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Sample records for antimycobacterial agent tetrahydrolipstatin

  1. Antimycobacterial agents from selected Mexican medicinal plants.

    PubMed

    Rivero-Cruz, Isabel; Acevedo, Laura; Guerrero, José A; Martínez, Sergio; Bye, Robert; Pereda-Miranda, Rogelio; Franzblau, Scott; Timmermann, Barbara N; Mata, Rachel

    2005-09-01

    As part of the ICBG program Bioactive Agents from Dryland Biodiversity of Latin America, the present investigation was undertaken to explore the possible antimycobacterial potential of compounds derived from selected Mexican medicinal plants. Bioassay-guided fractionation of the crude extracts of Rumex hymenosepalus (Polygonaceae), Larrea divaricata (Zygophyllaceae), Phoradendron robinsonii (Loranthaceae) and Amphipteryngium adstringens (Julianiaceae) led to the isolation of several antimycobacterial compounds. Four stilbenoids, two flavan-3-ols and three anthraquinones were isolated from R. hymenosepalus. Two flavonols and nordihydroguaiaretic acid were obtained from L. divaricata. Sakuranetin was the antimycobacterial agent isolated from P. robinsonii. Two known triterpenoids and the novel natural product 3-dodecyl-1,8-dihydroxy-2-naphthoic acid were obtained from A. adstringens. In general, the isolates were identified by spectral means. The antimycobacterial activity of the secondary compounds isolated from the analysed species, as well as that of nine pure compounds previously isolated in our laboratories, was investigated; the MIC values ranged from 16 to 128 microg mL-1. Among the tested compounds, the glycolipids, sesquiterpenoids and triterpenoids showed the best antimycobacterial activity. The antimycobacterial property of the glycolipids is reported for the first time. Although the tested compounds showed moderate antimycobacterial activity, their presence in the analysed species provides the rationale for their traditional use in the treatment of tuberculosis. PMID:16105233

  2. Peptide deformylase inhibitors as potent antimycobacterial agents.

    PubMed

    Teo, Jeanette W P; Thayalan, Pamela; Beer, David; Yap, Amelia S L; Nanjundappa, Mahesh; Ngew, Xinyi; Duraiswamy, Jeyaraj; Liung, Sarah; Dartois, Veronique; Schreiber, Mark; Hasan, Samiul; Cynamon, Michael; Ryder, Neil S; Yang, Xia; Weidmann, Beat; Bracken, Kathryn; Dick, Thomas; Mukherjee, Kakoli

    2006-11-01

    Peptide deformylase (PDF) catalyzes the hydrolytic removal of the N-terminal formyl group from nascent proteins. This is an essential step in bacterial protein synthesis, making PDF an attractive target for antibacterial drug development. Essentiality of the def gene, encoding PDF from Mycobacterium tuberculosis, was demonstrated through genetic knockout experiments with Mycobacterium bovis BCG. PDF from M. tuberculosis strain H37Rv was cloned, expressed, and purified as an N-terminal histidine-tagged recombinant protein in Escherichia coli. A novel class of PDF inhibitors (PDF-I), the N-alkyl urea hydroxamic acids, were synthesized and evaluated for their activities against the M. tuberculosis PDF enzyme as well as their antimycobacterial effects. Several compounds from the new class had 50% inhibitory concentration (IC50) values of <100 nM. Some of the PDF-I displayed antibacterial activity against M. tuberculosis, including MDR strains with MIC90 values of <1 microM. Pharmacokinetic studies of potential leads showed that the compounds were orally bioavailable. Spontaneous resistance towards these inhibitors arose at a frequency of < or =5 x 10(-7) in M. bovis BCG. DNA sequence analysis of several spontaneous PDF-I-resistant mutants revealed that half of the mutants had acquired point mutations in their formyl methyltransferase gene (fmt), which formylated Met-tRNA. The results from this study validate M. tuberculosis PDF as a drug target and suggest that this class of compounds have the potential to be developed as novel antimycobacterial agents. PMID:16966397

  3. Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents.

    PubMed

    Hampannavar, Girish A; Karpoormath, Rajshekhar; Palkar, Mahesh B; Shaikh, Mahamadhanif S; Chandrasekaran, Balakumar

    2016-07-14

    Series of styryl hydrazine thiazole hybrids inspired from dehydrozingerone (DZG) scaffold were designed and synthesized by molecular hybridization approach. In vitro antimycobacterial activity of synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv strain. Among the series, compound 6o exhibited significant activity (MIC = 1.5 μM; IC50 = 0.48 μM) along with bactericidal (MBC = 12 μM) and intracellular antimycobacterial activities (IC50 = <0.098 μM). Furthermore, 6o displayed prominent antimycobacterial activity under hypoxic (MIC = 46 μM) and normal oxygen (MIC = 0.28 μM) conditions along with antimycobacterial efficiency against isoniazid (MIC = 3.2 μM for INH-R1; 1.5 μM for INH-R2) and rifampicin (MIC = 2.2 μM for RIF-R1; 6.3 μM for RIF-R2) resistant strains of Mtb. Presence of electron donating groups on the phenyl ring of thiazole moiety had positive correlation for biological activity, suggesting the importance of molecular hybridization approach for the development of newer DZG clubbed hydrazine thiazole hybrids as potential antimycobacterial agents. PMID:27437078

  4. Design, diversity-oriented synthesis and structure activity relationship studies of quinolinyl heterocycles as antimycobacterial agents.

    PubMed

    Rachakonda, Venkatesham; Alla, Manjula; Kotipalli, Sudha Sravanti; Ummani, Ramesh

    2013-01-01

    The current study reports design and diversity oriented synthesis of novel bis heterocycles with a common 2-methyl, C-4 unsubstituted quinoline moiety as the central key heterocycle. Employing reagent based skeletal diversity approach; a facile synthesis of bis heterocycles with different heterocyclic rings at C-3 position of the quinoline moiety has been accomplished. A broad range of heterocyclic frameworks thus obtained were evaluated for their antimycobacterial activity. The active scaffolds were further explored by a parallel library generation in order to establish SAR. Further, low cytotoxicity against A549 cell line enhances the potential of the synthesized molecules as promising antimycobacterial agents. PMID:24189497

  5. The efflux pump inhibitor timcodar improves the potency of antimycobacterial agents.

    PubMed

    Grossman, Trudy H; Shoen, Carolyn M; Jones, Steven M; Jones, Peter L; Cynamon, Michael H; Locher, Christopher P

    2015-03-01

    Previous studies indicated that inhibition of efflux pumps augments tuberculosis therapy. In this study, we used timcodar (formerly VX-853) to determine if this efflux pump inhibitor could increase the potency of antituberculosis (anti-TB) drugs against Mycobacterium tuberculosis in in vitro and in vivo combination studies. When used alone, timcodar weakly inhibited M. tuberculosis growth in broth culture (MIC, 19 μg/ml); however, it demonstrated synergism in drug combination studies with rifampin, bedaquiline, and clofazimine but not with other anti-TB agents. When M. tuberculosis was cultured in host macrophage cells, timcodar had about a 10-fold increase (50% inhibitory concentration, 1.9 μg/ml) in the growth inhibition of M. tuberculosis and demonstrated synergy with rifampin, moxifloxacin, and bedaquiline. In a mouse model of tuberculosis lung infection, timcodar potentiated the efficacies of rifampin and isoniazid, conferring 1.0 and 0.4 log10 reductions in bacterial burden in lung, respectively, compared to the efficacy of each drug alone. Furthermore, timcodar reduced the likelihood of a relapse infection when evaluated in a mouse model of long-term, chronic infection with treatment with a combination of rifampin, isoniazid, and timcodar. Although timcodar had no effect on the pharmacokinetics of rifampin in plasma and lung, it did increase the plasma exposure of bedaquiline. These data suggest that the antimycobacterial drug-potentiating activity of timcodar is complex and drug dependent and involves both bacterial and host-targeted mechanisms. Further study of the improvement of the potency of antimycobacterial drugs and drug candidates when used in combination with timcodar is warranted. PMID:25534740

  6. 2-Aminothiazole derivatives as antimycobacterial agents: Synthesis, characterization, in vitro and in silico studies.

    PubMed

    Makam, Parameshwar; Kannan, Tharanikkarasu

    2014-11-24

    A series of 2-aminothiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed and synthesized using Hantzsch thiazole synthesis. These compounds were evaluated for their inhibitory potential against Mycobacterium tuberculosis (Mtb), H37Rv. The compound, 7n showed high antimycobacterial activity with MIC value of 6.25 μM and the succeeding compounds, 7b, 7e and 7f also exhibited antimycobacterial activity with MIC value of 12.50 μM. Docking studies of these molecules with β-Ketoacyl-ACP Synthase (KasA) protein of Mtb have been carried out to understand the mechanism of antimycobacterial action. The compound, 7n showed good interaction with KasA protein with the Ki value of 0.44 μM. PMID:25305331

  7. In-silico Metabolome Target Analysis Towards PanC-based Antimycobacterial Agent Discovery.

    PubMed

    Khoshkholgh-Sima, Baharak; Sardari, Soroush; Izadi Mobarakeh, Jalal; Khavari-Nejad, Ramezan Ali

    2015-01-01

    Mycobacterium tuberculosis, the main cause of tuberculosis (TB), has still remained a global health crisis especially in developing countries. Tuberculosis treatment is a laborious and lengthy process with high risk of noncompliance, cytotoxicity adverse events and drug resistance in patient. Recently, there has been an alarming rise of drug resistant in TB. In this regard, it is an unmet need to develop novel antitubercular medicines that target new or more effective biochemical pathways to prevent drug resistant Mycobacterium. Integrated study of metabolic pathways through in-silico approach played a key role in antimycobacterial design process in this study. Our results suggest that pantothenate synthetase (PanC), anthranilate phosphoribosyl transferase (TrpD) and 3-isopropylmalate dehydratase (LeuD) might be appropriate drug targets. In the next step, in-silico ligand analysis was used for more detailed study of chemical tractability of targets. This was helpful to identify pantothenate synthetase (PanC, Rv3602c) as the best target for antimycobacterial design procedure. Virtual library screening on the best ligand of PanC was then performed for inhibitory ligand design. At the end, five chemical intermediates showed significant inhibition of Mycobacterium bovis with good selectivity indices (SI) ≥10 according to Tuberculosis Antimicrobial Acquisition & Coordinating Facility of US criteria for antimycobacterial screening programs. PMID:25561926

  8. Growth inhibition of Mycobacterium smegmatis by prodrugs of deoxyxylulose phosphate reducto-isomerase inhibitors, promising anti-mycobacterial agents.

    PubMed

    Ponaire, Sarah; Zinglé, Catherine; Tritsch, Denis; Grosdemange-Billiard, Catherine; Rohmer, Michel

    2012-05-01

    Since Mycobacterium tuberculosis sets up several multiple anti-tuberculosis drug resistance mechanisms, development of new drugs with innovative target is urgent. The methylerythritol phosphate pathway (MEP) involved in the biosynthesis of essential metabolites for the survival of mycobacteria, represents such a target. Fosmidomycin 1a and FR900098 1b, two inhibitors of DXR, do not affect the viability of M. tuberculosis cells, due to a lack of uptake. To overcome the absence of the mycobacterial cell wall crossing of these compounds, we synthesized and tested the inhibition potency of acyloxymethyl phosphonate esters as prodrugs of fosmidomycin 1a, FR900098 1b and their analogs 2a and 2b on Mycobacterium smegmatis. Only the prodrugs 4b-6b inhibit the bacterial growth and could be effective anti-mycobacterial agents. PMID:22405649

  9. Comparative Study of Activities of a Diverse Set of Antimycobacterial Agents against Mycobacterium tuberculosis and Mycobacterium ulcerans.

    PubMed

    Scherr, Nicole; Pluschke, Gerd; Panda, Manoranjan

    2016-05-01

    A library of compounds covering a broad chemical space was selected from a tuberculosis drug development program and was screened in a whole-cell assay against Mycobacterium ulcerans, the causative agent of the necrotizing skin disease Buruli ulcer. While a number of potent antitubercular agents were only weakly active or inactive against M. ulcerans, five compounds showed high activity (90% inhibitory concentration [IC90], ≤1 μM), making screening of focused antitubercular libraries a good starting point for lead generation against M. ulcerans. PMID:26883701

  10. Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis.

    PubMed

    Kremer, L; Douglas, J D; Baulard, A R; Morehouse, C; Guy, M R; Alland, D; Dover, L G; Lakey, J H; Jacobs, W R; Brennan, P J; Minnikin, D E; Besra, G S

    2000-06-01

    Prevention efforts and control of tuberculosis are seriously hampered by the appearance of multidrug-resistant strains of Mycobacterium tuberculosis, dictating new approaches to the treatment of the disease. Thiolactomycin (TLM) is a unique thiolactone that has been shown to exhibit anti-mycobacterial activity by specifically inhibiting fatty acid and mycolic acid biosynthesis. In this study, we present evidence that TLM targets two beta-ketoacyl-acyl-carrier protein synthases, KasA and KasB, consistent with the fact that both enzymes belong to the fatty-acid synthase type II system involved in fatty acid and mycolic acid biosynthesis. Overexpression of KasA, KasB, and KasAB in Mycobacterium bovis BCG increased in vivo and in vitro resistance against TLM. In addition, a multidrug-resistant clinical isolate was also found to be highly sensitive to TLM, indicating promise in counteracting multidrug-resistant strains of M. tuberculosis. The design and synthesis of several TLM derivatives have led to compounds more potent both in vitro against fatty acid and mycolic acid biosynthesis and in vivo against M. tuberculosis. Finally, a three-dimensional structural model of KasA has also been generated to improve understanding of the catalytic site of mycobacterial Kas proteins and to provide a more rational approach to the design of new drugs. PMID:10747933

  11. Total Synthesis of Tetrahydrolipstatin and Stereoisomers via a Highly Regio- and Diastereoselective Carbonylation of Epoxyhomoallylic Alcohols

    PubMed Central

    2015-01-01

    A concise enantioselective synthesis of tetrahydrolipstatin (THL) and seven stereoisomers has been achieved. The synthesis of THL was accomplished in 10 steps and 31% overall yield from an achiral ynone. Key to the success of the approach is the use of a bimetallic [Lewis acid]+[Co(CO)4]− catalyst for a late-stage regioselective carbonylation of an enantiomerically pure cis-epoxide to a trans-β-lactone. The success of this route to THL and its stereoisomers also demonstrated the practicality of the carbonylation catalyst for complex molecule synthesis as well as its functional group compatibility. PMID:25004122

  12. Tetrahydrolipstatin Inhibition, Functional Analyses, and Three-dimensional Structure of a Lipase Essential for Mycobacterial Viability

    SciTech Connect

    Crellin, Paul K.; Vivian, Julian P.; Scoble, Judith; Chow, Frances M.; West, Nicholas P.; Brammananth, Rajini; Proellocks, Nicholas I.; Shahine, Adam; Le Nours, Jerome; Wilce, Matthew C.J.; Britton, Warwick J.; Coppel, Ross L.; Rossjohn, Jamie; Beddoe, Travis

    2010-09-17

    The highly complex and unique mycobacterial cell wall is critical to the survival of Mycobacteria in host cells. However, the biosynthetic pathways responsible for its synthesis are, in general, incompletely characterized. Rv3802c from Mycobacterium tuberculosis is a partially characterized phospholipase/thioesterase encoded within a genetic cluster dedicated to the synthesis of core structures of the mycobacterial cell wall, including mycolic acids and arabinogalactan. Enzymatic assays performed with purified recombinant proteins Rv3802c and its close homologs from Mycobacterium smegmatis (MSMEG{_}6394) and Corynebacterium glutamicum (NCgl2775) show that they all have significant lipase activities that are inhibited by tetrahydrolipstatin, an anti-obesity drug that coincidently inhibits mycobacterial cell wall biosynthesis. The crystal structure of MSMEG{_}6394, solved to 2.9 {angstrom} resolution, revealed an {alpha}/{beta} hydrolase fold and a catalytic triad typically present in esterases and lipases. Furthermore, we demonstrate direct evidence of gene essentiality in M. smegmatis and show the structural consequences of loss of MSMEG{_}6394 function on the cellular integrity of the organism. These findings, combined with the predicted essentiality of Rv3802c in M. tuberculosis, indicate that the Rv3802c family performs a fundamental and indispensable lipase-associated function in mycobacteria.

  13. Cryptolepine hydrochloride: a potent antimycobacterial alkaloid derived from Cryptolepis sanguinolenta.

    PubMed

    Gibbons, Simon; Fallah, Fatemeh; Wright, Colin W

    2003-04-01

    The activity of cryptolepine hydrochloride, a salt of the main indoloquinoline alkaloid from the West African medicinal plant Cryptolepis sanguinolenta, was assessed against the fast growing mycobacterial species Mycobacterium fortuitum, which has recently been shown to be of use in the evaluation of antitubercular drugs. The low minimum inhibitory concentration (MIC) of this compound (16 microg/mL) prompted further evaluation against other fast growing mycobacteria namely, M. phlei, M. aurum, M. smegmatis, M. bovis BCG and M. abcessus and the MICs ranged over 2-32 microg/mL for these species. The strong activity of this agent, the need for new antibiotics with activity against Mycobacterium tuberculosis, coupled with the ethnobotanical use of C. sanguinolenta extracts to treat infections, highlight the potential of the cryptolepine template for development of antimycobacterial agents. PMID:12722159

  14. Antimycobacterial and cytotoxic activity of selected medicinal plant extracts

    PubMed Central

    Nguta, Joseph M.; Appiah-Opong, Regina; Nyarko, Alexander K.; Yeboah-Manu, Dorothy; Addo, Phyllis G.A.; Otchere, Isaac; Kissi-Twum, Abena

    2016-01-01

    Ethnopharmacological relevance Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Several medicinal plants are used traditionally to treat tuberculosis in Ghana. The current study was designed to investigate the antimycobacterial activity and cytotoxicity of crude extracts from five selected medicinal plants. Material and methods The microplate alamar blue assay (MABA) was used for antimycobacterial studies while the CellTiter 96® AQueous Assay, which is composed of solutions of a novel tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] and an electron coupling reagent (phenazine methosulfate) PMS, was used for cytotoxic studies. Correlation coefficients were used to compare the activity of crude extracts against nonpathogenic strains and the pathogenic Mycobacterium tuberculosis subsp.tuberculosis. Results Results of the MIC determinations indicated that all the crude extracts were active on all the three tested mycobacterial strains. Minimum inhibitory concentration values as low as 156.3 µg/mL against M. tuberculosis; Strain H37Ra (ATCC® 25,177™) were recorded from the leaves of Solanum torvum Sw. (Solanaceae). Cytotoxicity of the extracts varied, and the leaves from S. torvum had the most promising selectivity index. Activity against M. tuberculosis; Strain H37Ra was the best predictor of activity against pathogenic Mycobacterium tuberculosis subsp.tuberculosis (correlation coefficient=0.8). Conclusion The overall results of the present study provide supportive data on the use of some medicinal plants for tuberculosis treatment. The leaves of Solanum torvum are a potential source of anti-TB natural products and deserve further investigations to develop novel anti-TB agents against sensitive and drug resistant strains of M. tuberculosis. PMID:26875647

  15. Design and synthesis of triazolopyrimidine acylsulfonamides as novel anti-mycobacterial leads acting through inhibition of acetohydroxyacid synthase.

    PubMed

    Patil, Vikas; Kale, Manoj; Raichurkar, Anandkumar; Bhaskar, Brahatheeswaran; Prahlad, Dwarakanath; Balganesh, Meenakshi; Nandan, Santosh; Shahul Hameed, P

    2014-05-01

    Novel triazolopyrimidine acylsulfonamides class of antimycobacterial agents, which are mycobacterial acetohydroxyacid synthase (AHAS) inhibitors were designed by hybridization of known AHAS inhibitors such as sulfonyl urea and triazolopyrimidine sulfonamides. This Letter describes the synthesis and SAR studies of this class of molecules by variation of two parts of the molecule, the phenyl and triazolopyrimidine rings. SAR study describes optimisation of enzyme potency, whole cell potency and evidence of mechanism of action. PMID:24703230

  16. Synthesis, antimycobacterial activity evaluation, and QSAR studies of chalcone derivatives.

    PubMed

    Sivakumar, P M; Seenivasan, S Prabu; Kumar, Vanaja; Doble, Mukesh

    2007-03-15

    In order to develop relatively small molecules as antimycobacterial agents, twenty-five chalcones were synthesized, their activity was evaluated, and quantitative structure-activity relationship (QSAR) was developed. The synthesis was based on the Claisen-Schimdt scheme and the resultant compounds were tested for antitubercular activity by luciferase reporter phage (LRP) assay. Compound C(24) was found to be the most active ( approximately 99%) in this series based on the percentage reduction in Relative Light Units at both 50 and 100 microg/ml levels, followed by compound C(21). Four compounds at the 50 microg/ml and eight compounds at the 100 microg/ml showed activity above 90% level. QSAR model was developed between activity and spatial, topological, and ADME descriptors for the 50 microg/ml data. The statistical measures such as r, r(2), q(2), and F values obtained for the training set were in acceptable range and hence this relationship was used for the test set. The predictive ability of the model is satisfactory (q(2)=0.56) and it can be used for designing similar group of compounds. PMID:17276682

  17. Antimycobacterial brominated metabolites from two species of marine sponges.

    PubMed

    de Oliveira, Maria Fernanda; de Oliveira, Jaine Honorata; Galetti, Fabio C; de Souza, Ana Olívia; Silva, Célio Lopes; Hajdu, Eduardo; Peixinho, Solange; Berlinck, Roberto G

    2006-04-01

    A screening of 500 crude extracts of marine invertebrates against the growth of Mycobacterium tuberculosis H37Rv yielded MeOH extracts of the sponges Aplysina cauliformis and Pachychalina sp. with significant activity. Further bioassay-guided fractionation of both crude extracts led to the isolation of four bromine-containing metabolites. The known (+)-fistularin-3 (1) and 11-deoxyfistularin-3 (2), and the new compound 2-(3-amino-2,4-dibromo-6-hydroxyphenyl)acetic acid (3) were isolated from the sponge A. cauliformis, while the new bromotyrosine-derived 3-(3,5-dibromo-4-methoxyphenyl)-2-methoxy- N-methylpropan-1-ammonium (4) was isolated from Pachychalina sp. Compound 4 exhibited weak antimycobacterial activity while compounds 1-3 displayed activity against Mycobacterium tuberculosis H37Rv, with MICs of 7.1, 7.3 and 49 microM, respectively. Compounds 1 and 2 also exhibited low cytotoxicity against J744 macrophages, indicating that both 1 and 2 are interesting leads for the development of new anti-tuberculosis agents. PMID:16557458

  18. Design of novel camphane-based derivatives with antimycobacterial activity.

    PubMed

    Stavrakov, Georgi; Valcheva, Violeta; Philipova, Irena; Doytchinova, Irini

    2014-06-01

    Although tuberculosis (TB) continues to be one of the leading infectious disease killers globally, it is curable and preventable. Despite the existence of safe, well tolerated and effective drugs used in the TB treatment, the interest in new entities, combinations and regimens increases during the last 10 years. Recently, we reported for a new class of anti-TB agents - camphane-based derivatives with nanomolar activity against Mycobacterium tuberculosis strains. The quantitative structure-activity relationship (QSAR) study on 12 compounds revealed several structural requirements for antimycobacterial activity: two hydrogen bond donors, two or three rings and no large branched substituents. Here, we describe the design of a set of nine novel camphane-based derivatives following these requirements. The compounds were synthesized and tested against M. tuberculosis strain H37Rv. Four of them showed activities in the nanomolar range, significantly higher than the activities in the initial set. The QSAR study based on all 21 derivatives pointed to two main structural requirements for anti-TB activity: two hydrogen bond donors and a side chain with aromatic ring. PMID:24859319

  19. Anti-mycobacterial peptides: from human to phage.

    PubMed

    Teng, Tieshan; Liu, Jiafa; Wei, Hongping

    2015-01-01

    Mycobacterium tuberculosis is the major pathogen of tuberculosis (TB). With the growing problem of M. tuberculosis resistant to conventional antibiotics, especially multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the need for new TB drugs is now more prominent than ever. Among the promising candidates for anti-TB drugs, anti-mycobacterial peptides have a few advantages, such as low immunogenicity, selective affinity to prokaryotic negatively charged cell envelopes, and diverse modes of action. In this review, we summarize the recent progress in the anti-mycobacterial peptides, highlighting the sources, effectiveness and bactericidal mechanisms of these antimicrobial peptides. Most of the current anti-mycobacterial peptides are derived either from host immune cells, bacterial extraction, or mycobacteriophages. Besides trans-membrane pore formation, which is considered to be the common bactericidal mechanism, many of the anti-mycobacterial peptides have the second non-membrane targets within mycobacteria. Additionally, some antimicrobial peptides play critical roles in innate immunity. However, a few obstacles, such as short half-life in vivo and resistance to antimicrobial peptides, need overcoming before clinical applications. Nevertheless, the multiple functions of anti-mycobacterial peptides, especially direct killing of pathogens and immune-modulators in infectious and inflammatory conditions, indicate that they are promising candidates for future drug development. PMID:25613372

  20. Antimycobacterial drugs modulate immunopathogenic matrix metalloproteinases in a cellular model of pulmonary tuberculosis.

    PubMed

    Singh, Shivani; Kubler, Andre; Singh, Utpal K; Singh, Ajay; Gardiner, Harriet; Prasad, Rajniti; Elkington, Paul T; Friedland, Jon S

    2014-08-01

    Tuberculosis is characterized by extensive destruction and remodelling of the pulmonary extracellular matrix. Stromal cell-derived matrix metalloproteinases (MMPs) are implicated in this process and may be a target for adjunctive immunotherapy. We hypothesized that MMPs are elevated in bronchoalveolar lavage fluid of tuberculosis patients and that antimycobacterial agents may have a modulatory effect on MMP secretion. Concentrations of MMP-1, -2, -3, -7, -8, and -9 were elevated in the bronchoalveolar lavage fluid from tuberculosis patients compared to those in bronchoalveolar lavage fluid from patients with other pulmonary conditions. There was a positive correlation between MMP-3, MMP-7, and MMP-8 and a chest radiological score of cavitation and parenchymal damage. Respiratory epithelial cell-derived MMP-3 was suppressed by moxifloxacin, rifampicin, and azithromycin in a dose-dependent manner. Respiratory epithelial cell-derived MMP-1 was suppressed by moxifloxacin and azithromycin, whereas MMP-9 secretion was only decreased by moxifloxacin. In contrast, moxifloxacin and azithromycin both increased MMP-1 and -3 secretion from MRC-5 fibroblasts, demonstrating that the effects of these drugs are cell specific. Isoniazid did not affect MMP secretion. In conclusion, MMPs are elevated in bronchoalveolar lavage fluid from tuberculosis patients and correlate with parameters of tissue destruction. Antimycobacterial agents have a hitherto-undescribed immunomodulatory effect on MMP release by stromal cells. PMID:24890593

  1. Novel pyrazine analogs of chalcones: synthesis and evaluation of their antifungal and antimycobacterial activity.

    PubMed

    Kucerova-Chlupacova, Marta; Kunes, Jiri; Buchta, Vladimir; Vejsova, Marcela; Opletalova, Veronika

    2015-01-01

    Infectious diseases, such as tuberculosis and invasive mycoses, represent serious health problems. As a part of our long-term efforts to find new agents for the treatment of these diseases, a new series of pyrazine analogs of chalcones bearing an isopropyl group in position 5 of the pyrazine ring was prepared. The structures of the compounds were corroborated by IR and NMR spectroscopy and their purity confirmed by elemental analysis. The susceptibility of eight fungal strains to the studied compounds was tested. The results have been compared with the activity of some previously reported propyl derivatives. The only strain that was susceptible to the studied compounds was Trichophyton mentagrophytes. It was found that replacing a non-branched propyl with a branched isopropyl did not have a decisive and unequivocal influence on the in vitro antifungal activity against T. mentagrophytes. In vitro activity against Trichophyton mentagrophytes comparable with that of fluconazole was exhibited by nitro-substituted derivatives. Unfortunately, no compound exhibited efficacy comparable with that of terbinafine, which is the most widely used agent for treating mycoses caused by dermatophytes. Some of the prepared compounds were assayed for antimycobacterial activity against M. tuberculosis H37Rv. The highest potency was also displayed by nitro-substituted compounds. The results of the present study are in a good agreement with our previous findings and confirm the positive influence of electron-withdrawing groups on the B-ring of chalcones on the antifungal and antimycobacterial activity of these compounds. PMID:25587786

  2. N-Alkoxyphenylhydroxynaphthalenecarboxamides and Their Antimycobacterial Activity.

    PubMed

    Gonec, Tomas; Pospisilova, Sarka; Kauerova, Tereza; Kos, Jiri; Dohanosova, Jana; Oravec, Michal; Kollar, Peter; Coffey, Aidan; Liptaj, Tibor; Cizek, Alois; Jampilek, Josef

    2016-01-01

    A series of nineteen N-(alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides and a series of their nineteen positional isomers N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides were prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, M. kansasii and M. smegmatis. Screening of the cytotoxicity of the compounds was performed using human monocytic leukemia THP-1 cells. Some of the tested compounds showed antimycobacterial activity comparable with or higher than that of rifampicin. For example, 2-hydroxy-N-(4-propoxyphenyl)-naphthalene-1-carboxamide showed the highest activity (MIC = 12 µM) against M. tuberculosis with insignificant cytotoxicity. N-[3-(But-2-yloxy)phenyl]- and N-[4-(but-2-yloxy)phenyl]-2-hydroxy-naphthalene-1-carboxamide demonstrated high activity against all tested mycobacterial strains and insignificant cytotoxicity. N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides demonstrated rather high effect against M. smegmatis and M. kansasii and strong antiproliferative effect against the human THP-1 cell line. Lipophilicity was found as the main physicochemical parameter influencing the activity. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Structure-activity relationships are discussed. PMID:27537867

  3. Trp-107 and trp-253 account for the increased steady state fluorescence that accompanies the conformational change in human pancreatic triglyceride lipase induced by tetrahydrolipstatin and bile salt.

    PubMed

    Bourbon-Freie, Angela; Dub, Rachel E; Xiao, Xunjun; Lowe, Mark E

    2009-05-22

    The conformation of a surface loop, the lid, controls activity of pancreatic triglyceride lipase (PTL) by moving from a position that sterically hinders substrate access to the active site into a new conformation that opens and configures the active site. Movement of the lid is accompanied by a large change in steady state tryptophan fluorescence. Although a change in the microenvironment of Trp-253, a lid residue, could account for the increased fluorescence, the mechanism and tryptophan residues have not been identified. To identify the tryptophan residues responsible for the increased fluorescence and to gain insight into the mechanism of lid opening and the structure of PTL in aqueous solution, we examined the effects of mutating individual tryptophan residues to tyrosine, alanine, or phenylalanine on lipase activity and steady state fluorescence. Substitution of tryptophans 86, 107, 253, and 403 reduced activity against tributyrin with the largest effects caused by substituting Trp-86 and Trp-107. Trp-107 and Trp-253 fluorescence accounts for the increased fluorescence emissions of PTL that is stimulated by tetrahydrolipstatin and sodium taurodeoxycholate. The largest contribution is from Trp-107. Contrary to the prediction from the crystal structure of PTL, Trp-107 is likely exposed to solvent. Both tetrahydrolipstatin and sodium taurodeoxycholate are required to produce the increased fluorescence in PTL. Alone, neither is sufficient. Colipase does not significantly influence the conformational changes leading to increased emission fluorescence. Thus, Trp-107 and Trp-253 contribute to the change in steady state fluorescence that is triggered by mixed micelles of inhibitor and bile salt. Furthermore, the results suggest that the conformation of PTL in solution differs significantly from the conformation in crystals. PMID:19346257

  4. Tricyclic sesquiterpenes from Vetiveria zizanoides (L.) Nash as antimycobacterial agents.

    PubMed

    Dwivedi, Gaurav R; Gupta, Shikha; Roy, Sudeep; Kalani, Komal; Pal, Anirban; Thakur, Jay P; Saikia, Dharmendra; Sharma, Ashok; Darmwal, Nandan S; Darokar, Mahendra P; Srivastava, Santosh K

    2013-11-01

    Two bioactive constituents, khusenic acid (1) and khusimol (2), were isolated and characterized from hexane fraction of Vetiveria zizanoides roots. Compounds, 1 and 2, were tested against the various drug-resistant mutants of Mycobacterium smegmatis. The results showed that compound 1 was 4 times more active than the standard drugs ciprofloxacin (CF) and nalidixic acid (NA) against the ciprofloxacin (CSC 101) and lomefloxacin(LOMR5)-resistant mutants, whereas the compound 2 was 2 times more active against the CSC 101 than the NA and CF. Further, these compounds were tested against the virulent strain H37Rv of Mycobacterium tuberculosis, which showed that 1 was two times more active than NA, while 2 was equally active to NA. In in silico docking study, 1 showed better binding affinity than 2 with both subunits of the bacterial DNA gyrase, which was further confirmed from the in vitro bacterial DNA gyrase inhibition study. The in silico ADME analysis of 1 and 2 showed better intestinal absorption, aqueous solubility and ability to penetrate blood-brain barrier. Finally, compound 2 was found safe at the highest dose of 2000 mg/kg body weight. Being edible, fragrant natural products, 1 and 2 will have advantage over the existing synthetic drugs. PMID:23841574

  5. Antimycobacterial activity in vitro of pigments isolated from Antarctic bacteria.

    PubMed

    Mojib, Nazia; Philpott, Rachel; Huang, Jonathan P; Niederweis, Michael; Bej, Asim K

    2010-11-01

    In this study, we describe the antimycobacterial activity of two pigments, violacein, a purple violet pigment from Janthinobacterium sp. Ant5-2 (J-PVP), and flexirubin, a yellow-orange pigment from Flavobacterium sp. Ant342 (F-YOP). These pigments were isolated from bacterial strains found in the land-locked freshwater lakes of Schirmacher Oasis, East Antarctica. The minimum inhibitory concentrations (MICs) of these pigments for avirulent and virulent mycobacteria were determined by the microplate Alamar Blue Assay (MABA) and Nitrate Reductase Assay (NRA). Results indicated that the MICs of J-PVP and F-YOP were 8.6 and 3.6 μg/ml for avirulent Mycobacterium smegmatis mc²155; 5 and 2.6 μg/ml for avirulent Mycobacterium tuberculosis mc²6230; and 34.4 and 10.8 μg/ml for virulent M. tuberculosis H₃₇Rv, respectively. J-PVP exhibited a ~15 times lower MIC for Mycobacterium sp. than previously reported for violacein pigment from Chromobacterium violaceum, while the antimycobacterial effect of F-YOP remains undocumented. Our results indicate these pigments isolated from Antarctic bacteria might be valuable lead compounds for new antimycobacterial drugs used for chemotherapy of tuberculosis. PMID:20556653

  6. Effects of Ascent to High Altitude on Human Antimycobacterial Immunity

    PubMed Central

    Aldridge, Robert W.; Siedner, Mark J.; Necochea, Alejandro; Leybell, Inna; Valencia, Teresa; Herrera, Beatriz; Wiles, Siouxsie; Friedland, Jon S.; Gilman, Robert H.; Evans, Carlton A.

    2013-01-01

    Background Tuberculosis infection, disease and mortality are all less common at high than low altitude and ascent to high altitude was historically recommended for treatment. The immunological and mycobacterial mechanisms underlying the association between altitude and tuberculosis are unclear. We studied the effects of altitude on mycobacteria and antimycobacterial immunity. Methods Antimycobacterial immunity was assayed in 15 healthy adults residing at low altitude before and after they ascended to 3400 meters; and in 47 long-term high-altitude residents. Antimycobacterial immunity was assessed as the extent to which participants’ whole blood supported or restricted growth of genetically modified luminescent Bacille Calmette-Guérin (BCG) mycobacteria during 96 hours incubation. We developed a simplified whole blood assay that could be used by a technician in a low-technology setting. We used this to compare mycobacterial growth in participants’ whole blood versus positive-control culture broth and versus negative-control plasma. Results Measurements of mycobacterial luminescence predicted the number of mycobacterial colonies cultured six weeks later. At low altitude, mycobacteria grew in blood at similar rates to positive-control culture broth whereas ascent to high altitude was associated with restriction (p≤0.002) of mycobacterial growth to be 4-times less than in culture broth. At low altitude, mycobacteria grew in blood 25-times more than negative-control plasma whereas ascent to high altitude was associated with restriction (p≤0.01) of mycobacterial growth to be only 6-times more than in plasma. There was no evidence of differences in antimycobacterial immunity at high altitude between people who had recently ascended to high altitude versus long-term high-altitude residents. Conclusions An assay of luminescent mycobacterial growth in whole blood was adapted and found to be feasible in low-resource settings. This demonstrated that ascent to or

  7. Interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: a biophysical approach to disease.

    PubMed

    Pinheiro, Marina; Giner-Casares, Juan J; Lúcio, Marlene; Caio, João M; Moiteiro, Cristina; Lima, José L F C; Reis, Salette; Camacho, Luis

    2013-02-01

    This work focuses on the interaction of mycolic acids (MAs) and two antimycobacterial compounds (Rifabutin and N'-acetyl-Rifabutin) at the pulmonary membrane level to convey a biophysical perspective of their role in disease. For this purpose, accurate biophysical techniques (Langmuir isotherms, Brewster angle microscopy, and polarization-modulation infrared reflection spectroscopy) and lipid model systems were used to mimic biomembranes: MAs mimic bacterial lipids of the Mycobacterium tuberculosis (MTb) membrane, whereas Curosurf® was used as the human pulmonary surfactant (PS) membrane model. The results obtained show that high quantities of MAs are responsible for significant changes on PS biophysical properties. At the dynamic inspiratory surface tension, high amounts of MAs decrease the order of the lipid monolayer, which appears to be a concentration dependent effect. These results suggest that the amount of MAs might play a critical role in the initial access of the bacteria to their targets. Both molecules also interact with the PS monolayer at the dynamic inspiratory surface. However, in the presence of higher amounts of MAs, both compounds improve the phospholipid packing and, therefore, the order of the lipid surfactant monolayer. In summary, this work discloses the putative protective effects of antimycobacterial compounds against the MAs induced biophysical impairment of PS lipid monolayers. These protective effects are most of the times overlooked, but can constitute an additional therapeutic value in the treatment of pulmonary tuberculosis (Tb) and may provide significant insights for the design of new and more efficient anti-Tb drugs based on their behavior as membrane ordering agents. PMID:23022131

  8. Gene encoded antimicrobial peptides, a template for the design of novel anti-mycobacterial drugs.

    PubMed

    Carroll, James; Field, Des; O'Connor, Paula M; Cotter, Paul D; Coffey, Aidan; Hill, Colin; Ross, R Paul; O'Mahony, Jim

    2010-01-01

    Nisin A is the most widely characterized lantibiotic investigated to date. It represents one of the many antimicrobial peptides which have been the focus of much interest as potential therapeutic agents. This has resulted in the search for novel lantibiotics and more commonly, the engineering of novel variants from existing peptides with a view to increasing their activity, stability and solubility.The aim of this study was to compare the activities of nisin A and novel bioengineered hinge derivatives, nisin S, nisin T and nisin V. The microtitre alamar blue assay (MABA) was employed to identify the enhanced activity of these novel variants against M. tuberculosis (H37Ra), M. kansasii (CIT11/06), M. avium subsp. hominissuis (CIT05/03) and M. avium subsp. paratuberculosis (MAP) (ATCC 19698). All variants displayed greater anti-mycobacterial activity than nisin A. Nisin S was the most potent variant against M. tuberculosis, M. kansasii and M. avium subsp. hominissuis, retarding growth by a maximum of 29% when compared with nisin A. Sub-species variations of inhibition were also observed with nisin S reducing growth of Mycobacterium avium subsp. hominissuis by 28% and Mycobacterium avium subsp. paratuberculosis by 19% and nisin T contrastingly reducing growth of MAP by 27% and MAC by 16%.Nisin S, nisin T and nisin V are potent novel anti-mycobacterial compounds, which have the capacity to be further modified, potentially generating compounds with additional beneficial characteristics. This is the first report to demonstrate an enhancement of efficacy by any bioengineered bacteriocin against mycobacteria. PMID:21468208

  9. Improved antimycobacterial activity of rifampin using solid lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Aboutaleb, Ehsan; Noori, Massoumeh; Gandomi, Narges; Atyabi, Fatemeh; Fazeli, Mohammad Reza; Jamalifar, Hossein; Dinarvand, Rassoul

    2012-10-01

    Rifampin (RIF) is one of the front-line drugs in therapy of tuberculosis (TB). The emergence of multidrug-resistant strains of mycobacteria has greatly contributed to the increased incidence of TB. Nano-based formulation of several antimicrobials has been shown to improve either antibacterial efficacy or pharmacokinetic behavior. In this study, RIF-loaded solid lipid nanoparticles (SLNs) were prepared by a modified microemulsion-based method and their particle size, zeta potential, encapsulation efficiency, morphology, and antibacterial activity against Mycobacterium fortuitum were evaluated. The resulting SLNs were spherical with diameter of about 100 nm, with low negative zeta potential, and an encapsulation efficiency of 82%. The formulation also sustained the drug release for 72 h. The antimycobacterial efficacy was greatly improved against M. fortuitum, and the minimum inhibitory concentration of drug-loaded SLNs was eight times less than free RIF. Drug-free SLNs and the ingredients showed no antibacterial effect. It can be concluded that as expected, solid lipid nanoparticles are promising vehicles for enhanced antimycobacterial effect of rifampin.

