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1

Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay  

PubMed Central

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

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

2007-01-01

2

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

PubMed

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

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

2007-02-01

3

Chemical Genetic Screening Identifies Tricyclic Compounds that Decrease Cellular Melanin Content  

Microsoft Academic Search

A screen of a library of 2,000 drugs and natural products in murine melanocytes identified 10 tricyclic antidepressants (TCAs) as compounds that potently decreased intracellular melanin content. The rank order of potency of these compounds for decreasing melanin content was different than their relative potencies as antidepressants. These compounds had no effect on either the level or the enzymatic activity

Li Ni-Komatsu; Seth J Orlow

2008-01-01

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

Sulfonamides identified as plant immune-priming compounds in high-throughput chemical screening increase disease resistance in Arabidopsis thaliana  

PubMed Central

Plant activators are agrochemicals that protect crops from diseases by activating the plant immune system. To isolate lead compounds for use as practical plant activators, we screened two different chemical libraries composed of various bioactive substances by using an established screening procedure that can selectively identify immune-priming compounds. We identified and characterized a group of sulfonamide compounds – sulfameter, sulfamethoxypyridazine, sulfabenzamide, and sulfachloropyridazine – among the various isolated candidate molecules. These sulfonamide compounds enhanced the avirulent Pseudomonas-induced cell death of Arabidopsis suspension cell cultures and increased disease resistance in Arabidopsis plants against both avirulent and virulent strains of the bacterium. These compounds did not prevent the growth of pathogenic bacteria in minimal liquid media at 200 ?M. They also did not induce the expression of defense-related genes in Arabidopsis seedlings, at least not at 24 and 48 h after treatment, suggesting that they do not act as salicylic acid analogs. In addition, although sulfonamides are known to be folate biosynthesis inhibitors, the application of folate did not restore the potentiation effects of the sulfonamides on pathogen-induced cell death. Our data suggest that sulfonamides potentiate Arabidopsis disease resistance by their novel chemical properties.

Noutoshi, Yoshiteru; Ikeda, Mika; Saito, Tamio; Osada, Hiroyuki; Shirasu, Ken

2012-01-01

6

Identification of chemical compounds  

Microsoft Academic Search

We consider chemical identification as a process of setting up, testing, and screening of hypotheses, and review principles, techniques, and errors of identification. We also trace the relations between qualitative analysis and metrology and outline the range of known chemical compounds that are candidates for identification in general. We differentiate between methods for confirming identity and those for identifying unknowns,

Boris L. Milman

2005-01-01

7

CHEMICAL ANALYSIS AND LABORATORY BIOASSAYS OF HOST ODORS TO IDENTIFY COMPOUNDS THAT ATTRACT OR INHIBIT THE ATTRACTION OF MOSQUITOES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Using various sampling techniques and gas chromatography/mass spectrometry (GC/MS), a comprehensive profile of odors from hosts can be obtained. The differences in chemicals emanated by different hosts may provide a clue to the structures of compounds used by anthropophilic mosquitoes compared to t...

8

Mining Chemical Compounds  

Microsoft Academic Search

In this chapter we study the problem of classifying chemical compound datasets. We present a substructure-based classification algorithm that decouples the substructure discovery process from the classification model construction and uses frequent subgraph discovery algorithms to find all topological and geometric substructures present in the dataset. The advantage of this approach is that during classification model construction, all relevant substructures

Mukund Deshpande; Michihiro Kuramochi; George Karypis

2005-01-01

9

Molecular recognition: identifying compounds and their targets.  

PubMed

As a result of gene sequencing and proteomic efforts, thousands of new genes and proteins are now available as potential drug targets. The milieu of these proteins is complex and interactive; thousands of proteins activate, inhibit, and control each other's actions. The effect of blocking or activating a protein in a cell is far-reaching, and can affect whole, as well as adjacent pathways. This network of pathways is dynamic and a cellular response can change depending on the stimulus. In this section, the identification and role of individual proteins within the context of networked pathways, and the regulation of the activity of these proteins is discussed. Diverse chemical libraries, combinatorial libraries, natural products, as well as unnatural natural products that are derived from combinatorial biology (Chiu [2001] Proc. Natl. Acad. Sci. USA. 98:8548-8553), provide the chemical diversity in the search for new drugs to block new targets. Identifying new compounds that can become drugs is a long, expensive, and arduous task and potential targets must be carefully defined so as not to waste valuable resources. Equally important is the selection of compounds to be future drug candidates. Target selectivity in no way guarantees clinical efficacy, as the compound must meet pharmaceutical requirements, such as solubility, absorption, tissue distribution, and lack of toxicity. Thus matching biological diversity with chemical diversity involves something more than tight interactions, it involves interactions of the compounds with a variety host factors that can modulate its activity. PMID:11842421

Fernandes, P B

2001-01-01

10

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

11

Making Models of Chemical Compounds.  

ERIC Educational Resources Information Center

Describes the benefits and techniques of having students create models of chemical compounds. This hands-on approach uses colored paper and other inexpensive materials to construct the models. A step-by-step approach provides objectives, materials, an explanation on how to calculate chemical ratios, procedures, follow-up activities, and a resource…

Hoehn, Robert G.

1992-01-01

12

Assignment kernels for chemical compounds  

Microsoft Academic Search

During the last years kernel methods like the support vector machine (SVM) have gained a growing interest in machine learning. One of the strengths of this approach is the ability to deal easily with arbitrarily structured data by means of the kernel function. In this paper we propose a kernel for chemical compounds which is based on the idea of

Holger Fröhlich; Jörg K. Wegner; Andreas Zell

2005-01-01

13

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

EPA Science Inventory

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

14

Discovery of a novel neuroprotective compound, AS1219164, by high-throughput chemical screening of a newly identified apoptotic gene marker  

Microsoft Academic Search

We have reported that tacrolimus (FK506), an immunosuppressive drug, and diclofenac, a non-steroidal anti-inflammatory drug, possess different modes of neuroprotective action. FK506 suppresses only thapsigargin-induced apoptosis in neuroblastoma SH-SY5Y cells while diclofenac reverses tunicamycin-induced as well as thapsigargin-induced apoptosis. The aim of this study is to discover novel compounds that exert neuroprotective properties by using the transcriptional response of a

Takao Yamazaki; Masakazu Muramoto; Osamu Okitsu; Noriyuki Morikawa; Yasuhiro Kita

2011-01-01

15

FREQUENCY OF ORGANIC COMPOUNDS IDENTIFIED IN WATER  

EPA Science Inventory

This study was initiated for the purpose of compiling a list of all organic compounds that have been found in water. This report contains the names of compounds found, their location or a reference to a published study, the type of water in which they are found, and the date of s...

16

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

17

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

18

IDENTIFYING CHEMICAL COMPOUNDS IN THE ENVIRONMENT  

EPA Science Inventory

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

19

Species-dependent variation in algal sensitivity to chemical compounds  

Microsoft Academic Search

Nineteen miscellaneous chemical compounds were tested on thirteen freshwater algal species grown in 250-microliter liquid cultures on plastic microtitration plates. It was demonstrated that the species-dependent variation in algal sensitivity (EC100) may reach over three orders of magnitude, the degree of variation depending on the chemical tested. No generally sensitive or generally insensitive species could be identified. An effort was

H. Blanck; G. Wallin; S. A. Waengberg

1984-01-01

20

Chemical Beam Epitaxy of Compound Semiconductors.  

National Technical Information Service (NTIS)

We made substantial progress in 1989 toward establishing a chemical beam epitaxy (CBE) facility for the epitaxial growth of compound semiconductors. The major part of our effort was in the development and assembly of the CBE hardware including the growth,...

L. A. Kolodziejski S. C. Shepard H. Nanto D. H. Lee A. R. Odoardi

1989-01-01

21

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

EPA Science Inventory

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

22

Kernels for Chemical Compounds in Biological Screening  

Microsoft Academic Search

Kernel methods are a class of algorithms for pattern analysis with a number of convenient features. This paper proposes extension\\u000a of the kernel method for biological screening data including chemical compounds. Our investigation of extending kernel aims\\u000a to combine properties of graphical structure and molecule descriptors. The use of such kernels allows comparison of compounds,\\u000a not only on graphs but

Karol Kozak; Marta Kozak; Katarzyna Stapor

2007-01-01

23

Chemical defenses: from compounds to communities.  

PubMed

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

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

2007-12-01

24

Interfacial energies and chemical compound formation  

Microsoft Academic Search

The limitations of using bulk thermochemical data to characterize the initial stages of chemical compound formation are discussed and a correction, involving the relevant interfacial energies, is proposed. Apparent anomalies in the variations of the surface energy of copper with oxygen potential are consistent with the proposed analysis.

M. McLean; E. D. Hondros

1973-01-01

25

Graphing Chemical Data to Identify Fractional Crystallization  

NSDL National Science Digital Library

Students are given major-element, whole-rock chemical analyses from ten samples of lava from the 1868 eruption of Mauna Loa. They do not know sequence of eruption, only that the lavas came from the same volcano. Students are asked to evaluate the hypothesis that the observed chemical variation is due to the fractional crystallization of olivine. The hypothesis can be tested any of a number of graphs. Several examples are given in the accompanying Excel workbook.

Brady, John

26

Primary Polymer Aging Processes Identified from Weapon Headspace Chemicals  

SciTech Connect

A current focus of our weapon headspace sampling work is the interpretation of the volatile chemical signatures that we are collecting. To help validate our interpretation we have been developing a laboratory-based material aging capability to simulate material decomposition chemistries identified. Key to establishing this capability has been the development of an automated approach to process, analyze, and quantify arrays of material combinations as a function of time and temperature. Our initial approach involves monitoring the formation and migration of volatile compounds produced when a material decomposes. This approach is advantageous in that it is nondestructive and provides a direct comparison with our weapon headspace surveillance initiative. Nevertheless, this approach requires us to identify volatile material residue and decomposition byproducts that are not typically monitored and reported in material aging studies. Similar to our weapon monitoring method, our principle laboratory-based method involves static headspace collection by solid phase microextraction (SPME) followed by gas chromatography/mass spectrometry (GC/MS). SPME is a sorbent collection technique that is ideally suited for preconcentration and delivery of trace gas-phase compounds for analysis by GC. When combined with MS, detection limits are routinely in the low- and sub-ppb ranges, even for semivolatile and polar compounds. To automate this process we incorporated a robotic sample processor configured for SPME collection. The completed system will thermally process, sample, and analyze a material sample. Quantification of the instrument response is another process that has been integrated into the system. The current system screens low-milligram quantities of material for the formation or outgas of small compounds as initial indicators of chemical decomposition. This emerging capability offers us a new approach to identify and non-intrusively monitor decomposition mechanisms that are accelerated by stockpile-relevant aging parameters such as heat, irradiation, material incompatibility and physical force. The primary organic material groups that make up many of the weapon systems are chlorofluoropolymers, polysiloxanes, and polyurethanes (PUR). In the weapon headspace we see the greatest residue from polysiloxanes and PUR and, therefore, are interested in identifying and quantifying the origin responsible for their presence. Although we have produced a number of significant findings concerning the chlorofluoropolymer and polysiloxane materials, this work focuses on the decomposition of PUR.

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

2002-03-25

27

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

2013-09-22

28

A forward chemical screen identifies antibiotic adjuvants in Escherichia coli.  

PubMed

Multi-drug-resistant infections caused by Gram-negative pathogens are rapidly increasing, highlighting the need for new chemotherapies. Unlike Gram-positive bacteria, where many different chemical classes of antibiotics show efficacy, Gram-negatives are intrinsically insensitive to many antimicrobials including the macrolides, rifamycins, and aminocoumarins, despite intracellular targets that are susceptible to these drugs. The basis for this insensitivity is the presence of the impermeant outer membrane of Gram-negative bacteria in addition to the expression of pumps and porins that reduce intracellular concentrations of many molecules. Compounds that sensitize Gram-negative cells to "Gram-positive antibiotics", antibiotic adjuvants, offer an orthogonal approach to addressing the crisis of multi-drug-resistant Gram-negative pathogens. We performed a forward chemical genetic screen of 30,000 small molecules designed to identify such antibiotic adjuvants of the aminocoumarin antibiotic novobiocin in Escherichia coli. Four compounds from this screen were shown to be synergistic with novobiocin including inhibitors of the bacterial cytoskeleton protein MreB, cell wall biosynthesis enzymes, and DNA synthesis. All of these molecules were associated with altered cell shape and small molecule permeability, suggesting a unifying mechanism for these antibiotic adjuvants. The potential exists to expand this approach as a means to develop novel combination therapies for the treatment of infections caused by Gram-negative pathogens. PMID:22698393

Taylor, Patricia L; Rossi, Laura; De Pascale, Gianfranco; Wright, Gerard D

2012-06-22

29

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...

30

A quantitative high throughput assay for identifying gametocytocidal compounds.  

PubMed

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 1536-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 IC(50) 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 1280 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. PMID:23454872

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

2013-02-27

31

Sorting inhibitors (Sortins): Chemical compounds to study vacuolar sorting in Arabidopsis  

Microsoft Academic Search

Chemical genomics is an interdisciplinary approach that unites the power of chemical screens and genomics strategies to dissect biological processes such as endomembrane trafficking. We have taken advantage of the evolutionary conservation between plants and Saccharomyces cerevisiae to identify such chemicals. Using S. cerevisiae, we screened a library of diverse chemical structures for compounds that induce the secretion of carboxypeptidase

Jan Zouhar; Glenn R. Hicks; Natasha V. Raikhel

2004-01-01

32

A high content screening assay for identifying lysosomotropic compounds.  

PubMed

Lysosomes are acidic organelles that are essential for the degradation of old organelles and engulfed microbes. Furthermore, lysosomes play a key role in cell death. Lipophilic or amphiphilic compounds with a basic moiety can become protonated and trapped within lysosomes, causing lysosomal dysfunction. Therefore, high-throughput screens to detect lysosomotropism, the accumulation of compounds in lysosomes, are desirable. Hence, we developed a 96-well format, high content screening assay that measures lysosomotropism and cytotoxicity by quantitative image analysis. Forty drugs, including antidepressants, antipsychotics, antiarrhythmics and anticancer agents, were tested for their effects on lysosomotropism and cytotoxicity in H9c2 cells. The assay correctly identified drugs known to cause lysosomotropism and revealed novel information showing that the anticancer drugs, gefitinib, lapatinib, and dasatinib, caused lysosomotropism. Although structurally and pharmacologically diverse, drugs that were lysosomotropic shared certain physicochemical properties, possessing a ClogP>2 and a basic pKa between 6.5 and 11. In contrast, drugs which did not lie in this physicochemical property space were not lysosomotropic. The assay is a robust, rapid screen that can be used to identify lysosomotropic, as well as, cytotoxic compounds, and can be positioned within a screening paradigm to understand the role of lysosomotropism as a contributor to drug-induced toxicity. PMID:21184822

Nadanaciva, Sashi; Lu, Shuyan; Gebhard, David F; Jessen, Bart A; Pennie, William D; Will, Yvonne

2010-12-22

33

InChI - the worldwide chemical structure identifier standard.  

PubMed

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

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

2013-01-24

34

InChI - the worldwide chemical structure identifier standard  

PubMed Central

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

2013-01-01

35

A probabilistic model for mining implicit 'chemical compound-gene' relations from literature  

Microsoft Academic Search

Motivation: The importance of chemical compounds has been emphasized more in molecular biology, and 'chemical genomics' has attracted a great deal of attention in recent years. Thus an important issue in current molecular biology is to identify biological-related chem- ical compounds (more specifically, drugs) and genes. Co-occurrence of biological entities in the literature is a simple, comprehensive and popular technique

Shanfeng Zhu; Yasushi Okuno; Gozoh Tsujimoto; Hiroshi Mamitsuka

2005-01-01

36

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

Microsoft Academic Search

High-throughput screening (HTS) of chemical compounds to identify modulators of molecular targets is a mainstay of pharmaceutical development. Increasingly, HTS is being used to identify chemical probes of gene, pathway, and cell functions, with the ultimate goal of comprehensively delineating relationships between chemical structures and biological activities. Achieving this goal will require methodologies that efficiently generate pharmacological data from the

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

2006-01-01

37

Device for collecting chemical compounds and related methods  

SciTech Connect

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

38

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

39

Development of an electronic nose to identify and quantify volatile hazardous compounds.  

PubMed

A new electronic nose was developed to identify the chemical compound released when a 2.5-L flask was broken inside a 3 m x 3 m x 2.5 m store-room. Flasks of 10 different hazardous compounds were initially present in the room: ammonia, propanone, hexane, acetic acid, toluene, methanol, tetrachloromethane, chloroform, ethanol and dichloromethane. Besides identification, quantification of the compound present in the air was also performed by the electronic nose, in order to evaluate the risk level for room cleaning. An array of six sensors based on coated piezoelectric quartz crystals was used. Although none of the individual sensors was specific for a single compound, an artificial neural network made it possible to identify and quantify the released vapour, among a series of 10 compounds, with six sensors. The neural network could be simplified, and the number of neurons reduced, provided it was used just for the identification task. Quantification could be performed later using the individual calibration of the sensor most sensitive to the identified compound. PMID:18804602

Fernandes, Daniel L A; Gomes, M Teresa S R

2008-06-05

40

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

41

CHEMICAL COMPOUND CLASSIFICATION WITH AUTOMATICALLY MINED STRUCTURE PATTERNS.  

PubMed

In this paper we propose new methods of chemical structure classification based on the integration of graph database mining from data mining and graph kernel functions from machine learning. In our method, we first identify a set of general graph patterns in chemical structure data. These patterns are then used to augment a graph kernel function that calculates the pairwise similarity between molecules. The obtained similarity matrix is used as input to classify chemical compounds via a kernel machines such as the support vector machine (SVM). Our results indicate that the use of a pattern-based approach to graph similarity yields performance profiles comparable to, and sometimes exceeding that of the existing state-of-the-art approaches. In addition, the identification of highly discriminative patterns for activity classification provides evidence that our methods can make generalizations about a compound's function given its chemical structure. While we evaluated our methods on molecular structures, these methods are designed to operate on general graph data and hence could easily be applied to other domains in bioinformatics. PMID:20448828

Smalter, A M; Huan, J; Lushington, G H

2008-01-01

42

EPA's efforts to identify and control harmful chemicals in use  

Microsoft Academic Search

Under the Toxic Substances Control Act of 1976, the Environmental Protection Agency (EPA) is responsible for identifying, assessing, and controlling unreasonable risks to health or the environment from the manufacture, processing, distribution, use, or disposal of new and existing chemicals - those currently in commerce. This report focuses on EPA's efforts to review and control existing chemicals. To date, EPA

Bowsher

1984-01-01

43

Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions  

PubMed Central

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

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

2011-01-01

44

Identification of Chemical Compounds that Induce HIF-1? Activity  

PubMed Central

Cellular metabolism depends on the availability of oxygen and the major regulator of oxygen homeostasis is hypoxia-inducible factor 1 (HIF-1), a highly conserved transcription factor that plays an essential role in cellular and systemic homeostatic responses to hypoxia. HIF-1 is a heterodimeric transcription factor composed of hypoxia-inducible HIF-1? and constitutively expressed HIF-1?. Under hypoxic conditions, the two subunits dimerize, allowing translocation of the HIF-1 complex to the nucleus where it binds to hypoxia-response elements (HREs) and activates expression of target genes implicated in angiogenesis, cell growth, and survival. The HIF-1 pathway is essential to normal growth and development, and is involved in the pathophysiology of cancer, inflammation, and ischemia. Thus, there is considerable interest in identifying compounds that modulate the HIF-1 signaling pathway. To assess the ability of environmental chemicals to stimulate the HIF-1 signaling pathway, we screened a National Toxicology Program collection of 1408 compounds using a cell-based ?-lactamase HRE reporter gene assay in a quantitative high-throughput screening (qHTS) format. Twelve active compounds were identified. These compounds were tested in a confirmatory assay for induction of vascular endothelial growth factor, a known hypoxia target gene, and confirmed compounds were further tested for their ability to mimic the effect of a reduced-oxygen environment on hypoxia-regulated promoter activity. Based on this testing strategy, three compounds (o-phenanthroline, iodochlorohydroxyquinoline, cobalt sulfate heptahydrate) were confirmed as hypoxia mimetics, whereas two compounds (7-diethylamino-4-methylcoumarin and 7,12-dimethylbenz(a)anthracence) were found to interact with HIF-1 in a manner different from hypoxia. These results demonstrate the effectiveness of qHTS in combination with secondary assays for identification of HIF-1? inducers and for distinguishing among inducers based on their pattern of activated hypoxic target genes. Identification of environmental compounds having HIF-1? activation activity in cell-based assays may be useful for prioritizing chemicals for further testing as hypoxia-response inducers in vivo.

Xia, Menghang; Huang, Ruili; Sun, Yi; Semenza, Gregg L.; Aldred, Shelley Force; Witt, Kristine L.; Inglese, James; Tice, Raymond R.; Austin, Christopher P.

2009-01-01

45

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...

46

Screening of chemical compounds purified from biological sources  

US Patent & Trademark Office Database

A method of producing a chemical compound library comprises extracting at least one extract from at least one species of plant; processing at least one of the extract(s) to remove at least one type of chemical interference to produce a processed extract; chromatographically separating the processed extract into a plurality of chromatographic fractions, each containing an amount of chemical compounds; determining the amount of chemical compounds in at least one of the chromatographic fractions; and normalizing the chromatographic fractions in which the amounts were determined to produce normalized chromatographic fractions, each such fraction comprising from about 1 microgram to about 500 micrograms of each of from one to seven chemical compounds that were present in lower concentrations in the extract and that each have a log P of from about -1 to about 5 and a molecular weight less than about 1000 Daltons; thereby to produce a chemical compound library from at least one species of plant.

2008-05-06

47

Frequent Substructure-Based Approaches for Classifying Chemical Compounds  

Microsoft Academic Search

Computational techniques that build models to correctly assign chemical compounds to various classes of interest have many applications in pharmaceutical research and are used extensively at various phases during the drug development process. These techniques are used to solve a number of classification problems such as predicting whether or not a chemical compound has the desired biological activity, is toxic

Mukund Deshpande; Michihiro Kuramochi; Nikil Wale; George Karypis

2005-01-01

48

Structure feature selection for chemical compound classification  

Microsoft Academic Search

With the development of highly efficient chemin- formatics data collection technology, classification of chemical structure data emerges as an important topic in cheminfor- matics. Towards building highly accurate predictive models for chemical data, here we present an efficient feature selection method. In our method, we first represent a chemical structure by its 2D connectivity map. We then use frequent subgraph

Hongliang Fei; Jun Huan

2008-01-01

49

Zebrafish screen identifies novel compound with selective toxicity against leukemia  

PubMed Central

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

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

2012-01-01

50

LIGAND: database of chemical compounds and reactions in biological pathways  

Microsoft Academic Search

LIGAND is a composite database comprising three sections: COMPOUND for the information about metabolites and other chemical compounds, REACTION for the collection of substrate-product relations representing metabolic and other reactions, and ENZYME for the information about enzyme molecules. The current release (as of September 7, 2001) includes 7298 compounds, 5166 reactions and 3829 enzymes. In addition to the keyword search

Susumu Goto; Yasushi Okuno; Masahiro Hattori; Takaaki Nishioka; Minoru Kanehisa

2002-01-01

51

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

52

Mining Chemical Compound Structure Data Using Inductive Logic Programming  

Microsoft Academic Search

\\u000a Discovering knowledge from chemical compound structure data is a challenge task in KDD. It aims to generate hypotheses describing\\u000a activities or characteristics of chemical compounds from their own structures. Since each compound composes of several parts\\u000a with complicated relations among them, traditional mining algorithms cannot handle this kind of data efficiently. In this\\u000a research, we apply Inductive Logic Programming (ILP)

Cholwich Nattee; Sukree Sinthupinyo; Masayuki Numao; Takashi Okada

2003-01-01

53

A high content screening assay for identifying lysosomotropic compounds  

Microsoft Academic Search

Lysosomes are acidic organelles that are essential for the degradation of old organelles and engulfed microbes. Furthermore, lysosomes play a key role in cell death. Lipophilic or amphiphilic compounds with a basic moiety can become protonated and trapped within lysosomes, causing lysosomal dysfunction. Therefore, high-throughput screens to detect lysosomotropism, the accumulation of compounds in lysosomes, are desirable.Hence, we developed a

Sashi Nadanaciva; Shuyan Lu; David F. Gebhard; Bart A. Jessen; William D. Pennie; Yvonne Will

2011-01-01

54

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

55

Identifying and Estimating the Genetic Impact of Chemical Mutagens.  

National Technical Information Service (NTIS)

A battery of short-term mutagenicity tests using bacteria and mammalian cells in culture can often identify chemicals with potential mutagenic risk to mammals. Tests with mice are reserved for rare cases when short-term tests are equivocal or when human e...

1983-01-01

56

Strategies and future trends to identify the mode of action of phytotoxic compounds.  

PubMed

Small molecules affecting plant processes have been widely used as probes to study basic physiology. In agricultural practices some of these molecules have served as herbicides or plant growth regulators. Historically, most of the compounds were identified in large screens by the agrochemical industry, but also as phytoactive natural products. More recently, novel phytoactive compounds originated from academic research by chemical screens performed to induce specific phenotypes of interest. In the present review different approaches were evaluated for the identification of the mode of action (MoA) of phytoactive compounds. Based on the methodologies used for MoA identification, three approaches are differentiated: a phenotyping approach, an approach based on a genetic screen and a biochemical screening approach. Target sites of compounds targeting primary or secondary metabolism were identified most successfully with a phenotyping approach. Target sites for compounds that influence cell structure, such as cell wall biosynthesis or the cytoskeleton, or compounds that interact with the hormone system, were in most cases discovered by using a genetic approach. Examples showing the strengths and weaknesses of the different approaches are discussed in detail. Additionally, new techniques that could contribute to future MoA identification projects are reviewed. In particular, next-generation sequencing techniques may be used for the fast-forward mapping of mutants identified in genetic screens. Finally, a revised three-tiered approach for the MoA identification of phytoactive compounds is proposed. The approach consists of a 1st tier, which addresses compound stability, uniformity of effects in different species, general cytotoxicity and the effect on common processes such as transcription and translation. Advanced studies based on these findings initiate the 2nd tier MoA characterization, either with further phenotypic characterization, starting a genetic screen or establishing a biochemical screen. At the 3rd tier, enzyme assays or protein affinity studies should show the activity of the compound on the hypothesized target and should associate the in vitro effects with the in vivo profile of the compound. PMID:24094055

Tresch, Stefan

2013-08-29

57

BioSM: Metabolomics Tool for Identifying Endogenous Mammalian Biochemical Structures in Chemical Structure Space.  

PubMed

The structural identification of unknown biochemical compounds in complex biofluids continues to be a major challenge in metabolomics research. Using LC/MS, there are currently two major options for solving this problem: searching small biochemical databases, which often do not contain the unknown of interest or searching large chemical databases which include large numbers of nonbiochemical compounds. Searching larger chemical databases (larger chemical space) increases the odds of identifying an unknown biochemical compound, but only if nonbiochemical structures can be eliminated from consideration. In this paper we present BioSM; a cheminformatics tool that uses known endogenous mammalian biochemical compounds (as scaffolds) and graph matching methods to identify endogenous mammalian biochemical structures in chemical structure space. The results of a comprehensive set of empirical experiments suggest that BioSM identifies endogenous mammalian biochemical structures with high accuracy. In a leave-one-out cross validation experiment, BioSM correctly predicted 95% of 1388 Kyoto Encyclopedia of Genes and Genomes (KEGG) compounds as endogenous mammalian biochemicals using 1565 scaffolds. Analysis of two additional biological data sets containing 2330 human metabolites (HMDB) and 2416 plant secondary metabolites (KEGG) resulted in biochemical annotations of 89% and 72% of the compounds, respectively. When a data set of 3895 drugs (DrugBank and USAN) was tested, 48% of these structures were predicted to be biochemical. However, when a set of synthetic chemical compounds (Chembridge and Chemsynthesis databases) were examined, only 29% of the 458?207 structures were predicted to be biochemical. Moreover, BioSM predicted that 34% of 883?199 randomly selected compounds from PubChem were biochemical. We then expanded the scaffold list to 3927 biochemical compounds and reevaluated the above data sets to determine whether scaffold number influenced model performance. Although there were significant improvements in model sensitivity and specificity using the larger scaffold list, the data set comparison results were very similar. These results suggest that additional biochemical scaffolds will not further improve our representation of biochemical structure space and that the model is reasonably robust. BioSM provides a qualitative (yes/no) and quantitative (ranking) method for endogenous mammalian biochemical annotation of chemical space and, thus, will be useful in the identification of unknown biochemical structures in metabolomics. BioSM is freely available at http://metabolomics.pharm.uconn.edu . PMID:23330685

Hamdalla, Mai A; Mandoiu, Ion I; Hill, Dennis W; Rajasekaran, Sanguthevar; Grant, David F

2013-02-27

58

Identifying new persistent and bioaccumulative organics among chemicals in commerce.  

PubMed

The goal of this study was to identify commercial chemicals that might be persistent and bioaccumulative (P&B) and that were not being considered in current Great Lakes, North American, and Arctic contaminant measurement programs. We combined the Canadian Domestic Substance List (DSL), a list of 3059 substances of "unknown or variable composition complex reaction products and biological materials" (UVCBs), and the U.S. Environmental Protection Agency (U.S. EPA) Toxic Substances Control Act (TSCA) Inventory Update Rule (IUR) database for years 1986, 1990, 1994, 1998, 2002, and 2006 yielding a database of 22263 commercial chemicals. From that list, 610 chemicals were identified by estimates from U.S EPA EPISuite software and using expert judgment. This study has yielded some interesting and probable P&B chemicals that should be considered for further study. Recent studies, following up our initial reports and presentations on this work, have confirmed the presence of many of these chemicals in the environment. PMID:20163179

Howard, Philip H; Muir, Derek C G

2010-04-01

59

Helping Students Distinguish between Mixtures and Chemical Compounds.  

