission characteristics below about 240 nm. A pair of windows with better transmission properties arrived as this report was being prepared. While waiting for the replacement windows for the flow cell, the concentration of reactants was monitored by withdrawing samples of the fluid stream for gas chromatographic analysis. This allowed progress to be made in determining some of the factors that affected the rates of reaction in a qualitative sense but the results had large error bars due to the difficulty in obtaining reproducible samples from the pressurized system using gas tight syringes. This problem was recently solved by incorporating a gas chromatograph with automatic sampling valves into the flow system. The two on line analytical methods will now result in reliable analytical data that can be used to follow the reaction kinetics and detect and identify reaction intermediates and by-products, if any are formed.'

Blake, D.M.

1998-06-01

227

Chemical applications of anthocyanins and related compounds. A source of bioinspiration.  

PubMed

Independently of the natural or synthetic origin, flavylium derivatives follow the same network of chemical reactions. Actually, the flavylium cation is stable only at low pH values. Increasing the pH gives rise to the formation of several species: quinoidal bases, hemiketal, cis- and trans-chalcones, and their deprotonated forms. A deep knowledge of the thermodynamics and kinetics of these species is an essential tool to practical applications of these compounds, in particular, in the domain of food chemistry. In this work the network of chemical reactions involving flavylium derivatives is presented, and the respective thermodynamics and kinetics are discussed in detail, including the mathematical expressions and a step-by-step procedure to calculate all of the rate and equilibrium constants of the system. Examples of systems possessing a high or low cis-trans isomerization barrier are shown. Recent practical applications of anthocyanins and related compounds illustrate the potentialities of the flavylium-based family of compounds. PMID:24397265

Pina, Fernando

2014-07-23

228

Mapping Asian anthropogenic emissions of non-methane volatile organic compounds to multiple chemical mechanisms  

NASA Astrophysics Data System (ADS)

An accurate speciation mapping of non-methane volatile organic compounds (NMVOC) emissions has an important impact on the performance of chemical transport models (CTMs) in simulating ozone mixing ratios and secondary organic aerosols. In this work, we developed an improved speciation framework to generate model-ready anthropogenic Asian NMVOC emissions for various gas-phase chemical mechanisms commonly used in CTMs by using an explicit assignment approach and updated NMVOC profiles, based on the total NMVOC emissions in the INTEX-B Asian inventory for the year 2006. NMVOC profiles were selected and aggregated from a wide range of new measurements and the SPECIATE database. To reduce potential uncertainty from individual measurements, composite profiles were developed by grouping and averaging source profiles from the same category. The fractions of oxygenated volatile organic compounds (OVOC) were corrected during the compositing process for those profiles which used improper sampling and analyzing methods. Emissions of individual species were then lumped into species in different chemical mechanisms used in CTMs by applying mechanism-dependent species mapping tables, which overcomes the weakness of inaccurate mapping in previous studies. Gridded emissions for eight chemical mechanisms are developed at 30 min × 30 min resolution using various spatial proxies and are provided through the website: http://mic.greenresource.cn/intex-b2006. Emission estimates for individual NMVOC species differ between one and three orders of magnitude for some species when different sets of profiles are used, indicating that source profile is the most important source of uncertainties of individual species emissions. However, those differences are diminished in lumped species as a result of the lumping in the chemical mechanisms.

Li, M.; Zhang, Q.; Streets, D. G.; He, K. B.; Cheng, Y. F.; Emmons, L. K.; Huo, H.; Kang, S. C.; Lu, Z.; Shao, M.; Su, H.; Yu, X.; Zhang, Y.

2013-12-01

229

Mapping Asian anthropogenic emissions of non-methane volatile organic compounds to multiple chemical mechanisms  

NASA Astrophysics Data System (ADS)

An accurate speciation mapping of non-methane volatile organic compounds (NMVOC) emissions has an important impact on the performance of chemical transport models (CTMs) in simulating ozone mixing ratios and secondary organic aerosols. Taking the INTEX-B Asian NMVOC emission inventory as the case, we developed an improved speciation framework to generate model-ready anthropogenic NMVOC emissions for various gas-phase chemical mechanisms commonly used in CTMs in this work, by using an explicit assignment approach and updated NMVOC profiles. NMVOC profiles were selected and aggregated from a wide range of new measurements and the SPECIATE database v.4.2. To reduce potential uncertainty from individual measurements, composite profiles were developed by grouping and averaging source profiles from the same category. The fractions of oxygenated volatile organic compounds (OVOC) were corrected during the compositing process for those profiles which used improper sampling and analyzing methods. Emissions of individual species were then lumped into species in different chemical mechanisms used in CTMs by applying mechanism-dependent species mapping tables, which overcomes the weakness of inaccurate mapping in previous studies. Emission estimates for individual NMVOC species differ between one and three orders of magnitude for some species when different sets of profiles are used, indicating that source profile is the most important source of uncertainties of individual species emissions. However, those differences are diminished in lumped species as a result of the lumping in the chemical mechanisms. Gridded emissions for eight chemical mechanisms at 30 min × 30 min resolution as well as the auxiliary data are available at http://mic.greenresource.cn/intex-b2006. The framework proposed in this work can be also used to develop speciated NMVOC emissions for other regions.

Li, M.; Zhang, Q.; Streets, D. G.; He, K. B.; Cheng, Y. F.; Emmons, L. K.; Huo, H.; Kang, S. C.; Lu, Z.; Shao, M.; Su, H.; Yu, X.; Zhang, Y.

2014-06-01

230

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

EPA Science Inventory

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

231

Chemicals identified in human biological media, a data base. Fifth annual report, October 1983. Volume VI, Part 1  

SciTech Connect

A comprehensive data base of chemicals identified in human biological media (tissues and body fluids) has been established under the direction of the Environmental Protection Agency's Office of Toxic Substances Exposure Evaluation Division. This centralized resource of body-burden information was inspired by the concern of government scientists over continuing reports of toxic chemicals in human tissues and body fluids. Data were obtained primarily from the open literature through manual searches of selected journals. The file contains information on over 1000 chemicals that have been found in human biological media. Part 1 contains introductory materials, references, literature citations, indices, and a chemical directory.

Cone, M.V.; Baldauf, M.F.; Opresko, D.M.; Uziel, M.S.; Chilton, B. (comps.)

1984-04-01

232

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

PubMed

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

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

2014-08-01

233

Chemical Genetics Identify eIF2? Kinase Heme Regulated Inhibitor as Anti-Cancer Target  

PubMed Central

Translation initiation plays a critical role in cellular homeostasis, proliferation, differentiation and malignant transformation. Consistently, increasing the abundance of the eIF2·GTP·Met-tRNAi translation initiation complex transforms normal cells and contributes to cancer initiation and the severity of some anemia. The chemical modifiers of the eIF2·GTP·Met-tRNAi ternary complex are therefore invaluable tools for studying its role in the pathobiology of human disorders and for determining if this complex can be pharmacologically targeted for therapeutic purposes. Using a cell based assay, we identified N,N’-diarylureas as novel inhibitors of the ternary complex abundance. Direct functional-genetics and biochemical evidence demonstrated that the N,N’-diarylureas activate heme regulated inhibitor kinase, thereby phosphorylate eIF2? and reduce abundance of the ternary complex. Using tumor cell proliferation in vitro and tumor growth in vivo as paradigms, we demonstrate that N,N’-diarylureas are potent and specific tools for studying the role eIF2·GTP·Met-tRNAi ternary complex in the pathobiology of human disorders.

Chen, Ting; Ozel, Duygu; Qiao, Yuan; Harbinski, Fred; Chen, Limo; Denoyelle, Severine; He, Xiaoying; Zvereva, Nela; Supko, Jeffrey G.; Chorev, Michael; Halperin, Jose A.; Aktas, Bertal H.

2013-01-01

234

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

NASA Astrophysics Data System (ADS)

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

Miranda-Sanchez, Oscar Ramon

235

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

SciTech Connect

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

Thornberg, S.M.; Mowry, C.D.; Keenan, M.R.; Bender, S.F.A. [Sandia National Labs., Albuquerque, NM (United States). Gas Analysis Lab.; Owen, T. [Intel Corp., Rio Rancho, NM (United States)

1997-04-01

236

Biological and chemical investigation of Allium cepa L. response to selenium inorganic compounds.  

PubMed

The aim of this study was to evaluate the biological and chemical response of Allium cepa L. exposed to inorganic selenium compounds. Besides the investigation of the total content of selenium as well as its chemical speciation, the Allium test was used to evaluate the growth of onion roots and mitotic activity in the roots' meristem. The total content of selenium was determined by inductively coupled plasma mass spectrometry (ICP MS). High-performance liquid chromatography (HPLC), coupled to ICP MS, was used for the selenium chemical speciation. Results indicated that A. cepa plants are able to biotransform inorganic selenium compounds into their organic derivatives, e.g., Se-methylselenocysteine from the Se(IV) inorganic precursor. Although the differences in the biotransformation of selenium are due mainly to the oxidation state of selenium, the experiment has also shown a fine effect of counter ions (H(+), Na(+), NH4 (+)) on the response of plants and on the specific metabolism of selenium. PMID:24652154

Michalska-Kacymirow, M; Kurek, E; Smolis, A; Wierzbicka, M; Bulska, E

2014-06-01

237

A complex relationship among chemical concentration, detection threshold, and suprathreshold intensity of bitter compounds.  

PubMed

Detection thresholds and psychophysical curves were established for caffeine, quinine-HCl (QHCl), and propylthiouracil (PROP) in a sample of 33 subjects (28 female mean age 24 +/- 4). The mean detection threshold (+/-standard error) for caffeine, QHCl, and PROP was 1.2 +/- 0.12, 0.0083 +/- 0.001, and 0.088 +/- 0.07 mM, respectively. Pearson product-moment analysis revealed no significant correlations between detection thresholds of the compounds. Psychophysical curves were constructed for each bitter compound over 6 concentrations. There were significant correlations between incremental points of the individual psychophysical curves for QHCl and PROP. Regarding caffeine, there was a specific concentration (6 mM) below and above which the incremental steps in bitterness were correlated. Between compounds, analysis of psychophysical curves revealed no correlations with PROP, but there were significant correlations between the bitterness of caffeine and QHCl at higher concentrations on the psychophysical curve (P<0.05). Correlation analysis of detection threshold and suprathreshold intensity within a compound revealed a significant correlation between PROP threshold and suprathreshold intensity (r=0.46-0.4, P<0.05), a significant negative correlation for QHCl (r=-0.33 to -0.4, P<0.05), and no correlation for caffeine. The results suggest a complex relationship between chemical concentration, detection threshold, and suprathreshold intensity. PMID:17220518

Keast, Russell S J; Roper, Jessica

2007-03-01

238

[Cytogenetic activity of metabolites of pesticides representing different classes of chemical compounds].  

PubMed

The cytogenetic activity of some substances formed in agricultural plants during metabolism of pesticides of four classes of chemical compounds was studied in the culture of human peripheric blood lymphocytes. Metabolites were shown either to have mutagenic properties similar to those of the initial compounds (ziramtetramethylthiourea, both being mutagens; captan-phthalimide, both possessing no cytogenetic activity) or to be considerably transformed in comparison with them as a result of deactivation (benomile-MBC) or activation (betanal-MHPC) processes. The latter variant if being determined for the genetic hazard of the pesticide necessitates to take into account data on the mutagenic character of those metabolites which really might enter the human organism. PMID:3705167

Pilinskaia, M A

1986-01-01

239

Effect of chemical pretreatment on anaerobic biodegradation of refractory organic compounds  

SciTech Connect

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

Wang, Y.T. (Univ. of Kentucky, Lexington, KY (United States))

1992-08-01

240

Chemical and sensory quality of processed carrot puree as influenced by stress-induced phenolic compounds.  

PubMed

Physicochemical analysis of processed strained product was performed on 10 carrot genotypes grown in Texas (TX) and Georgia (GA). Carrots from GA experienced hail damage during growth, resulting in damage to their tops. Measurements included pH, moisture, soluble phenolics, total carotenoids, sugars, organic acids, and isocoumarin (6-MM). Sensory analysis was conducted using a trained panel to evaluate relationships between chemical and sensory attributes of the genotypes and in carrots spiked with increasing levels of 6-MM. Preharvest stress conditions in GA carrots seemed to elicit a phytoalexic response, producing compounds that impacted the perception of bitter and sour flavors. Spiking 6-MM into strained carrots demonstrated the role bitter compounds have in lowering sweetness scores while increasing the perception of sour flavor. Screening fresh carrots for the phytoalexin 6-MM has the potential to significantly improve the sensory quality of processed products. PMID:10563981

Talcott, S T; Howard, L R

1999-04-01

241

Optimisation of solvent desorption conditions for chemical warfare agent and simulant compounds from Porapak Q using experimental design. I. Methyl salicylate and di(propylene glycol) monomethyl ether.  

PubMed

Factorial design (FD) was applied in order to develop an optimised method for the detection of chemical warfare (CW) agent simulant compounds on Porapak Q. Application of FD allowed study of the adsorption/desorption mechanism of analytes. Di(propylene glycol) monomethyl ether (DPM) and methyl salicylate (MS) were selected for study as both compounds are employed in agent simulation trials but are currently analysed by different methods. An analytical method for simultaneous determination of both compounds was developed using solvent desorption. The optimised method identified non-polar interactions as the primary adsorption/desorption mechanism. Steel tubes were shown to be more suited for sampling of simulants, due to lower variability in recovery compared to glass tubes. Atmospheric detection limits for both simulants were estimated to be 0.2 mg m(-3) allowing the trace analysis of these compounds by gas chromatography with flame ionisation detection (GC-FID). PMID:15233533

Muir, Bob; Duffy, Helen B; Moran, Mary C

2004-06-01

242

Reactivity of target compounds for chemical coal desulfurization. Final technical report, September 1, 1993--August 31, 1994.  

National Technical Information Service (NTIS)

The goal of this project is identification of organosulfur compounds which are removed from Illinois coal by chemical desulfurization reactions. IBC-101, -105 and -108 coals from the Illinois Basin Coal Sample Program and demineralized Argonne Premium Coa...

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

1994-01-01

243

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

NASA Astrophysics Data System (ADS)

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

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

2009-07-01

244

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

PubMed Central

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

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

2010-01-01

245

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

NASA Astrophysics Data System (ADS)

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

Bonetto, Rita; Trincavelli, Jorge; Vasconcellos, Marcos

2005-11-01

246

Chemical effect on the K shell x-ray fluorescence parameters of some Ce compounds.  

PubMed

Chemical effects on the K?/K? x-ray intensity ratios, fluorescence yields wK and vacancy transfer probabilities ?KL for some Ce compounds were investigated. In this study, the samples were excited by 59.54 keV ?-rays from a 5Ci (241)Am annular radioactive source. K x-rays emitted by samples were counted by an HPGe detector with a resolution of 182 eV at 5.9 keV. The experimental values were compared with the theoretical and other experimental values. The aim of these measurements was to characterize the dependence of the line position and line width with the chemical environment changes. PMID:23500654

Tur?ucu, A; Demir, D

2013-07-01

247

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

SciTech Connect

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

Kleinstreuer, N.C., E-mail: kleinstreuer.nicole@epa.gov [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States)] [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States)] [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States)] [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States)] [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States)] [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States) [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)

2011-11-15

248

Cell-Based Small-Molecule Compound Screen Identifies Fenretinide as Potential Therapeutic for Translocation-Positive Rhabdomyosarcoma  

PubMed Central

A subset of paediatric sarcomas are characterized by chromosomal translocations encoding specific oncogenic transcription factors. Such fusion proteins represent tumor specific therapeutic targets although so far it has not been possible to directly inhibit their activity by small-molecule compounds. In this study, we hypothesized that screening a small-molecule library might identify already existing drugs that are able to modulate the transcriptional activity of PAX3/FOXO1, the fusion protein specifically found in the pediatric tumor alveolar rhabdomyosarcoma (aRMS). Towards this end, we established a reporter cell line based on the well characterized PAX3/FOXO1 target gene AP2ß. A library enriched in mostly FDA approved drugs was screened using specific luciferase activity as read-out and normalized for cell viability. The most effective inhibitor identified from this screen was Fenretinide. Treatment with this compound resulted in down-regulation of PAX3/FOXO1 mRNA and protein levels as well as in reduced expression of several of its direct target genes, but not of wild-type FOXO1, in a dose- and time-dependent manner. Moreover, fenretinide induced reactive oxygen species and apoptosis as shown by caspase 9 and PARP cleavage and upregulated miR-9. Importantly, it demonstrated a significant anti-tumor effect in vivo. These results are similar to earlier reports for two other pediatric tumors, namely neuroblastoma and Ewing sarcoma, where fenretinide is under clinical development. Our results suggest that fenretinide might represent a novel treatment option also for translocation-positive rhabdomyosarcoma.

Herrero Martin, David; Boro, Aleksandar; Schafer, Beat W.

2013-01-01

249

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

NASA Astrophysics Data System (ADS)

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

Mariya, Vasilevich

2013-04-01

250

Optimisation of solvent desorption conditions for chemical warfare agent and simulant compounds from Porapak Q™ using experimental design  

Microsoft Academic Search

Factorial design (FD) was applied in order to develop an optimised method for the detection of chemical warfare (CW) agent simulant compounds on Porapak Q™. Application of FD allowed study of the adsorption\\/desorption mechanism of analytes. Di(propylene glycol) monomethyl ether (DPM) and methyl salicylate (MS) were selected for study as both compounds are employed in agent simulation trials but are

Bob Muir; Helen B Duffy; Mary C Moran

2004-01-01

251

The Role of Knowledge Artifacts in Innovation Management: The Case of a Chemical Compound Designer CoP  

Microsoft Academic Search

The paper describes how the experience we gained in the interaction with a community of professionals, the Compound Designer CoP (involved in tire production), led to the identification of the role Knowledge Artifacts can play in the definition of computational supports of innovation management in the specific domain of chemical formulation for rubber compounds. The paper reports on an experience

Stefania Bandini; Ettore Colombo; Gianluca Colombo; Fabio Sartori; Carla Simone

252

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

EPA Science Inventory

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

253

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

PubMed

The sensitivity of magnetic resonance imaging (MRI) contrast agents is highly dependent on the rate of water exchange between the inner sphere of a paramagnetic ion and bulk water. Normally, identifying a paramagnetic complex that has optimal water exchange kinetics is done by synthesizing and testing one compound at a time. We report here a rapid, economical on-bead combinatorial synthesis of a library of imaging agents. Eighty different 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid (DOTA)-tetraamide peptoid derivatives were prepared on beads using a variety of charged, uncharged but polar, hydrophobic, and variably sized primary amines. A single chemical exchange saturation transfer image of the on-bead library easily distinguished those compounds having the most favorable water exchange kinetics. This combinatorial approach will allow rapid screening of libraries of imaging agents to identify the chemical characteristics of a ligand that yield the most sensitive imaging agents. This technique could be automated and readily adapted to other types of MRI or magnetic resonance/positron emission tomography agents as well. PMID:21793515

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

2011-08-24

254

Exome Sequencing Identifies Compound Heterozygous Mutations in CYP4V2 in a Pedigree with Retinitis Pigmentosa  

PubMed Central

Retinitis pigmentosa (RP) is a heterogeneous group of progressive retinal degenerations characterized by pigmentation and atrophy in the mid-periphery of the retina. Twenty two subjects from a four-generation Chinese family with RP and thin cornea, congenital cataract and high myopia is reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family presented with bone spicule-shaped pigment deposits in retina, retinal vascular attenuation, retinal and choroidal dystrophy, as well as punctate opacity of the lens, reduced cornea thickness and high myopia. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. After mutation analysis in a few known RP candidate genes, exome sequencing was used to analyze the exomes of 3 patients III2, III4, III6 and the unaffected mother II2. A total of 34,693 variations shared by 3 patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in the rest family members by PCR and Sanger sequencing. Compound heterozygous c.802-8_810del17insGC and c.1091-2A>G mutations of the CYP4V2 gene, known as genetic defects for Bietti crystalline corneoretinal dystrophy, were identified as causative mutations for RP of this family.