  10. DFT-based QSAR models to predict the antimycobacterial activity of chalcones.

    PubMed

    Barua, Nilakshi; Sarmah, Pubalee; Hussain, Iftikar; Deka, Ramesh C; Buragohain, Alak K

    2012-04-01

    In this study, antimycobacterial activity of a set of synthesized chalcone derivatives against Mycobacterium tuberculosis H37Rv was investigated by quantitative structure-activity relationship (QSAR) analysis using density functional theory (DFT) and molecular mechanics (MM+)-based descriptors in both gas and solvent phases. The best molecular descriptors identified were hardness, E(HOMO) , MR(A-4) and MR(B-4') that contributed to the antimycobacterial activity of the chalcones as independent factors. The correlation of these four descriptors with their antimycobacterial activity increases with the inclusion of solvent medium, indicating their importance in studying biological activity. QSAR models revealed that in gas phase, lower values of E(HOMO) , MR(A-4) and MR(B-4') increase the antimycobacterial activity of the chalcone molecules. However, in solvent phase, lower values of E(HOMO) and MR(B-4') and higher values of MR(A-4) increase their activity. PMID:22151277

  11. In vitro antimycobacterial and cytotoxic data on medicinal plants used to treat tuberculosis

    PubMed Central

    Nguta, Joseph M.; Appiah-Opong, Regina; Nyarko, Alexander K.; Yeboah-Manu, Dorothy; Addo, Phyllis G.A.; Otchere, Isaac D.; Kissi-Twum, Abena

    2016-01-01

    This article contains data on in vitro antimycobacterial activity and cytotoxicity of hydroethanolic crude extracts from five selected medicinal plant species traditionally used to treat tuberculosis in Ghanaian ethnomedicine, see “Medicinal plants used to treat TB in Ghana” [1]. The interpretation and discussion of these data and further extensive insights into drug discovery against tuberculosis from natural products of plant biodiversity can be found in “Antimycobacterial and cytotoxic activity of selected medicinal plant extracts” [2]. PMID:27115026

  12. In vitro antimycobacterial and cytotoxic data on medicinal plants used to treat tuberculosis.

    PubMed

    Nguta, Joseph M; Appiah-Opong, Regina; Nyarko, Alexander K; Yeboah-Manu, Dorothy; Addo, Phyllis G A; Otchere, Isaac D; Kissi-Twum, Abena

    2016-06-01

    This article contains data on in vitro antimycobacterial activity and cytotoxicity of hydroethanolic crude extracts from five selected medicinal plant species traditionally used to treat tuberculosis in Ghanaian ethnomedicine, see "Medicinal plants used to treat TB in Ghana" [1]. The interpretation and discussion of these data and further extensive insights into drug discovery against tuberculosis from natural products of plant biodiversity can be found in "Antimycobacterial and cytotoxic activity of selected medicinal plant extracts" [2]. PMID:27115026

  13. A Novel Antimycobacterial Compound Acts as an Intracellular Iron Chelator

    PubMed Central

    Dragset, Marte S.; Poce, Giovanna; Alfonso, Salvatore; Padilla-Benavides, Teresita; Ioerger, Thomas R.; Kaneko, Takushi; Sacchettini, James C.; Biava, Mariangela; Parish, Tanya; Argüello, José M.

    2015-01-01

    Efficient iron acquisition is crucial for the pathogenesis of Mycobacterium tuberculosis. Mycobacterial iron uptake and metabolism are therefore attractive targets for antitubercular drug development. Resistance mutations against a novel pyrazolopyrimidinone compound (PZP) that is active against M. tuberculosis have been identified within the gene cluster encoding the ESX-3 type VII secretion system. ESX-3 is required for mycobacterial iron acquisition through the mycobactin siderophore pathway, which could indicate that PZP restricts mycobacterial growth by targeting ESX-3 and thus iron uptake. Surprisingly, we show that ESX-3 is not the cellular target of the compound. We demonstrate that PZP indeed targets iron metabolism; however, we found that instead of inhibiting uptake of iron, PZP acts as an iron chelator, and we present evidence that the compound restricts mycobacterial growth by chelating intrabacterial iron. Thus, we have unraveled the unexpected mechanism of a novel antimycobacterial compound. PMID:25645825

  14. Synthesis and evaluation of antimycobacterial activity of new benzimidazole aminoesters.

    PubMed

    Yoon, Yeong Keng; Ali, Mohamed Ashraf; Wei, Ang Chee; Choon, Tan Soo; Ismail, Rusli

    2015-03-26

    A total of 51 novel benzimidazoles were synthesized by a 4-step reaction starting from basic compound 4-fluoro-3-nitrobenzoic acid under relatively mild reaction conditions. The structure of the novel benzimidazoles was confirmed by mass spectra as well as (1)H NMR spectroscopic data. Out of the 51 novel synthesized compounds, 42 of them were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain using BacTiter-Glo™ Microbial Cell Viability (BTG) method. Results of activity screened using Alamar Blue method was also provided for comparison purposes. Two of the novel benzimidazoles synthesized showed moderately good activity with IC50 of less than 15 μM. Compound 5g, ethyl 2-(4-(trifluoromethyl)phenyl)-1-(2-morpholinoethyl)-1H-benzo[d]imidazole-5-carboxylate, was found to be the most active with IC50 of 11.52 μM. PMID:24996257

  15. Synthesis and Antimycobacterial Activity of some Triazole Derivatives–New Route to Functionalized Triazolopyridazines

    PubMed Central

    Tehrani, Kamaleddin Haj Mohammad Ebrahim; Mashayekhi, Vida; Azerang, Parisa; Minaei, Somayeh; Sardari, Soroush; Kobarfard, Farzad

    2015-01-01

    A series of cyclic analogues of bioactive thiosemicarbazide derivatives have been synthesized as potential antimycobacterial agents. The 4-amino-1,2,4-triazole-5-thione analogues (Ia-f) were prepared by heating a mixture of thiocarbohydrzide and appropriate carboxylic acids. Reaction of thiocarbohydrazide with γ-ketoesters in the presence of sodium methoxide furnished triazolopyridazine derivatives IIa-b. Finally, condensation of 4-amino-1,2,4-triazole-5-thione with some aldehydes gave Schiff bases IIIa-e. After characterization by different spectroscopic and analytical methods, the derivatives were tested for their inhibitory activity against Mycobacterium bovis BCG. Among the derivatives, compound Ib proved to be the most potent derivatives with MIC value of 31.25 µg/mL. Given the fact that 4-amino-1,2,4-triazole-5-thiones Ia-f were the most active derivatives, it could be suggested that this group of derivatives have the potential to be considered as lead compounds for future optimization efforts. PMID:26185506

  16. Synthesis and Antimycobacterial Activity of some Triazole Derivatives-New Route to Functionalized Triazolopyridazines.

    PubMed

    Tehrani, Kamaleddin Haj Mohammad Ebrahim; Mashayekhi, Vida; Azerang, Parisa; Minaei, Somayeh; Sardari, Soroush; Kobarfard, Farzad

    2015-01-01

    A series of cyclic analogues of bioactive thiosemicarbazide derivatives have been synthesized as potential antimycobacterial agents. The 4-amino-1,2,4-triazole-5-thione analogues (Ia-f) were prepared by heating a mixture of thiocarbohydrzide and appropriate carboxylic acids. Reaction of thiocarbohydrazide with γ-ketoesters in the presence of sodium methoxide furnished triazolopyridazine derivatives IIa-b. Finally, condensation of 4-amino-1,2,4-triazole-5-thione with some aldehydes gave Schiff bases IIIa-e. After characterization by different spectroscopic and analytical methods, the derivatives were tested for their inhibitory activity against Mycobacterium bovis BCG. Among the derivatives, compound Ib proved to be the most potent derivatives with MIC value of 31.25 µg/mL. Given the fact that 4-amino-1,2,4-triazole-5-thiones Ia-f were the most active derivatives, it could be suggested that this group of derivatives have the potential to be considered as lead compounds for future optimization efforts. PMID:26185506

  17. Antimycobacterial Activity of a New Peptide Polydim-I Isolated from Neotropical Social Wasp Polybia dimorpha

    PubMed Central

    das Neves, Rogerio Coutinho; Trentini, Monalisa Martins; de Castro e Silva, Juliana; Simon, Karina Smidt; Bocca, Anamelia Lorenzetti; Silva, Luciano Paulino; Mortari, Marcia Renata; Kipnis, Andre; Junqueira-Kipnis, Ana Paula

    2016-01-01

    Mycobacterium abscessus subsp. massiliense, a rapidly growing mycobacteria (RGM) that is becoming increasingly important among human infectious diseases, is virulent and pathogenic and presents intrinsic resistance to several antimicrobial drugs that might hamper their elimination. Therefore, the identification of new drugs to improve the current treatment or lower the risk of inducing resistance is urgently needed. Wasp venom primarily comprises peptides that are responsible for most of the biological activities in this poison. Here, a novel peptide Polydim-I, from Polybia dimorpha Neotropical wasp, was explored as an antimycobacterial agent. Polydim-I provoked cell wall disruption and exhibited non-cytotoxicity towards mammalian cells. Polydim-I treatment of macrophages infected with different M. abscessus subsp. massiliense strains reduced 40 to 50% of the bacterial load. Additionally, the Polydim-I treatment of highly susceptible mice intravenously infected with M. abscessus subsp. massiliense induced 0.8 to 1 log reduction of the bacterial load in the lungs, spleen, and liver. In conclusion, this is the first study to show the therapeutic potential of a peptide derived from wasp venom in treating mycobacteria infections. Polydim-I acts on the M. abscessus subsp. massiliense cell wall and reduce 40–90% of the bacterial load both in vitro and in vivo. The presented results encourage further studies on the use of Polydim-I as one of the components for M. abscessus subsp. massiliense treatment. PMID:26930596

  18. Comparative antimycobacterial activities of the newly synthesized quinolone AM-1155, sparfloxacin, and ofloxacin.

    PubMed Central

    Tomioka, H; Saito, H; Sato, K

    1993-01-01

    AM-1155 is a newly synthesized 6-fluoro-8-methoxy quinolone. We assessed its in vitro antimycobacterial activity using sparfloxacin (SPFX) and ofloxacin (OFLX) as comparison drugs. The MICs of these agents for various mycobacterial strains were determined by the agar dilution method with 7H11 medium. AM-1155 had lower MICs for 50 and 90% of tested strains of Mycobacterium kansasii, M. marinum, and M. fortuitum-M. chelonae complex than SPFX and OFLX, and the values for M. tuberculosis, M. scrofulaceum, and the M. avium-M. intracellulare complex were similar to those of SPFX and considerably lower than those of OFLX. In addition, the antimicrobial activity of AM-1155 against M. tuberculosis and M. intracellulare phagocytosed into murine peritoneal macrophages was compared with that of OFLX. AM-1155 (1 microgram/ml) inhibited the intracellular growth of both M. tuberculosis and M. intracellulare, whereas OFLX at the same concentration failed to show any such effect. Moreover, AM-1155 (10 micrograms/ml) exhibited a steady bactericidal action against M. tuberculosis, whereas OFLX at the same concentration had only a weak effect. AM-1155 (10 micrograms/ml) also inhibited the growth of M. intracellulare more effectively than OFLX. PMID:8392307

  19. Air Pollution Particulate Matter Alters Antimycobacterial Respiratory Epithelium Innate Immunity

    PubMed Central

    Rivas-Santiago, César E.; Sarkar, Srijata; Cantarella, Pasquale; Osornio-Vargas, Álvaro; Quintana-Belmares, Raúl; Meng, Qingyu; Kirn, Thomas J.; Ohman Strickland, Pamela; Chow, Judith C.; Watson, John G.; Torres, Martha

    2015-01-01

    Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 μm (PM2.5) and 10 μm (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human β-defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB. PMID:25847963

  20. Air pollution particulate matter alters antimycobacterial respiratory epithelium innate immunity.

    PubMed

    Rivas-Santiago, César E; Sarkar, Srijata; Cantarella, Pasquale; Osornio-Vargas, Álvaro; Quintana-Belmares, Raúl; Meng, Qingyu; Kirn, Thomas J; Ohman Strickland, Pamela; Chow, Judith C; Watson, John G; Torres, Martha; Schwander, Stephan

    2015-06-01

    Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 μm (PM2.5) and 10 μm (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human β-defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB. PMID:25847963

  1. Susceptibility of Mycobacterium abscessus to antimycobacterial drugs in preclinical models.

    PubMed

    Obregón-Henao, Andrés; Arnett, Kimberly A; Henao-Tamayo, Marcela; Massoudi, Lisa; Creissen, Elizabeth; Andries, Koen; Lenaerts, Anne J; Ordway, Diane J

    2015-11-01

    Over the last 10 years, Mycobacterium abscessus group strains have emerged as important human pathogens, which are associated with significantly higher fatality rates than any other rapidly growing mycobacteria. These opportunistic pathogens are widespread in the environment and can cause a wide range of clinical diseases, including skin, soft tissue, central nervous system, and disseminated infections; by far, the most difficult to treat is the pulmonary form. Infections with M. abscessus are often multidrug-resistant (MDR) and require prolonged treatment with various regimens and, many times, result in high mortality despite maximal therapy. We report here the evaluation of diverse mouse infection models for their ability to produce a progressive high level of infection with M. abscessus. The nude (nu/nu), SCID (severe combined immunodeficiency), gamma interferon knockout (GKO), and granulocyte-macrophage colony-stimulating factor (GMCSF) knockout mice fulfilled the criteria for an optimal model for compound screening. Thus, we set out to assess the antimycobacterial activity of clarithromycin, clofazimine, bedaquiline, and clofazimine-bedaquiline combinations against M. abscessus-infected GKO and SCID murine infection models. Treatment of GKO and SCID mice with a combination of clofazimine and bedaquiline was the most effective in decreasing the M. abscessus organ burden. PMID:26303795

  2. Susceptibility of Mycobacterium abscessus to Antimycobacterial Drugs in Preclinical Models

    PubMed Central

    Obregón-Henao, Andrés; Arnett, Kimberly A.; Henao-Tamayo, Marcela; Massoudi, Lisa; Creissen, Elizabeth; Andries, Koen; Lenaerts, Anne J.

    2015-01-01

    Over the last 10 years, Mycobacterium abscessus group strains have emerged as important human pathogens, which are associated with significantly higher fatality rates than any other rapidly growing mycobacteria. These opportunistic pathogens are widespread in the environment and can cause a wide range of clinical diseases, including skin, soft tissue, central nervous system, and disseminated infections; by far, the most difficult to treat is the pulmonary form. Infections with M. abscessus are often multidrug-resistant (MDR) and require prolonged treatment with various regimens and, many times, result in high mortality despite maximal therapy. We report here the evaluation of diverse mouse infection models for their ability to produce a progressive high level of infection with M. abscessus. The nude (nu/nu), SCID (severe combined immunodeficiency), gamma interferon knockout (GKO), and granulocyte-macrophage colony-stimulating factor (GMCSF) knockout mice fulfilled the criteria for an optimal model for compound screening. Thus, we set out to assess the antimycobacterial activity of clarithromycin, clofazimine, bedaquiline, and clofazimine-bedaquiline combinations against M. abscessus-infected GKO and SCID murine infection models. Treatment of GKO and SCID mice with a combination of clofazimine and bedaquiline was the most effective in decreasing the M. abscessus organ burden. PMID:26303795

  3. N-substituted 2-isonicotinoylhydrazinecarboxamides--new antimycobacterial active molecules.

    PubMed

    Rychtarčíková, Zuzana; Krátký, Martin; Gazvoda, Martin; Komlóová, Markéta; Polanc, Slovenko; Kočevar, Marijan; Stolaříková, Jiřina; Vinšová, Jarmila

    2014-01-01

    This report presents a new modification of the isoniazid (INH) structure linked with different anilines via a carbonyl group obtained by two synthetic procedures and with N-substituted 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-amines prepared by their cyclisation. All synthesised derivatives were characterised by IR, NMR, MS and elemental analyses and were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium 330/88, Mycobacterium kansasii 235/80 and one clinical isolated strain of M. kansasii 6509/96. 2-Isonicotinoyl-N-(4-octylphenyl)hydrazinecarboxamide displayed an in vitro efficacy comparable to that of INH for M. tuberculosis with minimum inhibitory concentrations (MICs) of 1-2 μM. Among the halogenated derivatives, the best anti-tuberculosis activity was found for 2-isonicotinoyl-N-(2,4,6-trichlorophenyl)hydrazinecarboxamide (MIC=4 μM). In silico modelling on the enoyl-acyl carrier protein reductase InhA confirmed that longer alkyl substituents are advantageous for the interactions and affinity to InhA. Most of the hydrazinecarboxamides, especially those derived from 4-alkylanilines, exhibited significant activity against INH-resistant nontuberculous mycobacteria. PMID:24686575

  4. Antimycobacterial action of a new glycolipid-peptide complex obtained from extracellular metabolites of Raoultella ornithinolytica.

    PubMed

    Fiołka, Marta J; Grzywnowicz, Krzysztof; Mendyk, Ewaryst; Zagaja, Mirosław; Szewczyk, Rafał; Rawski, Michał; Keller, Radosław; Rzymowska, Jolanta; Wydrych, Jerzy

    2015-12-01

    In this paper, an antimycobacterial component of extracellular metabolites of a gut bacterium Raoultella ornithinolytica from D. veneta earthworms was isolated and its antimycobacterial action was tested using Mycobacterium smegmatis. After incubation with the complex obtained, formation of pores and furrows in cell walls was observed using microscopic techniques. The cells lost their shape, stuck together and formed clusters. Surface-enhanced Raman spectroscopy analysis showed that, after incubation, the complex was attached to the cell walls of the Mycobacterium. Analyses of the component performed with Fourier transform infrared spectroscopy demonstrated high similarity to a bacteriocin nisin, but energy dispersive X-ray spectroscopy analysis revealed differences in the elemental composition of this antimicrobial peptide. The component with antimycobacterial activity was identified using mass spectrometry techniques as a glycolipid-peptide complex. As it exhibits no cytotoxicity on normal human fibroblasts, the glycolipid-peptide complex appears to be a promising compound for investigations of its activity against pathogenic mycobacteria. PMID:26547373

  5. Synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives.

    PubMed

    Al Matarneh, Cristina M; Mangalagiu, Ionel I; Shova, Sergiu; Danac, Ramona

    2016-06-01

    A study concerning design, synthesis, structure and in vitro antimycobacterial and anticancer evaluation of new fused derivatives with pyrrolo[2,1-c][4,7]phenanthroline skeleton is described. The strategy adopted for synthesis involves a [3 + 2] dipolar cycloaddition of several in situ generated 4,7-phenanthrolin-4-ium ylides to different substituted alkynes and alkenes. Stereo- and regiochemistry of cycloaddition reactions were discussed. The structure of the new compounds was proven unambiguously, single-crystal X-ray diffraction studies including. The antimycobacterial and anticancer activity of a selection of new synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv under aerobic conditions and 60 human tumour cell line panel, respectively. Five of the tested compounds possess a moderate antimycobacterial activity, while two of the compounds have a significant antitumor activity against renal cancer and breast cancer. PMID:25945747

  6. Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline-7-Acetic Acid Derivatives With Amino Acid Moieties.

    PubMed

    Stavrakov, Georgi; Valcheva, Violeta; Voynikov, Yulian; Philipova, Irena; Atanasova, Mariyana; Konstantinov, Spiro; Peikov, Plamen; Doytchinova, Irini

    2016-03-01

    The theophylline-7-acetic acid (7-TAA) scaffold is a promising novel lead compound for antimycobacterial activity. Here, we derive a model for antitubercular activity prediction based on 14 7-TAA derivatives with amino acid moieties and their methyl esters. The model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester derivatives of 7-TAA. The best three predicted compounds are synthesized and tested against Mycobacterium tuberculosis H37Rv. All of them are stable, non-toxic against human cells and show antimycobacterial activity in the nanomolar range being 60 times more active than ethambutol. PMID:26502828

  7. Novel Human In Vitro System for Evaluating Antimycobacterial Vaccines

    PubMed Central

    Kampmann, Beate; Tena, Gwen N.; Mzazi, Shumikazi; Eley, Brian; Young, Douglas B.; Levin, Michael

    2004-01-01

    Major research efforts are directed towards the development of a better antimycobacterial vaccine. But progress in the field of tuberculosis vaccine development has been hampered by the lack of human in vitro models to assess vaccine immunogenicity and efficacy. New candidate vaccines will have to be evaluated against the existing Mycobacterium bovis BCG “gold standard.” It is therefore important to understand the type of immune responses elicited by BCG vaccination to enable comparisons with potential new candidates. We used a novel human in vitro whole-blood model, which measures immune responses to mycobacteria by use of reporter gene-tagged BCG (BCG lux), to study immune responses to BCG vaccination in 50 neonates in a setting in Cape Town, Republic of South Africa, where tuberculosis is endemic. BCG vaccination significantly reduced growth of BCG lux in whole blood (prevaccination median growth ratio [GR], 9.6; range, 1.3 to 24; postvaccination median GR, 3.9; range, 0.6 to 12.2 [P < 0.0001]). Growth of BCG lux was better restricted in vaccinated infants than in unvaccinated age-matched controls (n = 4). BCG vaccination induced significantly higher gamma interferon production in response to BCG lux (P < 0.0001) and to purified protein derivative (P = 0.0001). No significant changes in either growth of BCG lux or cytokine production occurred in an adult control group (n = 6) over the study period. The whole-blood luminescence model detects changes in cellular immune responses to mycobacteria induced by BCG vaccination. It is therefore a useful new tool in studying the immunogenicity of newly developed vaccine candidates prior to large field trials assessing efficacy. PMID:15501770

  8. Antimycobacterial and Nitric Oxide Production Inhibitory Activities of Ocotea notata from Brazilian Restinga

    PubMed Central

    Costa, Isabela Francisca Borges; Calixto, Sanderson Dias; Heggdorne de Araujo, Marlon; Konno, Tatiana Ungaretti Paleo; Tinoco, Luzineide Wanderley; Guimarães, Denise Oliveira; Lasunskaia, Elena B.; Leal, Ivana Ramos Correa; Muzitano, Michelle Frazão

    2015-01-01

    The genus Ocotea (Lauraceae) is distributed mainly in tropical and subtropical regions. Some species of this genus as O. puberula and O. quixos have been described in the literature, showing antibacterial activity. And Ocotea macrophylla showed anti-inflammatory activity with inhibition of COX-1, COX-2, and LOX-5. The purpose of this study was the phytochemical investigation of the plant species Ocotea notata from Restinga Jurubatiba National Park, Macaé, RJ, Brazil, and the search for antimycobacterial fractions and compounds. The crude extract was evaluated for antimycobacterial activity and presented 95.75 ± 2.53% of growth inhibition at 100 µg/mL. Then, it was subjected to a liquid-liquid partition and subsequently was chemically investigated by HPLC, revealing the major presence of flavonoids. In this process the partition fractions hexane, ethyl acetate, and butanol are shown to be promising in the antimycobacterial assay. In addition, ethyl acetate fraction was chromatographed and afforded two flavonoids identified by MS and NMR as afzelin and isoquercitrin. The isolated flavonoids afzelin and isoquercitrin were evaluated for their antimycobacterial activity and for their ability to inhibit NO production by macrophages stimulated by LPS; both flavonoids isoquercitrin (Acet22) and afzelin (Acet32) were able to inhibit the production of NO by macrophages. The calculated IC50 of Acet22 and Acet32 was 1.03 and 0.85 µg/mL, respectively. PMID:25789338

  9. Antimycobacterial and nitric oxide production inhibitory activities of Ocotea notata from Brazilian restinga.

    PubMed

    Costa, Isabela Francisca Borges; Calixto, Sanderson Dias; Heggdorne de Araujo, Marlon; Konno, Tatiana Ungaretti Paleo; Tinoco, Luzineide Wanderley; Guimarães, Denise Oliveira; Lasunskaia, Elena B; Leal, Ivana Ramos Correa; Muzitano, Michelle Frazão

    2015-01-01

    The genus Ocotea (Lauraceae) is distributed mainly in tropical and subtropical regions. Some species of this genus as O. puberula and O. quixos have been described in the literature, showing antibacterial activity. And Ocotea macrophylla showed anti-inflammatory activity with inhibition of COX-1, COX-2, and LOX-5. The purpose of this study was the phytochemical investigation of the plant species Ocotea notata from Restinga Jurubatiba National Park, Macaé, RJ, Brazil, and the search for antimycobacterial fractions and compounds. The crude extract was evaluated for antimycobacterial activity and presented 95.75 ± 2.53% of growth inhibition at 100 µg/mL. Then, it was subjected to a liquid-liquid partition and subsequently was chemically investigated by HPLC, revealing the major presence of flavonoids. In this process the partition fractions hexane, ethyl acetate, and butanol are shown to be promising in the antimycobacterial assay. In addition, ethyl acetate fraction was chromatographed and afforded two flavonoids identified by MS and NMR as afzelin and isoquercitrin. The isolated flavonoids afzelin and isoquercitrin were evaluated for their antimycobacterial activity and for their ability to inhibit NO production by macrophages stimulated by LPS; both flavonoids isoquercitrin (Acet22) and afzelin (Acet32) were able to inhibit the production of NO by macrophages. The calculated IC50 of Acet22 and Acet32 was 1.03 and 0.85 µg/mL, respectively. PMID:25789338

  10. Tuberculosis and nature's pharmacy of putative anti-tuberculosis agents.

    PubMed

    Chinsembu, Kazhila C

    2016-01-01

    Due to the growing problem of drug resistant Mycobacterium tuberculosis strains, coupled with the twinning of tuberculosis (TB) to human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), the burden of TB is now difficult to manage. Therefore, new antimycobacterial agents are being sought from natural sources. This review focuses on natural antimycobacterial agents from endophytes and medicinal plants of Africa, Europe, Asia, South America and Canada. In the countries mentioned in this review, numerous plant species display putative anti-TB activity. Several antimycobacterial chemical compounds have also been isolated, including: ellagitannin punicalagin, allicin, anthraquinone glycosides, iridoids, phenylpropanoids, beta-sitosterol, galanthimine, crinine, friedelin, gallic acid, ellagic acids, anthocyanidin, taraxerol, termilignan B, arjunic acid, glucopyranosides, 1-epicatechol, leucopelargonidol, hydroxybenzoic acids, benzophenanthridine alkaloids, neolignans, and decarine. These compounds may provide leads to novel and more efficacious drugs to lessen the global burden of TB and drug-resistant M. tuberculosis strains. If there is a long-term remedy for TB, it must lie in nature's pharmacy of putative antimycobacterial agents. PMID:26464047

  11. Novel nicotine analogues with potential anti-mycobacterial activity.

    PubMed

    Gandhi, Paresh T; Athmaram, Thimmasandra Narayanappa; Arunkumar, Gundaiah Ramesh

    2016-04-15

    Tuberculosis (TB) is the second leading lethal infectious disease in the world after acquired immuno deficiency (AIDs). We have developed a series of twenty-five novel nicotine analogues with de-addiction property and tested them for their activity against Mycobacterium tuberculosis (MTB). In an effort to increase the specificity of action and directing nicotine analogues to target MTB, four promising compounds were further optimized via molecular docking studies against the Dihydrofolate reductase of MTB. After lead optimization, one nicotine analogue [3-(5-(3fluorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one] exhibited minimum inhibitory concentration of 1μg/mL (2.86nM) against M. tuberculosis (H37Rv strain), a human pathogenic strain of clinically significant importance. Pharmacokinetic analysis of [3-(5-(3fluorophenyl)nicotinoyl)-1methylpyrrolidin-2-one] with lowest MIC value via oral route in Wistar rats revealed that at a dosage of 5mg/kg body weight gave a maximum serum drug concentration (Cmax) of 2.86μg/mL, Tmax of one hour and a half-life (T1/2) of more than 24h and Volume of distribution (Vd) of 27.36L. Whereas the parenteral (intra venous) route showed a Cmax of 3.37μg/mL, Tmax of 0.05h, T1/2 of 24h and Vd equivalent to 23.18L. The acute oral toxicity and repeated oral toxicity studies in female Wistar rats had an LD50>2000mg/kg body weight. Our data suggests that nicotine derivatives developed in the present study has good metabolic stability with tunable pharmacokinetics (PK) with therapeutic potential to combat MTB. However, further in vivo studies for anti-tuberculosis activity and elucidation of mode of action could result in more promising novel drug for treating MTB. To the best of our knowledge this is the first report revealing the anti-mycobacterial potential of nicotine analogue at potential therapeutic concentrations. PMID:26951892

  12. Isolation of (-)-avenaciolide as the antifungal and antimycobacterial constituent of a Seimatosporium sp. Endophyte from the medicinal plant Hypericum perforatum .

    PubMed

    Clark, Trevor N; Bishop, Amanda I; McLaughlin, Mark; Calhoun, Larry A; Johnson, John A; Gray, Christopher A

    2014-10-01

    An extract of Seimatosporium sp., an endophyte from the Canadian medicinal plant Hypericum perforatum, exhibited significant antifungal and antimycobacterial activity against Candida albicans and Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation led to the isolation of (-)-avenaciolide as the only bioactive constituent of the extract. This is the first report of both the antimycobacterial activity of avenaciolide and its isolation from a Seimatosporium sp. fungus. PMID:25522544

  13. In vitro anti-mycobacterial activity of nine medicinal plants used by ethnic groups in Sonora, Mexico

    PubMed Central

    2013-01-01

    Background Sonoran ethnic groups (Yaquis, Mayos, Seris, Guarijíos, Pimas, Kikapúes and Pápagos) use mainly herbal based preparations as their first line of medicinal treatment. Among the plants used are those with anti-tuberculosis properties; however, no formal research is available. Methods Organic extracts were obtained from nine medicinal plants traditionally used by Sonoran ethnic groups to treat different kinds of diseases; three of them are mainly used to treat tuberculosis. All of the extracts were tested against Mycobacterium tuberculosis H37Rv using the Alamar Blue redox bioassay. Results Methanolic extracts from Ambrosia confertiflora, Ambrosia ambrosioides and Guaiacum coulteri showed minimal inhibitory concentration (MIC) values of 200, 790 and 1000 μg/mL, respectively, whereas no effect was observed with the rest of the methanolic extracts at the concentrations tested. Chloroform, dichloromethane, and ethyl acetate extracts from Ambrosia confertiflora showed a MIC of 90, 120 and 160 μg/mL, respectively. Conclusions A. confertiflora and A. ambrosioides showed the best anti-mycobacterial activity in vitro. The activity of Guaiacum coulteri is consistent with the traditional use by Sonoran ethnic groups as anti-tuberculosis agent. For these reasons, it is important to investigate a broader spectrum of medicinal plants in order to find compounds active against Mycobacterium tuberculosis. PMID:24267469

  14. Dibenz[b,f]oxepin and Antimycobacterial Chalcone Constituents of Empetrum nigrum.

    PubMed

    Li, Haoxin; Jean, Stéphanie; Webster, Duncan; Robichaud, Gilles A; Calhoun, Larry A; Johnson, John A; Gray, Christopher A

    2015-11-25

    Two new dibenz[b,f]oxepins, empetroxepins A and B (1 and 2), and seven known compounds (3-9) were isolated from an extract of the Canadian medicinal plant Empetrum nigrum that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structures of 1 and 2 were established through analysis of NMR and MS data. The antimycobacterial activity of the plant extract was attributed primarily to the presence of two chalcone derivatives (6 and 7) that exhibited selective antimycobacterial activity (IC50 values of 23.8 and 32.8 μM, respectively) in comparison to mammalian (HEK 293) cells (IC50 values of 109 and 249 μM, respectively). PMID:26473275

  15. Carboxylate Surrogates Enhance the Antimycobacterial Activity of UDP-Galactopyranose Mutase Probes.

    PubMed

    Winton, Valerie J; Aldrich, Claudia; Kiessling, Laura L

    2016-08-12

    Uridine diphosphate galactopyranose mutase (UGM also known as Glf) is a biosynthetic enzyme required for construction of the galactan, an essential mycobacterial cell envelope polysaccharide. Our group previously identified two distinct classes of UGM inhibitors; each possesses a carboxylate moiety that is crucial for potency yet likely detrimental for cell permeability. To enhance the antimycobacterial potency, we sought to replace the carboxylate with a functional group mimic-an N-acylsulfonamide group. We therefore synthesized a series of N-acylsulfonamide analogs and tested their ability to inhibit UGM. For each inhibitor scaffold tested, the N-acylsulfonamide group functions as an effective carboxylate surrogate. Although the carboxylates and their surrogates show similar activity against UGM in a test tube, several N-acylsulfonamide derivatives more effectively block the growth of Mycobacterium smegmatis. These data suggest that the replacement of a carboxylate with an N-acylsulfonamide group could serve as a general strategy to augment antimycobacterial activity. PMID:27626294

  16. Antimycobacterial activity of chemically defined natural substances from the Caribbean flora in Guadeloupe.

    PubMed

    Rastogi, N; Abaul, J; Goh, K S; Devallois, A; Philogène, E; Bourgeois, P

    1998-04-01

    Eight chemically defined, naturally occurring compounds were extracted from the tropical flora of the Caribbean island of Guadeloupe: pilocarpine, an alkaloid from Pilocarpus racemosus; heraclenol and isomeranzin, coumarins from Triphasia trifolia; lochnerin, an indole alkaloid from Rauwolfia biauriculata; ibogaine and voacangine, indole alkaloids from Tabernaemontana citrifolia; texalin, an oxazole from Amyris elemifera; and canellal, a sesquiterpene dialdehyde from Canella winterana. An essential oil fraction from Canella winterana was also tested. The antimycobacterial activity of these substances was tested against Mycobacterium tuberculosis, M. avium and M. kansasii using the Middlebrook 7H11 agar medium, the Bactec 460-TB radiometric methodology, and determination of bacterial viable counts. Three compounds, namely ibogaine, voacangine and texalin, showed antimycobacterial activity. Investigations on the structure-modification and structure-activity relationships of these compounds may help determine new targets for future drug development. PMID:9626931

  17. Synthesis and antimycobacterial activity of novel thiadiazolylhydrazones of 1-substituted indole-3-carboxaldehydes.

    PubMed

    Tehrani, Kamaleddin Haj Mohammad Ebrahim; Mashayekhi, Vida; Azerang, Parisa; Sardari, Soroush; Kobarfard, Farzad; Rostamizadeh, Kobra

    2014-02-01

    A series of novel thiocarbohydrazones of substituted indoles and their corresponding thiadiazole derivatives were prepared, and their structures were confirmed by different analytical and spectroscopic methods. The derivatives were prepared by a sequential synthetic strategy including substitution at N-1 position of indole ring by various aliphatic and benzylic substituents, followed by condensation with thiocarbohydrazide, and finally cyclization by triethyl orthoformate. The derivatives were tested for their antimycobacterial activity against Mycobacterium bovis BCG, and the results revealed that among the synthesized compounds, thiadiazole derivatives 4e, 4f, 4n, 4p, 4q, and 4t exhibited the highest activity with IC₅₀ value of 3.91 μg/mL. The results indicate that the thiadiazole moiety plays a vital role in exerting antimycobacterial activity. PMID:24103309

  18. Bioactive compounds from Bauhinia purpurea possessing antimalarial, antimycobacterial, antifungal, anti-inflammatory, and cytotoxic activities.

    PubMed

    Boonphong, Surat; Puangsombat, Pakawan; Baramee, Apiwat; Mahidol, Chulabhorn; Ruchirawat, Somsak; Kittakoop, Prasat

    2007-05-01

    Eleven new secondary metabolites (1-11), together with two known flavanones (12 and 13) and five known bibenzyls (14-18), were isolated from the root extract of Bauhinia purpurea. New compounds include eight dihydrodibenzoxepins (1-8), a dihydrobenzofuran (9), a novel spirochromane-2,1'-hexenedione (10), and a new bibenzyl (11). Antimycobacterial, antimalarial, antifungal, cytotoxic, and anti-inflammatory activities of the isolated compounds are reported, and biosynthetic pathways of these compounds are also discussed. PMID:17480099

  19. Synthesis and biological evaluation of propargyl acetate derivatives as anti-mycobacterial agents

    PubMed Central

    2012-01-01

    Background The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant to conventional drug therapies, is of particular interest. Methods This study is focused on propargyl acetate derivatives. Eight molecules were designed based on propargyl alcohols and different acid anhydrides. Results All the synthesized compounds and commercially available ones were evaluated for anti-tuberculosis activity. Conclusions Inhibitors against Mtb have been identified and characterized for further development into potential novel anti-tubercular drugs. PMID:23351675

  20. Isolation of Phomopsolide A and 6(E)-Phomopsolide A as Antimycobacterial Natural Products from an Unidentified Endophyte of the Canadian Medicinal Plant Heracleum maximum.

    PubMed

    Clark, Trevor N; Ellsworth, Katelyn T; Jean, Stephanie; Webster, Duncan; Webste, Duncan; Robichaud, Gilles A; Johnson, John A; Gray, Christopher A

    2015-10-01

    An extract of an unidentified endophyte from the Canadian medicinal plant Heracleum maximum exhibited a unique metabolomic profile and significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation of the extract led to the isolation of phomopsolide A (1) and 6(E)-phomopsolide A (2). This is the first report of antimycobacterial activity for 1 and 2. PMID:26669094

  1. Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levofloxacin, moxifloxacin, and four conventional antimycobacterial drugs against Mycobacterium kansasii.

    PubMed

    Alcaide, Fernando; Calatayud, Laura; Santín, Miguel; Martín, Rogelio

    2004-12-01

    Mycobacterium kansasii is one of the most pathogenic and frequent nontuberculous mycobacteria isolated from humans. Patients with adverse drug reactions, resistant isolates, or suboptimal response require alternative treatment regimens. One hundred forty-eight consecutive clinical isolates of M. kansasii were tested for antimicrobial susceptibilities by the BACTEC 460 system (NCCLS) with two different inoculation protocols, one conventional and one alternative. In the alternative protocol, the inoculum 12B vial was incubated until the growth index was between 250 and 500. Four conventional antimycobacterial drugs (isoniazid, rifampin, streptomycin, and ethambutol) were studied with standard critical concentrations. The in vitro activities of linezolid, telithromycin, clarithromycin, levofloxacin, and moxifloxacin were determined by measuring radiometric MICs. All isolates tested were identified as M. kansasii genotype I and were resistant to isoniazid at a concentration of 0.4 mug/ml. One hundred twenty isolates (81.1%) were inhibited by 1 microg of isoniazid per ml. A high level of resistance to isoniazid (>10 microg/ml) was observed in six isolates (4.1%). Only five strains (3.4%) were resistant to rifampin (>1 microg/ml). All isolates studied were susceptible to streptomycin and ethambutol. The MICs at which 90% of the isolates were inhibited (in micrograms per milliliter) were as follows: linezolid, 1 (range, < or =0.25 to 2); telithromycin, >16 (range, 4 to >16); clarithromycin, 0.5 (range, < or =0.03 to 1); levofloxacin, 0.12 (range, 0.12 to 0.25); and moxifloxacin, 0.06 (range, < or =0.06 to 0.12). The susceptibility testing results with both inoculation protocols showed perfect correlation. In conclusion, all M. kansasii isolates showed decreased susceptibility to isoniazid, but resistance to rifampin was infrequent. Quinolones, especially moxifloxacin, were the most active antimicrobial agents tested, followed by clarithromycin. Linezolid also showed good

  2. Suppression of the NF-κB Pathway by Diesel Exhaust Particles Impairs Human Antimycobacterial Immunity

    PubMed Central

    Sarkar, Srijata; Song, Youngmia; Sarkar, Somak; Kipen, Howard M.; Laumbach, Robert J.; Zhang, Junfeng (Jim); Strickland, Pamela A. Ohman; Gardner, Carol R.; Schwander, Stephan

    2012-01-01

    Epidemiological studies suggest that chronic exposure to air pollution increases susceptibility to respiratory infections including tuberculosis in humans. A possible link between particulate air pollutant exposure and antimycobacterial immunity has not been explored in human primary immune cells. We hypothesized that exposure to diesel exhaust particles (DEP), a major component of urban fine particulate matter, suppresses antimycobacterial human immune effector cell functions by modulating TLR-signaling pathways and NF-κB activation. We show that DEP and H37Ra, an avirulent laboratory strain of M.tb, were both taken up by the same peripheral human blood monocytes. To examine the effects of DEP on M.tb-induced production of cytokines, PBMC were stimulated with DEP and M.tb or PPD (purified protein derivative). The production of M.tb and PPD-induced IFN-γ, TNF-α, IL-1β, and IL-6 was reduced in a DEP dose-dependent manner. In contrast, the production of anti-inflammatory IL-10 remained unchanged. Furthermore, DEP stimulation prior to M.tb infection altered the expression of TLR 3, 4, 5, 7 and 10 mRNAs and of a subset of M.tb-induced host genes including inhibition of expression of many NF-κB (e.g. CSF3, IFNG, IFNA, IFNB, IL1A, IL6, NFKBIA) and IRF (e.g. IFNG, IFNA1, IFNB1, CXCL10) pathway target genes. We propose that DEP down-regulate M.tb-induced host gene expression via MyD88-dependent (IL6, IL1A, PTGS2) as well as MyD88-independent (IFNA, IFNB) pathways. Pre-stimulation of PBMC with DEP suppressed the expression of proinflammatory mediators upon M.tb infection inducing a hypo-responsive cellular state. Therefore, DEP alters crucial components of antimycobacterial host immune responses, providing a possible mechanism by which air pollutants alter antimicrobial immunity. PMID:22345648

  3. Activity of matrix metalloproteinases during antimycobacterial therapy in mice with simulated tuberculous inflammation.