ERIC Educational Resources Information Center

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

Papageorgiou, George

2002-01-01

60

Helping Students Distinguish between Mixtures and Chemical Compounds.  

ERIC Educational Resources Information Center

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

Papageorgiou, George

2002-01-01

61

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

62

Chemical Compounds with Path Frequency Using Multi-Core Technology  

Microsoft Academic Search

Drug design is the approach of finding drugs by design using computational tools. When designing a new drug, the structure\\u000a of the drug molecule can be modeled by classification of potential chemical compounds. Kernel Methods have been successfully\\u000a used in classifying chemical compounds, within which the most popular one is Support Vector Machine (SVM). In order to classify\\u000a the characteristics

Kun-ming Yu; Yi-yan Chang; Jiayi Zhou; Chun-yuan Huang; Whei-meih Chang; Chun-yuan Lin; Chuan Yi Tang

2009-01-01

63

Comparison of Descriptor Spaces for Chemical Compound Retrieval and Classification  

Microsoft Academic Search

Abstract. In recent years the development of computational techniques that build models to correctly assign chemical compounds,to various classes or to retrieve potential drug-like compounds,has been an active area of research. Many of the bestperforming techniques for these tasks utilize a descriptor-based representation of the compound,that captures various aspects of the underlying molecular graph’s topology. In this paper we compare

Nikil Wale; George Karypis

2006-01-01

64

Emissions of Chemical Compounds and Bioaerosols During the Secondary Treatment of Paper Mill Effluents  

Microsoft Academic Search

This study identified and quantified the main chemical compounds—the substances responsible for the disagreeable odors—and the bioaerosols emitted during the biological treatment of paper mill effluents. It also identified the characteristics of the process that effects the generation or diffusion of these substances. All treatment stages were evaluated. Measuring sites were located as closely as possible to the potential emission

Nicole Goyer; Jacques Lavoie

2001-01-01

65

Chemical reactions of organic compounds on clay surfaces  

SciTech Connect

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

Soma, Yuko; Soma, Mitsuyuki (National Institute for Environmental Studies, Ibaraki (Japan))

1989-11-01

66

Chemical reactions of organic compounds on clay surfaces.  

PubMed Central

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

Soma, Y; Soma, M

1989-01-01

67

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.

68

Chemical Polishing of II-VI Compounds  

Microsoft Academic Search

The chemical polishing of the anion face of ZnO, ZnS, CdSe, and ZnTe and the cation face of CdSe and ZnTe with bromine dissolved in methanol has been accomplished. The etch rates of the bromine-methanol solution on the anion and cation faces of BeO, ZnO, ZnS, CdS, CdSe, ZnTe, and InSb have been measured at room temperature. An empirical relationship

W. H. Strehlow

1969-01-01

69

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

70

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

PubMed

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

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

2013-02-13

71

Classifying Chemical Compounds Using Contrast and Common Patterns  

Microsoft Academic Search

The problem of classifying chemical compounds is studied in this paper. An approach based on minimal contrast and common topological\\u000a patterns discovered from compounds dataset is presented. The algorithm is strongly associated with the classical emerging\\u000a patterns techniques known from decision tables. We tested the proposed algorithm on real classification problems. Results\\u000a show that it provides better classification accuracy than

Andrzej Dominik; Zbigniew Walczak; Jacek Wojciechowski

2007-01-01

72

STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS  

PubMed Central

Experiments with guinea pigs are described which show that under special experimental conditions the intraperitoneal injection of conjugates made with homologous erythrocyte stromata leads to typical skin sensitization of the contact type towards the respective simple chemicals, namely picryl chloride or 2,4-dinitrofluorobenzene. Therefore such sensitivity can be brought about not only by low molecular chemical compounds but by a material which must be regarded as a typical antigen.

Landsteiner, K.; Chase, M. W.

1941-01-01

73

Chemical bath deposition of II-VI compound thin films  

NASA Astrophysics Data System (ADS)

II-VI compounds are direct bandgap semiconductors with great potentials in optoelectronic applications. Solar cells, where these materials are in greater demand, require a low cost production technology that will make the final product more affordable. Chemical bath deposition (CBD) a low cost growth technique capable of producing good quality thin film semiconductors over large area and at low temperature then becomes a suitable technology of choice. Heterogeneous reaction in a basic aqueous solution that is responsible for the II-VI compound film growth in CBD requires a metal complex. We have identified the stability constant (k) of the metal complex compatible with CBD growth mechanism to be about 106.9. This value is low enough to ensure that the substrate adsorbed complex relax for subsequent reaction with the chalcogen precursor to take place. It is also high enough to minimize the metal ion concentration in the bath participating in the precipitation of the bulk compounds. Homogeneous reaction that leads to precipitation in the reaction bath takes place because the solubility products of bulk II-VI compounds are very low. This reaction quickly depletes the bath of reactants, limit the film thickness, and degrade the film quality. While ZnS thin films are still hard to grow by CBD because of lack of suitable complexing agent, the homogeneous reaction still limits quality and thickness of both US and ZnS thin films. In this study, the zinc tetraammine complex ([Zn(NH3) 4]2+) with k = 108.9 has been forced to acquire its unsaturated form [Zn(NH3)3]2+ with a moderate k = 106.6 using hydrazine and nitrilotriacetate ion as complementary complexing agents and we have successfully grown ZnS thin films. We have also, minimized or eliminated the homogeneous reaction by using ammonium salt as a buffer and chemical bath with low reactant concentrations. These have allowed us to increase the saturation thickness of ZnS thin film by about 400% and raise that of US film form 0.2 to 0.5 mum with improved quality. A novel chemical activated diffusion of Cd into ZnS thin film at temperature lower than 100°C is also developed. This in conjunction with thermal activated diffusion at 400°C has enabled us to synthesize Cd1-xZn xS thin films suitable for solar cells from CBD grown CdS/ZnS multilayer. The potential application of the new Cd1-xZnxS/CdS/CdTe solar cell structure is also demonstrated. The unoptimized structure grown on transparent conducting oxide coated soda lime glass of 3mm thickness with no antireflection coating yielded a 10% efficiency. This efficiency is the highest ever recorded in any Cd1-xZnxS film containing CdTe solar cells.

Oladeji, Isaiah Olatunde

74

Identification of Chemical Compounds in a Liquid-Liquid Extraction System.  

National Technical Information Service (NTIS)

The objective of the present work is to identify the chemical compounds that are distributed in a liquid-liquid extraction system in which the third phase is observed; for this purpose the FeCl sub 3 (0.12M) - HCl (8.43M) - Diisopropilic ether - system wa...

1980-01-01

75

Chronic Rat Toxicity Prediction of Chemical Compounds Using Kernel Machines  

Microsoft Academic Search

A recently published study showed the feasibility of chronic rat toxicity prediction, an important task to reduce the number of animal experiments using the knowledge of previous experiments. We bench-marked various kernel learning approaches for the prediction of chronic toxicity on a set of 565 chemical compounds, labeled with the Lowest Observed Adverse Effect Level, and achieved a prediction error

Georg Hinselmann; Andreas Jahn; Nikolas Fechner; Andreas Zell

2009-01-01

76

Chemical Compound Classification with Automatically Mined Structure Patterns  

Microsoft Academic Search

In this paper we propose new methods of chemical structure classification based on the integration of graph database mining from data mining and graph kernel functions from machine learning. In our method, we first identify a set of general graph patterns in chemical structure data. These patterns are then used to augment a graph kernel function that calculates the pairwise

Aaron M. Smalter; J. Huan; Gerald H. Lushington

2008-01-01

77

Shock-induced chemical reactions and synthesis of binary compounds  

SciTech Connect

The results of an experimental program on shock-induced chemical reactions and synthesis of binary compounds are presented. Binary powder mixture systems that are investigated include: (1) intermetallic forming compounds (e.g., Ni--Al, Ni--Si, Nb--Si, etc.) associated with large negative heats of reaction; and (2) isomorphous (e.g., Ni--Cu) and fully immiscible (e.g., Nb--Cu) systems associated with zero (or positive) heat of reaction. The extent of shock induced chemical reactions and the type of shock synthesized compounds formed in these systems are observed to be dependent on (i) shock-loading condition, (ii) the relative volumetric distribution of the mixture constituents, and (iii) differences in respective material properties which affect relative particle flow. 5 refs., 9 figs.

Thadhani, N.N.; Advani, A.; Song, I.; Dunbar, E.; Grebe, A. (New Mexico Inst. of Mining and Technology, Socorro, NM (USA). Center for Explosives Technology Research); Graham, R.A. (Sandia National Labs., Albuquerque, NM (USA))

1990-01-01

78

Semantic Similarity for Automatic Classification of Chemical Compounds  

PubMed Central

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

Ferreira, Joao D.; Couto, Francisco M.

2010-01-01

79

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

NASA Astrophysics Data System (ADS)

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

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

2013-10-01

80

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

PubMed Central

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

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

2006-01-01

81

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

PubMed Central

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

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

2010-01-01

82

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/vsample, 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

2013-08-09

83

Studies in the chemical behaviour of some compounds of sulphur  

Microsoft Academic Search

Ir has been shown that hydrogen iodide is a valuable reagent in the study of the chemical behaviour of the oxides 1 and halides 2 of sulphur and of the esters of oxyacids 3 of the element. This paper deals with the reactions betw~n hydrogen iodide and the following compounds of sulphur:Sulphur nitride, Hexasulphamide, Tetrahydrosulphur nit¡ (H4S?91 N-N tetraethyl-dithio-diamine, Tetra-ethyl-thio-diamine,

A. R. Vasudeva Murthy

1953-01-01

84

STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS  

PubMed Central

A method has been described by which sensitization to a simple chemical, picryl chloride (2:4:6 trinitrochlorobenzene), can be satisfactorily attained by means of intraperitoneal injection of the compound when killed tubercle bacilli suspended in paraffin oil were used as adjuvant. Sensitivity of the contact dermatitis type results therefrom. It follows that although skin sensitization of this type is most easily obtained by dermal application this route of administration is no necessary condition for such sensitivity.

Landsteiner, K.; Chase, M. W.

1940-01-01

85

Chemical impurity produces extra compound eyes and heads in crickets  

SciTech Connect

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

Walton, B.T.

1981-04-03

86

Portable microprocessor-controlled instrument for sensing, identifying and monitoring gaseous chemicals  

NASA Astrophysics Data System (ADS)

To protect US Coast Guard personnel from exposure to hazardous chemicals, a portable detector that responds promptly to many different compounds, identifies the detected compounds, and monitors their concentrations was developed. The amperometric gas sensing offered the best prospects. One task was to extend the applicability of amperometric toxic gas sensors to electrochemically inactive species. This was achieve by exposing the electrochemically inactive constituents to heated, noble metalcatalysts before introducing them to the amperometric sensor. This breakthrough laid the groundwork for development of a prototype instrument based on an array of four amperometric toxic gas sensors and two heated noble metal filaments. The four sensors can be rapidly switched to one of several operating modes. Four modes and four sensors yield 16 measured parameters.

Stetter, J. R.; Zarcomb, S.; Penrose, W. R.

1984-07-01

87

GPU Accelerated Chemical Similarity Calculation for Compound Library Comparison  

PubMed Central

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

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

2012-01-01

88

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

89

Chemical-genetic profile analysis of five inhibitory compounds in yeast  

PubMed Central

Background Chemical-genetic profiling of inhibitory compounds can lead to identification of their modes of action. These profiles can help elucidate the complex interactions between small bioactive compounds and the cell machinery, and explain putative gene function(s). Results Colony size reduction was used to investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These compounds target the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletion mutant yeast strains. As expected, the overall profiles of the tested compounds were similar, with deletions for genes involved in protein biosynthesis being the major category followed by metabolism. This implies that novel genes involved in protein biosynthesis could be identified from these profiles. Further investigations were carried out to assess the activity of three profiled genes in the process of protein biosynthesis using relative fitness of double mutants and other genetic assays. Conclusion Chemical-genetic profiles provide insight into the molecular mechanism(s) of the examined compounds by elucidating their potential primary and secondary cellular target sites. Our follow-up investigations into the activity of three profiled genes in the process of protein biosynthesis provided further evidence concerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genes TAE2, TAE3 and TAE4 for translation associated elements 2-4.

2010-01-01

90

Chemical Genetic Screening for Compounds that Preferentially Inhibit Growth of Methylthioadenosine Phosphorylase (MTAP) Deficient Saccharomyces Cerevisiae  

PubMed Central

Methylthioadenosine phosphorylase (MTAP), a key enzyme in the methionine salvage pathway, is inactivated in a variety of human cancers. Since all human tissues express MTAP, it would be of potential interest to identify compounds that selectively inhibit the growth of MTAP deficient cells. To determine if MTAP inactivation could be targeted, we have performed a differential chemical genetic screen in isogenic MTAP+ and MTAP? S. cerevisiae. A low molecular weight compound library containing 30,080 unique compounds was screened for those that selectively inhibit growth of MTAP? yeast using a differential growth assay. One compound, containing a 1,3,4-thiadiazine ring, repeatedly showed a differential dose response, with MTAP? cells exhibiting a four-fold shift in IC50 compared to MTAP+ cells. Several structurally related derivatives of this compound also showed enhanced growth inhibition in MTAP? yeast. These compounds were also examined for growth inhibition of isogenic MTAP+ and MTAP? HT1080 fibrosarcoma cells, and four of the five compounds exhibited evidence of modest, but significant, increased potency in MTAP? cells. In summary, these studies show the feasibility of differential growth screening technology and have identified a novel class of compounds that can preferentially inhibit growth of MTAP? cells.

Kadariya, Yuwaraj; Tang, Baiqing; Myers, Cynthia B.; Fukui, Jami; Peterson, Jeffrey R.; Kruger, Warren D.

2010-01-01

91

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

NASA Astrophysics Data System (ADS)

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

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

1996-03-01

92

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

93

Identifying Indicators of Reactivity for Chemical Reductants in Sediments  

EPA Science Inventory

To conduct site-specific exposure assessments for contaminants containing reducible functional groups, it is imperative to know the identity and reactivity of chemical reductants in natural sediments and to associate their reactivity with easily measurable sediment properties. Fo...

94

A High-Throughput Method to Identify Novel Senescence-Inducing Compounds  

PubMed Central

Cellular senescence is a persistently growth-arrested phenotype in normal and transformed cells induced by non-cytotoxic stress. Cytostasis as a method of cancer treatment has recently generated significant interest. Research into the induction of cellular senescence as cancer therapy has been hindered by a lack of compounds that efficiently induce this response. We describe a semiautomated high-throughput method to identify library compounds that induce senescence using prostate cancer cells cultured in 96 well plates. Primary hits are identified by low cell numbers after 3 days in culture, measured by Hoechst 33342 fluorescence. A secondary visual assessment of senescence-associated ?-galactosidase staining and cellular morphology in the same wells distinguishes senescence from quiescence, apoptosis and other false-positives. This method was used to screen a 4160 compound library of known bioactive compounds and natural products at a 10?M dose. Candidate compounds were further selected based on persistent growth arrest after drug removal and increased expression of previously described senescence marker genes. Four lead compounds not previously associated with senescence were identified for further investigation. This is the first successful assay to identify novel agents from compound libraries based on senescence-induction in cancer cells.

Ewald, Jonathan A.; Peters, Noel; Desotelle, Joshua A.; Hoffmann, F. Michael; Jarrard, David F.

2010-01-01

95

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

SciTech Connect

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

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

2010-09-20

96

Electrolytic photodissociation of chemical compounds by iron oxide electrodes  

DOEpatents

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

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

1984-01-01

97

Electrolytic photodissociation of chemical compounds by iron oxide photochemical diodes  

DOEpatents

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

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

1985-01-01

98

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

2013-06-11

99

Degraded Lignin Compounds Identified in Silicified Wood 200 Million Years Old  

Microsoft Academic Search

Degraded lignin compounds have been identified in Triassic age (about 200 million years) silicified wood from the Petrified Forest National Park in Arizona. The pyrolysis products from black carbonaceous samples include carbon dioxide, low-molecular-weight alkanes and alkenes, benzene, alkyl-substituted benzenes, phenol, cresol, xylenols, indenes, benzofurans, trimethylindanone, and naphthalenes. These compounds are also the primary pyrolyzates of modern lignin above 500

Anne Colberg Sigleo

1978-01-01

100

Degraded lignin compounds identified in silicified wood 200 million years old.  

PubMed

Degraded lignin compounds have been identified in Triassic age (about 200 million years) silicified wood from the Petrified Forest National Park in Arizona. The pyrolysis products from black carbonaceous samples include carbon dioxide, low-molecular-weight alkanes and alkenes, benzene, alkyl-substituted benzenes, phenol, cresol, xylenols, indenes, benzofurans, trimethylindanone, and naphthalenes. These compounds are also the primary pyrolyzates of modern lignin above 500 degrees C. PMID:17740698

Sigleo, A C

1978-06-01

101

30 CFR 47.21 - Identifying hazardous chemicals.  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING HAZARD COMMUNICATION (HazCom) Hazard Determination § 47.21 Identifying...6) International Agency for Research on Cancer (IARC), Monographs and related supplements, Volumes 1 through 77....

2009-07-01

102

30 CFR 47.21 - Identifying hazardous chemicals.  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING HAZARD COMMUNICATION (HazCom) Hazard Determination § 47.21 Identifying...6) International Agency for Research on Cancer (IARC), Monographs and related supplements, Volumes 1 through 77....

2010-07-01

103

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

104

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

105

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

SciTech Connect

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

Jarabek, R.J.

1987-10-01

106

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

PubMed Central

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

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

2012-01-01

107

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...

108

Identifying indicators of reactivity for chemical reductants in sediments.  

PubMed

To conduct site-specific exposure assessments for contaminants containing reducible functional groups, it is imperative to know the identity and reactivity of chemical reductants in natural sediments and to associate their reactivity with easily measurable sediment properties. For this purpose the reactivity, as defined by pseudofirst order reduction rate constants for p-cyanonitrobenzene (pCNB), was measured in twenty-one natural sediments of different origins that were incubated to attain both anoxic (less reducing) and anaerobic (microbially reducing) conditions. The reactivity of the anoxic sediments increased with pH and an increasing amount of Fe(II) added. A good electron balance between pCNB reduction and Fe(II) consumption was observed for anaerobic sediments of high solids loading (50 g/L), but not when solids loading was 5 g/L. Based on cluster and regression analysis, pCNB reactivity in the anaerobic sediments correlates strongly with aqueous Fe(II) concentrations for sediments with low organic carbon (OC) content (<4.2%), but with dissolved OC concentrations (DOC) for the sediments with high OC content (>6.4%). These observations indicate surface-associated Fe(II) and reduced DOC are the predominant reductants in the anaerobic sediments, and that aqueous Fe(II) and DOC will serve as readily measurable indicators of pCNB reactivity in these systems. PMID:23088410

Zhang, Huichun; Weber, Eric J

2012-12-19

109

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

SciTech Connect

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

Li, DeQuan

1998-12-31

110

[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

111

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

Federal Register 2010, 2011, 2012, 2013

...Guidance for Industry on Incorporation of Physical-Chemical Identifiers Into Solid Oral...industry entitled ``Incorporation of Physical-Chemical Identifiers Into Solid Oral...design considerations for incorporating physical-chemical identifiers (PCIDs)...

2011-10-12

112

Parallel branch-and-bound approach with MPI technology in inferring chemical compounds with path frequency  

Microsoft Academic Search

Drug design is the approach of finding drugs by design using computational tools. When designing a new drug, the structure of the drug molecule can be modeled by classification of potential chemical compounds. Kernel Methods have been successfully used in classifying potential chemical compounds. Frequency of labeled paths has been proposed to map compounds into feature in order to classify

Kun-Ming Yu; Chun-Yuan Lin; Hui-Yuan Wang; Chuan Yi Tang; Jiayi Zhou

2009-01-01

113

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

Microsoft Academic Search

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

Steven Robery; Janina Mukanowa; Nathalie Percie Du Sert; Paul L. R. Andrews; Robin S. B. Williams; Adrian John Harwood

2011-01-01

114

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

115

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

Microsoft Academic Search

Master Chemical Mechanism containing over 2400 chemical species and over 7100 chemical reactions is employed here to describe the atmospheric degradation of 120 organic compounds and the associated regional scale ozone and PAN formation under conditions appropriate to the polluted boundary layer over northwest Europe. Photochemical ozone and PAN creation potentials (POCP and PPCP) are derived for each organic compound

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

1998-01-01

116

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

117

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

118

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

PubMed

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

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

2013-02-27

119

A Focused Small-Molecule Screen Identifies 14 Compounds with Distinct Effects on Toxoplasma gondii  

PubMed Central

Toxoplasma gondii is a globally ubiquitous pathogen that can cause severe disease in immunocompromised humans and the developing fetus. Given the proven role of Toxoplasma-secreted kinases in the interaction of Toxoplasma with its host cell, identification of novel kinase inhibitors could precipitate the development of new anti-Toxoplasma drugs and define new pathways important for parasite survival. We selected a small (n = 527) but diverse set of putative kinase inhibitors and screened them for effects on the growth of Toxoplasma in vitro. We identified and validated 14 noncytotoxic compounds, all of which had 50% effective concentrations in the nanomolar to micromolar range. We further characterized eight of these compounds, four inhibitors and four enhancers, by determining their effects on parasite motility, invasion, and the likely cellular target (parasite or host cell). Only two compounds had an effect on parasite motility and invasion. All the inhibitors appeared to target the parasite, and interestingly, two of the enhancers appeared to rather target the host cell, suggesting modulation of host cell pathways beneficial for parasite growth. For the four inhibitors, we also tested their efficacy in a mouse model, where one compound proved potent. Overall, these 14 compounds represent a new and diverse set of small molecules that are likely targeting distinct parasite and host cell pathways. Future work will aim to characterize their molecular targets in both the host and parasite.

Kamau, Edwin T.; Srinivasan, Ananth R.; Brown, Mark J.; Fair, Matthew G.; Caraher, Erin J.

2012-01-01

120

Preparation of Chemical Compounds for the U.S. Army Drug Development Program.  

National Technical Information Service (NTIS)

The purpose of this contract is to provide chemical compounds for the U.S. Army Medical R D Command. In the 12 months, 7 assignments were completed. Compounds submitted included a substituted 8-nitroquinoline, five dialkyltetrasulfides and a bisquaternary...

P. Blumbergs L. V. Dunkerton B. S. Ross D. A. Greening D. J. Dagli

1990-01-01

121

Microarray Compound Screening (&mgr;ARCS) to Identify Inhibitors of HIV Integrase  

Microsoft Academic Search

A novel high-throughput strand transfer assay has been developed, using Microarray Compound Screening (&mgr;ARCS) technology, to identify inhibitors of human immunodeficiency virus (HIV) integrase. This technology utilizes agarose matrices to introduce a majority of the reagents throughout the assay. Integration of biotinylated donor DNA with fluorescein isothiocyanate (FITC)-labeled target DNA occurs on a SAM membrane in the presence of integrase.

Caroline A. David; Tim Middleton; Debra Montgomery; Hock Ben Lim; Warren Kati; Akhter Molla; Xiaoling Xuei; Usha Warrior; James L. Kofron; David J. Burns

2002-01-01

122

Chemical Genetic Screening for Compounds That Preferentially Inhibit Growth of Methylthioadenosine Phosphorylase (MTAP)—Deficient Saccharomyces cerevisiae  

Microsoft Academic Search

Methylthioadenosine phosphorylase (MTAP), a key enzyme in the methionine salvage pathway, is inactivated in a variety of human cancers. Since all human tissues express MTAP, it would be of potential interest to identify compounds that selectively inhibit the growth of MTAP-deficient cells. To determine if MTAP inactivation could be targeted, the authors have performed a differential chemical genetic screen in

Yuwaraj Kadariya; Baiqing Tang; Cynthia B. Myers; Jami Fukui; Jeffrey R. Peterson; Warren D. Kruger

2011-01-01

123

Relationships between Chemical Structure and Rat Repellency. II. Compounds Screened Between 1950 and 1960.  

National Technical Information Service (NTIS)

Over 4,600 compounds, chiefly organic types, were evaluated using both a food acceptance test and a barrier penetration bioassay to correlate relationships between chemical structure and rodent repellency. These chemicals are indexed and classified accord...

J. B. DeWitt J. J. Pratt V. A. Adomaitis W. A. Bowles

1974-01-01

124

Are chemical compounds important for soybean resistance to Anticarsia gemmatalis?  

PubMed

The identification and quantification of flavonoids (rutin and genistin) present in extracts of soybean genotypes, and their effects on the biology and physiology of Anticarsia gemmatalis Hübner (Lep.: Noctuidae) were studied. Analysis of covariance and bicoordinate utilization plots were used to remove the effect of feeding time from pupal weight and consumption as well as to separate pre- and postingestive effects of treatment on A. gemmatalis growth. Genotypes PI 274454, PI 227687, and "IAC-100" extracts in general, caused higher mortality, negatively influenced initial larval and pupal weight, and elongated larval cycle. Larvae fed on the "IAC-100" extract diet ingested larger amounts of food per unit of time, but were less efficient in its conversion to biomass. Leaf extracts of PI 227687 had the largest concentration of rutin (quercitin 3-O-rhamnosylglucoside), followed by PI 274454, and "IAC-100"; PI 74454 also had the highest genistin (genistein 7-O-glucoside) content. The susceptible cultivar "BR-16" showed only a kaempferol-based flavonoid in its chemical profile, indicating that after successive crosses, secondary compounds responsible for plant defenses were eliminated. Genotypes PI 274454, PI 227687, and "IAC-100" showed accentuated resistance characteristics and were considered inadequate sources for the development of A. gemmatalis. Considering rutin and genistin concentration in these genotypes, it is suggested that flavonoids are important factors conferring resistance to A. gemmatalis. PMID:16222789

Piubelli, Giorla Carla; Hoffmann-Campo, Clara Beatriz; Moscardi, Flavio; Miyakubo, Sandra Hitomi; de Oliveira, Maria Cristina Neves

2005-07-01

125

Toward an efficient approach to identify molecular scaffolds possessing selective or promiscuous compounds.  

PubMed

The concept of a recurrent scaffold present in a series of structures is common in medicinal drug discovery. We present a scaffold analysis of compounds screened across 100 sequence-unrelated proteins to identify scaffolds that drive promiscuity or selectivity. Selectivity and promiscuity play a major role in traditional and poly-pharmacological drug design considerations. The collection employed here is the first publicly available data set containing the complete screening profiles of more than 15 000 compounds from different sources. In addition, no scaffold analysis of this data set has been reported. The protocol described here employs the Molecular Equivalence Index tool to facilitate the selection of Bemis-Murcko frameworks in the data set, which contain at least five compounds and Scaffold Hunter to generate a hierarchical tree of scaffolds. The annotation of the scaffold tree with protein-binding profile data enabled the successful identification of mostly highly specific compounds, due to data set constraints. We also applied this approach to a public set of 1497 small molecules screened non-uniformly across a panel of 172 protein kinases. The approach is general and can be applied to any other data sets and activity readout. PMID:23659738

Yongye, Austin B; Medina-Franco, José L

2013-09-10

126

Measurement of Infrared Spectra and Chemical Bonding of Inorganic Compounds.  

National Technical Information Service (NTIS)

Infra-red absorption spectra of selected families of inorganic solid compounds have been registered and discussed. The following types of compounds have been investigated: (1) Compounds with, or related to, the MgO (NaCl) structure. The spectrum, which is...

P. C. Tarte P. A. Flamee

1968-01-01

127

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

2013-01-23

128

In silico quantitative structure toxicity relationship of chemical compounds: some case studies.  

PubMed

Undesirable toxicity is still a major block in the drug discovery process. Obviously, capable techniques that identify poor effects at a very early stage of product development and provide reasonable toxicity estimates for the huge number of untested compounds are needed. In silico techniques are very useful for this purpose, because of their advantage in reducing time and cost. These case studies give the description of in silico validation techniques and applied modeling methods for the prediction of toxicity of chemical compounds. In silico toxicity prediction techniques can be classified into two categories: Molecular Modeling and methods that derive predictions from experimental data. Molecular modeling is a computational approach to mimic the behavior of molecules, from small molecules (e.g. in conformational analysis) to biomolecules. But the same approaches can also be applied for toxicological purposes, if the mechanism is receptor mediated. Quantitative Structure-Toxicity Relationships (QSTRs) models are typical examples for the prediction of toxicity which relates variations in the molecular structures to toxicity. There are many applied modeling techniques in QSTR such as Partial Least Squares, Artificial Neural Networks, and Principal Component Regression (PCR). The applicability of these techniques in predictive toxicology will be discussed with different examples of sets of chemical compounds. PMID:23062241

Deeb, Omar; Goodarzi, Mohammad

2012-09-01

129

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

PubMed

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

Galindo-Cuspinera, Veronica; Rankin, Scott A

2005-04-01

130

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

131

Chemical Genetic Screening Identifies a Novel Inhibitor of Parallel Alignment of Cortical Microtubules and Cellulose Microfibrils  

Microsoft Academic Search

It is a well-known hypothesis that cortical microtubules control the direction of cellulose microfibril deposition, and that the parallel cellulose microfibrils determine anisotropic cell expansion and plant cell morphogenesis. However, the molecular mechanism by which cortical microtubules regulate the orientation of cellulose microfibrils is still unclear. To investigate this mechanism, chemical genetic screening was performed. From this screening, 'SS compounds'

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

2007-01-01

132

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

ERIC Educational Resources Information Center

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

Cakmakci, Gultekin

2010-01-01

133

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

2012-08-23

134

Novel Dual-Reporter Preclinical Screen for Anti-Astrocytoma Agents Identifies Cytostatic and Cytotoxic Compounds  

PubMed Central

Astrocytoma/glioblastoma is the most common malignant form of brain cancer and is often unresponsive to current pharmacological therapies and surgical interventions. Despite several potential therapeutic agents against astrocytoma and glioblastoma (1), there are currently no effective therapies for astrocytoma, creating a great need for the identification of effective anti-tumor agents. We have developed a novel dual-reporter system in Trp53/Nf1-null astrocytoma cells to simultaneously and rapidly assay cell viability and cell cycle progression as evidenced by activity of the human E2F1 promoter in vitro. The dual-reporter high-throughput assay was used to screen experimental therapeutics for activity in Trp53/Nf1-null astrocytoma. Several compounds were identified demonstrating selectivity for astrocytoma over primary astrocytes. The dual-reporter system described here may be a valuable tool for identifying potential anti-tumor treatments that specifically target astrocytoma.