Yang, Qiaona; Yu, Wenhan; Yan, Naihong; Zhou, Xiaomin; Fu, Jin; Guo, Xinwu; Han, Pengfei; Wang, Jun; Liu, Xuyang

2012-01-01

255

Remote Continuous Wave and Pulsed Laser Raman Detection of Chemical Warfare Agents Simulants and Toxic Industrial Compounds  

Microsoft Academic Search

This study describes the design, assembly, testing and comparison of two Remote Raman Spectroscopy (RRS) systems intended for standoff detection of hazardous chemical liquids. Raman spectra of Chemical Warfare Agents Simulants (CWAS) and Toxic Industrial Compounds (TIC) were measured in the laboratory at a 6.6 m source-target distance using continuous wave (CW) laser detection. Standoff distances for pulsed measurements were

William Ortiz-Rivera; Leonardo C. Pacheco-Londoño; Samuel P. Hernández-Rivera

2010-01-01

256

Chemicals identified in human biological media, a data base. Fifth annual report, October 1983, Volume VI, Part 2  

SciTech Connect

A comprehensive data base of chemicals identified in human biological media (tissues and body fluids) has been established under the direction of the Environmental Protection Agency's Office of Toxic Substances Exposure Evaluation Division. This centralized resource of body-burden information was inspired by the concern of government scientists over continuing reports of toxic chemicals in human tissues and body fluids. Data were obtained primarily from the open literature through manual searches of selected journals. The file contains information on over 1000 chemicals that have been found in human biological media. Part 2 contains body burden data extracted since the last publication of the data base.

Cone, M.V.; Baldauf, M.F.; Opresko, D.M.; Uziel, M.S.; Chilton, B. (comps.)

1984-04-01

257

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

NASA Astrophysics Data System (ADS)

Atmospheric ice formation represents one of the least understood atmospheric processes with important implications for the hydrological cycle and climate. Current freezing descriptions assume that ice active sites on the particle surface initiate ice nucleation, however, the nature of these sites remains elusive. Here, we present a new experimental method that allows us to relate physical and chemical properties of individual particles with observed water uptake and ice nucleation ability using a combination of micro-spectroscopic and optical single particle analytical techniques. We apply this method to field-collected particles and particles generated via bursting of bubbles produced by glass frit aeration and plunging water impingement jets in a mesocosm containing artificial sea water and bacteria and/or phytoplankton. The most efficient ice nuclei (IN) within a particle population are identified and characterized. Single particle characterization is achieved by computer controlled scanning electron microscopy with energy dispersive analysis of X-rays (CCSEM/EDX) and scanning transmission X-ray microscopy with near edge X-ray absorption fine structure spectroscopy. A vapor controlled cooling-stage coupled to an optical microscope is used to determine the onsets of water uptake, immersion freezing, and deposition ice nucleation of the individual particles as a function of temperature (T) as low as 200 K and relative humidity (RH) up to water saturation. In addition, we perform CCSEM/EDX to obtain on a single particle level the elemental composition of the entire particle population. Thus, we can determine if the IN are exceptional in nature or belong to a major particle type class with respect to composition and size. We find that ambient and sea spray particles are coated by organic material and can induce ice formation under tropospheric relevant conditions. Micro-spectroscopic single particle analysis of the investigated particle samples invokes a potential paradigm shift: Individual ice nucleating particle composition indicates that IN are similar to the majority of particles in the population and not exceptional. This suggests that composition alone may not be a determinant for IN identification. Furthermore, the results suggest that particle abundance may be a crucial parameter for IN efficiency when predicting cloud glaciation processes. These findings would have important consequences for cloud modeling, laboratory ice nucleation experiments, and field measurements.

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

2013-12-01

258

Xlink-Identifier: An Automated Data Analysis Platform for Confident Identifications of Chemically Cross-linked Peptides using Tandem Mass Spectrometry  

SciTech Connect

Chemical cross-linking combined with mass spectrometry provides a powerful method for identifying protein-protein interactions and probing the structure of protein complexes. Cross-linking is the process of covalently joining two proteins using cross-linking reagents. After proteolytic cleavage, the cross-linked peptides can be identified using tandem mass spectrometry. A number of strategies have been reported that take advantage of the high sensitivity and high resolution of modern mass spectrometers. Approaches typically include synthesis of novel cross-linking compounds and/or isotopic labelling of the cross-linkering reagent and/or protein to aid both identification and quantitation. However, these approaches have various limitations. These limitations can be overcome with a label-free approach and application of associated data analysis algorithms described in this work.

Du, Xiuxia; Chowdhury, Saiful M.; Manes, Nathan P.; Wu, Si; Mayer, M. Uljana; Adkins, Joshua N.; Anderson, Gordon A.; Smith, Richard D.

2011-03-04

259

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

EPA Science Inventory

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

260

Portable sequential injection analyzer for onsite screening for chemical weapons degradation compounds  

NASA Astrophysics Data System (ADS)

In many circumstances, the ability to perform on-site, point-of-collection analysis can play a pivotal role in the goals or requirements of the inquiry. Toward this end, the use of commercial or customized kits, which require the analyst to manually perform the metering and mixing of reagents with the sample and the subsequent visual, spectrophotometric or other interpretation of the results, has become widespread. Often, these methods can suffer from poor reproducibility and sensitivity in addition to being tedious and time consuming. Flow analysis methods, such as traditional flow injection analysis (FIA) and the more recent sequential injection analysis (SIA), have found widespread use in the automation of sample and reagent handling and subsequent analysis for many important analytes. These methods can be completely automated and offer excellent reproducibility, minimized analysis time, and in certain configurations, very high sensitivity. We have developed a miniaturized, fully portable SIA-based instrument for on-site screening for chemical weapons degradation products during challenge inspections under the Chemical Weapons Convention, as well as for the sensitive analysis of other important environmental analytes. In this paper, we will discuss our portable SIA design, the analytical approaches utilized, and results obtained for the analysis of representative chemical weapons degradation compounds.

Postlethwaite, Timothy A.; Zhang, Peng; Lancaster, Herbert L.; Bacon, Christina P.; Mensch, David

2002-02-01

261

Energy decomposition analysis of the chemical bond in main group and transition metal compounds.  

PubMed

The nature of the chemical bond in the main group diborane(4) compounds X2B-BX2 (X = H,F,Cl,Br,I) and in the Fischer- and Schrock-type transition metal carbene and carbyne complexes and heavier homologues (CO)5W-CH2, (CO)5W-E(OH)2, Cl4W-EH2, Cl(CO)4W-EH and Cl3W-EH (E = C,Si,Ge,Sn,Pb) have been investigated with an energy decomposition analysis (EDA). The results give a deep insight into the nature of the chemical interactions. The EDA results can be used as a bridge between the heuristic models of experimental chemists which have been proven as useful ordering schemes for experimental observations and the physical mechanism which leads to a chemical bond. At the time the data give a well defined qantitative answer to the questions about the strength of the covalent and electrostatic interactions and about the contributions of sigma and pi electrons to the covalent bond. PMID:14527226

Lein, Matthias; Szabó, Andrea; Kovács, Attila; Frenking, Gernot

2003-01-01

262

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

PubMed Central

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

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

2011-01-01

263

Identification of volatile and semivolatile compounds in chemical ionization GC-MS using a mass-to-structure (MTS) Search Engine with integral isotope pattern ranking.  

PubMed

The mass-to-structure or MTS Search Engine is an Access 2010 database containing theoretical molecular mass information for 19,438 compounds assembled from common sources such as the Merck Index, pesticide and pharmaceutical compilations, and chemical catalogues. This database, which contains no experimental mass spectral data, was developed as an aid to identification of compounds in atmospheric pressure ionization (API)-LC-MS. This paper describes a powerful upgrade to this database, a fully integrated utility for filtering or ranking candidates based on isotope ratios and patterns. The new MTS Search Engine is applied here to the identification of volatile and semivolatile compounds including pesticides, nitrosoamines and other pollutants. Methane and isobutane chemical ionization (CI) GC-MS spectra were obtained from unit mass resolution mass spectrometers to determine MH(+) masses and isotope ratios. Isotopes were measured accurately with errors of <4% and <6%, respectively, for A + 1 and A + 2 peaks. Deconvolution of interfering isotope clusters (e.g., M(+) and [M - H](+)) was required for accurate determination of the A + 1 isotope in halogenated compounds. Integrating the isotope data greatly improved the speed and accuracy of the database identifications. The database accurately identified unknowns from isobutane CI spectra in 100% of cases where as many as 40 candidates satisfied the mass tolerance. The paper describes the development and basic operation of the new MTS Search Engine and details performance testing with over 50 model compounds. PMID:23248816

Liao, Wenta; Draper, William M

2013-02-21

264

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

EPA Science Inventory

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

265

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

PubMed

Autophagy is a cellular degradation process involved in the clearance of aggregate-prone proteins associated with neurodegenerative diseases. While the mTOR pathway has been known to be the major regulator of autophagy, recent advancements into the regulation of autophagy have identified mTOR-independent autophagy pathways that are amenable to chemical perturbations. Several chemical and genetic screens have been undertaken to identify small molecule and genetic regulators of autophagy, respectively. The small molecule autophagy enhancers offer great potential as therapeutic candidates not only for neurodegenerative diseases, but also for diverse human diseases where autophagy acts as a protective pathway. This review highlights the various chemical screening platforms for autophagy drug discovery pertinent for the treatment of neurodegenerative diseases. PMID:24050242

Sarkar, Sovan

2013-01-01

266

Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression.  

PubMed

Patient-specific induced pluripotent stem cells (iPSCs) represent a novel system for modeling human genetic disease and could provide a source of cells for large-scale drug-discovery screens. Here we demonstrate the feasibility of performing a primary screen in neural crest precursors derived from iPSCs that were generated from individuals with familial dysautonomia (FD), a rare, fatal genetic disorder affecting neural crest lineages. We tested 6,912 small-molecule compounds and characterized eight that rescued expression of IKBKAP, the gene responsible for FD. One of the hits, SKF-86466, was found to induce IKBKAP transcription through modulation of intracellular cAMP levels and PKA-dependent CREB phosphorylation. SKF-86466 also rescued IKAP protein expression and the disease-specific loss of autonomic neuronal marker expression. Our data implicate alpha-2 adrenergic receptor activity in regulating IKBKAP expression and demonstrate that small-molecule discovery using an iPSC-based disease model can identify candidate drugs for potential therapeutic intervention. PMID:23159879

Lee, Gabsang; Ramirez, Christina N; Kim, Hyesoo; Zeltner, Nadja; Liu, Becky; Radu, Constantin; Bhinder, Bhavneet; Kim, Yong Jun; Choi, In Young; Mukherjee-Clavin, Bipasha; Djaballah, Hakim; Studer, Lorenz

2012-12-01

267

40 CFR 721.10582 - Quaternary ammonium compound (generic).  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Quaternary ammonium compound (generic). 721.10582 Section... § 721.10582 Quaternary ammonium compound (generic). (a) Chemical substance...identified generically as quaternary ammonium compound (PMN P-10-571) is subject...

2013-07-01

268

National body-burden database: Chemicals identified in animals, 1985-1986: Volume 5, Part 1  

SciTech Connect

The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposures to environmental contaminants and the assessment of the significance of such exposure. Data are obtained primarily through routine, manual searches of selected, scientific journals. Information on chemical nomenclature and properties is from online sources and standard handbooks. This publication contains introductory materials, chemical and journal lists, indices and, in tabular form, the records added to the database since the 1984 publication.

Cone, M.V.; Wilson, M.; Powers, C.D.; Roesel, M.E.; Hammons, A.S.

1987-12-01

269

National body-burden database: Chemicals identified in humans, 1985-1986: Volume 8  

SciTech Connect

The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposures to environmental contaminants and the assessment of the significance of such exposure. Data are obtained primarily through routine, manual searches of selected, scientific journals. Information on chemical nomenclature and properties is from online sources and standard handbooks. This publication contains introductory materials, chemical and journal lists, indices and, in tabular form, the records added to the database since the 1984 publication.

Cone, M.V.; Wilson, M.; Powers, C.D.; Roesel, M.E.; Hammons, A.S.

1987-12-01

270

Chemical composition and antibacterial activity of selected essential oils and some of their main compounds.  

PubMed

The chemical composition of essential oils of cabreuva (Myrocarpus fastigiatus Allemao, Fabaceae) from Brazil, cedarwood (Juniperus ashei, Cupressaceae) from Texas, Juniper berries (Juniperus communis L., Cupressaceae) and myrrh (Commiphora myrrha (Nees) Engl., Burseraceae) were analyzed using GC/FID and GC/MS. The antimicrobial activity of these essential oils and some of their main compounds were tested against eleven different strains of Gram-positive and Gram-negative bacteria by using agar diffusion and agar serial dilution methods. Animal and plant pathogens, food poisoning and spoilage bacteria were selected. The volatile oils exhibited considerable inhibitory effects against all tested organisms, except Pseudomonas, using both test methods. Higher activity was observed against Gram-positive strains in comparison with Gram-negative bacteria. Cabreuva oil from Brazil showed similar results, but in comparison with the other oils tested, only when higher concentrations of oil were used. PMID:20922991

Wanner, Juergen; Schmidt, Erich; Bail, Stefanie; Jirovetz, Leopold; Buchbauer, Gerhard; Gochev, Velizar; Girova, Tanya; Atanasova, Teodora; Stoyanova, Albena

2010-09-01

271

Identification of compounds in heavy fuel oil that are chronically toxic to rainbow trout embryos by effects-driven chemical fractionation.  

PubMed

The present study isolated and identified compounds in heavy fuel oil 7102 (HFO 7102) that are bioavailable and chronically toxic to rainbow trout embryos (Oncorhynchus mykiss). An effects-driven chemical fractionation combined the chemical separation of oil with toxicity testing and chemical analyses of each fraction to identify the major classes of compounds associated with embryo toxicity. Toxicity was assessed with 2 exposure methods, a high-energy chemical dispersion of oil in water, which included oil droplets in test solutions, and water accommodated fractions which were produced by oiled gravel desorption columns, and which did not contain visible oil droplets. Fractions of HFO with high concentrations of naphthalenes, alkanes, asphaltenes, and resins were nontoxic to embryos over the range of concentrations tested. In contrast, fractions enriched with 3- to 4-ringed alkyl polycyclic aromatic hydrocarbons (PAHs) were embryotoxic, consistent with published studies of crude oils and individual alkyl PAHs. The rank order of fraction toxicity did not vary between the exposure methods and was consistent with their PAH content; fractions with higher-molecular weight alkyl PAHs were the most toxic. Exposure of juvenile trout to most fractions of HFO induced higher activities of cytochrome P450 enzymes, with a rank order of potency that varied with exposure method and differed somewhat from that of embryotoxicity. Induction reflected the bioavailability of PAHs but did not accurately predict embryotoxicity. PMID:24375932

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

2014-04-01

272

Relations between the structure of storage and the transport of chemical compounds in karstic aquifers  

NASA Astrophysics Data System (ADS)

Study of the movement of chemical compounds naturally present in the water, or which result from pollution, are examined according to the reservoir structure in karstic aquifers. Structure is represented by a simple geometrical model; slow flow takes place in blocks with a network of low-permeability cracks. The blocks are separated by highly permeable karstic conduits that allow rapid flow, and these form the aquifer drainage system. The karst studied covers 110 km 2. It is fed by an interrupted stream draining a 35 km 2 non-karstic basin, contaminated at the entry to the karst by effluents from a sewage treatment station. The underground water reappears as a resurgence with an annual average flow of approximately 1 m 3 s -1, after an apparent underground course of 8 km in the karst. Several local sources of pollution (effluent from septic tanks) contaminate the underground water during its course. Sixteen measurement operations were performed at 12 water points, between the interrupted stream and the spring. Some sampling points were at drains, and others were in the low-permeability fissured blocks. Comparison at each point of the concentrations of 14 chemical compounds gave the following results: when pollutant discharge occurs in a permeable zone, movement is rapid in the drainage network formed by the karstic conduits, and does not reach the less permeable fissured blocks which are thus protected; however, if discharge is in a low-permeability zone, the flow does not allow rapid movement of the polluted water, and this increases the pollutant concentration at the discharge. This simple pattern can be upset by a reversal of the apparent piezometric gradient between a block and a conduit during floods or pumping; this may reverse flow directions and hence modify the movement of contaminants. The study made it possible to site five boreholes whose positions in the karstic structure were unknown, showing the interest of such an approach for the forecasting of the impact of potential pollution.

Vaute, L.; Drogue, C.; Garrelly, L.; Ghelfenstein, M.

1997-12-01

273

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

PubMed

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

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

2013-01-01

274

Assessment of multi-chemical pollution in aquatic ecosystems using toxic units: compound prioritization, mixture characterization and relationships with biological descriptors.  

PubMed

Chemical pollution is typically characterized by exposure to multiple rather than to single or a limited number of compounds. Parent compounds, transformation products and other non-targeted compounds yield mixtures whose composition can only be partially identified by monitoring, while a substantial proportion remains unknown. In this context, risk assessment based on the application of additive ecotoxicity models, such as concentration addition (CA), is rendered somewhat misleading. Here, we show that ecotoxicity risk information can be better understood upon consideration of the probabilistic distribution of risk among the different compounds. Toxic units of the compounds identified in a sample fit a lognormal probability distribution. The parameters characterizing this distribution (mean and standard deviation) provide information which can be tentatively interpreted as a measure of the toxic load and its apportionment among the constituents in the mixture (here interpreted as mixture complexity). Furthermore, they provide information for compound prioritization tailored to each site and enable prediction of some of the functional and structural biological variables associated with the receiving ecosystem. The proposed approach was tested in the Llobregat River basin (NE Spain) using exposure and toxicity data (algae and Daphnia) corresponding to 29 pharmaceuticals and 22 pesticides, and 5 structural and functional biological descriptors related to benthic macroinvertebrates (diversity, biomass) and biofilm metrics (diatom quality, chlorophyll-a content and photosynthetic capacity). Aggregated toxic units based on Daphnia and algae bioassays provided a good indication of the pollution pattern of the Llobregat River basin. Relative contribution of pesticides and pharmaceuticals to total toxic load was variable and highly site dependent, the latter group tending to increase its contribution in urban areas. Contaminated sites' toxic load was typically dominated by fewer compounds as compared to cleaner sites where more compounds contribute. PMID:24070871

Ginebreda, Antoni; Kuzmanovic, Maja; Guasch, Helena; de Alda, Miren López; López-Doval, Julio C; Muñoz, Isabel; Ricart, Marta; Romaní, Anna M; Sabater, Sergi; Barceló, Damià

2014-01-15

275

Using Cs-137, C-14 and biomarker compounds to identify reasons for C and N losses in resampled profiles  

NASA Astrophysics Data System (ADS)

A New Zealand data set of archived and resampled pasture soil profiles has identified a systematic pattern large soil C and N losses and gains that appear to be related to land-use intensity. We use isotope and organic geochemistry techniques in selected archived and resampled soil horizons to identify reasons for the observed large soil C and N losses and gains in intensive flat non-allophanic pasture and hill country soil profiles, respectively. These techniques allow us to examine 3 of the ~10 hypotheses proposed to explain the large losses initially observed in intensive pasture soils. These three hypotheses are: (1) soil C and N changes may be due to erosion and deposition; (2) pre-European forest-derived organic matter is being lost; and (3) changes in litter quality are reducing the amount of plant C and N stabilized in soil. To test hypothesis (1), we use 137Cs, accumulated in the soil clay fraction from nuclear fallout between 1945 and 1965. Measurements comparing archived (post-1965) and resampled horizons show losses or gains of 137Cs, which we interpret as erosion and deposition, respectively. Apparent wind erosion of up to ~6 cm of surface soil explains large surface soil C losses in 2 flat profiles, while apparent deposition explains soil C gains in two hill country profiles. Measurements of 14C assist in the evaluation of hypothesis (2) by suggesting that, after accounting for 137Cs-estimated erosion or deposition, surface soils are mainly losing C fixed since bomb 14C was injected into the atmosphere (post-1950). In contrast, soil C losses below 40 cm depth are dominated by C derived from pre-European forests. Biomarker compounds, particularly lignin-derivatives, allow us to evaluate hypotheses (2) and (3). Results to date suggest that failure to stabilize grass-derived C is more important than losses of forest-derived C in explaining soil C losses in the upper 30 cm. More broadly, biomarker and 137Cs measurements suggest that steady-state assumptions must be carefully applied in models of C and N in New Zealand pasture soils, and will be inappropriate in some circumstances. Based on these studies of 3-5 selected profiles, we examine approaches to broaden the use of these techniques to identify reasons for C and N losses and gains as the resampling of archived New Zealand soil profiles continues.

Baisden, W. T.; Parfitt, R. L.; Schipper, L. A.; Filley, T. R.; Ross, C.