    PubMed

    Sumenkova, D V; Russkikh, G S; Poteryaeva, O N; Polyakov, L M; Panin, L E

    2013-05-01

    Matrix metalloproteinases are shown to be involved in the pathogenesis of tuberculosis inflammation. In the early stages of BCG-granuloma formation in mouse liver and lungs, the serum levels of matrix metalloproteinases 2 and 7 increased by 4.5 times and remained unchanged while the pathology developed. Antimycobacterial therapy with isoniazid reduced enzyme activity almost to the level of intact control. The decrease in activity of matrix metalloproteinases 2 and 7 that play the most prominent role in the development of destructive forms of tuberculosis is of great therapeutic importance. PMID:23667866

  4. Fullerene isoniazid conjugate--a tuberculostat with increased lipophilicity: synthesis and evaluation of antimycobacterial activity.

    PubMed

    Kumar, Anish; Patel, Gaurang; Menon, Shobhana Karuveettil

    2009-05-01

    A fullerene-isoniazid conjugate has been synthesized by 1, 3 dipolar cycloaddition reaction of fullerene (C(60)) with isonicotinic acid (4-formyl-benzylidene) hydrazide and N-methylglycine. The identity and purity of the compound was confirmed by elemental analysis, (1)H NMR, (13)C NMR and MALDI-TOF mass spectral analysis. Stable water suspension, in which the particles of the synthesized conjugate were made to aggregate in nanosize, was successfully tested for antimycobacterial activity against Mycobacterium avium and strains of Mycobacterium tuberculosis- H(37)Rv & H6/99 at concentration as low as 0.50 microg/mL. PMID:19366360

  5. Synthesis and antimycobacterial evaluation of new trans-cinnamic acid hydrazide derivatives.

    PubMed

    Carvalho, Samir A; da Silva, Edson F; de Souza, Marcus V N; Lourenço, Maria C S; Vicente, Felipe R

    2008-01-15

    In this work, we report the synthesis and the antimycobacterial evaluation of new trans-cinnamic acid derivatives of isonicotinic acid series (5) and benzoic acid series (6), designed by exploring the molecular hybridization approach between isoniazid (1) and trans-cinnamic acid derivative (3). The minimum inhibitory concentration (MIC) of the compounds 5a-d and 6c exhibited activity between 3.12 and 12.5 microg/mL and could be a good start point to find new lead compounds against multi-drug resistant tuberculosis. PMID:18068364

  6. Synthesis and Antimycobacterial Activity of 2,1′-Dihydropyridomycins

    PubMed Central

    2012-01-01

    Dihydropyridomycins 2 and 3, which lack the characteristic enol ester moiety of the potent antimycobacterial natural product pyridomycin (1), have been prepared from l-Thr, R- and S-hydroxy isovaleric acid, and 3-pyridinecarboxaldehyde. The 2R isomer 2 shows only 4-fold lower anti-Mtb activity than 1, indicating that the enol ester moiety in the natural product is not critical for its biological activity. This finding establishes 2 as a potent and more practical lead for anti-TB drug discovery. PMID:24900646

  7. Antimicrobial, antimycobacterial and antibiofilm properties of Couroupita guianensis Aubl. fruit extract

    PubMed Central

    2012-01-01

    Background Couroupita guianensis Aubl. (Lecythidaceae) is commonly called Ayahuma and the Cannonball tree. It is distributed in the tropical regions of northern South America and Southern Caribbean. It has several medicinal properties. It is used to treat hypertension, tumours, pain, inflammatory processes, cold, stomach ache, skin diseases, malaria, wounds and toothache. Methods The fruits of Couroupita guianensis were extracted with chloroform. Antimicrobial, antimycobacterial and antibiofilm forming activities of the chloroform extract were investigated. Quantitative estimation of Indirubin, one of the major constituent, was identified by HPLC. Results Chloroform extract showed good antimicrobial and antibiofilm forming activities; however it showed low antimycobacterial activity. The zones of inhibition by chloroform extract ranged from 0 to 26 mm. Chloroform extract showed effective antibiofilm activity against Pseudomonas aeruginosa starting from 2 mg/mL BIC, with 52% inhibition of biofilm formation. When the chloroform extract was subjected to HPLC-DAD analysis, along with Indirubin standard, in the same chromatographic conditions, it was found that Indirubin was one of the major compounds in this plant (0.0918% dry weight basis). Conclusions The chloroform extract showed good antimicrobial and antibiofilm properties. Chloroform extract can be evaluated further in drug development programmes. PMID:23206492

  8. Investigation of local anesthetic and antimycobacterial activity of Ottonia martiana Miq. (Piperaceae).

    PubMed

    Cunico, Miriam M; Trebien, Herbert A; Galetti, Fábio C; Miguel, Obdulio G; Miguel, Marilis D; Auer, Celso G; Silva, Célio L; de Souza, Ana Olívia

    2015-01-01

    Ottonia martiana is a plant popularly known in Brazil by the use for toothache. Ethanolic extract (EE), hexane fraction (HF), dichloromethane fraction (DF) and piperovatine obtained from O. martiana were assayed in vitro and in vivo. The acute toxicity of EE was determined, and LD50 values of 164.5 and 65.0 mg/kg by the oral and intraperitoneal routes, respectively, indicated a high toxicity for EE in vivo, explaining its popular use by topical administration only. A local anesthetic-like effect of EE and its fractions was observed in experimental models using pain induction, and such effect involved an analgesic action. The antimycobacterial activity of EE, HF, DF and piperovatine was evaluated against Mycobacterium tuberculosis H37Rv ATCC 27924. EE, HF, DF, and piperovatine showed a potential antimycobacterial effect with MICs of 16.0, 62.0, 62.0 and 8.0 μg/mL, respectively. Piperovatine was more effective than the EE or the other fractions. The selectivity index (SI=IC50/MIC) values calculated for EE, HF, DF and piperovatine based on the MICs and the cytotoxicity against J774 macrophages (IC50 by MTT assay) revealed values of 6.43, 2.34, 1.5 and 9.66, respectively. PMID:26628019

  9. Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy.

    PubMed

    Li, Shengke; Chan, Judy Yuet-Wa; Li, Yan; Bardelang, David; Zheng, Jun; Yew, Wing Wai; Chan, Denise Pui-Chung; Lee, Simon Ming Yuen; Wang, Ruibing

    2016-08-21

    Cucurbit[7]uril (CB[7]) has recently attracted increasing attention in pharmaceutical sciences due to its great potential in improving the physicochemical properties and bioactivity of drug molecules. Herein, we have investigated the influence of CB[7]'s complexation on the solubility, antimycobacterial activity, and cardiotoxicity of a model anti-tuberculosis drug, clofazimine (CFZ), that has poor water-solubility and inherent cardiotoxicity. In our study, CFZ was found to be complexed by CB[7], in a 1 : 1 binding mode with a relatively strong binding affinity (in the order of magnitude of 10(4)-10(5) M(-1)), as determined by the phase solubility method via HPLC-UV analysis and (1)H NMR titration, as well as UV-visible spectroscopic titration, and further confirmed by electrospray ionization mass spectrometry (ESI-MS). Upon complexation, the solubility of virtually insoluble CFZ was significantly increased, reaching a concentration of up to approximately 0.53-fold of the maximum solubility of CB[7]. The inherent cardiotoxicity of CFZ was dramatically reduced to almost nil in the presence of CB[7]. Importantly, on the other hand, such a supramolecular complexation of the drug did not compromise its therapeutic efficacy, as shown by the antimycobacterial activities examined against Mycobacterium smegmatis, demonstrating the significant potential of CB[7] as a functional pharmaceutical excipient. PMID:27439674

  10. Antibacterial, antifungal and antimycobacterial activities of some pyrazoline, hydrazone and chalcone derivatives.

    PubMed

    Evranos-Aksöz, Begüm; Onurdağ, Fatma Kaynak; Özgacar, Selda Özgen

    2015-07-01

    Twenty-seven previously reported chalcones and their pyrazoline and hydrazone derivatives as well as two further chalcones have been screened for their antimicrobial, antifungal and antimycobacterial activities against standard microbial strains and drug resistant isolates. The minimum inhibitory concentration (MIC) value of each compound was determined by a two-fold serial microdilution technique. The compounds were found to possess a broad spectrum of antimicrobial activities with MIC values of 8-128 μg/mL. One compound [(E)-1-(4-hydroxyphenyl)-3-p-tolylprop-2-en-1-one] had equal activity with gentamycin (8 μg/mL) against Enterococcus faecalis. Chalcones were found to be more active than their hydrazone and 2-pyrazoline derivatives against Staphylococcus aureus ATCC 29213 and E. faecalis ATCC 29212. PMID:26372110

  11. Synthesis, antimycobacterial, antiviral, antimicrobial activity and QSAR studies of N(2)-acyl isonicotinic acid hydrazide derivatives.

    PubMed

    Judge, Vikramjeet; Narasimhan, Balasubramanian; Ahuja, Munish; Sriram, Dharmarajan; Yogeeswari, Perumal; De Clercq, Erik; Pannecouque, Christophe; Balzarini, Jan

    2013-02-01

    A series of N(2)-acyl isonicotinic acid hydrazides (1-17) was synthesized and tested for its in vitro antimycobacterial activity against Mycobacterium tuberculosis and the results indicated that the compound, isonicotinic acid N'- tetradecanoyl-hydrazide (12) was more active than the reference compound isoniazid. The results of antimicrobial activity of the synthesized compounds against S. aureus, B. subtilis, E. coli, C. albicans and A. niger indicated that compounds with dichloro, hydroxyl, tri-iodo and N(2)-tetradecanoyl substituent were the most active ones. The antiviral activity studies depicted that none of the tested compounds were active against DNA or RNA viruses. The multi-target QSAR model was found to be effective in describing the antimicrobial activity of N(2)-acyl isonicotinic acid hydrazides. PMID:22762163

  12. Synthesis and Antimycobacterial Activity of Symmetric Thiocarbohydrazone Derivatives against Mycobacterium bovis BCG

    PubMed Central

    Haj Mohammad Ebrahim Tehrani, Kamaleddin; Kobarfard, Farzad; Azerang, Parisa; Mehravar, Maryam; Soleimani, Zohreh; Ghavami, Ghazaleh; Sardari, Soroush

    2013-01-01

    In this work, we reported the synthesis and evaluation of antimycobacterial and antifungal activity of a series of thiocarbohydrazone derivatives which are thiacetazone congeners. The target compounds were synthesized in superior yields by reacting thiocarbohydrazide with different aromatic aldehydes and methyl ketones. Compounds 8, 19 and 25 were found to be the most potent derivatives, exhibiting acceptable activity against Mycobacterium bovis BCG compared to thiacetazone and ethambutol as reference substances. Compounds 8, 15 and 25 exhibited the highest activity against Candida albicans. The most active compounds had a completely different aromatic ring system with various electronic, steric and lipophilic natures. This is understandable in light of the fact that carbohydrazone derivatives must undergo a metabolic activation step before exerting their anti-TB activity and different SAR rules govern each one of these two processes. PMID:24250608

  13. Secondary metabolites from the unripe pulp of Persea americana and their antimycobacterial activities.

    PubMed

    Lu, Ying-Chen; Chang, Hsun-Shuo; Peng, Chien-Fang; Lin, Chu-Hung; Chen, Ih-Sheng

    2012-12-15

    The fruits of Persea americana (Avocado) are nowadays used as healthy fruits in the world. Bioassay-guided fractionation of the active ethyl acetate soluble fraction has led to the isolation of five new fatty alcohol derivatives, avocadenols A-D (1-4) and avocadoin (5) from the unripe pulp of P. americana, along with 12 known compounds (6-17). These structures were elucidated by spectroscopic analysis. Among the isolates, avocadenol A (1), avocadenol B (2), (2R,4R)-1,2,4-trihydroxynonadecane (6), and (2R,4R)-1,2,4-trihydroxyheptadec-16-ene (7) showed antimycobacterial activity against Mycobacterium tuberculosis H(37)R(V)in vitro, with MIC values of 24.0, 33.8, 24.9, and 35.7 μg/ml, respectively. PMID:22980888

  14. Evaluation of the flora of Puerto Rico for in vitro antiplasmodial and antimycobacterial activities.

    PubMed

    Antoun, M D; Ramos, Z; Vazques, J; Oquendo, I; Proctor, G R; Gerena, L; Franzblau, S G

    2001-11-01

    The emergence of resistant strains of Plasmodium falciparum and Mycobacterium tuberculosis underscores the need for novel drugs that are effective against these microorganisms. As part of our screening programme of the flora of Puerto Rico, we tested a number of ethanol extracts of higher plants for antiplasmodial and antimycobacterial activities. A total of 40 extracts belonging to 23 plant families and 37 species were tested for antiplasmodial activity. Five extracts demonstrated activity against Plasmodium falciparum in vitro (50%-100% parasite suppression at 5 microg/mL). Another 63 extracts belonging to 30 plant families and 50 species were tested in vitro against Mycobacterium tuberculosis. Two extracts were found to be active, Ficus citrifolia and Pisonia borinquena (85% or more inhibition of microbial growth at 100 microg/mL of extract). PMID:11746852

  15. Antimycobacterial and HIV-1 Reverse Transcriptase Activity of Julianaceae and Clusiaceae Plant Species from Mexico

    PubMed Central

    Gómez-Cansino, Rocio; Espitia-Pinzón, Clara Inés; Campos-Lara, María Guadalupe; Guzmán-Gutiérrez, Silvia Laura; Segura-Salinas, Erika; Echeverría-Valencia, Gabriela; Torras-Claveria, Laura; Cuevas-Figueroa, Xochitl Marisol; Reyes-Chilpa, Ricardo

    2015-01-01

    The extracts of 14 Julianaceae and 5 Clusiaceae species growing in Mexico were tested in vitro (50 µg/mL) against Mycobacterium tuberculosis H37Rv and HIV reverse transcriptase (HIV-RT). The Julianaceae bark and leaf extracts inhibited M. tuberculosis (>84.67%) and HIV-RT (<49.89%). The Clusiaceae leaves extracts also inhibited both targets (>58.3% and >67.6%), respectively. The IC50 values for six selected extracts and their cytotoxicity (50 µg/mL) to human macrophages were then determined. Amphipterygium glaucum, A. molle, and A. simplicifolium fairly inhibited M. tuberculosis with IC50 of 1.87–2.35 µg/mL; but their IC50 against HIV-RT was 59.25–97.83 µg/mL. Calophyllum brasiliense, Vismia baccifera, and Vismia mexicana effect on M. tuberculosis was noteworthy (IC50 3.02–3.64 µg/mL) and also inhibited RT-HIV (IC50 26.24–35.17 µg/mL). These 6 extracts (50 µg/mL) presented low toxicity to macrophages (<23.8%). The HPLC profiles of A. glaucum, A. molle, and A. simplicifolium indicated that their antimycobacterial activity cannot be related to masticadienonic, 3α, or 3β-hydromasticadienonic acids, suggesting that other compounds may be responsible for the observed activity or this might be a synergy result. The anti-HIV-RT and antimycobacterial activities induced by C. brasiliense can be attributed to the content of calanolides A, B, as well as soulatrolide. PMID:25983849

  16. Antimycobacterial activity of new N(1)-[1-[1-aryl-3-[4-(1H-imidazol-1-yl)phenyl]-3-oxo]propyl]-pyridine-2-carboxamidrazone derivatives.

    PubMed

    Zampieri, Daniele; Mamolo, Maria Grazia; Vio, Luciano; Romano, Maurizio; Skoko, Nataša; Baralle, Marco; Pau, Valentina; De Logu, Alessandro

    2016-07-15

    N(1)-[1-[1-aryl-3-[4-(1H-imidazol-1-yl)phenyl]-3-oxo]propyl]-pyridine-2-carboxamidrazone derivatives were design, synthesized and tested for their in vitro antimycobacterial activity. The new compounds showed a moderate antimycobacterial activity against the tested strain of Mycobacterium tuberculosis H37Ra and a significant antimycobacterial activity against several mycobacteria other than tuberculosis strains. PMID:27241693

  17. In vitro α-glucosidase inhibition, antioxidant, anticancer, and antimycobacterial properties of ethyl acetate extract of Aegle tamilnadensis Abdul Kader (Rutaceae) leaf.

    PubMed

    R, Pratap Chandran; S, Nishanth Kumar; S, Manju; S, Abdul Kader; B S, Dileep Kumar

    2015-01-01

    The present study was aimed to investigate in vitro α-glucosidase inhibition, antioxidant, anticancer, and antimycobacterial activities of the ethyl acetate extract of A. tamilnadensis leaves. The extract recorded strong α-glucosidase inhibition with an IC50 value of 100 μg/ml. The antioxidant potential of the extract was evaluated by nitric oxide radical inhibition, lipid peroxidation inhibition, ferric thiocyanate, and ABTS radical scavenging assay, and the extract recorded significant antioxidant activity. The ferric thiocyanate activity of extract was superior to butylated hydroxyl anisol (BHA), the standard antioxidant agent. The anticancer activity of the extract was evaluated against (1) breast cancer cell lines (MDAM B-231), (2) cervical cancer cell lines (HeLa), and (3) lung cancer cell line (A 549) using MTT assay, and significant activity was recorded against A 549 with an IC50 value of 64 μg/ml. Further studies on the morphology, acridine orange/ethidium bromide staining, and cell cycle analysis by flow cytometry confirm the extract-induced apoptosis in A 549. This extract also recorded significant anti-tuberculosis activity against Mycobacterium smegmatis. The current study suggests that the ethyl acetate extract of A. tamilnadensis is a potential source of natural α-glucosidase inhibitor and antioxidant for protection as well as prevention of life-threatening diseases like cancer. PMID:25380641

  18. Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis.

    PubMed

    Taus, Francesco; Santucci, Marilina B; Greco, Emanuela; Morandi, Matteo; Palucci, Ivana; Mariotti, Sabrina; Poerio, Noemi; Nisini, Roberto; Delogu, Giovanni; Fraziano, Maurizio

    2015-01-01

    A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination. PMID:26023779

  19. Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis

    PubMed Central

    Taus, Francesco; Santucci, Marilina B.; Greco, Emanuela; Morandi, Matteo; Palucci, Ivana; Mariotti, Sabrina; Poerio, Noemi; Nisini, Roberto; Delogu, Giovanni; Fraziano, Maurizio

    2015-01-01

    A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination. PMID:26023779

  20. Penicillium chrysogenum DSOA associated with marine sponge (Tedania anhelans) exhibit antimycobacterial activity.

    PubMed

    Visamsetti, Amarendra; Ramachandran, Santhosh Sarojini; Kandasamy, Dhevendaran

    2016-04-01

    A strain of Penicillium chrysogenum was isolated from Tedania anhelans (marine sponge) collected from Indian Ocean (8°22'30″N latitude and 76°59'16″ longitude) and deposited in culture collection centers. The strain subjected to different culture conditions for production of extrolites were extracted using ethyl acetate and chloroform. When both extracts were subjected for antibacterial activity, latter had high activity. Minimum inhibitory concentration of chloroform extract ranged from 31.25-1000 μg/mL in tested microbes such as, Mycobacterium tuberculosis H37Ra, Mycobacterium avium, Mycobacterium fortuitum, Mycobacterium smegmatis, Mycobacterium vaccae, Staphylococcus aureus, Aeromonas hydrophila, Pseudomonas aeruginosa and Vibrio cholerae. No cytotoxicity was observed in Vero cell line up to 399.10 μg/mL. Antibacterial activity previously reported by Parameswaran et al. in 1997 from ethyl acetate extract of T. anhelans might be due to the diketopiperazines, Cyclo-(L-Pro-L-Phe) and Cyclo-(L-Leu-L-Pro) produced by the associated fungi-P. chrysogenum DSOA. It is producing a metabolites having antimycobacterial activity, a first report. PMID:26717859

  1. Antimycobacterial activity and cytotoxicity of flavonoids from the flowers of Chromolaena odorata.

    PubMed

    Suksamrarn, Apichart; Chotipong, Apinya; Suavansri, Tananit; Boongird, Somnuk; Timsuksai, Puntip; Vimuttipong, Saovaluk; Chuaynugul, Aporn

    2004-05-01

    From the flowers of Chromolaena odorata (Eupatorium odoratum) four flavanones, isosakuranetin (5,7-dihydroxy-4'-methoxyflavanone) (1), persicogenin (5,3'-dihydroxy-7,4'-dimethoxyflavanone) (2), 5,6,7,4'-tetramethoxyflavanone (3) and 4'-hydroxy-5,6,7-trimethoxyflavanone (4), two chalcones, 2'-hydroxy-4,4',5',6'-tetramethoxychalcone (5) and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (6), and two flavones, acacetin (5,7-dihydroxy-4'-methoxyflavone) (7) and luteolin (5,7,3',4'-tetrahydroxyflavone) (8) were isolated and identified. Compound 1 exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with the MIC value of 174.8 microM, whereas compounds 4, 7, and 8 exhibited weak activity with the MIC values of 606.0, 704.2 and 699.3 microM respectively. Compound 7 showed moderate cytotoxicity against human small cell lung cancer (NCI-H187) cells with the MIC value of 24.6 microM, whereas compound 8 exhibited moderate toxicity against NCI-H187 cells and week toxicity against human breast cancer (BC) cells with the MIC values of 19.2 and 38.4 microM respectively. PMID:15202555

  2. Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds.

    PubMed

    Alvin, Alfonsus; Miller, Kristin I; Neilan, Brett A

    2014-01-01

    Natural product drug discovery has regained interest due to low production costs, structural diversity, and multiple uses of active compounds to treat various diseases. Attention has been directed towards medicinal plants as these plants have been traditionally used for generations to treat symptoms of numerous diseases. It is established that plants harbour microorganisms, collectively known as endophytes. Exploring the as-yet untapped natural products from the endophytes increases the chances of finding novel compounds. The concept of natural products targeting microbial pathogens has been applied to isolate novel antimycobacterial compounds, and the rapid development of drug-resistant Mycobacterium tuberculosis has significantly increased the need for new treatments against this pathogen. It remains important to continuously screen for novel compounds from natural sources, particularly from rarely encountered microorganisms, such as the endophytes. This review focuses on bioprospecting for polyketides and small peptides exhibiting antituberculosis activity, although current treatments against tuberculosis are described. It is established that natural products from these structure classes are often biosynthesised by microorganisms. Therefore it is hypothesised that some bioactive polyketides and peptides originally isolated from plants are in fact produced by their endophytes. This is of interest for further endophyte natural product investigations. PMID:24582778

  3. Potent antimycobacterial activity of the pyridoxal isonicotinoyl hydrazone analog 2-pyridylcarboxaldehyde isonicotinoyl hydrazone: a lipophilic transport vehicle for isonicotinic acid hydrazide.

    PubMed

    Ellis, Samantha; Kalinowski, Danuta S; Leotta, Lisa; Huang, Michael L H; Jelfs, Peter; Sintchenko, Vitali; Richardson, Des R; Triccas, James A

    2014-02-01

    The rise in drug-resistant strains of Mycobacterium tuberculosis is a major threat to human health and highlights the need for new therapeutic strategies. In this study, we have assessed whether high-affinity iron chelators of the pyridoxal isonicotinoyl hydrazone (PIH) class can restrict the growth of clinically significant mycobacteria. Screening a library of PIH derivatives revealed that one compound, namely, 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH), exhibited nanomolar in vitro activity against Mycobacterium bovis bacille Calmette-Guérin and virulent M. tuberculosis. Interestingly, PCIH is derived from the condensation of 2-pyridylcarboxaldehyde with the first-line antituberculosis drug isoniazid [i.e., isonicotinic acid hydrazide (INH)]. PCIH displayed minimal host cell toxicity and was effective at inhibiting growth of M. tuberculosis within cultured macrophages and also in vivo in mice. Further, PCIH restricted mycobacterial growth at high bacterial loads in culture, a property not observed with INH, which shares the isonicotinoyl hydrazide moiety with PCIH. When tested against Mycobacterium avium, PCIH was more effective than INH at inhibiting bacterial growth in broth culture and in macrophages, and also reduced bacterial loads in vivo. Complexation of PCIH with iron decreased its effectiveness, suggesting that iron chelation may play some role in its antimycobacterial efficacy. However, this could not totally account for its potent efficacy, and structure-activity relationship studies suggest that PCIH acts as a lipophilic vehicle for the transport of its intact INH moiety into the mammalian cell and the mycobacterium. These results demonstrate that iron-chelating agents such as PCIH may be of benefit in the treatment and control of mycobacterial infection. PMID:24243647

  4. Synthesis and antimycobacterial activity of N-(2-aminopurin-6-yl) and N-(purin-6-yl) amino acids and dipeptides.

    PubMed

    Krasnov, Victor P; Vigorov, Alexey Yu; Musiyak, Vera V; Nizova, Irina A; Gruzdev, Dmitry A; Matveeva, Tatyana V; Levit, Galina L; Kravchenko, Marionella A; Skornyakov, Sergey N; Bekker, Olga B; Danilenko, Valery N; Charushin, Valery N

    2016-06-01

    Synthetic routes to novel N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates with amino acids and glycine-containing dipeptides were developed. In vitro testing of 42 new and known compounds made it possible to reveal a series of N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates exhibiting significant antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium, Mycobacterium terrae, and multidrug-resistant M. tuberculosis strain isolated from tuberculosis patients in the Ural region (Russia). N-(2-Aminopurin-6-yl)- and N-(purin-6-yl)-glycyl-(S)-glutamic acids were the most active compounds. PMID:27107949

  5. CHEMICAL CHARACTERIZATION AND EVALUATION OF ANTIBACTERIAL, ANTIFUNGAL, ANTIMYCOBACTERIAL, AND CYTOTOXIC ACTIVITIES OF Talinum paniculatum.

    PubMed

    Dos Reis, Luis F C; Cerdeira, Cláudio D; De Paula, Bruno F; Silva, Jeferson J da; Coelho, Luiz F L; Silva, Marcelo A; Marques, Vanessa B B; Chavasco, Jorge K; Alves-Da-Silva, Geraldo

    2015-01-01

    In this study, the bioactivity of Talinum paniculatum was evaluated, a plant widely used in folk medicine. The extract from the T. paniculatum leaves (LE) was obtained by percolation with ethanol-water and then subjecting it to liquid-liquid partitions, yielding hexane (HX), ethyl acetate (EtOAc), butanol (BuOH), and aqueous (Aq) fractions. Screening for antimicrobial activity of the LE and its fractions was evaluated in vitro through broth microdilution method, against thirteen pathogenic and non-pathogenic microorganisms, and the antimycobacterial activity was performed through agar diffusion assay. The cytotoxic concentrations (CC90) for LE, HX, and EtOAc were obtained on BHK-21 cells by using MTT reduction assay. The LE showed activity against Serratia marcescens and Staphylococcus aureus, with Minimum Inhibitory Concentration (MIC) values of 250 and 500 µg/mL, respectively. Furthermore, HX demonstrated outstanding activity against Micrococcus luteus and Candida albicans with a MIC of 31.2 µg/mL in both cases. The MIC for EtOAc also was 31.2 µg/mL against Escherichia coli. Conversely, BuOH and Aq were inactive against all tested microorganisms and LE proved inactive against Mycobacterium tuberculosis and Mycobacterium bovis as well. Campesterol, stigmasterol, and sitosterol were the proposed structures as main compounds present in the EF and HX/EtOAc fractions, evidenced by mass spectrometry. Therefore, LE, HX, and EtOAc from T. paniculatum showed potential as possible sources of antimicrobial compounds, mainly HX, for presenting low toxicity on BHK-21 cells with excellent Selectivity Index (SI = CC90/MIC) of 17.72 against C. albicans. PMID:26603226

  6. CHEMICAL CHARACTERIZATION AND EVALUATION OF ANTIBACTERIAL, ANTIFUNGAL, ANTIMYCOBACTERIAL, AND CYTOTOXIC ACTIVITIES OF Talinum paniculatum

    PubMed Central

    REIS, Luis F.C. DOS; CERDEIRA, Cláudio D.; PAULA, Bruno F. DE; da SILVA, Jeferson J.; COELHO, Luiz F.L.; SILVA, Marcelo A.; MARQUES, Vanessa B.B.; CHAVASCO, Jorge K.; ALVES-DA-SILVA, Geraldo

    2015-01-01

    SUMMARY In this study, the bioactivity of Talinum paniculatum was evaluated, a plant widely used in folk medicine. The extract from the T. paniculatum leaves (LE) was obtained by percolation with ethanol-water and then subjecting it to liquid-liquid partitions, yielding hexane (HX), ethyl acetate (EtOAc), butanol (BuOH), and aqueous (Aq) fractions. Screening for antimicrobial activity of the LE and its fractions was evaluated in vitro through broth microdilution method, against thirteen pathogenic and non-pathogenic microorganisms, and the antimycobacterial activity was performed through agar diffusion assay. The cytotoxic concentrations (CC90) for LE, HX, and EtOAc were obtained on BHK-21 cells by using MTT reduction assay. The LE showed activity against Serratia marcescens and Staphylococcus aureus, with Minimum Inhibitory Concentration (MIC) values of 250 and 500 µg/mL, respectively. Furthermore, HX demonstrated outstanding activity against Micrococcus luteusand Candida albicans with a MIC of 31.2 µg/mL in both cases. The MIC for EtOAc also was 31.2 µg/mL against Escherichia coli. Conversely, BuOH and Aq were inactive against all tested microorganisms and LE proved inactive against Mycobacterium tuberculosis and Mycobacterium bovis as well. Campesterol, stigmasterol, and sitosterol were the proposed structures as main compounds present in the EF and HX/EtOAc fractions, evidenced by mass spectrometry. Therefore, LE, HX, and EtOAc from T. paniculatum showed potential as possible sources of antimicrobial compounds, mainly HX, for presenting low toxicity on BHK-21 cells with excellent Selectivity Index (SI = CC90/MIC) of 17.72 against C. albicans. PMID:26603226

  7. In vitro and in vivo antimycobacterial activities of a new quinolone, DU-6859a.

    PubMed Central

    Saito, H; Tomioka, H; Sato, K; Dekio, S

    1994-01-01

    A new fluoroquinolone, DU-6859a, was studied for its in vitro and in vivo antimycobacterial activities. MIC determination by the agar dilution method with 7H11 medium revealed that DU-6859a had MICs at which 90% of M. kansasii (0.78 microgram/ml), M. marinum (1.56 micrograms/ml), M. scrofulaceum (1.56 micrograms/ml), M. fortuitum (0.39 microgram/ml), M. chelonae subsp. abscessus (6.25 micrograms/ml), and M. chelonae subsp. chelonae (1.56 micrograms/ml) were inhibited were 4 to 32 times lower than those of ofloxacin and sparfloxacin. The MICs of DU-6859a at which 90% of M. tuberculosis (0.2 microgram/ml) and M. avium-M. intracellulare complex (12.5 micrograms/ml each) were inhibited were comparable to those of sparfloxacin but were four- to eightfold lower than those of ofloxacin. Thus, DU-6859a possessed more potent in vitro activity than sparfloxacin and ofloxacin against most mycobacterial species. DU-6859a exerted significant efficacy against infections caused by M. intracellulare and M. chelonae subsp. abscessus induced in mice when it was given at a dose of 1 mg per mouse (ca. 50 mg/kg of body weight) in terms of reducing the frequency of occurrence and the degree of gross pulmonary or renal lesions and bacterial loads in the lungs, spleens, or kidneys. The efficacy of DU-6859a was greater than that of ofloxacin and was more pronounced against M. chelonae infections than against M. intracellulare infections. PMID:7695276

  8. Structure-Activity Analysis of Gram-positive Bacterium-producing Lasso Peptides with Anti-mycobacterial Activity

    PubMed Central

    Inokoshi, Junji; Koyama, Nobuhiro; Miyake, Midori; Shimizu, Yuji; Tomoda, Hiroshi

    2016-01-01

    Lariatin A, an 18-residue lasso peptide encoded by the five-gene cluster larABCDE, displays potent and selective anti-mycobacterial activity. The structural feature is an N-terminal macrolactam ring, through which the C-terminal passed to form the rigid lariat-protoknot structure. In the present study, we established a convergent expression system by the strategy in which larA mutant gene-carrying plasmids were transformed into larA-deficient Rhodococcus jostii, and generated 36 lariatin variants of the precursor protein LarA to investigate the biosynthesis and the structure-activity relationships. The mutational analysis revealed that four amino acid residues (Gly1, Arg7, Glu8, and Trp9) in lariatin A are essential for the maturation and production in the biosynthetic machinery. Furthermore, the study on structure-activity relationships demonstrated that Tyr6, Gly11, and Asn14 are responsible for the anti-mycobacterial activity, and the residues at positions 15, 16 and 18 in lariatin A are critical for enhancing the activity. This study will not only provide a useful platform for genetically engineering Gram-positive bacterium-producing lasso peptides, but also an important foundation to rationally design more promising drug candidates for combatting tuberculosis. PMID:27457620

  9. Validation of Antimycobacterial Plants Used by Traditional Healers in Three Districts of the Limpopo Province (South Africa)

    PubMed Central

    Masoko, Peter; Nxumalo, Kulani Mashudu

    2013-01-01

    The aim of the study was to scientifically evaluate the antimycobacterial activity of selected indigenous medicinal plants from the Limpopo Province used for the treatment of humans with symptoms of Mycobacterium tuberculosis. The leaves of five plant species (Apodytes dimidiata, Artemisia, Combretum hereroense, Lippia javanica, and Zanthoxylum capense) were collected from the Lowveld National Botanical Garden in Nelspruit, South Africa. The dried leaves were powdered and extracted using hexane, dichloromethane, acetone, and methanol. Antimycobacterial activity was evaluated using microdilution assay and bioautography and ρ-iodonitrotetrazolium violet (INT) as indicator. Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH). Phytochemical content of extracts was further evaluated. The acetone extracts of L. javanica displayed antioxidant activity on BEA chromatogram. T Acetone extracts of A. afra had MIC value of 0.39 mg/mL against Mycobacterium smegmatis ATCC 1441. Acetone extracts of C. hereroense and L. javanica had MIC value of 0.47 mg/mL. Four bands that inhibited the growth of M. smegmatis were observed at Rf values of 0.12, 0.63, and 0.87 on BEA and 0.73 on EMW. The plant species A. dimidiata, A. afra, C. hereroense, and L. javanica in this study demonstrated their potential as sources of anti-TB drug leads. PMID:23956776

  10. Antimycobacterial, antiprotozoal and cytotoxic potential of twenty-one brown algae (Phaeophyceae) from British and Irish waters.

    PubMed

    Spavieri, Jasmine; Allmendinger, Andrea; Kaiser, Marcel; Casey, Rosalyn; Hingley-Wilson, Suzie; Lalvani, Ajit; Guiry, Michael D; Blunden, Gerald; Tasdemir, Deniz

    2010-11-01

    In the continuation of our research on seaweeds, crude extracts of 21 brown algae collected from the south coast of England and the west coast of Ireland were screened for in vitro trypanocidal, leishmanicidal and antimycobacterial activities. Mammalian stages of a small set of parasitic protozoa; i.e. Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, and the tubercle bacillus Mycobacterium tuberculosis were used as test organisms. The extracts were also evaluated for selectivity by testing on a mammalian cell line (L6 cells). Only four extracts were moderately active against T. cruzi, whereas all algal extracts showed significant activity against T. brucei rhodesiense, with Halidrys siliquosa and Bifurcaria bifurcata (Sargassaceae) being the most potent (IC50 values 1.2 and 1.9 μg/mL). All algal extracts also displayed leishmanicidal activity, with H. siliquosa and B. bifurcata again being the most active (IC50s 6.4 and 8.6 μg/mL). When tested against M. tuberculosis, only the B. bifurcata extract was found to have some antitubercular potential (MIC value 64.0 μg/mL). Only three seaweed extracts, i.e. H. siliquosa, B. bifurcata and Cystoseira tamariscifolia showed some cytotoxicity. To our knowledge, this is the first study on the antiprotozoal and antimycobacterial activity of brown algae from British and Irish waters. PMID:20564461

  11. Structure-Activity Analysis of Gram-positive Bacterium-producing Lasso Peptides with Anti-mycobacterial Activity

    NASA Astrophysics Data System (ADS)

    Inokoshi, Junji; Koyama, Nobuhiro; Miyake, Midori; Shimizu, Yuji; Tomoda, Hiroshi

    2016-07-01

    Lariatin A, an 18-residue lasso peptide encoded by the five-gene cluster larABCDE, displays potent and selective anti-mycobacterial activity. The structural feature is an N-terminal macrolactam ring, through which the C-terminal passed to form the rigid lariat-protoknot structure. In the present study, we established a convergent expression system by the strategy in which larA mutant gene-carrying plasmids were transformed into larA-deficient Rhodococcus jostii, and generated 36 lariatin variants of the precursor protein LarA to investigate the biosynthesis and the structure-activity relationships. The mutational analysis revealed that four amino acid residues (Gly1, Arg7, Glu8, and Trp9) in lariatin A are essential for the maturation and production in the biosynthetic machinery. Furthermore, the study on structure-activity relationships demonstrated that Tyr6, Gly11, and Asn14 are responsible for the anti-mycobacterial activity, and the residues at positions 15, 16 and 18 in lariatin A are critical for enhancing the activity. This study will not only provide a useful platform for genetically engineering Gram-positive bacterium-producing lasso peptides, but also an important foundation to rationally design more promising drug candidates for combatting tuberculosis.

  12. The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity

    PubMed Central

    Wilson, Gillian J.; Marakalala, Mohlopheni J.; Hoving, Jennifer C.; van Laarhoven, Arjan; Drummond, Rebecca A.; Kerscher, Bernhard; Keeton, Roanne; van de Vosse, Esther; Ottenhoff, Tom H.M.; Plantinga, Theo S.; Alisjahbana, Bachti; Govender, Dhirendra; Besra, Gurdyal S.; Netea, Mihai G.; Reid, Delyth M.; Willment, Janet A.; Jacobs, Muazzam; Yamasaki, Sho; van Crevel, Reinout; Brown, Gordon D.

    2015-01-01

    Summary The interaction of microbes with pattern recognition receptors (PRRs) is essential for protective immunity. While many PRRs that recognize mycobacteria have been identified, none is essentially required for host defense in vivo. Here, we have identified the C-type lectin receptor CLECSF8 (CLEC4D, MCL) as a key molecule in anti-mycobacterial host defense. Clecsf8−/− mice exhibit higher bacterial burdens and increased mortality upon M. tuberculosis infection. Additionally, Clecsf8 deficiency is associated with exacerbated pulmonary inflammation, characterized by enhanced neutrophil recruitment. Clecsf8−/− mice show reduced mycobacterial uptake by pulmonary leukocytes, but infection with opsonized bacteria can restore this phagocytic defect as well as decrease bacterial burdens. Notably, a CLECSF8 polymorphism identified in humans is associated with an increased susceptibility to pulmonary tuberculosis. We conclude that CLECSF8 plays a non-redundant role in anti-mycobacterial immunity in mouse and in man. PMID:25674984

  13. Effect of Antiretroviral Therapy on HIV-mediated Impairment of the Neutrophil Antimycobacterial Response

    PubMed Central

    Bangani, Nonzwakazi; Goliath, Rene; Kampmann, Beate; Wilkinson, Katalin A.; Wilkinson, Robert J.; Martineau, Adrian R.

    2015-01-01

    Rationale: Experimental and epidemiological evidence suggests that neutrophils are important in the host response to tuberculosis. HIV infection, which increases the risk of tuberculosis, adversely affects neutrophil function. Objectives: To determine the impact of HIV and antiretroviral therapy on neutrophil antimycobacterial activity. Methods: We performed a cross-sectional comparison of neutrophil functions in 20 antiretroviral-naive HIV-infected and 20 HIV-uninfected individuals using luminescence-, flow cytometry–, and ELISA-based assays. We then conducted a prospective study in the HIV-infected individuals investigating these parameters during the first 6 months of antiretroviral therapy. Surface markers of neutrophil activation were investigated in a separate cohort using flow cytometry. Measurements and Main Results: HIV infection impaired control of Mycobacterium tuberculosis by neutrophils (mean ratio of mycobacterial luminescence in neutrophil samples vs. serum controls at 1 hour in HIV-infected participants, 0.88 ± 0.13 vs. HIV-uninfected participants, 0.76 ± 0.14; P = 0.01; at 24 hours, 0.82 ± 0.13 vs. 0.71 ± 0.13; P = 0.01). The extent of impairment correlated with log[HIV viral load]. Neutrophil cell death after 24 hours’ incubation with M. tuberculosis was higher in the HIV-infected cohort (85.3 ± 11.8% vs. 57.9 ± 22.4% necrotic cells; P < 0.0001). Neutrophils from HIV-infected participants demonstrated significantly more CD62L-negative cells (median, 23.0 vs. 8.5%; P = 0.008) and CD16-negative cells (3.2 vs. 1.3%, P = 0.03). Antiretroviral therapy restored mycobacterial restriction and pattern of neutrophil death toward levels seen in HIV-uninfected persons. Conclusions: Neutrophils in antiretroviral-naive HIV-infected persons are hyperactivated, eliminate M. tuberculosis less effectively than in HIV-uninfected individuals, and progress rapidly to necrotic cell death. These factors are

  14. Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.