Hawes, Jessica J.; Nerva, John D.; Reilly, Karlyne M.

2009-01-01

135

Xenobiotic organic compounds in leachates from ten Danish MSW landfills—chemical analysis and toxicity tests  

Microsoft Academic Search

A monitoring program comprising chemical analysis and biological toxicity testing of leachate samples from 10 Danish landfills (six engineered and four uncontrolled) revealed the presence of 55 different xenobiotic organic compounds (XOCs) and 10 degradation products of XOCs. The compounds belong to the following groups: BTEX, C3-benzenes, bicyclo compounds, napthalenes, chlorinated aliphatics, phenols (chloro-, methyl-, dimethyl, nonyl-), pesticides, and phthalates.

A. Baun; A. Ledin; L. A. Reitzel; P. L. Bjerg; T. H. Christensen

2004-01-01

136

Numerical simulation of the chemical-signature-compounds transport from a mine field  

Microsoft Academic Search

The transport of the chemical signature compounds from buried landmines in a three-dimensional minefield array has been numerically modeled using the finite-volume technique. Compounds such as trinitrotoluene and dinitrotoluene are semi-volatile and somewhat soluble in water; furthermore, they can strongly adsorb to the soil and undergo chemical and biological degradation. Consequently, the spatial and temporal distributions of such chemicals depend

Ernesto E. Borrero; Julio G. Briano; Miguel E. Castro; Samuel P. Hernandez-Rivera

2004-01-01

137

A chemical genomic study identifying diversity in cell migration signaling in cancer cells  

PubMed Central

The aim of this study was to analyze the diversity and consistency of regulatory signaling in cancer cell migration, using a chemical genomic approach. The effects of 34 small molecular compounds were assessed quantitatively by wound healing assay in ten types of migrating cells. Hierarchical clustering was performed on the subsequent migration inhibition profile of the compounds and cancer cell types. The result was that hierarchical clustering accurately classified the compounds according to their targets. Furthermore, the cancer cells tested in this study were classified into three clusters, and the compounds were grouped into four clusters. An inhibitor of JNK suppressed all types of cell migration; however, inhibitors of ROCK, GSK-3 and p38MAPK only inhibited the migration of a subset of cell lines. Thus, our analytical system could easily distinguish between the common and cell type-specific signals responsible for cell migration.

Magi, Shigeyuki; Tashiro, Etsu; Imoto, Masaya

2012-01-01

138

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

139

Portable chemical gas sensor prototype for nitroaromatic compounds detection  

Microsoft Academic Search

This paper presents the conception and the development of portable gas sensor prototypes for nitroaromatic compounds detection. It is based on quartz crystal microbalance (QCM) principle and a data processing. The sensitive material is a polymer which was chosen for its good sensibility and robustness. This prototype is able to detect 3 ppm of nitroaromatic compound with a high selectivity.

F. Thery-Merland; P. Montmeat; E. Pasquinet; L. Hairault

2004-01-01

140

GPM: A graph pattern matching kernel with diffusion for chemical compound classification  

Microsoft Academic Search

Classifying chemical compounds is an active topic in drug design and other cheminformatics applications. Graphs are general tools for organizing information from heterogenous sources and have been applied in modelling many kinds of biological data. With the fast accumulation of chemical structure data, building highly accurate predictive models for chemical graphs emerges as a new challenge . In this paper,

Aaron M. Smalter; Jun Huan; Gerald H. Lushington

2008-01-01

141

Data mining of protein-binding profiling data identifies structural modifications that distinguish selective and promiscuous compounds.  

PubMed

Activity profiling of compound collections across multiple targets is increasingly being used in probe and drug discovery. Herein, we discuss an approach to systematically analyzing the structure-activity relationships of a large screening profile data with emphasis on identifying structural changes that have a significant impact on the number of proteins to which a compound binds. As a case study, we analyzed a recently released public data set of more than 15?000 compounds screened across 100 sequence-unrelated proteins. The screened compounds have different origins and include natural products, synthetic molecules from academic groups, and commercial compounds. Similar synthetic structures from academic groups showed, overall, greater promiscuity differences than do natural products and commercial compounds. The method implemented in this work readily identified structural changes that differentiated highly specific from promiscuous compounds. This approach is general and can be applied to analyze any other large-scale protein-binding profile data. PMID:22856455

Yongye, Austin B; Medina-Franco, José L

2012-08-17

142

T-Screen as a tool to identify thyroid hormone receptor active compounds.  

PubMed

The T-Screen represents an in vitro bioassay based on thyroid hormone dependent cell proliferation of a rat pituitary tumour cell line (GH3) in serum-free medium. It can be used to study interference of compounds with thyroid hormone at the cellular level, thus bridging the gap between limitations of assays using either isolated molecules (enzymes, transport proteins) or complex in vivo experiments with all the complex feedback mechanisms present. Compounds are tested both in the absence and presence of thyroid hormone (EC(50) concentration of T(3)) to test for both agonistic and antagonistic potency. Thyroid hormones (3,3'-5-triiodothyronine: T(3) and 3,3',5,5'-tetraiodothyroxine: T(4)) and compounds resembling the structure of thyroid hormones (3,3'-5-triiodothyroacetic acid: Triac; 3,3',5,5'-tetraiodothyroacetic acid: Tetrac) induced cell growth, with the rank order Triac > T(3) > Tetrac > T(4) (relative potency = 1.35 > 1 > 0.29 > 0.07), which is identical to published affinities of these compounds for nuclear thyroid hormone receptors. Exposure to 5,5'-diphenylhydantoin (DPH) in the presence of 0.25nM T(3) resulted in up to 60% decreased cell growth at 200?M DPH. No effect of DPH on basal metabolic activity of GH3 cells was observed at this concentration. Fentinchloride (IC(50) = 21nM) decreased cell growth induced by 0.25nM T(3), whereas parallel exposure to these concentrations in the absence of T(3) did not alter basal metabolic activities of GH3 cells. Apolar sediment extracts from the Dommel (34%) and Terneuzen (14%) decreased cell growth in the presence of 0.25nM T(3), whereas the extract from Hoogeveen increased cell growth (26%) and the extract from North Sea Channel had no effect. The T-Screen proved to be a fast and functional assay for assessing thyroid hormone receptor active potencies of pure chemicals or environmental mixtures. PMID:21783481

Gutleb, Arno C; Meerts, Ilonka A T M; Bergsma, Joost H; Schriks, Merijn; Murk, Albertinka J

2005-02-01

143

Polyphenolic compounds as chemical markers of wine ageing in contact with cherry, chestnut, false acacia, ash and oak wood.  

PubMed

The nonanthocyanic phenolic composition of four red wines, one white, and one rosé aged using barrels and chips of cherry, chestnut, false acacia, ash and oak wood was studied by LC-DAD-ESI/MS, to identify the phenolic compounds that woods other than oak contribute to wines, and if some of them can be used as chemical markers of ageing with them. A total of 68 nonanthocyanic phenolic compounds were identified, 15 found only in wines aged with acacia wood, 6 with cherry wood, and 1 with chestnut wood. Thus, the nonanthocyanic phenolic profile could be a useful tool to identify wines aged in contact with these woods. In addition, some differences in the nonanthocyanic phenolic composition of wines were detected related to both the levels of compounds provided by each wood species and the different evolution of flavonols and flavanols in wines during ageing in barrels or in contact with chips. PMID:24054214

Fernández de Simón, B; Sanz, M; Cadahía, E; Martínez, J; Esteruelas, E; Muñoz, A M

2013-07-27

144

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

2012-08-07

145

Introduction of Chemical Compounds Into Drinking Water during Distribution.  

National Technical Information Service (NTIS)

Contents: Piping materials used for water distribution in the European Communities; Processes causing the release of compounds from piping materials; Results of a study in the Netherlands on changes of the levels of some water contaminants during distribu...

B. C. J. Zoeteman B. J. A. Haring

1978-01-01

146

Environmental Fate of Organophosphorus Compounds Related to Chemical Weapons.  

National Technical Information Service (NTIS)

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...

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

2005-01-01

147

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

148

Chemical weapons: documented use and compounds on the horizon.  

PubMed

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

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

2004-04-01

149

Investigation of chemical compounds, antioxidant and antimicrobial properties of teucrium arduini L. (lamiaceae).  

PubMed

In this paper chemical composition of the essential oil (analysed by GC and GC-MS), the content of phenolic compounds (analysed by HPLC), quantity of total phenols and total flavonoids (analysed by UV/Vis spectrophotometer), antioxidant and antimicrobial activities of ethanolic extracts were investigated in endemic Teucrium arduini L. in population of Mt Biokovo (Croatia). The oil was characterized by a high concentration of sesquiterpene hydrocarbons (70.4%) of which ?-caryophyllene (35.2%) and germacrene D (18.7%) being the major compounds. Three phenolic compounds (quercetin, ferulic acid and rosmarinic acid) were identified and quantified in ethanolic extract of T. arduini using HPLC. The results also showed that T. arduini is a source of polyphenolic and other antioxidants with radical-scavenging and chelating properties. The ethanol extracts prepared from the leaf of T. arduini showed broad spectrum of antimicrobial activity on Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus brasiliensis, which are susceptible on concentration below or equal to 4.00 mg/mL, whilst Microsporum gypseum was resistant at investigated concentrations. PMID:23597042

Kremer, Dario; Kosir, Iztok Joze; Kosalec, Ivan; Koncic, Marijana Zovko; Potocnik, Tanja; Cerenak, Andreja; Bezic, Nada; Srecec, Sinisa; Dunkic, Valerija

2013-08-01

150

Quantum-chemical Calculations in the Study of Antitumour Compounds  

NASA Astrophysics Data System (ADS)

The results of quantum-chemical calculations on antitumour preparations concerning the mechanism of their action at the electronic and molecular levels and structure-activity correlations are discussed in this review. Preparations whose action involves alkylating and free-radial mechanisms, complex-forming agents, and antimetabolites are considered. Modern quantum-chemical methods for calculations on biologically active substances are described. The bibliography includes 106 references.

Luzhkov, V. B.; Bogdanov, G. N.

1986-01-01

151

A Novel Histone Deacetylase Inhibitor Identified by High-Throughput Transcriptional Screening of a Compound Library1  

Microsoft Academic Search

Libraries of compounds are increasingly becoming commercially avail- able for the use of individual academic laboratories. A high-throughput system based on a stably integrated transcriptional reporter was used to screen a library of random compounds to identify agents that conferred robust augmentation of a signal transduction pathway. A novel histone deacetylase (HDAC) inhibitor, termed scriptaid, conferred the greatest effect, a

Gloria H. Su; Taylor A. Sohn; Byungwoo Ryu; Scott E. Kern

2000-01-01

152

Emission and Chemical Transformation of Biogenic Volatile Organic Compounds (echo)  

Microsoft Academic Search

Forests are complex sources of biogenic volatile organic compounds (VOC) in the planetary boundary layer. The impact of biogenic VOC on tropospheric photochem- istry, air quality, and the formation of secondary products affects our climate on a regional and global scale but is far from being understood. A considerable lack of knowledge exists concerning a forest stand as a net

R. Koppmann; T. Hoffmann; J. Kesselmeier; M. Schatzmann

2002-01-01

153

Determination of Organobromide Compounds in Water by Gas Chromatography-Negative Ion Chemical Ionisation Mass Spectrometry.  

National Technical Information Service (NTIS)

Gas chromatography-negative ion chemical ionization mass spectrometry (GC-NCIMS) was evaluated as a method for qualitative and quantitative determination of organobromine compounds in water. The negative ion mass spectra of bromine-containing trihalometha...

K. Koida Y. Kohno Y. Fukuda K. Sekigawa S. Yoshizaki

1985-01-01

154

Syntheses and Characterization of Model Imide Compounds and Chemical Imidization Study. (Reannouncement with New Availability Information).  

National Technical Information Service (NTIS)

In order to characterize various depolymerization and imidization reactions involved during thermal and chemical imidization of poly(amic acid) by UV-visible and fluorescence spectroscopies, several model compounds have been synthesized and characterized ...

M. H. Kailani C. S. Sung S. J. Huang

1992-01-01

155

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...

156

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 ...

157

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 ...

158

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

PubMed Central

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

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

2006-01-01

159

A 3D-QSAR model based screen for dihydropyridine-like compound library to identify inhibitors of amyloid beta (A?) production.  

PubMed

Abnormal accumulation of amyloid beta peptide (A?) is one of the hallmarks of Alzheimer's disease progression. Practical limitations such as cost , poor hit rates and a lack of well characterized targets are a major bottle neck in the in vitro screening of a large number of chemical libraries and profiling them to identify A? inhibitors. We used a limited set of 1,4 dihydropyridine (DHP)-like compounds from our model set (MS) of 24 compounds which inhibit A? as a training set and built 3D-QSAR (Three-dimensional Quantitative Structure-Activity Relationship) models using the Phase program (SchrÖdinger, USA). We developed a 3D-QSAR model that showed the best prediction for A? inhibition in the test set of compounds and used this model to screen a 1,043 DHP-like small library set of (LS) compounds. We found that our model can effectively predict potent hits at a very high rate and result in significant cost savings when screening larger libraries. We describe here our in silico model building strategy, model selection parameters and the chemical features that are useful for successful screening of DHP and DHP-like chemical libraries for A? inhibitors. PMID:21364791

Mathura, Venkatarajan S; Patel, Nikunj; Bachmeier, Corbin; Mullan, Michael; Paris, Daniel

2010-09-20

160

A 3D-QSAR model based screen for dihydropyridine-like compound library to identify inhibitors of amyloid beta (A?) production  

PubMed Central

Abnormal accumulation of amyloid beta peptide (A?) is one of the hallmarks of Alzheimer's disease progression. Practical limitations such as cost , poor hit rates and a lack of well characterized targets are a major bottle neck in the in vitro screening of a large number of chemical libraries and profiling them to identify A? inhibitors. We used a limited set of 1,4 dihydropyridine (DHP)-like compounds from our model set (MS) of 24 compounds which inhibit A? as a training set and built 3D-QSAR (Three-dimensional Quantitative Structure-Activity Relationship) models using the Phase program (SchrÖdinger, USA). We developed a 3D-QSAR model that showed the best prediction for A? inhibition in the test set of compounds and used this model to screen a 1,043 DHP-like small library set of (LS) compounds. We found that our model can effectively predict potent hits at a very high rate and result in significant cost savings when screening larger libraries. We describe here our in silico model building strategy, model selection parameters and the chemical features that are useful for successful screening of DHP and DHP-like chemical libraries for A? inhibitors.

Mathura, Venkatarajan S; Patel, Nikunj; Bachmeier, Corbin; Mullan, Michael; Paris, Daniel

2010-01-01

161

Effect of some chemical and herbal compounds on growth of Aspergillus parasiticus and aflatoxin production  

Microsoft Academic Search

The anti-fungal properties of a series of chemical and herbal compounds at different levels was tested on potato dextrose agar. Among the chemical compounds, propionic acid at 0.1–0.5%, ammonia at 0.5%, copper sulphate at 0.08–0.5% and benzoic acid at 0.1–0.5% completely inhibited Aspergillus parasiticus growth. Urea, citric acid and sodium propionate had moderate anti-fungal properties (36–64% reduction). Among the herbal

N. K. S. Gowda; V. Malathi; R. U. Suganthi

2004-01-01

162

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

Microsoft Academic Search

The transport of the chemical signature compounds from buried landmines in a three-dimensional (3D) array has been numerically modeled using the finite-volume technique. Compounds such as trinitrotoluene, dinitrotoluene, and their degradation products, are semi volatile and somewhat soluble in water. Furthermore, they can strongly adsorb to the soil and undergo chemical and biological degradation. Consequently, the spatial and temporal concentration

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

2005-01-01

163

Chemical-genetic profile analysis of five inhibitory compounds in yeast  

Microsoft Academic Search

BACKGROUND: Chemical-genetic profiling of inhibitory compounds can lead to identification of their modes of action. These profiles can help elucidate the complex interactions between small bioactive compounds and the cell machinery, and explain putative gene function(s). RESULTS: Colony size reduction was used to investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These

Veronika Erukova; Matthew Jessulat; Ali Azizi; Ashkan Golshani

2010-01-01

164

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

PubMed Central

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

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

2009-01-01

165

Chemical class separation and characterization of organic compounds in synthetic fuels  

Microsoft Academic Search

A separation method is described for the identification of organic compounds in synthetic fuel products. Prefractionation of crude synfuel materials into discrete chemical classes was prformed by adsorption column chromatography using small quantities of neutral aluminum oxide and silicic acid. Subsequent high-resolution separation of individual components was achieved by using capillary column gas chromatography, and specific compound types were determined

Douglas W. Later; Milton L. Lee; Keith D. Bartle; Robert C. Kong; Daniel L. Vassilaros

1981-01-01

166

Have Chemical Compounds a Definite Critical Temperature and Pressure of Decomposition?  

Microsoft Academic Search

So far nobody seems to have considered the question whether to every chemical compound there exists a definite critical temperature and pressure of decomposition. Yet I think the following considerations show that such constants probably do exist. Suppose we place a given compound (say CaCO3) in a closed cylinder and subject it to a continually increasing temperature, keeping the pressure

Geoffrey Martin

1905-01-01

167

Extending the Capabilities of the Portable Chemical Parameter Spectrometer to Identification of Up to 100 Compounds.  

National Technical Information Service (NTIS)

An algorithm has been developed that will extend the capability of the Chemical Parameter Spectrometer (CPS) to identification of any one of up to 100 compounds. The algorithm divides a given set of compounds into smaller subsets according to empirical cr...

S. Zaromb R. Battin W. R. Penrose J. R. Stetter V. C. Stamoudis

1986-01-01

168

Acyclic Subgraph based 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 potential drug-like compounds has been an active area of research. These techniques are used extensively at various phases during the drug development process. Many of the best-performing techniques for these tasks, utilize a descriptor- based representation of the

Nikil Wale; George Karypis

169

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

170

Data mining on carcinogenicity of chemical compounds by the JSM method  

Microsoft Academic Search

Prediction of the carcinogenicity of chemical compounds to rats was carried out by data mining analysis based on the logic\\u000a of John Stuart Mill (JSM) and the fragmentary code of the substructure superposition (FCSS) data presentation language. The\\u000a learning (608 compounds) and test (156 compounds) samples were taken from the database on the carcinogenicity of substances\\u000a for laboratory animals developed

N. V. Kharchevnikova; V. G. Blinova; D. A. Dobrynin; N. Fedorova; M. Novich; M. Vrachko

2009-01-01

171

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

Federal Register 2010, 2011, 2012, 2013

...ICCVAM Recommendations on Using Fewer Animals to Identify Chemical Eye Hazards: Revised...classification criteria using results from 3-animal tests that would provide eye hazard classification...regulations, which require the use of 6 to 18 animals. The results showed that using a...

2011-08-12

172

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

EPA Science Inventory

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

173

Frequent Sub-Structure-Based Approaches for Classifying Chemical Compounds  

Microsoft Academic Search

In this paper we study the problem of classifying chemical com- pound datasets. We present a sub-structure-based classifica- tion algorithm that decouples the sub-structure discovery pro- cess from the classification model construction and uses frequent subgraph discovery algorithms to find all topological and geo- metric sub-structures present in the dataset. The advantage of our approach is that during classification model

Mukund Deshpande; Michihiro Kuramochi; George Karypis

2003-01-01

174

Model of growth for long-range chemically ordered compounds : application to quasicrystals  

Microsoft Academic Search

We propose an electronic model for the growth of long-range chemically ordered binary compounds. By varying one parameter, we show that a specific concentration can be dinamically selected and the associated chemical order propagated during a rapid solidification. The basic assumptions of the model are: 1) the diffusion inside the growing structure is frozen out, and 2) the \\

Pascal Quémerais

1994-01-01

175

Factors influencing nominal effective concentrations of chemical compounds in vitro: cell concentration  

Microsoft Academic Search

In vitro potency data (e.g. EC50 values), used to characterise the biological activity of chemicals, are generally based on nominal effective concentrations and thus depend on any factor influencing the availability of a compound. In this study the significance of cell binding for the availability of chemicals in vitro is (i) theoretically investigated by means of a simple equilibrium distribution

M Gülden; S Mörchel; H Seibert

2001-01-01

176

Factors influencing nominal effective concentrations of chemical compounds in vitro: medium protein concentration  

Microsoft Academic Search

Quantitative data used to characterise biological activities of chemicals in vitro (e. g. EC50 values) are generally based on nominal concentrations and thus depend on factors influencing the availability of a compound. In this study, the impact of protein binding on the availability of chemicals in vitro is theoretically investigated and experimentally examined using a bovine sperm cell assay to

H. Seibert; S. Mörchel; M. Gülden

2002-01-01

177

Symbolic, Neural, and Bayesian Machine Learning Models for Predicting Carcinogenicity of Chemical Compounds  

Microsoft Academic Search

Experimental programs have been underway for several years to determine the environmental efiects of chemical compounds, mixtures, and the like. Among these programs is the National Toxicology Pro- gram (NTP) on rodent carcinogenicity. Because these experiments are costly and time consuming, the rate at which test articles (i.e., chemicals) can be tested is limited. The ability to predict the out-

Dennis Bahler; Brian Stone; Carol Wellington; Douglas W. Bristol

2000-01-01

178

Effect of Selected Chemical Compounds on the Lubrication of Silicon Carbide  

Microsoft Academic Search

A systematic study has been conducted to investigate the interactions between selected chemical compounds and silicon carbide under boundary lubrication conditions. A modified four-ball wear tester was used to evaluate the additive effectiveness on silicon carbides lubricated with a paraffinic base oil containing one weight percent of additives. Friction, wear, and film morphology were observed for a range of chemical

Douglas E. Deckman; Chun-I Chen; Stephen M. Hsu

1999-01-01

179

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

180

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

PubMed

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

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

2012-01-18

181

Halenaquinone, a chemical compound that specifically inhibits the secondary DNA binding of RAD51.  

PubMed

Mutations and single-nucleotide polymorphisms affecting RAD51 gene function have been identified in several tumors, suggesting that the inappropriate expression of RAD51 activity may cause tumorigenesis. RAD51 is an essential enzyme for the homologous recombinational repair (HRR) of DNA double-strand breaks. In the HRR pathway, RAD51 catalyzes the homologous pairing between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), which is the central step of the HRR pathway. To identify a chemical compound that regulates the homologous-pairing activity of RAD51, in the present study, we screened crude extract fractions from marine sponges by the RAD51-mediated homologous-pairing assay. Halenaquinone was identified as an inhibitor of the RAD51 homologous-pairing activity. A surface plasmon resonance analysis indicated that halenaquinone directly bound to RAD51. Intriguingly, halenaquinone specifically inhibited dsDNA binding by RAD51 alone or the RAD51-ssDNA complex, but only weakly affected the RAD51-ssDNA binding. In vivo, halenaquinone significantly inhibited the retention of RAD51 at double-strand break sites. Therefore, halenaquinone is a novel type of RAD51 inhibitor that specifically inhibits the RAD51-dsDNA binding. PMID:21375680

Takaku, Motoki; Kainuma, Takashi; Ishida-Takaku, Takako; Ishigami, Shintaro; Suzuki, Hidekazu; Tashiro, Satoshi; van Soest, Rob W M; Nakao, Yoichi; Kurumizaka, Hitoshi

2011-03-06

182

Bioluminescence and exogenous compounds: physico-chemical basis for bioluminescent assay.  

PubMed

Bioluminescent systems are convenient objects to study mechanisms of influence of exogenous molecules on living organisms. Classification of physical and physico-chemical mechanisms of the effects of luminous bacteria Photobacterium leiognathi on bioluminescent reactions is suggested. Five mechanisms are discussed: (1) change of electron-excited states' population and energy transfer, (2) change of efficiency of S-T conversion in the presence of external heavy atom, (3) change of rates of coupled reactions, (4) interactions with enzymes and variation of enzymatic activity, (5) nonspecific effects of electron acceptors. Effects of various groups of chemical compounds are discussed according to the classification suggested. The compounds are: a series of fluorescent dyes, organic oxidizers, organic and inorganic heavy-atom containing compounds, and metallic salts. Applications of fluorescence time-resolved and steady-state techniques, as well as bioluminescence kinetics study, are discussed. The patterns of exogenous compounds' influence form a physico-chemical basis for bioluminescent ecological assay. PMID:16413195

Kudryasheva, Nadezhda S

2006-01-18

183

Chemical-Genetic Screen Identifies Riluzole as an Enhancer of Wnt/?-catenin signaling in Melanoma  

PubMed Central

SUMMARY To identify new protein and pharmacological regulators of Wnt/?-catenin signaling we used a cell-based reporter assay to screen a collection of 1857 human-experienced compounds for their ability to enhance activation of the ?-catenin reporter by a low concentration of WNT3A. This identified 44 unique compounds, including the FDA-approved drug riluzole, which is presently in clinical trials for treating melanoma. We found that treating melanoma cells with riluzole in vitro enhances the ability of WNT3A to regulate gene expression, to promote pigmentation, and to decrease cell proliferation. Furthermore riluzole, like WNT3A, decreases metastases in a mouse melanoma model. Interestingly, siRNAs targeting the metabotropic glutamate receptor, GRM1, a reported indirect target of riluzole, enhance ?-catenin signaling. The unexpected regulation of ?-catenin signaling by both riluzole and GRM1 has implications for the future uses of this drug.

Biechele, Travis L.; Camp, Nathan D.; Fass, Daniel M.; Kulikauskas, Rima M.; Robin, Nick C.; White, Bryan D.; Taraska, Corinne M.; Moore, Erin C.; Muster, Jeanot; Karmacharya, Rakesh; Haggarty, Stephen J.; Chien, Andy J.; Moon, Randall T.

2010-01-01

184

A predictive nuclear translocation assay for spliced x-box-binding protein 1 identifies compounds with known organ toxicities.  

PubMed

Compound toxicity is still the main cause of attrition, emphasizing the need for novel predictive assays to identify toxic compounds early during drug development. Endoplasmic reticulum (ER) stress has recently been discovered as a molecular event that links cellular dysfunction to drug-induced organ toxicity in humans. Among higher organisms the inositol-requiring transmembrane kinase/endoribonuclease pathway plays a major role in mediating the ER stress response. Inositol-requiring transmembrane kinase/endoribonuclease achieves this through its endoribonuclease activity causing a frameshift in the translation of the X-box-binding protein 1 (XBP1) to produce spliced XBP1 (XBP1s), which translocates into the nucleus, where it initiates transcription of ER stress response genes. Based on this biology, we have designed a novel ?-galactosidase-based XBP1s-enzyme fragment complementation assay, which enables identification of compound-induced ER stress in human U2OS cells. The XBP1s-enzyme fragment complementation assay was established in a 384-well format and validated using a library of 1280 pharmacologically active compounds. Importantly, the library of pharmacologically active compounds screen identified both well-established ER stress inducers and several compounds that are known organ toxicants but not previously reported to induce ER stress. Implementation of this assay to assess compound-induced ER stress will facilitate decision making for compound selection and we believe that it will significantly increase the ability to reduce toxicity of preclinical drug candidates. PMID:20858054

Hahmann, Christa; Weiser, Amiee; Duckett, Derek; Schroeter, Thomas

2010-09-21

185

A Graph Mining Algorithm for Classifying Chemical Compounds  

Microsoft Academic Search

Graph data mining algorithms are increasingly applied to biological graph dataset. However, while existing graph mining algorithms can identify frequently occurring sub-graphs, these do not necessarily represent useful patterns. In this paper, we propose a novel graph mining algorithm, MIGDAC (Mining Graph DAta for Classification), that applies graph theory and an interestingness measure to discover interesting sub-graphs which can be

Winnie W. M. Lam; Keith C. C. Chan

2008-01-01

186

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

2012-08-26

187

A new in vitro method for identifying chemical sensitizers combining peptide binding with ARE/EpRE-mediated gene expression in human skin cells.  