2008-12-01

276

Effect of chemical degradation on fluxes of reactive compounds - a study with a stochastic Lagrangian transport model  

NASA Astrophysics Data System (ADS)

In the analyses of VOC fluxes measured above plant canopies, one usually assumes the flux above canopy to equal the exchange at the surface. Thus one assumes the chemical degradation to be much slower than the turbulent transport. We used a stochastic Lagrangian transport model in which the chemical degradation was described as first order decay in order to study the effect of the chemical degradation on above canopy fluxes of chemically reactive species. With the model we explored the sensitivity of the ratio of the above canopy flux to the surface emission on several parameters such as chemical lifetime of the compound, friction velocity, stability, and canopy density. Our results show that friction velocity and chemical lifetime affected the loss during transport the most. The canopy density had a significant effect if the chemically reactive compound was emitted from the forest floor. We used the results of the simulations together with oxidant data measured during HUMPPA-COPEC-2010 campaign at a Scots pine site to estimate the effect of the chemistry on fluxes of three typical biogenic VOCs, isoprene, ?-pinene, and ?-caryophyllene. Of these, the chemical degradation had a major effect on the fluxes of the most reactive species ?-caryophyllene, while the fluxes of ?-pinene were affected during nighttime. For these two compounds representing the mono- and sesquiterpenes groups, the effect of chemical degradation had also a significant diurnal cycle with the highest chemical loss at night. The different day and night time loss terms need to be accounted for, when measured fluxes of reactive compounds are used to reveal relations between primary emission and environmental parameters.

Rinne, J.; Markkanen, T.; Ruuskanen, T. M.; Petäjä, T.; Keronen, P.; Tang, M. J.; Crowley, J. N.; Rannik, Ü.; Vesala, T.

2012-06-01

277

Compound  

NASA Astrophysics Data System (ADS)

We have prepared Ce-doped polycrystalline AgSbTe2.01 compounds from high-purity elements by a melt-quench technique followed by spark plasma sintering, and their thermoelectric transport properties have been investigated in the temperature range of 300 K to 625 K. The actual concentration of Ce was much less than the initial composition, but roughly proportional to it. Small additions of Ce shifted the composition of the homogeneity range from the nearly ideal atomic ratio Ag:Sb:Te = 0.98:1.02:2.01 toward Sb rich (Ag poor), and led to the reemergence of Ag2Te impurity in AgSbTe2 compound. The Ce-doped samples possessed lower electrical conductivity compared with the undoped AgSbTe2.01 compound at room temperature, but the carrier mobility and effective mass were essentially constant, indicating intact band structure near the covalent band maximum upon Ce substitution for Sb. Due to the decrease of lattice vibration anharmonicity resulting from Ce substitution for Sb, the lattice conductivity of the Ce-doped samples was about 0.1 W m-1 K-1 higher than that of the AgSbTe2.01 sample, and the magnitude spanned the range from 0.30 W m-1 K-1 to 0.55 W m-1 K-1. A ZT of 1.20 was achieved at about 615 K for the AgSb0.99Ce0.01Te2.01 sample.

Du, B.; Li, H.; Tang, X.

2014-06-01

278

Reactions of molybdenum-sulphur compounds with cyanide: chemical evolution and deactivation of molybdoenzymes.  

PubMed

Reactions of molybdenum-sulphur compounds with cyanide are reported which may be relevant to (1) the chemical evolution of molybdoenzymes and (2) deactivation of molybdoenzymes by cyanide. (1) With aqueous cyanide MoS2 gave thio-bridged complex anions [(Mo(CN)6)2(mu-S)]6- and [(Mo(CN)4(mu-S))2]6-. Under prebiotic conditions such complexes could have been formed similarly from molybdenite and may have been precursors of molybdoenzymes. (2) Only those compounds which contained terminal sulphur bound to molybdenum (i.e., Mo = S groups), viz. oxothiomolybdates and the complex [(Mo(mu-S)(S)(Et2NCS2))2], reacted with cyanide; thiocyanate was formed and the molybdenum underwent two-electron reduction. That the cyanolysable sulphur of xanthine oxidase reacts in the same way with cyanide suggests the presence of a Mo = S group which could be a structural feature of the enzyme or could have been formed by initial cyanolysis of a bound persulphide or cysteine residue. PMID:479877

Mitchell, P C; Pygall, C F

1979-08-01

279

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

NASA Astrophysics Data System (ADS)

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

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

2013-12-01

280

Chemical-physical analysis of a tartrate model compound for TACE inhibition.  

PubMed

We have synthesized and done an extensive chemical-physical analysis of the behavior of a new compound, named MBET306, a synthetic precursor of the recently discovered tartrate-based inhibitors of the protein Tumor Necrosis factor-? Converting Enzyme (TACE). Experimental and theoretical data have shown that in water solution MBET306 is overwhelmingly found as a monoanion at physiological pH, in a conformation that differs substantially from that detected in the known co-crystal structures of MBET306 derivatives bound to TACE. The body of collected experimental and theoretical data indicates that the monoanionic species binds Zn(ii) inducing a strong stabilization of the crystal-like arrangement of the central tartrate zinc-binding group, lending support for a two step TACE docking mechanism via a zinc-bound intermediate. The thorough chemical-physical characterization of the conformational behavior of free and zinc-bound MBET306 in water bulk solution opens new avenues for the rational drug design of tartrate-based highly specific TACE inhibitors. PMID:24089197

Banchelli, Martina; Guardiani, Carlo; Tenori, Eleonora; Menichetti, Stefano; Caminati, Gabriella; Procacci, Piero

2013-11-21

281

Chemical composition and major odor-active compounds of essential oil from PINELLIA TUBER (dried rhizome of Pinellia ternata) as crude drug.  

PubMed

The chemical composition of the essential oil from PINELLIA TUBER (Japanese name: Hange), the dried rhizome of Pinellia ternata, was investigated by capillary gas chromatography (GC) and GC-mass spectrometry (MS) analyses. The oil obtained from Pinellia tuber was revealed the presence of 114 compounds, representing 90.6% of the total oil identified. This colorless oil had a spicy and woody odor. The main components of the oil were ?-cubebene (8.8%), atractylon (7.8%), methyl eugenol (6.2%), and ?-cadinene (5.3%). Fifteen major odor-active compounds were identified in the essential oil from PINELLIA TUBER by the GC-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). Among these, safrole (spicy) and ?-vatirenene (woody) showed the highest flavor dilution (FD) factor (128), followed by paeonol (FD = 64; woody, spicy), ?-humulene (FD = 64; woody), and ?-phenylnaphthalene (FD = 64; spicy). PMID:24500103

Iwasa, Megumi; Iwasaki, Toshiki; Ono, Toshirou; Miyazawa, Mitsuo

2014-01-01

282

Method of Identifying Chemical Agents which Stimulate Odorant Receptors of Sensory Neurons.  

National Technical Information Service (NTIS)

The present invention provides methods for identifying agents which modulate mosquito odorant receptors. The methods disclosed herein use genetic material of mosquito odorant receptors to express those receptors in a foreign host system in which the endog...

L. J. Swiebel

2004-01-01

283

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

SciTech Connect

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

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

2009-11-01

284

National body-burden database: Chemicals identified in animals, 1985-1986: Volume 5, Part 2  

SciTech Connect

The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposures to environmental contaminants and the assessment of the significance of such exposure. Data are obtained primarily through routine, manual searches of selected, scientific journals. Information on chemical nomenclature and properties is from online sources and standard handbooks. This publication contains records added to the database since the 1984 publication.

Cone, M.V.; Wilson, M.; Powers, C.D.; Roesel, M.E.; Hammons, A.S.

1987-12-01

285

National body-burden database: Chemicals identified in animals, 1985-1986: Volume 5, Part 3  

SciTech Connect

The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposures to environmental contaminants and the assessment of the significance of such exposure. Data are obtained primarily through routine, manual searches of selected, scientific journals. Information on chemical nomenclature and properties is from online sources and standard handbooks. The publication contains records added to the database since the 1984 publication.

Cone, M.V.; Wilson, M.; Powers, C.D.; Roesel, M.E.; Hammons, A.S.

1987-12-01

286

National body-burden database: Chemicals identified in animals, 1985-1986: Volume 5, Part 4  

SciTech Connect

The database provides a central source of systematically collected and organized body-burden data that facilitates the early identification of actual or potential human exposures to environmental contaminants and the assessment of the significance of such exposure. Data are obtained primarily through routine, manual searches of selected, scientific journals. Information on chemical nomenclature and properties is from online sources and standard handbooks. This publication contains records added to the database since the 1984 publication.

Cone, M.V.; Wilson, M.; Powers, C.D.; Roesel, M.E.; Hammons, A.S.

1987-12-01

287

Chemical genetics identify eIF2? kinase heme-regulated inhibitor as an anticancer target  

Microsoft Academic Search

Translation initiation plays a critical role in cellular homeostasis, proliferation, differentiation and malignant transformation. Consistently, increasing the abundance of the eIF2–GTP–tRNAiMet translation initiation complex transforms normal cells and contributes to cancer initiation and the severity of some anemias. The chemical modifiers of the eIF2–GTP–tRNAiMet ternary complex are therefore invaluable tools for studying its role in the pathobiology of human disorders

Ting Chen; Duygu Ozel; Yuan Qiao; Fred Harbinski; Limo Chen; Séverine Denoyelle; Xiaoying He; Nela Zvereva; Jeffrey G Supko; Michael Chorev; Jose A Halperin; Bertal H Aktas

2011-01-01

288

Chemical genetics approach to restoring p27Kip1 reveals novel compounds with antiproliferative activity in prostate cancer cells  

PubMed Central

Background The cyclin-dependent kinase (CDK) inhibitor p27Kip1 is downregulated in a majority of human cancers due to ectopic proteolysis by the ubiquitin-proteasome pathway. The expression of p27 is subject to multiple mechanisms of control involving several transcription factors, kinase pathways and at least three different ubiquitin ligases (SCFSKP2, KPC, Pirh2), which regulate p27 transcription, translation, protein stability and subcellular localization. Using a chemical genetics approach, we have asked whether this control network can be modulated by small molecules such that p27 protein expression is restored in cancer cells. Results We developed a cell-based assay for measuring the levels of endogenous nuclear p27 in a high throughput screening format employing LNCaP prostate cancer cells engineered to overexpress SKP2. The assay platform was optimized to Z' factors of 0.48 - 0.6 and piloted by screening a total of 7368 chemical compounds. During the course of this work, we discovered two small molecules of previously unknown biological activity, SMIP001 and SMIP004, which increase the nuclear level of p27 at low micromolar concentrations. SMIPs (small molecule inhibitors of p27 depletion) also upregulate p21Cip1, inhibit cellular CDK2 activity, induce G1 delay, inhibit colony formation in soft agar and exhibit preferential cytotoxicity in LNCaP cells relative to normal human fibroblasts. Unlike SMIP001, SMIP004 was found to downregulate SKP2 and to stabilize p27, although neither SMIP is a proteasome inhibitor. Whereas the screening endpoint - nuclear p27 - was robustly modulated by the compounds, SMIP-mediated cell cycle arrest and apoptosis were not strictly dependent on p27 and p21 - a finding that is explained by parallel inhibitory effects of SMIPs on positive cell cycle regulators, including cyclins E and A, and CDK4. Conclusions Our data provide proof-of-principle that the screening platform we developed, using endogenous nuclear p27 as an endpoint, presents an effective means of identifying bioactive molecules with cancer selective antiproliferative activity. This approach, when applied to larger and more diverse sets of compounds with refined drug-like properties, bears the potential of revealing both unknown cellular pathways globally impinging on p27 and novel leads for chemotherapeutics targeting a prominent molecular defect of human cancers.

2010-01-01

289

Chemicals identified in human biological media, a data base. First annual report, October 1979 (Records 1-1580)  

SciTech Connect

A comprehensive data base of chemicals identified in human biological media (tissues and body fluids) has been established under the direction of the Environmental Protection Agency's Office of Toxic Substances Survey and Analysis Division. This centralized resource of body-burden information has grown out of the concern of government scientists over continuing reports of toxic chemicals in human tissues and body fluids. These two volumes are the first annual publication of the data base. Body burden is a reflection of exposures to food, air, and water contaminants, as well as pharmaceutical administration. The systematic acquisition of body-burden data will facilitate a more relevant assessment of human exposure to xenobiotics (including toxic chemicals) than previously possible using environmental contamination levels.

Cone, M.V.; Baldauf, M.F.; Martin, F.M.; Ensminger, J.T. (comps.)

1980-03-01

290

Identifying Stereoisomers by ab-initio Calculation of Secondary Isotope Shifts on NMR Chemical Shieldings.  

PubMed

We present ab-initio calculations of secondary isotope effects on NMR chemical shieldings. The change of the NMR chemical shift of a certain nucleus that is observed if another nucleus is replaced by a different isotope can be calculated by computing vibrational corrections on the NMR parameters using electronic structure methods. We demonstrate that the accuracy of the computational results is sufficient to even distinguish different conformers. For this purpose, benchmark calculations for fluoro(2-2H)ethane in gauche and antiperiplanar conformation are carried out at the HF, MP2 and CCSD(T) level of theory using basis sets ranging from double- to quadruple-zeta quality. The methodology is applied to the secondary isotope shifts for 2-fluoronorbornane in order to resolve an ambiguity in the literature on the assignment of endo- and exo-2-fluoronorbornanes with deuterium substituents in endo-3 and exo-3 positions, also yielding insight into mechanistic details of the corresponding synthesis. PMID:24762967

Böhm, Karl-Heinz; Banert, Klaus; Auer, Alexander A

2014-01-01

291

Screening method to identify preclinical liquid and semi-solid formulations for low solubility compounds: miniaturization and automation of solvent casting and dissolution testing.  

PubMed

We have developed an efficient screening method to identify liquid and semisolid formulations for low-solubility compounds. The method is most suitable for identifying dosing vehicles for compounds in lead optimization, where compound supply is limited and long-term stability is not a requirement. Dilute compound and excipient stock solutions are prepared in organic solvent and then dispensed and mixed in 96-well plates. The solvent is removed in a vacuum centrifuge evaporator, leaving neat formulation (e.g., 10-40 microg compound, 0.4 mg excipient) at the bottom of each well. After an aging step, an aqueous dilution medium is added and the plates are incubated (agitation by orbital shaking). The diluted formulations are then filtered and analyzed by ultraviolet (UV) absorbance or high-performance liquid chromatography (HPLC). To illustrate the method, two compounds (aqueous solubility compound/surfactant/oil formulations is also presented. PMID:17094139

Mansky, Paul; Dai, Wei-Guo; Li, Shu; Pollock-Dove, Crystal; Daehne, Klaus; Dong, Liang; Eichenbaum, Gary

2007-06-01

292

Remote Continuous Wave and Pulsed Laser Raman Detection of Chemical Warfare Agents Simulants and Toxic Industrial Compounds  

Microsoft Academic Search

This study describes the design, assembly, testing and comparison of two Remote Raman Spectroscopy (RRS) systems intended\\u000a for standoff detection of hazardous chemical liquids. Raman spectra of Chemical Warfare Agents Simulants (CWAS) and Toxic\\u000a Industrial Compounds (TIC) were measured in the laboratory at a 6.6 m source-target distance using continuous wave (CW) laser\\u000a detection. Standoff distances for pulsed measurements were 35 m

William Ortiz-Rivera; Leonardo C. Pacheco-Londoño; Samuel P. Hernández-Rivera

2010-01-01

293

Xlink-Identifier: An Automated Data Analysis Platform for Confident Identifications of Chemically Cross-linked Peptides using Tandem Mass Spectrometry  

PubMed Central

Chemical cross-linking combined with mass spectrometry provides a powerful method for identifying protein-protein interactions and probing the structure of protein complexes. A number of strategies have been reported that take advantage of the high sensitivity and high resolution of modern mass spectrometers. Approaches typically include synthesis of novel cross-linking compounds, and/or isotopic labelling of the cross-linking reagent and/or protein, and label-free methods. We report Xlink-Identifier, a comprehensive data analysis platform that has been developed to support label-free analyses. It can identify inter-peptide, intra-peptide, and deadend cross-links as well as underivatized peptides. The software streamlines data pre-processing, peptide scoring, and visualization and provides an overall data analysis strategy for studying protein-protein interactions and protein structure using mass spectrometry. The software has been evaluated using a custom synthesized cross-linking reagent that features an enrichment tag. Xlink-Identifier offers the potential to perform large-scale identifications of protein-protein interactions using tandem mass spectrometry.

Du, Xiuxia; Chowdhury, Saiful M.; Manes, Nathan P.; Wu, Si; Mayer, M. Uljana; Adkins, Joshua N.; Anderson, Gordon A.; Smith, Richard D.

2011-01-01

294

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

USGS Publications Warehouse

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

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

1988-01-01

295

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

SciTech Connect

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

Smith, S.B.; Savino, J.F.; Blouin, M.A. (Fish and Wildlife Service, Ann Arbor, MI (USA))

1988-01-01

296

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

NASA Technical Reports Server (NTRS)

The structural. electronic and therinochemical properties of indium compounds which are of interest in halide transport and organometallic chemical vapor deposition processes have been studied by ab initio and statistical mechanics methods. The compounds reported include: indium halides and hydrides (InF, InCl, InCl3, InH, InH2, InH3); indium clusters (In2, In3); methylindium, dimethylindium, and their hydrogen derivatives [In(CH3), In(CH3)H, In(CH3)H2, In(CH3)2, In(CH3)2H]; dimethyl-indium dimer [In2(CH3)4], trimethyl-indium [In(CH3)3]; dehydrogenated methyl, dimethyl and trimethylindium [In(CH3)2CH2, In(CH3)CH2, In(CH2)], trimethylindium adducts with ammonia, trimethylamine and hydrazine [(CH3)3In:NH3, (CH3)3In:N(CH3)3, (CH3)3In:N(H2)N(H2)]; dimethylamino-indium and methylimino-indium [In(CH3)2(NH2), In(CH3)(NH)]; indium nitride and indium nitride dimer (InN, In2N2), indium phosphide, arsenide and antimonide ([InP, InAs, InSb). The predicted electronic properties are based on density functional theory calculations; the calculated thermodynamic properties are reported following the format of the JANAF (Joint Army, Navy, NASA, Air Force) Tables. Equilibrium compositions at two temperatures (298 and 1000 K) have been analyzed for groups of competing simultaneous reactions.

Cardelino, B. H.; Moore, C. E.; Cardelino, C. A.; Frazier, D. O.; Backmann, K. J.

2000-01-01

297

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

NASA Astrophysics Data System (ADS)

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

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

2012-12-01

298

Antibody purification by affinity chromatography based on small molecule affinity ligands identified by SPR-based screening of chemical microarrays  

Microsoft Academic Search

Libraries of small molecules were searched for Fc-fragment selective binders to a recombinant human antibody (“MDJ8?, IgG1-subtype, ?-light chain) via SPR-based screening of chemical microarrays. Identified hit structures were immobilised on NHS-activated Sepharose for the determination of MDJ8 binding and selectivity versus typical proteineous impurities represented by the spend cell culture supernatant. Columns were packed and the most promising ligands

Marc Arnold; Holger Bittermann; Bernd Kalbfuss-Zimmermann; Thomas Neumann; Kristina Schmidt; Renate Sekul; Frank Hilbrig; Heiko Ludolph; Ruth Freitag

2011-01-01

299

Sampling criteria for identifying human biomonitoring chemical differences in the Canadian Arctic  

PubMed Central

Human biomonitoring studies in the Canadian Arctic have measured a wide range of metals and persistent organic pollutants in Aboriginal and non-Aboriginal mothers during two time periods in the Northwest Territories and Nunavut. This analysis provides preliminary estimates on sample sizes and sampling frequencies required to measure significant changes in maternal blood concentrations for PCB 153 and total mercury. For example, sample sizes of 35–40 mothers permit the detection of a 40% decrease in these chemical concentrations between two groups (e.g. communities or regions). Improvements in method sensitivity can be achieved by on-going sampling over multiple time periods (e.g. 4 or 5) in these regions, or increasing sample sizes.

Curren, Meredith S.; Davis, Karelyn; Van Oostdam, Jay

2014-01-01

300

Sampling criteria for identifying human biomonitoring chemical differences in the Canadian Arctic.  