    PubMed

    Tomioka, Haruaki; Sano, Chiaki; Sato, Katsumasa; Shimizu, Toshiaki

    2002-02-01

    We studied the activities of clarithromycin and fluoroquinolones (gatifloxacin, sitafloxacin, levofloxacin) in combination with other antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex (MAC). Clarithromycin potentiated the activities of rifampicin and rifalazil against both extracellular and intramacrophage MAC. In contrast, all the test quinolones exhibited antagonistic effects against extracellular MAC when combined with either clarithromycin or rifamycins. Such an antagonism was not observed for the activity of these combinations against intramacrophage MAC. Combined effects were observed with combinations of these fluoroquinolones with either ethambutol or streptomycin. Similar profiles were seen for the activities of two-drug combinations of clarithromycin or fluoroquinolones with other drugs against intramacrophage MAC isolated from pulmonary and disseminated MAC infections. PMID:11850167

  15. Antimycobacterial constituents from Juniperus procera, Ferula communis and Plumbago zeylanica and their in vitro synergistic activity with isonicotinic acid hydrazide.

    PubMed

    Mossa, Jaber S; El-Feraly, Farouk S; Muhammad, Ilias

    2004-11-01

    The synergistic activity of antimycobacterial constituents from Saudi plants was evaluated in combination with isonicotinic acid hydrazide (INH) against four atypical organisms, namely, Mycobacterium intracellulare, M. smegmatis, M. xenopei and M. chelonei. The potency of INH was increased four-fold, using an in vitro checkerboard method, against each mycobacteria when tested with a subtoxic concentration of the totarol, isolated from J. procera. The MIC values of totarol, ferulenol (from Ferula communis) and plumbagin (from Plumbago zeylanica) were thus lowered from 1.25-2.5 to 0.15-0.3 microg/mL due to synergism with INH. When tested against the resistant strain of M. tuberculosis H37Rv, plumbagin and 7beta-hydroxyabieta-8,13-dien-11,12-dione exhibited inhibitory activity at <12.5 microg/mL, while others were inactive at this concentration. PMID:15597311

  16. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... millions of gallons of Agent Orange and other herbicides on trees and vegetation during the Vietnam War. ...

  17. Benzo[d]thiazol-2-yl(piperazin-1-yl)methanones as new anti-mycobacterial chemotypes: Design, synthesis, biological evaluation and 3D-QSAR studies.

    PubMed

    Pancholia, Sahaj; Dhameliya, Tejas M; Shah, Parth; Jadhavar, Pradeep S; Sridevi, Jonnalagadda Padma; Yogeshwari, Perumal; Sriram, Dharmarajan; Chakraborti, Asit K

    2016-06-30

    The benzo[d]thiazol-2-yl(piperazin-1-yl)methanones scaffold has been identified as new anti-mycobacterial chemotypes. Thirty-six structurally diverse benzo[d]thiazole-2-carboxamides have been prepared and subjected to assessment of their potential anti-tubercular activity through in vitro testing against Mycobacterium tuberculosis H37Rv strain and evaluation of cytotoxicity against RAW 264.7 cell lines. Seventeen compounds showed anti-mycobacterial potential having MICs in the low (1-10) μM range. The 5-trifluoromethyl benzo[d]thiazol-2-yl(piperazin-1-yl)methanones emerged to be the most promising resulting in six positive hits (2.35-7.94 μM) and showed low-cytotoxicity (<50% inhibition at 50 μg/mL). The therapeutic index of these hits is 8-64. The quantitative structure activity relationship has been established adopting a statistically reliable CoMFA model showing high prediction (rpred(2)=0.718,rncv(2)=0.995). PMID:27061982

  18. Evaluation of a Human BCG Challenge Model to Assess Antimycobacterial Immunity Induced by BCG and a Candidate Tuberculosis Vaccine, MVA85A, Alone and in Combination

    PubMed Central

    Harris, Stephanie A.; Meyer, Joel; Satti, Iman; Marsay, Leanne; Poulton, Ian D.; Tanner, Rachel; Minassian, Angela M.; Fletcher, Helen A.; McShane, Helen

    2014-01-01

    Background. A new vaccine is urgently needed to combat tuberculosis. However, without a correlate of protection, selection of the vaccines to take forward into large-scale efficacy trials is difficult. Use of bacille Calmette-Guérin (BCG) as a surrogate for human Mycobacterium tuberculosis challenge is a novel model that could aid selection. Methods. Healthy adults were assigned to groups A and B (BCG-naive) or groups C and D (BCG-vaccinated). Groups B and D received candidate tuberculosis vaccine MVA85A. Participants were challenged with intradermal BCG 4 weeks after those who received MVA85A. Skin biopsies of the challenge site were taken 2 weeks post challenge and BCG load quantified by culture and quantitative polymerase chain reaction (qPCR). Results. Volunteers with a history of BCG showed some degree of protective immunity to challenge, having lower BCG loads compared with volunteers without prior BCG, regardless of MVA85A status. There was a significant inverse correlation between antimycobacterial immunity at peak response after MVA85A and BCG load detected by qPCR. Conclusion. Our results support previous findings that this BCG challenge model is able to detect differences in antimycobacterial immunity induced by vaccination and could aid in the selection of candidate tuberculosis vaccines for field efficacy testing. Clinical Trials Registration NCT01194180. PMID:24273174

  19. RP-HPLC analysis and in vitro identification of antimycobacterial activity of novel thiosemicarbazides and 1,2,4-triazole derivatives.

    PubMed

    Flieger, Jolanta; Tatarczak-Michalewska, Małgorzata; Wujec, Monika; Pitucha, Monika; Świeboda, Ryszard

    2015-03-25

    It has been widely recognized that chromatography can be applied to derive parameters useful for anticipation of the pharmacological properties of xenobiotics. The purpose of this study was to evaluate the use of C18 stationary phase in chromatographic experiments as to assess antimycobacterial activity of series of novel thiosemicarbazides and their cyclization products: 1,2,4-triazole derivatives. Chromatographically determined lipophilicity descriptors log k(w), S and φ0 and computer generated molecular descriptors were obtained for 32 compounds and Rifampicin as a representative anti-tuberculosis drug. As experimental parameters were not significantly related to the calculated values, the data were analyzed by the principal component analysis PCA allowing for the extraction of "dipole moment" and "energy due to solvation" as the most powerful parameters from large set of diverse data. The approach ranked the examined analytes as active and inactive against Mycobacterium strains. More significant clustering of examined compounds was achieved by construction of 3D graph relating computational (dipole moment, energy due to solvation) and experimental log k(w) (MeOH) descriptors. It was proved that lack of substituent in the C5 position in the triazole ring appears to be characteristic for active derivatives. Provided conclusions can be taken into account in planning further synthesis of new derivatives with antimycobacterial activity. PMID:25700183

  20. Design and synthesis of novel anti-tuberculosis agents from the celecoxib pharmacophore.

    PubMed

    Salunke, Santosh B; Azad, Abul K; Kapuriya, Naval P; Balada-Llasat, Joan-Miquel; Pancholi, Preeti; Schlesinger, Larry S; Chen, Ching-Shih

    2015-05-01

    The identification of compounds with anti-mycobacterial activity within classes of molecules that have been developed for other purposes is a fruitful approach for the development of anti-tuberculosis (TB) agents. In this study we used the scaffold of celecoxib which exhibits several activities against different pathogens, for the design and focused synthesis of a library of 64 compounds. For the primary screen, we used a bioluminescence-based method by constructing a luciferase-expressing reporter M.tb strain which contains the entire bacterial Lux operon cloned in a mycobacterial integrative expression vector. Through the screening of this library, we identified 6 hit compounds with high in vitro anti-mycobacterial activity (IC₅₀ ∼0.18-0.48 μM). In particular, compounds 41, 51 and 53 were capable of inhibiting M.tb as effectively as the anti-TB drug isoniazid (INH) at 5 μM over a 72-h period, as analyzed by both bioluminescence- and colony forming unit (CFU)-based assays. All hit compounds also showed anti-M.tb activities against several multi-drug-resistant (MDR) strains. Most of the hit compounds showed no cytotoxicity for human macrophages at concentrations as high as 40 μM, setting the stage for further optimization and development of these anti-TB hit compounds both ex vivo and in vivo. PMID:25818768

  1. Synthesis, biological evaluation and structure-activity relationship of 2-styrylquinazolones as anti-tubercular agents.

    PubMed

    Jadhavar, Pradeep S; Dhameliya, Tejas M; Vaja, Maulikkumar D; Kumar, Dinesh; Sridevi, Jonnalagadda Padma; Yogeeswari, Perumal; Sriram, Dharmarajan; Chakraborti, Asit K

    2016-06-01

    2-Styrylquinazolones are reported as a novel class of potent anti-mycobacterial agents. Forty-six target compounds have been synthesized using one pot reaction involving isatoic anhydride, amine, and triethyl orthoacetate followed by aldehyde to construct the 2-styrylquinazolone scaffold. The anti-mycobacterial potency of the compounds was determined against H37Rv strain. Twenty-six compounds exhibited anti-Mtb activity in the range of 0.40-6.25μg/mL. Three compounds 8c, 8d and 8ab showed MIC of 0.78μg/mL and were found to be non-toxic (<50% inhibition at 50μg/mL) to HEK 293T cell lines with the therapeutic index >64. The most potent compound 8ar showed MIC of 0.40μg/mL with the therapeutic index >125. An early structure activity relationship for this class of compounds has been established. The computational studies indicate the possibility of these compounds binding to the penicillin binding proteins (PBPs). PMID:27095514

  2. Biological Agents

    MedlinePlus

    ... to Z Index Contact Us FAQs What's New Biological Agents This page requires that javascript be enabled ... and Health Topics A-Z Index What's New Biological agents include bacteria, viruses, fungi, other microorganisms and ...

  3. Nitric Oxide Production Inhibition and Anti-Mycobacterial Activity of Extracts and Halogenated Sesquiterpenes from the Brazilian Red Alga Laurencia Dendroidea J. Agardh

    PubMed Central

    Biá Ventura, Thatiana Lopes; da Silva Machado, Fernanda Lacerda; de Araujo, Marlon Heggdorne; de Souza Gestinari, Lísia Mônica; Kaiser, Carlos Roland; de Assis Esteves, Francisco; Lasunskaia, Elena B.; Soares, Angélica Ribeiro; Muzitano, Michelle Frazão

    2015-01-01

    Background: Red algae of the genus Laurencia J. V. Lamouroux are a rich source of secondary metabolites with important pharmacological activities such as anti-tumoral, anti-inflammatory, anti-fungal, anti-viral, anti-leishmanial, anti-helminthic, anti-malarial, anti-trypanosomal, anti-microbial as well as anti-bacterial against Mycobacterium tuberculosis. Objective: In the present study, we evaluated the inhibition of nitric oxide (NO) and tumor necrosis factor-α production and the anti-mycobacterial activity of crude extracts from the red Alga Laurencia dendroidea (from the South-Eastern coast of Brazil). Halogenated sesquiterpenes elatol (1), obtusol (2) and cartilagineol (3), previously isolated from this Alga by our group, were also studied. Materials and Methods: The lipopolysaccharide-activated macrophage cells (RAW 264.7) were used as inflammation model. Cytotoxic effect was determined using a commercial lactate dehydrogenase (LDH) kit and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The growing Mycobacterium inhibition was verified against Mycobacterium bovis Bacillus Calmette–Guérin and M. tuberculosis H37 Rv strains. Results: The crude extract from Alga collected at Angra dos Reis, RJ, Brazil, was the most active inhibitor of both mycobacterial growth (half maximal inhibitory concentration [IC50] 8.7 ± 1.4 μg/mL) and NO production by activated macrophages (IC50 5.3 ± 1.3 μg/mL). The assays with isolated compounds revealed the anti-mycobacterial activity of obtusol (2), whereas (-)-elatol (1) inhibited the release of inflammatory mediators, especially NO. To our knowledge, this is the first report describing an anti-mycobacterial effect of L. dendroidea extract and demonstrating the association of this activity with obtusol (2). Conclusion: The described effects of active compounds from L. dendroidea are promising for the control of inflammation in infectious diseases and specifically, against mycobacterial infections

  4. Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

    PubMed Central

    Saifullah, Bullo; El Zowalaty, Mohamed E; Arulselvan, Palanisamy; Fakurazi, Sharida; Webster, Thomas J; Geilich, Benjamin M; Hussein, Mohd Zobir

    2014-01-01

    The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis. PMID:25114509

  5. Susceptibility of Mycobacterium tuberculosis to first-line antimycobacterial agents in a Brazilian hospital: assessing the utility of the tetrazolium (MTT) microplate assay.

    PubMed

    Ferrari, Michela De Luca; Telles, Maria Alice da Silva; Ferrazoli, Lucilaine; Levy, Carlos Emílio; Villares, Maria Cecília Barison; Moretti, Maria Luiza; Resende, Mariângela Ribeiro

    2010-08-01

    We conducted a cross-sectional, hospital-based study between January 2006-March 2008 to estimate the resistance of Mycobacterium tuberculosis to first-line drugs in patients with tuberculosis at a Brazilian hospital. We evaluated the performance of the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) microplate assay compared with the Bactec-MGIT 960 system for mycobacteria testing. The prevalence of resistance in M. tuberculosis was 6.7%. Multidrug-resistance [resistance to rifampicin (RMP) and isoniazid (INH)], INH-resistance and streptomycin (SM)-resistance accounted for 1%, 3.8% and 3.8% of all resistance, respectively, and all isolates were susceptible to ethambutol (EM). The resistance was primary in four cases and acquired in three cases and previous treatment was associated with resistance (p = 0.0129). Among the 119 M. tuberculosis isolates, complete concordance of the results for INH and EM was observed between the MTT microplate and Bactec-MGIT 960TM methods. The observed agreement for RMP was 99% (sensitivity: 90%) and 95.8% for SM (sensitivity 90.9%), lower than those for other drugs. The MTT colourimetric method is an accurate, simple and low-cost alternative in settings with limited resources. PMID:20835613

  6. IgG1 antimycobacterial antibodies can reverse the inhibitory effect of pentoxifylline on tumour necrosis factor alpha (TNF-α) secreted by mycobacterial antigen-stimulated adherent cells

    PubMed Central

    THAKURDAS, S M; HASAN, Z; HUSSAIN, R

    2004-01-01

    Chronic inflammation associated with cachexia, weight loss, fever and arthralgia is the hallmark of advanced mycobacterial diseases. These symptoms are attributed to the chronic stimulation of tumour necrosis factor (TNF)-α. Mycobacterial components directly stimulate adherent cells to secrete TNF-α. We have shown recently that IgG1 antimycobacterial antibodies play a role in augmenting TNF-α in purified protein derivative (PPD)-stimulated adherent cells from non-BCG-vaccinated donors. We now show that IgG1 antibodies can also augment TNF-α expression in stimulated adherent cells obtained from BCG-vaccinated donors and this augmentation is not linked to interleukin (IL)-10 secretion. In addition IgG1 antimycobacterial antibodies can reverse the effect of TNF-α blockers such as pentoxifylline and thalidomide. These studies therefore have clinical implications for anti-inflammatory drug treatments which are used increasingly to alleviate symptoms associated with chronic inflammation. PMID:15086397

  7. Synthesis, Biological Evaluation and 2D-QSAR Study of Halophenyl Bis-Hydrazones as Antimicrobial and Antitubercular Agents

    PubMed Central

    Abdel-Aziz, Hatem A.; Eldehna, Wagdy M.; Fares, Mohamed; Al-Rashood, Sara T. A.; Al-Rashood, Khalid A.; Abdel-Aziz, Marwa M.; Soliman, Dalia H.

    2015-01-01

    In continuation of our endeavor towards the development of potent and effective antimicrobial agents, three series of halophenyl bis-hydrazones (14a–n, 16a–d, 17a and 17b) were synthesized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the identification of five molecules 14c, 14g, 16b, 17a and 17b (MIC range from 0.12 to 7.81 μg/mL) with broad antimicrobial activity against Mycobacterium tuberculosis; Aspergillus fumigates; Gram positive bacteria, Staphylococcus aureus, Streptococcus pneumonia, and Bacillis subtilis; and Gram negative bacteria, Salmonella typhimurium, Klebsiella pneumonia, and Escherichia coli. Three of the most active compounds, 16b, 17a and 17b, were also devoid of apparent cytotoxicity to lung cancer cell line A549. Amphotericin B and ciprofloxacin were used as references for antifungal and antibacterial screening, while isoniazid and pyrazinamide were used as references for antimycobacterial activity. Furthermore, three Quantitative Structure Activity Relationship (QSAR) models were built to explore the structural requirements controlling the different activities of the prepared bis-hydrazones. PMID:25903147

  8. Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates.

    PubMed

    Ferraz-Carvalho, Rafaela S; Pereira, Marcela A; Linhares, Leonardo A; Lira-Nogueira, Mariane Cb; Cavalcanti, Isabella Mf; Santos-Magalhães, Nereide S; Montenegro, Lílian Ml

    2016-05-01

    Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb. PMID:27143488

  9. Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates

    PubMed Central

    Ferraz-Carvalho, Rafaela S; Pereira, Marcela A; Linhares, Leonardo A; Lira-Nogueira, Mariane CB; Cavalcanti, Isabella MF; Santos-Magalhães, Nereide S; Montenegro, Lílian ML

    2016-01-01

    Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb. PMID:27143488

  10. Antimycobacterial activity of peptide conjugate of pyridopyrimidine derivative against Mycobacterium tuberculosis in a series of in vitro and in vivo models.

    PubMed

    Horváti, Kata; Bacsa, Bernadett; Szabó, Nóra; Fodor, Kinga; Balka, Gyula; Rusvai, Miklós; Kiss, Éva; Mező, Gábor; Grolmusz, Vince; Vértessy, Beáta; Hudecz, Ferenc; Bősze, Szilvia

    2015-06-01

    New pyridopyrimidine derivatives were defined using a novel HTS in silico docking method (FRIGATE). The target protein was a dUTPase enzyme (EC 3.6.1.23; Rv2697) which plays a key role in nucleotide biosynthesis of Mycobacterium tuberculosis (Mtb). Top hit molecules were assayed in vitro for their antimycobacterial effect on Mtb H37Rv culture. In order to enhance the cellular uptake rate, the TB820 compound was conjugated to a peptid-based carrier and a nanoparticle type delivery system (polylactide-co-glycolide, PLGA) was applied. The conjugate had relevance to in vitro antitubercular activity with low in vitro and in vivo toxicity. In a Mtb H37Rv infected guinea pig model the in vivo efficacy of orally administrated PLGA encapsulated compound was proven: animals maintained a constant weight gain and no external clinical signs of tuberculosis were observed. All tissue homogenates from lung, liver and kidney were found negative for Mtb, and diagnostic autopsy showed that no significant malformations on the tissues occurred. PMID:25728610

  11. Doubly end-on azido bridged mixed-valence cobalt trinuclear complex: Spectral study, VTM, inhibitory effect and antimycobacterial activity on human carcinoma and tuberculosis cells

    NASA Astrophysics Data System (ADS)

    Datta, Amitabha; Das, Kuheli; Sen, Chandana; Karan, Nirmal Kumar; Huang, Jui-Hsien; Lin, Chia-Her; Garribba, Eugenio; Sinha, Chittaranjan; Askun, Tulin; Celikboyun, Pinar; Mane, Sandeep B.

    2015-09-01

    Doubly end-on azido-bridged mixed-valence trinuclear cobalt complex, [Co3(L)2(N3)6(CH3OH)2] (1) is afforded by employing a potential monoanionic tetradentate-N2O2 Schiff base precursor (2-[{[2-(dimethylamino)ethyl]imino}methyl]-6-methoxyphenol; HL). Single crystal X-ray structure reveals that in 1, the adjacent CoII and CoIII ions are linked by double end-on azido bridges and thus the full molecule is generated by the site symmetry of a crystallographic twofold rotation axis. Complex 1 is subjected on different spectral analysis such as IR, UV-vis, emission and EPR spectroscopy. On variable temperature magnetic study, we observe that during cooling, the χMT values decrease smoothly until 15 K and then reaches to the value 1.56 cm3 K mol-1 at 2 K. Complex 1 inhibits the cell growth on human lung carcinoma (A549 cells), human colorectal (COLO 205 and HT-29 cells), and human heptacellular (PLC5 cells) carcinoma cells. Complex 1 exhibits anti-mycobacterial activity and considerable efficacy on Mycobacterium tuberculosis H37Rv ATCC 27294 and H37Ra ATCC 25177 strains.

  12. Pyrrolo[3,4-c]pyridine-1,3(2H)-diones: A Novel Antimycobacterial Class Targeting Mycobacterial Respiration.

    PubMed

    van der Westhuyzen, Renier; Winks, Susan; Wilson, Colin R; Boyle, Grant A; Gessner, Richard K; Soares de Melo, Candice; Taylor, Dale; de Kock, Carmen; Njoroge, Mathew; Brunschwig, Christel; Lawrence, Nina; Rao, Srinivasa P S; Sirgel, Frederick; van Helden, Paul; Seldon, Ronnett; Moosa, Atica; Warner, Digby F; Arista, Luca; Manjunatha, Ujjini H; Smith, Paul W; Street, Leslie J; Chibale, Kelly

    2015-12-10

    High-throughput screening of a library of small polar molecules against Mycobacterium tuberculosis led to the identification of a phthalimide-containing ester hit compound (1), which was optimized for metabolic stability by replacing the ester moiety with a methyl oxadiazole bioisostere. A route utilizing polymer-supported reagents was designed and executed to explore structure-activity relationships with respect to the N-benzyl substituent, leading to compounds with nanomolar activity. The frontrunner compound (5h) from these studies was well tolerated in mice. A M. tuberculosis cytochrome bd oxidase deletion mutant (ΔcydKO) was hyper-susceptible to compounds from this series, and a strain carrying a single point mutation in qcrB, the gene encoding a subunit of the menaquinol cytochrome c oxidoreductase, was resistant to compounds in this series. In combination, these observations indicate that this novel class of antimycobacterial compounds inhibits the cytochrome bc1 complex, a validated drug target in M. tuberculosis. PMID:26551248

  13. Sunscreening Agents

    PubMed Central

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  14. Synthesis, molecular docking and anti-mycobacterial evaluation of new imidazo[1,2-a]pyridine-2-carboxamide derivatives.

    PubMed

    Jose, Gilish; Suresha Kumara, T H; Nagendrappa, Gopalpur; Sowmya, H B V; Sriram, Dharmarajan; Yogeeswari, Perumal; Sridevi, Jonnalagadda Padma; Guru Row, Tayur N; Hosamani, Amar A; Sujan Ganapathy, P S; Chandrika, N; Narendra, L V

    2015-01-01

    New anti-tubercular agents, imidazo[1,2-a]pyridine-2-carboxamide derivatives (5a-q) have been designed and synthesized. The structural considerations of the designed molecules were further supported by the docking study with a long-chain enoyl-acyl carrier protein reductase (InhA). The chemical structures of the new compounds were characterized by IR, (1)H NMR, (13)C NMR, HRMS and elemental analysis. In addition, single crystal X-ray diffraction has also been recorded for compound 5f. Compounds were evaluated in vitro against Mycobacterium tuberculosis H37Rv, and cytotoxicity against HEK-293T cell line. Amongst the tested compounds 5j, 5l and 5q were emerged as good anti-tubercular agents with low cytotoxicity. The structure-anti TB activity relationship of these derivatives was explained by molecular docking. PMID:25462270

  15. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  16. Antiparasitic agents.

    PubMed

    Rosenblatt, J E

    1999-11-01

    Several important developments have occurred in recent years in the chemotherapy for and prophylaxis of parasitic infections. Although mefloquine is clearly the most effective agent for prevention of chloroquine-resistant falciparum malaria, its use has been compromised by side effects, both real and imagined. Well-designed studies have shown that side effects occur no more frequently with low-dose mefloquine than with chloroquine. Use of mefloquine in pregnant women has not been associated with birth defects, but the incidence of stillbirths may be increased. Malarone is a new agent that combines atovaquone and proguanil, and it may be as effective as mefloquine; however, it is not yet available in the United States. Several newer agents have appeared in response to the development of multidrug resistant Plasmodium falciparum, especially in Southeast Asia. Halofantrine is available for the treatment of mild to moderate malaria due to P. falciparum and for P. vivax infections. Because of severe toxic effects, use of halofantrine should be restricted to only those unusual and rare situations in which other agents cannot be used. Artemisinin (an extract of the Chinese herbal remedy qinghaosu) and two derivatives, artesunate and artemether, are active against multidrug resistant P. falciparum and are widely used in Asia in oral, parenteral, and rectal forms. The antibacterial azithromycin in combination with atovaquone or quinine has now been reported to treat babesiosis effectively in experimental animals and in a few patients. Azithromycin in combination with paromomycin has also shown promise in the treatment of cryptosporidiosis (and toxoplasmosis when combined with pyrimethamine) in patients with the acquired immunodeficiency syndrome (AIDS). Albendazole is currently the only systemic agent available for treatment of microsporidiosis, an infection primarily of patients with AIDS. In addition, albendazole and ivermectin have emerged as effective broad

  17. Antifungal agents.

    PubMed

    Ryder, N S

    1999-12-01

    At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps. PMID:16113946

  18. KGB agents

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    A short story is reported in which the activity of Communist Party of the USSR and secret KGB agents, which were payed by the State, in view of controlling of the conscience of population. The story reffers to the Physics Department of the Moscow University, Planing Institute of the Gosplan of Moldavian S.S.R. and Chishinau Technical University (actually: Technical University of Moldova), where the author has worked during Soviet times. Almost every 6-th citizen in the USSR was engaged in this activity, while actually the former communists rule in the Republic of Moldova.

  19. Health care agents

    MedlinePlus

    Durable power of attorney for health care; Health care proxy; End-of-life - health care agent; Life support treatment - ... Respirator - health care agent; Ventilator - health care agent; Power of attorney - health care agent; POA - health care ...

  20. Agent Building Software

    NASA Technical Reports Server (NTRS)

    2000-01-01

    AgentBuilder is a software component developed under an SBIR contract between Reticular Systems, Inc., and Goddard Space Flight Center. AgentBuilder allows software developers without experience in intelligent agent technologies to easily build software applications using intelligent agents. Agents are components of software that will perform tasks automatically, with no intervention or command from a user. AgentBuilder reduces the time and cost of developing agent systems and provides a simple mechanism for implementing high-performance agent systems.

  1. In vitro drug susceptibility of 40 international reference rapidly growing mycobacteria to 20 antimicrobial agents

    PubMed Central

    Pang, Hui; Li, Guilian; Wan, Li; Jiang, Yi; Liu, Haican; Zhao, Xiuqin; Zhao, Zhongfu; Wan, Kanglin

    2015-01-01

    Rapidly growing mycobacteria (RGM) are human pathogens that are relatively easily identified by acid-fast staining but are proving difficult to treat in the clinic. In this study, we performed susceptibility testing of 40 international reference RGM species against 20 antimicrobial agents using the cation-adjusted Mueller-Hinton (CAMH) broth microdilution based on the minimum inhibitory concentration (MIC) assay recommended by the guidelines of the Clinical and Laboratory Standards Institute (CLSI). The results demonstrated that RGM organisms were resistant to the majority of first-line antituberculous agents but not to second-line fluoroquinolones or aminoglycosides. Three drugs (amikacin, tigecycline and linezolid) displayed potent antimycobacterial activity against all tested strains. Capreomycin, levofloxacin and moxifloxacin emerged as promising candidates for the treatment of RGM infections, and cefoxitin and meropenem were active against most strains. Mycobacterium chelonae (M. chelonae), M. abscessus, M. bolletii, M. fortuitum, M. boenickei, M. conceptionense, M. pseudoshottsii, M. septicum and M. setense were the most resistant RGM species. These results provide significant insight into the treatment of RGM species and will assist optimization of clinical criteria. PMID:26629031

  2. Design of novel dispirooxindolopyrrolidine and dispirooxindolopyrrolothiazole derivatives as potential antitubercular agents.

    PubMed

    Mhiri, Chourouk; Boudriga, Sarra; Askri, Moheddine; Knorr, Michael; Sriram, Dharmarajan; Yogeeswari, Perumal; Nana, Frédéric; Golz, Christopher; Strohmann, Carsten

    2015-10-01

    With the aim to develop new potent antitubercular agents, a series of novel dispirooxindolopyrrolidines and dispirooxindolopyrrolothiazoles have been synthesized via a three-component 1,3-dipolar cycloaddition of (Z)-3-arylidenebenzofuran-2-ones, substituted isatin derivatives and α-aminoacids. The stereochemistry of the spiroadducts has been confirmed by an X-ray diffraction analysis. All the target heterocycles were evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain and the most active compounds were subjected to cytotoxicity studies against (RAW 264.7) cell lines. Among them, twelve compounds showed potent anti-tubercular activity with MIC ranging from 1.56 to 6.25 μg/mL. In particular dispirooxindolopyrrolothiazole derivatives 5c and 5f were found to be the most active (MIC of 1.56 μg/mL) with a good safety profile (27.53% and 20.74% at 50 μM, respectively). This is the first report demonstrating the benzofuranone oxindole hybrids as potential antimycobacterial agents. PMID:26271585

  3. Synthesis, in vitro antimycobacterial evaluation and docking studies of some new 5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one schiff bases.

    PubMed

    Malothu, Narender; Bhandaru, Jaswanth S; Kulandaivelu, Umasankar; Jojula, Malathi; Adidala, Raghuram Reddy; K R, Umadevi; A V N, Dusthackeer; Kaki, Venkat Rao; Akkinepally, Raghuram R

    2016-02-01

    Development of multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) has been considered as major health burden, globally. In order to develop novel, potential molecules against drug resistant TB, twenty two (22) new 3-substituted-7-benzyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one (6a-k) and 3-substituted-7-benzyl-2-methyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one (7a-k) derivatives were designed and synthesized by using appropriate synthetic protocols. Pantothenate synthetase (PS) was considered as the target for the molecular docking studies and evaluated the binding pattern at active site, as PS plays a significant role in the biosynthesis of pantothenate in Mycobacterium tuberculosis (MTB). The preliminary in vitro antibacterial screening of test compounds was carried out against two strains of Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria. The antimycobacterial screening was performed against MTB H37Rv and an isoniazid-resistant clinical isolate of MTB. The compounds 6b, 6c, 6d, 6k, 7b, 7c, 7d and 7k exhibited promising antibacterial activity MIC in the range of 15-73 μM against all bacterial strains used and compounds 6d and 7b showed antimycobacterial activity (IC50 <340 μM in LRP assay) and (MIC <9 μM in broth microdilution method). PMID:26755393

  4. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  5. Remote Agent Demonstration

    NASA Technical Reports Server (NTRS)

    Dorais, Gregory A.; Kurien, James; Rajan, Kanna

    1999-01-01

    We describe the computer demonstration of the Remote Agent Experiment (RAX). The Remote Agent is a high-level, model-based, autonomous control agent being validated on the NASA Deep Space 1 spacecraft.

  6. Natural antimycobacterial metabolites: current status.

    PubMed

    Okunade, Adewole L; Elvin-Lewis, Memory P F; Lewis, Walter H

    2004-04-01

    Over the years the introduction of very effective drugs has revolutionized the treatment of tuberculosis. In recent years, however, emerging multiple drug resistance has become a major threat and thus calls for an urgent search for new and effective treatments for this deadly disease. This review is complementary to earlier reviews and covers more recent reports of naturally occurring compounds, and in some cases synthetic analogs, largely from plants, fungi and marine organisms that demonstrate significant activity in the in vitro bioassays against Mycobacterium tuberculosis, and other mycobacterial species. Included also are traditional medicinal uses of specific plants when utilized to treat tuberculosis and other pulmonary diseases. PMID:15110681

  7. Spacecraft sanitation agent development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

  8. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided.

  9. Mobile Agents Applications.

    ERIC Educational Resources Information Center

    Martins, Rosane Maria; Chaves, Magali Ribeiro; Pirmez, Luci; Rust da Costa Carmo, Luiz Fernando

    2001-01-01

    Discussion of the need to filter and retrieval relevant information from the Internet focuses on the use of mobile agents, specific software components which are based on distributed artificial intelligence and integrated systems. Surveys agent technology and discusses the agent building package used to develop two applications using IBM's Aglet…

  10. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, Steven Y.

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

  11. Agent Architectures for Compliance

    NASA Astrophysics Data System (ADS)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  12. Chemical crowd control agents.

    PubMed

    Menezes, Ritesh G; Hussain, Syed Ather; Rameez, Mansoor Ali Merchant; Kharoshah, Magdy A; Madadin, Mohammed; Anwar, Naureen; Senthilkumaran, Subramanian

    2016-03-01

    Chemical crowd control agents are also referred to as riot control agents and are mainly used by civil authorities and government agencies to curtail civil disobedience gatherings or processions by large crowds. Common riot control agents used to disperse large numbers of individuals into smaller, less destructive, and more easily controllable numbers include chloroacetophenone, chlorobenzylidenemalononitrile, dibenzoxazepine, diphenylaminearsine, and oleoresin capsicum. In this paper, we discuss the emergency medical care needed by sufferers of acute chemical agent contamination and raise important issues concerning toxicology, safety and health. PMID:26658556

  13. Change Agent Survival Guide

    ERIC Educational Resources Information Center

    Dunbar, Folwell L.

    2011-01-01

    Consulting is a rough racket. Only a tarantula hair above IRS agents, meter maids and used car sales people, the profession is a prickly burr for slings and arrows. Throw in education, focus on dysfunctional schools and call oneself a "change agent," and this bad rap all but disappears. Unfortunately, though, consulting/coaching/mentoring in…

  14. Travel Agent Course Outline.

    ERIC Educational Resources Information Center

    British Columbia Dept. of Education, Victoria.

    Written for college entry-level travel agent training courses, this course outline can also be used for inservice training programs offered by travel agencies. The outline provides information on the work of a travel agent and gives clear statements on what learners must be able to do by the end of their training. Material is divided into eight…

  15. Pediatric Antifungal Agents

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Smith, P Brian

    2009-01-01

    Purpose of review In immunocompromised hosts, invasive fungal infections are common and fatal. In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of this report is to review the most recent literature addressing the use of antifungal agents in children. Recent findings Most studies evaluating the safety and efficacy of antifungal agents are limited to adults. However, important progress has been made in describing the pharmacokinetics and safety of newer antifungal agents in children, including the echinocandins. Summary Dosage guidelines for newer antifungal agents are currently based on adult and limited pediatric data. Because important developmental pharmacology changes occur throughout childhood impacting the pharmacokinetics of these agents, antifungal studies specifically designed for children are necessary. PMID:19741525

  16. How do agents represent?

    NASA Astrophysics Data System (ADS)

    Ryan, Alex

    Representation is inherent to the concept of an agent, but its importance in complex systems has not yet been widely recognised. In this paper I introduce Peirce's theory of signs, which facilitates a definition of representation in general. In summary, representation means that for some agent, a model is used to stand in for another entity in a way that shapes the behaviour of the agent with respect to that entity. Representation in general is then related to the theories of representation that have developed within different disciplines. I compare theories of representation from metaphysics, military theory and systems theory. Additional complications arise in explaining the special case of mental representations, which is the focus of cognitive science. I consider the dominant theory of cognition — that the brain is a representational device — as well as the sceptical anti-representational response. Finally, I argue that representation distinguishes agents from non-representational objects: agents are objects capable of representation.

  17. Standard Agent Framework 1

    Energy Science and Technology Software Center (ESTSC)

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4)more » Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.« less

  18. Biological warfare agents

    PubMed Central

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-01-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

  19. Dioxin, agent orange

    SciTech Connect

    Gough, M.

    1986-01-01

    This book presents information on the following topics: dioxin, a prevalent problem; nobody wanted dioxin; agent organe and Vietnam; what we know about and may learn about agent orange and Veterans' health; agent organe and birth defects; dioxin in Missouri; 2, 4, 5-T: the U.S.' disappearing herbicide; Seveso: high-level environmental exposure; the nitro explosion; industrial exposures to dioxin; company behavior in the face of dioxin exposures; dioxin and specific cancers; animal tests of dioxin toxicity; dioxin decions; the present and the future.

  20. Agent oriented programming

    NASA Technical Reports Server (NTRS)

    Shoham, Yoav

    1994-01-01

    The goal of our research is a methodology for creating robust software in distributed and dynamic environments. The approach taken is to endow software objects with explicit information about one another, to have them interact through a commitment mechanism, and to equip them with a speech-acty communication language. System-level applications include software interoperation and compositionality. A government application of specific interest is an infrastructure for coordination among multiple planners. Daily activity applications include personal software assistants, such as programmable email, scheduling, and new group agents. Research topics include definition of mental state of agents, design of agent languages as well as interpreters for those languages, and mechanisms for coordination within agent societies such as artificial social laws and conventions.

  1. Radioactive diagnostic agent

    SciTech Connect

    Shigematsu, A.; Aihara, M.; Matsuda, M.; Suzuki, A.; Tsuya, A.

    1984-02-07

    A radioactive diagnostic agent for renal cortex, adrenal cortex, myocardium, brain stem, spinal nerve, etc., which comprises as an essential component monoiodoacetic acid wherein the iodine atom is radioactive.

  2. Riot Control Agents

    MedlinePlus

    ... your clothing, rapidly wash your entire body with soap and water, and get medical care as quickly ... agent from your skin with large amounts of soap and water. Washing with soap and water will ...

  3. Agent amplified communication

    SciTech Connect

    Kautz, H.; Selman, B.; Milewski, A.

    1996-12-31

    We propose an agent-based framework for assisting and simplifying person-to-person communication for information gathering tasks. As an example, we focus on locating experts for any specified topic. In our approach, the informal person-to-person networks that exist within an organization are used to {open_quotes}referral chain{close_quotes} requests for expertise. User-agents help automate this process. The agents generate referrals by analyzing records of e-mail communication patterns. Simulation results show that the higher responsiveness of an agent-based system can be effectively traded for the higher accuracy of a completely manual approach. Furthermore, preliminary experience with a group of users on a prototype system has shown that useful automatic referrals can be found in practice. Our experience with actual users has also shown that privacy concerns are central to the successful deployment of personal agents: an advanced agent-based system will therefore need to reason about issues involving trust and authority.

  4. Encapsulation of zinc-rifampicin complex into transferrin-conjugated silver quantum-dots improves its antimycobacterial activity and stability and facilitates drug delivery into macrophages

    PubMed Central

    Pati, Rashmirekha; Sahu, Rojalin; Panda, Jagannath; Sonawane, Avinash

    2016-01-01

    In order to improve the chemotherapy of tuberculosis, there is an urgent need to enhance the efficacy of existing agents and also to develop more efficient drug delivery systems. Here, we synthesized a novel anti-TB drug complex consisting of zinc and rifampicin (Zn-RIF), and encapsulated it into transferrin-conjugated silver quantum-dots (Zn-RIF-Tf-QD) to improve delivery in macrophages. Successful synthesis of Zn-RIF and Zn-RIF-Tf-QD was confirmed by UV/Vis-spectroscopy, TEM, FTIR, photoluminescence, XRD, XPS, and NMR. The sizes of silver QDs and transferrin-conjugated QDs were found to be in the range of 5–20 nm. Activity assays showed that Zn-RIF-Tf-QD exhibited 10-fold higher antibacterial activity against Mycobacterium smegmatis and Mycobacterium bovis-BCG as compared to Zn-RIF, RIF and Zn. Immunofluorescence studies showed that Zn-RIF-Tf-QD-conjugates were actively endocytosed by macrophages and dendritic cells, but not by lung epithelial cells. Treatment with Zn-RIF-Tf-QD efficiently killed mycobacteria residing inside macrophages without exhibiting cytotoxicity and genotoxicity. Moreover, the conjugates remained stable for upto 48 h, were taken up into the late endosomal compartment of macrophages, and released the drug in a sustainable manner. Our data demonstrate that Zn-RIF-Tf-QDs have a great potential as anti-TB drugs. In addition, transferrin-conjugated QDs may constitute an effective drug delivery system for tuberculosis therapy. PMID:27113139

  5. Encapsulation of zinc-rifampicin complex into transferrin-conjugated silver quantum-dots improves its antimycobacterial activity and stability and facilitates drug delivery into macrophages.

    PubMed

    Pati, Rashmirekha; Sahu, Rojalin; Panda, Jagannath; Sonawane, Avinash

    2016-01-01

    In order to improve the chemotherapy of tuberculosis, there is an urgent need to enhance the efficacy of existing agents and also to develop more efficient drug delivery systems. Here, we synthesized a novel anti-TB drug complex consisting of zinc and rifampicin (Zn-RIF), and encapsulated it into transferrin-conjugated silver quantum-dots (Zn-RIF-Tf-QD) to improve delivery in macrophages. Successful synthesis of Zn-RIF and Zn-RIF-Tf-QD was confirmed by UV/Vis-spectroscopy, TEM, FTIR, photoluminescence, XRD, XPS, and NMR. The sizes of silver QDs and transferrin-conjugated QDs were found to be in the range of 5-20 nm. Activity assays showed that Zn-RIF-Tf-QD exhibited 10-fold higher antibacterial activity against Mycobacterium smegmatis and Mycobacterium bovis-BCG as compared to Zn-RIF, RIF and Zn. Immunofluorescence studies showed that Zn-RIF-Tf-QD-conjugates were actively endocytosed by macrophages and dendritic cells, but not by lung epithelial cells. Treatment with Zn-RIF-Tf-QD efficiently killed mycobacteria residing inside macrophages without exhibiting cytotoxicity and genotoxicity. Moreover, the conjugates remained stable for upto 48 h, were taken up into the late endosomal compartment of macrophages, and released the drug in a sustainable manner. Our data demonstrate that Zn-RIF-Tf-QDs have a great potential as anti-TB drugs. In addition, transferrin-conjugated QDs may constitute an effective drug delivery system for tuberculosis therapy. PMID:27113139

  6. Agent independent task planning

    NASA Technical Reports Server (NTRS)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  7. MpcAgent

    SciTech Connect

    Nutaro, James

    2013-11-29

    MpcAgent software is a module for the VolltronLite platform from PNNL that regulates the operation of rooftop air conditioning units in small to medium commercial buildings for the purpose of reducing peak power consumption. The MpcAgent accomplishes this by restricting the number of units that may operate simultaneously and using a model predictive control strategy to select which units to operate in each control period. The outcome of this control is effective control of the building air temperature at the user specified set point while avoiding expensive peak demand charges that result from running all HVAC units simultaneously.