PubMed

Allergic contact dermatitis (ACD) is a significant safety concern for developers of cosmetic, personal care, chemical, pharmaceutical, and medical device products. The guinea pig maximization test (GMPT) and the murine local lymph node assay (LLNA) are accepted methods for determining chemical sensitization. Recent legislative initiatives in Europe require the development of new in vitro alternatives to animal tests for chemical sensitization. The aim of this project was to develop an in vitro screening method that uses a human skin cell line (HaCaT), chemical reactivity, and gene expression profiling to identify positive and negative responses, to place chemicals into potency categories of extreme/strong (ES), moderate (M), weak (W), and nonsensitizers (N), and to provide an estimate of corresponding LLNA values. The method and processing algorithm were developed from a training set of 39 chemicals possessing a wide range of sensitization potencies. Three cationic metals, chromium (Cr), nickel (Ni), and silver (Ag), were also evaluated in this model. Chemical reactivity was determined by measuring glutathione (GSH) depletion in a cell free matrix. Three signaling pathways (Keap1/Nrf 2/ARE/EpRE, ARNT/AhR/XRE, and Nrf1/MTF/MRE) that are known to be activated by sensitizing agents were monitored by measuring the relative abundance of 11 genes whose expression is controlled by one of these 3 pathways. Final exposure concentrations were based on toxicity and solubility. A range-finding experiment was conducted with each compound to determine cytotoxicity and solubility. Six exposure concentrations (0.1 to 2,500 microM) and an exposure time of 24 hours were used in the final experiments. Glutathione depletion alone did not provide the accuracy necessary to differentiate potency categories. However, chemical reactivity combined with gene expression profiles significantly improved the in vitro predictions. A predicted toxicity index (PTI) was determined for each test chemical. A comparison of LLNA values with PTI values revealed an inverse relationship. The large variation in LLNA data for compounds in the same potency category makes direct extrapolation from PTI to LLNA difficult. To challenge the system, 58 additional compounds were submitted in a blinded manner. Compounds placed into ES and M categories were considered positive, whereas compounds classified as W or N were considered negative. Accuracy was approximately 84%, with a sensitivity of 81% and a specificity of 92%. The model correctly identified 2 of 3 cationic metals as positive. In conclusion, the method described here demonstrates a valuable in vitro method for identifying chemicals and metals that induce skin sensitization. PMID:20491607

McKim, James M; Keller, Don J; Gorski, Joel R

2010-09-01

188

Electrophysiological and Behavioral Responses of Female Helicoverpa armigera to Compounds Identified in Flowers of African Marigold, Tagetes erecta  

Microsoft Academic Search

Seven electrophysiologically active compounds were detected in air-entrained headspace samples of live flowers of Tagetes erectaanalyzed by gas chromatography (GC) linked to a female Helicoverpa armigeraelectroantennograph (EAG) using polar and nonpolar capillary columns. These compounds were subsequently identified using GC linked to mass spectrometry as benzaldehyde, (S)-(-)-limonene, (R,S)-(±)-linalool, (E)-myroxide, (Z)-ß-ocimene, phenylacetaldehyde, and (R)-(-)-piperitone. Electrophysiological activity was confirmed by EAG with

Toby J. Bruce; Alan Cork

2001-01-01

189

Title III section 313 release reporting guidance: Estimating chemical releases from rubber production and compounding  

SciTech Connect

Facilities engaged in rubber production and compounding may be required to report annually any releases to the environment of certain chemicals regulated under Section 313, Title III, of the Superfund Amendments and Reauthorization Act (SARA) of 1986. The document has been developed to assist those who produce rubber in the completion of Part III (Chemical Specific Information) of the Toxic Chemical Release Inventory Reporting Form. Included herein is general information on toxic chemicals used and process wastes generated, along with several examples to demonstrate the types of data needed and various methodologies available for estimating releases.

Not Available

1988-03-01

190

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

191

Small molecule screening in zebrafish: an in vivo approach to identifying new chemical tools and drug leads  

Microsoft Academic Search

In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology. More recently, chemical screens in zebrafish have identified small molecules that can modulate specific developmental and behavioural processes. Zebrafish are a unique vertebrate system in which to study chemical genetic systems, identify drug leads,

Kerrie L Taylor; Nicola J Grant; Nicholas D Temperley; E. Elizabeth Patton

2010-01-01

192

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

193

Identification strategy for unknown pollutants using high-resolution mass spectrometry: Androgen-disrupting compounds identified through effect-directed analysis  

Microsoft Academic Search

Effect-directed analysis has been applied to a river sediment sample of concern to identify the compounds responsible for\\u000a the observed effects in an in vitro (anti-)androgenicity assay. For identification after non-target analysis performed on\\u000a a high-resolution LTQ-Orbitrap, we developed a de novo identification strategy including physico-chemical parameters derived\\u000a from the effect-directed analysis approach. With this identification strategy, we were able

Jana M. Weiss; Eszter Simon; Gerard J. Stroomberg; Ronald de Boer; Jacob de Boer; Sander C. van der Linden; Pim E. G. Leonards; Marja H. Lamoree

2011-01-01

194

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

Microsoft Academic Search

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

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

1996-01-01

195

Chemical class separation and characterization of organic compounds in synthetic fuels  

SciTech Connect

A separation method is described for the identification of organic compounds in synthetic fuel products. Prefractionation of crude synfuel materials into discrete chemical classes was prformed by adsorption column chromatography using small quantities of neutral aluminum oxide and silicic acid. Subsequent high-resolution separation of individual components was achieved by using capillary column gas chromatography, and specific compound types were determined by gas chromatographic retention data and combined gas chromatography-mass spectrometry. The principal chemical classes investigated in a solvent-refined coal liquid were aliphatic hydrocarbons, polycyclic aromatic hydrocarbons, polycyclic aromatic sulfur heterocycles nitrogen polycyclic aromatic compounds, and hydroxyl polycyclic aromatic hydrocarbons. The nitrogen-containing aromatic compounds were further separated into secondary nitrogen polycyclic aromatic heterocycles, amino polycyclic aromatic hydrocarbons, and tertiary nitrogen polycyclic aromatic heterocycles to facilitate their identification.

Later, D.W.; Lee, M.L.; Bartle, K.D.; Kong, R.C.; Vassilaros, D.L.

1981-09-01

196

High-throughput screening of libraries of compounds to identify CFTR modulators.  

PubMed

Small molecules acting as selective activators (potentiators), inhibitors, or "correctors" of the CFTR chloride channel represent candidate drugs for various pathological conditions including cystic fibrosis and secretory diarrhea. The identification of CFTR pharmacological modulators may be achieved by screening highly diverse synthetic or natural compound libraries using high-throughput methods. A convenient assay for CFTR function is based on the halide sensitivity of the yellow fluorescent protein (YFP). CFTR activity can be simply assessed by measuring the rate of YFP signal decrease caused by iodide influx. This assay can be automated to test thousands of compounds per day. PMID:21594775

Pedemonte, Nicoletta; Zegarra-Moran, Olga; Galietta, Luis J V

2011-01-01

197

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

198

Quantum chemical studies on corrosion inhibition forseries of thio compounds on mild steel in hydrochloric acid  

Microsoft Academic Search

Quantum chemical calculations were performed on tenthio compounds using semi-empirical method PM3 within program package of Material Studio 5.5.The effect of molecular structure on the corrosion inhibition efficiency was investigated using the quantum chemical calculations. The electronic properties such as highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) energy levels, (LUMO–HOMO) energy gap, dipole moment (?) and fraction

Ahmed Y. Musa; Abu Bakar Mohamad; Abdul Amir H. Kadhum; Mohd SobriTakriff; Waleed Ahmoda

199

The Chemical Constitution of Compounds Which Protect Erythrocytes against Freezing Damage  

PubMed Central

Eleven simple neutral water-miscible compounds were tested for protective action against freezing damage to human red blood cells. All the compounds penetrated the cells at room temperature without damage, but only four, N-substituted amides, were active. These results are considered together with previously published work on freezing protection by other low molecuar weight solutes. The affinity of the compounds for water is gauged in two independent ways, and correlates well with protective ability. The chemical constitutional factors responsible for high affinity for water are discussed. It appears that basic character is most important.

Nash, T.

1962-01-01

200

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

NASA Astrophysics Data System (ADS)

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

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

2005-06-01

201

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

USGS Publications Warehouse

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

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

1974-01-01

202

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

USGS Publications Warehouse

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

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

1974-01-01

203

Chemical genetic screen identifies Toxoplasma DJ-1 as a regulator of parasite secretion, attachment, and invasion.  

PubMed

Toxoplasma gondii is a member of the phylum Apicomplexa that includes several important human pathogens, such as Cryptosporidium and Plasmodium falciparum, the causative agent of human malaria. It is an obligate intracellular parasite that can cause severe disease in congenitally infected neonates and immunocompromised individuals. Despite the importance of attachment and invasion to the success of the parasite, little is known about the underlying mechanisms that drive these processes. Here we describe a screen to identify small molecules that block the process of host cell invasion by the T. gondii parasite. We identified a small molecule that specifically and irreversibly blocks parasite attachment and subsequent invasion of host cells. Using tandem orthogonal proteolysis-activity-based protein profiling, we determined that this compound covalently modifies a single cysteine residue in a poorly characterized protein homologous to the human protein DJ-1. Mutation of this key cysteine residue in the native gene sequence resulted in parasites that were resistant to inhibition of host cell attachment and invasion by the compound. Further analysis of the invasion phenotype confirmed that modification of Cys127 on TgDJ-1 resulted in a block of microneme secretion and motility, even in the presence of direct stimulators of calcium release. Together, our results suggest that TgDJ-1 plays an important role that is likely downstream of the calcium flux required for microneme secretion, parasite motility, and subsequent invasion of host cells. PMID:21670272

Hall, Carolyn I; Reese, Michael L; Weerapana, Eranthie; Child, Matthew A; Bowyer, Paul W; Albrow, Victoria E; Haraldsen, Jeralyn D; Phillips, MacDonald R; Sandoval, Edgar Deu; Ward, Gary E; Cravatt, Benjamin F; Boothroyd, John C; Bogyo, Matthew

2011-06-13

204

Chemical genetic screen identifies Toxoplasma DJ-1 as a regulator of parasite secretion, attachment, and invasion  

PubMed Central

Toxoplasma gondii is a member of the phylum Apicomplexa that includes several important human pathogens, such as Cryptosporidium and Plasmodium falciparum, the causative agent of human malaria. It is an obligate intracellular parasite that can cause severe disease in congenitally infected neonates and immunocompromised individuals. Despite the importance of attachment and invasion to the success of the parasite, little is known about the underlying mechanisms that drive these processes. Here we describe a screen to identify small molecules that block the process of host cell invasion by the T. gondii parasite. We identified a small molecule that specifically and irreversibly blocks parasite attachment and subsequent invasion of host cells. Using tandem orthogonal proteolysis–activity-based protein profiling, we determined that this compound covalently modifies a single cysteine residue in a poorly characterized protein homologous to the human protein DJ-1. Mutation of this key cysteine residue in the native gene sequence resulted in parasites that were resistant to inhibition of host cell attachment and invasion by the compound. Further analysis of the invasion phenotype confirmed that modification of Cys127 on TgDJ-1 resulted in a block of microneme secretion and motility, even in the presence of direct stimulators of calcium release. Together, our results suggest that TgDJ-1 plays an important role that is likely downstream of the calcium flux required for microneme secretion, parasite motility, and subsequent invasion of host cells.

Hall, Carolyn I.; Reese, Michael L.; Weerapana, Eranthie; Child, Matthew A.; Bowyer, Paul W.; Albrow, Victoria E.; Haraldsen, Jeralyn D.; Phillips, MacDonald R.; Sandoval, Edgar Deu; Ward, Gary E.; Cravatt, Benjamin F.; Boothroyd, John C.; Bogyo, Matthew

2011-01-01

205

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

PubMed Central

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

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

2009-01-01

206

Sensitive Markers Used to Identify Compounds That Trigger Apoptosis in Cultured Hepatocytes  

Microsoft Academic Search

Apoptosis may be a major event in chemical-induced injury, and therefore the detection of apoptotic effects when developing new drugs is highly relevant in screening for pharmacotoxicological risk assessment. However, as apoptosis in vitro normally degener- ates to secondary necrosis, it is possible that it is underestimated, unless sensitive and specific parameters are used. In this present study we have

M. J. Gomez-Lechon; JoseVicente Castell; Ramiro Jover

2002-01-01

207

Closed tube sample introduction for gas chromatography–ion mobility spectrometry analysis of water contaminated with a chemical warfare agent surrogate compound  

Microsoft Academic Search

Ion mobility spectrometry (IMS) is a proven technology for detection of vapor phase chemical warfare agents. The technology is suitable for field portable instrumentation due to its small size, high sensitivity, speed of analysis, and low power consumption. However, it suffers from a limited dynamic range and potential difficulties in identifying compounds in complex matrices. The use of gas chromatography

Richard P. Erickson; Ashish Tripathi; Waleed M. Maswadeh; A. Peter Snyder; Philip A. Smith

2006-01-01

208

Utilization of Microarrayed Compound Screening (?ARCS) to Identify Inhibitors of p56lck Tyrosine Kinase  

Microsoft Academic Search

Protein tyrosine kinases play critical roles in cell signaling and are considered attractive targets for drug discovery. The authors have applied ?ARCS (microarrayed compound screening) technology to develop a high-throughput screen for finding inhibitors of the p56lck tyrosine kinase. Initial assay development was performed in a homogeneous time-resolved (LANCE™) format in 96-well microplates and then converted into the gel-based ?ARCS

Gail Freiberg; Julie Wilkins; Caroline David; James Kofron; Yong Jia; Gavin C. Hirst; David J. Burns; Usha Warrior

2004-01-01

209

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

210

Support vector machines in the prediction of mutagenicity of chemical compounds  

Microsoft Academic Search

In this paper we introduce the problem of predicting the mutagenic toxicity property of chemical compounds and we discuss how this can be partially formulated as a computational intelligence problem. Then we develop a statistical model based on a selected set of descriptors of the molecular structure. The classifier, that we derived from SVM methods, outperforms the available methods in

Thomas Ferrari; Giuseppina Gini; Emilio Benfenati

2009-01-01

211

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

212

Comparison of chemical compositions and bioactive compounds of germinated rough rice and brown rice  

Microsoft Academic Search

The aim of the study was to compare changes in the chemical compositions and bioactive compounds of germinated rough rice and germinated brown rice. Ungerminated rice (brown rice) and germinated rice extract powder were also prepared, for comparison purposes. In general, the concentration of crude protein, total free amino acids, ?-tocopherol, ?-oryzanol, thiamine, niacin and pyridoxine, in the germinated rough

Anuchita Moongngarm; Nattawat Saetung

2010-01-01

213

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

Microsoft Academic Search

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,

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

1997-01-01

214

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

215

Association of feature gene expression with structural fingerprints of chemical compounds.  

PubMed

Exploring the relationship between a chemical structure and its biological function is of great importance for drug discovery. For understanding the mechanisms of drug action, researchers traditionally focused on the molecular structures in the context of interactions with targets. The newly emerged high-throughput "omics" technology opened a new dimension to study the structure-function relationship of chemicals. Previous studies made attempts to introduce transcriptomics data into chemical function investigation. But little effort has been made to link structural fingerprints of compounds with defined intracellular functions, i.e. expression of particular genes and altered pathways. By integrating the chemical structural information with the gene expression profiles of chemical-treated cells, we developed a novel method to associate the structural difference between compounds with the expression of a definite set of genes, which were called feature genes. A subtraction protocol was designed to extract a minimum gene set related to chemical structural features, which can be utilized in practice as markers for drug screening. Case studies demonstrated that our approach is capable of finding feature genes associated with chemical structural fingerprints. PMID:21776606

Li, Yun; Tu, Kang; Zheng, Siyuan; Wang, Jingfang; Li, Yixue; Hao, Pei; Li, Xuan

2011-08-01

216

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

PubMed

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

Almeida, Ana Amélia P; Farah, Adriana; Silva, Daniela A M; Nunan, Elzíria A; Glória, M Beatriz A

2006-11-15

217

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

218

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

PubMed

Natural bioactive compounds have been studied for a long time for their chemopreventive and therapeutic potential in several chronic inflammatory diseases, including cancer. However, their physicochemical properties generally result in poor chemical stability and lack of in vivo bioavailability. Very few human clinical trials have addressed absorption, distribution, metabolism, and excretion of these compounds in relation to efficacy. This limits the use of these valuable natural compounds in the clinic. In this study, we examined caffeic acid (derivatives), carvacrol (derivatives), thymol, pterostilbene (derivatives), and N-(3-oxo-dodecanoyl)-l-homoserine lactone. These are natural compounds with strong anti-inflammatory properties derived from plants and bacteria. However, these compounds have poor water solubility or are chemically unstable. To overcome these limitations we have prepared liposomal formulations. Our results show that lipophilic 3-oxo-C(12)-homoserine lactone and stilbene derivatives can be loaded into liposomal lipid bilayer with efficiencies of 50-70%. Thereby, the liposomes solubilize these compounds, allowing intravenous administration without use of solvents. When compounds could not be loaded into the lipid bilayer (carvacrol and thymol) or are rapidly extracted from the liposomes in the presence of serum albumin (3-oxo-C(12)-homoserine lactone and pterostilbene derivatives), derivatization of the compound into a water-soluble prodrug was shown to improve loading efficiency and encapsulation stability. The phosphate forms of carvacrol and pterostilbene were loaded into the aqueous interior of the liposomes and encapsulation was unaffected by the presence of serum albumin. Chemical instability of resveratrol was improved by liposome-encapsulation, preventing inactivating cis-trans isomerization. For caffeic acid, liposomal encapsulation did not prevent oxidation into a variety of products. Still, by derivatization into a phenyl ester, the compound could be stably encapsulated without chemical degradation. Despite the instability of liposome-association of 3-oxo-C(12)-homoserine lactone and resveratrol, intravenous administration of these compounds inhibited tumor growth for approximately 70% in a murine tumor model, showing that simple solubilization can have important therapeutic benefits. PMID:21291975

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

2011-02-01

219

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.

220

High-Throughput Chemical Screen Identifies a Novel Potent Modulator of Cellular Circadian Rhythms and Reveals CKI? as a Clock Regulatory Kinase  

PubMed Central

The circadian clock underlies daily rhythms of diverse physiological processes, and alterations in clock function have been linked to numerous pathologies. To apply chemical biology methods to modulate and dissect the clock mechanism with new chemical probes, we performed a circadian screen of ?120,000 uncharacterized compounds on human cells containing a circadian reporter. The analysis identified a small molecule that potently lengthens the circadian period in a dose-dependent manner. Subsequent analysis showed that the compound also lengthened the period in a variety of cells from different tissues including the mouse suprachiasmatic nucleus, the central clock controlling behavioral rhythms. Based on the prominent period lengthening effect, we named the compound longdaysin. Longdaysin was amenable for chemical modification to perform affinity chromatography coupled with mass spectrometry analysis to identify target proteins. Combined with siRNA-mediated gene knockdown, we identified the protein kinases CKI?, CKI?, and ERK2 as targets of longdaysin responsible for the observed effect on circadian period. Although individual knockdown of CKI?, CKI?, and ERK2 had small period effects, their combinatorial knockdown dramatically lengthened the period similar to longdaysin treatment. We characterized the role of CKI? in the clock mechanism and found that CKI?-mediated phosphorylation stimulated degradation of a clock protein PER1, similar to the function of CKI?. Longdaysin treatment inhibited PER1 degradation, providing insight into the mechanism of longdaysin-dependent period lengthening. Using larval zebrafish, we further demonstrated that longdaysin drastically lengthened circadian period in vivo. Taken together, the chemical biology approach not only revealed CKI? as a clock regulatory kinase but also identified a multiple kinase network conferring robustness to the clock. Longdaysin provides novel possibilities in manipulating clock function due to its ability to simultaneously inhibit several key components of this conserved network across species.

Hirota, Tsuyoshi; Lee, Jae Wook; Lewis, Warren G.; Zhang, Eric E.; Breton, Ghislain; Liu, Xianzhong; Garcia, Michael; Peters, Eric C.; Etchegaray, Jean-Pierre; Traver, David; Schultz, Peter G.; Kay, Steve A.

2010-01-01

221

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

PubMed Central

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

Willard, F. L.; Kodras, Rudolph

1967-01-01

222

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

223

A disease-relevant high-content screening assay to identify anti-inflammatory compounds for use in cystic fibrosis.  

PubMed

Chronic lung inflammation caused by bacterial pathogenesis through activation of nuclear factor kappa B (NF?B)-responsive proinflammatory genes is a major hurdle in the management of lung disease in cystic fibrosis (CF) patients. The authors generated a disease-relevant cell-based high-content screen to identify novel anti-inflammatory compounds for treating lung inflammation in CF. The human bronchial epithelial cell line KKLEB, harboring the most common form of mutation that causes CF, was modified to express an NF?B-responsive green fluorescent protein (GFP) reporter. After creation, the cell line was tested for its ability to respond to disease-relevant inflammatory stimuli elicited by treatment of cells with filtrates of Pseudomonas aeruginosa isolated from the airways of a CF patient. P. aeruginosa filtrates potently activated NF?B-responsive GFP reporter expression in cells. Subsequently, the assay was optimized for high-throughput screening (HTS) through generation of a Z factor (~0.5) and by testing its tolerance to the commonly used solvents ethanol and DMSO. A pilot library of clinically approved compounds was screened for assay validation. Several compounds with known NF?B inhibitory activity were identified, including several steroidal compounds that have been clinically tested in CF. Thus, the assay can be used in a broader HTS campaign to find anti-inflammatory agents for use in CF. PMID:20944057

Giddings, Angela M; Maitra, Rangan

2010-10-13

224

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 3.49mgmalonaldehyde/kg, 20.33kg and 5.05kg?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 433.7mg/100g of fat in the raw pieces to 2655.5mg/100g 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

2013-06-28

225

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

226

Chemical Variations Along the EPR Identify Melt Flow and Influence Segmentation  

NASA Astrophysics Data System (ADS)

We have analyzed at high "density" samples from the EPR between 8-18N for trace elements and isotopes. At the EPR we observe a systematic variation in the chemical composition of the basalts related to ridge discontinuities, both fracture zones and overlapping spreading centers. At migrating ridges such as the EPR leading (LE) and trailing edges (TE) of ridge segments have been identified. LEs have thicker crust suggesting a larger accumulation of melt. The low degree melts generated of-axis on the TE of the ridge segment can find a shorter route to the ridge by crossing the transform fault plane. The LE therefore has additional low-degree melts which are missing at the TE. The area on the EPR we covered contains four fracture zones (Siqueros, Clipperton, Orozco and 18N) as well as three overlapping spreading centers. We observe discontinuities in the chemical composition of the basalts at all seven ridge discontinuity. The changes in the trace element ratios like Ce/Yb, Ba/La, Sm/Nd at six of the seven discontinuities are consistent with the LE receiving a larger amount of low degree melt, as predicted by the geophysical model. The Clipperton Fracture zone is the only discontinuity that has chemical variations that are the reverse of what is expected based on the model. A second aspect of the chemistry is the consistent offset in Hf and Nd isotopic composition at ridge discontinuities. These variations can be explained if the sources of the EPR basalts has two lithologies with different solidi, whereby the lithology with the lower solidus also has a less radiogenic Nd and Hf isotopic composition. This material will melt earlier and will be concentrated in the low degree melts. Crossing the transform fault plane of these low degree melts could explain the observed isotopic variations. This supports the Carbotte et al. model for the explanation of the crustal thickness variations. And again the only exception is the variation across the Clipperton Fracture Zone. Lastly and perhaps most importantly, the chemical variations within the individual ridge segments are distinct from each other. The coincidence of chemical discontinuities with ridge discontinuities is consistent for all eight ridge segments and indicates that the segmentation is influenced by the mantle composition. It is hypothesized that changes in mantle source composition, like variations in the amount veining present, can potentially result in changes in the melting regime like depth of melting and melt rate that causes enough stresses to locate the ridge discontinuities.

Sachi-Kocher, A.; Mallick, S.; Langmuir, C. E.; Salters, V. J.

2008-12-01

227

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

NASA Astrophysics Data System (ADS)

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

Peterson, B.; Wheeler, R.

228

Experiment on the thermal conductivity and permeability of physical and chemical compound adsorbents for sorption process  

NASA Astrophysics Data System (ADS)

For the adsorbents in the application of refrigeration, the density of the material inside the adsorber changes because the adsorption/desorption of the refrigerant inside the adsorbents. Consequently the thermal conductivity and permeability of the adsorbents also change. In order to investigate the heat and mass transfer performance of consolidated compound adsorbent under the different equilibrium state of adsorption/desorption, the thermal conductivity and permeability test system is set up using the guarded hot plate measuring method and the principle of Ergun equation. Then various mass ratios between adsorbent and matrix of consolidated physical and chemical compound adsorbents are developed and tested under different ammonia adsorption quantity. Result shows that the thermal conductivity and permeability have strong dependence with the ratios and consolidated density of the compound adsorbent. Meanwhile, the thermal conductivity and permeability of the chemical compound adsorbents vary significantly with different adsorption quantity of ammonia, and the values for the physical compound adsorbents almost maintain a constant value with different values of adsorption quantity.

Jin, Z. Q.; Wang, L. W.; Jiang, L.; Wang, R. Z.

2013-08-01

229

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

230

Chemical hydrogenation effects on R2Fe14B compounds with (R = Ce, Nd and Gd)  

NASA Astrophysics Data System (ADS)

The structural and magnetic properties of R2Fe14BHx compounds with R = Ce, Nd and Gd have been investigated by X-ray diffraction (XRD) and magnetic measurements. XRD patterns show that all samples are single phase and crystallize in the quadratic structure. The hydrogen insertion increases the lattice constants a, c and the unit cell volume. The lattice parameters values of the hydrides obtained by chemical method are very close to those elaborated by the classical method. Thermomagnetic analysis shows that the Curie temperature of the hydrides are larger than that of the parent compounds. Hydrogen insertion leads to an increase of the saturated magnetization at room temperature.

Ben Kraiem, M. S.; Ellouze, M.; Cheikh-Rouhou, A.; L'Héritier, Ph.

2004-05-01

231

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

2012-03-08

232

Neutron interrogation to identify chemical elements with an ion-tube neutron source (INS)  

SciTech Connect

A non-destructive analysis technique using a portable, electric ion-tube neutron source (INS) and gamma ray detector has been used to identify the key constituent elements in a number of sealed munitions, and from the elemental makeup, infer the types of agent within each. The high energy (14 MeV) and pulsed character of the neutron flux from an INS provide a method of measuring, quantitatively, the oxygen, carbon, and fluorine content of materials in closed containers, as well as the other constituents that can be measured with low-energy neutron probes. The broad range of elements that can be quantitatively measured with INS-based instruments provides a capability of verifying common munition fills; it provides the greatest specificity of any portable neutron-based technique for determining the full matrix of chemical elements in completely unrestricted sample scenarios. The specific capability of quantifying the carbon and oxygen content of materials should lead to a fast screening technique which, can discriminate very quickly between high-explosive and chemical agent-filled containers.

Alvarez, R.A.; Dougan, A.D.; Rowland, M.R.; Wang, T.F.

1994-04-07

233

Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination  

PubMed Central

The 3D structures of human therapeutic targets are enabling for drug discovery. However, their purification and crystallization remain rate determining. In individual cases, ligands have been used to increase the success rate of protein purification and crystallization, but the broad applicability of this approach is unknown. We implemented two screening platforms, based on either fluorimetry or static light scattering, to measure the increase in protein thermal stability upon binding of a ligand without the need to monitor enzyme activity. In total, 221 different proteins from humans and human parasites were screened against one or both of two sorts of small-molecule libraries. The first library comprised different salts, pH conditions, and commonly found small molecules and was applicable to all proteins. The second comprised compounds specific for protein families of particular interest (e.g., protein kinases). In 20 cases, including nine unique human protein kinases, a small molecule was identified that stabilized the proteins and promoted structure determination. The methods are cost-effective, can be implemented in any laboratory, promise to increase the success rates of purifying and crystallizing human proteins significantly, and identify new ligands for these proteins.

Vedadi, Masoud; Niesen, Frank H.; Allali-Hassani, Abdellah; Fedorov, Oleg Y.; Finerty, Patrick J.; Wasney, Gregory A.; Yeung, Ron; Arrowsmith, Cheryl; Ball, Linda J.; Berglund, Helena; Hui, Raymond; Marsden, Brian D.; Nordlund, Par; Sundstrom, Michael; Weigelt, Johan; Edwards, Aled M.

2006-01-01

234

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

SciTech Connect

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

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

1999-05-14

235

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

SciTech Connect

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

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

1999-06-03

236

Small molecule screening in zebrafish: an in vivo approach to identifying new chemical tools and drug leads  

PubMed Central

In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology. More recently, chemical screens in zebrafish have identified small molecules that can modulate specific developmental and behavioural processes. Zebrafish are a unique vertebrate system in which to study chemical genetic systems, identify drug leads, and explore new applications for known drugs. Here, we discuss some of the advantages of using zebrafish in chemical biology, and describe some important and creative examples of small molecule screening, drug discovery and target identification.

2010-01-01

237

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

PubMed

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

Fernández-Ibáñez, V; Fearn, T; Soldado, A; de la Roza-Delgado, B

2009-06-17

238

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

239

Thermal Decomposition of Some Chemical Compounds Used As Food Preservatives and Kinetic Parameters of This Process  

Microsoft Academic Search

Thermal decomposition processes of selected chemicals used as food preservatives such as sodium formate, sodium propionate,\\u000a sodium nitrates(V and III) and sodium sulphate(IV) were examined by the derivatographic method. Based on the curves obtained,\\u000a the number of decomposition stages and characteristic temperatures of these compounds have been found. Mass decrements calculated\\u000a from TG curves ranged from 28.9% for sodium formate

J. Mas?owska; M. Wi?d?ocha

2000-01-01

240

Visualizing excipient composition and homogeneity of Compound Liquorice Tablets by near-infrared chemical imaging  

Microsoft Academic Search

This study demonstrated that near-infrared spectroscopy chemical imaging (NIR-CI) was a promising technology for visualizing the spatial distribution and homogeneity of Compound Liquorice Tablets. The starch distribution (indirectly, plant extraction) could be spatially determined using basic analysis of correlation between analytes (BACRA) method. The correlation coefficients between starch spectrum and spectrum of each sample were greater than 0.95. Depending on

Zhisheng Wu; Ou Tao; Wei Cheng; Lu Yu; Xinyuan Shi; Yanjiang Qiao

241

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

PubMed Central

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

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

1960-01-01

242

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

SciTech Connect

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

Wahl, Jon H.; Colburn, Heather A.

2009-10-29

243

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

244

Equations of State and Physical-Chemical Transformations of Shocked Organic Compounds  

NASA Astrophysics Data System (ADS)

The equation of state (EOS) for matter over wide range of temperatures and pressures is essential for modelling of hydrodynamic processes under extreme conditions of high energy densities. An analysis of the shock wave data for organic compounds indicates that these substances undergo a physical-chemical transformation under the action of the intense dynamic loading, resulting in properties of the denser state that differ appreciably from these observed under normal conditions. Traditionally this is explained by breaking of chemical bonds of the original compound, and the formation of a low-compressibility mixture of a diamondlike phase of carbon and various low-molecular weight components. It is characteristic for aromatic compounds, that the conversion on the shock Hugoniots involves a significant change in the density (by ?20%) and compressibility of the medium. In this paper, we propose the semiempirical EOS model, which takes into account the transformation of shocked compounds. Wide-range EOS for some aromatic polymers, namely polystyrene, aramid, and polyimide, are constructed on the basis of model developed, and the critical analysis of calculated results in comparison with experimental data is made. Typical form of phase diagram for aromatic substances at high temperature and pressure is discussed.