PubMed

Human biomonitoring studies in the Canadian Arctic have measured a wide range of metals and persistent organic pollutants in Aboriginal and non-Aboriginal mothers during two time periods in the Northwest Territories and Nunavut. This analysis provides preliminary estimates on sample sizes and sampling frequencies required to measure significant changes in maternal blood concentrations for PCB 153 and total mercury. For example, sample sizes of 35-40 mothers permit the detection of a 40% decrease in these chemical concentrations between two groups (e.g. communities or regions). Improvements in method sensitivity can be achieved by on-going sampling over multiple time periods (e.g. 4 or 5) in these regions, or increasing sample sizes. PMID:24624369

Curren, Meredith S; Davis, Karelyn; Van Oostdam, Jay

2014-01-01

301

Using Fewer Animals to Identify Chemical Eye Hazards: Revised Criteria Necessary to Maintain Equivalent Hazard Classification  

PubMed Central

U.S. Federal Hazardous Substances Act (FHSA) regulations specify eye safety testing procedures and hazard classification criteria for substances regulated by the U.S. Consumer Product Safety Commission (CPSC). Current regulations require up to three sequential 6-animal tests. Testing consistent with the Organisation for Economic Cooperation and Development (OECD) test guideline for eye irritation/corrosion, which specifies 3 animals, can also be submitted to U.S. agencies. However, current FHSA regulations do not provide criteria to classify results from 3-animal tests. An analysis was conducted to determine criteria using results from 3-animal tests that would provide equivalent labeling to FHSA regulations. The frequency that FHSA requirements identify substances as ocular irritants was compared with the frequency that a criterion of either ?1/3 or ?2/3 positive animals would identify these substances. A database of rabbit eye tests was also used to estimate over- and underprediction rates for each criterion. In each instance, a criterion of ?1/3 positive animals more closely matched the expected outcome based on FHSA requirements, while a criterion of ?2/3 positive animals identified far fewer irritants. Using a classification criterion of ?1/3 positive animals provided equivalent or greater eye hazard labeling as current FHSA requirements, while using 50–83% fewer animals.

Haseman, Joseph K.; Allen, David G.; Lipscomb, Elizabeth A.; Truax, James F.; Stokes, William S.

2011-01-01

302

National body-burden database: chemicals identified in feral and food animals, 1984. Volume IV, Part 1  

SciTech Connect

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

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

1986-01-01

303

National body-burden database. Chemicals identified in feral and food animals, 1984. Volume IV, Part 2  

SciTech Connect

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

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

1986-01-01

304

Comparison of predicted and derived measures of volatile organic compounds inside four relocatable classrooms due to identified interior finish sources  

SciTech Connect

Indoor exposures to toxic and odorous volatile organic compounds (VOCs) are of general concern. Recently, VOCs in portable or relocatable classrooms (RCs) have received particular attention. However, very little was known about indoor environmental quality (IEQ) and the sources, composition, and indoor concentrations of VOCs in RCs. This project task focused on developing and demonstrating a process for selecting interior finish materials for RCs that have relatively low impacts with respect to their emissions of toxic and odorous VOCs. This task was part of a larger project to demonstrate the potential for simultaneous improvements in IEQ and energy efficiency in four new RCs equipped both with a continuously ventilating advanced heating, ventilating, and air conditioning system (HVAC) and a standard HVAC system. These HVACs were operated on alternate weeks. One RC per pair was constructed with standard interior finish materials, and the other included alternate interior materials identified in our prior laboratory study to have low VOC emissions. The RCs were sited in side-by-side pairs at two elementary schools in distinct northern California climate zones. Classroom VOC emission rates (mg hr{sup -1}) and concentrations were predicted based on VOC emission factors ({micro}g m{sup -2} hr{sup -1}) measured for individual materials in the laboratory, the quantities of installed materials and design ventilation rates. Predicted emission rates were compared to values derived from classroom measurements of VOC concentrations and ventilation rates made at pre-occupancy, eight weeks, and 27 weeks. Predicted concentrations were compared to measured integrated VOC indoor minus outdoor concentrations during school hours in the fall cooling season with the advanced HVAC operated. These measured concentrations also were compared between standard and material-modified RCs. Our combined laboratory and field process proved effective by correctly predicting that IEQ impacts of material VOC emissions would be minor when RCs were ventilated at or above code-minimum requirements. Assuming code-minimum ventilation rates are maintained, the benefits attributable to the use of alternate interior finish materials in RC's constructed by the manufacturer associated with this study are small, implying that it is not imperative to use such alternative finishing materials. However, it is essential to avoid materials that can degrade IEQ, and the results of this study demonstrate that laboratory-based material testing combined with modeling and field validation can help to achieve that aim.

Hodgson, Alfred T.; Shendell, Derek G.; Fisk, William J.; Apte, Michael G.

2003-06-01

305

DEVELOPMENT OF A NOVEL, CELL-BASED CHEMICAL SCREEN TO IDENTIFY INHIBITORS OF INTRAPHAGOSOMAL LIPOLYSIS IN MACROPHAGES  

PubMed Central

Macrophages play a central role in tissue homeostasis and the immune system. Their primary function is to internalize cellular debris and microorganisms for degradation within their phagosomes. In this context, their capacity to process and sequester lipids such as triacylglycerides and cholesteryl esters makes them key players in circulatory diseases such as atheroclerosis. To discover new inhibitors of lipolytic processing within the phagosomal system of the macrophage we have developed a novel, cell-based assay suitable for high-throughput screening. We employed particles carrying a fluorogenic triglyceride substrate and a calibration fluor to screen for inhibitors of phagosomal lipolysis. A panel of secondary assays were employed to discriminate between lipase inhibitors and compounds that perturbed general phagosomal trafficking events. This process enabled us to identify a new structural class of pyrazole-methanone compounds that directly inhibit lysosomal and lipoprotein lipase activity.

VanderVen, Brian C.; Hermetter, Albin; Huang, Amy; Maxfield, Fredrick R; Russell, David G; Yates, Robin M.

2010-01-01

306

Diverging DOS strategy using an allene-containing tryptophan scaffold and a library design that maximizes biologically relevant chemical space while minimizing the number of compounds.  

PubMed

A diverging diversity-oriented synthesis (DOS) strategy using an allene-containing tryptophan as a key starting material was investigated. An allene-yne substituted derivative of tryptophan 12 gave indolylmethylazabicyclooctadiene 17 when subjected to a microwave-assisted allenic [2 + 2] cycloaddition reaction. This same tryptophan-derived precursor afforded an indolylmethyldihydrocyclopentapyridinone 14 when subjected to a rhodium(I)-catalyzed cyclocarbonylation reaction and an indolylmethylpyrrolidinocyclopentenones 16 when reacted with molybdenum hexacarbonyl. Construction of allenic tetrahydro-?-carboline scaffolds via a Pictet-Spengler reaction and subsequent silver(I)-catalyzed cycloisomerization afforded tetrahydroindolizinoindoles (21). Attachment of allene and alkyne groups to the tetrahydro-?-carboline, followed by a microwave-assisted allenic [2 + 2] cycloaddition reaction, provided tetrahydrocyclobutaindoloquinolizinones 24 and the tetrahydrocyclopentenone indolizinoindolone 26 when reacted with molybdenum hexacarbonyl. These six scaffolds were used as templates for the construction of a virtual library of 11?748 compounds employing 44 indoles, 12 aldehydes, and 51 alkynes. Diversity analyses using a combination of cell-based chemistry space computations using BCUT (Burden (B) CAS (C) Pearlman at the University of Texas (UT)) metrics and Tanimoto coefficient (Tc) similarity calculations using two-dimensional (2D) fingerprints showed that the compounds in the virtual library occupied new chemical space when compared to the 327,000 compounds in the molecular libraries small molecule repository (MLSMR). A subset of fifty-three compounds was identified from the virtual library using the DVS package of Sybyl 8.0; this subset represents the most diverse compounds within the chemical space defined by these compounds and will be synthesized and screened for biological activity. PMID:21332123

Painter, Thomas O; Wang, Lirong; Majumder, Supriyo; Xie, Xiang-Qun; Brummond, Kay M

2011-03-14

307

Development of a fission yeast-based high throughput screen to identify chemical regulators of cAMP phosphodiesterases  

PubMed Central

Cyclic nucleotide phosphodiesterases (PDEs) comprise a superfamily of enzymes that serve as drug targets in many human diseases. There is a continuing need to identify high-specificity inhibitors that affect individual PDE families or even subtypes within a single family. We describe a fission yeast-based high throughput screen to detect inhibitors of heterologously-expressed cAMP PDEs. The utility of this system is demonstrated by the construction and characterization of strains that express mammalian PDE2A, PDE4A, PDE4B, and PDE8A and respond appropriately to known PDE2A and PDE4 inhibitors. High throughput screens of two bioactive compound libraries for PDE inhibitors using strains expressing PDE2A, PDE4A, PDE4B, and the yeast PDE Cgs2 identified known PDE inhibitors and members of compound classes associated with PDE inhibition. We verified that the furanocoumarin imperatorin is a PDE4 inhibitor based on its ability to produce a PDE4-specific elevation of cAMP levels. This platform can be used to identify PDE activators, as well as genes encoding PDE regulators, which could serve as targets for future drug screens.

Ivey, F. Douglas; Wang, Lili; Demirbas, Didem; Allain, Christina; Hoffman, Charles S.

2010-01-01

308

Identification of chlorinated solvents degradation zones in clay till by high resolution chemical, microbial and compound specific isotope analysis.  

PubMed

The degradation of chlorinated ethenes and ethanes in clay till was investigated at a contaminated site (Vadsby, Denmark) by high resolution sampling of intact cores combined with groundwater sampling. Over decades of contamination, bioactive zones with degradation of trichloroethene (TCE) and 1,1,1-trichloroethane (1,1,1-TCA) to 1,2-cis-dichloroethene (cis-DCE) and 1,1-dichloroethane, respectively, had developed in most of the clay till matrix. Dehalobacter dominated over Dehalococcoides (Dhc) in the clay till matrix corresponding with stagnation of sequential dechlorination at cis-DCE. Sporadically distributed bioactive zones with partial degradation to ethene were identified in the clay till matrix (thickness from 0.10 to 0.22 m). In one sub-section profile the presence of Dhc with the vcrA gene supported the occurrence of degradation of cis-DCE and VC, and in another enriched ?(13)C for TCE, cis-DCE and VC documented degradation. Highly enriched ?(13)C for 1,1,1-TCA (25‰) and cis-DCE (-4‰) suggested the occurrence of abiotic degradation in a third sub-section profile. Due to fine scale heterogeneity the identification of active degradation zones in the clay till matrix depended on high resolution subsampling of the clay till cores. The study demonstrates that an integrated approach combining chemical analysis, molecular microbial tools and compound specific isotope analysis (CSIA) was required in order to document biotic and abiotic degradations in the clay till system. PMID:23357226

Damgaard, Ida; Bjerg, Poul L; Bælum, Jacob; Scheutz, Charlotte; Hunkeler, Daniel; Jacobsen, Carsten S; Tuxen, Nina; Broholm, Mette M

2013-03-01

309

Identification of chlorinated solvents degradation zones in clay till by high resolution chemical, microbial and compound specific isotope analysis  

NASA Astrophysics Data System (ADS)

The degradation of chlorinated ethenes and ethanes in clay till was investigated at a contaminated site (Vadsby, Denmark) by high resolution sampling of intact cores combined with groundwater sampling. Over decades of contamination, bioactive zones with degradation of trichloroethene (TCE) and 1,1,1-trichloroethane (1,1,1-TCA) to 1,2-cis-dichloroethene (cis-DCE) and 1,1-dichloroethane, respectively, had developed in most of the clay till matrix. Dehalobacter dominated over Dehalococcoides (Dhc) in the clay till matrix corresponding with stagnation of sequential dechlorination at cis-DCE. Sporadically distributed bioactive zones with partial degradation to ethene were identified in the clay till matrix (thickness from 0.10 to 0.22 m). In one sub-section profile the presence of Dhc with the vcrA gene supported the occurrence of degradation of cis-DCE and VC, and in another enriched ?13C for TCE, cis-DCE and VC documented degradation. Highly enriched ?13C for 1,1,1-TCA (25‰) and cis-DCE (- 4‰) suggested the occurrence of abiotic degradation in a third sub-section profile. Due to fine scale heterogeneity the identification of active degradation zones in the clay till matrix depended on high resolution subsampling of the clay till cores. The study demonstrates that an integrated approach combining chemical analysis, molecular microbial tools and compound specific isotope analysis (CSIA) was required in order to document biotic and abiotic degradations in the clay till system.

Damgaard, Ida; Bjerg, Poul L.; Bælum, Jacob; Scheutz, Charlotte; Hunkeler, Daniel; Jacobsen, Carsten S.; Tuxen, Nina; Broholm, Mette M.

2013-03-01

310

Determination of chemical classes from mass spectra of toxic organic compounds by SIMCA pattern recognition and information theory  

Microsoft Academic Search

The low-resolution mass spectra of a set of 78 toxic volatile organic compounds were examined for information concerning chemical classes. The Shannon information content for each mass channel was calculated for the binary encoded and the full intensity spectra, using 1% of the base peak as the threshold level. The 17 masses with the highest binary information content were retained

Donald R. Scott

1986-01-01

311

Low temperature selective epitaxy of III V compounds by laser assisted chemical vapor deposition  

NASA Astrophysics Data System (ADS)

Laser Assisted Chemical Vapor Deposition (LCVD) is a new approach for low temperature selective epitaxy of III-V compounds with great potential for maskless multicomponent device integration on the same wafer. GaAs substrates were thermally biased to temperatures as low as 250°C and exposed simultaneously to fluxes of trimethylgallium (TMG) and arsine (AsH 3). Ar ion laser scanning of the substrate, at carefully selected growth conditions, resulted in epitaxial selective deposition at rates as low as a few Å/s per scan. The LCVD growth rates as a function of deposition temperatures are reported for different laser powers and seem to follow an Arrhenius type relation. Activation energies in the range 10-13 kcal/mol were estimated for growth temperatures in the range 250-400°C. X-ray diffraction topography is demonstrated as a powerful nondestructive tool for structural characterization. We have utilized this technique to optimize the LCVD growth conditions in order to achieve device quality films that are free from lattice distortion. Low temperature photoluminescence shows the presence of impurity peaks that can be related to carbon.

Karam, N. H.; Liu, H.; Yoshida, I.; Jiang, B.-L.; Bedair, S. M.

1988-12-01

312

Device quality Sb-based compound semiconductor surface: A comparative study of chemical cleaning  

NASA Astrophysics Data System (ADS)

We have studied the surface cleaning of Sb-based compound semiconductors using HF, NH4OH, and HCl cleans and the metal-oxide-semiconductor (MOS) capacitors fabricated subsequently. GaSb, InGaSb, and AlGaSb surfaces are investigated using low-energy radiation from the synchrotron. Capacitance-voltage (C-V) and photoluminescence measurements are carried out on capacitors made with Al2O3 from atomic layer deposition and corroborated with the results from synchrotron spectroscopy. Excellent C-V characteristics with a mid-band-gap interface state density of 3 × 1011/cm2eV are obtained on samples with the HCl clean. This is consistent with the finding that only the HCl acid clean is able to remove the native oxides present on GaSb and InGaSb surfaces, and produce clean and stable surfaces suitable for MOSFET development. Complete removal of AlOx on the AlGaSb surface was not possible using chemical cleaning. Termination of AlGaSb with two monolayers of GaSb is proposed as a solution.

Nainani, Aneesh; Sun, Yun; Irisawa, Toshifumi; Yuan, Ze; Kobayashi, Masaharu; Pianetta, Piero; Bennett, Brian. R.; Brad Boos, J.; Saraswat, Krishna C.

2011-06-01

313

Two-Dimensional Carbon Compounds Derived from Graphyne with Chemical Properties Superior to Those of Graphene  

PubMed Central

Computational studies considering both thermodynamic and kinetic aspects revealed that graphyne, a carbon material that has recently been of increasing interest, favours unprecedented homogeneous “in-plane” addition reactions. The addition of dichlorocarbene to the C(sp)-C(sp) bond, a site with outstanding regioselectivity in graphyne, proceeds via a stepwise mechanism. Due to their homogeneous nature, additions occurring at C(sp)-C(sp) bonds yield structurally ordered two-dimensional carbon compounds (2DCCs). 2DCCs have electronic band structures near the Fermi level that are similar to those of graphene and are either electrically semi-conductive or metallic depending on whether the reactions break the hexagonal symmetry. Notably, 2DCCs can be further functionalised through substitution reactions with little damage to the extended ?-electron conjugation system. These results suggest that 2DCCs derived from graphyne have physical properties comparable to those of graphene and chemical properties superior to those of graphene. Therefore, 2DCCs are expected to be better suited to practical applications.

Zheng, Jia-Jia; Zhao, Xiang; Zhao, Yuliang; Gao, Xingfa

2013-01-01

314

Catalytic conversion of biomass pyrolysis-derived compounds with chemical liquid deposition (CLD) modified ZSM-5.  

PubMed

Chemical liquid deposition (CLD) with KH550, TEOS and methyl silicone oil as the modifiers was used to modify ZSM-5 and deposit its external acid sites. The characteristics of modified catalysts were tested by catalytic conversion of biomass pyrolysis-derived compounds. The effects of different modifying conditions (deposited amount, temperature, and time) on the product yields and selectivities were investigated. The results show KH550 modified ZSM-5 (deposited amount of 4%, temperature of 20°C and time of 6h) produced the maximum yields of aromatics (24.5%) and olefins (16.5%), which are much higher than that obtained with original ZSM-5 catalyst (18.8% aromatics and 9.8% olefins). The coke yield decreased from 44.1% with original ZSM-5 to 26.7% with KH550 modified ZSM-5. The selectivities of low-molecule-weight hydrocarbons (ethylene and benzene) decreased, while that of higher molecule-weight hydrocarbons (propylene, butylene, toluene, and naphthalene) increased comparing with original ZSM-5. PMID:24413482

Zhang, Huiyan; Luo, Mengmeng; Xiao, Rui; Shao, Shanshan; Jin, Baosheng; Xiao, Guomin; Zhao, Ming; Liang, Junyu

2014-03-01

315

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

PubMed

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity. PMID:23345455

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

2013-05-01

316

Pheromonal activity of compounds identified from male Phyllotreta cruciferae: field tests of racemic mixtures, pure enantiomers, and combinations with allyl isothiocyanate.  

PubMed

Four himachalene sesquiterpenes and (+)-gamma-cadinene, previously identified as possible pheromone components from males of a North American population of Phyllotreta cruciferae Goeze (Coleoptera, Chrysomelidae), were tested for attractiveness in field trapping experiments in Hungary. A mixture of the four synthetic racemic himachalene derivatives and (+)-gamma-cadinene from a botanical source was slightly attractive to beetles, but much more attractive when blended with the known host-plant-derived attractant allyl isothiocyanate. This result was consistent with a previous study in North America. In tests with optically pure synthetic compounds, a blend of the same himachalene enantiomers found from male beetles was equivalent to the corresponding blend of racemic compounds, whereas a blend of the opposite enantiomers was not active. Through subtraction tests, it was found that the single compound, (6R,7S)-2,2,6,10-tetramethylbicyclo[5.4.0.]undeca-9,11-diene [compound (+)-A in this study], was as active as the whole mixture, suggesting that this compound is the key pheromone component of the European population of P. cruciferae. During field trials, several congeneric species, including P. vittula, P. nemorum, P. nodicornis, and P. ochripes, also were caught, suggesting that the same compound(s) may be relatively widespread as pheromone components in this genus. PMID:16273436

Tóth, Miklós; Csonka, Eva; Bartelt, Robert J; Cossé, Allard A; Zilkowski, Bruce W; Muto, Shin-Etsu; Mori, Kenji

2005-11-01

317

Investigation of the Chemical Identity of Soluble Organophosphorus Compounds Found in Natural Waters.  

National Technical Information Service (NTIS)

The ability of various laboratory algal cultures to generate substantial quantities of dissolved organic phosphorus (DOP) compounds has been demonstrated. After isolation and concentration of these compounds by low pressure filtration, freeze drying and r...

R. A. Minear K. A. Walanski

1974-01-01

318

A High-Resolution Genetic Map of Yellow Monkeyflower Identifies Chemical Defense QTLs and Recombination Rate Variation  

PubMed Central

Genotyping-by-sequencing methods have vastly improved the resolution and accuracy of genetic linkage maps by increasing both the number of marker loci as well as the number of individuals genotyped at these loci. Using restriction-associated DNA sequencing, we construct a dense linkage map for a panel of recombinant inbred lines derived from a cross between divergent ecotypes of Mimulus guttatus. We used this map to estimate recombination rate across the genome and to identify quantitative trait loci for the production of several secondary compounds (PPGs) of the phenylpropanoid pathway implicated in defense against herbivores. Levels of different PPGs are correlated across recombinant inbred lines suggesting joint regulation of the phenylpropanoid pathway. However, the three quantitative trait loci identified in this study each act on a distinct PPG. Finally, we map three putative genomic inversions differentiating the two parental populations, including a previously characterized inversion that contributes to life-history differences between the annual/perennial ecotypes.

Holeski, Liza M.; Monnahan, Patrick; Koseva, Boryana; McCool, Nick; Lindroth, Richard L.; Kelly, John K.

2014-01-01

319

Chemical Synthesis Database  

NSDL National Science Digital Library

This database provides information on thousands of chemical compounds, including synthesis references and physical properties. The database is searchable by keyword and browseable by journal title. For each compound, the information includes molecular formula and weight, Chemical Abstracts Service (CAS) numbers, International Chemical Identifier (InChIKey), and Simplified Molecular Input Line Entry System (SMILES) notation. There is also information on synonyms, physical properties (boiling and melting points, density), an illustration of chemical structure, spectral data, and links to additional data.