  8. MpcAgent

    Energy Science and Technology Software Center (ESTSC)

    2013-11-29

    MpcAgent software is a module for the VolltronLite platform from PNNL that regulates the operation of rooftop air conditioning units in small to medium commercial buildings for the purpose of reducing peak power consumption. The MpcAgent accomplishes this by restricting the number of units that may operate simultaneously and using a model predictive control strategy to select which units to operate in each control period. The outcome of this control is effective control of themore » building air temperature at the user specified set point while avoiding expensive peak demand charges that result from running all HVAC units simultaneously.« less

  9. Gadofullerene MRI contrast agents.

    PubMed

    Bolskar, Robert D

    2008-04-01

    A promising new class of MRI contrast-enhancing agents with high relaxivities is based on gadolinium-containing metallofullerenes, which are also termed gadofullerenes. Detailed study of the water-proton relaxivity properties and intermolecular nanoclustering behavior of gadofullerene derivatives has revealed valuable information about their relaxivity mechanisms and given a deeper understanding of this new class of paramagnetic contrast agent. Here, the latest findings on water-solubilized gadofullerene materials and how these findings relate to their future applications in MRI are reviewed and discussed. PMID:18373426

  10. Agent Persuasion Mechanism of Acquaintance

    NASA Astrophysics Data System (ADS)

    Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

    Agent persuasion can improve negotiation efficiency in dynamic environment based on its initiative and autonomy, and etc., which is being affected much more by acquaintance. Classification of acquaintance on agent persuasion is illustrated, and the agent persuasion model of acquaintance is also illustrated. Then the concept of agent persuasion degree of acquaintance is given. Finally, relative interactive mechanism is elaborated.

  11. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 107.1620 Section 107.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance...

  12. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 108.1620 Section 108.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA...

  13. Can Subscription Agents Survive?

    ERIC Educational Resources Information Center

    Tuttle, Marcia

    1985-01-01

    With the saturation of traditional markets for their services, subscription agents have evolved from orders and invoices to serving customers by communicating with librarians and publishers and making automated and paper products available. Magazine fulfillment centers, publisher discounts, and electronic publishing will influence the subscription…

  14. Remote Agent Experiment

    NASA Technical Reports Server (NTRS)

    Benard, Doug; Dorais, Gregory A.; Gamble, Ed; Kanefsky, Bob; Kurien, James; Millar, William; Muscettola, Nicola; Nayak, Pandu; Rouquette, Nicolas; Rajan, Kanna; Norvig, Peter (Technical Monitor)

    2000-01-01

    Remote Agent (RA) is a model-based, reusable artificial intelligence (At) software system that enables goal-based spacecraft commanding and robust fault recovery. RA was flight validated during an experiment on board of DS1 between May 17th and May 21th, 1999.

  15. E-Learning Agents

    ERIC Educational Resources Information Center

    Gregg, Dawn G.

    2007-01-01

    Purpose: The purpose of this paper is to illustrate the advantages of using intelligent agents to facilitate the location and customization of appropriate e-learning resources and to foster collaboration in e-learning environments. Design/methodology/approach: This paper proposes an e-learning environment that can be used to provide customized…

  16. Battlefield agent collaboration

    NASA Astrophysics Data System (ADS)

    Budulas, Peter P.; Young, Stuart H.; Emmerman, Philip J.

    2001-09-01

    Small air and ground physical agents (robots) will be ubiquitous on the battlefield of the 21st century, principally to lower the exposure to harm of our ground forces in urban and open terrain scenarios. Teams of small collaborating physical agents conducting tasks such as Reconnaissance, Surveillance, and Target Acquisition (RSTA), intelligence, chemical and biological agent detection, logistics, decoy, sentry; and communications relay will have advanced sensors, communications, and mobility characteristics. It is anticipated that there will be many levels of individual and team collaboration between the soldier and robot, robot to robot, and robot to mother ship. This paper presents applications and infrastructure components that illustrate each of these levels. As an example, consider the application where a team of twenty small robots must rapidly explore and define a building complex. Local interactions and decisions require peer to peer collaboration. Global direction and information fusion warrant a central team control provided by a mother ship. The mother ship must effectively deliver/retrieve, service, and control these robots as well as fuse the information gathered by these highly mobile robot teams. Any level of collaboration requires robust communications, specifically a mobile ad hoc network. The application of fixed ground sensors and mobile robots is also included in this paper. This paper discusses on going research at the U.S. Army Research Laboratory that supports the development of multi-robot collaboration. This research includes battlefield visualization, intelligent software agents, adaptive communications, sensor and information fusion, and multi-modal human computer interaction.

  17. Mobility control agent

    SciTech Connect

    Argabright, P.A.; Phillips, B.L.; Rhudy, J.S.

    1983-05-17

    Polymer mobility control agents useful in supplemental oil recovery processes, which give improved reciprocal relative mobilities, are prepared by initiating the polymerization of a monomer containing a vinyl group with a catalyst comprising a persulfate and ferrous ammonium sulfate. The vinyl monomer is an acrylyl, a vinyl cyanide, a styryl and water soluble salts thereof.

  18. Distributed Agents for Autonomy

    NASA Astrophysics Data System (ADS)

    Blake, Rick; Amigoni, Francesco; Brambilla, Andrea; de la Rosa Steinz, Sonia; Lavagna, Michele; le Duc, Ian; Page, Jonathan; Page, Oliver; Steel, Robin; Wijnands, Quirien

    2010-08-01

    The Distributed Agents for Autonomy (DAFA) Study has been performed for ESA by SciSys UK Ltd, Vega GmbH and Politecnico di Milano. An analysis of past, present and future space missions has been conducted, structured around a set of three pre-defined mission scenarios: Formation Flying, Earth Observation and Planetary Exploration. This analysis led to the definition of a framework of use cases where the application of distributed autonomy seems necessary or appropriate, and a set of metrics that may be used to assess such deployments. Agent technology and architectures were extensively surveyed and the results used to elaborate each of the mission scenarios to the point where a software prototype could be constructed. Such a prototype was developed for a scenario based on the ExoMars mission and this has been used to highlight the advantages of a DAFA approach to the mission architecture.

  19. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    1998-07-21

    Bicyclo›2.2.2! octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo›2.2.1! heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  20. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    2000-02-08

    Bicyclo[2.2.2]octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo[2.2.1]heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  1. Surface polymerization agents

    SciTech Connect

    Taylor, C.; Wilkerson, C.

    1996-12-01

    This is the final report of a 1-year, Laboratory-Directed R&D project at LANL. A joint technical demonstration was proposed between US Army Missile Command (Redstone Arsenal) and LANL. Objective was to demonstrate that an unmanned vehicle or missile could be used as a platform to deliver a surface polymerization agent in such a manner as to obstruct the filters of an air-breathing mechanism, resulting in operational failure.

  2. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, M.P.; Mease, R.C.; Srivastava, S.C.

    1998-07-21

    Bicyclo[2.2.2] octane-2,3 diamine-N,N,N`,N`-tetraacetic acids (BODTA) and bicyclo[2.2.1] heptane-2,3 diamine-N,N,N`,N`-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  3. Perioperative allergy: uncommon agents.

    PubMed

    Caimmi, S; Caimmi, D; Cardinale, F; Indinnimeo, L; Crisafulli, G; Peroni, D G; Marseglia, G L

    2011-01-01

    Anesthesia may often be considered as a high-risk procedure and anaphylaxis remains a major cause of concern for anesthetists who routinely administer many potentially allergenic agents. Neuromuscular blocking agents, latex and antibiotics are the substances involved in most of the reported reactions. Besides these three agents, a wide variety of substances may cause an anaphylactic reaction during anesthesia. Basically all the administered drugs or substances may be potential causes of anaphylaxis. Among them, those reported the most in literature include hypnotics, opioids, local anesthetics, colloids, dye, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Iodinated Contrast Media (ICM), antiseptics, aprotinin, ethylene oxyde and formaldehyde, and protamine and heparins. No premedication can effectively prevent an allergic reaction and a systematic preoperative screening is not justified for all patients; nevertheless, an allergy specialist should evaluate those patients with a history of anesthesia-related allergy. Patients must be fully informed of investigation results, and advised to provide a detailed report prior to future anesthesia. PMID:22014927

  4. Liposome encapsulation of chelating agents

    DOEpatents

    Rahman, Yueh Erh

    1976-01-13

    A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

  5. Hydroxypyridonate and hydroxypyrimidinone chelating agents

    SciTech Connect

    Raymond, Kenneth N.; Doble, Daniel M.; Sunderland, Christopher J.; Thompson, Marlon

    2005-01-25

    The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

  6. Collaborating with Autonomous Agents

    NASA Technical Reports Server (NTRS)

    Trujillo, Anna C.; Cross, Charles D.; Fan, Henry; Hempley, Lucas E.; Motter, Mark A.; Neilan, James H.; Qualls, Garry D.; Rothhaar, Paul M.; Tran, Loc D.; Allen, B. Danette

    2015-01-01

    With the anticipated increase of small unmanned aircraft systems (sUAS) entering into the National Airspace System, it is highly likely that vehicle operators will be teaming with fleets of small autonomous vehicles. The small vehicles may consist of sUAS, which are 55 pounds or less that typically will y at altitudes 400 feet and below, and small ground vehicles typically operating in buildings or defined small campuses. Typically, the vehicle operators are not concerned with manual control of the vehicle; instead they are concerned with the overall mission. In order for this vision of high-level mission operators working with fleets of vehicles to come to fruition, many human factors related challenges must be investigated and solved. First, the interface between the human operator and the autonomous agent must be at a level that the operator needs and the agents can understand. This paper details the natural language human factors e orts that NASA Langley's Autonomy Incubator is focusing on. In particular these e orts focus on allowing the operator to interact with the system using speech and gestures rather than a mouse and keyboard. With this ability of the system to understand both speech and gestures, operators not familiar with the vehicle dynamics will be able to easily plan, initiate, and change missions using a language familiar to them rather than having to learn and converse in the vehicle's language. This will foster better teaming between the operator and the autonomous agent which will help lower workload, increase situation awareness, and improve performance of the system as a whole.

  7. Chemical warfare agents.

    PubMed

    Ganesan, K; Raza, S K; Vijayaraghavan, R

    2010-07-01

    Among the Weapons of Mass Destruction, chemical warfare (CW) is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided. PMID:21829312

  8. Pharmacologic agents targeting autophagy

    PubMed Central

    Vakifahmetoglu-Norberg, Helin; Xia, Hong-guang; Yuan, Junying

    2015-01-01

    Autophagy is an important intracellular catabolic mechanism critically involved in regulating tissue homeostasis. The implication of autophagy in human diseases and the need to understand its regulatory mechanisms in mammalian cells have stimulated research efforts that led to the development of high-throughput screening protocols and small-molecule modulators that can activate or inhibit autophagy. Herein we review the current landscape in the development of screening technology as well as the molecules and pharmacologic agents targeting the regulatory mechanisms of autophagy. We also evaluate the potential therapeutic application of these compounds in different human pathologies. PMID:25654545

  9. Chemical warfare agents

    PubMed Central

    Ganesan, K.; Raza, S. K.; Vijayaraghavan, R.

    2010-01-01

    Among the Weapons of Mass Destruction, chemical warfare (CW) is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided. PMID:21829312

  10. Antimycobacterial activity of lichen metabolites in vitro.

    PubMed

    Ingólfsdóttir, K; Chung, G A; Skúlason, V G; Gissurarson, S R; Vilhelmsdóttir, M

    1998-04-01

    Several compounds, whose structures represent the most common chemical classes of lichen metabolites, were screened for in vitro activity against Mycobacterium aurum, a non-pathogenic organism with a similar sensitivity profile to M. tuberculosis. Of the compounds tested, usnic acid from Cladonia arbuscula exhibited the highest activity with an MIC value of 32 microg/ml. Atranorin and lobaric acid, both isolated from Stereocaulon alpinum, salazinic acid from Parmelia saxatilis and protolichesterinic acid from Cetraria islandica all showed MIC values >/=125 microg/ml. PMID:9795033

  11. Cleaning agents and asthma.

    PubMed

    Quirce, S; Barranco, P

    2010-01-01

    Although cleaners represent a significant part of the working population worldwide, they remain a relatively understudied occupational group. Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. Cleaning workers are exposed to a large variety of cleaning products containing both irritants and sensitizers, as well as to common indoor allergens and pollutants. Thus, the onset or aggravation of asthma in this group could be related to an irritant-induced mechanism or to specific sensitization. The main sensitizers contained in cleaning products are disinfectants, quaternary ammonium compounds (such as benzalkonium chloride), amine compounds, and fragrances.The strongest airway irritants in cleaning products are bleach (sodium hypochlorite), hydrochloric acid, and alkaline agents (ammonia and sodium hydroxide), which are commonly mixed together. Exposure to the ingredients of cleaning products may give rise to both new-onset asthma, with or without a latency period, and work-exacerbated asthma. High-level exposure to irritants may induce reactive airways dysfunction syndrome. Cleaning workers may also have a greater relative risk of developing asthma due to prolonged low-to-moderate exposure to respiratory irritants. In addition, asthma-like symptoms without confirmed asthma are also common after exposure to cleaning agents. In many cleaners, airway symptoms induced by chemicals and odors cannot be explained by allergic or asthmatic reactions. These patients may have increased sensitivity to inhaled capsaicin, which is known to reflect sensory reactivity, and this condition is termed airway sensory hyperreactivity. PMID:21313993

  12. [New agents for hypercholesterolemia].

    PubMed

    Pintó, Xavier; García Gómez, María Carmen

    2016-02-19

    An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. PMID:25817449

  13. Holograms as Teaching Agents

    NASA Astrophysics Data System (ADS)

    Walker, Robin A.

    2013-02-01

    Hungarian physicist Dennis Gabor won the Pulitzer Prize for his 1947 introduction of basic holographic principles, but it was not until the invention of the laser in 1960 that research scientists, physicians, technologists and the general public began to seriously consider the interdisciplinary potentiality of holography. Questions around whether and when Three-Dimensional (3-D) images and systems would impact American entertainment and the arts would be answered before educators, instructional designers and students would discover how much Three-Dimensional Hologram Technology (3DHT) would affect teaching practices and learning environments. In the following International Symposium on Display Holograms (ISDH) poster presentation, the author features a traditional board game as well as a reflection hologram to illustrate conventional and evolving Three-Dimensional representations and technology for education. Using elements from the American children's toy Operation® (Hasbro, 2005) as well as a reflection hologram of a human brain (Ko, 1998), this poster design highlights the pedagogical effects of 3-D images, games and systems on learning science. As teaching agents, holograms can be considered substitutes for real objects, (human beings, organs, and animated characters) as well as agents (pedagogical, avatars, reflective) in various learning environments using many systems (direct, emergent, augmented reality) and electronic tools (cellphones, computers, tablets, television). In order to understand the particular importance of utilizing holography in school, clinical and public settings, the author identifies advantages and benefits of using 3-D images and technology as instructional tools.

  14. Learning models of intelligent agents

    SciTech Connect

    Carmel, D.; Markovitch, S.

    1996-12-31

    Agents that operate in a multi-agent system need an efficient strategy to handle their encounters with other agents involved. Searching for an optimal interactive strategy is a hard problem because it depends mostly on the behavior of the others. In this work, interaction among agents is represented as a repeated two-player game, where the agents` objective is to look for a strategy that maximizes their expected sum of rewards in the game. We assume that agents` strategies can be modeled as finite automata. A model-based approach is presented as a possible method for learning an effective interactive strategy. First, we describe how an agent should find an optimal strategy against a given model. Second, we present an unsupervised algorithm that infers a model of the opponent`s automaton from its input/output behavior. A set of experiments that show the potential merit of the algorithm is reported as well.

  15. Flexible, secure agent development framework

    DOEpatents

    Goldsmith; Steven Y.

    2009-04-07

    While an agent generator is generating an intelligent agent, it can also evaluate the data processing platform on which it is executing, in order to assess a risk factor associated with operation of the agent generator on the data processing platform. The agent generator can retrieve from a location external to the data processing platform an open site that is configurable by the user, and load the open site into an agent substrate, thereby creating a development agent with code development capabilities. While an intelligent agent is executing a functional program on a data processing platform, it can also evaluate the data processing platform to assess a risk factor associated with performing the data processing function on the data processing platform.

  16. New antifungal agents.

    PubMed

    Gupta, Aditya K; Tomas, Elizabeth

    2003-07-01

    Currently, use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. New formulations are being prepared to improve absorption and efficacy of some of these standard therapies. Various new antifungals have demonstrated therapeutic potential. These new agents may provide additional options for the treatment of superficial fungal infections and they may help to overcome the limitations of current treatments. Liposomal formulations of AmB have a broad spectrum of activity against invasive fungi, such as Candida spp., C. neoformans, and Aspergillus spp., but not dermatophyte fungi. The liposomal AmB is associated with significantly less toxicity and good rates of efficacy, which compare or exceed that of standard AmB. These factors may provide enough of an advantage to patients to overcome the increased costs of these formulations. Three new azole drugs have been developed, and may be of use in both systemic and superficial fungal infections. Voriconazole, ravuconazole, and posaconazole are triazoles, with broad-spectrum activity. Voriconazole has a high bioavailability, and has been used with success in immunocompromised patients with invasive fungal infections. Ravuconazole has shown efficacy in candidiasis in immunocompromised patients, and onychomycosis in healthy patients. Preliminary in vivo studies with posaconazole indicated potential use in a variety of invasive fungal infections including oropharyngeal candidiasis. Echinocandins and pneumocandins are a new class of antifungals, which act as fungal cell wall beta-(1,3)-D-glucan synthase enzyme complex inhibitors. Caspofungin (MK-0991) is the first of the echinocandins to receive Food and Drug Administration approval for patients with invasive aspergillosis not responding or intolerant to other antifungal therapies, and has been effective in patients with oropharyngeal and esophageal candidiasis. Standardization of MIC value determination has improved the

  17. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  18. Hepatocytes as Immunological Agents.

    PubMed

    Crispe, Ian N

    2016-01-01

    Hepatocytes are targeted for infection by a number of major human pathogens, including hepatitis B virus, hepatitis C virus, and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses, including ischemia, physical trauma, and sepsis. Hepatocytes express a variety of innate immune receptors and, when challenged with pathogen- or damage-associated molecular patterns, can deliver cell-autonomous innate immune responses that may result in host defense or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias toward immune tolerance. PMID:26685314

  19. Agent Assignment for Process Management: Pattern Based Agent Performance Evaluation

    NASA Astrophysics Data System (ADS)

    Jablonski, Stefan; Talib, Ramzan

    In almost all workflow management system the role concept is determined once at the introduction of workflow application and is not reevaluated to observe how successfully certain processes are performed by the authorized agents. This paper describes an approach which evaluates how agents are working successfully and feed this information back for future agent assignment to achieve maximum business benefit for the enterprise. The approach is called Pattern based Agent Performance Evaluation (PAPE) and is based on machine learning technique combined with post processing technique. We report on the result of our experiments and discuss issues and improvement of our approach.

  20. Agent-based enterprise integration

    SciTech Connect

    N. M. Berry; C. M. Pancerella

    1998-12-01

    The authors are developing and deploying software agents in an enterprise information architecture such that the agents manage enterprise resources and facilitate user interaction with these resources. The enterprise agents are built on top of a robust software architecture for data exchange and tool integration across heterogeneous hardware and software. The resulting distributed multi-agent system serves as a method of enhancing enterprises in the following ways: providing users with knowledge about enterprise resources and applications; accessing the dynamically changing enterprise; locating enterprise applications and services; and improving search capabilities for applications and data. Furthermore, agents can access non-agents (i.e., databases and tools) through the enterprise framework. The ultimate target of the effort is the user; they are attempting to increase user productivity in the enterprise. This paper describes their design and early implementation and discusses the planned future work.

  1. Collaborating Fuzzy Reinforcement Learning Agents

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1997-01-01

    Earlier, we introduced GARIC-Q, a new method for doing incremental Dynamic Programming using a society of intelligent agents which are controlled at the top level by Fuzzy Relearning and at the local level, each agent learns and operates based on ANTARCTIC, a technique for fuzzy reinforcement learning. In this paper, we show that it is possible for these agents to compete in order to affect the selected control policy but at the same time, they can collaborate while investigating the state space. In this model, the evaluator or the critic learns by observing all the agents behaviors but the control policy changes only based on the behavior of the winning agent also known as the super agent.

  2. New agents for prostate cancer.

    PubMed

    Agarwal, N; Di Lorenzo, G; Sonpavde, G; Bellmunt, J

    2014-09-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid

  3. Broad-spectrum antiviral agents

    PubMed Central

    Zhu, Jun-Da; Meng, Wen; Wang, Xiao-Jia; Wang, Hwa-Chain R.

    2015-01-01

    Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents. PMID:26052325

  4. The Agent of Change: The Agent of Conflict.

    ERIC Educational Resources Information Center

    Hatfield, C. R., Jr.

    This speech examines the role of change agents in third world societies and indicates that the change agent must, to some extent, manipulate the social situation, even if his view of society is a more optimistic one than he finds in reality. If he considers strains and stresses to be the lubricants of change, then his focus on conflict as a…

  5. Incorporating BDI Agents into Human-Agent Decision Making Research

    NASA Astrophysics Data System (ADS)

    Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

    Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

  6. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  7. TACtic- A Multi Behavioral Agent for Trading Agent Competition

    NASA Astrophysics Data System (ADS)

    Khosravi, Hassan; Shiri, Mohammad E.; Khosravi, Hamid; Iranmanesh, Ehsan; Davoodi, Alireza

    Software agents are increasingly being used to represent humans in online auctions. Such agents have the advantages of being able to systematically monitor a wide variety of auctions and then make rapid decisions about what bids to place in what auctions. They can do this continuously and repetitively without losing concentration. To provide a means of evaluating and comparing (benchmarking) research methods in this area the trading agent competition (TAC) was established. This paper describes the design, of TACtic. Our agent uses multi behavioral techniques at the heart of its decision making to make bidding decisions in the face of uncertainty, to make predictions about the likely outcomes of auctions, and to alter the agent's bidding strategy in response to the prevailing market conditions.

  8. Gelled Anti-icing Agents

    NASA Technical Reports Server (NTRS)

    Markles, O. F.; Sperber, H. H.

    1983-01-01

    Pectin added to antifreeze/water mixture. Formulations include water with dimethyl sulfoxide (DMSO) as deicer and pectin as gel former. Without gelling agent, deicer runs off vertical surfaces. Without pectin solution will completely evaporate in far less time. Agents developed have wide potential for ice prevention on runways, highways, bridges and sidewalks.

  9. Agent-Based Literacy Theory

    ERIC Educational Resources Information Center

    McEneaney, John E.

    2006-01-01

    The purpose of this theoretical essay is to explore the limits of traditional conceptualizations of reader and text and to propose a more general theory based on the concept of a literacy agent. The proposed theoretical perspective subsumes concepts from traditional theory and aims to account for literacy online. The agent-based literacy theory…

  10. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs. PMID:18991707

  11. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  12. Markov Tracking for Agent Coordination

    NASA Technical Reports Server (NTRS)

    Washington, Richard; Lau, Sonie (Technical Monitor)

    1998-01-01

    Partially observable Markov decision processes (POMDPs) axe an attractive representation for representing agent behavior, since they capture uncertainty in both the agent's state and its actions. However, finding an optimal policy for POMDPs in general is computationally difficult. In this paper we present Markov Tracking, a restricted problem of coordinating actions with an agent or process represented as a POMDP Because the actions coordinate with the agent rather than influence its behavior, the optimal solution to this problem can be computed locally and quickly. We also demonstrate the use of the technique on sequential POMDPs, which can be used to model a behavior that follows a linear, acyclic trajectory through a series of states. By imposing a "windowing" restriction that restricts the number of possible alternatives considered at any moment to a fixed size, a coordinating action can be calculated in constant time, making this amenable to coordination with complex agents.

  13. Knowledge focus via software agents

    NASA Astrophysics Data System (ADS)

    Henager, Donald E.

    2001-09-01

    The essence of military Command and Control (C2) is making knowledge intensive decisions in a limited amount of time using uncertain, incorrect, or outdated information. It is essential to provide tools to decision-makers that provide: * Management of friendly forces by treating the "friendly resources as a system". * Rapid assessment of effects of military actions againt the "enemy as a system". * Assessment of how an enemy should, can, and could react to friendly military activities. Software agents in the form of mission agents, target agents, maintenance agents, and logistics agents can meet this information challenge. The role of each agent is to know all the details about its assigned mission, target, maintenance, or logistics entity. The Mission Agent would fight for mission resources based on the mission priority and analyze the effect that a proposed mission's results would have on the enemy. The Target Agent (TA) communicates with other targets to determine its role in the system of targets. A system of TAs would be able to inform a planner or analyst of the status of a system of targets, the effect of that status, adn the effect of attacks on that system. The system of TAs would also be able to analyze possible enemy reactions to attack by determining ways to minimize the effect of attack, such as rerouting traffic or using deception. The Maintenance Agent would scheudle maintenance events and notify the maintenance unit. The Logistics Agent would manage shipment and delivery of supplies to maintain appropriate levels of weapons, fuel and spare parts. The central idea underlying this case of software agents is knowledge focus. Software agents are createad automatically to focus their attention on individual real-world entities (e.g., missions, targets) and view the world from that entities perspective. The agent autonomously monitors the entity, identifies problems/opportunities, formulates solutions, and informs the decision-maker. The agent must be

  14. Agent Communications using Distributed Metaobjects

    SciTech Connect

    Goldsmith, Steven Y.; Spires, Shannon V.

    1999-06-10

    There are currently two proposed standards for agent communication languages, namely, KQML (Finin, Lobrou, and Mayfield 1994) and the FIPA ACL. Neither standard has yet achieved primacy, and neither has been evaluated extensively in an open environment such as the Internet. It seems prudent therefore to design a general-purpose agent communications facility for new agent architectures that is flexible yet provides an architecture that accepts many different specializations. In this paper we exhibit the salient features of an agent communications architecture based on distributed metaobjects. This architecture captures design commitments at a metaobject level, leaving the base-level design and implementation up to the agent developer. The scope of the metamodel is broad enough to accommodate many different communication protocols, interaction protocols, and knowledge sharing regimes through extensions to the metaobject framework. We conclude that with a powerful distributed object substrate that supports metaobject communications, a general framework can be developed that will effectively enable different approaches to agent communications in the same agent system. We have implemented a KQML-based communications protocol and have several special-purpose interaction protocols under development.

  15. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, Paul H.; Brainard, James R.; Jarvinen, Gordon D.; Ryan, Robert R.

    1997-01-01

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC.sub.16 H.sub.14 N.sub.6. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques.

  16. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, P.H.; Brainard, J.R.; Jarvinen, G.D.; Ryan, R.R.

    1997-12-30

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC{sub 16}H{sub 14}N{sub 6}. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques. 10 figs.

  17. Introducing Infectious Agents and Cancer

    PubMed Central

    Buonaguro, Franco M; Lewis, George K; Pelicci, PierGiuseppe

    2006-01-01

    Infectious Agents and Cancer is a new open access, peer-reviewed, online journal, which encompasses all aspects of basic, clinical and translational research that provide an insight into the association between chronic infections and cancer. PMID:23509916

  18. Diamine curing agents for polyurethanes

    NASA Technical Reports Server (NTRS)

    Bell, V. L.; St. Clair, T. L.

    1975-01-01

    Three aromatic diamines have properties that make them promising candidates as curing agents for converting isocyanates to polyurethanes with higher adhesive strengths, higher softening temperatures, better toughness, and improved abrasion resistance.

  19. Triggered pore-forming agents

    DOEpatents

    Bayley, Hagan; Walker, Barbara J.; Chang, Chung-yu; Niblack, Brett; Panchal, Rekha

    1998-01-01

    An inactive pore-forming agent which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell.

  20. Tissue Penetration of Antifungal Agents

    PubMed Central

    Felton, Timothy; Troke, Peter F.

    2014-01-01

    SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137

  1. AL Amyloidosis and Agent Orange

    MedlinePlus

    ... for survivors' benefits . Research on AL amyloidosis and herbicides The Health and Medicine Division (formally known as ... to the compounds of interest found in the herbicide Agent Orange and AL amyloidosis." VA made a ...

  2. Agent-based forward analysis

    SciTech Connect

    Kerekes, Ryan A.; Jiao, Yu; Shankar, Mallikarjun; Potok, Thomas E.; Lusk, Rick M.

    2008-01-01

    We propose software agent-based "forward analysis" for efficient information retrieval in a network of sensing devices. In our approach, processing is pushed to the data at the edge of the network via intelligent software agents rather than pulling data to a central facility for processing. The agents are deployed with a specific query and perform varying levels of analysis of the data, communicating with each other and sending only relevant information back across the network. We demonstrate our concept in the context of face recognition using a wireless test bed comprised of PDA cell phones and laptops. We show that agent-based forward analysis can provide a significant increase in retrieval speed while decreasing bandwidth usage and information overload at the central facility. n

  3. Launch Commit Criteria Monitoring Agent

    NASA Technical Reports Server (NTRS)

    Semmel, Glenn S.; Davis, Steven R.; Leucht, Kurt W.; Rowe, Dan A.; Kelly, Andrew O.; Boeloeni, Ladislau

    2005-01-01

    The Spaceport Processing Systems Branch at NASA Kennedy Space Center has developed and deployed a software agent to monitor the Space Shuttle's ground processing telemetry stream. The application, the Launch Commit Criteria Monitoring Agent, increases situational awareness for system and hardware engineers during Shuttle launch countdown. The agent provides autonomous monitoring of the telemetry stream, automatically alerts system engineers when predefined criteria have been met, identifies limit warnings and violations of launch commit criteria, aids Shuttle engineers through troubleshooting procedures, and provides additional insight to verify appropriate troubleshooting of problems by contractors. The agent has successfully detected launch commit criteria warnings and violations on a simulated playback data stream. Efficiency and safety are improved through increased automation.

  4. What makes virtual agents believable?

    NASA Astrophysics Data System (ADS)

    Bogdanovych, Anton; Trescak, Tomas; Simoff, Simeon

    2016-01-01

    In this paper we investigate the concept of believability and make an attempt to isolate individual characteristics (features) that contribute to making virtual characters believable. As the result of this investigation we have produced a formalisation of believability and based on this formalisation built a computational framework focused on simulation of believable virtual agents that possess the identified features. In order to test whether the identified features are, in fact, responsible for agents being perceived as more believable, we have conducted a user study. In this study we tested user reactions towards the virtual characters that were created for a simulation of aboriginal inhabitants of a particular area of Sydney, Australia in 1770 A.D. The participants of our user study were exposed to short simulated scenes, in which virtual agents performed some behaviour in two different ways (while possessing a certain aspect of believability vs. not possessing it). The results of the study indicate that virtual agents that appear resource bounded, are aware of their environment, own interaction capabilities and their state in the world, agents that can adapt to changes in the environment and exist in correct social context are those that are being perceived as more believable. Further in the paper we discuss these and other believability features and provide a quantitative analysis of the level of contribution for each such feature to the overall perceived believability of a virtual agent.

  5. 46 CFR Sec. 2 - General Agents' authority.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE EMERGENCY REPAIRS IN FOREIGN PORTS Sec. 2 General Agents' authority. The General Agents are hereby delegated authority to undertake for the account of the...

  6. A amphoteric copolymer profile modification agent

    SciTech Connect

    Wang HongGuan; Yu LianCheng; Tian HongKun

    1995-11-01

    This report provides a new gel profile modification agent prepared by an amphoteric copolymer (FT-213) and a novel crosslinking agent (BY), and introduces the preparations of the amphoteric polymer, the crosslinking agent and the profile modification agent, the action mechanism, the test conditions and the evaluations of the performance of the agent. The 45 well treatments in oilfields demonstrate that the agent can be prepared conveniently, the agent has better compatibility and application performances, and the treatment life is longer with the use of the agent. 80,000 tons incremental oil and 60,000 m{sup 3} decreasing water production have been achieved.

  7. A multi-agent architecture for geosimulation of moving agents

    NASA Astrophysics Data System (ADS)

    Vahidnia, Mohammad H.; Alesheikh, Ali A.; Alavipanah, Seyed Kazem

    2015-10-01

    In this paper, a novel architecture is proposed in which an axiomatic derivation system in the form of first-order logic facilitates declarative explanation and spatial reasoning. Simulation of environmental perception and interaction between autonomous agents is designed with a geographic belief-desire-intention and a request-inform-query model. The architecture has a complementary quantitative component that supports collaborative planning based on the concept of equilibrium and game theory. This new architecture presents a departure from current best practices geographic agent-based modelling. Implementation tasks are discussed in some detail, as well as scenarios for fleet management and disaster management.

  8. Next Generation Remote Agent Planner

    NASA Technical Reports Server (NTRS)

    Jonsson, Ari K.; Muscettola, Nicola; Morris, Paul H.; Rajan, Kanna

    1999-01-01

    In May 1999, as part of a unique technology validation experiment onboard the Deep Space One spacecraft, the Remote Agent became the first complete autonomous spacecraft control architecture to run as flight software onboard an active spacecraft. As one of the three components of the architecture, the Remote Agent Planner had the task of laying out the course of action to be taken, which included activities such as turning, thrusting, data gathering, and communicating. Building on the successful approach developed for the Remote Agent Planner, the Next Generation Remote Agent Planner is a completely redesigned and reimplemented version of the planner. The new system provides all the key capabilities of the original planner, while adding functionality, improving performance and providing a modular and extendible implementation. The goal of this ongoing project is to develop a system that provides both a basis for future applications and a framework for further research in the area of autonomous planning for spacecraft. In this article, we present an introductory overview of the Next Generation Remote Agent Planner. We present a new and simplified definition of the planning problem, describe the basics of the planning process, lay out the new system design and examine the functionality of the core reasoning module.

  9. Optical recognition of biological agents

    NASA Astrophysics Data System (ADS)

    Baumgart, Chris W.; Linder, Kim Dalton; Trujillo, Josh J.

    2008-04-01

    Differentiation between particulate biological agents and non-biological agents is typically performed via a time-consuming "wet chemistry" process or through the use of fluorescent and spectroscopic analysis. However, while these methods can provide definitive recognition of biological agents, many of them have to be performed in a laboratory environment, or are difficult to implement in the field. Optical recognition techniques offer an additional recognition approach that can provide rapid analysis of a material in-situ to identify those materials that may be biological in nature. One possible application is to use these techniques to "screen" suspicious materials and to identify those that are potentially biological in nature. Suspicious materials identified by this screening process can then be analyzed in greater detail using the other, more definitive (but time consuming) analysis techniques. This presentation will describe the results of a feasibility study to determine whether optical pattern recognition techniques can be used to differentiate biological related materials from non-biological materials. As part of this study, feature extraction algorithms were developed utilizing multiple contrast and texture based features to characterize the macroscopic properties of different materials. In addition, several pattern recognition approaches using these features were tested including cluster analysis and neural networks. Test materials included biological agent simulants, biological agent related materials, and non-biological materials (suspicious white powders). Results of a series of feasibility tests will be presented along with a discussion of the potential field applications for these techniques.

  10. Inhalational exposure to nerve agents.

    PubMed

    Niven, Alexander S; Roop, Stuart A

    2004-03-01

    The respiratory system plays a major role in the pathogenesis of nerve agent toxicity. It is the major route of entry and absorption of nerve agent vapor, and respiratory failure is the most common cause of death follow-ing exposure. Respiratory symptoms are mediated by chemical irritation,muscarinic and nicotinic receptor overstimulation, and central nervous system effects. Recent attacks have demonstrated that most patients with an isolated vapor exposure developed respiratory symptoms almost immediately. Most patients had only mild and transient respiratory effects, and those that did develop significant respiratory compromise did so rapidly. These observations have significant ramifications on triage of patients in a mass-casualty situation, because patients with mild-to-moderate exposure to nerve agent vapor alone do not require decontamination and are less likely to develop progressive symptoms following initial antidote therapy. Limited data do not demonstrate significant long-term respiratory effects following nerve agent exposure and treatment. Provisions for effective respiratory protection against nerve agents is a vital consideration in any emergency preparedness or health care response plan against a chemical attack. PMID:15062227

  11. Investigational antimicrobial agents of 2013.

    PubMed

    Pucci, Michael J; Bush, Karen

    2013-10-01

    New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  12. Investigational Antimicrobial Agents of 2013

    PubMed Central

    Pucci, Michael J.

    2013-01-01

    SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  13. Environmentally responsive MRI contrast agents

    PubMed Central

    Davies, Gemma-Louise; Kramberger, Iris; Davis, Jason J.

    2015-01-01

    Biomedical imaging techniques can provide a vast amount of anatomical information, enabling diagnosis and the monitoring of disease and treatment profile. MRI uniquely offers convenient, non-invasive, high resolution tomographic imaging. A considerable amount of effort has been invested, across several decades, in the design of non toxic paramagnetic contrast agents capable of enhancing positive MRI signal contrast. Recently, focus has shifted towards the development of agents capable of specifically reporting on their local biochemical environment, where a switch in image contrast is triggered by a specific stimulus/biochemical variable. Such an ability would not only strengthen diagnosis but also provide unique disease-specific biochemical insight. This feature article focuses on recent progress in the development of MRI contrast switching with molecular, macromolecular and nanoparticle-based agents. PMID:24040650

  14. Polycatechol Nanoparticle MRI Contrast Agents.

    PubMed

    Li, Yiwen; Huang, Yuran; Wang, Zhao; Carniato, Fabio; Xie, Yijun; Patterson, Joseph P; Thompson, Matthew P; Andolina, Christopher M; Ditri, Treffly B; Millstone, Jill E; Figueroa, Joshua S; Rinehart, Jeffrey D; Scadeng, Miriam; Botta, Mauro; Gianneschi, Nathan C

    2016-02-01

    Amphiphilic triblock copolymers containing Fe(III) -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles (SMN and CMN, respectively) are described as new T1-weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape-dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN. These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement. PMID:26681255

  15. Chemical warfare. Nerve agent poisoning.

    PubMed

    Holstege, C P; Kirk, M; Sidell, F R

    1997-10-01

    The threat of civilian and military casualties from nerve agent exposure has become a greater concern over the past decade. After rapidly assessing that a nerve agent attack has occurred, emphasis must be placed on decontamination and protection of both rescuers and medical personnel from exposure. The medical system can become rapidly overwhelmed and strong emotional reactions can confuse the clinical picture. Initially, care should first be focused on supportive care, with emphasis toward aggressive airway maintenance and decontamination. Atropine should be titrated, with the goal of therapy being drying of secretions and the resolution of bronchoconstriction and bradycardia. Early administration of pralidoxime chloride maximizes antidotal efficacy. Benzodiazepines, in addition to atropine, should be administered if seizures develop. Early, aggressive medical therapy is the key to prevention of the morbidity and mortality associated with nerve agent poisoning. PMID:9330846

  16. Agent review phase one report.

    SciTech Connect

    Zubelewicz, Alex Tadeusz; Davis, Christopher Edward; Bauer, Travis LaDell

    2009-12-01

    This report summarizes the findings for phase one of the agent review and discusses the review methods and results. The phase one review identified a short list of agent systems that would prove most useful in the service architecture of an information management, analysis, and retrieval system. Reviewers evaluated open-source and commercial multi-agent systems and scored them based upon viability, uniqueness, ease of development, ease of deployment, and ease of integration with other products. Based on these criteria, reviewers identified the ten most appropriate systems. The report also mentions several systems that reviewers deemed noteworthy for the ideas they implement, even if those systems are not the best choices for information management purposes.

  17. Haloprogin: a Topical Antifungal Agent

    PubMed Central

    Harrison, E. F.; Zwadyk, P.; Bequette, R. J.; Hamlow, E. E.; Tavormina, P. A.; Zygmunt, W. A.