Khishchenko, K. V.; Fortov, V. E.; Lomonosov, I. V.

1999-06-01

245

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

SciTech Connect

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

Yoshida, M.; Sunaga, M.; Hara, I. (Kansai Medical Univ., Osaka (Japan))

1990-09-01

246

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

Microsoft Academic Search

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

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

2010-01-01

247

Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens  

PubMed Central

Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sustaining tumour growth, metastases and relapse. Here, we describe a strategy to identify compounds that selectively target patient-derived cancer stem cell-like tumour-initiating cells (TICs) while sparing normal paediatric stem cells (skin-derived precursors, SKPs) and characterize two therapeutic candidates. DECA-14 and rapamycin were identified as NB TIC-selective agents. Both compounds induced TIC death at nanomolar concentrations in vitro, significantly reduced NB xenograft tumour weight in vivo, and dramatically decreased self-renewal or tumour-initiation capacity in treated tumours. These results demonstrate that differential drug sensitivities between TICs and normal paediatric stem cells can be exploited to identify novel, patient-specific and potentially less toxic therapies.

Smith, Kristen M; Datti, Alessandro; Fujitani, Mayumi; Grinshtein, Natalie; Zhang, Libo; Morozova, Olena; Blakely, Kim M; Rotenberg, Susan A; Hansford, Loen M; Miller, Freda D; Yeger, Herman; Irwin, Meredith S; Moffat, Jason; Marra, Marco A; Baruchel, Sylvain; Wrana, Jeffrey L; Kaplan, David R

2010-01-01

248

Flue gas compounds and microalgae: (bio-)chemical interactions leading to biotechnological opportunities.  

PubMed

Flue gases are a resource yet to be fully utilised in microalgal biotechnology, not only to moderate the anthropogenic effects on our climate, but also to steer microalgal resource management towards innovative applications of microalgal biomass compounds. These gases, both untreated and treated into current discharge standards, contain CO2, N2, H2O, O2, NOx, SOx, CxHy, CO, particulate matter, halogen acids and heavy metals. To better steer and engineer flue gas-fed microalgal cultures, all these compounds need to be considered. Therefore, here, we review (i) the chemical composition and treatment technologies of flue gas, (ii) the uptake pathways and removal of the different compounds in microalgae reactors, and (iii) the tolerance and effects on microalgae of all flue gas compounds. By emphasising the interactions between microalgae and flue gas compounds, we envisage new pathways for microalgal biomass valorisation such as enzyme production for environmental technology, novel biogas production and biosequestration of minerals. Furthermore, we highlight fundamental and applied research niches that merit further investigation. PMID:22425735

Van Den Hende, Sofie; Vervaeren, Han; Boon, Nico

2012-03-09

249

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...

250

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

251

Phase analysis identifies compound heterozygous deletions of the PARK2 gene in patients with early-onset Parkinson disease.  

PubMed

Exon rearrangements and point mutations are common in PARK2, the most important causative gene of autosomal recessive early-onset Parkinson disease (EOPD). However, gene dosage analysis alone cannot conclusively determine the phase of exon rearrangements and the incidence of molecularly confirmed parkin-type EOPD may be underestimated. To fully characterize the mutation spectrum, we performed sequencing and gene dosage analyses of SNCA, PARK2, PINK1, and PARK7 in 114 unrelated EOPD patients with onset age ?40 years. Mutational phase of exon rearrangements was determined by reverse-transcriptase PCR (RT-PCR) and sequence analysis using a patient's own RNA. Fourteen different PARK2 mutations (3 point mutations plus 11 exon rearrangements) were identified in 18 patients, comprising 1 homozygote (0.9%), 13 compound heterozygotes (11.4%), 3 single heterozygotes (2.6%), and 1 with unknown phase (0.9%). By phase determination, more than 80% (5 of 6) of patients with apparently contiguous multi-exon deletions and 30% (5 of 18) of all PARK2 mutation carriers were additionally diagnosed as compound heterozygotes, respectively. This study shows that compound heterozygous mutations constituted a significant portion of patients with apparently contiguous multi-exon deletions. Phase determination is a prerequisite to molecular diagnosis for autosomal recessive EOPD, especially in subjects with PARK2 exon rearrangements. PMID:21534944

Kim, S Y; Seong, M W; Jeon, B S; Kim, S Y; Ko, H S; Kim, J Y; Park, S S

2011-05-29

252

[Quantification assessment of the relationship between chemical and olfactory concentrations for malodorous volatile organic compounds].  

PubMed

Using self-made cold-traps and gas bags, the odor samples were collected from 6 sewage treatment workshops of a typical municipal sewage treatment plant in Guangzhou City. The chemical composition and olfactory concentrations of these samples were respectively analyzed by thermal-desorption/GC-MS and triangle odor bag method. Finally, a mathematical equation was built for assessing the relationship between principal organic odorants and the olfactory concentrations. The result showing that: (1) More than 70 volatile organic compounds were detected in municipal sewage treatment plant, among which were 30 malodorous volatile organic compounds (MVOCs), ranging from 0.37 to 1 872.24 microg x m(-3) and appearing in sludge dewatering, thickening and aeration tank with the highest concentrations. (2) Principle component analysis was used to group the target MVOCs into 5 categories: benzenes, halohydrocarbons, aldehydes, hydrocarbons and S, N-containing organic compounds. (3) Multiple lineal regression analysis was used to build a quantified relationship between chemical and olfactory concentrations of MVOCs. The result indicated that 25% of the odor problem of sewage treatment unit was due to MVOCs. The predicted values were fitting well with measured values. The sensitivity of mathematical equation for measuring odor concentration was higher than that of human olfactory system. PMID:22468522

Liu, Shu-Le; Wang, Bo-Guang; He, Jie; Tang, Xiao-Dong; Zhao, De-Jun; Guo, Wei

2011-12-01

253

Numerical simulation of the chemical-signature-compounds transport from a mine field  

NASA Astrophysics Data System (ADS)

The transport of the chemical signature compounds from buried landmines in a three-dimensional minefield array has been numerically modeled using the finite-volume technique. Compounds such as trinitrotoluene and dinitrotoluene are semi-volatile and somewhat soluble in water; furthermore, they can strongly adsorb to the soil and undergo chemical and biological degradation. Consequently, the spatial and temporal distributions of such chemicals depend on the mobility of the water and gaseous phases, their molecular and mechanical diffusion, adsorption characteristics, soil water content and compaction, and environmental factors. Surface concentrations decrease, when precipitation occurs due to advective flux around the object. Deformation in the concentrations contours after rainfall is observed in the inclined surface case and it is attributed to both: the advective flux, and to the water flux at the surface caused by the inclination. The LaGrit code developed at Los Alamos National Laboratory (LANL) was used to generate the 3D grid array and to place several landmines at different underground positions. The simulations were performed by using the Finite-Element Heat and Mass-transfer code also developed originally at LANL.

Borrero, Ernesto E.; Briano, Julio G.; Castro, Miguel E.; Hernandez-Rivera, Samuel P.

2004-09-01

254

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

PubMed

The Rapid Assessment of Compound Exposure (RACE) assay is an easy and efficient method for estimating the pharmacokinetic parameter of exposure (AUC: area under the curve) 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. Curr. Protoc. Chem. Biol. 4:299-309 © 2012 by John Wiley & Sons, Inc. PMID:23788556

McAnally, Danielle; Vicchiarelli, Michael; Siddiquee, Khandaker; Smith, Layton H

2012-12-01

255

Quantum chemical and statistical study of megazol-derived compounds with trypanocidal activity  

NASA Astrophysics Data System (ADS)

In this work we performed a structure-activity relationship (SAR) study with the aim to correlate molecular properties of the megazol compound and 10 of its analogs with the biological activity against Trypanosoma cruzi (trypanocidal or antichagasic activity) presented by these molecules. The biological activity indication was obtained from in vitro tests and the molecular properties (variables or descriptors) were obtained from the optimized chemical structures by using the PM3 semiempirical method. It was calculated ˜80 molecular properties selected among steric, constitutional, electronic, and lipophilicity properties. In order to reduce dimensionality and investigate which subset of variables (descriptors) would be more effective in classifying the compounds studied, according to their degree of trypanocidal activity, we employed statistical methodologies (pattern recognition and classification techniques) such as principal component analysis (PCA), hierarchical cluster analysis (HCA), K-nearest neighbor (KNN), and discriminant function analysis (DFA). These methods showed that the descriptors molecular mass (MM), energy of the second lowest unoccupied molecular orbital (LUMO+1), charge on the first nitrogen at substituent 2 (qN'), dihedral angles (D1 and D2), bond length between atom C4 and its substituent (L4), Moriguchi octanol-partition coefficient (MLogP), and length-to-breadth ratio (L/Bw) were the variables responsible for the separation between active and inactive compounds against T. cruzi. Afterwards, the PCA, KNN, and DFA models built in this work were used to perform trypanocidal activity predictions for eight new megazol analog compounds.

Rosselli, F. P.; Albuquerque, C. N.; da Silva, A. B. F.

256

Chemical Shifts and Coupling Constants in Pentafluorophenyl Derivatives. Ii. Application to a Study of Bonding in Selected Compounds.  

National Technical Information Service (NTIS)

The pi interactions within molecules containing the pentafluorophenyl group are examined using the coupling constant-chemical shift relationship as proposed in the preceding paper. The following series, selected from the 73 pentafluorophenyl compounds stu...

M. G. Hogben R. S. Gay A. J. Oliver J. A. J. Thompson W. A. G. Graham

1968-01-01

257

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

258

X-ray spectroscopic investigation of chemical bonding in some organosilicon compounds  

Microsoft Academic Search

The chemical shifts of the SiKal,2 lines and the structure of the SiK~ spectra have been determined for a series of silatranes RSi(OCHsCH3)3N, triphenylsilanes Ph3SiR, Si(NHPh)4, and the cyclic compound (Ph2SiNH) s. It is shown that in the silatranes the strength of interaction increases as the R-Si-O angle approaches 90 ~ and the pv(Si)-pv(O) value of the effective charge on

A. T. Shuvaev; A. P. Zemlyanov; Yu. V. Kolodyazhnyi; O. A. Osipov; V. N. Eliseev; M. M. Morgunova

1974-01-01

259

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

260

Identifying the Source of Mystery Waterborne Oil Spills—A Case for Quantitative Chemical Fingerprinting  

Microsoft Academic Search

Oil spills of unknown origin, so-called “mystery” spills, occur routinely in rivers, open water, and navigable coastal waterways. The natural resources damage (NRD) liability associated with even a small volume of oil released into the environment warrants that a thorough chemical characterization of the spilled oil be conducted by agencies and potentially responsible parties (PRPs). Chemical fingerprinting methods have played

Scott A. Stout; Gregory S. Douglas; Allen D. Uhler; Kevin J. McCarthy; Stephen D. Emsbo-Mattingly

2005-01-01

261

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...

262

High-Resolution Transcriptional Profiling of Chemical-Stimulated Dendritic Cells Identifies Immunogenic Contact Allergens, but Not Prohaptens  

Microsoft Academic Search

Allergic contact dermatitis is a complex syndrome and knowledge about the in vitro detection of small-molecular-weight compounds, particularly prohaptens, is limited. Therefore, we investigated chemical-induced gene expression changes in human antigen-presenting cells upon stimulation with immunogenic contact allergens, prohaptens and irritants. Monocyte-derived dendritic cells (moDCs) and THP-1 cells were stimulated with the prohapten cinnamic alcohol (CAlc), the hapten cinnamic aldehyde

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

2010-01-01

263

Chemical compounds of past soluble aerosols preserved in the NEEM and Dome Fuji ice cores  

NASA Astrophysics Data System (ADS)

We will present a study on chemical compounds of past soluble aerosols preserved in the NEEM and Dome Fuji (DF) ice cores. We have developed a new method, called the 'ice sublimation method', for detecting large amounts of aerosol particles in polar ice cores #1. The elemental components of detected single particles were measured by SEM-EDS, and then chemical compounds of each single particle are obtained such as insoluble dust, soluble sulfate salts, and soluble chloride salts. We have applied this sublimation method to the NEEM and DF ice cores in order to compare chemical compounds of past aerosols during Holocene and Last Glacial Maximum (LGM) in Arctic and Antarctic regions. The results showed that the primary soluble aerosols are sodium sulfate during Holocene #2, and sodium sulfate, calcium sulfate and sodium chloride during LGM #1 in the DF ice core. On the other hand, soluble aerosols in NEEM core is more chloride rich (less sulfate) than that of the DF core. The chloride rich aerosols in NEEM ice core indicate that sea salt in Arctic atmosphere is likely to survive against oxidation from nitric and sulfuric acid. During LGM in the NEEM core, there are many particles of 1) coexistence of dust, sulfate salt, and chloride salt, and of 2) calcium chloride. The coexistence is a result of both sulfate and chloride salts formation on/in dust by attached from hydrochloric and sulfuric acid. Calcium chloride is secondary aerosol, and is probably formed by chemical reaction in atmosphere of calcium carbonate and hydrochloric acid. Hydrochloric acid is also a reacted product from sea salt and strong acid (nitric and sulfuric acid). The existence of these particles implies that multiple chemical reactions occurred in the Arctic atmosphere during LGM. #1: Iizuka et al., 2009 Constituent elements of insoluble and non-volatile particles during the Last Glacial Maximum of the Dome Fuji ice core. J. Glaciol., 55, 552-562. #2: Iizuka et al., 2012 The rates of sea salt sulfatization in the atmosphere and surface snow of inland Antarctica. J. Geophys. Res. In press

Iizuka, Y.; Hansson, M.; Oyabu, I.; Karlin, T.; Goto-Azuma, K.

2012-04-01

264

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

PubMed Central

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

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

2011-01-01

265

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

266

Investigation of Physical-Chemical Characteristics of Radiation-Exposed Lithium Compounds Like Oxide, Aluminate and Silicates.  

National Technical Information Service (NTIS)

Investigation of physico-chemical characteristics of radiation-exposed lithium compounds like oxide, aluminate and silicates. At present inorganic lithium compounds, in particular thermal enduring Li sub 2 O, LiAlO sub 2 , LiSiO sub 3 , Li sub 4 SO sub 4 ...

V. G. Vasil'ev S. R. Borisov N. N. Ryazantseva A. A. Vashman

1980-01-01

267

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

268

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

269

Catalytic conversion of a biomass-derived oil to fuels and chemicals I: Model compound studies and reaction pathways  

Microsoft Academic Search

The reactions over HZSM-5 catalyst of a number of model compounds were studied in a fixed-bed micro-reactor operating at 3.6 WHSV, atmospheric pressure and temperature range 330–410°C. The compounds were propanoic acid, methyl ester of acetic acid, 4-methylcyclohexanol, cyclopentanone, 2-methylcyclopentanone, methoxybenzene, ethoxybenzene, phenol and 2-methoxy-4-(2-propenyl)phenol. These compounds represented the acid, ester, alcohol, aldehyde and ketone, ether and phenol chemical groups,

J. D. Adjaye; N. N. Bakhshi

1995-01-01

270

Cell-based small-molecule compound screen identifies fenretinide as potential therapeutic for translocation-positive rhabdomyosarcoma.  

PubMed

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. PMID:23372815

Herrero Martín, David; Boro, Aleksandar; Schäfer, Beat W

2013-01-25

271

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

PubMed

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

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

2012-04-01

272

Development of a Biosensor for Identifying Novel Endocrine-Disrupting Chemicals.  

National Technical Information Service (NTIS)

Substantial evidence indicates that endocrine disrupting chemicals (EDCs) particularly those that interact with the estrogen receptor may play a role in reproduction and hormonal cancers in humans and animals. EDCs can mimic or alter the action of the end...

L. J. Standley

2008-01-01

273

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

EPA Science Inventory

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

274

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

275

Determination of total N-nitroso compounds by chemical denitrosation using CuCl.  

PubMed

A method for the determination of total N-nitroso compounds (NOC) by chemical denitrosation and subsequent chemiluminescence detection of evolved NO is described. Denitrosation was accomplished with CuCl in HCl at 70 degrees C. The detection limit for N-nitrosoproline (NPRO) was 1 pmol. NO formation from NPRO was linear (R(2) = 0.999) from 4 pmol to 2 nmol. Among the possible interfering compounds tested, only S-nitroso compounds contribute any significant interference. This method had several advantages over other similar methods: (1) A commercially available one-piece reaction vessel and a NO analyzer with software were used. (2) NO release occurred rapidly and was easily measured and quantified. (3) Compared to HBr or HI, CuCl was more convenient to work with and safe. (4) CuCl was suitable for samples in aqueous and most organic solvents. The application of this method to food, personal care products, and human body fluids demonstrates its utility. PMID:15941300

Wang, Jia; Chan, W Geoffrey; Haut, Stephen A; Krauss, Marc R; Izac, Richard R; Hempfling, Walter P

2005-06-15

276

Phenolic, polysaccharidic, and lipidic fractions of mushrooms from northeastern Portugal: chemical compounds with antioxidant properties.  

PubMed

Mushrooms do not constitute a significant portion of the human diet, but their consumption continues to increase due to their functional benefits and presence of bioactive compounds. Some of those compounds can be found in the phenolic, polysaccharidic, and lipidic fractions of edible and inedible species. Herein, those fractions of five wild mushrooms (Coprinopsis atramentaria, Lactarius bertillonii, Lactarius vellereus, Rhodotus palmatus, and Xerocomus chrysenteron) from northeastern Portugal were studied for their chemical composition and antioxidant properties. Protocatechuic, p-hydroxybenzoic, p-coumaric, and cinnamic acids were found in the phenolic fraction; rhamnose, xylose, fucose, arabinose, fructose, glucose, manose, mannitol, sucrose, maltose, and trehalose were quantified in polysaccharidic fraction; and linoleic and stearic (only in Lactarius sp.) acids, and ?- and ?-tocopherols were the main compounds in the lipidic fraction. C. atramentaria and X. chrysenteron phenolic fractions gave the highest free radical scavenging activity, reducing properties, and lipid peroxidation inhibition in brain homogenates, which is in agreement with its highest content in total phenolics. Furthermore, among the polysaccharidic fractions C. atramentaria also gave the highest antioxidant activity, which is in agreement with its highest total polysaccharides content and sugars obtained after hydrolysis. PMID:22515547

Heleno, Sandrina A; Barros, Lillian; Martins, Anabela; Queiroz, Maria João R P; Santos-Buelga, Celestino; Ferreira, Isabel C F R

2012-04-27

277

Visualizing excipient composition and homogeneity of Compound Liquorice Tablets by near-infrared chemical imaging.  

PubMed

This study demonstrated that near-infrared chemical imaging (NIR-CI) was a promising technology for visualizing the spatial distribution and homogeneity of Compound Liquorice Tablets. The starch distribution (indirectly, plant extraction) could be spatially determined using basic analysis of correlation between analytes (BACRA) method. The correlation coefficients between starch spectrum and spectrum of each sample were greater than 0.95. Depending on the accurate determination of starch distribution, a method to determine homogeneous distribution was proposed by histogram graph. The result demonstrated that starch distribution in sample 3 was relatively heterogeneous according to four statistical parameters. Furthermore, the agglomerates domain in each tablet was detected using score image layers of principal component analysis (PCA) method. Finally, a novel method named Standard Deviation of Macropixel Texture (SDMT) was introduced to detect agglomerates and heterogeneity based on binary image. Every binary image was divided into different sizes length of macropixel and the number of zero values in each macropixel was counted to calculate standard deviation. Additionally, a curve fitting graph was plotted on the relationship between standard deviation and the size length of macropixel. The result demonstrated the inter-tablet heterogeneity of both starch and total compounds distribution, simultaneously, the similarity of starch distribution and the inconsistency of total compounds distribution among intra-tablet were signified according to the value of slope and intercept parameters in the curve. PMID:22079891

Wu, Zhisheng; Tao, Ou; Cheng, Wei; Yu, Lu; Shi, Xinyuan; Qiao, Yanjiang

2011-10-20

278

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

279

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

PubMed Central

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

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

2004-01-01

280

Carbon-13 chemical shielding tensors in polycyclic aromatic compounds. 1. single-crystal study of pyrene  

SciTech Connect

The carbon-13 chemical shielding tensors measured in single-crystal pyrene are reported. The two internal bridgehead carbons have principal values of 197, 191, and -18 ppm and the four peripheral bridgehead carbons 213, 187, and -7 ppm with respect to liquid Me/sub 4/Si. The high field component of every tensor is determined to be perpendicular to the molecular plane, as in benzene. The protonated carbons have principal values similar to benzene, with the low-field components lying approximately along the C-H bonds. The rotation of the principal axes away from the C-H bond direction is measured experimentally and interpreted by quantum chemical calculations. By use of a MNDO wave function and the Pople model of chemical shielding, the magnitudes of the experimental in-plane components are reproduced very well and the calculated orientations of the principal axes are consistent with the experimental data. The results reported here demonstrate that the measurement of /sup 13/C shielding tensors in polycyclic aromatic compounds can be used as a measurement of the aromatic character of bonds adjacent to /sup 13/C nuclei.

Carter, C.M.; Alderman, D.W.; Facelli, J.C.; Grant, D.M.

1987-04-29

281

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

282

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

283

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

EPA Science Inventory

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

284

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

285

Chemical intermediate detection following corona discharge on volatile organic compounds: general method using molecular beam techniques  

NASA Astrophysics Data System (ADS)

Nonthermal plasma (NTP)-based treatments of volatile organic compounds (VOCs) have potential for effective environmental remediation. Theory and experiment that consider the basic science pertaining to discharge events have helped improve NTP remediation outcomes. If direct information on early post-discharge chemical intermediates were also available, it would likely lead to additional improvement in NTP remediation outcomes. To this point, however, experiments yielding direct information on post-NTP VOC intermediates have been limited. An approach using supersonic expansion molecular beam methods offers general promise for detection of post-discharge VOC intermediates. To illustrate the potential utility of these methods, we present mass spectra showing the growth of early products formed when pulsed corona discharges were carried out on toluene in He and then in He with added O2. Good general detection of neutral post-discharge species was obtained using 800 nm 150 fs photoionization pulses.

He, Luning; Sulkes, Mark

2011-07-01

286

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

287

Taxonomy, purification and chemical characterization of four bioactive compounds from new Streptomyces sp. TN256 strain.  

PubMed

A new actinomycete strain designated TN256, producing antimicrobial activity against pathogenic bacteria and fungi, was isolated from a Tunisian Saharan soil. Morphological and chemical studies indicated that strain TN256 belonged to the genus Streptomyces. Analysis of the 16S rDNA sequence of strain TN256 showed a similarity level ranging between 99.79 and 97.8% within Streptomyces microflavus DSM 40331(T) and Streptomyces griseorubiginosus DSM 40469(T) respectively. The comparison of its physiological characteristics showed significant differences with the nearest species. Combined analysis of the 16 S rRNA gene sequences (FN687758), fatty acids profile, and results of physiological and biochemical tests indicated that there were genotypic and phenotypic differentiations of that isolate from other Streptomyces species neighbours. These date strongly suggest that strain TN256 represents a novel species with the type strain Streptomyces TN256 (=CTM50228(T)). Experimental validation by DNA-DNA hybridization would be required for conclusive confirmation. Four active products (1-4) were isolated from the culture broth of Streptomyces TN256 using various separation and purification steps and procedures. 1: N-[2-(1H-indol-3-yl)-2 oxo-ethyl] acetamide 'alkaloid' derivative; 2: di-(2-ethylhexyl) phthalate, a phthalate derivative; 3: 1-Nonadecene and 4: Cyclo (L: -Pro-L: -Tyr) a diketopiperazine 'DKP' derivative. The chemical structure of these four active compounds was established on the basis of spectroscopic studies NMR and by comparing with data from the literature. According to our biological studies, we showed in this work that the pure compounds (1-4) possess antibacterial and antifungal activities. PMID:22805798

Smaoui, S; Mathieu, F; Elleuch, L; Coppel, Y; Merlina, G; Karray-Rebai, I; Mellouli, L

2011-09-14

288

EPA's (Environmental Protection Agency's) Efforts to Identify and Control Harmful Chemicals in Use.  

National Technical Information Service (NTIS)

The Toxic Substances Control Act of 1976 gave the Environmental Protection Agency (EPA) the responsibility for identifying, assessing, and controlling unreasonable risks to health or the environment from the manufacture, processing, distribution, use, or ...

1984-01-01

289

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

2012-11-25

290

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

2013-10-16

291

High-throughput screening for GPR119 modulators identifies a novel compound with anti-diabetic efficacy in db/db mice.  

PubMed

G protein-coupled receptor 119 (GPR119) is highly expressed in pancreatic ? cells and enteroendocrine cells. It is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, thereby representing a promising target for the treatment of type 2 diabetes. Although a number of GPR119 agonists were developed, no positive allosteric modulator (PAM) to this receptor has been reported. Here we describe a high-throughput assay for screening GPR119 PAMs and agonists simultaneously. Following screening of a small molecule compound library containing 312,000 synthetic and natural product-derived samples, one potent GPR119 agonist with novel chemical structure, MW1219, was identified. Exposure of MIN6 and GLUTag cells to MW1219 enhanced glucose-stimulated insulin secretion and GLP-1 release; once-daily oral dosing of MW1219 for 6 weeks in diabetic db/db mice reduced hemoglobin A1c (HbA1c) and improved plasma glucose, insulin and GLP-1 levels; it also increased glucose tolerance. The results demonstrate that MW1219 is capable of effectively controlling blood glucose level and may have the potential to be developed as a new class of anti-diabetic agents. PMID:23704946

Zhang, Meng; Feng, Yang; Wang, Jia; Zhao, Jianwei; Li, Ting; He, Min; Yang, Dehua; Nosjean, Olivier; Boutin, Jean; Renard, Pierre; Wang, Ming-Wei

2013-05-21

292

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

293

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

EPA Science Inventory

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

294

Design of a system for storing and predicting physico-chemical properties for compounds and mixtures dealing with pharmaceutical chemistry  

Microsoft Academic Search

In-house Data Bank for storing a large variety of physico-chemical properties, names, formulae and other characteristics of compounds and mixtures dealing with fine and pharmaceutical chemistry was developed for personnel computers (PCs).Among the large quantity and variety of existing estimation methods the more appropriate ones were selected for each property. These selected methods offered the best results for pure compounds

Eladio Pardillo; Jorge Marrero; Alejandro Suárez; Ulises Jáuregui; Silvia Fernández; Rubèn Frederick

1997-01-01

295

Structure and quantum chemical characterization of chloroperoxidase compound 0, a common reaction intermediate of diverse heme enzymes  

Microsoft Academic Search

We have determined the crystal structure of the chloroperoxidase (CPO) hydroperoxo reaction intermediate (CPO compound 0) at 1.75-Å resolution. The intermediate was generated through controlled photoreduction of the CPO oxygen complex during x-ray data collection, which was monitored by recording of the crystal absorption spectra. Initially, the peroxo-anion species was formed and then protonated to yield compound 0. Quantum chemical

Karin Kühnel; Etienne Derat; James Terner; Sason Shaik; Ilme Schlichting

2007-01-01

296

The chemical processing of gas-phase carbonyl compounds by sulfuric acid aerosols: 2,4-pentanedione  

Microsoft Academic Search

This work investigates the interactions between gas-phase carbonyl compounds and sulfuric acid aerosols. It focuses on understanding the chemical processes, giving a first estimate of their importance in the atmosphere, and suggesting directions for further investigations. The solubility and reactivity of a compound with a large enolization constant, 2,4-pentanedione, in water\\/sulfuric acid solutions 0–96wt% have been investigated at room temperature

Barbara Nozière; Daniel D Riemer

2003-01-01

297

Found in translation: high-throughput chemical screening in Arabidopsis thaliana identifies small molecules that reduce Fusarium head blight disease in wheat.  

PubMed

Despite the tremendous economic impact of cereal crop pathogens such as the fungus Fusarium graminearum, the development of strategies for enhanced crop protection is hampered by complex host genetics and difficulties in performing high-throughput analyses. To bypass these challenges, we have developed an assay in which the interaction between F. graminearum and the model plant Arabidopsis thaliana is monitored in liquid media in 96-well plates. In this assay, fungal infection is associated with the development of dark lesion-like spots on the cotyledons of Arabidopsis seedlings by 4 days postinoculation. These symptoms can be alleviated by the application of known defense-activating small molecules and in previously described resistant host genetic backgrounds. Based on this infection phenotype, we conducted a small-scale chemical screen to identify small molecules that protect Arabidopsis seedlings from infection by F. graminearum. We identified sulfamethoxazole and the indole alkaloid gramine as compounds with strong protective activity in the liquid assay. Remarkably, these two chemicals also significantly reduced the severity of F. graminearum infection in wheat. As such, the Arabidopsis-based liquid assay represents a biologically relevant surrogate system for high-throughput studies of agriculturally important plant-pathogen interactions. PMID:21303209

Schreiber, Karl J; Nasmith, Charles G; Allard, Ghislaine; Singh, Jasbir; Subramaniam, Rajagopal; Desveaux, Darrell

2011-06-01

298

Xlink-identifier: an automated data analysis platform for confident identifications of chemically cross-linked peptides using tandem mass spectrometry.  