320

Screening of novel chemical compounds as possible inhibitors of carbonic anhydrase and photosynthetic activity of photosystem II.  

PubMed

Thirty novel chemical compounds were designed and synthesized expecting that they would be possible inhibitors. From this number eleven were organic bases, twenty-four were their organic derivatives and fourteen were metal complexes. Screening of these chemicals by their action on photosynthetic electron transfer (PET) and carbonic anhydrase (CA) activity (CAA) of photosystem II (PSII), ?-CA, as well as ?-CA was done. Several groups were revealed among them. Some of them are capable to suppress either one, two, three, or even all of the measured activities. As example, one of the Cu(II)-phenyl sulfonylhydrazone complexes (compound 25) suppresses CAA of ?-CA by 88%, CAA of ?-CA by 100% inhibition; CAA of PSII by 100% and the PSII photosynthetic activity by 66.2%. The Schiff base compounds (12, 15) and Cu(II)-phenyl sulfonylhydrazone complexes (25, 26) inhibited the CAA and PET of PSII significantly. The obtained data indicate that the PSII donor side is a target of the inhibitory action of these agents. Some physico- or electrochemical properties such as diffusion coefficient, number of transferred electrons, peak potential and heterogeneous standard rate constants of the compounds were determined in nonaqueous media. pKa values were also determined in nonaqueous and aqueous media. Availability in the studied group of novel chemical agents possessing different inhibitory activity allow in future to isolate the "active part" in the structure of the inhibitors responsible for different inhibitory mechanisms, as well as to determine the influence of side substituters on its inhibitory efficiency. PMID:24418071

Karacan, Mehmet Say?m; Zharmukhamedov, Sergei K; Mama?, Serhat; Kupriyanova, Elena V; Shitov, Alexandr V; Klimov, Vyacheslav V; Ozbek, Neslihan; Ozmen, Ummühan; Gündüzalp, Ayla; Schmitt, Franz-Josef; Karacan, Nurcan; Friedrich, Thomas; Los, Dmitry A; Carpentier, Robert; Allakhverdiev, Suleyman I

2014-08-01

321

Eryngial (trans-2-dodecenal), a bioactive compound from Eryngium foetidum: its identification, chemical isolation, characterization and comparison with ivermectin in vitro.  

PubMed

Methanol-water (4:1, v/v) crude extracts (50 mg mL(-1)) of 25 Jamaican medicinal plants were screened in vitro for anthelmintic activity using infective third-stage larvae of Strongyloides stercoralis. The most effective extract was further chemically scrutinized to isolate and identify the source of the bioactivity, and the efficacy of this compound was compared with ivermectin. Eosin exclusion (0.1 mg mL(-1)) served as the indicator of mortality in all bioassays. A crude extract of Eryngium foetidum (Apiaceae) was significantly (Probit Analysis, P<0.05) more potent than the other plant extracts, taking 18.9 h to kill 50% (LT50) of the larvae. Further, the petrol extract of E. foetidum was significantly more effective (Probit Analysis, P<0.05) at killing the larvae (LT50, 4.7 h) than either its methanol-water or dichloromethane extract. The latter two effected less than 1% larval mortality after 120 h. With bioassay-driven column chromatography of the petrol extract, trans-2-dodecenal (eryngial) was identified and chemically isolated as the main anthelmintic compound in E. foetidum. There was a significant difference between the 24 h LD50 values (mm) of trans-2-dodecenal (0.461) and ivermectin (2.251) but there was none between the 48 h LD50 values (mm): trans-2-dodecenal (0.411) and ivermectin (0.499) in vitro. PMID:24139239

Forbes, W M; Gallimore, W A; Mansingh, A; Reese, P B; Robinson, R D

2014-02-01

322

Integrated supercritical fluid extraction, bioassay and chemical screening methods for analyzing vapor-phase compounds of an environmental complex mixture: Diesel exhaust  

Microsoft Academic Search

The integration of bioassay and chemical analyses for vapor-phase compounds in environmental complex mixtures is a challenging process due to the volatility and the limited amounts of compounds collected and subsequently assayed. The advantage of an integrated approach is that the bioassay could aid in determining the most biologically active fractions for further chemical analyses. Previously, we reported on the

Norman Y. Kado; Robert A. Okamoto; Paul A. Kuzmicky; Christine J. Rathbun; Dennis P. H. Hsieh

1996-01-01

323

High Throughput Screening for Compounds That Alter Muscle Cell Glycosylation Identifies New Role for N-Glycans in Regulating Sarcolemmal Protein Abundance and Laminin Binding*  

PubMed Central

Duchenne muscular dystrophy is an X-linked disorder characterized by loss of dystrophin, a cytoskeletal protein that connects the actin cytoskeleton in skeletal muscle cells to extracellular matrix. Dystrophin binds to the cytoplasmic domain of the transmembrane glycoprotein ?-dystroglycan (?-DG), which associates with cell surface ?-dystroglycan (?-DG) that binds laminin in the extracellular matrix. ?-DG can also associate with utrophin, and this differential association correlates with specific glycosylation changes on ?-DG. Genetic modification of ?-DG glycosylation can promote utrophin binding and rescue dystrophic phenotypes in mouse dystrophy models. We used high throughput screening with the plant lectin Wisteria floribunda agglutinin (WFA) to identify compounds that altered muscle cell surface glycosylation, with the goal of finding compounds that increase abundance of ?-DG and associated sarcolemmal glycoproteins, increase utrophin usage, and increase laminin binding. We identified one compound, lobeline, from the Prestwick library of Food and Drug Administration-approved compounds that fulfilled these criteria, increasing WFA binding to C2C12 cells and to primary muscle cells from wild type and mdx mice. WFA binding and enhancement by lobeline required complex N-glycans but not O-mannose glycans that bind laminin. However, inhibiting complex N-glycan processing reduced laminin binding to muscle cell glycoproteins, although O-mannosylation was intact. Glycan analysis demonstrated a general increase in N-glycans on lobeline-treated cells rather than specific alterations in cell surface glycosylation, consistent with increased abundance of multiple sarcolemmal glycoproteins. This demonstrates the feasibility of high throughput screening with plant lectins to identify compounds that alter muscle cell glycosylation and identifies a novel role for N-glycans in regulating muscle cell function.

Cabrera, Paula V.; Pang, Mabel; Marshall, Jamie L.; Kung, Raymond; Nelson, Stanley F.; Stalnaker, Stephanie H.; Wells, Lance; Crosbie-Watson, Rachelle H.; Baum, Linda G.

2012-01-01

324

Dimensionality and Topology of Chemical Bonding Manifolds in Metal Clusters and Related Compounds.  

National Technical Information Service (NTIS)

The chemical bonding manifolds in metal cluster skeletons (as well as in skeletons of clusters of other elements such as boron or carbon) may be classified according to their dimensionalities and their chemical homeomorphism to various geometric structure...

R. B. King

1987-01-01

325

Study of the Connection of the Chemical Composition of Organometallic Compounds with Their Toxicity for Hydrobionts (Izuchenie Svyazi Khimicheskogo Sostava Metallogranicheskikh Soedinenii S ikh Toksichnostyu dlya Gidrobiont ov).  

National Technical Information Service (NTIS)

In the report the authors present new data on the effect of organometallic compounds on algae and Daphnia and compare the toxicity of the action of these compounds with their chemical composition. The compounds studied were of the formula, R(n)MeX where R...

N. S. Stroganov V. G. Khobotev L. V. Kolosova

1972-01-01

326

Quantitative Chemical Proteomics Identifies Novel Targets of the Anti-cancer Multi-kinase Inhibitor E-3810*  

PubMed Central

Novel drugs are designed against specific molecular targets, but almost unavoidably they bind non-targets, which can cause additional biological effects that may result in increased activity or, more frequently, undesired toxicity. Chemical proteomics is an ideal approach for the systematic identification of drug targets and off-targets, allowing unbiased screening of candidate interactors in their natural context (tissue or cell extracts). E-3810 is a novel multi-kinase inhibitor currently in clinical trials for its anti-angiogenic and anti-tumor activity. In biochemical assays, E-3810 targets primarily vascular endothelial growth factor and fibroblast growth factor receptors. Interestingly, E-3810 appears to inhibit the growth of tumor cells with low to undetectable levels of these proteins in vitro, suggesting that additional relevant targets exist. We applied chemical proteomics to screen for E-3810 targets by immobilizing the drug on a resin and exploiting stable isotope labeling by amino acids in cell culture to design experiments that allowed the detection of novel interactors and the quantification of their dissociation constant (Kd imm) for the immobilized drug. In addition to the known target FGFR2 and PDGFR?, which has been described as a secondary E-3810 target based on in vitro assays, we identified six novel candidate kinase targets (DDR2, YES, LYN, CARDIAK, EPHA2, and CSBP). These kinases were validated in a biochemical assay and—in the case of the cell-surface receptor DDR2, for which activating mutations have been recently discovered in lung cancer—cellular assays. Taken together, the success of our strategy—which integrates large-scale target identification and quality-controlled target affinity measurements using quantitative mass spectrometry—in identifying novel E-3810 targets further supports the use of chemical proteomics to dissect the mechanism of action of novel drugs.

Colzani, Mara; Noberini, Roberta; Romanenghi, Mauro; Colella, Gennaro; Pasi, Maurizio; Fancelli, Daniele; Varasi, Mario; Minucci, Saverio; Bonaldi, Tiziana

2014-01-01

327

Quantitative Chemical Proteomics Identifies Novel Targets of the Anti-cancer Multi-kinase Inhibitor E-3810.  

PubMed

Novel drugs are designed against specific molecular targets, but almost unavoidably they bind non-targets, which can cause additional biological effects that may result in increased activity or, more frequently, undesired toxicity. Chemical proteomics is an ideal approach for the systematic identification of drug targets and off-targets, allowing unbiased screening of candidate interactors in their natural context (tissue or cell extracts). E-3810 is a novel multi-kinase inhibitor currently in clinical trials for its anti-angiogenic and anti-tumor activity. In biochemical assays, E-3810 targets primarily vascular endothelial growth factor and fibroblast growth factor receptors. Interestingly, E-3810 appears to inhibit the growth of tumor cells with low to undetectable levels of these proteins in vitro, suggesting that additional relevant targets exist. We applied chemical proteomics to screen for E-3810 targets by immobilizing the drug on a resin and exploiting stable isotope labeling by amino acids in cell culture to design experiments that allowed the detection of novel interactors and the quantification of their dissociation constant (Kd imm) for the immobilized drug. In addition to the known target FGFR2 and PDGFR?, which has been described as a secondary E-3810 target based on in vitro assays, we identified six novel candidate kinase targets (DDR2, YES, LYN, CARDIAK, EPHA2, and CSBP). These kinases were validated in a biochemical assay and-in the case of the cell-surface receptor DDR2, for which activating mutations have been recently discovered in lung cancer-cellular assays. Taken together, the success of our strategy-which integrates large-scale target identification and quality-controlled target affinity measurements using quantitative mass spectrometry-in identifying novel E-3810 targets further supports the use of chemical proteomics to dissect the mechanism of action of novel drugs. PMID:24696502

Colzani, Mara; Noberini, Roberta; Romanenghi, Mauro; Colella, Gennaro; Pasi, Maurizio; Fancelli, Daniele; Varasi, Mario; Minucci, Saverio; Bonaldi, Tiziana

2014-06-01

328

Screening for Inhibition of Vibrio cholerae VipA-VipB Interaction Identifies Small-Molecule Compounds Active against Type VI Secretion.  

PubMed

The type VI secretion system (T6SS) is the most prevalent bacterial secretion system and an important virulence mechanism utilized by Gram-negative bacteria, either to target eukaryotic cells or to combat other microbes. The components show much variability, but some appear essential for the function, and two homologues, denoted VipA and VipB in Vibrio cholerae, have been identified in all T6SSs described so far. Secretion is dependent on binding of an ?-helical region of VipA to VipB, and in the absence of this binding, both components are degraded within minutes and secretion is ceased. The aim of the study was to investigate if this interaction could be blocked, and we hypothesized that such inhibition would lead to abrogation of T6S. A library of 9,600 small-molecule compounds was screened for their ability to block the binding of VipA-VipB in a bacterial two-hybrid system (B2H). After excluding compounds that showed cytotoxicity toward eukaryotic cells, that inhibited growth of Vibrio, or that inhibited an unrelated B2H interaction, 34 compounds were further investigated for effects on the T6SS-dependent secretion of hemolysin-coregulated protein (Hcp) or of phospholipase A1 activity. Two compounds, KS100 and KS200, showed intermediate or strong effects in both assays. Analogues were obtained, and compounds with potent inhibitory effects in the assays and desirable physicochemical properties as predicted by in silico analysis were identified. Since the compounds specifically target a virulence mechanism without affecting bacterial replication, they have the potential to mitigate the virulence with minimal risk for development of resistance. PMID:24798289

Sun, Kun; Bröms, Jeanette; Lavander, Moa; Gurram, Bharat Kumar; Enquist, Per-Anders; Andersson, C David; Elofsson, Mikael; Sjöstedt, Anders

2014-07-01

329

Thickness dependence of ZnO:In thin films doped with different indium compounds and deposited by chemical spray  

Microsoft Academic Search

Indium-doped zinc oxide thin films were deposited on glass substrates by the chemical spray technique. Hydrated zinc 2,4-pentanedionate was used as zinc source. Four different indium compounds were separately used as dopants (indium nitrate, indium sulfate, indium acetate, and indium chloride). The effect of the thickness on the electrical, structural, morphological and optical characteristics of ZnO:In thin films was studied.

M. A. Lucio-López; A. Maldonado; R. Castanedo-Pérez; G. Torres-Delgado; M. de la L. Olvera

2006-01-01

330

Nuclear magnetic resonance shielding constants and chemical shifts in linear 199Hg compounds: A comparison of three relativistic computational methods  

Microsoft Academic Search

We investigate the importance of relativistic effects on NMR shielding constants and chemical shifts of linear HgL2 (L = Cl, Br, I, CH3) compounds using three different relativistic methods: the fully relativistic four-component approach and the two-component approximations, linear response elimination of small component (LR-ESC) and zeroth-order regular approximation (ZORA). LR-ESC reproduces successfully the four-component results for the C shielding

Vaida Arcisauskaite; Juan I. Melo; Lars Hemmingsen; Stephan P. A. Sauer

2011-01-01

331

The chemical composition of plant galls: are levels of nutrients and secondary compounds controlled by the gall-former?  

Microsoft Academic Search

The chemical composition of galled and ungalled plant tissue was compared in a series of experiments. Gall and adjacent plant\\u000a tissue was analysed for 20 species of gall-former on 11 different plant species. There were clear differences between galled\\u000a and ungalled tissue in levels of nutrients and secondary compounds. Gall tissue generally contained lower levels of nitrogen\\u000a and higher levels

S. E. Hartley

1998-01-01

332

A novel energy-efficient plasma chemical process for the destruction of volatile toxic compounds. 1998 annual progress report  

SciTech Connect

'Removal of low-concentrations (below several percent) of volatile toxic compounds (VTCs) from contaminated air streams is encountered at DOE waste sites in two instances: (1) off-gases resulting from air-stripping of contaminated soils; and (2) effluent from the incineration of highly-concentrated combustible hazardous wastes The objective of the research program is to develop a novel plasma chemical process for the destruction of VTC''s in low-concentration waste streams.'

Pinnaduwage, L.A.

1998-06-01

333

Chemically modified polymeric resin used as sorbent in a solid-phase extraction process to determine phenolic compounds in water  

Microsoft Academic Search

A chemically modified polymeric resin with an acetyl group is developed for use in a solid-phase extraction process. The breakthrough volumes and selectivity of several phenolic compounds were studied and compared with the ones obtained for several commercial sorbents such as PLRP-s, Amberchrom, Envi-Chrom P and LiChrolut EN. The study was carried out by coupling an on-line solid-phase extraction system

N. Masqué; M. Galià; R. M. Marcé; F. Borrull

1997-01-01

334

Extraction, chemical characterization and biological activity determination of broccoli health promoting compounds.  

PubMed

Broccoli (Brassica oleracea L. var. Italica) contains substantial amount of health-promoting compounds such as vitamins, glucosinolates, phenolic compounds, and dietary essential minerals; thus, it benefits health beyond providing just basic nutrition, and consumption of broccoli has been increasing over the years. This review gives an overview on the extraction and separation techniques, as well as the biological activity of some of the above mentioned compounds which have been published in the period January 2008 to January 2013. The work has been distributed according to the different families of health promoting compounds discussing the extraction procedures and the analytical techniques employed for their characterization. Finally, information about the different biological activities of these compounds has been also provided. PMID:23899380

Ares, Ana M; Nozal, María J; Bernal, José

2013-10-25

335

Novel metal organic chemical vapor deposition routes to solid state ionic compounds  

NASA Astrophysics Data System (ADS)

Four new chemical vapor deposition routes to thin film solid state ionic compounds have been discovered. Tetraallyl tungsten and tris (methylvinylketone) tungsten, two novel organometallic precursors were used to deposit tungsten oxide films. These films showed unique properties including lower density (ca. 4.3 g/cm3), fast coloration times (<1s at 1.0 V vs Ag/AgCl) and low coloration efficiency (25 cm2/C). These electrochemical properties are believed to be related to the low density as determined by Rutherford Backscattering Spectrometry (RBS). As-deposited films contained between 7 and 25 at.% carbon, and contained a mixture of the monoclinic and triclinic phases as determined by powder X-ray diffraction measurements. Two new lithium precursors were developed for synthesis of ion conducting and secondary cathode material thin films. Lithium triethyl carboxide was used to deposit lithium cobalt oxide thin films in conjunction with tris (tetramethylheptanedionato) cobalt. To our knowledge, this is the first example of a practical lithium precursor which has sufficient volatility (100 mT at 130°C) and is not air sensitive. X-ray diffraction data of these films indicate the presence of a lithium cobalt oxide system, although the phase composition needs further characterization. Thermogravimetric analysis of the lithium precursor indicates a gradual vapor pressure curve and thus the potential to fine tune vapor transport rates according to the desired properties of the films. Lithium hexamethyldisilazide was used to deposit ion conducting lithium silicate films. The precursor was found to decompose upon transport under hot wall conditions, and an optimization of delivery of silicon and lithium remains under investigation. In an oxygen environment, Li/Si ratios were typically 0.1 in the films, compared to a value of 0.5 in the precursor. A precursor decomposition mechanism was inferred from mass spectral data and decomposition product analysis, which indicated the tendency for cleavage of the Si-N bond and formation of polydimethyl siloxane species. Ionic conductivities of 5*10--8S/cm were achieved. Further work is required to optimize delivery of this precursor, including changing reactor geometry and energetics.

Breitkopf, Richard Charles

336

Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells  

PubMed Central

Background Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method. Methods Here we present a novel method to identify efficient inhibitors of CSN-associated kinases. Using curcumin and emodin as lead structures an in silico screening with our in-house database containing more than 106 structures was carried out. Thirty-five compounds were identified and further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be clearly discriminated according to their structures: the curcumin-group and the emodin-group. The compounds were evaluated in in vitro kinase assays and in cell culture experiments. Results The data revealed 3 compounds of the curcumin-group (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent inhibitors of CSN-associated kinases. Identified agents increased p53 levels and induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA fragmentation and caspase activity assays. Conclusion Our data demonstrate that the new in silico screening method is highly efficient for identifying potential anti-tumor drugs.

Fullbeck, Melanie; Huang, Xiaohua; Dumdey, Renate; Frommel, Cornelius; Dubiel, Wolfgang; Preissner, Robert

2005-01-01

337

Quantitative comparison of chemical, biological and mechanical induction of secondary compounds in Pinus pinaster seedlings  

Microsoft Academic Search

Chemical elicitors and mechanical treatments simulating real insect herbivory have been increasingly used to study induced\\u000a defensive responses in woody plants. However, simultaneous quantitative comparisons of plant chemical defences elicited by\\u000a real and simulated herbivory have received little attention. In this paper we compared the effects of real herbivory, simulated\\u000a herbivory using two chemical elicitors, and mechanical damage treatments on

Xoaquín Moreira; Rafael Zas; Luis Sampedro

338

Thymine vanadyl(II) compound as a diabetic drug model: Chemical spectroscopic and antimicrobial assessments  

NASA Astrophysics Data System (ADS)

The aim of this study was to synthesize a novel bifunctionalized thymine vanadyl(II) compound. The solid vanadyl(II) compound has been characterized by elemental analyses (CHN), Raman laser, infrared spectra, molar conductivity, electronic spectra, thermogravimetric analyses (TGA), scanning electron microscopy (SEM) and X-ray powder diffraction (XRD) studies. Electronic and magnetic measurements have confirmed that the speculated geometry of vanadyl(II) compound is square pyramidal geometry. The microbial test was performed for the vanadyl complex against some kinds of bacteria and fungi. The results suggested that [VO(Thy)2] adduct has an anti-diabetic profile.