    1970-01-01

    Haloprogin was shown to be a highly effective agent for the treatment of experimentally induced topical mycotic infections in guinea pigs. Its in vitro spectrum of activity also includes yeasts, yeastlike fungi (Candida species), and certain gram-positive bacteria. The in vitro and in vivo antifungal activity of haloprogin against dermatophytes was equal to that observed with tolnaftate. The striking differences between the two agents were the marked antimonilial and selective antibacterial activities shown by haloprogin, contrasted with the negligible activities found with tolnaftate. Addition of serum decreased the in vitro antifungal activity of haloprogin to a greater extent than that of tolnaftate; however, diminished antifungal activity was not observed when haloprogin was applied topically to experimental dermatophytic infections. Based on its broad spectrum of antimicrobial activity, haloprogin may prove to be a superior topical agent in the treatment of dermatophytic and monilial infections in man. PMID:5422306

  18. Thyroid dysfunction from antineoplastic agents.

    PubMed

    Hamnvik, Ole-Petter Riksfjord; Larsen, P Reed; Marqusee, Ellen

    2011-11-01

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

  19. Erythropoietic agents and the elderly.

    PubMed

    Agarwal, Neeraj; Prchal, Josef T

    2008-10-01

    Erythropoietin (Epo) is a peptide hormone that stimulates erythropoiesis. There are several agents in clinical use and in development that either act as ligands for the cell surface receptors of Epo or promote Epo production, which stimulates erythropoiesis. These are known as erythropoietic agents. The agents already in use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents under active investigation include continuous erythropoietin receptor activator (CERA) or proline hydroxylase inhibitors that increase hypoxia-inducible factor-1 (HIF-1), thereby stimulating Epo production and iron availability and supply. Erythropoietic agents have been shown to promote neuronal regeneration and to decrease post-stroke infarct size in mouse models. They have also been reported to shorten survival when used to treat anemia in many cancer patients and to increase thromboembolism. In contrast, rapid decrease of Epo levels as observed in astronauts and high-altitude dwellers upon rapid descent to sea level leads to the decrease of erythroid mass, a phenomenon known as "neocytolysis." The relative decrease in the serum Epo level is known to occur in some subjects with otherwise unexplained anemia of aging. Anemia by itself is a predictor of poor physical function in the elderly and is a significant economic burden on society. One out of every five persons in the United States will be elderly by 2050. Erythropoietic agents, by preventing and treating otherwise unexplained anemias of the elderly and anemia associated with other disease conditions of the elderly, have the potential to improve the functional capacity and to decrease the morbidity and mortality in the elderly, thereby alleviating the overall burden of medical care in society. PMID:18809098

  20. Erythropoietic Agents and the Elderly

    PubMed Central

    Agarwal, Neeraj; Prchal, Josef T.

    2008-01-01

    Erythropoietin is a peptide hormone that stimulates erythropoiesis. There are several agents in clinical use and in development, which either act as ligands for the cell surface receptors of erythropoietin or promote erythropoietin production that stimulates erythropoiesis. These are known as erythropoietic agents. The agents already in use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents stimulating erythropoiesis (such as continuous erythropoietin receptor activator (CERA) or proline hydroxylase inhibitors that increase HIF-1 thereby stimulating erythropoietin production and iron availability and supply) are under active investigation. Erythropoietic agents have been shown to promote neuronal regeneration and to decrease post-stroke infarct size in mouse models. They have also been reported to shorten survival when used to treat anemia in many cancer patients and to increase thromboembolism. In contrast, rapid decrease of erythropoietin levels as observed in astronauts and high-altitude dwellers upon rapid descent to sea level leads to the decrease of erythroid mass, a phenomenon known as neocytolysis. The relative decrease in the serum erythropoietin level is known to occur in some subjects with otherwise unexplained anemia of aging. Anemia by itself is a predictor of poor physical function in the elderly and is a significant economic burden on society. One out of every five persons in the United States will be elderly by 2050. Erythropoietic agents, by preventing and treating otherwise unexplained anemias of the elderly and anemia associated with other disease conditions of the elderly, have the potential to improve the functional capacity and to decrease the morbidity and mortality in the elderly, thereby alleviating the overall burden of medical care in society. PMID:18809098

  1. Autonomous sensor manager agents (ASMA)

    NASA Astrophysics Data System (ADS)

    Osadciw, Lisa A.

    2004-04-01

    Autonomous sensor manager agents are presented as an algorithm to perform sensor management within a multisensor fusion network. The design of the hybrid ant system/particle swarm agents is described in detail with some insight into their performance. Although the algorithm is designed for the general sensor management problem, a simulation example involving 2 radar systems is presented. Algorithmic parameters are determined by the size of the region covered by the sensor network, the number of sensors, and the number of parameters to be selected. With straight forward modifications, this algorithm can be adapted for most sensor management problems.

  2. An overview of inotropic agents.

    PubMed

    Vroom, Margreeth B

    2006-09-01

    The use of inotropic agents has been surrounded by many controversies. Recent guidelines for the treatment of patients with chronic and acute heart failure have elucidated some of the issues, but many remain. As a result, a substantial variability in the use of agents between institutions and caregivers remains, which mainly results from the lack of uniform data in the literature. Prospective randomized trials with a long-term follow-up and sufficient power are clearly needed, and a number of trials are currently in progress. PMID:16959760

  3. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome and... 7 Agriculture 3 2013-01-01 2013-01-01 false Flavoring agents. 58.629 Section 58.629 Agriculture.... Flavoring agents shall be one or more of those approved in § 58.605....

  4. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome and... 7 Agriculture 3 2012-01-01 2012-01-01 false Flavoring agents. 58.629 Section 58.629 Agriculture.... Flavoring agents shall be one or more of those approved in § 58.605....

  5. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome and... 7 Agriculture 3 2014-01-01 2014-01-01 false Flavoring agents. 58.629 Section 58.629 Agriculture.... Flavoring agents shall be one or more of those approved in § 58.605....

  6. Why Do Extension Agents Resign?

    ERIC Educational Resources Information Center

    Manton, Linda Nunes; van Es, J. C.

    1985-01-01

    Past and current Illinois extension agents were surveyed via mail questionnaires as to reasons for staying or leaving extension programs. Reasons for leaving included family changes, family moves, opportunity to advance, better salary/benefits, dissatisfaction with administration, and too much time away from family. (CT)

  7. Foodborne illness and microbial agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foodborne illnesses result from the consumption of food containing microbial agents such as bacteria, viruses, parasites or food contaminated by poisonous chemicals or bio-toxins. Pathogen proliferation is due to nutrient composition of foods, which are capable of supporting the growth of microorgan...

  8. Superintendents: The Key Influence Agents.

    ERIC Educational Resources Information Center

    Powell, Randy

    1990-01-01

    By the nature of their positions in schools, administrators are either influence agents or targets. Based on personal interviews with 140 Oregon administrators and a survey of 319 administrators around the state, this article highlights administrators' comments about their administrative influence and about constraints on their influence.…

  9. Triggered pore-forming agents

    DOEpatents

    Bayley, H.; Walker, B.J.; Chang, C.Y.; Niblack, B.; Panchal, R.

    1998-07-07

    An inactive pore-forming agent is revealed which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell. 30 figs.

  10. Nucleotide cleaving agents and method

    DOEpatents

    Que, Jr., Lawrence; Hanson, Richard S.; Schnaith, Leah M. T.

    2000-01-01

    The present invention provides a unique series of nucleotide cleaving agents and a method for cleaving a nucleotide sequence, whether single-stranded or double-stranded DNA or RNA, using and a cationic metal complex having at least one polydentate ligand to cleave the nucleotide sequence phosphate backbone to yield a hydroxyl end and a phosphate end.

  11. SEM: A Cultural Change Agent

    ERIC Educational Resources Information Center

    Barnes, Bradley; Bourke, Brian

    2015-01-01

    The authors advance the concept that institutional culture is a purposeful framework by which to view SEM's utility, particularly as a cultural change agent. Through the connection of seemingly independent functions of performance and behavior, implications emerge that deepen the understanding of the influence of culture on performance outcomes…

  12. Direct Vasodilators and Sympatholytic Agents.

    PubMed

    McComb, Meghan N; Chao, James Y; Ng, Tien M H

    2016-01-01

    Direct vasodilators and sympatholytic agents were some of the first antihypertensive medications discovered and utilized in the past century. However, side effect profiles and the advent of newer antihypertensive drug classes have reduced the use of these agents in recent decades. Outcome data and large randomized trials supporting the efficacy of these medications are limited; however, in general the blood pressure-lowering effect of these agents has repeatedly been shown to be comparable to other more contemporary drug classes. Nevertheless, a landmark hypertension trial found a negative outcome with a doxazosin-based regimen compared to a chlorthalidone-based regimen, leading to the removal of α-1 adrenergic receptor blockers as first-line monotherapy from the hypertension guidelines. In contemporary practice, direct vasodilators and sympatholytic agents, particularly hydralazine and clonidine, are often utilized in refractory hypertension. Hydralazine and minoxidil may also be useful alternatives for patients with renal dysfunction, and both hydralazine and methyldopa are considered first line for the treatment of hypertension in pregnancy. Hydralazine has also found widespread use for the treatment of systolic heart failure in combination with isosorbide dinitrate (ISDN). The data to support use of this combination in African Americans with heart failure are particularly robust. Hydralazine with ISDN may also serve as an alternative for patients with an intolerance to angiotensin antagonists. Given these niche indications, vasodilators and sympatholytics are still useful in clinical practice; therefore, it is prudent to understand the existing data regarding efficacy and the safe use of these medications. PMID:26033778

  13. Improving agents using reliable communication

    NASA Astrophysics Data System (ADS)

    Zheng, Jinbin

    2013-10-01

    Recent advances in introspective modalities and linear time symmetries do not necessarily obviate the need for web browsers [1]. In our research, we disprove the exploration of agents, which embodies the appropriate principles of electrical engineering. Here we demonstrate that even though semaphores and XML [1] are mostly incompatible, randomized algorithms and write-back caches are mostly incompatible.

  14. Echographic studies of osmotic agents.

    PubMed

    Vucicevic, Z M; Tark, E; Ahmad, S

    1979-09-01

    The effectiveness of osmotic agents, acetazolamide (Diamox), urea, glycerol, and mannitol, and massages (5 and 10 minutes) for inducing hypotony in rabbit eyes was evaluated by ultrasonography. Mannitol was found to have the greatest hypotonic effect followed closely by urea and glycerol, then acetazolamide. The difference between the 5 and 10 minute massages was negligible. PMID:122221

  15. An Autonomous Spacecraft Agent Prototype

    NASA Technical Reports Server (NTRS)

    Pell, Barney; Bernard, Douglas E.; Chien, Steve A.; Gat, Erann; Muscettola, Nicola; Nayak, P. Pandurang; Wagner, Michael D.; Williams, Brian C.

    1997-01-01

    This paper describes the New Millennium Remote Agent (NMRA) architecture for autonomous spacecraft control systems. This architecture integrates traditional real-time monitoring and control with constraint-based planning and scheduling, robust multi-threaded execution, and model-based diagnosis and reconfiguration.

  16. Limonene and tetrahydrofurfurly alcohol cleaning agent

    SciTech Connect

    Bohnert, George W.; Carter, Richard D.; Hand, Thomas E.; Powers, Michael T.

    1997-10-21

    The present invention is a tetrahydrofurfuryl alcohol and limonene cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  17. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    DOEpatents

    Bohnert, George W.; Carter, Richard D.; Hand, Thomas E.; Powers, Michael T.

    1996-05-07

    The present invention is a tetrahydrofurfuryl alcohol and limonene or terpineol cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  18. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    DOEpatents

    Bohnert, G.W.; Carter, R.D.; Hand, T.E.; Powers, M.T.

    1997-10-21

    The present invention is a tetrahydrofurfuryl alcohol and limonene cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  19. Halide test agent replacement study

    SciTech Connect

    Banks, E.M.; Freeman, W.P.; Kovach, B.J.

    1995-02-01

    The intended phaseout of the chlorofluorocarbons (CFCs) from commercial use required the evaluation of substitute materials for the testing for leak paths through both individual adsorbers and installed adsorbent banks. The American Society of Mechanical Engineers (ASME) Committee on Nuclear Air and Gas Treatment (CONAGT) is in charge of maintaining the standards and codes specifying adsorbent leak test methods for the nuclear safety related air cleaning systems. The currently published standards and codes cite the use of R-11, R-12 and R-112 for leak path test agents. All of these compounds are CFCs. There are other agencies and organizations (USDOE, USDOD and USNRC) also specifying testing for leak paths or in some cases for special life tests using the above compounds. The CONAGT has recently developed criteria for the suitability evaluation of substitute test agents. On the basis of these criteria, several compounds were evaluated for their acceptability as adsorbent bed leak and life test agents. The ASME CONAGT Test Agent Qualification Criteria. The test agent qualification is based on the following parameters: (1) Similar retention times on activated carbons at the same concentration levels as one of the following: R-11, R-12, R-112 or R-112a. (2) Similar lower detection limit sensitivity and precision in the concentration range of use as R-11, R-12, R-112 and R-112a. (3) Gives the same in-place leak test results as R-11, R-12, R-112, or R-112a. (4) Chemical and radiological stability under the use conditions. (5) Causes no degradation of the carbon and its impregnant or of the other NATS components under the use conditions. (6) Is listed in the USEPA Toxic Substances Control Act (TSCA) inventory for commercial use.

  20. Biologic agents in juvenile spondyloarthropathies.

    PubMed

    Katsicas, María Martha; Russo, Ricardo

    2016-01-01

    The juvenile spondyloarthropathies (JSpA) are a group of related rheumatic diseases characterized by involvement of peripheral large joints, axial joints, and entheses (enthesitis) that begin in the early years of life (prior to 16(th) birthday).The nomenclature and concept of spondyloarthropathies has changed during the last few decades. Although there is not any specific classification of JSpA, diseases under the spondyloarthropathy nomenclature umbrella in the younger patients include: the seronegative enthesitis and arthropathy (SEA) syndrome, juvenile ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease-associated arthritis. Moreover, the ILAR criteria for Juvenile Idiopathic Arthritis includes two categories closely related to spondyloarthritis: Enthesitis-related arthritis and psoriatic arthritis.We review the pathophysiology and the use of biological agents in JSpA. JSpA are idiopathic inflammatory diseases driven by an altered balance in the proinflammatory cytokines. There is ample evidence on the role of tumor necrosis factor (TNF) and interleukin-17 in the physiopathology of these entities. Several non-biologic and biologic agents have been used with conflicting results in the treatment of these complex diseases. The efficacy and safety of anti-TNF agents, such as etanercept, infliximab and adalimumab, have been analysed in controlled and uncontrolled trials, usually showing satisfactory outcomes. Other biologic agents, such as abatacept, tocilizumab and rituximab, have been insufficiently studied and their role in the therapy of SpA is uncertain. Interleukin-17-blocking agents are promising alternatives for the treatment of JSpA patients in the near future. Recommendations for the treatment of patients with JSpA have recently been proposed and are discussed in the present review. PMID:26968522

  1. Laser interrogation of surface agents (LISA) for chemical agent reconnaissance

    NASA Astrophysics Data System (ADS)

    Higdon, N. S.; Chyba, Thomas H.; Richter, Dale A.; Ponsardin, Patrick L.; Armstrong, Wayne T.; Lobb, C. T.; Kelly, Brian T.; Babnick, Robert D.; Sedlacek, Arthur J., III

    2002-06-01

    Laser Interrogation of Surface Agents (LISA) is a new technique which exploits Raman scattering to provide standoff detection and identification of surface-deposited chemical agents. ITT Industries, Advanced Engineering and Sciences Division is developing the LISA technology under a cost-sharing arrangement with the US Army Soldier and Biological Chemical Command for incorporation on the Army's future reconnaissance vehicles. A field-engineered prototype LISA-Recon system is being designed to demonstrate on-the- move measurements of chemical contaminants. In this article, we will describe the LISA technique, data form proof-of- concept measurements, the LISA-Recon design, and some of the future realizations envisioned for military sensing applications.

  2. The New Agent: A Qualitative Study to Strategically Adapt New Agent Professional Development

    ERIC Educational Resources Information Center

    Baker, Lauri M.; Hadley, Gregg

    2014-01-01

    The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and…

  3. Neuroprotective "agents" in surgery. Secret "agent" man, or common "agent" machine?

    NASA Technical Reports Server (NTRS)

    Andrews, R. J.

    1999-01-01

    The search for clinically-effective neuroprotective agents has received enormous support in recent years--an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent "magic bullet" even more remote. On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated. In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery. The progress over the last 20 years in guidance during surgery (CT and MRI image-guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real-time. As an example of such technology, the NASA Smart Probe project is considered. In the long run (i.e., in 10 years or more), pharmacologic "agents" aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane "agents" based on computers, microsensors, and microeffectors will be the major impetus to improved

  4. CATS-based Agents That Err

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.

    2002-01-01

    This report describes preliminary research on intelligent agents that make errors. Such agents are crucial to the development of novel agent-based techniques for assessing system safety. The agents extend an agent architecture derived from the Crew Activity Tracking System that has been used as the basis for air traffic controller agents. The report first reviews several error taxonomies. Next, it presents an overview of the air traffic controller agents, then details several mechanisms for causing the agents to err in realistic ways. The report presents a performance assessment of the error-generating agents, and identifies directions for further research. The research was supported by the System-Wide Accident Prevention element of the FAA/NASA Aviation Safety Program.

  5. Software agents in molecular computational biology.

    PubMed

    Keele, John W; Wray, James E

    2005-12-01

    Progress made in applying agent systems to molecular computational biology is reviewed and strategies by which to exploit agent technology to greater advantage are investigated. Communities of software agents could play an important role in helping genome scientists design reagents for future research. The advent of genome sequencing in cattle and swine increases the complexity of data analysis required to conduct research in livestock genomics. Databases are always expanding and semantic differences among data are common. Agent platforms have been developed to deal with generic issues such as agent communication, life cycle management and advertisement of services (white and yellow pages). This frees computational biologists from the drudgery of having to re-invent the wheel on these common chores, giving them more time to focus on biology and bioinformatics. Agent platforms that comply with the Foundation for Intelligent Physical Agents (FIPA) standards are able to interoperate. In other words, agents developed on different platforms can communicate and cooperate with one another if domain-specific higher-level communication protocol details are agreed upon between different agent developers. Many software agent platforms are peer-to-peer, which means that even if some of the agents and data repositories are temporarily unavailable, a subset of the goals of the system can still be met. Past use of software agents in bioinformatics indicates that an agent approach should prove fruitful. Examination of current problems in bioinformatics indicates that existing agent platforms should be adaptable to novel situations. PMID:16420735

  6. [Alternative agents used in ADHD].

    PubMed

    Hässler, Frank; Dück, Alexander; Reis, Olaf; Buchmann, Johannes

    2009-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is, with a prevalence of 2% to 6%, one of the most common neurobehavioral disorder affecting children and adolescents, persisting into adulthood. Comorbidity and psychosocial circumstances enter into the choice of intervention strategies. Several agents have been demonstrated effective in treating individuals with ADHD. Direct or indirect attenuation of dopamine and norepinephrine neurotransmission appears closely related to both the stimulant and nonstimulant medications efficacious in ADHD. However, important differences concerning efficacy and side effects exist both between and with the specific classes of agents like neuroleptics, antidepressants, antiepileptics, alpha-agonists, beta-blockers, buspiron, l-dopa, melatonin, pycnogenol, zinc, magnesium, polyunsaturated fatty acids, and homeopathy. Elucidating the various mechanisms of action of ADHD medications may lead to better choices in matching potential responses to the characteristics of individuals. We review the purported mechanism of action and available evidence for selected complementary and alternative medicine therapies for ADHD in childhood and adolescence. PMID:19105161

  7. [Infectious agents and autoimmune diseases].

    PubMed

    Riebeling-Navarro, C; Madrid-Marina, V; Camarena-Medellín, B E; Peralta-Zaragoza, O; Barrera, R

    1992-01-01

    In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID:1615352

  8. Oral agents in multiple sclerosis.

    PubMed

    Lorefice, L; Fenu, G; Frau, J; Coghe, G C; Marrosu, M G; Cocco, E

    2015-01-01

    Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. Disease-modifying drugs licensed for MS treatment have been developed to reduce relapse rates and halt disease progression. The majority of current MS drugs involve regular, parenteral administration, affecting long-term adherence and thus reducing treatment efficacy. Over the last two decades great progress has been made towards developing new MS therapies with different modes of action and biologic effects. In particular, oral drugs have generated much interest because of their convenience and positive impact on medication adherence. Fingolimod was the first launched oral treatment for relapsing-remitting MS; recently, Teriflunomide and Dimethyl fumarate have also been approved as oral disease-modifying agents. In this review, we summarize and discuss the history, pharmacodynamics, efficacy, and safety of oral agents that have been approved or are under development for the selective treatment of MS. PMID:25924620

  9. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  10. Injectable agents affecting subcutaneous fats.

    PubMed

    Chen, David Lk; Cohen, Joel L; Green, Jeremy B

    2015-09-01

    Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. PMID:26566569

  11. Agent planning in AgScala

    NASA Astrophysics Data System (ADS)

    Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

    2013-10-01

    Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

  12. New therapeutic agents for acromegaly.

    PubMed

    Melmed, Shlomo

    2016-02-01

    The currently available somatostatin receptor ligands (SRLs) and growth hormone (GH) antagonists are used to control levels of GH and insulin-like growth factor 1 (IGF-1) in patients with acromegaly. However, these therapies are limited by wide variations in efficacy, associated adverse effects and the need for frequent injections. A phase III trial of oral octreotide capsules demonstrated that this treatment can safely sustain suppressed levels of GH and IGF-1 and reduce the severity of symptoms in patients with acromegaly previously controlled by injectable SRL therapy, with the added benefit of no injection-site reactions. Phase I and phase II trials of the pan-selective SRL DG3173, the liquid crystal octreotide depot CAM2029 and an antisense oligonucleotide directed against the GH receptor have shown that these agents can be used to achieve biochemical suppression in acromegaly and have favourable safety profiles. This Review outlines the need for new therapeutic agents for patients with acromegaly, reviews clinical trial data of investigational agents and considers how these therapies might best be integrated into clinical practice. PMID:26610414

  13. Chemotherapy and Dietary Phytochemical Agents

    PubMed Central

    Sak, Katrin

    2012-01-01

    Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way. PMID:23320169

  14. Pharmacologic Agents for Chronic Diarrhea

    PubMed Central

    2015-01-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  15. Multi-agent autonomous system

    NASA Technical Reports Server (NTRS)

    Fink, Wolfgang (Inventor); Dohm, James (Inventor); Tarbell, Mark A. (Inventor)

    2010-01-01

    A multi-agent autonomous system for exploration of hazardous or inaccessible locations. The multi-agent autonomous system includes simple surface-based agents or craft controlled by an airborne tracking and command system. The airborne tracking and command system includes an instrument suite used to image an operational area and any craft deployed within the operational area. The image data is used to identify the craft, targets for exploration, and obstacles in the operational area. The tracking and command system determines paths for the surface-based craft using the identified targets and obstacles and commands the craft using simple movement commands to move through the operational area to the targets while avoiding the obstacles. Each craft includes its own instrument suite to collect information about the operational area that is transmitted back to the tracking and command system. The tracking and command system may be further coupled to a satellite system to provide additional image information about the operational area and provide operational and location commands to the tracking and command system.

  16. Pharmacologic Agents for Chronic Diarrhea.

    PubMed

    Lee, Kwang Jae

    2015-10-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  17. Chelating agents and cadmium intoxication

    SciTech Connect

    Shinobu, L.A.

    1985-01-01

    A wide range of conventional chelating agents have been screened for (a) antidotal activity in acute cadmium poisoning and (b) ability to reduce aged liver and kidney deposits of cadmium. Chelating agents belonging to the dithiocarbamate class have been synthesized and tested in both the acute and chronic modes of cadmium intoxication. Several dithiocarbamates, not only provide antidotal rescue, but also substantially decrease the intracellular deposits of cadmium associated with chronic cadmium intoxication. Fractionating the cytosol from the livers and kidneys of control and treated animals by Sephadex G-25 gel filtration clearly demonstrates that the dithiocarbamates are reducing the level of metallothionein-bound cadmium. However, the results of cell culture (Ehrlich ascites) studies designed to investigate the removal of cadmium from metallothionein and subsequent transport of the resultant cadmium complex across the cell membrane were inconclusive. In other in vitro investigations, the interaction between isolated native Cd, Zn-metallothionein and several chelating agents was explored. Ultracentrifugation, equilibrium dialysis, and Sephadex G-25 gel filtration studies have been carried out in an attempt to determine the rate of removal of cadmium from metallothionein by these small molecules. Chemical shifts for the relevant cadmium-dithiocarbamate complexes have been determined using natural abundance Cd-NMR.

  18. Chemopreventive Agent Development | Division of Cancer Prevention

    Cancer.gov

    This group promotes and supports research on early chemopreventive agent development, from preclinical studies to phas | Research on early chemopreventive agent development, from preclinical studies to phase I clinical trials.

  19. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  20. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  1. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  2. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  3. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  4. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  5. Intelligent Agent Architectures: Reactive Planning Testbed

    NASA Technical Reports Server (NTRS)

    Rosenschein, Stanley J.; Kahn, Philip

    1993-01-01

    An Integrated Agent Architecture (IAA) is a framework or paradigm for constructing intelligent agents. Intelligent agents are collections of sensors, computers, and effectors that interact with their environments in real time in goal-directed ways. Because of the complexity involved in designing intelligent agents, it has been found useful to approach the construction of agents with some organizing principle, theory, or paradigm that gives shape to the agent's components and structures their relationships. Given the wide variety of approaches being taken in the field, the question naturally arises: Is there a way to compare and evaluate these approaches? The purpose of the present work is to develop common benchmark tasks and evaluation metrics to which intelligent agents, including complex robotic agents, constructed using various architectural approaches can be subjected.

  6. Security Measures to Protect Mobile Agents

    NASA Astrophysics Data System (ADS)

    Dadhich, Piyanka; Govil, M. C.; Dutta, Kamlesh

    2010-11-01

    The security issues of mobile agent systems have embarrassed its widespread implementation. Mobile agents that move around the network are not safe because the remote hosts that accommodate the agents initiates all kinds of attacks. These hosts try to analyze the agent's decision logic and their accumulated data. So, mobile agent security is the most challenging unsolved problems. The paper analyzes various security measures deeply. Security especially the attacks performed by hosts to the visiting mobile agent (the malicious hosts problem) is a major obstacle that prevents mobile agent technology from being widely adopted. Being the running environment for mobile agent, the host has full control over them and could easily perform many kinds of attacks against them.

  7. Intelligent Agents as Cognitive Tools for Education.

    ERIC Educational Resources Information Center

    Baylor, Amy

    1999-01-01

    Examines the educational potential for intelligent agents as cognitive tools. Discusses the role of intelligent agents: managing large amounts of information (information overload), serving as a pedagogical expert, and creating programming environments for the learner. (AEF)

  8. Learning other agents` preferences in multiagent negotiation

    SciTech Connect

    Bui, H.H.; Kieronska, D.; Venkatesh, S.

    1996-12-31

    In multiagent systems, an agent does not usually have complete information about the preferences and decision making processes of other agents. This might prevent the agents from making coordinated choices, purely due to their ignorance of what others want. This paper describes the integration of a learning module into a communication-intensive negotiating agent architecture. The learning module gives the agents the ability to learn about other agents` preferences via past interactions. Over time, the agents can incrementally update their models of other agents` preferences and use them to make better coordinated decisions. Combining both communication and learning, as two complement knowledge acquisition methods, helps to reduce the amount of communication needed on average, and is justified in situations where communication is computationally costly or simply not desirable (e.g. to preserve the individual privacy).

  9. Extinguishing agent for combustible metal fires

    DOEpatents

    Riley, John F.; Stauffer, Edgar Eugene

    1976-10-12

    A low chloride extinguishing agent for combustible metal fires comprising from substantially 75 to substantially 94 weight percent of sodium carbonate as the basic fire extinguishing material, from substantially 1 to substantially 5 weight percent of a water-repellent agent such as a metal stearate, from substantially 2 to substantially 10 weight percent of a flow promoting agent such as attapulgus clay, and from substantially 3 to substantially 15 weight percent of a polyamide resin as a crusting agent.

  10. Synthesis, characterization and pharmacological studies of copper complexes of flavone derivatives as potential anti-tuberculosis agents.

    PubMed

    Joseph, J; Nagashri, K; Suman, A

    2016-09-01

    Novel series of different hydroxyflavone derivatives and their copper complexes were synthesized. They were characterized using analytical and spectral techniques. The superoxide dismutase (SOD) mimetic activity of the synthesized complexes demonstrated that copper complex of L(10) has promising SOD-mimetic activity than other ligands & complexes. The in vitro antimicrobial activities of the synthesized compounds were tested against the bacterial species and fungal species. The DNA binding properties of copper complexes were studied using cyclic voltametry and electronic absorption techniques. Anti-tuberculosis activity was also performed. The effective complexes was subjected to antimycobacterial activity using MABA method and summarized. The antimycobacterial activity of copper complexes have been evaluated and discussed. PMID:27371912

  11. 14 CFR 221.11 - Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Agent. 221.11 Section 221.11 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Who is Authorized To Issue and File Tariffs § 221.11 Agent. An agent may issue and...

  12. STUDIES OF WATERBORNE AGENTS OF VIRAL GASTROENTERITIS

    EPA Science Inventory

    The etiologic agent of a large outbreak of waterborne viral gastroenteritis was detected employing immune electron microscopy (IEM) and a newly developed solid phase radioimmunoassay (RIA). This agent, referred to as the Snow Mountain Agent (SMA), is 27-32 nm. in diameter, has cu...

  13. Agent-based modeling of complex infrastructures

    SciTech Connect

    North, M. J.

    2001-06-01

    Complex Adaptive Systems (CAS) can be applied to investigate complex infrastructures and infrastructure interdependencies. The CAS model agents within the Spot Market Agent Research Tool (SMART) and Flexible Agent Simulation Toolkit (FAST) allow investigation of the electric power infrastructure, the natural gas infrastructure and their interdependencies.

  14. 24 CFR 232.1011 - Management agents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Management agents. 232.1011 Section... Management agents. (a) An operator or borrower may, with the prior written approval of HUD, execute a management agent agreement setting forth the duties and procedures for matters related to the management...

  15. 24 CFR 232.1011 - Management agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Management agents. 232.1011 Section... Management agents. (a) An operator or borrower may, with the prior written approval of HUD, execute a management agent agreement setting forth the duties and procedures for matters related to the management...

  16. 46 CFR 153.1106 - Cleaning agents.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cleaning agents. 153.1106 Section 153.1106 Shipping... Handling of Categories A, B, C, and D Cargo and Nls Residue § 153.1106 Cleaning agents. No tank cleaning agent other than water or steam may be used to clean an NLS residue from a cargo tank except...

  17. Online Deception Detection Using BDI Agents

    ERIC Educational Resources Information Center

    Merritts, Richard A.

    2013-01-01

    This research has two facets within separate research areas. The research area of Belief, Desire and Intention (BDI) agent capability development was extended. Deception detection research has been advanced with the development of automation using BDI agents. BDI agents performed tasks automatically and autonomously. This study used these…

  18. The Ontogenesis of Agent: Linguistic Expression.

    ERIC Educational Resources Information Center

    Olswang, Lesley Barrett; Carpenter, Robert L.

    1982-01-01

    Some of the findings of a longitudinal study of three infants between their 11th and 22nd months to document development of linguistic expression of the agent concept indicated that first vocalizations were inconsistently associated with nonverbal agentive behaviors and later mature utterances coded agent-action-recipient events. (MC)

  19. Infants Attribute to Agents Goals and Dispositions

    ERIC Educational Resources Information Center

    Luo, Yuyan; Choi, You-jung

    2012-01-01

    This commentary article is to be published alongside: Hernik, M., & Southgate, V. (2012). What do infants know about agents' goals? The authors see this issue consisting of two closely related questions. First, what is an agent to infants? Second, how do infants attribute goals to agents? Hernik and Southgage (H&S) focused on the second question.…

  20. Construction and Evaluation of Animated Teachable Agents

    ERIC Educational Resources Information Center

    Bodenheimer, Bobby; Williams, Betsy; Kramer, Mattie Ruth; Viswanath, Karun; Balachandran, Ramya; Belynne, Kadira; Biswas, Gautam

    2009-01-01

    This article describes the design decisions, technical approach, and evaluation of the animation and interface components for an agent-based system that allows learners to learn by teaching. Students learn by teaching an animated agent using a visual representation. The agent can answer questions about what she has been taught and take quizzes.…

  1. Hydroxypyridonate chelating agents and synthesis thereof

    DOEpatents

    Raymond, K.N.; Scarrow, R.C.; White, D.L.

    1985-11-12

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

  2. Honey - A Novel Antidiabetic Agent

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd S. Ab

    2012-01-01

    Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT), on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise) of these experimental data in diabetic human subjects. PMID:22811614

  3. Copper complexes as anticancer agents.

    PubMed

    Marzano, Cristina; Pellei, Maura; Tisato, Francesco; Santini, Carlo

    2009-02-01

    Metal-based antitumor drugs play a relevant role in antiblastic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. The variety of metal ion functions in biology has stimulated the development of new metallodrugs other than Pt drugs with the aim to obtain compounds acting via alternative mechanisms of action. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. Actually, since many years a lot of researches have actively investigated copper compounds based on the assumption proposal that endogenous metals may be less toxic. It has been established that the properties of copper-coordinated compounds are largely determined by the nature of ligands and donor atoms bound to the metal ion. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of copper(I,II) complexes. This work was motivated by the observation that no comprehensive surveys of copper complexes as anticancer agents were available in the literature. Moreover, up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. This overview, collecting the most significant strategies adopted in the last ten years to design promising anticancer copper(I,II) compounds, would be a help to the researchers working in this field. PMID:19199864

  4. Pathogenic agents in freshwater resources

    NASA Astrophysics Data System (ADS)

    Geldreich, Edwin E.

    1996-02-01

    Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

  5. Anticancer agents from marine sponges.

    PubMed

    Ye, Jianjun; Zhou, Feng; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics. PMID:25402340

  6. Fluorescent whitening agents in detergents.

    PubMed

    Eckhardt, C; von Rütte, R

    1975-01-01

    Washing is a form of textile care which is characterized by its repetitive nature. Washing methods vary enormously in different parts of the world. The main types of detergents and fluorescent whitening agents (FWAs) are described. Washing slows down the deterioration in use of white goods, and yellowing is counteracted by FWAs. FWAs also enhance the freshness and brightness of most pale shades. Cost calculations show clearly the economic advantages of using FWAs in washing: the useful life of textiles can be prolonged considerably for a very small additional cost. PMID:1064549

  7. Method For Detecting Biological Agents

    DOEpatents

    Chen, Liaohai; McBranch, Duncan W.; Wang, Hsing-Lin; Whitten, David G.

    2005-12-27

    A sensor is provided including a polymer capable of having an alterable measurable property from the group of luminescence and electrical conductivity, the polymer having an intermediate combination of a recognition element, a tethering element and a property-altering element bound thereto and capable of altering the measurable property, the intermediate combination adapted for subsequent separation from the polymer upon exposure to an agent having an affinity for binding to the recognition element whereupon the separation of the intermediate combination from the polymer results in a detectable change in the alterable measurable property, and, detecting said detectable change in the alterable measurable property.

  8. Mobile agent location in distributed environments

    NASA Astrophysics Data System (ADS)

    Fountoukis, S. G.; Argyropoulos, I. P.

    2012-12-01

    An agent is a small program acting on behalf of a user or an application which plays the role of a user. Artificial intelligence can be encapsulated in agents so that they can be capable of both behaving autonomously and showing an elementary decision ability regarding movement and some specific actions. Therefore they are often called autonomous mobile agents. In a distributed system, they can move themselves from one processing node to another through the interconnecting network infrastructure. Their purpose is to collect useful information and to carry it back to their user. Also, agents are used to start, monitor and stop processes running on the individual interconnected processing nodes of computer cluster systems. An agent has a unique id to discriminate itself from other agents and a current position. The position can be expressed as the address of the processing node which currently hosts the agent. Very often, it is necessary for a user, a processing node or another agent to know the current position of an agent in a distributed system. Several procedures and algorithms have been proposed for the purpose of position location of mobile agents. The most basic of all employs a fixed computing node, which acts as agent position repository, receiving messages from all the moving agents and keeping records of their current positions. The fixed node, responds to position queries and informs users, other nodes and other agents about the position of an agent. Herein, a model is proposed that considers pairs and triples of agents instead of single ones. A location method, which is investigated in this paper, attempts to exploit this model.

  9. Triazole: A Promising Antitubercular Agent.

    PubMed

    Keri, Rangappa S; Patil, Siddappa A; Budagumpi, Srinivasa; Nagaraja, Bhari Mallanna

    2015-10-01

    Tuberculosis is a contagious disease with comparatively high mortality worldwide. The statistics shows that around three million people throughout the world die annually from tuberculosis and there are around eight million new cases each year, of which developing countries showed major share. Therefore, the discovery and development of effective antituberculosis drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. The literature reveals that, heterocyclic moieties have drawn attention of the chemists, pharmacologists, microbiologists, and other researchers owing to its indomitable biological potential as anti-infective agents. Among heterocyclic compounds, triazole (1,2,3-triazole/1,2,4-triazole) nucleus is one of the most important and well-known heterocycles, which is a common and integral feature of a variety of natural products and medicinal agents. Triazole core is considered as a privileged structure in medicinal chemistry and is widely used as 'parental' compounds to synthesize molecules with medical benefits, especially with infection-related activities. In the present review, we have collated published reports on this versatile core to provide an insight so that its complete therapeutic potential can be utilized for the treatment of tuberculosis. This review also explores triazole as a potential targeted core moiety against tuberculosis and various research ongoing worldwide. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic triazole-based antituberculosis drugs. PMID:25643871

  10. Chemopreventive agents targeting tumor microenvironment.

    PubMed

    Sharma, Sharada H; Thulasingam, Senthilkumar; Nagarajan, Sangeetha

    2016-01-15

    Recent studies have shown that tumor development and progression depend not only on the perturbed genes that govern cell proliferation, but is also highly determined by the non-tumor cells of the stromal compartment surrounding the tumor called tumor microenvironment (TME). These findings highlight the importance of targeting the microenvironment in combination with therapies aimed at tumor cells as a valuable approach. The innate and adaptive immune cells in the TME interact among themselves and also with the endothelial cells, pericytes and mast cells of the stromal compartment through various autocrine and paracrine manner to regulate abnormal cell proliferation. Direct cytotoxic killing of cancer cells and/or reversion of the immunosuppressive TME are to be considered as better strategies for chemoprevention and chemotherapy. With a growing emphasis on a "hallmark targeting" strategy for cancer therapy, the TME now appears as a promising target for cancer prevention using natural products. Clarification on the nontumor stromal cells, the mediators involved, interactions with immune response cells, and immune-evasive mechanisms are needed in order to manipulate the characteristics of the TME by natural pharmacological agents to design effective therapies. This review will provide a glimpse on the roles played by various non-tumor cells in tumor progression and their intervention by pharmacological agents. PMID:26679106

  11. A Review of Luting Agents

    PubMed Central

    Pameijer, Cornelis H.

    2012-01-01

    Due to the availability of a large number of luting agents (dental cements) proper selection can be a daunting task and is usually based on a practitioner's reliance on experience and preference and less on in depth knowledge of materials that are used for the restoration and luting agent properties. This review aims at presenting an overview of current cements and discusses physical properties, biocompatibility and other properties that make a particular cement the preferred choice depending on the clinical indication. Tables are provided that outline the different properties of the generic classification of cements. It should be noted that no recommendations are made to use a particular commercial cement for a hypothetical clinical situation. The choice is solely the responsibility of the practitioner. The appendix is intended as a guide for the practitioner towards a recommended choice under commonly encountered clinical scenarios. Again, no commercial brands are recommended although the author recognizes that some have better properties than others. Please note that this flowchart strictly presents the author's opinion and is based on research, clinical experience and the literature. PMID:22505909

  12. Nanoparticle-based theranostic agents

    PubMed Central

    Xie, Jin; Lee, Seulki; Chen, Xiaoyuan

    2010-01-01

    Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology. PMID:20691229

  13. Innovative Agents in Multiple Myeloma

    PubMed Central

    Faiman, Beth; Richards, Tiffany

    2014-01-01

    Multiple myeloma (MM) remains an incurable cancer of the bone marrow plasma cells. However, the overall survival of patients with MM has increased dramatically within the past decade. This is due, in part, to newer agents such as immunomodulatory drugs (lenalidomide, thalidomide, and pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib, MLN9708). These and several other new classes of drugs have arisen from an improved understanding of the complex environment in which genetic changes occur. Improved understanding of genetic events will enable clinicians to better stratify risk before and during therapy, tailor treatment, and test the value of personalized interventions. The ultimate goal in this incurable disease setting is to reduce the impact of cancer- or chemotherapy-related side effects. Nurses and advanced practitioners are integral to the treatment team. Thus, each should be aware of changes to the current drug landscape. Targeted drugs with sophisticated mechanisms of action are currently under investigation. Patients gain access to newer drugs within the context of clinical trials. Awareness of such trials will help accrual and determine if therapeutic benefit exists. In this article, we will describe new agents with unique and targeted mechanisms of action that have activity in patients with relapsed and/or refractory multiple myeloma. PMID:25089218

  14. Surfactants as blackbird stressing agents

    USGS Publications Warehouse

    Lefebvre, P.W.; Seubert, J.L.

    1970-01-01

    Applications of wetting-agent solutions produce mortality in birds. The exact cause of death is undetermined but it is believed that destruction of the insulating qualities of the plumage permits ambient cold temperatures and evaporation to lower the body temperature to a lethal level. The original concept of using these materials as bird-control tools was developed in 1958 at the Patuxent Wildlife Research Center, Bureau of Sport Fisheries and Wildlife Laurel, Maryland. Early field trials by personnel of the Division of Wildlife Services and the Denver Wildlife Research Center indicated that ground-application techniques had promise but limitations of the equipment precluded successful large-scale roost treatments. In 1966, Patuxent Center personnel began using tanker-type aircraft to evaluate high-volume aerial applications of wetting agents. The success of these tests led to the use of small aircraft to make low-volume, high-concentration aerial applications just prior to expected rainfall. Recent trials of the low-volume method show that, with some limitations, it is effective, inexpensive, and safe to the environment. Current research emphasizes the screening of new candidate materials for efficacy, biodegradability, and toxicity to plants and non-target animals, as well as basic investigations of the avian physiological mechanisms involved. Field trials to develop more effective application techniques will continue.