PubMed

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 labeling 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 interpeptide, intrapeptide, and deadend cross-links as well as underivatized peptides. The software streamlines data preprocessing, 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. PMID:21175198

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

2011-02-16

299

Physical basis of the effect of hemoglobin on the /sup 31/P NMR chemical shifts of various phosphoryl compounds  

SciTech Connect

The marked difference between the intra- and extracellular /sup 31/P NMR chemical shifts of various phosphoryl compounds when added to a red cell suspension may be largely understood in terms of the effects of hemoglobin on the /sup 31/P NMR chemical shifts. The presence of (oxy- or (carbonmonoxy)-) hemoglobin inside the red cell causes the bulk magnetic susceptibility of the cell cytoplasm to be significantly less than that of the external solution. This difference is sufficient to account for the difference in the intra- and extracellular chemical shifts of the two phosphate esters trimethyl phosphate and triethyl phosphate. However, in the case of the compounds dimethyl methylphosphonate, diethyl methylphosphonate, and trimethylphosphine oxide as well as the hypophosphite, phenylphosphinate, and diphenylphosphinate ions, hemoglobin exerts an additional, much larger, effect, causing the /sup 31/P NMR resonances to shift to lower frequency in a manner that cannot be accounted for in terms of magnetic susceptibility. Lysozyme is a protein structurally unrelated to hemoglobin and was shown to cause similar shifts to lower frequency of the resonances of these six compounds; this suggests that the mechanism may involve a property of proteins in general and not a specific property of hemoglobin. The effect of different solvents on the chemical shifts of the eight phosphoryl compounds provided an insight into the possible physical basis of the effect. It is proposed that, in addition to magnetic susceptibility effects, hemoglobin exerts its influence on phosphoryl chemical shifts by disrupting the hydrogen bonding of the phosphoryl group to solvent water.

Kirk, K.; Kuchel, P.W.

1988-11-29

300

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

ERIC Educational Resources Information Center

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

Bretherick, Leslie

1989-01-01

301

Comparative transcriptome analysis of tobacco (Nicotiana tabacum) leaves to identify aroma compound-related genes expressed in different cultivated regions.  

PubMed

To identify genes that are differentially expressed in tobacco in response to environmental changes and to decipher the mechanisms by which aromatic carotenoids are formed in tobacco, an Agilent Tobacco Gene Expression microarray was adapted for transcriptome comparison of tobacco leaves derived from three cultivated regions of China, Kaiyang (KY), Weining (WN) and Tianzhu (TZ). A total of 1,005 genes were differentially expressed between leaves derived from KY and TZ, 733 between KY and WN, and 517 between TZ and WN. Genes that were upregulated in leaves from WN and TZ tended to be involved in secondary metabolism pathways, and included several carotenoid pathway genes, e.g., NtPYS, NtPDS, and NtLCYE, whereas those that were down-regulated tended to be involved in the response to temperature and light. The expression of 10 differentially expressed genes (DEGs) was evaluated by real-time quantitative polymerase chain reaction (qRT-PCR) and found to be consistent with the microarray data. Gene Ontology and MapMan analyses indicate that the genes that were differentially expressed among the three cultivated regions were associated with the light reaction of photosystem II, response to stimuli, and secondary metabolism. High-performance liquid chromatography (HPLC) analysis showed that leaves derived from KY had the lowest levels of lutein, ?-carotene, and neoxanthin, whereas the total carotenoid content in leaves from TZ was greatest, a finding that could well be explained by the expression patterns of DEGs in the carotenoid pathway. These results may help elucidate the molecular mechanisms underlying environmental adaptation and accumulation of aroma compounds in tobacco. PMID:23079704

Lei, Bo; Zhao, Xue-Hua; Zhang, Kai; Zhang, Jie; Ren, Wei; Ren, Zhu; Chen, Yi; Zhao, Hui-Na; Pan, Wen-Jie; Chen, Wei; Li, Hong-Xun; Deng, Wen-Ya; Ding, Fu-Zhang; Lu, Kun

2012-10-19

302

Optimal Design of Experiments for Identifying the Model Parameters of Gyroscope on a Centrifuge and Vibration Table Compound Test Syste  

Microsoft Academic Search

Overloading and vibration compound test system which is combined by centrifuge and vibration table offers a new way for ground test to simulate flight. It is an important thing must be solved in the design of experiments for gyroscope under compound environment how to meet the requirement of linear acceleration and avoid influence of angle velocity of centrifuge. After analyzing

Wang Yuegang

2006-01-01

303

New chemically modified polymeric resin for solid-phase extraction of pesticides and phenolic compounds from water  

Microsoft Academic Search

A new chemically modified polymeric resin, with an o-carboxybenzoyl moiety, is developed to be used in the on-line solid-phase extraction (SPE) of some pesticides and phenolic compounds from aqueous samples, in order to obtain better breakthrough volumes than other commercial sorbents. The chemical introduction of this moiety improves the efficiency of SPE by providing better surface contact with aqueous samples.

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

1998-01-01

304

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

305

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

306

An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling pathway  

PubMed Central

Misregulated ?-catenin responsive transcription (CRT) has been implicated in the genesis of various malignancies, including colorectal carcinomas, and it is a key therapeutic target in combating various cancers. Despite significant effort, successful clinical implementation of CRT inhibitory therapeutics remains a challenging goal. This is, in part, because of the challenge of identifying inhibitory compounds that specifically modulate the nuclear transcriptional activity of ?-catenin while not affecting its cytoskeletal function in stabilizing adherens junctions at the cell membrane. Here, we report an RNAi-based modifier screening strategy for the identification of CRT inhibitors. Our data provide support for the specificity of these inhibitory compounds in antagonizing the transcriptional function of nuclear ?-catenin. We show that these inhibitors efficiently block Wnt/?-catenin–induced target genes and phenotypes in various mammalian and cancer cell lines. Importantly, these Wnt inhibitors are specifically cytotoxic to human colon tumor biopsy cultures as well as colon cancer cell lines that exhibit deregulated Wnt signaling.

Gonsalves, Foster C.; Klein, Keren; Carson, Brittany B.; Katz, Shauna; Ekas, Laura A.; Evans, Steve; Nagourney, Robert; Cardozo, Timothy; Brown, Anthony M. C.; DasGupta, Ramanuj

2011-01-01

307

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

2013-01-23

308

Chemical decomposition of iron in Spanish coal pyrolysis identified by Moessbauer spectroscopy at different temperatures  

SciTech Connect

Three chars from lignite (Se), sub bituminous (AA6), bituminous (BCA) Spanish coals produced at 673 K, 773 K, and 873 K were analyzed by Moessbauer spectroscopy at room temperature, and 80 K, except BCA char produced at 873 K, its analysis was extended down to 10 K. Least square fit analysis for the spectra of Se chars showed that, jarosite/Fe{sup 3+} was hydrolyzed into rozenite/Fe2+ at 873 K. Pyrite was reduced to troilite (FeS) at 773 K. Both jarosite and very broad doublet were observed at T = 673 K. The hyperfine parameters of this phase gave close values to microcrystalline iron in either Fe (II) or Fe (III) states. On the other hand, the spectral analysis of AA6 chars ascertained that rozenite was hydrolyzed to goethite (FeOOH) in the range of 773 K-873 K, whereas pyrite was reduced to pyrrohotite (Fe{sub 1-x}S). However, no chemical changes were observed for jarosite in all AA6-chars. Likewise, siderite was changed into magnetite in the BCA chars produced at 673 K and 773 K. Spectrum performed at 10 K for char produced at 873 K proved the presence of ferrihydrite (H = 489.2 kOe), troilite (H = 355.3 kOe) and a broad paramagnetic doublet belonging to an organic iron. These phases and still remaining siderite inferred also that such transformations are incomplete.

Ahmed, M.A.; Blesa, M.J.; Moliner, R. [Taif University, El Taif (Saudi Arabia). Faculty of Science

2007-07-01

309

Characterization, chemical optimization and anti-tumour activity of a tubulin poison identified by a p53-based phenotypic screen  

PubMed Central

A robust p53 cell-based assay that exploits p53’s function as a transcription factor was used to screen a small molecule library and identify bioactive small molecules with potential antitumor activity. Unexpectedly, the majority of the highest ranking hit compounds from this screen arrest cells in mitosis and most of them impair polymerization of tubulin in cells and in vitro. One of these novel compounds, JJ78:1, was subjected to structure-activity relationship studies and optimized leading to the identification of JJ78:12. This molecule is significantly more potent than the original hit JJ78:1, as it is active in cells at two-digit nanomolar concentrations and shows clear antitumor activity in a mouse xenograft model as a single agent. The effects of nocodazole, a well established tubulin poison, and JJ78:12 on p53 levels are remarkably similar, supporting that tubulin depolymerization is the main mechanism by which JJ78:12 treatment leads to p53 activation in cells. In summary, these results identify JJ78:12 as a potential cancer therapeutic, demonstrate that screening for activators of p53 in a cell-based assay is an effective way to identify inhibitors of mitosis progression and highlights p53’s sensitivity to alterations during mitosis.

Staples, Oliver D.; Hollick, Jonathan J.; Campbell, Johanna; Higgins, Maureen; McCarthy, Anna R.; Appleyard, Virginia; Murray, Karen E.; Baker, Lee; Thompson, Alastair; Ronseaux, Sebastien; Slawin, Alexandra M.Z.; Lane, David P.; Westwood, Nicholas J.; Lain, Sonia

2009-01-01

310

Exploring new 129Xe chemical shift ranges in HXeY compounds: hydrogen more relativistic than xenon.  

PubMed

Among rare gases, xenon features an unusually broad nuclear magnetic resonance (NMR) chemical shift range in its compounds and as a non-bonded Xe atom introduced into different environments. In this work we show that (129)Xe NMR chemical shifts in the recently prepared, matrix-isolated xenon compounds appear in new, so far unexplored (129)Xe chemical shift ranges. State-of-the-art theoretical predictions of NMR chemical shifts in compounds of general formula HXeY (Y = H, F, Cl, Br, I, -CN, -NC, -CCH, -CCCCH, -CCCN, -CCXeH, -OXeH, -OH, -SH) as well as in the recently prepared ClXeCN and ClXeNC species are reported. The bonding situation of Xe in the studied compounds is rather different from the previously characterized cases as Xe appears in the electronic state corresponding to a situation with a low formal oxidation state, between I and II in these compounds. Accordingly, the predicted (129)Xe chemical shifts occur in new NMR ranges for this nucleus: ca. 500-1000 ppm (wrt Xe gas) for HXeY species and ca. 1100-1600 ppm for ClXeCN and ClXeNC. These new ranges fall between those corresponding to the weakly-bonded Xe(0) atom in guest-host systems (? < 300 ppm) and in the hitherto characterized Xe molecules (? > 2000 ppm). The importance of relativistic effects is discussed. Relativistic effects only slightly modulate the (129)Xe chemical shift that is obtained already at the nonrelativistic CCSD(T) level. In contrast, spin-orbit-induced shielding effects on the (1)H chemical shifts of the H1 atom directly bonded to the Xe center largely overwhelm the nonrelativistic deshielding effects. This leads to an overall negative (1)H chemical shift in the range between -5 and -25 ppm (wrt CH(4)). Thus, the relativistic effects induced by the heavy Xe atom appear considerably more important for the chemical shift of the neighbouring, light hydrogen atom than that of the Xe nucleus itself. The predicted NMR parameters facilitate an unambiguous experimental identification of these novel compounds. PMID:22782133

Lantto, Perttu; Standara, Stanislav; Riedel, Sebastian; Vaara, Juha; Straka, Michal

2012-07-10

311

jCompoundMapper: An open source Java library and command-line tool for chemical fingerprints  

Microsoft Academic Search

BACKGROUND: The decomposition of a chemical graph is a convenient approach to encode information of the corresponding organic compound. While several commercial toolkits exist to encode molecules as so-called fingerprints, only a few open source implementations are available. The aim of this work is to introduce a library for exactly defined molecular decompositions, with a strong focus on the application

Georg Hinselmann; Lars Rosenbaum; Andreas Jahn; Nikolas Fechner; Andreas Zell

2011-01-01

312

CHEM-DECK: How to Learn to Write the Formulas of Chemical Compounds (or Lose Your Shirt).  

ERIC Educational Resources Information Center

|Explains three games played with Chem-Deck, a card game which gives students practice in forming chemical compounds by familiarizing them with the charges of various ions. Effectiveness of this technique in terms of cognitive and affective components is supported by statistical data. (CS)|

Sherman, Alan; Sherman, Sharon J.

1980-01-01

313

Microwave heating of different commercial categories of olive oil: Part I. Effect on chemical oxidative stability indices and phenolic compounds  

Microsoft Academic Search

The effect of microwave heating of extra virgin olive oil (EVOo), olive oil (Oo) and pomace olive oil (Po) in domestic appliances, was investigated in terms of chemical oxidative indices (peroxide, p-anisidine and Totox values), free acidity, water content, total phenol content and different classes of phenolic compounds.Water content of unheated EVOo was higher as compared to the other two

Lorenzo Cerretani; Alessandra Bendini; Maria Teresa Rodriguez-Estrada; Elena Vittadini; Emma Chiavaro

2009-01-01

314

Coupling FT Raman and FT SERS microscopy with TLC plates for in situ identification of chemical compounds  

Microsoft Academic Search

Direct analysis of sub-femtogram quantities of chemical compounds on thin layer chromatography plates has been made possible by associating Fourier transform Raman microspectroscopy with SERS spectroscopy. The interfacing elements of the FT Raman microscope system are discussed and optimised such that a lateral resolution on the micron scale is achieved in the sample plane. Micro-FT SERS results obtained from a

J. P Caudin; A Beljebbar; G. D Sockalingum; J. F Angiboust; M Manfait

1995-01-01

315

Overview of Toxicity Data and Risk Assessment Methods for Evaluating the Chemical Effects of Depleted Uranium Compounds  

Microsoft Academic Search

In the United States, depleted uranium is handled or used in several chemical forms by both governmental agencies and private industry (primarily companies producing and machining depleted uranium metal for military applications). Human exposure can occur as a result of handling these compounds, routine low-level effluent releases to the environment from processing facilities, or materials being accidentally released from storage

Heidi M. Hartmann; Frederick A. Monette; Halil I. Avci

2000-01-01

316

Physical basis of the effect of hemoglobin on the 31P NMR chemical shifts of various phosphoryl compounds.  

PubMed

The marked difference between the intra- and extracellular 31P NMR chemical shifts of various phosphoryl compounds when added to a red cell suspension may be largely understood in terms of the effects of hemoglobin on the 31P NMR chemical shifts. The presence of [oxy- or (carbonmonoxy)-] hemoglobin inside the red cell causes the bulk magnetic susceptibility of the cell cytoplasm to be significantly less than that of the external solution. This difference is sufficient to account for the difference in the intra- and extracellular chemical shifts of the two phosphate esters trimethyl phosphate and triethyl phosphate. However, in the case of the compounds dimethyl methylphosphonate, diethyl methylphosphonate, and trimethyl-phosphine oxide as well as the hypophosphite, phenylphosphinate, and diphenylphosphinate ions, hemoglobin exerts an additional, much larger, effect, causing the 31P NMR resonances to shift to lower frequency in a manner that cannot be accounted for in terms of magnetic susceptibility. Lysozyme is a protein structurally unrelated to hemoglobin and was shown to cause similar shifts to lower frequency of the resonances of these six compounds; this suggests that the mechanism may involve a property of proteins in general and not a specific property of hemoglobin. The effect of different solvents on the chemical shifts of the eight phosphoryl compounds provided an insight into the possible physical basis of the effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3242610

Kirk, K; Kuchel, P W

1988-11-29

317

Study on the Chemical Character of Water Soluble Organic Compounds in Fine Atmospheric Aerosol at the Jungfraujoch  

Microsoft Academic Search

In this study the chemical nature of the bulk of water soluble organic compounds in fine atmospheric aerosol collected during summer 1998 at the Jungfraujoch, Switzerland (3580 m asl) is characterised. The mass concentration of water soluble organic substances was similar to those of major inorganic ions, and the water soluble organic matter was found to be composed of two

Zoltán Krivácsy; András Gelencsér; Gyula Kiss; Ern? Mészáros; Ágnes Molnár; András Hoffer; Tamás Mészáros; Zsolt Sárvári; Dóra Temesi; Bálint Varga; Urs Baltensperger; Stephan Nyeki; Ernest Weingartner

2001-01-01

318

Standardization of alumina and silica adsorbents used for chemical class separations of polycyclic aromatic compounds  

SciTech Connect

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/sup 0/ 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 acid, two adsorbents used in a previously reported separation method designed to provide chemical class separation of complex, coal-derived mixtures, were determined by using the R/sup 0/ calibration-curve method. The optimum activity ranges for these adsorbents, as used in this separation method, were 1.0-1.5% H/sub 2/O (w/w) for alumina and 5-8% H/sub 2/O (w/w) for silicic acid. Once the R/sup 0/ calibration curves were constructed for these two adsorbents, they were used to standardize and routinely monitor their activities. Finally, this standardization technique was used to determine the required oven temperature at which alumina (150/sup 0/C) and silicic acid (50/sup 0/C) could be stored so that they reached and maintained their determined activity levels. 18 references, 7 figures, 3 tables.

Later, D.W.; Wilson, B.W.; Lee, M.L.

1985-12-01

319

Photocatalytic and Chemical Oxidation of Organic Compounds in Supercritical Carbon Dioxide  

SciTech Connect

The goal of the proposed research is to develop new chemistry for the removal of organic contaminants from supercritical carbon dioxide. This has application in processes used for continuous cleaning and extraction of parts and waste materials. Cleaning and extraction using supercritical carbon dioxide (scCO2) can be applied to the solution of a wide range of environmental and pollution prevention problems in the DOE complex. The objectives at the outset of the project were to: (1) determine if photocatalytic or other clean oxidation chemistry can be applied to the removal of organic or inorganic contaminants that are introduced into supercritical carbon dioxide during its use as an extraction and cleaning medium. The target will be contaminants left in solution after the bulk of solutes have been separated from the fluid phase by changing pressure and/or temperature (but not evaporating the CO2). This is applicable to development of efficient separations and will strengthen pollution prevention strategies that eliminate hazardous solvents and cleaning agents. (2) explore the use of supercritical carbon dioxide as a solvent for the photocatalytic oxidation of organic compounds and to compare it to other types of oxidation chemistry. This will add to the fundamental understanding of photocatalytic oxidation chemistry of particulate semiconductors and provide new knowledge about conditions that have relevance to the chemical fixation of carbon dioxide.

Blake, Daniel M.

2000-12-31

320

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

321

New chemically modified polymeric resin for solid-phase extraction of pesticides and phenolic compounds from water.  

PubMed

A new chemically modified polymeric resin, with an o-carboxybenzoyl moiety, is developed to be used in the on-line solid-phase extraction (SPE) of some pesticides and phenolic compounds from aqueous samples, in order to obtain better breakthrough volumes than other commercial sorbents. The chemical introduction of this moiety improves the efficiency of SPE by providing better surface contact with aqueous samples. This synthesized sorbent enables higher volumes of sample to be concentrated for determining polar compounds. When analyzing real samples, tap and river waters, different quantities of sulphite were added to decrease the initial band due to fulvic and humic acids. The matrix peaks decreased and there were no losses in the studied compounds observed when 500 and 1000 microliters of 10% Na2SO3 solution for every 100 ml of sample were added to tap and river water, respectively. PMID:9604330

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

1998-04-17

322

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.

323

Identifying signature of chemical applications on indigenous and invasive nontarget arthropod communities in vineyards.  

PubMed

Communities of arthropods providing ecosystem services (e.g., pest control, pollination, and soil nutrient cycling) to agricultural production systems are influenced by pesticide inputs, yet the impact of pesticide applications on nontarget organisms is normally evaluated through standardized sets of laboratory tests involving individual pesticides applied to a few representative species. By combining season-long pesticide applications of various insecticides and fungicides into a metric based on the International Organization for Biological and Integrated Control (IOBC) toxicity ratings, we evaluate season-long pesticide impacts on communities of indigenous and exotic arthropods across 61 vineyards assessed for an entire growing season. The composition of arthropod communities, identified mostly at the family level, but in some cases at the species level, was altered depending on season-long pesticide use. Numbers of mostly indigenous parasitoids, predatory mites, and coccinellids in the canopy, as well as carabid/tenebrionid beetles and some spider families on the ground, were decreased at higher cumulative pesticide metric scores. In contrast, numbers of one invasive millipede species (Ommatoiulus moreletti Lucas, Julida: Julidae) increased under higher cumulative pesticide metric scores. These changing community patterns were detected despite the absence of broad-spectrum insecticide applications in the vineyards. Pesticide effects were mostly due to indoxacarb and sulphur, applied as a fungicide. The reduction of beneficial arthropods and increase in an invasive herbivorous millipede under high cumulative pesticide metric scores highlights the need to manage nontarget season-long pesticide impacts in vineyards. A cumulative pesticide metric, based on IOBC toxicity ratings, provides a way of assessing overall toxicity effects, giving managers a means to estimate and consider potential negative season-long pesticide impacts on ecosystem services provided through arthropod communities. PMID:20945768

Nash, Michael A; Hoffmann, Ary A; Thomson, Linda J

2010-09-01

324

Phenocopy - A Strategy to Qualify Chemical Compounds during Hit-to-Lead and/or Lead Optimization  

PubMed Central

A phenocopy is defined as an environmentally induced phenotype of one individual which is identical to the genotype-determined phenotype of another individual. The phenocopy phenomenon has been translated to the drug discovery process as phenotypes produced by the treatment of biological systems with new chemical entities (NCE) may resemble environmentally induced phenotypic modifications. Various new chemical entities exerting inhibition of the kinase activity of Transforming Growth Factor ? Receptor I (TGF-?R1) were qualified by high-throughput RNA expression profiling. This chemical genomics approach resulted in a precise time-dependent insight to the TGF-? biology and allowed furthermore a comprehensive analysis of each NCE's off-target effects. The evaluation of off-target effects by the phenocopy approach allows a more accurate and integrated view on optimized compounds, supplementing classical biological evaluation parameters such as potency and selectivity. It has therefore the potential to become a novel method for ranking compounds during various drug discovery phases.

Ittrich, Carina; Rust, Werner; Fundel-Clemens, Katrin; Siewert, Susanne; Baur, Martin; Mara, Lisa; Gruenbaum, Lore; Heckel, Armin; Eils, Roland; Kontermann, Roland E.; Roth, Gerald J.; Gantner, Florian; Schnapp, Andreas; Park, John E.; Weith, Andreas; Quast, Karsten; Mennerich, Detlev

2010-01-01

325

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

Microsoft Academic Search

Pellicin ([2E]-3-phenyl-1-[2,3,4,5-tetrahydro-1,6-benzodioxocin-8-yl]prop-2-en-1-one) was identified in a chemical genetics screen of 10,000 small molecules for its ability to completely abolish pellicle production in Gluconacetobacter xylinus. Cells grown in the presence of pellicin grew 1.5 times faster than untreated cells. Interestingly, growth in pellicin also caused G. xylinus cells to elongate. Measurement of cellulose synthesis in vitro showed that cellulose synthase activity

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

2011-01-01

326

Chemicals identified in feral and food animals: a data base. Volume II. Records 533-1515. Second annual report, October 1982  

Microsoft Academic Search

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

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

1982-01-01

327

A comparison of {sup 252}Cf and 14-MeV neutron excitation to identify chemical warfare agents by PGNAA  

SciTech Connect

Since 1992, Idaho National Engineering and Environmental Laboratory's portable isotopic neutron spectrometry (PINS) system has been widely used for the nondestructive assessment of munitions suspected to contain chemical warfare agents, such as the nerve agent sarin. PINS is a {sup 252}Cf-based prompt gamma-ray neutron activation analysis (PGNAA) system. The standard PINS system employs a partially moderated 5-{micro}g {sup 252}Cf source emitting 10{sup 7} n/s to excite the atomic nuclei inside the item under test. The chemical elements inside the item are revealed by their characteristic gamma-ray spectrum, measured by a high-resolution high-purity germanium gamma-ray spectrometer. The system computer then infers the fill compound or mixture from the elemental data extracted from the gamma-ray spectrum. Reliable PINS assessments can be completed in as little as 100 s for favorable cases such as white phosphorus smoke munitions, but normally, a 1000 to 3000 live-second counting interval is required. To improve PINS throughput when hundreds or more munitions must be assessed, they are evaluating the possible advantages of 14-MeV neutron excitation over their current radioisotopic source.

Caffrey, A.J.; Harlow, B.D.; Edwards, A.J.; Krebs, K.M.; Jones, J.L.; Yoon, W.; Zabriskie, J.M.; Dougan, A.D.

2000-07-01

328

Classification of compounds with distinct or overlapping multi-target activities and diverse molecular mechanisms using emerging chemical patterns.  

PubMed

The emerging chemical patterns (ECP) approach has been introduced for compound classification. Thus far, only very few ECP applications have been reported. Here, we further investigate the ECP methodology by studying complex classification problems. The analysis involves multi-target data sets with systematically organized subsets of compounds having distinct or overlapping target activities and, in addition, data sets containing classes of specifically active compounds with different mechanism-of-action. In systematic classification trials focusing on individual compound subsets or mechanistic classes, ECP calculations utilizing numerical descriptors achieve moderate to high sensitivity, dependent on the data set, and consistently high specificity. Accurate ECP predictions are already obtained on the basis of very small learning sets with only three positive training instances, which distinguishes the ECP approach from many other machine learning techniques. PMID:23692475

Namasivayam, Vigneshwaran; Hu, Ye; Balfer, Jenny; Bajorath, Jürgen

2013-06-03

329

N?nitroso compounds: Their chemical and in vivo formation and possible importance as environmental carcinogens  

Microsoft Academic Search

Brief reviews are presented on the occurrence of N?nitroso (NNO) compounds, the chemistry and kinetics of NNO compound formation from nitrite and amines or amides, the in vivo formation of these compounds (as detected by tumor induction) on feeding nitrite with amines or amides to rodents, and the carcinogenicity for rats of some new nitrosamides. The possible human hazard caused

Sidney S. Mirvish

1977-01-01

330

The Chemical Constitution of Compounds Which Protect Erythrocytes against Freezing Damage  

Microsoft Academic Search

Eleven simple neutral water-miscible compounds were tested for protective action against freezing damage to human red blood cells. All the compounds penetrated the cells at room temperature without damage, but only four, N-substituted amides, were active. These results are considered together with previously published work on freezing protection by other low molecuar weight solutes. The affinity of the compounds for

T. Nash

1962-01-01

331

An array of Escherichia coli clones over-expressing essential proteins: A new strategy of identifying cellular targets of potent antibacterial compounds  

Microsoft Academic Search

With the advancement of high throughput screening, it has become easier and faster to discover hit compounds that inhibit proliferation of bacterial cells. However, development in technologies used to identify cellular targets of potent antibacterial inhibitors has lagged behind. Here, we describe a novel strategy of target identification for antibacterial inhibitors using an array of Escherichia coli clones each over-expressing

H. Howard. Xu; Lilian Real; Melissa Wu Bailey

2006-01-01

332

Callicarpenal and Intermedeol: Two Natural Arthropod Feeding Deterrent and Repellent Compounds Identified from the Southern Folk Remedy Plant, Callicarpa americana  

Technology Transfer Automated Retrieval System (TEKTRAN)

In previous studies on the American beautyberry (Callicarpa americana), it was demonstrated that callicarpenal and intermedeol were responsible for the arthropod repellent and feeding deterrent activity of this folk remedy. Both compounds showed significant bite-deterring activity against Aedes aeg...

333

Chemical data for predictinng the fate of organic compounds in water: Volume 1, Technical basis: Final report  

SciTech Connect

In 1987, EPRI's Land and Water Quality Studies Program initiated a multi-phase project entitled ''Environment Behavior of Organic Substances''. The objectives of this project are to develop data and methods for predicting the release, transport, transformation, and fate of organic compounds. Tetra Tech was contracted to compile and evaluate available data for 53 organic compounds. The chemicals include polycyclic aromatic hydrocarbons, monocyclic aromatics, heterocyclics, and halogenated aliphatics. The types of data compiled for each compound include physical and thermodynamic properties, equilibrium coefficients (for acid-base dissociation and adsorption-desorption), and reaction rate constants (for volatilization, hydrolysis, photolysis, and biotransformation). Data were evaluated for over 330 experiments described in about 250 references. The values selected were entered into an interactive data base management system. This report is the first volume of a two-volume series. It describes the physical and chemical properties compiled and the relative importance of the different transformation processes influencing the environmental fate of the compounds. Methods used to evaluate the data are discussed along with the methods used to estimate some of the data not available in the literature. Guidance and examples are presented on how the data can be used to estimate concentrations of organic compounds in surface and groundwater. 342 refs., 39 figs., 13 tabs.

Gherini, S.A.; Summers, K.V.; Munson, R.K.; Mills, W.B.

1989-06-01

334

The chemical processing of gas-phase carbonyl compounds by sulfuric acid aerosols: 2,4-pentanedione  

NASA Astrophysics Data System (ADS)

This work investigates the interactions between gas-phase carbonyl compounds and sulfuric acid aerosols. It focuses on understanding the chemical processes, giving a first estimate of their importance in the atmosphere, and suggesting directions for further investigations. The solubility and reactivity of a compound with a large enolization constant, 2,4-pentanedione, in water/sulfuric acid solutions 0-96 wt% have been investigated at room temperature using the bubble column/GC-FID technique. 2,4-pentanedione was found to undergo aldol condensation at acidities as low as 20 wt% H 2SO 4, that is, well in the tropospheric range of aerosol composition. In agreement with well-established organic chemical knowledge, this reaction resulted in changes of color of the solutions of potential importance for the optical properties of the aerosols. 2,4-pentanedione was also found to undergo retroaldol reaction, specific to dicarbonyl compounds, producing acetone and acetaldehyde. The Henry's law coefficient for 2,4-pentanedione was found to be a factor 5 larger than the one of acetone over the whole range of acidity, with a value in water of H (297 K)=(155±27) M atm -1. A chemical system is proposed to describe the transformations of carbonyl compounds in sulfuric acid aerosols. Aldol condensation is likely to be the most common reaction for these compounds, probably involving a large number of the ones present in the atmosphere and a wide range of aerosol compositions. The enolization constant contributes as a proportional factor to the rate constant for aldol condensation, and is shown in this work to contribute as an additive constant to the Henry's law coefficient. In addition to the many important aspects of these reactions illustrated in this work, the rate of aldol condensation was estimated to be potentially fast enough for the losses of some compounds in acidic aerosols to compete with their gas-phase chemistry in the atmosphere.

Nozière, Barbara; Riemer, Daniel D.