El-Sayed, Mohamed Y.; Refat, Moamen S.

2014-09-01

339

Thymine vanadyl(II) compound as a diabetic drug model: chemical spectroscopic and antimicrobial assessments.  

PubMed

The aim of this study was to synthesize a novel bifunctionalized thymine vanadyl(II) compound. The solid vanadyl(II) compound has been characterized by elemental analyses (CHN), Raman laser, infrared spectra, molar conductivity, electronic spectra, thermogravimetric analyses (TGA), scanning electron microscopy (SEM) and X-ray powder diffraction (XRD) studies. Electronic and magnetic measurements have confirmed that the speculated geometry of vanadyl(II) compound is square pyramidal geometry. The microbial test was performed for the vanadyl complex against some kinds of bacteria and fungi. The results suggested that [VO(Thy)2] adduct has an anti-diabetic profile. PMID:24785088

El-Sayed, Mohamed Y; Refat, Moamen S

2014-09-15

340

Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening.  

PubMed

Mitochondrial production of reactive oxygen species is often considered an unavoidable consequence of aerobic metabolism and currently cannot be manipulated without perturbing oxidative phosphorylation. Antioxidants are widely used to suppress effects of reactive oxygen species after formation, but they can never fully prevent immediate effects at the sites of production. To identify site-selective inhibitors of mitochondrial superoxide/H2O2 production that do not interfere with mitochondrial energy metabolism, we developed a robust small-molecule screen and secondary profiling strategy. We describe the discovery and characterization of a compound (N-cyclohexyl-4-(4-nitrophenoxy)benzenesulfonamide; CN-POBS) that selectively inhibits superoxide/H2O2 production from the ubiquinone-binding site of complex I (site I(Q)) with no effects on superoxide/H2O2 production from other sites or on oxidative phosphorylation. Structure/activity studies identified a core structure that is important for potency and selectivity for site I(Q). By employing CN-POBS in mitochondria respiring on NADH-generating substrates, we show that site I(Q) does not produce significant amounts of superoxide/H2O2 during forward electron transport on glutamate plus malate. Our screening platform promises to facilitate further discovery of direct modulators of mitochondrially derived oxidative damage and advance our ability to understand and manipulate mitochondrial reactive oxygen species production under both normal and pathological conditions. PMID:23994103

Orr, Adam L; Ashok, Deepthi; Sarantos, Melissa R; Shi, Tong; Hughes, Robert E; Brand, Martin D

2013-12-01

341

Stochastic voyages into uncharted chemical space produce a representative library of all possible drug-like compounds  

PubMed Central

The “small molecule universe” (SMU), the set of all synthetically feasible organic molecules of 500 Daltons molecular weight or less, is estimated to contain over 1060 structures, making exhaustive searches for structures of interest impractical. Here, we describe the construction of a “representative universal library” spanning the SMU that samples the full extent of feasible small molecule chemistries. This library was generated using the newly developed Algorithm for Chemical Space Exploration with Stochastic Search (ACSESS). ACSESS makes two important contributions to chemical space exploration: it allows the systematic search of the unexplored regions of the small molecule universe, and it facilitates the mining of chemical libraries that do not yet exist, providing a near-infinite source of diverse novel compounds.

Virshup, Aaron M.; Contreras-Garcia, Julia; Wipf, Peter; Yang, Weitao; Beratan, David N.

2013-01-01

342

Response of portable VOC (volatile organic compounds) analyzers to chemical mixtures. Final report Dec 80-May 81  

SciTech Connect

The report gives the responses of two types of portable VOC analyzers (Century Systems OVA-108 and Bacharach TLV Sniffer), calibrated with methane and used to measure a variety of chemical vapor mixtures. Instrument response data for both binary and ternary mixtures of selected chemicals are presented. Various empirical models were evaluated to determine an appropriate method of estimating mixture concentration based on instrument response. The evaluation concluded that the instrument response for a mixture falls between the responses expected for the pure compounds in the mixture. Thus, an interpolation or weighted average model can be used to predict the response for mixtures based on known responses for individual chemicals. Both linear and logarithmic weighted average models are applied to the data and presented with estimates of accuracy. In general, these models predicted the instrument response to within 30% of the observed value.

DuBose, D.A.; Brown, G.E.; Harris, G.E.

1981-06-01

343

Alternative Utilization of Processes for Anaerobic Digestion: Production of Combustible Liquids and Compound Chemicals.  

National Technical Information Service (NTIS)

The anaerobic digestion process can be utilized for the production of alternative compounds to biogas. Acidogenic fermentation can convert with high yields complex biomass feedstocks into a mixture of organic acids, which, after separation from the fermen...

G. Di Giorgio M. Gamboni A. R. Sprocati

1982-01-01

344

Investigation of the Chemical Identity of Soluble Organophosphorus Compounds Found in Natural Waters.  

National Technical Information Service (NTIS)

Four algal species (Chlamydomonas reinhardtii, Chlorella pyrenoidosa, Anacystis nidulans, and Anabaena flos-aquae) were grown in batch culture on 32p labelled media to yield dissolved organic phosphorus (DOP) compounds containing a radioactive tag. The DO...

R. A. Minear

1978-01-01

345

Metabolic footprinting: a new approach to identify physiological changes in complex microbial communities upon exposure to toxic chemicals.  

PubMed

Metabolic footprinting coupled with statistical analysis was applied to multiple, chemically stressed activated sludge cultures to identify probable biomarkers that indicate community stress. The impact of cadmium (Cd), 2,4-dinitrophenol (DNP), and N-ethyl-maleimide (NEM) shock loads on the composition of the soluble fraction of activated sludge cultures was analyzed by gross biomolecular analyses and liquid chromatography-mass spectrometry (LC-MS). Fresh mixed liquor from four distinct treatment plants was each divided in four different batches and was subjected to no chemical addition (control) and spike additions of the stressors Cd, DNP, or NEM. The results indicate that chemical stress caused a significant release of proteins, carbohydrates, and humic acids from the floc structure into the bulk liquid. Using discriminant function analysis (DFA) with genetic algorithm variable selection (GA-DFA), the samples subjected to the different stress conditions plus control could be differentiated, thereby indicating that the footprints of the soluble phase generated by LC-MS were different for the four conditions tested and, therefore, were toxin-specific but community-independent. These footprints, thus, contain information about specific biomolecular differences between the stressed samples, and we found that only a limited number of m/z (mass to charge) ratios from the mass spectra were needed to differentiate between the control and each stressed sample. Since the experiments were conducted with mixed liquor from four distinct wastewater treatment plants, the discriminant m/z ratios may potentially be used as universal stress biomarkers in activated sludge systems. PMID:17612173

Henriques, Inês D S; Aga, Diana S; Mendes, Pedro; O'Connor, Seamus K; Love, Nancy G

2007-06-01

346

Agents that stabilize mutated von Hippel-Lindau (VHL) protein: results of a high-throughput screen to identify compounds that modulate VHL proteostasis.  

PubMed

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that affects multiple organs. Treatment is mainly surgical, and effective systemic therapies are needed. We developed a cell-based screening tool to identify compounds that stabilize or upregulate full-length, point-mutated VHL protein. The 786-0 cell line was infected with full-length W117A-mutated VHL linked to a C-terminal Venus fluorescent protein. This VHL-W117A-Venus line was used to screen the Prestwick drug library and was tested against proteasome inhibitors MG132 and bortezomib. Western blot validation and evaluation of functional readouts, including hypoxia-inducible factor 2? (HIF2?) and glucose transporter 1 (Glut1) levels, were performed. We found that bortezomib, MG132, and the Prestwick compounds 8-azaguanine, thiostrepton, and thioguanosine upregulated VHL-W117A-Venus in 786-0 cells. 8-Azaguanine downregulated HIF2? levels and was augmented by the presence of VHL W117A. VHL p30 band intensities varied as a function of compound used, suggesting alternate posttranslational processing. Nuclear-cytoplasmic localization of VHL-W117A-Venus varied among the different compounds. In conclusion, a 786-0 cell line containing VHL-W117A-Venus was successfully used to identify compounds that upregulate VHL levels, with differential effect on VHL intracellular localization and posttranslational processing. Further screening efforts will broaden the number of pharmacophores available to develop therapeutic agents that will upregulate and refunctionalize mutated VHL. PMID:22357874

Ding, Zhiyong; German, Peter; Bai, Shanshan; Feng, Zhehui; Gao, Meng; Si, Wendy; Sobieski, Mary M; Stephan, Clifford C; Mills, Gordon B; Jonasch, Eric

2012-06-01

347

Transport of chemical and microbial compounds from known wastewater discharges: Potential for use as indicators of human fecal contamination  

USGS Publications Warehouse

The quality of drinking and recreational water is currently (2005) determined using indicator bacteria. However, the culture tests used to analyze forthese bacteria require a long time to complete and do not discriminate between human and animal fecal material sources. One complementary approach is to use chemicals found in human wastewater, which would have the advantages of (1) potentially shorter analysis times than the bacterial culture tests and (2) being selected for human-source specificity. At 10 locations, water samples were collected upstream and at two successive points downstream from a wastewaster treatment plant (WWTP); a treated effluent sample was also collected at each WWTP. This sampling plan was used to determine the persistence of a chemically diverse suite of emerging contaminants in streams. Samples were also collected at two reference locations assumed to have minimal human impacts. Of the 110 chemical analytes investigated in this project, 78 were detected at least once. The number of compounds in a given sample ranged from 3 at a reference location to 50 in a WWTP effluent sample. The total analyte load at each location varied from 0.018 ??g/L at the reference location to 97.7 ??g/L in a separate WWTP effluent sample. Although most of the compound concentrations were in the range of 0.01-1.0 ??g/L, in some samples, individual concentrations were in the range of 5-38 ??g/L The concentrations of the majority of the chemicals present in the samples generally followed the expected trend: they were either nonexistent or at trace levels in the upstream samples, had their maximum concentrations in the WWTP effluent samples, and then declined in the two downstream samples. This research suggests that selected chemicals are useful as tracers of human wastewater discharge. ?? 2005 American Chemical Society.

Glassmeyer, S. T.; Furlong, E. T.; Kolpin, D. W.; Cahill, J. D.; Zaugg, S. D.; Werner, S. L.; Meyer, M. T.; Kryak, D. D.

2005-01-01

348

Feasibility studies on newly identified LiCrP2O7 compound for lithium insertion behavior  

NASA Astrophysics Data System (ADS)

A new category of lithium intercalating cathode candidates, namely LiCrP2O7, was synthesized at 800°C using a citric acid assisted modified (CAM) sol-gel method and examined for possible lithium insertion behavior. The formation of a phase pure and monoclinic LiCrP2O7 compound with finer crystallite size was confirmed from the X-ray diffraction patterns. The presence of nano-sized particles as observed from a transmittance electron microscope image of LiCrP2O7 and the presence of a preferred local cation environment, evidenced from Fourier transform infra-red and 7Li nuclear magnetic resonance studies, are the added advantages of the present study. Further, cyclic voltametry study performed on 2016 coin cells consisting of the synthesized LiCrP2O7 cathode revealed an excellent cycling reversibility and structural stability. Hence, CAM sol-gel synthesized LiCrP2O7 is found to possess desirable physical as well as electrochemical properties, leading one to consider the same as a possible lithium intercalating cathode material.

Gangulibabu; Bhuvaneswari, D.; Kalaiselvi, N.

2009-08-01

349

Identification of Three Classes of Heteroaromatic Compounds with Activity against Intracellular Trypanosoma cruzi by Chemical Library Screening  

PubMed Central

The development of new drugs against Chagas disease is a priority since the currently available medicines have toxic effects, partial efficacy and are targeted against the acute phase of disease. At present, there is no drug to treat the chronic stage. In this study, we have optimized a whole cell-based assay for high throughput screening of compounds that inhibit infection of mammalian cells by Trypanosoma cruzi trypomastigotes. A 2000-compound chemical library was screened using a recombinant T. cruzi (Tulahuen strain) expressing ?-galactosidase. Three hits were selected for their high activity against T. cruzi and low toxicity to host cells in vitro: PCH1, NT1 and CX1 (IC50: 54, 190 and 23 nM, respectively). Each of these three compounds presents a different mechanism of action on intracellular proliferation of T. cruzi amastigotes. CX1 shows strong trypanocidal activity, an essential characteristic for the development of drugs against the chronic stage of Chagas disease where parasites are found intracellular in a quiescent stage. NT1 has a trypanostatic effect, while PCH1 affects parasite division. The three compounds also show high activity against intracellular T. cruzi from the Y strain and against the related kinetoplastid species Leishmania major and L. amazonensis. Characterization of the anti–T. cruzi activity of molecules chemically related to the three library hits allowed the selection of two compounds with IC50 values of 2 nM (PCH6 and CX2). These values are approximately 100 times lower than those of the medicines used in patients against T. cruzi. These results provide new candidate molecules for the development of treatments against Chagas disease and leishmaniasis.

Bettiol, Esther; Samanovic, Marie; Murkin, Andrew S.; Raper, Jayne; Buckner, Frederick; Rodriguez, Ana

2009-01-01

350

Screening Compounds with a Novel High-Throughput ABCB1-Mediated Efflux Assay Identifies Drugs with Known Therapeutic Targets at Risk for Multidrug Resistance Interference  

PubMed Central

ABCB1, also known as P-glycoprotein (P-gp) or multidrug resistance protein 1 (MDR1), is a membrane-associated multidrug transporter of the ATP-binding cassette (ABC) transporter family. It is one of the most widely studied transporters that enable cancer cells to develop drug resistance. Reliable high-throughput assays that can identify compounds that interact with ABCB1 are crucial for developing new therapeutic drugs. A high-throughput assay for measuring ABCB1-mediated calcein AM efflux was developed using a fluorescent and phase-contrast live cell imaging system. This assay demonstrated the time- and dose-dependent accumulation of fluorescent calcein in ABCB1-overexpressing KB-V1 cells. Validation of the assay was performed with known ABCB1 inhibitors, XR9576, verapamil, and cyclosporin A, all of which displayed dose-dependent inhibition of ABCB1-mediated calcein AM efflux in this assay. Phase-contrast and fluorescent images taken by the imaging system provided additional opportunities for evaluating compounds that are cytotoxic or produce false positive signals. Compounds with known therapeutic targets and a kinase inhibitor library were screened. The assay identified multiple agents as inhibitors of ABCB1-mediated efflux and is highly reproducible. Among compounds identified as ABCB1 inhibitors, BEZ235, BI 2536, IKK 16, and ispinesib were further evaluated. The four compounds inhibited calcein AM efflux in a dose-dependent manner and were also active in the flow cytometry-based calcein AM efflux assay. BEZ235, BI 2536, and IKK 16 also successfully inhibited the labeling of ABCB1 with radiolabeled photoaffinity substrate [125I]iodoarylazidoprazosin. Inhibition of ABCB1 with XR9576 and cyclosporin A enhanced the cytotoxicity of BI 2536 to ABCB1-overexpressing cancer cells, HCT-15-Pgp, and decreased the IC50 value of BI 2536 by several orders of magnitude. This efficient, reliable, and simple high-throughput assay has identified ABCB1 substrates/inhibitors that may influence drug potency or drug-drug interactions and predict multidrug resistance in clinical treatment.

Ansbro, Megan R.; Shukla, Suneet; Ambudkar, Suresh V.; Yuspa, Stuart H.; Li, Luowei

2013-01-01

351

Isolation and Chemical Structural Characterisation of a Compound with Antioxidant Activity from the Roots of Senna italica  

PubMed Central

Senna italica, a member of the Fabaceae family (subfamily Caesalpiniaceae), is widely used in South African traditional medicine to treat a number of disease conditions. Aqueous extracts of the plant are mainly used to treat sexually transmitted infections and intestinal complications. The roots of S. italica were ground to a fine powder and sequentially extracted with n-hexane, dichloromethane, acetone, and methanol using serial exhaustive extraction (SEE) method. Thin layer chromatography was used to analyse the phytochemical composition of the extracts and DPPH radical scavenging method to detect the presence of antioxidant compounds. The bioassay guided fractionation of the acetone fraction afforded an antioxidant compound with free radical scavenging activity. The isolated compound was subsequently identified as 3,4?,5-trihydroxystilbene (resveratrol). This study represents the first report of the stilbene resveratrol in S. italica.

Mokgotho, Matlou Phineas; Gololo, Stanley Sechene; Masoko, Peter; Shai, Leshwene Jeremiah; Bagla, Victor Patrick; Eloff, Jacobus Nicolaas

2013-01-01

352

Evaluation of an evanescent fiber optic chemical sensor for monitoring aqueous volatile organic compounds.  

National Technical Information Service (NTIS)

Linear chemometric algorithms were used to model the quantitative response of an evanescent fiber optic chemical sensor in aqueous mixtures with concentrations between 20 and 300 ppm. Four data sets were examined with two different experimental arrangemen...

D. S. Blair

1997-01-01

353

Some Chemical and Structural Factors Related to the Metastabilities of Energetic Compounds.  

National Technical Information Service (NTIS)

We have presented an overview of various attempts to relate the impact and shock sensitivities of energetic materials to their molecular structures. The objectives of such efforts are to better understand the chemical and structural determinants of these ...

P. Politzer J. S. Murray

1998-01-01

354

ANALYSIS OF SOCMI (SYNTHETIC ORGANIC CHEMICAL MANUFACTURING INDUSTRY) VOC (VOLATILE ORGANIC COMPOUND) FUGITIVE EMISSIONS DATA  

EPA Science Inventory

The report gives results of an examination of fugitive emission data from Synthetic Organic Chemical Manufacturing Industry (SOCMI) processing units (Collected under earlier EPA studies) for correlations between process variables and leak frequency. Although line temperature did ...

355

EXPOSURE-DOSE-EFFECT LINKAGES FOR CHEMICALLY REACTIVE AIR TOXIC COMPOUNDS  

EPA Science Inventory

This project represents a multidisciplinary collaboration to develop and test methods for more precisely predicting human exposure-dose-response relationships of respiratory tract irritants. These irritants have the unique property of reacting chemically with proteins and lipids ...

356

Chemical Probe Identification Platform for Orphan GPCRs Using Focused Compound Screening: GPR39 as a Case Example.  

PubMed

Orphan G protein-coupled receptors (oGPCRs) are a class of integral membrane proteins for which endogenous ligands or transmitters have not yet been discovered. Transgenic animal technologies have uncovered potential roles for many of these oGPCRs, providing new targets for the treatment of various diseases. Understanding signaling pathways of oGPCRs and validating these receptors as potential drug targets requires the identification of chemical probe compounds to be used in place of endogenous ligands to interrogate these receptors. A novel chemical probe identification platform was created in which GPCR-focused libraries were screened against sets of oGPCR targets, with a goal of discovering fit-for-purpose chemical probes for the more druggable members of the set. Application of the platform to a set of oGPCRs resulted in the discovery of the first reported small molecule agonists for GPR39, a receptor implicated in the regulation of insulin secretion and preservation of beta cells in the pancreas. Compound 1 stimulated intracellular calcium mobilization in recombinant and native cells in a GPR39-specific manner but did not potentiate glucose-stimulated insulin secretion in human islet preparations. PMID:24900608

Boehm, Markus; Hepworth, David; Loria, Paula M; Norquay, Lisa D; Filipski, Kevin J; Chin, Janice E; Cameron, Kimberly O; Brenner, Martin; Bonnette, Peter; Cabral, Shawn; Conn, Edward; Ebner, David C; Gautreau, Denise; Hadcock, John; Lee, Esther C Y; Mathiowetz, Alan M; Morin, Michelle; Rogers, Lucy; Smith, Aaron; VanVolkenburg, Maria; Carpino, Philip A

2013-11-14

357

Liquid chromatography, chemical oxidation, and online carbon isotope dilution mass spectrometry as a universal quantification system for nonvolatile organic compounds.  