  15. Electric power market agent design

    NASA Astrophysics Data System (ADS)

    Oh, Hyungseon

    The electric power industry in many countries has been restructured in the hope of a more economically efficient system. In the restructured system, traditional operating and planning tools based on true marginal cost do not perform well since information required is strictly confidential. For developing a new tool, it is necessary to understand offer behavior. The main objective of this study is to create a new tool for power system planning. For the purpose, this dissertation develops models for a market and market participants. A new model is developed in this work for explaining a supply-side offer curve, and several variables are introduced to characterize the curve. Demand is estimated using a neural network, and a numerical optimization process is used to determine the values of the variables that maximize the profit of the agent. The amount of data required for the optimization is chosen with the aid of nonlinear dynamics. To suggest an optimal demand-side bidding function, two optimization problems are constructed and solved for maximizing consumer satisfaction based on the properties of two different types of demands: price-based demand and must-be-served demand. Several different simulations are performed to test how an agent reacts in various situations. The offer behavior depends on locational benefit as well as the offer strategies of competitors.

  16. Camouflaging Agents for Vitiligo Patients.

    PubMed

    Hossain, Claudia; Porto, Dennis A; Hamzavi, Iltefat; Lim, Henry W

    2016-04-01

    Vitiligo is an acquired condition resulting in patches of depigmented skin that is cosmetically disfiguring and can subsequently be psychologically disturbing. For patients seeking to mask their vitiligo, camouflage options have historically been limited and been designated as a cosmetic, rather than a medical, concern. As research has indicated that proper concealment of vitiligo lesions can vastly improve quality of life, we believe it is essential that dermatologists become aware of all the options available to their patients and that discussions of camouflage options be broached from the first visit. Methods for concealment include cosmetic tattoos, dihydroxyacetone, general cosmetics, and various topical camouflage agents, including the newest product, Microskin™. We conducted a literature review of all of the available options for vitiligo concealment and evaluated their advantages and disadvantages. Ultimately, temporary methods of concealment are recommended; but the particular agent used can come from discussion with the patient based on the location of the lesions, degree of concealment desired, cost, and availability. PMID:27050692

  17. Anchor Toolkit - a secure mobile agent system

    SciTech Connect

    Mudumbai, Srilekha S.; Johnston, William; Essiari, Abdelilah

    1999-05-19

    Mobile agent technology facilitates intelligent operation insoftware systems with less human interaction. Major challenge todeployment of mobile agents include secure transmission of agents andpreventing unauthorized access to resources between interacting systems,as either hosts, or agents, or both can act maliciously. The Anchortoolkit, designed by LBNL, handles the transmission and secure managementof mobile agents in a heterogeneous distributed computing environment. Itprovides users with the option of incorporating their security managers.This paper concentrates on the architecture, features, access control anddeployment of Anchor toolkit. Application of this toolkit in a securedistributed CVS environment is discussed as a case study.

  18. SAF1. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, S.Y

    1997-06-01

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

  19. Nerve agents: implications for anesthesia providers.

    PubMed

    Hrobak, Paula Kay

    2008-04-01

    Anesthesia providers may be called to treat injuries from chemical weapons or spills, for which prompt treatment is vital. It is therefore important to understand the mechanism of action of nerve agents and the resultant pathophysiology and to be able to quickly recognize the signs and symptoms of nerve agent exposure. This review article addresses the different types of nerve agents that are currently being manufactured as well as the symptomatic and definitive treatment of the patient who presents with acute nerve agent toxicity. This article also reviews the physiology of the neuromuscular junction and the autonomic nervous system receptors that nerve agent toxicity affects. PMID:18478812

  20. Reversal agents in anaesthesia and critical care

    PubMed Central

    Pani, Nibedita; Dongare, Pradeep A; Mishra, Rajeeb Kumar

    2015-01-01

    Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice. PMID:26644615

  1. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the Department authorized to serve as passport...

  2. 30 CFR 250.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false How do I designate an agent or a local agent? 250.145 Section 250.145 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND... SHELF General Special Types of Approvals § 250.145 How do I designate an agent or a local agent? (a)...

  3. Mother ship and physical agents collaboration

    NASA Astrophysics Data System (ADS)

    Young, Stuart H.; Budulas, Peter P.; Emmerman, Philip J.

    1999-07-01

    This paper discusses ongoing research at the U.S. Army Research Laboratory that investigates the feasibility of developing a collaboration architecture between small physical agents and a mother ship. This incudes the distribution of planning, perception, mobility, processing and communications requirements between the mother ship and the agents. Small physical agents of the future will be virtually everywhere on the battlefield of the 21st century. A mother ship that is coupled to a team of small collaborating physical agents (conducting tasks such as Reconnaissance, Surveillance, and Target Acquisition (RSTA); logistics; sentry; and communications relay) will be used to build a completely effective and mission capable intelligent system. The mother ship must have long-range mobility to deploy the small, highly maneuverable agents that will operate in urban environments and more localized areas, and act as a logistics base for the smaller agents. The mother ship also establishes a robust communications network between the agents and is the primary information disseminating and receiving point to the external world. Because of its global knowledge and processing power, the mother ship does the high-level control and planning for the collaborative physical agents. This high level control and interaction between the mother ship and its agents (including inter agent collaboration) will be software agent architecture based. The mother ship incorporates multi-resolution battlefield visualization and analysis technology, which aids in mission planning and sensor fusion.

  4. Intelligent agent support for automated radiology exam

    NASA Astrophysics Data System (ADS)

    Shang, Yi; Popescu, Mihail

    2000-10-01

    A difficult problem in automatic medical image understanding is that for every image type such as x-ray and every body organ such as heart, there exist specific solutions that do not allow for generalization. Just collecting all the specific solutions will not achieve the vision of a computerized physician. To address this problem, we propose an intelligent agent approach that is based on agent-oriented programming is that it combines the benefits of object-oriented programming and expert system. For radiology image understanding, we present a multi- agent system that is composed of two major types of intelligent agents: radiologist agents and patient agents. A patient agent asks for multiple opinions from radiologists agents in interpreting a given set of images and then integrates the opinions. A radiologist agent decomposes the image recognition task into smaller problems that are solved collectively by multiple intelligent sub-agents. Finally, we present a preliminary implementation and running examples of the multi-agent system.

  5. Knowledge Management in Role Based Agents

    NASA Astrophysics Data System (ADS)

    Kır, Hüseyin; Ekinci, Erdem Eser; Dikenelli, Oguz

    In multi-agent system literature, the role concept is getting increasingly researched to provide an abstraction to scope beliefs, norms, goals of agents and to shape relationships of the agents in the organization. In this research, we propose a knowledgebase architecture to increase applicability of roles in MAS domain by drawing inspiration from the self concept in the role theory of sociology. The proposed knowledgebase architecture has granulated structure that is dynamically organized according to the agent's identification in a social environment. Thanks to this dynamic structure, agents are enabled to work on consistent knowledge in spite of inevitable conflicts between roles and the agent. The knowledgebase architecture is also implemented and incorporated into the SEAGENT multi-agent system development framework.

  6. Other potentially useful new injectable anesthetic agents.

    PubMed

    Ilkiw, J E

    1992-03-01

    Ultrashort barbiturates are not ideal injectable anesthetic agents, and new agents continue to be released as investigators pursue the goal of finding a more ideal agent. Of the new injectable agents discussed, propofol seems to be the most promising drug. Propofol should find a place in veterinary practice as an outpatient anesthetic agent because it has a rapid, smooth, and complete recovery even after repeated or continuous administration. Midazolam does not induce anesthesia in healthy, small animals and, as such, can only be used in combination with other injectable agents, such as ketamine or the thiobarbiturates. In our practice, Telazol has found a place in the anesthetic management of feral cats and aggressive dogs, where it is used for heavy sedation or to induce anesthesia. The role of flumazenil, as a reversal agent, in veterinary practice remains to be determined; however, the role in small domestic animals is unlikely to be significant. PMID:1585555

  7. Repurposing of a drug scaffold: Identification of novel sila analogues of rimonabant as potent antitubercular agents.

    PubMed

    Ramesh, Remya; Shingare, Rahul D; Kumar, Vinod; Anand, Amitesh; B, Swetha; Veeraraghavan, Sridhar; Viswanadha, Srikant; Ummanni, Ramesh; Gokhale, Rajesh; Srinivasa Reddy, D

    2016-10-21

    The structural similarity between an MmpL3 inhibitor BM212, and a cannabinoid receptor modulator rimonabant, prompted us to investigate the anti-tubercular activity of rimonabant and its analogues. Further optimization, particularly through incorporation of silicon into the scaffold, resulted in new compounds with significant improvement in anti-tubercular activity against Mycobacterium tuberculosis (H37Rv). The sila analogue 18a was found to be the most potent antimycobacterial compound (MIC, 31 ng/mL) from this series with an excellent selectivity index. PMID:27476117

  8. Drug therapy reviews: antirheumatic agents.

    PubMed

    Evens, R P

    1979-05-01

    The pathophysiology, symptoms and drug treatment of rheumatic disease are reviewed. Antirheumatic drugs reviewed are salicylates (including aspirin, sodium salicylate, choline salicylate, choline magnesium salicylate, salsalate), phenylpropionic acid derivatives (fenoprofen, ibuprofen, naproxen), indole derivatives (sulindac, tolmetin and indomethacin), pyrazolone derivatives (phenylbutazone, oxyphenbutazone), gold compounds, penicillamine, antimalarials mefenamic acid, corticosteroids and immunosuppressives. Simple analgesic therapy (acetaminophen, aspirin, propoxyphene) is used in the early stage of the disease. As the disease progresses, aspirin remains the drug of choice for antiinflammatory activity but the phenylpropionic acid or indole derivatives may be preferred in patients unable to tolerate salicylates. If such nonsteroidal antiinflammatory agents are not effective, parenteral therapy with gold compounds or oral penicillamine usually is indicated. Indomethacin or phenylbutazone, then antimalarials, are resorted to next. Corticosteroids or immunosuppressives are reserved for patients who are unsuccessfully controlled or who have major side effects with the other drugs. Mefenamic acid occupies a very secondary place in rheumatoid arthritis treatment. PMID:377958

  9. [Anticonvulsant agents in neuralgic pain.].

    PubMed

    Jurna, I; Zenz, M

    1992-06-01

    The anticonvulsants, carbamazepine, clonazepam, phenytoin, and valproic acid are capable of depressing attacks of shooting pain in neuralgia. Shooting pain is perceived in trigeminal, intercostal, and other neuralgias, as a consequence of infectious diseases such as herpes zoster, and in the course of polyneuropathies of various causes. It is due to injury of nociceptive afferents, which generate bursts of activity in response to appropriate environmental changes. The anticonvulsant agents have no analgesic property per se, so that background pain remains unchanged. The depression of shooting pain results from the anticonvulsant action of the compounds. Both carbamazepine and phenytoin block synaptic transmission of neuronal hyperactivity by a direct depressant action that includes reduction of sodium conductance and by activation of inhibitory control. Clonazepam and valproic acid act by enhancing GABA-mediated inhibition of synaptic transmission. Carbamazepine is by far the most widely used compound; phenytoin, clonazepam, and valproic acid are not so popular because of their side effects. PMID:18415623

  10. Biotherapeutic agents and vaginal health.

    PubMed

    Al-Ghazzewi, F H; Tester, R F

    2016-07-01

    Treatment of vaginal infection requires different drugs although the recurrence rate post treatment remains high due to adverse effects on the beneficial microbiota. Thus, there are clear clinical advantages for the use of biotherapeutic agents (prebiotics and/or probiotics) for treating these infections. Pre- and probiotic beneficial effects can be delivered topically or systemically. In general, both approaches have the potential to optimize, maintain and restore the ecology of the vaginal ecosystem. Specific carbohydrates provide a therapeutic approach for controlling infections by stimulating the growth of the indigenous lactobacilli but inhibiting the growth and adhesion of pathogens to the vaginal epithelial cells. Overall, little evidence exists to promote the prevention or treatment of vaginal disease with prebiotic carbohydrates in formulations such as pessaries, creams or douches. However, recent reports have promoted prebiotic applications in ecosystems other than the gut and include the mouth, skin and vagina. This review focuses on the utilization of pre- and probiotics for vaginal health. PMID:26757173

  11. Agent Reward Shaping for Alleviating Traffic Congestion

    NASA Technical Reports Server (NTRS)

    Tumer, Kagan; Agogino, Adrian

    2006-01-01

    Traffic congestion problems provide a unique environment to study how multi-agent systems promote desired system level behavior. What is particularly interesting in this class of problems is that no individual action is intrinsically "bad" for the system but that combinations of actions among agents lead to undesirable outcomes, As a consequence, agents need to learn how to coordinate their actions with those of other agents, rather than learn a particular set of "good" actions. This problem is ubiquitous in various traffic problems, including selecting departure times for commuters, routes for airlines, and paths for data routers. In this paper we present a multi-agent approach to two traffic problems, where far each driver, an agent selects the most suitable action using reinforcement learning. The agent rewards are based on concepts from collectives and aim to provide the agents with rewards that are both easy to learn and that if learned, lead to good system level behavior. In the first problem, we study how agents learn the best departure times of drivers in a daily commuting environment and how following those departure times alleviates congestion. In the second problem, we study how agents learn to select desirable routes to improve traffic flow and minimize delays for. all drivers.. In both sets of experiments,. agents using collective-based rewards produced near optimal performance (93-96% of optimal) whereas agents using system rewards (63-68%) barely outperformed random action selection (62-64%) and agents using local rewards (48-72%) performed worse than random in some instances.

  12. Antagonistic formation motion of cooperative agents

    NASA Astrophysics Data System (ADS)

    Lu, Wan-Ting; Dai, Ming-Xiang; Xue, Fang-Zheng

    2015-02-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonistic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all of the agents make an antagonistic formation motion in a distributed manner. It is shown that all of the agents can be spontaneously divided into several groups and that agents in the same group collaborate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results. Project supported by the National Natural Science Foundation of China (Grant Nos. 61203080 and 61473051) and the Natural Science Foundation of Chongqing City (Grant No. CSTC 2011BB0081).

  13. Persuasive Conversational Agent with Persuasion Tactics

    NASA Astrophysics Data System (ADS)

    Narita, Tatsuya; Kitamura, Yasuhiko

    Persuasive conversational agents persuade people to change their attitudes or behaviors through conversation, and are expected to be applied as virtual sales clerks in e-shopping sites. As an approach to create such an agent, we have developed a learning agent with the Wizard of Oz method in which a person called Wizard talks to the user pretending to be the agent. The agent observes the conversations between the Wizard and the user, and learns how to persuade people. In this method, the Wizard has to reply to most of the user's inputs at the beginning, but the burden gradually falls because the agent learns how to reply as the conversation model grows.

  14. Pinning synchronization of a mobile agent network

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Sun, You-xian

    2009-11-01

    We investigate the problem of controlling a group of mobile agents in a plane in order to move them towards a desired orbit via pinning control, in which each agent is associated with a chaotic oscillator coupled with those of neighboring agents, and the pinning strategy is to have the common linear feedback acting on a small fraction of agents by random selection. We explore the effects of the pinning probability, feedback gains and agent density in the pinning synchronization of a mobile agent network under a fast-switching constraint, and perform numerical simulations for validation. In particular, we show that there exists a critical pinning density for network synchronization with an unbounded region: above the threshold, the dynamical network can be controlled by pinning; below it, anarchy prevails. And for the network with a single bounded synchronization region, pinning control has little effect as regards enhancing network synchronizability.

  15. Evolutionary algorithms and multi-agent systems

    NASA Astrophysics Data System (ADS)

    Oh, Jae C.

    2006-05-01

    This paper discusses how evolutionary algorithms are related to multi-agent systems and the possibility of military applications using the two disciplines. In particular, we present a game theoretic model for multi-agent resource distribution and allocation where agents in the environment must help each other to survive. Each agent maintains a set of variables representing actual friendship and perceived friendship. The model directly addresses problems in reputation management schemes in multi-agent systems and Peer-to-Peer distributed systems. We present algorithms based on evolutionary game process for maintaining the friendship values as well as a utility equation used in each agent's decision making. For an application problem, we adapted our formal model to the military coalition support problem in peace-keeping missions. Simulation results show that efficient resource allocation and sharing with minimum communication cost is achieved without centralized control.

  16. A New Understanding of Chemical Agent Release

    SciTech Connect

    Nakafuji, G; Greenman, R; Theofanous, T

    2002-07-24

    The evolution of thickened chemical agent released at supersonic velocities, due to a missile defense intercept or a properly functioning warhead, has been misunderstood. Current and historical experimental and modeling efforts have attributed agent breakup to a variety of droplet breakup mechanisms. According to this model, drops of agent fragment into subsequent generations of smaller drops until a stable drop size is reached. Recent experimental data conducted in a supersonic wind tunnel show that agent breakup is not driven by any droplet breakup mechanism. The breakup of agent is instead governed by viscoelastic behavior and aerodynamic history effects. This viscoelastic breakup mechanism results in the formation of threads and sheets of liquid, instead of drops. The evolution and final state of agent released has broad implications not only for aerobreakup models, but also for all atmospheric dispersion models.

  17. Multi-Agent Information Classification Using Dynamic Acquaintance Lists.

    ERIC Educational Resources Information Center

    Mukhopadhyay, Snehasis; Peng, Shengquan; Raje, Rajeev; Palakal, Mathew; Mostafa, Javed

    2003-01-01

    Discussion of automated information services focuses on information classification and collaborative agents, i.e. intelligent computer programs. Highlights include multi-agent systems; distributed artificial intelligence; thesauri; document representation and classification; agent modeling; acquaintances, or remote agents discovered through…

  18. Anaphylactoid and adverse reactions to radiocontrast agents.

    PubMed

    Hagan, John B

    2004-08-01

    Over the past 75 years, radiocontrast agents have provided numerous diagnostic and therapeutic advances. The benefits of these agents must be weighed against the potential risks for each individual undergoing radiologic tests. This summary is intended to be a guide for the allergy and immunology specialist to direct him or her to the current literature regarding adverse reactions to traditional and less commonly used radiologic contrast agents. PMID:15242724

  19. Massive Multi-Agent Systems Control

    NASA Technical Reports Server (NTRS)

    Campagne, Jean-Charles; Gardon, Alain; Collomb, Etienne; Nishida, Toyoaki

    2004-01-01

    In order to build massive multi-agent systems, considered as complex and dynamic systems, one needs a method to analyze and control the system. We suggest an approach using morphology to represent and control the state of large organizations composed of a great number of light software agents. Morphology is understood as representing the state of the multi-agent system as shapes in an abstract geometrical space, this notion is close to the notion of phase space in physics.

  20. The EO-1 Autonomous Science Agent Architecture

    NASA Technical Reports Server (NTRS)

    Chien, Steve; Sherwood, Rob; Tran, Daniel; Cichy, Benjamin; Rabideau, Gregg; Castano, Rebecca; Davies, Ashley; Lee, Rachel; Mandl, Dan; Frye, Stuart; Trout, Bruce; Hengemihle, Jerry; D'Agostino, Jeff; Shulman, Seth; Ungar, Stephen; Brakke, Thomas; Boyer, Darrell; Van Gaasbeck, Jim; Greeley, Ronald; Doggett, Thomas; Baker, Victor; Dohm, James; Ip, Felipe

    2004-01-01

    An Autonomous Science Agent is currently flying onboard the Earth Observing One Spacecraft. This software enables the spacecraft to autonomously detect and respond to science events occurring on the Earth. The package includes software systems that perform science data analysis, deliberative planning, and run-time robust execution. Because of the deployment to a remote spacecraft, this Autonomous Science Agent has stringent constraints of autonomy, reliability, and limited computing resources. We describe these constraints and how they are reflected in our agent architecture.

  1. Departments as Agents of Change

    NASA Astrophysics Data System (ADS)

    Lagowski, J. J.

    1996-07-01

    Higher education is changing because it has no choice. And, for the most part, outside influences are dictating the processes of change. The more fortunate institutions have had a flat budget during this period, but most have been forced to deal with a declining revenue stream as well. Legislators seem bent on micromanaging state-supported institutions, even as they cut their support. Regulators demand greater institutional accountability. Students and their parents expect more service at lower prices and increased flexibility. Technological advances have dramatically affected the availability and accessibility of extant knowledge. It is no longer a question of whether institutions will change, but rather, who will control the change. Most institutions possess long-standing academic traditions, but these are placed at risk in an increasingly competitive market that holds little sympathy for such traditions and may even see them as obstacles or barriers. As a result, the change agents will undoubtedly have a profound effect on the very nature of academic institutions. From the academic point of view, it would seem prudent to attempt to manage the changes that will inevitably occur. A number of concerned observers, notably the Pew Higher Education Roundtable and the American Association for Higher Education, argue persuasively that the academic department is the logical focus for responding to the current winds of change. Using a marketing metaphor, the academic department has been likened to a "producers' cooperative" of services that consumers seek. Thus, the department should be held accountable for the quality of teaching delivered by its members, for the coherence of its major, for its contributions to the general education curriculum, and for supervising and rewarding its individual faculty members. If departments are to be held accountable, it is surely in their best interest to act in such a way that they are accountable. Expecting academic departments to be

  2. Radioiodine: the classic theranostic agent.

    PubMed

    Silberstein, Edward B

    2012-05-01

    Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and

  3. Emergency department management of nerve agent exposure.

    PubMed

    Pfaff, B L

    1998-01-01

    Nerve agents are toxic chemicals developed for use by the military, but used by terrorists against civilian populations. As threats of terrorism increase, it is possible that health care providers will be confronted with multiple victims of nerve agent exposure. Nerve agents are highly toxic forms of organophosphate poisons that potentially could cause harm to anyone who comes in contact. Emergency personnel need to be familiar with the agents, know how to prepare for encountering and treating victims, and know how to protect all people involved from further poisoning. PMID:9855972

  4. Characterization of chemical agent transport in paints.

    PubMed

    Willis, Matthew P; Gordon, Wesley; Lalain, Teri; Mantooth, Brent

    2013-09-15

    A combination of vacuum-based vapor emission measurements with a mass transport model was employed to determine the interaction of chemical warfare agents with various materials, including transport parameters of agents in paints. Accurate determination of mass transport parameters enables the simulation of the chemical agent distribution in a material for decontaminant performance modeling. The evaluation was performed with the chemical warfare agents bis(2-chloroethyl) sulfide (distilled mustard, known as the chemical warfare blister agent HD) and O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), an organophosphate nerve agent, deposited on to two different types of polyurethane paint coatings. The results demonstrated alignment between the experimentally measured vapor emission flux and the predicted vapor flux. Mass transport modeling demonstrated rapid transport of VX into the coatings; VX penetrated through the aliphatic polyurethane-based coating (100 μm) within approximately 107 min. By comparison, while HD was more soluble in the coatings, the penetration depth in the coatings was approximately 2× lower than VX. Applications of mass transport parameters include the ability to predict agent uptake, and subsequent long-term vapor emission or contact transfer where the agent could present exposure risks. Additionally, these parameters and model enable the ability to perform decontamination modeling to predict how decontaminants remove agent from these materials. PMID:23872337

  5. Oak Ridge Mobile Agent Community (ORMAC)

    Energy Science and Technology Software Center (ESTSC)

    2003-06-30

    The Oak Ridge Mobile Agent Community (ORMAC) framework software facilitates the execution of a collection of mobile software agents across a heterogeneous collection of computer systems. ORMAC provides the software agents with the ability to communicate with each other in a synchronous and asynchronous manner. Also, ORMAC allows the software agents to move to any computer system in the community and continue execution there. ORMAC is intended to aid programmers in solving a very generalmore » set of distributed software problems.« less

  6. Dentine and enamel bonding agents.

    PubMed

    Bowen, R L; Tung, M S; Blosser, R L; Asmussen, E

    1987-09-01

    Previous studies have shown that sequential use of aqueous FO (ferric oxalate containing a small concentration of HNO3), acetone solutions of NPG (N-phenylglycine), and PMDM (the reaction product of pyromellitic dianhydride and 2-hydroxyethylmethacrylate) yields strong adhesive bonding of composite resins to both dentine and enamel. The purpose of this study was to determine if aluminum ions could be substituted for ferric ions and if the procedure could be simplified. Aqueous solutions containing aluminum oxalate and aluminum nitrate, followed in sequence by acetone solutions of NPG and PMDM, gave strong tensile adhesive bond strengths between a composite and extracted human teeth. Comparable values have been obtained with FO, NPG and PMDM. Aluminum oxalate solutions containing no nitrate gave lower bond strengths, as was the case with FO. Aqueous solutions of acidified aluminum oxalate can dissolve NPG, thereby allowing a simplification of the procedure. Tested for comparison, commercially available dentine bonding agents gave lower average bond strengths on dentine than did some of the experimental materials. PMID:3316044

  7. Cold as a therapeutic agent.

    PubMed

    Wang, H; Olivero, W; Wang, D; Lanzino, G

    2006-05-01

    The use of cold as a therapeutic agent has a long and colorful history. The Edwin Smith Papyrus, the most ancient medical text known, dated 3500 B.C., made numerous references to the use of cold as therapy. Baron de Larrey, a French army surgeon during Napoleon's Russian campaign, packed the limbs in ice prior to amputations to render the procedures painless. In the early twentieth century, a neurosurgeon, Temple Fay, pioneered "human refrigeration" as a treatment for malignancies and head injuries. In 1961, Irving Cooper developed the first closed cryoprobe system and ushered in the modern era of cryogenic surgery with his imperturbable convictions. Fay's early work fell victim to the disruptive sequel of the World War II. The Nazis confiscated his data (presented before the Third International Cancer Congress in 1939) forwarded to Belgium for publication and brutally applied his refrigeration techniques experimentally without any benefit of anesthesia in the concentration camps, especially Dachau. Hypothermia became associated in the public mind with the atrocities exposed at the war trials in Nürnberg. After lying dormant for decades, the interest was rekindled in the late 80s when mild hypothermia was shown to confer dramatic neuroprotection in a number of experimental models of brain injury. With several large multi-center clinical studies currently under way, hypothermia is receiving unprecedented attention from the medical and scientific communities. PMID:16489500

  8. Direct anti-HCV agents.

    PubMed

    Zhang, Xingquan

    2016-01-01

    Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the "cure HCV" goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others. PMID:26904396

  9. Departments as Agents of Change

    NASA Astrophysics Data System (ADS)

    Lagowski, J. J.

    1996-07-01

    Higher education is changing because it has no choice. And, for the most part, outside influences are dictating the processes of change. The more fortunate institutions have had a flat budget during this period, but most have been forced to deal with a declining revenue stream as well. Legislators seem bent on micromanaging state-supported institutions, even as they cut their support. Regulators demand greater institutional accountability. Students and their parents expect more service at lower prices and increased flexibility. Technological advances have dramatically affected the availability and accessibility of extant knowledge. It is no longer a question of whether institutions will change, but rather, who will control the change. Most institutions possess long-standing academic traditions, but these are placed at risk in an increasingly competitive market that holds little sympathy for such traditions and may even see them as obstacles or barriers. As a result, the change agents will undoubtedly have a profound effect on the very nature of academic institutions. From the academic point of view, it would seem prudent to attempt to manage the changes that will inevitably occur. A number of concerned observers, notably the Pew Higher Education Roundtable and the American Association for Higher Education, argue persuasively that the academic department is the logical focus for responding to the current winds of change. Using a marketing metaphor, the academic department has been likened to a "producers' cooperative" of services that consumers seek. Thus, the department should be held accountable for the quality of teaching delivered by its members, for the coherence of its major, for its contributions to the general education curriculum, and for supervising and rewarding its individual faculty members. If departments are to be held accountable, it is surely in their best interest to act in such a way that they are accountable. Expecting academic departments to be

  10. Novel antibodies as anticancer agents.

    PubMed

    Zafir-Lavie, I; Michaeli, Y; Reiter, Y

    2007-05-28

    In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents. PMID:17530025

  11. New therapeutic agents for hypertension

    PubMed Central

    REID, JOHN L.

    1996-01-01

    1Over the last 40 years a range of therapeutic strategies has been introduced for the long term treatment of hypertension. 2Although safe effective agents are available a significant number of patients are unable or unwilling to take these drugs as long term treatment. 3Both insufficient efficacy and adverse effects justify the search for new antihypertensive strategies. 4Recent developments include orally active angiotensin (AT1) receptor antagonists (ARA) which appear to offer the benefits of prevention of angiotensin II effects without the adverse effects of bradykinin potentiation, such as cough, which limit the usefulness of angiotensin converting enzyme (ACE) inhibitors. 5Imidazoline receptor agonists offer the potential of centrally active antihypertensives without the adverse effects of sedation and dry mouth. Further clinical experience is necessary to confirm whether the clinical efficacy and good tolerability are confirmed with long term use. 6Both ARA and imidazoline preferring substances offer the bonus of a desirable haemodynamic profile in patients with heart failure and may open new therapeutic avenues in the management of cardiac failure. PMID:8807142

  12. Direct anti-HCV agents

    PubMed Central

    Zhang, Xingquan

    2015-01-01

    Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others. PMID:26904396

  13. Radiation recall with anticancer agents.

    PubMed

    Burris, Howard A; Hurtig, Jane

    2010-01-01

    Radiation recall is an acute inflammatory reaction confined to previously irradiated areas that can be triggered when chemotherapy agents are administered after radiotherapy. It remains a poorly understood phenomenon, but increased awareness may aid early diagnosis and appropriate management. A diverse range of drugs used in the treatment of cancer has been associated with radiation recall. As most data come from case reports, it is not possible to determine the true incidence, but to date the antineoplastic drugs for which radiation recall reactions have been most commonly reported include the anthracycline doxorubicin, the taxanes docetaxel and paclitaxel, and the antimetabolites gemcitabine and capecitabine. Radiation recall is drug-specific for any individual patient; it is not possible to predict which patients will react to which drugs, and rechallenge does not uniformly induce a reaction. There are no identifiable characteristics of drugs that cause radiation recall, and thus, it is a possibility that must be kept in mind with use of any drug after radiotherapy, including those from new drug classes. Although it is not yet possible to design treatment regimens to eliminate the risk of radiation recall, it seems likely that risks can be minimized by prolonging the interval between completion of radiotherapy and initiation of chemotherapy. PMID:21045191

  14. Safe motion planning for mobile agents: A model of reactive planning for multiple mobile agents

    SciTech Connect

    Fujimura, Kikuo.

    1990-01-01

    The problem of motion planning for multiple mobile agents is studied. Each planning agent independently plans its own action based on its map which contains a limited information about the environment. In an environment where more than one mobile agent interacts, the motions of the robots are uncertain and dynamic. A model for reactive agents is described and simulation results are presented to show their behavior patterns. 18 refs., 2 figs.

  15. The Design of Motivational Agents and Avatars

    ERIC Educational Resources Information Center

    Baylor, Amy L.

    2011-01-01

    While the addition of an anthropomorphic interface agent to a learning system generally has little direct impact on learning, it potentially has a huge impact on learner motivation. As such agents become increasingly ubiquitous on the Internet, in virtual worlds, and as interfaces for learning and gaming systems, it is important to design them to…

  16. VIRAL GASTROENTERITIS AGENTS AND WATERBORNE DISEASE

    EPA Science Inventory

    The application of electron microscopic techniques in the study of human gastroenteritis led in the 1970's to the identification of new viral agents that had previously escaped detection by routine cell culture procedures. These agents have been the focus of study by researchers ...

  17. Improving Disability Awareness among Extension Agents

    ERIC Educational Resources Information Center

    Mahadevan, Lakshmi; Peterson, Rick L.; Grenwelge, Cheryl

    2014-01-01

    Increasing prevalence rates and legislative mandates imply that educators, parents, and Extension agents will need better tools and resources to meet the needs of special populations. The Texas A&M AgriLife Extension Service addresses this issue by using e-learning tools. Extension agents can take advantage of these courses to gain critical…

  18. 21 CFR 178.3125 - Anticorrosive agents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... section may be used as anticorrosive agents in food-contact materials subject to the provisions of this... component of resinous and polymeric food-contact coatings intended for repeated use in contact with dry... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Anticorrosive agents. 178.3125 Section...

  19. 21 CFR 178.3125 - Anticorrosive agents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... section may be used as anticorrosive agents in food-contact materials subject to the provisions of this... component of resinous and polymeric food-contact coatings intended for repeated use in contact with dry... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Anticorrosive agents. 178.3125 Section...

  20. 21 CFR 178.3125 - Anticorrosive agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... agents in food-contact materials subject to the provisions of this section: Substances Limitations Zinc... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Anticorrosive agents. 178.3125 Section 178.3125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  1. 46 CFR Sec. 3 - General Agents' responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false General Agents' responsibilities. Sec. 3 Section 3 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY AUTHORITY AND RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE EMERGENCY REPAIRS IN FOREIGN PORTS Sec. 3 General...

  2. 46 CFR Sec. 2 - General Agents' authority.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false General Agents' authority. Sec. 2 Section 2 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY AUTHORITY AND RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE IN CONTINENTAL UNITED STATES PORTS VOYAGE REPAIRS AND...

  3. 7 CFR 58.722 - Emulsifying agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.722 Emulsifying agents. Emulsifying agents shall be those permitted by the Food and Drug Administration for the specific pasteurized process cheese product, and shall be free from extraneous...

  4. 7 CFR 58.722 - Emulsifying agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.722 Emulsifying agents. Emulsifying agents shall be those permitted by the Food and Drug Administration for the specific pasteurized process cheese product, and shall be free from extraneous...

  5. Security of Mobile Agents on the Internet.

    ERIC Educational Resources Information Center

    Corradi, Antonio; Montanari, Rebecca; Stefanelli, Cesare

    2001-01-01

    Discussion of the Internet focuses on new programming paradigms based on mobile agents. Considers the security issues associated with mobile agents and proposes a security architecture composed of a wide set of services and components capable of adapting to a variety of applications, particularly electronic commerce. (Author/LRW)

  6. Marine Natural Products as Prototype Agrochemical Agents

    PubMed Central

    Peng, Jiangnan; Shen, Xiaoyu; El Sayed, Khalid A.; Dunbar, D. C Harles; Perry, Tony L.; Wilkins, Scott P.; Hamann, Mark T.; Bobzin, Steve; Huesing, Joseph; Camp, Robin; Prinsen, Mike; Krupa, Dan; Wideman, Margaret A.

    2016-01-01

    In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents. PMID:12670165

  7. 13 CFR 120.952 - Fiscal agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Fiscal agent. 120.952 Section 120.952 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company... Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production...

  8. Assurance in Agent-Based Systems

    SciTech Connect

    Gilliom, Laura R.; Goldsmith, Steven Y.

    1999-05-10

    Our vision of the future of information systems is one that includes engineered collectives of software agents which are situated in an environment over years and which increasingly improve the performance of the overall system of which they are a part. At a minimum, the movement of agent and multi-agent technology into National Security applications, including their use in information assurance, is apparent today. The use of deliberative, autonomous agents in high-consequence/high-security applications will require a commensurate level of protection and confidence in the predictability of system-level behavior. At Sandia National Laboratories, we have defined and are addressing a research agenda that integrates the surety (safety, security, and reliability) into agent-based systems at a deep level. Surety is addressed at multiple levels: The integrity of individual agents must be protected by addressing potential failure modes and vulnerabilities to malevolent threats. Providing for the surety of the collective requires attention to communications surety issues and mechanisms for identifying and working with trusted collaborators. At the highest level, using agent-based collectives within a large-scale distributed system requires the development of principled design methods to deliver the desired emergent performance or surety characteristics. This position paper will outline the research directions underway at Sandia, will discuss relevant work being performed elsewhere, and will report progress to date toward assurance in agent-based systems.

  9. Practice among Novice Change Agents in Schools

    ERIC Educational Resources Information Center

    Blossing, Ulf

    2016-01-01

    The aim of the article is to understand practice as negotiation of meaning among novice and internal change agents in school organisations. The research question is as follows: What themes of participation and reification/management occur among the change agents? The study was qualitative in design using the social learning theory of community of…

  10. Kromoscopy for detection of chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Ewing, Kenneth J.; Sanghera, Jas; Aggarwal, Ishwar D.; Block, Myron J.

    2004-12-01

    The ability of a Kromoscope to discriminate between chemical warfare agent simulants and toxic industrial chemicals is evaluated. The Kromoscope response to the simulants DMMP and DIMP is compared to a pesticide (diazanon) and cyclopentanol. The response of a mid-infrared Kromoscope to the nerve agents VX and GB and the stimulant DF are calculated.

  11. Explor@ Advisory Agent: Tracing the Student's Trail.

    ERIC Educational Resources Information Center

    Lundgren-Cayrol, Karin; Paquette, Gilbert; Miara, Alexis; Bergeron, Frederick; Rivard, Jacques; Rosca, Ioan

    This paper presents research and development of an adaptive World Wide Web-based system called Explor@ Advisory Agent, capable of tailoring advice to the individual student's needs, actions, and reactions toward pedagogical events, as well as according to diagnosis of content acquisition. Explor@ Advisory Agent consists of two sub-systems, the…

  12. The Change Agent's Guide. Second Edition.

    ERIC Educational Resources Information Center

    Havelock, Ronald G.; Zlotolow, Steve

    This guidebook describes how successful change happens and how change agents can organize their work to make it happen. It is designed to help change agents in various organizational settings understand the dimensions of the problem and the social situation; organize a plan for change; know what to look for and what to avoid in one's self, team,…

  13. Your company's secret change agents.

    PubMed

    Pascale, Richard Tanner; Sternin, Jerry

    2005-05-01

    Organizational change has traditionally come about through top-down initiatives such as hiring experts or importing best-of-breed practices. Such methods usually result in companywide rollouts of templates mandated from on high. These do little to get people excited. But within every organization, there are a few individuals who find unique ways to look at problems that seem impossible to solve. Although these change agents start out with the same tools and access to resources as their peers, they are able to see solutions where others do not. They find a way to bridge the divide between what is happening and what is possible. These positive deviants are the key, the authors believe, to a better way of creating organizational change. Your company can make the most of their methods by following six steps. In Step 1, Make the group the guru, the members of the community are engaged in the process of their own evolution. Step 2, Reframe through facts, entails restating the problem in a way that opens minds to new possibilities. Step 3, Make it safe to learn, involves creating an environment that supports innovative ideas. In Step 4, Make the problem concrete, the community combats abstraction by stating uncomfortable truths. In Step 5, Leverage social proof, the community looks to the larger society for examples of solutions that have worked in parallel situations. In Step 6, Confound the immune defense response, solutions are introduced organically from within the group in a way that promotes acceptance. Throughout the steps, the leader must suspend his or her traditional role in favor of more facilitatory practices. The positive-deviance approach has unearthed solutions to such complicated and diverse problems as malnutrition in Mali and human trafficking in East Java. This methodology can help solve even the most extreme dilemmas. PMID:15929405

  14. Trust method for multi-agent consensus

    NASA Astrophysics Data System (ADS)

    Mikulski, Dariusz G.; Lewis, Frank L.; Gu, Edward Y.; Hudas, Greg R.

    2012-06-01

    The consensus problem in multi-agent systems often assumes that all agents are equally trustworthy to seek agreement. But for multi-agent military applications - particularly those that deal with sensor fusion or multi-robot formation control - this assumption may create the potential for compromised network security or poor cooperative performance. As such, we present a trust-based solution for the discrete-time multi-agent consensus problem and prove its asymptotic convergence in strongly connected digraphs. The novelty of the paper is a new trust algorithm called RoboTrust, which is used to calculate trustworthiness in agents using observations and statistical inferences from various historical perspectives. The performance of RoboTrust is evaluated within the trust-based consensus protocol under different conditions of tolerance and confirmation.

  15. Can Space Applications Benefit from Intelligent Agents?

    NASA Astrophysics Data System (ADS)

    Varghese, Blesson; McKee, Gerard

    The work reported in this paper proposes a Swarm-Array computing approach based on 'Intelligent Agents' to apply autonomic computing concepts to parallel computing systems and build reliable systems for space applications. Swarm-array computing is a swarm robotics inspired, novel computing approach considered as a path to achieve autonomy in parallel computing systems. In the intelligent agent approach, a task to be executed on parallel computing cores is considered as a swarm of autonomous agents. A task is carried to a computing core by carrier agents and can be seamlessly transferred between cores in the event of a predicted failure, thereby achieving self-* objectives of autonomic computing. The approach is validated on a multi-agent simulator.

  16. An agent based model of genotype editing

    SciTech Connect

    Rocha, L. M.; Huang, C. F.

    2004-01-01

    This paper presents our investigation on an agent-based model of Genotype Editing. This model is based on several characteristics that are gleaned from the RNA editing system as observed in several organisms. The incorporation of editing mechanisms in an evolutionary agent-based model provides a means for evolving agents with heterogenous post-transcriptional processes. The study of this agent-based genotype-editing model has shed some light into the evolutionary implications of RNA editing as well as established an advantageous evolutionary computation algorithm for machine learning. We expect that our proposed model may both facilitate determining the evolutionary role of RNA editing in biology, and advance the current state of research in agent-based optimization.