335

Chemical characterization of volatile organic compounds near the World Trade Center: Ambient concentrations and source apportionment  

NASA Astrophysics Data System (ADS)

Concentrations of 53 volatile organic compounds (VOCs) are reported from four locations near the World Trade Center (WTC) (New York, USA) complex for canister samples collected from September 2001 through January 2002. Across the four sampling sites, mean concentrations ranged from 94.5 to 219?gm-3 for total VOCs. The highest mean concentrations for individual VOCs at any site were for ethane (18.7?gm-3), isopentane (17.1?gm-3), and m,p-xylenes (17.0?gm-3). VOC concentrations were generally highest for samples collected north and west of the WTC complex. Concentrations of total VOCs (and most individual VOCs) decreased from the period when fires were present at the WTC complex (before 19 December 2001) to the period after fires. The EPA Unmix Version 5.0 receptor model was used to assess the impact of WTC fires and recovery efforts on ambient VOC concentrations. Four factors were identified: burning of building debris, a mixed recovery/heating source, motor vehicle exhaust, and a mixed gasoline source.

Olson, David A.; Norris, Gary A.; Seila, Robert L.; Landis, Matthew S.; Vette, Alan F.

336

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

National Technical Information Service (NTIS)

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 previ...

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

2001-01-01

337

Detection of dopaminergic modulators in a tier I screening battery for identifying endocrine-active compounds (EACs)  

Microsoft Academic Search

Apomorphine (APO; D2 receptor agonist), haloperidol (HAL; D2 receptor antagonist), and reserpine (RES; a dopamine depletor that acts to lower brain dopamine levels by depleting central nervous system monoamines via disrupting storage vesicle function) have been examined in a Tier I screening battery, which has been designed to detect endocrine-active compounds (EACs). The Tier I battery incorporates two short-term in

John C O’Connor; Leonard G Davis; Steven R Frame; Jon C Cook

2000-01-01

338

Effect of Selected Chemical Compounds on the Lubrication of Silicon Nitride  

Microsoft Academic Search

Successful use of advanced ceramics in many tribological applications requires an understanding of the physical, chemical, and mechanical properties of the material. Physical and mechanical data are relatively abundant for most ceramics. However, information on the chemical interactions of ceramics is scarce. This is especially true for chemical interactions with regard to lubrication of these materials.This paper investigates the influence

Richard S. Gates; Stephen M. Hsu

1991-01-01

339

Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis.  

PubMed

Lymphangiogenesis plays an important role in promoting cancer metastasis to sentinel lymph nodes and beyond and also promotes organ transplant rejection. We used human lymphatic endothelial cells to establish a reliable three-dimensional lymphangiogenic sprouting assay with automated image acquisition and analysis for inhibitor screening. This high-content phenotype-based assay quantifies sprouts by automated fluorescence microscopy and newly developed analysis software. We identified signaling pathways involved in lymphangiogenic sprouting by screening the Library of Pharmacologically Active Compounds (LOPAC)(1280) collection of pharmacologically relevant compounds. Hit characterization revealed that mitogen-activated protein kinase kinase (MEK) 1/2 inhibitors substantially block lymphangiogenesis in vitro and in vivo. Importantly, the drug class of statins, for the first time, emerged as potent inhibitors of lymphangiogenic sprouting in vitro and of corneal and cutaneous lymphangiogenesis in vivo. This effect was mediated by inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and subsequently the isoprenylation of Rac1. Supplementation with the enzymatic products of HMG-CoA reductase functionally rescued lymphangiogenic sprouting and the recruitment of Rac1 to the plasma membrane. PMID:22949700

Schulz, Martin Michael Peter; Reisen, Felix; Zgraggen, Silvana; Fischer, Stephanie; Yuen, Don; Kang, Gyeong Jin; Chen, Lu; Schneider, Gisbert; Detmar, Michael

2012-09-04

340

Theoretical calculations of 95 Mo-NMR chemical shifts for compounds [MoO 4? n S n ] 2?  

Microsoft Academic Search

Summary Theoretical calculation of95Mo-NMR chemical shifts for [MoO4-nSn]2- (n=0-4) compounds is reported here for the first time on the basis of Fenske-Hall method and Sum-Over-State (SOS) perturbation theory. A systematic decrease in shielding of95Mo nuclei with increase of number of sulfur in [MoO4-nSn]2-, which is observed experimentally, can be reasonably explained by our calculation. A good linear relationship between chemical

Sun Yue-ming; Zhu Long-geng; You Xiao-zeng; Jiang Yuang-sheng

1992-01-01

341

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

Microsoft Academic Search

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\\u000a (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

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

2010-01-01

342

Chemical compound containing a superoxide scavenger and an organic nitrate or nitrite moiety  

US Patent & Trademark Office Database

Compounds for use in the treatment of heart disease include a superoxide scavenger and an organic nitrate or nitrite moiety. The compounds can be represented by the formula (A)n(B)m, in which A is a superoxide scavenger, B is an organic nitrate or organic nitrite moiety, and n and m are values between 1 and 8. These compounds do not suffer from the problem of patient tolerance that is associated with the use of conventional agents such as organic nitrates.

Zhang; Zhi (London, GB); Naughton; Declan P. (Brighton, GB); Sumi; Yoshihiko (Tokyo, JP); Imaizumi; Atsushi (Tokyo, JP)

2002-02-12

343

The radiolysis of aqueous acetonitrile - Compounds of interest to chemical evolution studies  

SciTech Connect

Oxygen free aqueous solutions of CH3CN (0.1 M, pH 6) were exposed to gamma rays from a Co-60 source, the mixtures of nonvolatile radiolytic products was fractionated and the fractions were analysed. Succinic, maleic, fumaric, malonic and pyruvic acids were identified. Glycol aldehyde, glucose and probably ribose were observed in the hydrolysate of fractionated material. It has been suggested that an oligomer is formed which has a fragment with the polyhydroxy structure and on hydrolysis releases the carbohydrates. Radiolytic products which release amino acids on hydrolysis were found in several fractions. The amino acid contents of the hydrolysates were up to about 2.8% of the fraction mass. The presence of several protein and nonprotein amino acids suggests that their origin should be in a peptidic structure, which is probably a fragment of an oligomer radiolytically produced. A direct analysis of the irradiated solution shows the presence of acetaldehyde, propionaldehyde, glyoxal and of biacetyl. Experimental findings are discussed and a free-radical mechanism is proposed to account for the chemical changes observed.

Draganic, I.G. (Institut za Nuclearne Nauke, Belgrade, Yugoslavia); Jovanovic, S. (Beograd, Univerzitet, Belgrade, Yugoslavia)

1980-07-01

344

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

Duchenne muscular dystrophy is an X-linked disorder characterized by loss of dystrophin, a cytoskeletal protein that connects the actin cytoskeleton in skeletal muscle cells to extracellular matrix. Dystrophin binds to the cytoplasmic domain of the transmembrane glycoprotein ?-dystroglycan (?-DG), which associates with cell surface ?-dystroglycan (?-DG) that binds laminin in the extracellular matrix. ?-DG can also associate with utrophin, and this differential association correlates with specific glycosylation changes on ?-DG. Genetic modification of ?-DG glycosylation can promote utrophin binding and rescue dystrophic phenotypes in mouse dystrophy models. We used high throughput screening with the plant lectin Wisteria floribunda agglutinin (WFA) to identify compounds that altered muscle cell surface glycosylation, with the goal of finding compounds that increase abundance of ?-DG and associated sarcolemmal glycoproteins, increase utrophin usage, and increase laminin binding. We identified one compound, lobeline, from the Prestwick library of Food and Drug Administration-approved compounds that fulfilled these criteria, increasing WFA binding to C2C12 cells and to primary muscle cells from wild type and mdx mice. WFA binding and enhancement by lobeline required complex N-glycans but not O-mannose glycans that bind laminin. However, inhibiting complex N-glycan processing reduced laminin binding to muscle cell glycoproteins, although O-mannosylation was intact. Glycan analysis demonstrated a general increase in N-glycans on lobeline-treated cells rather than specific alterations in cell surface glycosylation, consistent with increased abundance of multiple sarcolemmal glycoproteins. This demonstrates the feasibility of high throughput screening with plant lectins to identify compounds that alter muscle cell glycosylation and identifies a novel role for N-glycans in regulating muscle cell function. PMID:22570487

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

2012-05-08

345

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

346

Pharmacophore modeling and molecular dynamics simulation to identify the critical chemical features against human sirtuin 2 inhibitors  

NASA Astrophysics Data System (ADS)

Sirtuin 2 (SIRT2) is one of the emerging targets in chemotherapy field and mainly associated with many diseases such as cancer and Parkinson's. Hence, quantitative hypothesis was developed using Discovery Studio v2.5. Top ten resultant hypotheses were generated, among them Hypo1 was selected as a best hypothesis based on the statistical parameters like high cost difference (52), lowest RMS (0.71), and good correlation coefficient (0.96). Hypo1 has been validated by using well known methodologies such as Fischer's randomization method (95% confidence level), test set which has shown the correlation coefficient of 0.93 as well as the goodness of hit (0.65), and enrichment factor (8.80). All the above statistical validations confirm that the chemical features in Hypo1 (1 hydrogen bond acceptor, 1 hydrophobic, and 2 ring aromatic features) was able to inhibit the function of SIRT2. Hence, Hypo1 was used as a query in virtual screening to find a novel scaffolds by screening the various chemical databases. The screened molecules from the databases were checked for the ADMET as well as the drug-like properties. Due to the lack of SIRT2-ligand complex structure in PDB, molecular docking and molecular dynamics (MD) simulation was carried out to find the suitable orientation of ligand in the active site. The representative structure from MD simulations was used as a receptor to dock the molecules which passed the drug-like properties from the virtual screening. Finally, 29 compounds were selected as a potent candidate leads based on the interactions with the active site residues of SIRT2. Thus, the resultant pharmacophore can be used to discover and design the SIRT2 inhibitors with desired biological activity.

Sakkiah, Sugunadevi; Baek, Ayoung; Lee, Keun Woo

2012-03-01

347

Development of a chemical genetic approach for human aurora B kinase identifies novel substrates of the chromosomal passenger complex.  

PubMed

To understand how the chromosomal passenger complex ensures chromosomal stability, it is crucial to identify its substrates and to find ways to specifically inhibit the enzymatic core of the complex, Aurora B. We therefore developed a chemical genetic approach to selectively inhibit human Aurora B. By mutating the gatekeeper residue Leu-154 in the kinase active site, the ATP-binding pocket was enlarged, but kinase function was severely disrupted. A unique second site suppressor mutation was identified that rescued kinase activity in the Leu-154 mutant and allowed the accommodation of bulky N(6)-substituted adenine analogs. Using this analog-sensitive Aurora B kinase, we found that retention of the chromosomal passenger complex at the centromere depends on Aurora B kinase activity. Furthermore, analog-sensitive Aurora B was able to use bulky ATP?S analogs and could thiophosphorylate multiple proteins in cell extracts. Utilizing an unbiased approach for kinase substrate mapping, we identified several novel substrates of Aurora B, including the nucleosomal-binding protein HMGN2. We confirmed that HMGN2 is a bona fide Aurora B substrate in vivo and show that its dynamic association to chromatin is controlled by Aurora B. PMID:22267324

Hengeveld, Rutger C C; Hertz, Nicholas T; Vromans, Martijn J M; Zhang, Chao; Burlingame, Alma L; Shokat, Kevan M; Lens, Susanne M A

2012-01-20

348

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

349

Feasibility studies on newly identified LiCrP 2 O 7 compound for lithium insertion behavior  

Microsoft Academic Search

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\\u000a 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\\u000a as observed from a

Gangulibabu; D. Bhuvaneswari; N. Kalaiselvi

2009-01-01

350

Chemical Theory and Computation Special Feature: Free energies of ligand binding for structurally diverse compounds  

Microsoft Academic Search

The one-step perturbation approach is an efficient means to calculate many relative free energies from a common reference compound. Combining lessons learned in previous studies, an application of the method is presented that allows for the calculation of relative binding free energies for structurally rather diverse compounds from only a few simulations. Based on the well known statistical-mechanical perturbation formula,

Chris Oostenbrink; Wilfred F. van Gunsteren

2005-01-01

351

Prediction of the acute toxicity of chemical compounds to the fathead minnow by machine learning approaches  

Microsoft Academic Search

Support vector machines (SVM) and artificial neural networks (ANN) are applied for prediction of the acute toxicity of compounds to fathead minnow from molecular structure. A diverse set of 611 compounds, including 442 fathead minnow toxicity (FMT) agents and 169 non-FMT agents, are adopted to develop the classification models. A hybrid feature selection method, which combines Fischer's score and Monte

Ning-Xin Tan; Ping Li; Han-Bing Rao; Ze-Rong Li; Xiang-Yuan Li

2010-01-01

352

Two-hybrid yeast test system for assessment of estrogenic activity of chemical compounds  

Microsoft Academic Search

The search for natural and synthetic compounds exhibiting estrogenic and antiestrogenic activity is a topical problem of modern biology and medicine. Compounds exhibiting estrogenic activity are widely used in medical practice to correct functioning and to treat a number of endocrine disorders and sexual diseases. Antagonists of steroid hormones may be used for designing antitumor preparation to treat hormonedependent malignancies.

V. B. Kozhemyako; S. N. Koval’chuk; V. A. Rasskazov; D. L. Aminin

2005-01-01

353

Direct atmospheric pressure chemical ionisation ion trap mass spectrometry for aroma analysis: Speed, sensitivity and resolution of isobaric compounds  

NASA Astrophysics Data System (ADS)

Atmospheric pressure chemical ionisation (APCI) sources were developed for real time analysis of volatile release from foods using an ion trap (IT) mass spectrometer (MS). Key objectives were spectral simplicity (minimal fragmentation), response time and signal to noise ratio. The benefits of APCI-IT-MS were assessed by comparing the performance for in vivo and headspace analyses with that obtained using APCI coupled to a quadrupole mass analyser. Using MS-MS, direct APCI-IT-MS was able to differentiate mixtures of some C6 and terpene isobaric aroma compounds. Resolution could be achieved for some compounds by monitoring specific secondary ions. Direct resolution was also achieved with two of the three isobaric compounds released from chocolate with time as the sample was eaten.

Jublot, Lionel; Linforth, Robert S. T.; Taylor, Andrew J.

2005-06-01

354

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

2013-07-16

355

A combinatorial in silico and cellular approach to identify a new class of compounds that target VEGFR2 receptor tyrosine kinase activity and angiogenesis  

PubMed Central

BACKGROUND AND PURPOSE Vascular endothelial growth factor receptor 2 (VEGFR2) is an attractive therapeutic target for the treatment of diseases such as cancer. Small-molecule VEGFR2 inhibitors of a variety of chemical classes are currently under development or in clinical use. In this study, we describe the de novo design of a new generation pyrazole-based molecule (JK-P3) that targets VEGFR2 kinase activity and angiogenesis. EXPERIMENTAL APPROACH JK-P compound series were designed using de novo structure-based identification methods. Compounds were tested in an in vitro VEGFR2 kinase assay. Using primary endothelial cells, JK-P compounds were assessed for their ability to inhibit VEGF-A-stimulated VEGFR2 activation and intracellular signalling. We tested these compounds in cell migration, proliferation and angiogenesis assays. KEY RESULTS JK-P3 and JK-P5 were predicted to bind the VEGFR2 kinase domain with high affinity, and both compounds showed pronounced inhibition of endogenous VEGFR2 kinase activity in primary human endothelial cells. Only JK-P3 inhibited VEGF-A-stimulated VEGFR2 activation and intracellular signalling. Interestingly, JK-P3 inhibited endothelial monolayer wound closure and angiogenesis but not endothelial cell proliferation. Both compounds inhibited fibroblast growth factor receptor kinase activity in vitro, but not basic fibroblast growth factor-mediated signalling in endothelial cells. CONCLUSIONS AND IMPLICATIONS This is the first report that describes an anti-angiogenic inhibitor based on such a pyrazole core. Using a de novo structure-based identification approach is an attractive method to aid such drug discovery. These results thus provide an important basis for the development of multi-tyrosine kinase inhibitors for clinical use in the near future.

Kankanala, J; Latham, AM; Johnson, AP; Homer-Vanniasinkam, S; Fishwick, CWG; Ponnambalam, S

2012-01-01

356

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

PubMed

The "small molecule universe" (SMU), the set of all synthetically feasible organic molecules of 500 Da molecular weight or less, is estimated to contain over 10(60) structures, making exhaustive searches for structures of interest impractical. Here, we describe the construction of a "representative universal library" spanning the SMU that samples the full extent of feasible small molecule chemistries. This library was generated using the newly developed Algorithm for Chemical Space Exploration with Stochastic Search (ACSESS). ACSESS makes two important contributions to chemical space exploration: it allows the systematic search of the unexplored regions of the small molecule universe, and it facilitates the mining of chemical libraries that do not yet exist, providing a near-infinite source of diverse novel compounds. PMID:23548177

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

2013-05-02

357

JV Task 86 - Identifying the Source of Benzene in Indoor Air Using Different Compound Classes from TO-15 Data  

SciTech Connect

Volatile organic compound (VOC) data that had already been collected using EPA method TO-15 at four different sites under regulatory scrutiny (a school, strip mall, apartment complex, and business/residential neighborhood) were evaluated to determine whether the source of indoor air benzene was outdoor air or vapor intrusion from contaminated soil. Both the use of tracer organics characteristic of different sources and principal component statistical analysis demonstrated that the source of indoor air at virtually all indoor sampling locations was a result of outdoor air, and not contaminated soil in and near the indoor air-sampling locations. These results show that proposed remediation activities to remove benzene-contaminated soil are highly unlikely to reduce indoor air benzene concentrations. A manuscript describing these results is presently being prepared for submission to a peer-reviewed journal.

Steven B. Hawthorne

2007-04-15

358

Catalytic decomposition of diazomethane as a general method for the methylenation of chemical compounds  

NASA Astrophysics Data System (ADS)

The principal advances and trends in the application of diazomethane as a methylenating agent in synthetic chemistry using transition and non-transition metal compounds as catalysts are surveyed and analysed. The catalytic reactions of diazomethane with olefins, acethylenes, aromatic compounds, ketones, alcohols and amines are examined. A systematic account is given of data concerning the influence of the structure of the initial substrates and of the nature of the catalyst components on the regio- and stereo-selectivity of the reactions considered. The possibilities of the catalytic conversion by diazomethane (generated in situ) of unsaturated compounds into cyclopropane derivatives are considered. The bibliography includes 284 references.

Tomilov, Yury V.; Dokitchev, V. A.; Dzhemilev, Usein M.; Nefedov, Oleg M.

1993-09-01

359

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

PubMed

We investigate the importance of relativistic effects on NMR shielding constants and chemical shifts of linear HgL(2) (L = Cl, Br, I, CH(3)) 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 constant in Hg(CH(3))(2) within 6 ppm, but fails to reproduce the Hg shielding constants and chemical shifts. The latter is mainly due to an underestimation of the change in spin-orbit contribution. Even though ZORA underestimates the absolute Hg NMR shielding constants by ?2100 ppm, the differences between Hg chemical shift values obtained using ZORA and the four-component approach without spin-density contribution to the exchange-correlation (XC) kernel are less than 60 ppm for all compounds using three different functionals, BP86, B3LYP, and PBE0. However, larger deviations (up to 366 ppm) occur for Hg chemical shifts in HgBr(2) and HgI(2) when ZORA results are compared with four-component calculations with non-collinear spin-density contribution to the XC kernel. For the ZORA calculations it is necessary to use large basis sets (QZ4P) and the TZ2P basis set may give errors of ?500 ppm for the Hg chemical shifts, despite deceivingly good agreement with experimental data. A Gaussian nucleus model for the Coulomb potential reduces the Hg shielding constants by ?100-500 ppm and the Hg chemical shifts by 1-143 ppm compared to the point nucleus model depending on the atomic number Z of the coordinating atom and the level of theory. The effect on the shielding constants of the lighter nuclei (C, Cl, Br, I) is, however, negligible. PMID:21806118

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

2011-07-28

360

Students' Predictions about the Sensory Properties of Chemical Compounds: Additive versus Emergent Frameworks  

ERIC Educational Resources Information Center

We investigated general chemistry students' intuitive ideas about the expected properties of the products of a chemical reaction. In particular, we analyzed college chemistry students' predictions about the color, smell, and taste of the products of chemical reactions represented at the molecular level. The study was designed to explore the extent…

Talanquer, Vicente

2008-01-01

361

Students' Predictions about the Sensory Properties of Chemical Compounds: Additive versus Emergent Frameworks  

ERIC Educational Resources Information Center

|We investigated general chemistry students' intuitive ideas about the expected properties of the products of a chemical reaction. In particular, we analyzed college chemistry students' predictions about the color, smell, and taste of the products of chemical reactions represented at the molecular level. The study was designed to explore the…

Talanquer, Vicente

2008-01-01

362

NICOTINIC ACID POTENCY OF FOOD MATERIALS AND CERTAIN CHEMICAL COMPOUNDS 1  

Microsoft Academic Search

The extensive use of nicotinic acid in the treatment of human pellagra (Spies, Bean and Ashe, '39) renders a knowl edge of its quantitative distribution in various food materials of considerable interest. A number of assay methods, both chemical and biological, have been worked out, but quantita tive data have been made available only through use of the chemical methods.

HARRY A. WAISMAN; OLAF MICKELSEN; C. A. ELVEHJEM

363

Analysis of Ambient Polar Volatile Organic Compounds Using Chemical Ionization-Ion Trap Detector.  

National Technical Information Service (NTIS)

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 refocusing onto a column for analysis by capillary gas chrom...

S. M. Gordon M. Miller

1989-01-01

364

New electrochemical and chemical routes for the synthesis of lithium rich graphite intercalation compounds  

Microsoft Academic Search

New lithium rich graphite intercalation compounds have been synthesized. They display a van der Waals space containing five alternating intercalated layers, three of lithium and two of oxygen corresponding to an interplanar distance dI equal to 665 pm. The compound ideally formulated as Li2C6O0.5 has been obtained from the second-stage NaC6O0.5 either by its electrochemical reduction in LiClO4-ethylene carbonate electrolyte

D Billaud; L Thevenot; P Willmann

1999-01-01

365

Chemical characterization of water soluble organic compounds in tropospheric fine aerosol  

NASA Astrophysics Data System (ADS)

Water soluble organic compounds were investigated in aerosol samples collected in a rural station in Hungary. The share of water soluble organic carbon (WSOC) reached 58% of the total carbon and 40% of the water soluble species (both organic and inorganic). Most of the WSOC was characterized by polyconjugated (e.g. aromatic) structure, acidic functional groups and a continuous distribution in the mass to charge ratio between 100 and 700. Individual compounds with molecular weight of several hundreds have also been detected. .

Kiss, G.; Gelencsér, A.; Hoffer, A.; Krivácsy, Z.; Mészáros, E.; Molnár, A.; Varga, B.

2000-08-01

366

Chemicals identified in feral and food animals, a data base. Third annual report, October 1983. Volume III. Records 1516-2627  

Microsoft Academic Search

A comprehensive data base of chemicals identified in feral and food animals has been established under the direction of the Exposure Evaluation Division in the Environmental Protection Agency's Office of Toxic Substances. 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

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

1984-01-01

367

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

368

REDUCTION OF TOXIC AND UNDESIRABLE CHEMICAL COMPOUNDS IN FOOD BY IONIZING IRRADIATION  

Technology Transfer Automated Retrieval System (TEKTRAN)

Possible toxic and carcinogenic chemicals such as furan, acrylamide, nitrosamines, biogenic amines, and mycotoxins (aflatoxin B1, patulin, fumonisin, etc.) can accumulate in various foods during thermal processing, preservation and storage. Recent studies have suggested that irradiation reduces leve...

369

Estimation of Physical Properties and Chemical Reactivity Parameters of Organic Compounds for Environmental Modeling by SPARC  

EPA Science Inventory

Mathematical models for predicting the transport and fate of pollutants in the environment require reactivity parameter values that is value of the physical and chemical constants that govern reactivity. Although empirical structure activity relationships have been developed th...

370

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 ...

371

Investigation of the role of structural domains identified in sedimentary organic matter in the sorption of hydrophobic organic compounds.  

PubMed

The role of composition and structure of sedimentary organic matter (SOM) in the sorption of hydrophobic organic compounds (HOCs) was investigated by spiking 13C-labeled phenanthrene onto six estuarine sediments known to vary in SOM content and character. After equilibration and HF treatment, 13C NMR cross polarization and stable carbon isotope analyses indicated that the amount of desorption-resistant phenanthrene was related to aromatic carbon content. Application of the 13C NMR spectral editing technique proton spin relaxation editing (PSRE) demonstrated that all samples consisted of a rapidly relaxing and a slowly relaxing component, further evidence that SOM can be described as a structurally heterogeneous sorbent. Further, comparison of corresponding control and spiked PSRE subspectra revealed that, for each of the six sediments, desorption-resistant phenanthrene had become associated almost exclusively with the rapidly relaxing component. In only two of the sediments were there even small amounts of phenanthrene discernible in the slowly relaxing component, which is signficant as it was not always true that aromatic carbon was concentrated exclusively in the rapidly relaxing phase. The implication of these findings is that not all aromatic fractions have the same affinity for phenanthrene and that some fractions may indeed have little affinity at all. These results were interpreted as indicative that rapidly relaxing aromatic carbon associated with either sediment-associated charcoal or diagenetic organic matter plays a controlling role in the sorption of HOCs. However, the exact manner in which this rapidly relaxing aromatic phase relates to models presented elsewhere remains unclear. PMID:15984766

Golding, Christopher J; Smernik, Ronald J; Birch, Gavin F

2005-06-01

372

Chemical reaction process and the single crystal growth of CuInS 2 compound  

Microsoft Academic Search

In order to establish the preparation method of high-quality CuInS2 single crystals, we have investigated the chemical reaction process by means of differential thermal analysis and powder X-ray diffraction measurements. In the chemical reaction process of a Cu+In+2S mixture, an explosive exothermic reaction occurs at 640°C, which is ascribed to the formation of products of the In–S system. In the

Hiroaki Matsushita; Tomohiro Mihira; Takeo Takizawa

1999-01-01

373

hERGAPDbase: a database documenting hERG channel inhibitory potentials and APD-prolongation activities of chemical compounds.  

PubMed

Drug-induced QT interval prolongation is one of the most common reasons for the withdrawal of drugs from the market. In the past decade, at least nine drugs, i.e. terfenadine, astemizole, grepafloxacin, terodiline, droperidol, lidoflazine, sertindole, levomethadyl and cisapride, have been removed from the market or their use has been severely restricted because of drug-induced QT interval prolongation. Therefore, this irregularity is a major safety concern in the case of drugs submitted for regulatory approval. The most common mechanism of drug-induced QT interval prolongation may be drug-related inhibition of the human ether-á-go-go-related gene (hERG) channel, which subsequently results in prolongation of the cardiac action potential duration (APD). hERGAPDbase is a database of electrophysiological experimental data documenting potential hERG channel inhibitory actions and the APD-prolongation activities of chemical compounds. All data entries are manually collected from scientific papers and curated by a person. With hERGAPDbase, we aim to provide useful information for chemical and pharmacological scientists and enable easy access to electrophysiological experimental data on chemical compounds. Database URL: http://www.grt.kyushu-u.ac.jp/hergapdbase/. PMID:21586548

Hishigaki, Haretsugu; Kuhara, Satoru

2011-05-17

374

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

375

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...

376

Synthesis, crystal structure and chemical bonding of the novel compound IrGa 2  

Microsoft Academic Search

The crystal structure of the novel constant composition compound IrGa2 was determined from X-ray single-crystal diffraction data. The compound crystallizes in the space group Cmcm with the lattice parameters a=3.9021(3) Å, b=12.9925(8) Å and c=10.8808(7) Å. Its structure represents a new type with the Pearson symbol oC36. Analysis of the electron localization function (ELF) showed that the d electrons of both iridium atoms

Magnus Boström; Yurii Prots; Yuri Grin

2004-01-01

377

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

2013-01-07

378

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

379

Identification of Compounds in Water above a Pollutant Plume by High Resolution Mass Spectrometry.  

National Technical Information Service (NTIS)

Identification of compounds in contaminated media is essential for determining sources of pollution and for assessing risks posed by the chemicals to ecosystems or human health. Eighty-five compounds were identified or tentatively identified in a 1-L extr...

A. H. Grange G. W. Sovocool

2007-01-01

380

Mycosporine-like amino acids (MAAs): chemical structure, biosynthesis and significance as UV-absorbing/screening compounds.  

PubMed

Continuous depletion of the stratospheric ozone layer has resulted in an increase in ultraviolet-B (UV-B; 280-315 nm) radiation on the earth's surface which inhibits photochemical and photobiological processes. However, certain photosynthetic organisms have evolved mechanisms to counteract the toxicity of ultraviolet or high photosynthetically active radiation by synthesizing the UV-absorbing/screening compounds, such as mycosporine-like amino acids (MAAs) and scytonemin besides the repair of UV-induced damage of DNA and accumulation of carotenoids and detoxifying enzymes or radical quenchers and antioxidants. Chemical structure of various MAAs, their possible biochemical routes of synthesis and role as photoprotective compounds in various organisms are discussed. PMID:18697565

Singh, Shailendra P; Kumari, Sunita; Rastogi, Rajesh P; Singh, Kanchan L; Sinha, Rajeshwar P

2008-01-01

381

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

382

Chemically Engineered Extracts as an Alternative Source of Bioactive Natural Product-Like Compounds  

Microsoft Academic Search

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

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

2007-01-01

383

ISOTOPIC (14C) AND CHEMICAL COMPOSITION OF ATMOSPHERIC VOLATILE ORGANIC COMPOUND FRACTIONS - PRECURSORS TO OZONE FORMATION  

EPA Science Inventory

Atmospheric volatile organic compounds (VOCs) are an important factor in the production of ozone near ground level [3]. Many hydrocarbons originate from auto exhaust. However, a number of VOCs, e.g., isoprene, are known to be natural in origin. To develop reliable models for un...