PubMed

A procedure for the universal detection and quantification of polar organic compounds separated by liquid chromatography (LC) based on postcolumn carbon isotope dilution mass spectrometry (IDMS) was developed. The eluent from the LC column is mixed online with a continuous flow of (13)C-enriched sodium bicarbonate, and the sodium persulfate oxidation reaction in acidic media is employed to achieve isotope equilibration. All carbon-containing compounds eluting from the column are oxidized to (12)CO(2) and (13)CO(2), respectively, and the carbon dioxide is separated from the aqueous phase using a gas-permeable membrane. The gaseous carbon dioxide is then carried to the mass spectrometer for isotope ratio measurements. Different water-soluble organic compounds were evaluated using a flow injection configuration to assess the efficiency of the oxidation process. Most water-soluble organic compounds tested showed quantitative oxidation. However, chemical structures involving conjugated C?N double bounds and guanidinium-like structures were found to be resistant to the oxidation and were further studied. For this purpose, (13)C(1)-labeled creatine (with the isotopic label in the guanidinium group) was employed as model compound. Specific conditions for the quantitative oxidation of these compounds required lower flow rates and the addition of metallic catalysts. This novel approach was tested as a universal detection and quantification system for LC. A simple standard mixture of four amino acids was separated under 100% aqueous conditions and quantified without the need for specific standards with good accuracy and precision using potassium hydrogen phthalate as internal standard. The main field of application of the developed method is for the purity assessment of organic standards with direct traceability to the International System of Units (SI). PMID:23252800

Díaz, Sergio Cueto; Encinar, Jorge Ruiz; Sanz-Medel, Alfredo; Alonso, J Ignacio García

2013-02-01

358

The UV-filter benzophenone-1 inhibits 17?-hydroxysteroid dehydrogenase type 3: Virtual screening as a strategy to identify potential endocrine disrupting chemicals  

Microsoft Academic Search

The prevalence of male reproductive disorders and testicular cancer is steadily increasing. Because the exposure to chemicals disrupting natural hormone action has been associated with these diseases, it is important to identify endocrine disrupting chemicals (EDCs) and their targets of action. Here, a 3D-structural database that can be applied for virtual screening approaches to facilitate the identification of EDCs was

Lyubomir G. Nashev; Daniela Schuster; Christian Laggner; Seloni Sodha; Thierry Langer; Gerhard Wolber; Alex Odermatt

2010-01-01

359

Selective growth-inhibiting effects of compounds identified in Tabebuia impetiginosa inner bark on human intestinal bacteria.  

PubMed

The growth-inhibiting activity of anthraquinone-2-carboxylic acid and lapachol identified in the inner bark of taheebo, Tabebuia impetiginosa, toward 10 human intestinal bacteria was evaluated by using a paper disk diffusion bioassay and compared to those of seven lapachol congeners (1,4-naphthoquinone, naphthazarin, menadione, lawsone, plumbagin, juglone, and dichlone) as well as two commercially available antibiotics, chloramphenicol and tetracycline. Anthraquinone-2-carboxylic acid exhibited very strong growth inhibition of Clostridium paraputrificum at 1 microg/disk while 100 microg/disk of lapachol was needed for moderate growth inhibition of the same organism. These two isolates exhibited weak inhibition of Clostridium perfringens and Escherichia coli at 100 microg/disk while no adverse effects were observed on the growth of Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus acidophilus, and Lactobacillus casei at 1000 microg/disk. Structure-activity relationships indicate that a methyl group in the C-2 position of 1,4-naphthoquinone derivatives might play an important role in antibacterial activity. PMID:15713033

Park, Byeoung-Soo; Kim, Jun-Ran; Lee, Sung-Eun; Kim, Kyoung Soon; Takeoka, Gary R; Ahn, Young-Joon; Kim, Jeong-Han

2005-02-23

360

Potassium Tris (Oxalato) Ferrate (III): A Versatile Compound to Illustrate the Principles of Chemical Equilibria  

ERIC Educational Resources Information Center

The potassium salt is an easy product to synthesize in an introductory course on inorganic chemistry and the students are required to prepare this product in order to improve their laboratory skills and as an introduction to the synthesis of coordination compounds. The complex potassium tris (oxalato) ferrate (III) is used to illustrate the…

Gonzalez, Gabriel; Seco, Miquel

2004-01-01

361

A NOVEL ENERGY-EFFICIENT PLASMA CHEMICAL PROCESS FOR THE DESTRUCTION OF VOLATILE TOXIC COMPOUNDS  

EPA Science Inventory

Removal of low-concentrations (below several percent) of toxic volatile compounds from contaminated air streams is encountered at DOE waste sites in two instances:(i) off-gases resulting from air-stripping of contaminated soils and (ii) effluent from the incineration of highly-co...

362

Stachybotrin C and parvisporin, novel neuritogenic compounds. I. Taxonomy, isolation, physico-chemical and biological properties.  

PubMed

Stachybotrin C and parvisporin, novel neuritogenic compounds, were isolated from the culture broth of Stachybotrys parvispora F4708. Stachybotrin C induced significant neurite outgrowth in PC12 cells and showed cell survival activity in the primary culture of cerebral cortical neurons. Parvisporin demonstrated only weak neuritogenic activity. PMID:9315074

Nozawa, Y; Yamamoto, K; Ito, M; Sakai, N; Mizoue, K; Mizobe, F; Hanada, K

1997-08-01

363

EVALUATION OF THE SEMIVOST METHOD FOR HALOGENATED COMPOUNDS AT A CHEMICAL MANUFACTURING FACILITY  

EPA Science Inventory

A field test was conducted to determine the applicability of the SemiVOST method (SW-846 Method 0010 (Sampling), SW-846 Draft Method 3542 (Sample Preparation), and SW-846 Method 8270 (Analysis)) to semivolatile halogenated organic compounds listed in Title Ill of the 1990 Clean A...

364

ANALYSIS OF AMBIENT POLAR VOLATILE ORGANIC COMPOUNDS USING CHEMICAL IONIZATION -- ION TRAP DETECTOR  

EPA Science Inventory

The current approach to measuring trace levels of volatile organic compounds (VOCs) in ambient air requires cryogenic trapping of the analytes, followed by thermal desorption and low-temperature refocussing onto a column for analysis by capillary gas chromatography/mass spectrome...

365

Chemical fractionation and analysis of organic compounds in process streams of low Btu gasifier effluents  

Microsoft Academic Search

Low Btu gas must be purified before it will be suitable for use in a turbine. Many cleanup devices have been used on the output stream of the stirred-bed gasifier at the Morgantown Energy Technology Center. Both vapor phase and particulate phase organic compounds were sampled at several locations in the purification process. The results indicate that the complex nature

R. L. Hanson; R. E. Royer; J. M. Benson; R. L. Carpenter; G. J. Newton; R. F. Henderson

1982-01-01

366

EFFECTS OF CHEMICAL SPECIATION ON THE MINERALIZATION OF ORGANIC COMPOUNDS BY MICROORGANISMS  

EPA Science Inventory

The mineralization of 1.0 to 100 ng/ml of four complexing compounds--oxalate, citrate, nitrilotriacetate (NTA), and ethylene diaminetetraacetate (EDTA)--was tested in media prepared according to equilibrium calculations by a computer program so that the H, Ca, Mg, Fe, or Al compl...

367

A combined impedance and AlphaLISA-based approach to identify anti-inflammatory and barrier-protective compounds in human endothelium.  

PubMed

Chronic inflammation is at least partially mediated by the chemokine-mediated attraction and by the adhesion molecule-directed binding of leukocytes to the activated endothelium. Therefore, it is therapeutically important to identify anti-inflammatory compounds able to control the interaction between leukocytes and the endothelial compartments of the micro- and macrocirculation. When testing novel drug candidates, it is, however, of the utmost importance to detect side effects, such as potential cytotoxic and barrier-disruptive activities. Indeed, minor changes in the endothelial monolayer integrity may increase the permeability of small blood vessels and capillaries, which, in extreme cases, can lead to edema development. Here, we describe the development of a high-throughput screening (HTS) platform, based on AlphaLISA technology, able to identify anti-inflammatory nontoxic natural or synthetic compounds capable of reducing tumor necrosis factor (TNF)-induced chemokine (interleukin [IL]-8) and adhesion molecule (ICAM-1) expression in human lung microvascular endothelial cells. Quantification of cell membrane-expressed ICAM-1 and of cell culture supernatant-associated levels of IL-8 was analyzed in HTS. In parallel, we monitored monolayer integrity and endothelial cell viability using the electrical cell substrate impedance sensing method. This platform allowed us to identify natural secondary metabolites from cyanobacteria, capable of reducing ICAM-1 and IL-8 levels in TNF-activated human microvascular endothelial cells in the absence of endothelial monolayer barrier disruption. PMID:22941294

Pflüger, Maren; Kapuscik, Aleksandra; Lucas, Rudolf; Koppensteiner, Anita; Katzlinger, Michael; Jokela, Jouni; Eger, Andreas; Jacobi, Nico; Wiesner, Christoph; Hofmann, Elisabeth; Onder, Kamil; Kopecky, Jiri; Schütt, Wolfgang; Hundsberger, Harald

2013-01-01

368

Anti-Prion Activity of a Panel of Aromatic Chemical Compounds: In Vitro and In Silico Approaches  

PubMed Central

The prion protein (PrP) is implicated in the Transmissible Spongiform Encephalopathies (TSEs), which comprise a group of fatal neurodegenerative diseases affecting humans and other mammals. Conversion of cellular PrP (PrPC) into the scrapie form (PrPSc) is the hallmark of TSEs. Once formed, PrPSc aggregates and catalyzes PrPC misfolding into new PrPSc molecules. Although many compounds have been shown to inhibit the conversion process, so far there is no effective therapy for TSEs. Besides, most of the previously evaluated compounds failed in vivo due to poor pharmacokinetic profiles. In this work we propose a combined in vitro/in silico approach to screen for active anti-prion compounds presenting acceptable drugability and pharmacokinetic parameters. A diverse panel of aromatic compounds was screened in neuroblastoma cells persistently infected with PrPSc (ScN2a) for their ability to inhibit PK-resistant PrP (PrPRes) accumulation. From ?200 compounds, 47 were effective in decreasing the accumulation of PrPRes in ScN2a cells. Pharmacokinetic and physicochemical properties were predicted in silico, allowing us to obtain estimates of relative blood brain barrier permeation and mutagenicity. MTT reduction assays showed that most of the active compounds were non cytotoxic. Compounds that cleared PrPRes from ScN2a cells, were non-toxic in the MTT assay, and presented a good pharmacokinetic profile were investigated for their ability to inhibit aggregation of an amyloidogenic PrP peptide fragment (PrP109–149). Molecular docking results provided structural models and binding affinities for the interaction between PrP and the most promising compounds. In summary, using this combined in vitro/in silico approach we have identified new small organic anti-scrapie compounds that decrease the accumulation of PrPRes in ScN2a cells, inhibit the aggregation of a PrP peptide, and possess pharmacokinetic characteristics that support their drugability. These compounds are attractive candidates for prion disease therapy.

Ferreira, Natalia C.; Marques, Icaro A.; Conceicao, Wesley A.; Macedo, Bruno; Machado, Clarice S.; Mascarello, Alessandra; Chiaradia-Delatorre, Louise Domeneghini; Yunes, Rosendo Augusto; Nunes, Ricardo Jose; Hughson, Andrew G.; Raymond, Lynne D.; Pascutti, Pedro G.; Caughey, Byron; Cordeiro, Yraima

2014-01-01

369

A novel energy-efficient plasma chemical process for the destruction of volatile toxic compounds. 1997 annual progress report  

SciTech Connect

'The objective of this research program is to develop new plasma chemical processes for the destruction of volatile toxic compounds (VTCs) in contaminated air streams where the contamination levels are below a few percent. The authors plan to exploit the large cross sections associated with dissociative electron attachment to highly excited molecular states. Such highly excited states are to be populated in glow discharges via excitation transfer from high- lying, metastable states of rare gases. Basic knowledge of the excitation transfer processes and the electron attachment processes are crucial to the development of the proposed techniques, and these processes will be studied in detail.'

Pinnaduwage, L.A.; Ma, C.Y.L.

1997-09-01

370

Chemicals identified in feral and food animals: a data base. Volume II. Records 533-1515. Second annual report, October 1982  

SciTech Connect

A comprehensive data base of chemicals identified in feral and food animals has been established. This effort has grown out of the concern over continuing reports of toxic chemicals in human tissues and body fluids. Feral populations and food animals are regarded as indicators of environmental contamination and subsequent human body burden. This data file is a companion to Chemicals Identified in Human Biological Media, A Data Base, and follows basically the same format. Data were obtained primarily from the open literature through manual searches (retrospective to 1979). The data base contains information on 134 different substances.

Cone, M.V.; Faust, R.A.; Baldauf, M.F. (comps.)

1982-12-01

371

TOXICOGENOMIC STUDY OF TRIAZOLE FUNGICIDES AND PERFLUOROALKYL ACIDS IN RAT LIVERS ACCURATELY CATEGORIZES CHEMICALS AND IDENTIFIES MECHANISMS OF TOXICITY  

EPA Science Inventory

Toxicogenomic analysis of five environmental chemicals was performed to investigate the ability of genomics to predict toxicity, categorize chemicals, and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole, and triadimefon) and two perfluori...

372

Stimulation of Ideas through Compound-Based Bibliometrics: Counting and Mapping Chemical Compounds for Analyzing Research Topics in Chemistry, Physics, and Materials Science  

PubMed Central

Counting compounds (rather than papers or citations) offers a new perspective for quantitative analyses of research activities. First of all, we can precisely define (compound-related) research topics and access the corresponding publications (scientific papers as well as patents) as a measure of research activity. We can also establish the time evolution of the publications dealing with specific compounds or compound classes. Moreover, the mapping of compounds by establishing compound-based landscapes has some potential to visualize the compound basis of research topics for further research activities. We have analyzed the rare earth compounds to give an example of a broad compound class. We present the number of the currently existing compounds and of the corresponding publications as well as the time evolution of the papers and patents. Furthermore, we have analyzed the rare earth cuprates (copper oxides) as an example of a narrower compound class to demonstrate the potential of mapping compounds by compound-based landscapes. We have quantified the various element combinations of the existing compounds and revealed all element combinations not yet realized in the synthesis within this compound class. Finally, we have analyzed the quasicrystal compound category as an example of a compound class that is not defined by a specific element combination or a molecular structure.

Barth, Andreas; Marx, Werner

2012-01-01

373

Stimulation of Ideas through Compound-Based Bibliometrics: Counting and Mapping Chemical Compounds for Analyzing Research Topics in Chemistry, Physics, and Materials Science.  

PubMed

Counting compounds (rather than papers or citations) offers a new perspective for quantitative analyses of research activities. First of all, we can precisely define (compound-related) research topics and access the corresponding publications (scientific papers as well as patents) as a measure of research activity. We can also establish the time evolution of the publications dealing with specific compounds or compound classes. Moreover, the mapping of compounds by establishing compound-based landscapes has some potential to visualize the compound basis of research topics for further research activities. We have analyzed the rare earth compounds to give an example of a broad compound class. We present the number of the currently existing compounds and of the corresponding publications as well as the time evolution of the papers and patents. Furthermore, we have analyzed the rare earth cuprates (copper oxides) as an example of a narrower compound class to demonstrate the potential of mapping compounds by compound-based landscapes. We have quantified the various element combinations of the existing compounds and revealed all element combinations not yet realized in the synthesis within this compound class. Finally, we have analyzed the quasicrystal compound category as an example of a compound class that is not defined by a specific element combination or a molecular structure. PMID:24551517

Barth, Andreas; Marx, Werner

2012-12-01

374

Predicting physical properties of emerging compounds with limited physical and chemical data: QSAR model uncertainty and applicability to military munitions.  

PubMed

Reliable, up-front information on physical and biological properties of emerging materials is essential before making a decision and investment to formulate, synthesize, scale-up, test, and manufacture a new material for use in both military and civilian applications. Multiple quantitative structure-activity relationships (QSARs) software tools are available for predicting a material's physical/chemical properties and environmental effects. Even though information on emerging materials is often limited, QSAR software output is treated without sufficient uncertainty analysis. We hypothesize that uncertainty and variability in material properties and uncertainty in model prediction can be too large to provide meaningful results. To test this hypothesis, we predicted octanol water partitioning coefficients (logP) for multiple, similar compounds with limited physical-chemical properties using six different commercial logP calculators (KOWWIN, MarvinSketch, ACD/Labs, ALogP, CLogP, SPARC). Analysis was done for materials with largely uncertain properties that were similar, based on molecular formula, to military compounds (RDX, BTTN, TNT) and pharmaceuticals (Carbamazepine, Gemfibrizol). We have also compared QSAR modeling results for a well-studied pesticide and pesticide breakdown product (Atrazine, DDE). Our analysis shows variability due to structural variations of the emerging chemicals may be several orders of magnitude. The model uncertainty across six software packages was very high (10 orders of magnitude) for emerging materials while it was low for traditional chemicals (e.g. Atrazine). Thus the use of QSAR models for emerging materials screening requires extensive model validation and coupling QSAR output with available empirical data and other relevant information. PMID:19793608

Bennett, Erin R; Clausen, Jay; Linkov, Eugene; Linkov, Igor

2009-11-01

375

Chemical characterization and mutagenic properties of polycyclic aromatic compounds in sediment from tributaries of the Great Lakes  

USGS Publications Warehouse

Sediments from four inshore industrial sites and a reference site in the Great Lakes were extracted with solvents and characterized chemically for polycyclic aromatic compounds (PACs). An aqueous phase and a crude organic extract were obtained. The crude organic extract was further resolved into fractions A-2 (polycyclic aromatic hydrocarbons) and A-3 (nitrogen-containing polycyclic aromatic compounds), which were analyzed for PACs by gas chromatography and gas chromatography-mass spectrometry. The extracts and fractions were tested for mutagenicity in three assays: Ames, rat hepatocyte unscheduled DNA synthesis, and Chinese hamster ovary hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT). Sediments from the industrial sites contained 27 to 363 I?g/g total PACs; the reference site, less than 1 I?g/g. Qualitative differences in the residue profiles among the sites were attributable to the probable sources of the PACs (petroleum versus combustion). Only one industrial site yielded measurable (0.1 I?g/g or more) concentrations of individual nitrogen-containing PACs. In the Ames assay, only the highest doses of the A-2 fractions from two sites approached positive results. Conversely, the crude organic extract and A-2 and A-3 fractions from all sites induced unscheduled DNA synthesis. Crude organic extracts and the A-2 and A-3 fractions from all industrial sites gave well-defined dose-response relations in the CHO/HGPRT assay. We established the presence of chemical mutagens in sediment that could be correlated with neoplasms in fish from many of the sites; however, the mutagenicity of the sediment extracts was not completely related to the degree of contamination by PACs. We also discuss the utility of mutagenicity assays in the evaluation of complex chemical mixtures and the presence of potential interfering chemicals.

Fabacher, David L.; Schmitt, Christopher J.; Besser, John M.; Mac, Michael J.

1988-01-01

376

Identifying and quantifying secondhand smoke in source and receptor rooms: logistic regression and chemical mass balance approaches.  