384

Chemical characterization of bioactive compounds from the endophytic fungus Diaporthe helianthi isolated from Luehea divaricata  

PubMed Central

Endophytic microorganisms, defined as fungi or bacteria that colonize the interior of plants without causing any immediate negative effects or damages, have reciprocal relationships with host plants. In some cases their presence is beneficial to the host due to the synthesis of bioactive compounds, among which several alcohols, esters, ketones and others that may react with other compounds and may be lethal to pathogenic microorganisms. Diaporthe helianthi (Phomopsis helianthi in its anamorphic phase) is available worldwide, especially in Europe, Asia and America. Isolated in Europe as an agent of the sunflower stem cancer, it has also been endophytically isolated from tropical and temperate plants. A D. helianthi strain isolated from Luehea divaricata has been employed in current research. An investigation of the secondary metabolite from D. helianthi by CC and NMR of 1H and 13C yielded the separation of 10 fractions and the identification of the phenolic compound 2(-4 hydroxyphenyl)-ethanol (Tyrosol). Its antimicrobial reaction was tested and the ensuing antagonistic effects on the human pathogenic bacteria Enterococcus hirae, Escherichia coli, Micrococcus luteus, Salmonella typhi, Staphylococcus aureus, phytopathogenic Xanthomonas asc. phaseoli and phytopathogenic fungi were demonstrated. Results show that bioactive compounds and Tyrosol produced by D. helianthi have a biotechnological potential.

Specian, Vania; Sarragiotto, Maria Helena; Pamphile, Joao Alencar; Clemente, Edmar

2012-01-01

385

In planta biocatalysis screen of P450s identifies 8-methoxypsoralen as a substrate for the CYP82C subfamily, yielding original chemical structures.  

PubMed

An in vivo plant screen that allows for the analysis of exogenously applied substrates against transgenic Arabidopsis lines overexpressing individual cytochrome P450s has been developed. By deploying this screen with a subset of 91 P450s, we have identified an original substrate for members of the CYP82C subfamily. The therapeutic compound 8-methoxypsoralen was hydroxylated by plants overexpressing CYP82C2 or CYP82C4, forming 5-hydroxy-8-methoxypsoralen. Additionally, plants further modified this product to create a glycosylated compound, likely the compound 5-O-beta-D-glucopyranosyl-8-methoxypsoralen. The discovery of adducts of therapeutic compounds demonstrates the potential of this biocatalysis screening approach to create compounds that may be of pharmacological value. Additionally, this platform provides a means to expand the general knowledge base of P450 enzyme/substrate combinations and may provide valuable tools for a vast array of biocatalytic and bioremediation processes. PMID:18291319

Kruse, Tanya; Ho, Kwongling; Yoo, Hye-Dong; Johnson, Thomas; Hippely, Matt; Park, Joon-Hyun; Flavell, Richard; Bobzin, Steve

2008-02-01

386

[Chemical compound safety: typology of competency accreditation for assay centers and analytical laboratories].  

PubMed

The use of chemicals warrants many benefits on which modern society is entirely dependent. On the other hand, the lack of reliable information about the impact of the use of chemicals raises increasing concern. In order to guarantee the safety of chemicals it is mandatory to proceed to risk assessment, which in turn consists of hazard evaluation and exposure estimation. These activities are strictly dependent upon the availability of reliable data and information, produced by, e.g., test facilities, test laboratories and clinical laboratories, the specific competence of which has been properly recognised. All this applies in the pre-marketing phase as well as during the use of chemical substances. In this latter phase it is necessary to carry out an appropriate monitoring of environment, food and, in specific situations, human beings (biological monitoring). In the field of chemical safety, standards, legal instruments and operative instruments are nowadays available. These tools make it possible to assess both the quality of data and the competence of the entities involved in the production of the data themselves. PMID:12122899

Menditto, Antonio; Chiodo, Ferdinando

2002-01-01

387

Analysis of gaseous toxic industrial compounds and chemical warfare agent simulants by atmospheric pressure ionization mass spectrometry.  

PubMed

The suitability of atmospheric pressure chemical ionization mass spectrometry as sensing instrumentation for the real-time monitoring of low levels of toxic compounds is assessed, especially with respect to public safety applications. Gaseous samples of nine toxic industrial compounds, NH3, H2S, Cl2, CS2, SO2, C2H4O, HBr, C6H6 and AsH3, and two chemical warfare agent simulants, dimethyl methylphosphonate (DMMP) and methyl salicylate (MeS), were studied. API-MS proves highly suited to this application, with speedy analysis times (<30 seconds), high sensitivity, high selectivity towards analytes, good precision, dynamic range and accuracy. Tandem MS methods were implemented in selected cases for improved selectivity, sensitivity, and limits of detection. Limits of detection in the parts-per-billion and parts-per-trillion range were achieved for this set of analytes. In all cases detection limits were well below the compounds' permissible exposure limits (PELs), even in the presence of added complex mixtures of alkanes. Linear responses, up to several orders of magnitude, were obtained over the concentration ranges studied (sub-ppb to ppm), with relative standard deviations less than 3%, regardless of the presence of alkane interferents. Receiver operating characteristic (ROC) curves are presented to show the performance trade-off between sensitivity, probability of correct detection, and false positive rate. A dynamic sample preparation system for the production of gas phase analyte concentrations ranging from 100 pptr to 100 ppm and capable of admixing gaseous matrix compounds and control of relative humidity and temperature is also described. PMID:16568176

Cotte-Rodríguez, Ismael; Justes, Dina R; Nanita, Sergio C; Noll, Robert J; Mulligan, Christopher C; Sanders, Nathaniel L; Cooks, R Graham

2006-01-18

388

Comparisons of Classification Methods for Screening Potential Compounds  

Microsoft Academic Search

We compare a number of data mining and statistical methods on the drug design problem of modeling molecular structure-activity relationships. The relationships can be used to identify active compounds based on their chemical structures from a large inventory of chemical compounds. The data set of this application has a highly skewed class distribution, in which only 2% of the compounds

An Aijun; Yuanyuan Wang

2001-01-01

389

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

390

Identifying students' misconceptions in writing balanced equations for dissolving ionic compounds in water and using multiple-choice questions at the symbolic and particulate levels to confront these misconceptions  

NASA Astrophysics Data System (ADS)

Students who harbor misconceptions often find chemistry difficult to understand. To improve teaching about the dissolving process, first semester introductory chemistry students were asked to complete a free-response questionnaire on writing balanced equations for dissolving ionic compounds in water. To corroborate errors and misconceptions identified from students' generated balanced equations, another sample of students participated in semi-structured interviews where they were asked to explain their thought processes involved in writing the balanced equations for the dissolving ionic compounds dissolving in water. Misconceptions of the dissolving process were identified and described in detail. The most popular misconception was that water chemically reacts with an ionic compound through double displacement to form a metal oxide and an acid. The second popular misconception was that an ionic compound dissolves as neutral atoms or molecules. The third popular misconception was that students confused subscripts and coefficients. Another sample of introductory chemistry students were assessed on the dissolving process using the three popular misconceptions as three of the four choices in multiple-choice questions at the symbolic- and particulate-level. The symbolic-level questions involved symbolic balanced equations and the particulate-level questions involved dynamic animations or static pictures of the same four choices. Students' responses to these questions were discussed in terms of four variables---Answer (the correct answer and three misconceptions), Representation (symbolic or particulate questions), Visualization (static or animated pictures), and Representation Order (symbolic questions before or after the particulate questions). The same test instrument was used on the same student sample to assess how two types of subscripts affected students understanding of dissolving ionic compounds in water. Two of the ionic compounds had monatomic subscripts (MgCl2, Ag2SO4) and two did not (NaBr, KNO 3). Two had polyatomic subscripts (KNO3, K2SO 4) and two did not (NaBr, MgC12). Students' responses to these questions were also discussed in terms of four variables---Answer (the four choices), Representation (symbolic or particulate questions), Monatomic subscripts, and Polyatomic subscripts. The subscript misconception was more popular for symbolic questions compared to particulate questions, and the correct answer was less popular for particulate and symbolic questions when the question contained a monatomic subscript.

Naah, Basil M.

391

Handling a very large data set for determination of surface tension of chemical compounds using Quantitative Structure–Property Relationship strategy  

Microsoft Academic Search

In this work, the Quantitative Structure–Property Relationship (QSPR) strategy is applied to represent\\/predict the surface tension of pure chemical compounds at (66.36–977.40)K temperature range. To propose a comprehensive, reliable, and predictive model, 18298 data belonging to experimental surface tension values of 1604 chemical compounds at different temperatures are studied. The Sequential Search mathematical method has been observed to be the

Farhad Gharagheizi; Ali Eslamimanesh; Behnam Tirandazi; Amir H. Mohammadi; Dominique Richon

2011-01-01

392

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

2012-08-30

393

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

2009-09-29

394

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

395

Quantum-chemical calculations of triphenyl compounds of the VB group elements  

Microsoft Academic Search

Various approximations of the MO-LCAO method were used to study the effect of the electronic structure upon the spectra of triphenyl derivatives of the VB group elements. Both the chemical and optical properties of aromatic derivatives of these elements in their trivalent states have to be interpreted on the basis of the overall influence of electronic effects operating in opposite

N. P. Borisova; L. N. Petrov

1972-01-01

396

Quantitative global studies of reactomes and metabolomes using a vectorial representation of reactions and chemical compounds  

Microsoft Academic Search

BACKGROUND: Global studies of the protein repertories of organisms are providing important information on the characteristics of the protein space. Many of these studies entail classification of the protein repertory on the basis of structure and\\/or sequence similarities. The situation is different for metabolism. Because there is no good way of measuring similarities between chemical reactions, there is a barrier

Juan C Triviño; Florencio Pazos

2010-01-01

397

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

Microsoft Academic Search

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 Delta-polyhedral clusters has been examined. The principle of isolobal analogy has been discussed, and its unique importance for an understanding of the structure of

Nina P. Gambaryan; Ivan V. Stankevich

1989-01-01

398

Application of theoretically computed chemical shifts to structure determination of novel heterocyclic compounds  

NASA Astrophysics Data System (ADS)

Combined use of 2D NMR correlation methods (1H 13C and 1H 15N 2D HMBC) and the DFT-GIAO chemical shift calculations allows unequivocal determination of structure for novel quinoxaline. Such interplay of experiment and theory is really reliable and convenient way for structure elucidation of complex heterocycles.

Balandina, Alsu; Saifina, Dina; Mamedov, Vakhid; Latypov, Shamil

2006-06-01

399

Foliage Age and Pollution Alter Content of Phenolic Compounds and Chemical Elements in Pinus nigra Needles  

Microsoft Academic Search

Changes of phenolics and chemical elements [nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), manganese (Mn), iron (Fe), boron (B), copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), chromium (Cr), nickel (Ni) and cobalt (Co)] content in needles of black pine ( Pinus nigra) as dependent on age of needles (5–6 classes) and pollution were examined. The content

Marian J. Giertych; Piotr Karolewski; Ludwig O. de Temmerman

1999-01-01

400

Levels of chemical contaminants in nonoccupationally exposed US residents. [Tabulated listing of 100 elements or compounds, analytical methods, and tissues found  

Microsoft Academic Search

This report is a compilation of information on chemical contaminants found in nonoccupationally exposed US residents. Listed in tabular form for each of approximately 100 elements or compounds are: the tissue the compound was found in; the range and means or medians of concentrations found; the number of cases; the analytical methods used for detection, identification, and quantitation; the bibliographic

J. W. Holleman; A. S. Hammons

1980-01-01

401

Catalytic hydrocracking of fused-ring aromatic compounds: Chemical reaction pathways, kinetics, and mechanisms  

SciTech Connect

Five-carbon-membered-ring-containing (5-CMRC) aromatic hydrocarbons are important but little-studied components of heavy oils and coal liquids. Reaction pathways of three 5-CMRC compounds, fluoranthene, fluorene, and 9-ethylfluorene, have been deduced from batch autoclave experiments involving an isothermal reaction catalyzed by a presulfided NiMo catalyst containing zeolite-Y at temperatures ranging from 310 to 380{degree}C, and a pressure of 153 atm. Results of derivative experiments with the model compounds, 2-phenylnaphthalene, 9-phenylanthracene, diphenylmethane, and 2-methylbiphenyl, are also presented. Terminal-ring hydrogenation followed by cracking of the five-carbon-membered ring is the predominant pathway of the 5-CMRC compound class. Two key reactions within the major pathways involve biphenyl-like bond scission without prior hydrogenation: (1) 1-phenyltetralin cracks, giving equimolar yields of tetralin and benzene within the fluoranthene network, and (2) the 9-ethylfluorene network includes a pathway that may proceed via cracking of 2-propylbiphenyl to give propylbenzena and benzene. A novel 1,5-hydride shift mechanism has been postulated to explain these unique reactions. Consistent mechanistic operations, characteristic of bifunctional hydrocracking catalysts containing a metal-sulfide hydrogenation component and zeolitic acid-cracking component, have been proposed. Relationships between the molecular structure of various heavy oil feed components and the mechanistic operations that they lend themselves to have been classified.

Lapinas, A.T.

1989-01-01

402

Biomarker responses and chemical analyses in fish indicate leakage of polycyclic aromatic hydrocarbons and other compounds from car tire rubber.  

PubMed

Rubber tire material contains toxic compounds including oils rich in polycyclic aromatic hydrocarbons (PAH), so-called highly aromatic (HA) oils, as well as other reactive additives used as antioxidants, antiozonants, and vulcanization accelerators. The toxicity of rubber tire leachates to aquatic organisms has been demonstrated before. However, previous studies have focused on lethal rather than sublethal effects. We kept rainbow trout (Oncorhynchus mykiss) in tanks with two types of tires: a tire containing HA oils in the tread or a tire free of HA oils in the tread. After 1 d of exposure, an induction of cytochrome P4501A1 (CYP1A1) was evident in both exposed groups, measured as elevated ethoxyresorufin-O-deethylase (EROD) activity and increased CYP1A1 mRNA levels. After two weeks of exposure, EROD activity and CYP1A1 mRNA were still high in fish exposed to leachate from HA oil-containing tire, whereas the effect was somewhat lower in fish exposed to leachate from HA oil-free tread tire. Compounds in the tire leachates also affected antioxidant parameters. Total glutathione concentration in liver as well as hepatic glutathione reductase, glutathione S-transferase, and glucose-6-phosphate dehydrogenase activities were markedly elevated after two weeks of exposure in both groups. The responses were greater in the group exposed to leachate from HA oil-free tread tire. Vitellogenin measurements did not indicate leakage of estrogenic compounds from the tires. Chemical analyses of bile from exposed fish revealed the presence of hydroxylated PAH as well as aromatic nitrogen compounds indicating uptake of these compounds by the fish. PMID:14713032

Stephensen, Eiríkur; Adolfsson-Erici, Margaretha; Celander, Malin; Hulander, Mats; Parkkonen, Jari; Hegelund, Tove; Sturve, Joachim; Hasselberg, Linda; Bengtsson, Madeleine; Förlin, Lars

2003-12-01

403

Correlations between chemical reactivity and mutagenic activity against S. typhimurium TA100 for alpha-dicarbonyl compounds as a proof of the mutagenic mechanism.  

PubMed

The mutagenic activities in the Ames test against S. typhimurium TA100 for a series of alpha-dicarbonyl compounds are examined together with the formation constants of the adducts formed between such compounds and guanine and guanosine. Correlations between the equilibrium constants, the apparent reaction enthalpies, and the mutagenic activity are presented. These correlations imply that the mutagenic activity is related to the chemical reactivity of the dicarbonyl compounds with the puric bases. PMID:7506369

Rodríguez Mellado, J M; Ruiz Montoya, M

1994-01-16

404

Surface Chemical Analysis and Electrokinetic Properties of Spherical Hematite Particles Coated with Yttrium Compounds  

Microsoft Academic Search

We describe in this work the chemical and electrokinetic surface characterization of core–shell particles consisting of a practically spherical hematite nucleus coated by a layer of yttrium basic carbonate or yttrium oxide (obtained after calcination of the carbonate-coated particles, following the method of E. Matijevi? and B. Aiken (J. Colloid Interface Sci.126,645 (1988))). The morphological and surface characteristics of the

R. C. Plaza; J. D. G. Durán; A. Quirantes; M. J. Ariza; A. V. Delgado

1997-01-01

405

Graph-Based Induction for General Graph Structured Data and Its Application to Chemical Compound Data  

Microsoft Academic Search

Most of the relations are represented by a graph structure, e.g., chemical bonding, Web browsing record, DNA sequence, Inference\\u000a pattern (program trace), to name a few. Thus, efficiently finding characteristic substructures in a graph will be a useful\\u000a technique in many important KDD\\/ML applications. However, graph pattern matching is a hard problem. We propose a machine learning\\u000a technique called Graph-

Takashi Matsuda; Tadashi Horiuchi; Hiroshi Motoda; Takashi Washio

2000-01-01

406

Chemical grafting of molecular and biomolecular layers to compound semiconductor surfaces  

NASA Astrophysics Data System (ADS)

Chemical grafting of organic molecules to semiconductors is emerging as an important growth area in the development of new semiconductor-based materials and devices. The first part of this thesis reports the chemical grafting of organic layers to gallium nitride thin films. One method is the photochemical grafting of alkenes to H-terminated GaN (0001) surface with formation of dense, self-terminating molecular layers. After photochemical functionalization, the organic layers were used to immobilize DNA biomolecules onto the GaN surface. The DNA-modified GaN surfaces showed excellent selectivity for hybridization with fluorescence tagged complementary and non-complementary DNA, and they showed good stability over repeated cycles of hybridization and denaturation. These results demonstrate that GaN can be used a substrate for integrating organic molecules into wet-chemical and biological environments. The other method is the thereto grafting of organophosphonic acids to the oxide layer of GaN surface. The density and stability of molecular layers produced using photochemical method are compared with those produced using chemical attachment via phosphonate groups. The second part of this thesis shows that this photochemical grafting of alkenes can be extended to oxide materials such as titanium dioxide in both anatase and rutile forms when illuminated with UV light. This provides a versatile way to covalently link functional organic molecules directly to oxide semiconductors. Measurements have been performed on epitaxial thin films of anatase (001), bulk crystals of anatase(101), rutile (001), rutile (110), and nanocrystalline anatase. Quantitative XPS and FTIR measurements have been used to investigate the kinetics of functionalization and its dependence on the structure of the bulk samples, exposed crystal face, photon energy and functional groups of alkenes. The mechanism of photochemical grafting of alkenes to titanium dioxide is discussed based on these results.

Kim, Heesuk

407

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

408

The chemical nature of very strong hydrogen bonds in some categories of compounds  

Microsoft Academic Search

In the current research, chemical nature of very strong hydrogen bonds in their three fundamental cases, resonance assisted hydrogen bond [RAHB], negative charge assisted hydrogen bond [(?)CAHB], and positive charge assisted hydrogen bond [(+)CAHB] is studied. The results are obtained at B3LYP\\/6-311++G** and MP2\\/6-311++G** level of theories. Attention is focused on topological parameters such as electron density, its Laplacian, kinetic

A. H. Pakiari; K. Eskandari

2006-01-01

409

Determination of ultratrace neodymium in high-purity lanthanum compounds by high-accuracy isotope dilution inductively coupled plasma mass spectrometric analysis with chemical preconcentration  

Microsoft Academic Search

Direct, accurate quantitation of ultratrace Nd in La compounds was not possible by ICPMS. The La\\/Nd ratio of > 10[sup 6] required chemical separations to provide a suitable sample solution for instrumental analysis. Separation of Nd from the La matrix is problematic since the two elements are close in mass and similar in chemical behavior. The ICPMS in a semiquantitative

Ellyn S. Beary; Paul J. Paulsen

1994-01-01

410

Allocation of reliable analytical procedures for human biomonitoring published by the DFG Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area  

Microsoft Academic Search

In 1955 the Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) was founded by the Deutsche Forschungsgemeinschaft (DFG). The Commission is responsible for analysing health risks by chemical exposure at the workplace and for advising public authorities accordingly. Within the Commission, the working group “Analyses of Hazardous Substances in Biological Materials”

Thomas Göen; Elisabeth Eckert; Anja Schäferhenrich; Andrea Hartwig

411

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

412

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); Li, G. [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); Owaki, E. [Taisei Corp., Yokohama (Japan). Technology Research Center

1997-10-01

413

Design and investigation of coumarin based photoactive compounds for a new non-chemically amplified deep ultraviolet photoresist  

NASA Astrophysics Data System (ADS)

A non-chemically amplified deep ultraviolet photoresist would be of significant value to the semiconductor industry because of both the image resolution advantages of using deep ultraviolet (DUV or 248 nm) light and because of the inherent robustness of this type of resist when compared to the chemically amplified systems currently used for DUV lithography. New exposure tools are now available which could eliminate the need for chemical amplification and make non-chemically amplified resists a viable technology. Currently available non-chemically amplified I-line (365 nm) resists based on diazonaphthoquinone (DNQ) photoactive compounds (PACs) do not function well when exposed at 248 nm because the PACs do not bleach effectively at this lower wavelength. This dissertation describes the design and synthesis of a series of new PACs using the 3-diazo-4-oxocoumarin chromophore which bleaches effectively at 248 nm and lithographically functions analogously to the DNQ's. In order to optimize the design of this system, the influence of both the electronic and steric nature of substituents on the rate of reaction of the ketene formed by the photolysis of these PACs with novolac resin has been studied. The reactivity of this key ketene intermediate helps determine the usefulness of the new PACs in the photolithographic process because after it is photochemically generated within the resist film, the selectivity of the ketenes reaction between water and the matrix resin greatly effects the solubility differential between the exposed and unexposed areas of the film. Both electron donating and sterically bulky substituents were found to reduce the reactivity of the ketene. This knowledge, combined with the synthetic procedures developed, allows the properties of these materials to be tailored for their use in lithography and will allow optimization of their performance in new resins.

Leeson, Michael John

414

A review on botanical species and chemical compounds with appetite suppressing properties for body weight control.  

PubMed

As obesity has reached epidemic proportions, the management of this global disease is of clinical importance. The availability and popularity of natural dietary supplements for the treatment of obesity has risen dramatically in recent years. The purpose of this paper was to review the effect of commonly available over the counter plant-derived supplements used to suppress appetite for obesity control and management. The data were obtained from the electronic databases PubMed, SpringerLink, Google Scholar, ScienceDirect, and MEDLINE with full text (via EBSCOHost) and the databases were accessed during late 2012 - early January 2013. The botanical species discussed in this review include Camellia sinensis, Caralluma fimbriata, Citrus aurantium, Coleus forskohlii, Garcinia cambogia and Phaseolus vulgaris. This review found that many botanical species including crude extracts and isolated compounds from plants have been shown to provide potentially promising therapeutic effects including appetite control and weight loss. However, many of these crude extracts and compounds need to be further investigated to define the magnitude of the effects, optimal dosage, mechanisms of action, long term safety, and potential side effects. PMID:23666454

Astell, Katie J; Mathai, Michael L; Su, Xiao Q

2013-09-01

415

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

416

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

2011-11-11

417

Chemical Structure of Retro-2, a Compound That Protects Cells against Ribosome-Inactivating Proteins  

PubMed Central

Shiga-like toxins and ricin are ribosome-inactivating proteins (RIPs) that are lethal to mammals and pose a global health threat. No clinical vaccines or therapeutics currently exist to protect against these RIPs. Two small molecules (Retro-1 and Retro-2) were discovered with high-throughput screening and reported for their protection of cells against RIPs. Of great significance, Retro-2, reported as (E)-2-(((5-methylthiophen-2-yl)methylene)amino)-N-phenylbenzamide, fully protected mice from lethal nasal challenge with ricin. Herein, we report studies showing that the chemical structure of Retro-2 is (±)-2-(5-methylthiophen-2-yl)-3-phenyl-2,3-dihydroquinazolin-4(1H)-one rather than (E)-2-(((5-methylthiophen-2-yl)methylene)amino)-N-phenylbenzamide. The latter is an achiral molecule that converts spontaneously to the former, which is a racemate and showed cell protection against RIPs. This calls for attention to (±)-2-(5-methylthiophen-2-yl)-3-phenyl-2,3-dihydroquinazolin-4(1H)-one as a promising RIP inhibitor and for chemical characterization of drug leads obtained from high-throughput screens.

Park, Jewn Giew; Kahn, Jennifer Nielsen; Tumer, Nilgun E.; Pang, Yuan-Ping

2012-01-01

418

A wireless hybrid chemical sensor for detection of environmental volatile organic compounds  

PubMed Central

A hybrid sensor for monitoring volatile organic compounds (VOCs) in air is developed. The device combines two orthogonal sensing principles, selective molecular binding with a microfabricated quartz tuning fork detector and separation of analytes with a column. The tuning fork detector is functionalized with molecular imprinted polymers for selective binding to benzene, toluene, ethylbenzene, and xylenes (BTEX), and the separation column provides further discrimination of the analytes for real world complex sample analysis. The device is wireless, portable, battery-powered, and cell-phone operated, and it allows reliable detection in parts per billion (ppb) by volume-levels of BTEX in the presence of complex interferents. The hybrid device is suitable for occupational, environmental health, and epidemiological applications.

Chen, Cheng; Tsow, Francis; Campbell, Katherine Driggs; Iglesias, Rodrigo; Forzani, Erica; Tao, N.J.

2013-01-01

419

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

420

[Simultaneous determination of o-phthalaldehyde, p-chloro-m-xylenol and triclosan in compound chemical disinfectants and daily chemicals by micellar electrokinetic chromatography].  

PubMed

A novel method for the separation and determination of o-phthalaldehyde (OPA), p-chloro-m-xylenol (PCMX) and triclosan in daily chemicals and compound chemical disinfectants in a single run by micellar electrokinetic chromatography (MEKC) was established. The factors such as the buffer concentration and pH, the concentration of sodium dodecyl sulfate (SDS), and the sample buffer, were investigated in detail. The analysis was carried out using a 50 microm uncoated capillary of 40.2 cm in total length (effective length: 30 cm). The running buffer was 20 mmol/L Na2B4O7, and 80 mmol/L SDS. The sample buffer was 2 mmol/L Na2B4O7-8 mmol/L SDS (without pH adjustment) containing 10% (v/v) methanol. The detection wavelength was 214 nm. The relative standard deviations (RSDs) of the corrected peak areas of the three components were in the range of 1.1% - 3.8%, and the RSDs of migration times were less than 0.9%. The limits of detection (LODs, S/N = 3) were 4.0, 0.4 and 0.4 mg/L, and the limits of quantification (LOQs, S/N = 10) were 12, 1.2, and 1.2 mg/L for OPA, PCMX and triclosan, respectively. The corrected peak areas and the concentrations of the three components showed good linear relationship within the ranges of 12 - 2 000 mg/L, 1.2 - 200 mg/L and 1.2 - 200 mg/L with the correlation coefficients of 0.999 4, 0.999 3 and 0.999 5 for OPA, PCMX and triclosan, respectively. The method was used for the determination of the three components in compound chemical disinfectants, hand washing liquids, soaps and a toothpaste. The results showed that the three components could be assayed in a single run with simple sample pretreatment, rapidity, accuracy and low cost, and the method is convenient for routine analysis. PMID:23667992

Xie, N; Ding, Xiaojing; Song, Baohu; Li, Jia; Wang, Zhi

2013-01-01

421

Mass-Spectrometric Studies of Catalytic Chemical Vapor Deposition Processes of Organic Silicon Compounds Containing Nitrogen  

NASA Astrophysics Data System (ADS)

The mechanism of catalytic chemical vapor deposition (Cat-CVD) processes for hexamethyldisilazane (HMDS) and trisdimethylaminosilane (TDMAS), which are used as source gases to prepare SiNx or SiCxNy films, was studied using three different mass spectrometric techniques: ionization by Li+ ion attachment, vacuum-ultraviolet radiation and electron impact. The results for HMDS show that Si-N bonds dissociate selectively, although Si-C bonds are weaker, and (CH3)3SiNH should be one of the main precursors of deposited films. This decomposition mechanism did not change when NH3 was introduced, but the decomposition efficiency was slightly increased. Similar results were obtained for TDMAS.

Morimoto, Takashi; Ansari, S. G.; Yoneyama, Koji; Nakajima, Teppei; Masuda, Atsushi; Matsumura, Hideki; Nakamura, Megumi; Umemoto, Hironobu

2006-02-01

422

Spectroscopic Studies of Azide compounds: Thermochemistry, Chemical Kinetics and Photodissociation Dynamics  

NASA Astrophysics Data System (ADS)

Some of the most difficult chemical systems, either to observe or produce in significant quantities, are polynitrogen molecules. One example of this type of molecules in the early stages of investigation is cyclic-N3, whose molecular geometry and promising technological applications have attracted our attention to define optimal experimental conditions for being photoproduced. High-resolution synchrotron-radiation-based Photoionization Mass Spectrometry (PIMS) was applied to study the dissociative photoionization of three azide precursors for cyclic-N3; chlorine azide (ClN3), hydrogen azide (HN3), and methyl azide (CH3N3). In our attempts to detect cyclic-N3, the thermochemistry derived in the PIMS studies stimulated our work to perform photodissociation dynamics experiments of CH3N3 at 193 nm using Photofragment Translational Spectroscopy (PTS) with electron impact (EI) detection under collision-free conditions, and chemical kinetic studies based on Infrared Spectroscopy (IR) in matrix-isolated ices formed from rare gases (Argon, Nitrogen and Xenon). PTS experiments lead us to derive the branching ratio between reactions CH 3+N3 (radical channel) vs CH3N+N2 (molecular channel), and to conclude that cyclic-N3 is the dominant product in the radical channel. In contrast, in the matrix isolation experiments we found no evidence of the radical channel, possibly due to barrier-less recombination. However, since no mechanistic reports of methyl azide dissociation exist at these conditions, these studies could have significant implications for future experiments addressed to detect cylic-N3 under matrix environments.

Quinto Hernandez, Alfredo

423

Crystal chemical aspects of superconductivity in BaFe2As2 and related compounds  

NASA Astrophysics Data System (ADS)

BaFe2As2 is the parent compound of the 122-type iron arsenides.^1 Superconductivity can