PubMed

Identifying and quantifying secondhand tobacco smoke (SHS) that drifts between multiunit homes is critical to assessing exposure. Twenty-three different gaseous and particulate measurements were taken during controlled emissions from smoked cigarettes and six other common indoor source types in 60 single-room and 13 two-room experiments. We used measurements from the 60 single-room experiments for (i) the fitting of logistic regression models to predict the likelihood of SHS and (ii) the creation of source profiles for chemical mass balance (CMB) analysis to estimate source apportionment. We then applied these regression models and source profiles to the independent data set of 13 two-room experiments. Several logistic regression models correctly predicted the presence of cigarette smoke more than 80% of the time in both source and receptor rooms, with one model correct in 100% of applicable cases. CMB analysis of the source room provided significant PM2.5 concentration estimates of all true sources in 9 of 13 experiments and was half-correct (i.e., included an erroneous source or missed a true source) in the remaining four. In the receptor room, CMB provided significant estimates of all true sources in 9 of 13 experiments and was half-correct in another two. PMID:23631597

Dacunto, P J; Cheng, K-C; Acevedo-Bolton, V; Jiang, R-T; Klepeis, N E; Repace, J L; Ott, W R; Hildemann, L M

2014-02-01

377

Standardization of alumina and silica adsorbents used for chemical class separations of polycyclic aromatic compounds  

Microsoft Academic Search

The reproducibility of separating polycyclic aromatic compounds (PAC) by adsorption chromatography is known to be a function of the adsorbent's activity, i.e., water content. In this work, a multiple-point R° calibration curve (equivalent retention volume vs. adsorbent activity) was constructed by using a model solute\\/solvent system (naphthalene\\/hexane) for two commonly used adsorbents. The optimum activities for neutral alumina and silicic

Douglas W. Later; Bary W. Wilson; Milton L. Lee

1985-01-01

378

Attomole detection of isotope-labeled compounds in chemical defense research  

Microsoft Academic Search

AMS detects 14C at zeptomole to femtomole sensitivities. We detected the effect of ChE-blocking pyridostigmine bromide on the CNS uptake of a pyrethroid insecticide at scaled human-equivalent exposures in rats. Significant blood to brain protection from permethrin dosed at 5mg\\/kg is seen in the CNS of rats receiving pyridostigmine bromide pretreatments in chow at 2mg\\/kg\\/day. The synergy of these compounds

J. S. Vogel; B. A. Buchholz; N. H. Pawley; R. E. Mauthe; K. Dingley; K. Turteltaub

1996-01-01

379

Chemical synthesis of hydraulic calcium aluminate compounds using the Pechini technique  

Microsoft Academic Search

3CaO·Al2O3 and 4CaO·Al2O3·Fe2O3 are two of the main compounds in portland cement and are conventionally prepared by sintering the solid oxide mixture above 1350°C for many hours. The Pechini technique is a polymeric precursor route for the synthesis of ceramics. In this work, an equimolar mixture of C3A and C4AF was prepared by the Pechini technique. The preparation of the

A. Gaki; R. Chrysafi; G. Kakali

2007-01-01

380

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

Microsoft Academic Search

The volatile organic compound (VOC) distribution in the Mexico City Metropolitan Area (MCMA) and its evolution as it is uplifted and transported out of the MCMA basin was studied during the 2006 MILAGRO\\/MIRAGE-Mex field campaign. The results show that in the morning hours in the city center, the VOC distribution is dominated by non-methane hydrocarbons (NMHCs) but with a substantial

E. C. Apel; L. K. Emmons; T. Karl; F. Flocke; A. J. Hills; S. Madronich; J. Lee-Taylor; A. Fried; P. Weibring; J. Walega; D. Richter; X. Tie; L. Mauldin; T. Campos; B. Sive; L. Kleinman; S. Springston; R. Zaveri; J. Ortega; P. Voss; D. Blake; A. Baker; C. Warneke; D. Welsh-Bon; J. de Gouw; J. Zheng; R. Zhang; J. Rudolph; W. Junkermann; D. D. Riemer

2009-01-01

381

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

Microsoft Academic Search

The volatile organic compound (VOC) distribution in the Mexico City Metropolitan Area (MCMA) and its evolution as it is uplifted and transported out of the MCMA basin was studied during the 2006 MILAGRO\\/MIRAGE-Mex field campaign. The results show that in the morning hours in the city center, the VOC distribution is dominated by non-methane hydrocarbons (NMHCs) but with a substantial

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

2010-01-01

382

Chemical mutagenesis testing in Drosophila. IX. Results of 50 coded compounds tested for the National Toxicology Program.  

PubMed

Fifty chemicals were tested for mutagenic activity in post-meiotic and meiotic germ cells of male Drosophila melanogaster using the sex-linked recessive lethal (SLRL) assay. As in the previous studies in this series, feeding was chosen as the first route of administration. If the compound failed to induce mutations by this route, injection exposure was used. One gaseous chemical (1,3-butadiene) was tested only by inhalation. Those chemicals that were mutagenic in the sex-linked recessive lethal assay were further tested for the ability to induce reciprocal translocations. Eleven of the 50 chemicals tested were mutagenic in the SLRL assay. These included bis(2-chloroethyl) ether, 1,4-butanediol diglycidyl ether, 1-chloro-2-propanol, dimethyl methylphosphonate, dimethyl morpholinophosphoramidate, dimethyloldihydroxyethylene urea, 2,2-dimethyl vinyl chloride, hexamethylphosphoramide, isatin-5-sulfonic acid (Na salt), isopropyl glycidyl ether, and urethane. Five of these, including 1,4-butanediol diglycidyl ether, 2,2-dimethyl vinyl chloride, hexamethylphosphoramide, isopropyl glycidyl ether, and urethane, also induced reciprocal translocations. PMID:8125083

Foureman, P; Mason, J M; Valencia, R; Zimmering, S

1994-01-01

383

Preliminary Lists of PFOS, PFAS, PFOA and Related Compounds and Chemicals that May Degrade to PFCA  

Microsoft Academic Search

The OECD conducted a survey in 2004 on Perfluorooctane Sulfonate (PFOS), Perfluoroalkyl Sulfonate (PFAS), Perfluorooctanoic Acid (PFOA), related substances and products\\/mixtures containing these substances within OECD and non-OECD member countries. The information sought were quantities manufactured or imported, concentration of the chemicals in the products or mixtures, uses, use in consumer products, availability of alternatives or substitutes and essential uses

2006-01-01

384

Ultrafast magnetization dynamics in Co-based Heusler compounds with tuned chemical ordering  

NASA Astrophysics Data System (ADS)

We have studied thin film samples of C{{o}_{2}}FeSi and C{{o}_{2}}MnSi with different degrees of chemical ordering using the time-resolved magneto-optical Kerr effect to elucidate the influence of defects in the crystal structure on magnetization dynamics. Surprisingly, we find that the presence of defects does not influence the optically induced magnetization dynamics on the ultrashort timescale (some 100 fs). However, we observe a second demagnetization stage with a timescale of tens of picoseconds in C{{o}_{2}}MnSi for low chemical ordering; that is, a large number of defects. We interpret this second demagnetization step as originating from scattering of mostly thermalized majority electrons into unoccupied minority defect states.

Steil, D.; Schmitt, O.; Fetzer, R.; Kubota, T.; Naganuma, H.; Oogane, M.; Ando, Y.; Suszka, A. K.; Idigoras, O.; Wolf, G.; Hillebrands, B.; Berger, A.; Aeschlimann, M.; Cinchetti, M.

2014-06-01

385

In silico identification of novel lead compounds with AT1 receptor antagonist activity: successful application of chemical database screening protocol  

PubMed Central

Background AT1 receptor antagonists are clinically effective drugs for the treatment of hypertension, cardiovascular, and related disorders. In an attempt to identify new AT1 receptor antagonists, a pharmacophore-based virtual screening protocol was applied. The pharmacophore models were generated from 30 training set compounds. The best model was chosen on the basis of squared correlation coefficient of training set and internal test set. The validity of the developed model was also ensured using catScramble validation method and external test set prediction. Results The final model highlighted the importance of hydrogen bond acceptor, hydrophobic aliphatic, hydrophobic, and ring aromatic features. The model satisfied all the statistical criteria such as cost function analysis and correlation coefficient. The result of estimated activity for internal and external test set compounds reveals that the generated model has high prediction capability. The validated pharmacophore model was further used for mining of 56000 compound database (MiniMaybridge). Total 141 hits were obtained and all the hits were checked for druggability, this led to the identification of two active druggable AT1 receptor antagonists with diverse structure. Conclusion A highly validated pharmacophore model generated in this study identified two novel druggable AT1 receptor antagonists. The developed model can also be further used for mining of other virtual database.

2012-01-01

386

Chemical reactivities of hafnium and its derived boride, carbide and nitride compounds at relatively mild temperature  

Microsoft Academic Search

MB2\\/SiC composites are materials of choice for ultra-high-temperature structural applications, primarily in the aerospace arena. These composites are processed in a hot-press operation at a temperature range of 1900 to 2200°C. This article assesses potential “mild-temperature” (below 1500°C) chemical reactions that may lead to structures and coatings made of HfB2\\/SiC under pressureless or mild-pressure conditions. The reactions are anticipated to

Y. D. Blum; H.-J. Kleebe

2004-01-01

387

Analysis of gas phase compounds in chemical vapor deposition of carbon from light hydrocarbons  

Microsoft Academic Search

Product distributions in the pyrolysis of ethylene, acetylene, and propylene are studied to obtain an experimental database for a detailed kinetic modeling of gas phase reactions in chemical vapor deposition of carbon from these light hydrocarbons. Experiments were performed with a vertical flow reactor at 900°C and pressures from 2 to 15kPa. Gas phase components were analyzed by both on-line

Koyo Norinaga; Olaf Deutschmann; Klaus J. Hüttinger

2006-01-01

388

Electrochemical stabilization of porous silicon multilayers for sensing various chemical compounds  

Microsoft Academic Search

Porous silicon rugate filters are fabricated and investigated for their ability to sense chemical species. The durability of the filter is tested by allowing the structure to undergo many cycles of adsorption and desorption of vapor-phase ethanol molecules. The characteristic reflectivity peak of the structure exhibits a relative blueshift of 2.7% after 86 adsorption\\/desorption cycles. The observed shift is ascribed

M. S. Salem; M. J. Sailor; F. A. Harraz; T. Sakka; Y. H. Ogata

2006-01-01

389

Electrochemical stabilization of porous silicon multilayers for sensing various chemical compounds  

Microsoft Academic Search

Porous silicon rugate filters are fabricated and investigated for their ability to sense chemical species. The durability of the filter is tested by allowing the structure to undergo many cycles of adsorption and desorption of vapor-phase ethanol molecules. The characteristic reflectivity peak of the structure exhibits a relative blueshift of 2.7% after 86 adsorption?desorption cycles. The observed shift is ascribed

M. S. Salem; M. J. Sailor; F. A. Harraz; T. Sakka; Y. H. Ogata

2006-01-01

390

Preliminary chemical characterization of particle-phase organic compounds in New Delhi, India  

Microsoft Academic Search

This work describes a pilot study for the investigation of the chemical composition of organic species present in PM10 collected at a residential site in New Delhi during December 2001–March 2002, and in TSP emissions from in-use two-stroke vehicles. Both ambient and emissions samples were analyzed using gas chromatography-mass spectrometry (GC-MS), with an emphasis on quantification of non-volatile polycyclic aromatic

Dhruv N Sharma; Aniket A Sawant; R Uma; David R Cocker

2003-01-01

391

Attomole detection of isotope-labeled compounds in chemical defense research  

SciTech Connect

AMS detects 14C at zeptomole to femtomole sensitivities. We detected the effect of ChE-blocking pyridostigmine bromide on the CNS uptake of a pyrethroid insecticide at scaled human-equivalent exposures in rats. Significant blood to brain protection from permethrin dosed at 5mg/kg is seen in the CNS of rats receiving pyridostigmine bromide pretreatments in chow at 2mg/kg/day. The synergy of these compounds was suggested as a precursor to some symptoms of `Gulf War Syndrome`.

Vogel, J.S.; Buchholz, B.A.; Pawley, N.H.; Mauthe, R.E.; Dingley, K.; Turteltaub, K.

1996-11-01

392

Physico-chemical transformations of sulfated compounds during the leaching of highly sulfated cemented wastes  

SciTech Connect

Cementation of sulfated evaporator concentrates leads to highly sulfated low level wastes, (ca. 25% w/w sodium sulfate solution as mix water), which exhibit the presence of U-phase, a sodium-bearing calcium monosulfphoaluminate-like phase. During the leaching of simulated highly sulfated OPC/BFS cements, cured at room temperature and containing U-phase, sodium sulfate, and ettringite, physico-chemical transformations have been pointed out (transformation of U-phase into ettringite). Samples having the same chemical composition, but cured at high temperature (maximal temperature during curing: 120 C), do not contain ettringite initially, but secondary ettringite is formed during leaching. XRD spectra point out the existence of precipitation fronts (or of phase formation fronts) varying linearly versus the square root of time. The analysis of leaching solutions has provided complementary data used in a code, the aim of which is to assess cement degradation, based on coupling between transport by diffusion and chemical reactions (DIFFUZON code). The U-phase-ettringite transformation is confirmed.

Lovera, P.; Bescop, P. le; Adenot, F. [CEA Centre de`Etudes de Saclay, Gif/Yvette (France)] [CEA Centre de`Etudes de Saclay, Gif/Yvette (France); Li, G. [CEA Centre d`Etudes de Saclay, Gif/Yvette (France)] [CEA Centre d`Etudes de Saclay, Gif/Yvette (France); [Ecole Normale Superieure de Cachan (France). Lab. de Mecanique et de Technologie; Tanaka, Y. [Japan Nuclear Fuel Ltd., Tokyo (Japan)] [Japan Nuclear Fuel Ltd., Tokyo (Japan); Owaki, E. [Taisei Corp., Yokohama (Japan). Technology Research Center] [Taisei Corp., Yokohama (Japan). Technology Research Center

1997-10-01

393

Chemical composition and antioxidant effect of glycosidically bound volatile compounds from oregano ( Origanum vulgare L. ssp. hirtum)  

Microsoft Academic Search

The present work examines the content and chemical composition of the glycosidically bound volatiles from oregano as well as their antioxidative properties. The glycosidically bound volatiles amounted to 20 mg kg?1 in dried leaves and flowers of oregano. Fourteen volatile aglycones were identified with thymoquinone as the major component. Other important aglycones were benzyl alcohol, eugenol, 2-phenyl-ethanol, thymol, 3-hexen-1-ol and

M Milos; J Mastelic; I Jerkovic

2000-01-01

394

Chemically modified siRNAs and miRNAs bearing urea/thiourea-bridged aromatic compounds at their 3'-end for RNAi therapy.  

PubMed

We have developed chemically modified siRNAs and miRNAs bearing urea/thiourea-bridged aromatic compounds at their 3'-end for RNAi therapy. Chemically modified RNAs possessing urea/thiourea-bridged aromatic compounds instead of naturally occurring dinucleotides at the 3'-overhang region were easily prepared in good yields and were more resistant to nucleolytic hydrolysis than unmodified RNA. siRNAs containing urea or thiourea derivatives showed the desired knockdown effect. Furthermore, modified miR-143 duplexes carrying the urea/thiourea compounds in the 3'-end of each strand were able to inhibit the growth of human bladder cancer T24 cells. PMID:23791869

Kitamura, Yoshiaki; Masegi, Yuki; Ogawa, Shunsuke; Nakashima, Remi; Akao, Yukihiro; Ueno, Yoshihito; Kitade, Yukio

2013-08-01

395

Effect of Chemical Reactions of Compounds of an Analyte Element on Characteristic Features of Its Injection into an Electrical Discharge Plasma  

NASA Astrophysics Data System (ADS)

A mathematical model is proposed for the process of injection of material from a sample of limited weight into a discharge plasma in atomic emission spectral analysis, taking into account the occurrence of chemical reactions involving compounds of the analyte element. The effect of formation of new compounds of the analyte element on the nature of injection of this element into the discharge plasma is studied for different parameters of the processes occurring. Results are presented from experimental studies of processes of injection of an element when its compounds undergo chemical reactions during analysis.

Frantskevich, K. V.

2014-03-01

396

Identification of polycyclic aromatic compounds containing two heteroatoms in coal liquids and shale oils. Technical progress report, March 1, 1983-October 31, 1985. [More tran 200 compounds identified and synthesized; ring structure given  

SciTech Connect

The methodology has been developed for isolating and identifying components of five new classes of PAC in coal liquids. The methods have been applied to one coal liquid (and a coal tar for comparison). The major contributions of this work to DOE health and environmental science issues are as follows: (a) A superior sulfur heterocycle isolation method, based on ligand exchange chromatography, has been developed. (b) Methods have been developed using adsorption chromatography and gas chromatographic selective detection to isolate, detect, identify, and quantify the amino sulfur heterocycles, the amino nitrogen heterocycles, the hydroxy sulfur heterocycles, the hydroxy nitrogen heterocycles, and the azathiophenic compounds in coal-derived materials. (c) A large number of standard reference compounds have been synthesized. (d) Two new gas chromatographic stationary phases have been applied to the resolution of these isomeric PAC. (e) The aminodibenzothiophenes have been found to possess significant mutagenic activity in the Ames Assay. (f) A fractionation method for PAC based on the number of aromatic rings using supercritical carbon dioxide has been developed. Recommendations for future work in this area are given. 68 refs.

Lee, M.L.; Castle, R.N.

1985-01-01

397

Hiding in plain sight: cuticular compound profile matching conceals a larval tortoise beetle in its host chemical cloud.  

PubMed

Larvae of tortoise beetles are postulated to have fecal shields as the main defensive strategy against predators. Such a device protects beetles both physically and chemically. In order to examine how larvae Chelymorpha reimoseri are protected against predatory ants, which frequently visit extrafloral nectaries in their host plant, the morning glory Ipomoea carnea, we conducted anti-predation bioassays with live 5th instars. In the field, larvae in contact with ants had survival between 40 and 73 %, independently of shield presence. In the laboratory, when exposed to Camponotus crassus, larvae with shields had significantly higher survival (85 %) than those without shields (64 %). In both scenarios, larval survival was significantly higher when compared with palatable Spodoptera frugiperda larvae, as the latter were all consumed. We also observed that when C. reimoseri larvae showed no movement, the ants walked on them without attacking. We hypothesized that if the larval integument has a pattern of cuticular compounds (CCs) similar to that of its host plant, larvae would be rendered chemically camouflaged. In the field and laboratory, the freeze-dried palatable larvae of S. frugiperda treated with CCs of 5th instar C. reimoseri and left on I. carnea leaves were significantly less removed by ants than controls without these compounds. We also found a similarity of approximately 50 % between the CCs in C. reimoseri larvae and I. carnea host leaves. Both findings provide evidence in support of the hypothesis that chemical camouflage plays an important role in larval defense, which is reported for the first time in an ectophagous leaf beetle larva. PMID:24744044

Massuda, Kamila Ferreira; Trigo, José Roberto

2014-04-01

398

The application of discriminant analysis and Machine Learning methods as tools to identify and classify compounds with potential as transdermal enhancers.  

PubMed

Discriminant analysis (DA) has previously been shown to allow the proposal of simple guidelines for the classification of 73 chemical enhancers of percutaneous absorption. Pugh et al. employed DA to classify such enhancers into simple categories, based on the physicochemical properties of the enhancer molecules (Pugh et al., 2005). While this approach provided a reasonable accuracy of classification it was unable to provide a consistently reliable estimate of enhancement ratio (ER, defined as the amount of hydrocortisone transferred after 24h, relative to control). Machine Learning methods, including Gaussian process (GP) regression, have recently been employed in the prediction of percutaneous absorption of exogenous chemicals (Moss et al., 2009; Lam et al., 2010; Sun et al., 2011). They have shown that they provide more accurate predictions of these phenomena. In this study several Machine Learning methods, including the K-nearest-neighbour (KNN) regression, single layer networks, radial basis function networks and the SVM classifier were applied to an enhancer dataset reported previously. The SMOTE sampling method was used to oversample chemical compounds with ER>10 in each training set in order to improve estimation of GP and KNN. Results show that models using five physicochemical descriptors exhibit better performance than those with three features. The best classification result was obtained by using the SVM method without dealing with imbalanced data. Following over-sampling, GP gives the best result. It correctly assigned 8 of the 12 "good" (ER>10) enhancers and 56 of the 59 "poor" enhancers (ER<10). Overall success rates were similar. However, the pharmaceutical advantages of the Machine Learning methods are that they can provide more accurate classification of enhancer type with fewer false-positive results and that, unlike discriminant analysis, they are able to make predictions of enhancer ability. PMID:22101136

Moss, G P; Shah, A J; Adams, R G; Davey, N; Wilkinson, S C; Pugh, W J; Sun, Y

2012-01-23

399

Lysergic acid diethylamide antagonizes shaking induced in rats by five chemically different compounds  

Microsoft Academic Search

Thyrotropin-releasing hormone (TRH), sodium valproate, AG-3-5 (1-[2-hydroxyphenyl]-4-[3-nitrophenyl]-1,2,3,6-tetrahydropyrimidine-2-one), RX336-M (7,8-dihydro-5', 6'-dimethylcyclohex-5'-eno-1',2',8',14 codeinone), and Sgd 8473 (a-[(4-chlorobenzylideneamino)-oxy]-isobutyric acid) each induced repetitive shaking of the body of rats after intraperitoneal injection. This action of the five diverse chemicals appears to be subserved by a common pharmacological component, because pretreatment with d-lysergic acid diethylamide (0.03–1.0 mg kg-1, s.c.) attenuated the shaking behavior in a

Alan Cowan; Trevor Watson

1978-01-01

400

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

PubMed Central

In continuation of previous work sensitization experiments have been made with various substances such as urushiol, benzyl chlorides, and acyl chlorides. In the case of a series of substituted benzenes (Cl, NO2) a connection between sensitizing capacity and lability of the Cl or NO2 groups has been shown, indicating the formation of conjugated antigens in the animal. This led to the study of benzyl and acyl chlorides which, actually, were found to have sensitizing capacity. Most informative as to the relationship between reactions of the skin surface and anaphylaxis were experiments with acyl chlorides. Guinea pigs sensitized with p-chlorobenzoyl chloride showed, on the one hand, the usual surface lesions after application of the substance, and on the other typical anaphylactic shock following intravenous injection of a compound of p-chlorobenzoyl chloride and guinea pig serum; from which it may be inferred that the two types of allergic manifestation are closely related conditions.

Landsteiner, K.; Jacobs, John

1936-01-01