  17. Ecology Based Decentralized Agent Management System

    NASA Technical Reports Server (NTRS)

    Peysakhov, Maxim D.; Cicirello, Vincent A.; Regli, William C.

    2004-01-01

    The problem of maintaining a desired number of mobile agents on a network is not trivial, especially if we want a completely decentralized solution. Decentralized control makes a system more r e bust and less susceptible to partial failures. The problem is exacerbated on wireless ad hoc networks where host mobility can result in significant changes in the network size and topology. In this paper we propose an ecology-inspired approach to the management of the number of agents. The approach associates agents with living organisms and tasks with food. Agents procreate or die based on the abundance of uncompleted tasks (food). We performed a series of experiments investigating properties of such systems and analyzed their stability under various conditions. We concluded that the ecology based metaphor can be successfully applied to the management of agent populations on wireless ad hoc networks.

  18. For whom will the Bayesian agents vote?

    NASA Astrophysics Data System (ADS)

    Caticha, Nestor; Cesar, Jonatas; Vicente, Renato

    2015-04-01

    Within an agent-based model where moral classifications are socially learned, we ask if a population of agents behaves in a way that may be compared with conservative or liberal positions in the real political spectrum. We assume that agents first experience a formative period, in which they adjust their learning style acting as supervised Bayesian adaptive learners. The formative phase is followed by a period of social influence by reinforcement learning. By comparing data generated by the agents with data from a sample of 15000 Moral Foundation questionnaires we found the following. 1. The number of information exchanges in the formative phase correlates positively with statistics identifying liberals in the social influence phase. This is consistent with recent evidence that connects the dopamine receptor D4-7R gene, political orientation and early age social clique size. 2. The learning algorithms that result from the formative phase vary in the way they treat novelty and corroborative information with more conservative-like agents treating it more equally than liberal-like agents. This is consistent with the correlation between political affiliation and the Openness personality trait reported in the literature. 3. Under the increase of a model parameter interpreted as an external pressure, the statistics of liberal agents resemble more those of conservative agents, consistent with reports on the consequences of external threats on measures of conservatism. We also show that in the social influence phase liberal-like agents readapt much faster than conservative-like agents when subjected to changes on the relevant set of moral issues. This suggests a verifiable dynamical criterium for attaching liberal or conservative labels to groups.

  19. A user-system interface agent

    NASA Technical Reports Server (NTRS)

    Wakim, Nagi T.; Srivastava, Sadanand; Bousaidi, Mehdi; Goh, Gin-Hua

    1995-01-01

    Agent-based technologies answer to several challenges posed by additional information processing requirements in today's computing environments. In particular, (1) users desire interaction with computing devices in a mode which is similar to that used between people, (2) the efficiency and successful completion of information processing tasks often require a high-level of expertise in complex and multiple domains, (3) information processing tasks often require handling of large volumes of data and, therefore, continuous and endless processing activities. The concept of an agent is an attempt to address these new challenges by introducing information processing environments in which (1) users can communicate with a system in a natural way, (2) an agent is a specialist and a self-learner and, therefore, it qualifies to be trusted to perform tasks independent of the human user, and (3) an agent is an entity that is continuously active performing tasks that are either delegated to it or self-imposed. The work described in this paper focuses on the development of an interface agent for users of a complex information processing environment (IPE). This activity is part of an on-going effort to build a model for developing agent-based information systems. Such systems will be highly applicable to environments which require a high degree of automation, such as, flight control operations and/or processing of large volumes of data in complex domains, such as the EOSDIS environment and other multidisciplinary, scientific data systems. The concept of an agent as an information processing entity is fully described with emphasis on characteristics of special interest to the User-System Interface Agent (USIA). Issues such as agent 'existence' and 'qualification' are discussed in this paper. Based on a definition of an agent and its main characteristics, we propose an architecture for the development of interface agents for users of an IPE that is agent-oriented and whose resources

  20. Biological agents database in the armed forces.

    PubMed

    Niemcewicz, Marcin; Kocik, Janusz; Bielecka, Anna; Wierciński, Michał

    2014-10-01

    Rapid detection and identification of the biological agent during both, natural or deliberate outbreak is crucial for implementation of appropriate control measures and procedures in order to mitigate the spread of disease. Determination of pathogen etiology may not only support epidemiological investigation and safety of human beings, but also enhance forensic efforts in pathogen tracing, collection of evidences and correct inference. The article presents objectives of the Biological Agents Database, which was developed for the purpose of the Ministry of National Defense of the Republic of Poland under the European Defence Agency frame. The Biological Agents Database is an electronic catalogue of genetic markers of highly dangerous pathogens and biological agents of weapon of mass destruction concern, which provides full identification of biological threats emerging in Poland and in locations of activity of Polish troops. The Biological Agents Database is a supportive tool used for tracing biological agents' origin as well as rapid identification of agent causing the disease of unknown etiology. It also provides support in diagnosis, analysis, response and exchange of information between institutions that use information contained in it. Therefore, it can be used not only for military purposes, but also in a civilian environment. PMID:25033774

  1. [Decorporation agents for internal radioactive contamination].

    PubMed

    Ohmachi, Yasushi

    2015-01-01

    When radionuclides are accidentally ingested or inhaled, blood circulation or tissue/organ deposition of the radionuclides causes systemic or local radiation effects. In such cases, decorporation therapy is used to reduce the health risks due to their intake. Decorporation therapy includes reduction and/or inhibition of absorption from the gastrointestinal tract, isotopic dilution, and the use of diuretics, adsorbents, and chelating agents. For example, penicillamine is recommended as a chelating agent for copper contamination, and diethylene triamine pentaacetic acid is approved for the treatment of internal contamination with plutonium. During chelation therapy, the removal effect of the drugs should be monitored using a whole-body counter and/or bioassay. Some authorities, such as the National Council on Radiation Protection and Measurements and International Atomic Energy Agency, have reported recommended decorporation agents for each radionuclide. However, few drugs are approved by the US Food and Drug Administration, and many are off-label-use agents. Because many decontamination agents are drugs that have been available for a long time and have limited efficacy, the development of new, higher-efficacy drugs has been carried out mainly in the USA and France. In this article, in addition to an outline of decorporation agents for internal radioactive contamination, an outline of our research on decorporation agents for actinide (uranium and plutonium) contamination and for radio-cesium contamination is also presented. PMID:25832835

  2. Scoping Planning Agents With Shared Models

    NASA Technical Reports Server (NTRS)

    Bedrax-Weiss, Tania; Frank, Jeremy D.; Jonsson, Ari K.; McGann, Conor

    2003-01-01

    In this paper we provide a formal framework to define the scope of planning agents based on a single declarative model. Having multiple agents sharing a single model provides numerous advantages that lead to reduced development costs and increase reliability of the system. We formally define planning in terms of extensions of an initial partial plan, and a set of flaws that make the plan unacceptable. A Flaw Filter (FF) allows us to identify those flaws relevant to an agent. Flaw filters motivate the Plan Identification Function (PIF), which specifies when an agent is is ready hand control to another agent for further work. PIFs define a set of plan extensions that can be generated from a model and a plan request. FFs and PIFs can be used to define the scope of agents without changing the model. We describe an implementation of PIFsand FFswithin the context of EUROPA, a constraint-based planning architecture, and show how it can be used to easily design many different agents.

  3. Biological agents as occupational hazards - selected issues.

    PubMed

    Dutkiewicz, Jacek; Cisak, Ewa; Sroka, Jacek; Wójcik-Fatla, Angelina; Zając, Violetta

    2011-01-01

    There are two main groups of biological agents regarded as occupational hazards: allergenic and/or toxic agents forming bioaerosols, and agents causing zoonoses and other infectious diseases. Bioaerosols occurring in the agricultural work environments comprise: bacteria, fungi, high molecular polymers produced by bacteria (endotoxin) or by fungi (β-glucans), low molecular secondary metabolites of fungi (mycotoxins, volatile organic compounds) and various particles of plant and animal origin. All these agents could be a cause of allergic and/or immunotoxic occupational diseases of respiratory organ (airways inflammation, rhinitis, toxic pneumonitis, hypersensitivity pneumonitis and asthma), conjunctivitis and dermatitis in exposed workers. Very important among zoonotic agents causing occupational diseases are those causing tick-borne diseases: Lyme borreliosis, anaplasmosis, babesiosis, bartonellosis. Agricultural workers in tropical zones are exposed to mosquito bites causing malaria, the most prevalent vector-borne disease in the world. The group of agents causing other, basically not vector-borne zoonoses, comprises those evoking emerging or re-emerging diseases of global concern, such as: hantaviral diseases, avian and swine influenza, Q fever, leptospiroses, staphylococcal diseases caused by the methicillin-resistant Staphylococcus aureus (MRSA) strains, and diseases caused by parasitic protozoa. Among other infectious, non-zoonotic agents, the greatest hazard for health care workers pose the blood-borne human hepatitis and immunodeficiency viruses (HBV, HCV, HIV). Of interest are also bacteria causing legionellosis in people occupationally exposed to droplet aerosols, mainly from warm water. PMID:22216801

  4. Agent-Supported Mission Operations Teamwork

    NASA Technical Reports Server (NTRS)

    Malin, Jane T.

    2003-01-01

    This slide presentation reviews the development of software agents to support of mission operations teamwork. The goals of the work was to make automation by agents easy to use, supervise and direct, manage information and communication to decrease distraction, interruptions, workload and errors, reduce mission impact of off-nominal situations and increase morale and decrease turnover. The accomplishments or the project are: 1. Collaborative agents - mixed initiative and creation of instructions for mediating agent 2. Methods for prototyping, evaluating and evolving socio-technical systems 3. Technology infusion: teamwork tools in mISSIons 4. Demonstrations in simulation testbed An example of the use of agent is given, the use of an agent to monitor a N2 tank leak. An incomplete instruction to the agent is handled with mediating assistants, or Intelligent Briefing and Response Assistant (IBRA). The IBRA Engine also watches data stream for triggers and executes Act-Whenever actions. There is also a Briefing and Response Instruction (BRI) which is easy for a discipline specialist to create through a BRI editor.

  5. Persistent agents in Axelrod's social dynamics model

    NASA Astrophysics Data System (ADS)

    Reia, Sandro M.; Neves, Ubiraci P. C.

    2016-01-01

    Axelrod's model of social dynamics has been studied under the effect of external media. Here we study the formation of cultural domains in the model by introducing persistent agents. These are agents whose cultural traits are not allowed to change but may be spread through local neighborhood. In the absence of persistent agents, the system is known to present a transition from a monocultural to a multicultural regime at some critical Q (number of traits). Our results reveal a dependence of critical Q on the occupation probability p of persistent agents and we obtain the phase diagram of the model in the (p,Q) -plane. The critical locus is explained by the competition of two opposite forces named here barrier and bonding effects. Such forces are verified to be caused by non-persistent agents which adhere (adherent agents) to the set of traits of persistent ones. The adherence (concentration of adherent agents) as a function of p is found to decay for constant Q. Furthermore, adherence as a function of Q is found to decay as a power law with constant p.

  6. Metareasoning and Social Evaluations in Cognitive Agents

    NASA Astrophysics Data System (ADS)

    Pinyol, Isaac; Sabater-Mir, Jordi

    Reputation mechanisms have been recognized one of the key technologies when designing multi-agent systems. They are specially relevant in complex open environments, becoming a non-centralized mechanism to control interactions among agents. Cognitive agents tackling such complex societies must use reputation information not only for selecting partners to interact with, but also in metareasoning processes to change reasoning rules. This is the focus of this paper. We argue about the necessity to allow, as a cognitive systems designers, certain degree of freedom in the reasoning rules of the agents. We also describes cognitive approaches of agency that support this idea. Furthermore, taking as a base the computational reputation model Repage, and its integration in a BDI architecture, we use the previous ideas to specify metarules and processes to modify at run-time the reasoning paths of the agent. In concrete we propose a metarule to update the link between Repage and the belief base, and a metarule and a process to update an axiom incorporated in the belief logic of the agent. Regarding this last issue we also provide empirical results that show the evolution of agents that use it.

  7. Natural chelating agents for radionuclide decorporation

    DOEpatents

    Premuzic, E.T.

    1985-06-11

    This invention relates to the production of metal-binding compounds useful for the therapy of heavy metal poisoning, for biological mining and for decorporation of radionuclides. The present invention deals with an orderly and effective method of producing new therapeutically effective chelating agents. This method uses challenge biosynthesis for the production of chelating agents that are specific for a particular metal. In this approach, the desired chelating agents are prepared from microorganisms challenged by the metal that the chelating agent is designed to detoxify. This challenge induces the formation of specific or highly selective chelating agents. The present invention involves the use of the challenge biosynthetic method to produce new complexing/chelating agents that are therapeutically useful to detoxify uranium, plutonium, thorium and other toxic metals. The Pseudomonas aeruginosa family of organisms is the referred family of microorganisms to be used in the present invention to produce the new chelating agent because this family is known to elaborate strains resistant to toxic metals.

  8. Designing Agent Utilities for Coordinated, Scalable and Robust Multi-Agent Systems

    NASA Technical Reports Server (NTRS)

    Tumer, Kagan

    2005-01-01

    Coordinating the behavior of a large number of agents to achieve a system level goal poses unique design challenges. In particular, problems of scaling (number of agents in the thousands to tens of thousands), observability (agents have limited sensing capabilities), and robustness (the agents are unreliable) make it impossible to simply apply methods developed for small multi-agent systems composed of reliable agents. To address these problems, we present an approach based on deriving agent goals that are aligned with the overall system goal, and can be computed using information readily available to the agents. Then, each agent uses a simple reinforcement learning algorithm to pursue its own goals. Because of the way in which those goals are derived, there is no need to use difficult to scale external mechanisms to force collaboration or coordination among the agents, or to ensure that agents actively attempt to appropriate the tasks of agents that suffered failures. To present these results in a concrete setting, we focus on the problem of finding the sub-set of a set of imperfect devices that results in the best aggregate device. This is a large distributed agent coordination problem where each agent (e.g., device) needs to determine whether to be part of the aggregate device. Our results show that the approach proposed in this work provides improvements of over an order of magnitude over both traditional search methods and traditional multi-agent methods. Furthermore, the results show that even in extreme cases of agent failures (i.e., half the agents failed midway through the simulation) the system's performance degrades gracefully and still outperforms a failure-free and centralized search algorithm. The results also show that the gains increase as the size of the system (e.g., number of agents) increases. This latter result is particularly encouraging and suggests that this method is ideally suited for domains where the number of agents is currently in the

  9. Pharmacologic agents for mucus clearance in bronchiectasis.

    PubMed

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis. PMID:22640851

  10. Fluorescence quenching of flavins by reductive agents

    NASA Astrophysics Data System (ADS)

    Penzkofer, A.; Bansal, A. K.; Song, S.-H.; Dick, B.

    2007-07-01

    The fluorescence behaviour of the flavins riboflavin, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and lumiflavin in aqueous solution at pH 8 in the presence of the reducing agents β-mercaptoethanol (β-ME), dithiothreitol (DTT), and sodium nitrite (NaNO 2) is studied under aerobic conditions. The fluorescence quantum yields and fluorescence lifetimes are determined as a function of the reducing agent concentration. For all three reducing agents diffusion controlled dynamic fluorescence quenching is observed which is thought to be due to photo-induced reductive electron transfer. For DTT additionally static fluorescence quenching occurs.

  11. Knowledge Acquisition Ubiquitous Agent Infrastructure (KAUAI)

    SciTech Connect

    2009-09-15

    Mobile agents are autonomous software programs that can move from one host to another during the course of execution. The KAUAI computer code is a middleware that supports the rapid development and deployment of mobile agent based applications. It is built on the J2ME (CLDC) technology. KAUAI handles the instantiation, execution, transportation, and disposal of mobile agents. KAUAI masks the underlying hardware and communication details from application developers and provides flexible functionality for distributed computing. KAUAI supports software development in systems that involve a large number of heterogeneous computing platforms ranging from workstations to handheld devices.

  12. Resuscitative challenges in nerve agent poisoning.

    PubMed

    Ben Abraham, Ron; Weinbroum, Avi A

    2003-09-01

    The threat of weapons of mass destruction such as nerve agents has become real since last year. The medical community has established protocols for the rapid evacuation and decontamination of affected civilians. However, protocols for resuscitative measures or acute perioperative care in cases of life-saving surgical interventions in toxic-traumatized casualties are still lacking. The database concerning the effects of nerve agent poisoning in humans is limited, and is largely based on reports of unintentional exposures to pesticide organophosphate poisoning and similar chemical substances. In this review, we summarize the knowledge on the possible pharmacological interactions between nerve agents and acute care. PMID:12972890

  13. Fennel and anise as estrogenic agents.

    PubMed

    Albert-Puleo, M

    1980-12-01

    Fennel, Foeniculum vulgare, and anise, Pimpinella anisum, are plants which have been used as estrogenic agents for millennia. Specifically, they have been reputed to increase milk secretion, promote menstruation, facilitate birth, alleviate the symptoms of the male climacteric, and increase libido. In the 1930s, some interest was shown in these plants in the development of synthetic estrogens. The main constituent of the essential oils of fennel and anise, anethole, has been considered to be the active estrogenic agent. However, further research suggests that the actual pharmacologically active agents are polymers of anethole, such as dianethole and photoanethole. PMID:6999244

  14. Dynamics of adaptive agents with asymmetric information

    NASA Astrophysics Data System (ADS)

    DeMartino, Andrea; Galla, Tobias

    2005-08-01

    We apply path integral techniques to study the dynamics of agent-based models with asymmetric information structures. In particular, we devise a batch version of a model proposed originally by Berg et al (2001 Quantitative Finance 1 203), and convert the coupled multi-agent processes into an effective-agent problem from which the dynamical order parameters in ergodic regimes can be derived self-consistently together with the corresponding phase structure. Our dynamical study complements and extends the available static theory. Results are confirmed by numerical simulations.

  15. The search for scrapie agent nucleic acid.

    PubMed Central

    Aiken, J M; Marsh, R F

    1990-01-01

    Despite decades of research, the identity of the scrapie agent has remained elusive. Recent studies have discovered much about the influence of the host genome upon scrapie infection, yet relatively little is known about the causative agent itself. The predominant hypothesis in the scrapie field (the prion hypothesis) argues that the disease is the result of an infectious protein and that nucleic acid is not required for infection. Biological studies of the scrapie agent, however, suggest that a nucleic acid may be involved in the disease. Sensitive molecular biology techniques have yet to identify this putative nucleic acid. PMID:2120561

  16. Knowledge Acquisition Ubiquitous Agent Infrastructure (KAUAI)

    Energy Science and Technology Software Center (ESTSC)

    2009-09-15

    Mobile agents are autonomous software programs that can move from one host to another during the course of execution. The KAUAI computer code is a middleware that supports the rapid development and deployment of mobile agent based applications. It is built on the J2ME (CLDC) technology. KAUAI handles the instantiation, execution, transportation, and disposal of mobile agents. KAUAI masks the underlying hardware and communication details from application developers and provides flexible functionality for distributed computing.more » KAUAI supports software development in systems that involve a large number of heterogeneous computing platforms ranging from workstations to handheld devices.« less

  17. Learning-by-Teaching: Designing Teachable Agents with Intrinsic Motivation

    ERIC Educational Resources Information Center

    Zhao, Guopeng; Ailiya; Shen, Zhiqi

    2012-01-01

    Teachable agent is a type of pedagogical agent which instantiates Learning-by-Teaching theory through simulating a "naive" learner in order to motivate students to teach it. This paper discusses the limitation of existing teachable agents and incorporates intrinsic motivation to the agent model to enable teachable agents with initiative behaviors…

  18. Web Search Agents: "One-Stop Shopping" for Researchers.

    ERIC Educational Resources Information Center

    Perez, Ernest

    2002-01-01

    Explains Web search agents as tools that apply intelligent agent software technology for the purpose of automating, improving, and speeding up online search operations. Topics include intelligent desktop agents; search agent marketplace; comparing Web search agents; subjective evaluations; and use by researchers. (LRW)

  19. Synthesis, 3D-QSAR analysis and biological evaluation of quinoxaline 1,4-di-N-oxide derivatives as antituberculosis agents.

    PubMed

    Pan, Yuanhu; Li, Panpan; Xie, Shuyu; Tao, Yanfei; Chen, Dongmei; Dai, Menghong; Hao, Haihong; Huang, Lingli; Wang, Yulian; Wang, Liye; Liu, Zhenli; Yuan, Zonghui

    2016-08-15

    A series of quinoxaline 1,4-di-N-oxide derivatives variously substituted at C-2 position were synthesized and evaluated for in vitro antimycobacterial activity. Seventeen compounds exhibited potential activity (MIC ⩽6.25μg/mL) against Mycobacterium tuberculosis (H37Rv), in particular the compounds 3d and 3j having an MIC value of 0.39μg/mL. None of the compounds exhibited cytotoxicity when using an MTT assay in VERO cells. To further investigate the structure-activity relationship, CoMFA (q(2)=0.507, r(2)=0.923) and CoMSIA (q(2)=0.665, r(2)=0.977) models were performed on the basis of antimycobacterial activity data. The 3D-QSAR study of these compounds can provide useful information for further rational design of novel quinoxaline 1,4-di-N-oxides for treatment of tuberculosis. PMID:27426298

  20. 21 CFR 178.3860 - Release agents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... be safely used as release agents in petroleum wax complying with § 178.3710 and in polymeric resins... bran wax For use only in plastics intended for contact with dry foods identified as Type VIII in...

  1. 21 CFR 178.3860 - Release agents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... be safely used as release agents in petroleum wax complying with § 178.3710 and in polymeric resins... bran wax For use only in plastics intended for contact with dry foods identified as Type VIII in...

  2. 21 CFR 178.3860 - Release agents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... be safely used as release agents in petroleum wax complying with § 178.3710 and in polymeric resins... bran wax For use only in plastics intended for contact with dry foods identified as Type VIII in...

  3. 21 CFR 178.3860 - Release agents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... be safely used as release agents in petroleum wax complying with § 178.3710 and in polymeric resins... bran wax For use only in plastics intended for contact with dry foods identified as Type VIII in...

  4. Opportunistic Behavior in Motivated Learning Agents.

    PubMed

    Graham, James; Starzyk, Janusz A; Jachyra, Daniel

    2015-08-01

    This paper focuses on the novel motivated learning (ML) scheme and opportunistic behavior of an intelligent agent. It extends previously developed ML to opportunistic behavior in a multitask situation. Our paper describes the virtual world implementation of autonomous opportunistic agents learning in a dynamically changing environment, creating abstract goals, and taking advantage of arising opportunities to improve their performance. An opportunistic agent achieves better results than an agent based on ML only. It does so by minimizing the average value of all need signals rather than a dominating need. This paper applies to the design of autonomous embodied systems (robots) learning in real-time how to operate in a complex environment. PMID:25291798

  5. Engineering Agent Organisations in a Business Environment

    NASA Astrophysics Data System (ADS)

    Traskas, Dimitris; Padget, Julian

    Motivated by demands from the commercial world for software systems that can assist in the reorganisation of processes for the purpose of reducing business complexity, we discuss the benefits and challenges of the multi-agent approach. We concentrate on the engineering aspects of large scale multi-agent systems and begin our exploration by focusing on a real world example from the call centre industry. The critical call routing process seems appropriate and useful in presenting our ideas and provides a good starting point for the development of agent organisations capable of self-management and coordination. The main contributions of this work can be summarised as the demonstration of the value of agent organisational models that do not replicate the typical hierarchical structures observed in human organisations and that a quite basic peer-to-peer structure produces very similar performance indicators to a mature simulator that uses conventional techniques, suggesting further improvements may readily be realized.

  6. Tax Examiners, Revenue Agents, and Collectors.

    ERIC Educational Resources Information Center

    McCarron, Kevin M.

    2001-01-01

    Describes the nature of the work of tax examiners, revenue agents, and collectors. Includes employment outlook; benefits and drawbacks; qualifications, training, and advancement; and sources of additional information. (JOW)

  7. Natural compounds as anticancer agents: Experimental evidence

    PubMed Central

    Wang, Jiao; Jiang, Yang-Fu

    2012-01-01

    Cancer prevention research has drawn much attention worldwide. It is believed that some types of cancer can be prevented by following a healthy life style. Cancer chemoprevention by either natural or synthetic agents is a promising route towards lowering cancer incidence. In recent years, the concept of cancer chemoprevention has evolved greatly. Experimental studies in animal models demonstrate that the reversal or suppression of premalignant lesions by chemopreventive agents is achievable. Natural occurring agents such as dietary phytochemicals, tea polyphenols and resveratrol show chemopreventive activity in animal models. Moreover, clinical trials for testing the safety and efficacy of a variety of natural agents in preventing or treating human malignancy have been ongoing. Here, we summarize experimental data on the chemopreventive or tumor suppressive effects of several natural compounds including curcumin, (-)-epigallocatechin-3-gallate, resveratrol, indole-3-carbinol, and vitamin D. PMID:24520533

  8. Porphyria Cutanea Tarda and Agent Orange

    MedlinePlus

    ... survivors' benefits . Research on porphyria cutanea tarda and herbicides The Health and Medicine Division (HMD) (formally known ... on " Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam " that there was sufficient evidence ...

  9. Soft Tissue Sarcomas and Agent Orange

    MedlinePlus

    ... survivors' benefits . Research on soft tissue sarcoma and herbicides The Health and Medicine Division (formally known as ... report " Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam " and other updates that there ...

  10. What Are Anticoagulants and Antiplatelet Agents?

    MedlinePlus

    ... Anticoagulants and antiplatelet agents are medicines that reduce blood clotting in an artery, a vein or the heart. ... are drugs that are given to prevent your blood from clotting or prevent existing clots from getting larger. They ...

  11. Chronic gastrointestinal haemorrhage controlled by antifibrinolytic agents.

    PubMed Central

    Willoughby, J. M.

    1989-01-01

    Antifibrinolytic agents are used chiefly for control of acute haemorrhage. Their applicability to chronic bleeding from inflammatory lesions of the gastrointestinal tract is illustrated by two case histories. PMID:2813242

  12. Does Agent Orange cause birth defects?

    PubMed

    Friedman, J M

    1984-04-01

    Large quantities of the defoliant, Agent Orange, were sprayed in Vietnam during the war. Agent Orange was composed of two herbicides: 2,4-D and 2,4,5-T, the latter contaminated by small amounts of a highly toxic dioxin (TCDD). The constituents of Agent Orange are capable of producing gene mutations and chromosomal aberrations, at least in some experimental circumstances. TCDD and 2,4,5-T are teratogenic in mice and perhaps in other mammals, but the teratogenicity of these chemicals has not been convincingly demonstrated in humans. There is currently no scientific evidence which indicates that men who were previously exposed to Agent Orange are at increased risk of having children with birth defects, but available data are inadequate to assess this possibility critically. PMID:6377557

  13. A Highly Secure Mobile Agent System Architecture

    NASA Astrophysics Data System (ADS)

    Okataku, Yasukuni; Okutomi, Hidetoshi; Yoshioka, Nobukazu; Ohgishi, Nobuyuki; Honiden, Shinichi

    We propose a system architecture for mobile agents to improve their security in the environments of insecure networks and non-sophisticated terminals such as PDAs. As mobile agents freely migrate onto their favorite terminals through insecure networks or terminals, it is not appropriate for them to store some secret information for authentication and encryption/decryption. We introduce one and more secure nodes(OASIS NODE) for securely generating and verifying authentication codes. The each agent’s data are encrypted by a pseudo-chaos cipher mechanism which doesn’t need any floating processing co-processor. We’ve constructed a prototype system on a Java mobile agent framework, “Bee-gent" which implements the proposed authentication and cipher mechanisms, and evaluated their performances and their applicability to business fields such as an auction system by mobile agents.

  14. Competing intelligent search agents in global optimization

    SciTech Connect

    Streltsov, S.; Vakili, P.; Muchnik, I.

    1996-12-31

    In this paper we present a new search methodology that we view as a development of intelligent agent approach to the analysis of complex system. The main idea is to consider search process as a competition mechanism between concurrent adaptive intelligent agents. Agents cooperate in achieving a common search goal and at the same time compete with each other for computational resources. We propose a statistical selection approach to resource allocation between agents that leads to simple and efficient on average index allocation policies. We use global optimization as the most general setting that encompasses many types of search problems, and show how proposed selection policies can be used to improve and combine various global optimization methods.

  15. Efficacy of "mucoregulatory" agents in Young's syndrome.

    PubMed Central

    Currie, D C; Greenstone, M; Pavia, D; Agnew, J E; Pellow, P; Clarke, S W; Hendry, W F; Cole, P J

    1988-01-01

    Eight patients with Young's syndrome were treated with four "mucoregulatory" agents for eight weeks in a randomised, open crossover study. There was no improvement in tracheobronchial clearance, pulmonary function, or sperm count. PMID:3047900

  16. Change Agent Research and Organizational Change

    ERIC Educational Resources Information Center

    Ragab, A. Megid; And Others

    1977-01-01

    Change Agent Research (CAR) is a "people" change approach that contrasts what a group (or individual) thinks it is doing with the actual behavior that exists. The applicability of CAR methodology to organizations is discussed. (Author)

  17. 21 CFR 181.28 - Release agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... heating 4 hours at 200 °C.; viscosity 300 centisokes, 600 centisokes at 25 °C, specific gravity 0.96 to 0... FOOD INGREDIENTS Specific Prior-Sanctioned Food Ingredients § 181.28 Release agents....

  18. Anti-mycobacterial activity of thymine derivatives bearing boron clusters.

    PubMed

    Adamska, Anna; Rumijowska-Galewicz, Anna; Ruszczynska, Anna; Studzińska, Mirosława; Jabłońska, Agnieszka; Paradowska, Edyta; Bulska, Ewa; Munier-Lehmann, Hélene; Dziadek, Jarosław; Leśnikowski, Zbigniew J; Olejniczak, Agnieszka B

    2016-10-01

    A series of novel thymine derivatives bearing lipophilic, electron-neutral 1,2-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane or hydrophilic 7,8-dicarba-nido-undecaborate anions were synthesized. Synthesis was performed via copper(I)-catalysed Huisgen-Meldal-Sharpless 1,3-dipolar cycloaddition of N(1)-propargylthymine or N(1),N(3)-bispropargylthymine to 1-(3-azidopropyl)-1,2-dicarba-closo-dodecaborane. The obtained compounds were tested in vitro against Mycobacterium tuberculosis thymidylate kinase (TMPKmt) and as inhibitors of mycobacteria growth in culture using both saprophytic Mycobacterium smegmatis (M. smegmatis) and pathogenic Mycobacterium tuberculosis (M. tuberculosis) strains. The most potent TMPKmt inhibitor in the series contained two negatively charged 7,8-dicarba-nido-undecaborate modifications at positions 1 and 3 of thymine (9) and exhibited a Ki value of 1.5 μM. The most potent inhibitors of mycobacteria growth was compound 5 with one electron-neutral 1,2-dicarba-closo-dodecaborane modification at position 1 of thymine, and compound 8 with two modifications, at position 1 and 3. Both compounds completely inhibited M. smegmatis proliferation at a concentration of 100 μg/mL (0.25 mM and 0.15 mM, respectively). PMID:27236064

  19. Triterpenes and the Antimycobacterial Activity of Duroia macrophylla Huber (Rubiaceae)

    PubMed Central

    Martins, Daiane; Carrion, Lillian Lucas; Ramos, Daniela Fernandes; Salomé, Kahlil Schwanka; da Silva, Pedro Eduardo Almeida; Barison, Andersson; Nunez, Cecilia Veronica

    2013-01-01

    Duroia macrophylla popularly known as “cabeça-de-urubú,” “apuruí,” or “puruí-grande-da-mata” occurs in the Amazon Forest. Its leaves and branches were collected twice and extracted with dichloromethane and methanol. All extracts were subjected to phytochemical investigation and terpenes and flavonoids were found in all dichloromethane and methanol extracts, respectively. Methanol extracts from both branches (1st collection) and leaves (2nd collection) presented hydrolyzed tannins, yet alkaloids were only detected in the dichloromethane and methanol extracts from branches at the 2nd collection. Phenol compounds were found in both dichloromethane extracts' collections. The action of every extract was assayed against Mycobacterium tuberculosis (RMPr, H37Rv, and INHr strains), showing that the dichloromethane extract from leaves (1st collection) has the major biological activity, with a MIC of 6.25 μg/mL for the INHr strain, 25.0 μg/mL for the RMPr strain, and ≤6.25 μg/mL for the H37Rv strain. The chromatographic fractioning of the dichloromethane extract from leaves (1st collection) yielded the isolation of two triterpenes: oleanolic and ursolic acids, which were identified by NMR analysis and reported for the first time in the Duroia genus. PMID:23509750

  20. Antiprotozoal and antimycobacterial activities of Persea americana seeds

    PubMed Central

    2013-01-01

    Background Persea americana seeds are widely used in traditional Mexican medicine to treat rheumatism, asthma, infectious processes as well as diarrhea and dysentery caused by intestinal parasites. Methods The chloroformic and ethanolic extracts of P. americana seeds were prepared by maceration and their amoebicidal, giardicidal and trichomonicidal activity was evaluated. These extracts were also tested against Mycobacterium tuberculosis H37Rv, four mono-resistant and two multidrug resistant strains of M. tuberculosis as well as five non tuberculosis mycobacterium strains by MABA assay. Results The chloroformic and ethanolic extracts of P. americana seeds showed significant activity against E. histolytica, G. lamblia and T. vaginalis (IC50 <0.634 μg/ml). The chloroformic extract inhibited the growth of M. tuberculosis H37Rv, M. tuberculosis MDR SIN 4 isolate, three M. tuberculosis H37Rv mono-resistant reference strains and four non tuberculosis mycobacteria (M. fortuitum, M. avium, M. smegmatis and M. absessus) showing MIC values ≤50 μg/ml. Contrariwise, the ethanolic extract affected only the growth of two mono-resistant strains of M. tuberculosis H37Rv and M. smegmatis (MIC ≤50 μg/ml). Conclusions The CHCl3 and EtOH seed extracts from P. americana showed amoebicidal and giardicidal activity. Importantly, the CHCl3 extract inhibited the growth of a MDR M. tuberculosis isolate and three out of four mono-resistant reference strains of M. tuberculosis H37Rv, showing a MIC = 50 μg/ml. This extract was also active against the NTM strains, M. fortuitum, M. avium, M. smegmatis and M. abscessus, with MIC values <50 μg/ml. PMID:23680126

  1. Antimycobacterial Furofuran Lignans from the Roots of Anemopsis californica

    PubMed Central

    Bussey, Robert O; Sy-Cordero, Arlene A; Figueroa, Mario; Carter, Fredrick S.; Falkinham, Joseph O.; Oberlies, Nicholas H.; Cech, Nadja B.

    2015-01-01

    Topical preparations of Anemopsis californica have been used by Native American tribes in the southwestern United States and northern Mexico to treat inflammation and infections. We report results of bioassay-guided isolation conducted on a sample of A. californica roots. The furofuran lignans sesamin (1) and asarinin (2) were isolated and shown to have MIC values ranging from 23 to 395 µM against five different species of environmental nontuberculous mycobacteria. These findings are significant given that these bacteria can cause skin, pulmonary, and lymphatic infections. Crude A. californica extracts were analyzed by liquid chromatography - mass spectrometry (LC-MS), and it was determined that sesamin and asarinin were extracted at relatively high levels from roots (1.7–3.1g/kg and 1.1–1.7 g/kg, respectively), but lower levels from leaves (0.13 g/kg for both compounds). Our findings suggest that the majority of activity of crude A. californica root extracts against nontuberculous mycobacteria can be attributed to the presence of sesamin and asarinin. This paper is the first to report isolation of these compounds from a member of the Saururaceae family, and the first to describe their activity against nontuberculous mycobacteria. PMID:24687738

  2. Antimycobacterial activity of bacteriocins and their complexes with liposomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacteriocins (Bcn) are natural peptides that are secreted by taxonomically distinct bacteria which exert bactericidal activity against other bacterial species. Their capacity to inhibit growth of virulent Mycobacterium tuberculosis H37Rv was evaluated in this study. Five Bcn were purified from sel...

  3. Novel agents for chronic lymphocytic leukemia

    PubMed Central

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is a heterogeneous group of B-cell neoplasm. CLL is typically sensitive to a variety of cytotoxic agents, but relapse frequently occurs with conventional approaches. The treatment of CLL is evolving rapidly with the introduction of novel drugs, such as bendamustine, ofatumumab, lenalidomide, ibrutinib, idelalisib, veltuzumab, XmAb5574, navitoclax, dasatinib, alvespimycin, and TRU-016. This review summarizes the most current clinical experiences with these agents in the treatment of CLL. PMID:23680477

  4. Precursors to radiopharmaceutical agents for tissue imaging

    DOEpatents

    Srivastava, Prem C.; Knapp, Jr., Furn F.

    1988-01-01

    A class of radiolabeled compounds to be used in tissue imaging that exhibits rapid brain uptake, good brain:blood radioactivity ratios, and long retention times. The imaging agents are more specifically radioiodinated aromatic amines attached to dihydropyridine carriers, that exhibit heart as well as brain specificity. In addition to the radiolabeled compounds, classes of compounds are also described that are used as precursors and intermediates in the preparation of the imaging agents.

  5. Fertility regulating agents from traditional Chinese medicines.

    PubMed

    Kong, Y C; Xie, J X; But, P P

    1986-01-01

    Chinese scientists have capitalized on the rich flora and the ethnomedical experience in China, in their pursuit of fertility regulating agents from natural products. Discoveries range from anti-implantation agents to abortifacient and pregnancy-terminating compounds, as well as a male contraceptive. Chemistry and bioactivity of these compounds and materials are reviewed in this paper, with the hope that further research and collaboration will take place to help solve the problem of population explosion. PMID:3520152

  6. MATE: The multi-agent test environment

    NASA Technical Reports Server (NTRS)

    Mason, Cindy L.

    1992-01-01

    In this report we present the Multi-Agent Test Environment, MATE. MATE is a collection of experiment management tools for assisting in the design, testing, and evaluation of distributed problem-solvers. It provides the experimenter with an automated tool for executing and monitoring experiments choosing among rule bases, number of agents, communication strategies, and inference engines. Using MATE the experimenter can run a series of distributed problem-solving experiments without human intervention.

  7. Anti-arthritic agents: progress and potential.

    PubMed

    Laev, Sergey S; Salakhutdinov, Nariman F

    2015-07-01

    Osteoarthritis and rheumatoid arthritis are the two most common types of arthritis. Cartilage breakdown is a key feature of both diseases which contributes to the pain and joint deformity experienced by patients. Therefore, anti-arthritis drugs are of great importance. The aim of this review is to present recent progress in studies of various agents against osteoarthritis and rheumatoid arthritis. The structures and activities of anti-arthritic agents, which used in medical practice or are in development, are presented and discussed. The effects and mechanisms of action of opioids, glucocorticoids, non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, natural products derived from plants, nutraceuticals, and a number of new and perspective agents are considered. Various perspective targets for the treatment of osteoarthritis and rheumatoid arthritis are also discussed. Trials of good quality are needed to draw solid conclusions regarding efficacy of many of the studied agents. Unfortunately, to date, there is no pharmacologic agent proven to prevent the progression of both diseases, and there is an urgent need for further development of better anti-arthritic agents. PMID:26014481

  8. Distributed knowledge model for multiple intelligent agents

    SciTech Connect

    Li, Y.P.

    1987-01-01

    In the Distributed AI context, there have been some general principles developed to manage the problem solving activities of multiple agents. But there is not yet a domain-independent structure available for organizing multiple agents and managing of the interactions among agents. An organization metaphor is proposed to establish the hierarchical organization as the preferable takes environment for the decision-oriented applications of Distributed AI. As such, distributed problem solving is modeled as organizational problem solving. A generic structure for multiple intelligent agents is then developed. The organization metaphor is a problem-solving method. It outlines the organizational principles for distributed problem solving. However, a problem-solving model does not specify how it itself is to be realized as a computational entity. Therefore, a distributed knowledge model (DKM) is proposed to define the computational constructs in order to realize a distributed problem-solving environment for multiple intelligent agents. A prototype was implemented to show the feasibility of building a multi-agent environment based on DKM.

  9. CHI: A General Agent Communication Framework

    SciTech Connect

    Goldsmith, S.Y.; Phillips, L.R.; Spires, S.V.

    1998-12-17

    We have completed and exercised a communication framework called CHI (CLOS to HTML Interface) by which agents can communicate with humans. CHI follows HTTP (HyperText Transfer Protocol) and produces HTML (HyperText Markup Language) for use by WWW (World-Wide Web) browsers. CHI enables the rapid and dynamic construction of interface mechanisms. The essence of CHI is automatic registration of dynamically generated interface elements to named objects in the agent's internal environment. The agent can access information in these objects at will. State is preserved, so an agent can pursue branching interaction sequences, activate failure recovery behaviors, and otherwise act opportunistically to maintain a conversation. The CHI mechanism remains transparent in multi-agent, multi-user environments because of automatically generated unique identifiers built into the CHI mechanism. In this paper we discuss design, language, implementation, and extension issues, and, by way of illustration, examine the use of the general CHI/HCHI mechanism in a specific international electronic commerce system. We conclude that the CHI mechanism is an effective, efficient, and extensible means of the agent/human communication.

  10. History of chemical and biological warfare agents.

    PubMed

    Szinicz, L

    2005-10-30

    Chemical and biological warfare agents constitute a low-probability, but high-impact risk both to the military and to the civilian population. The use of hazardous materials of chemical or biological origin as weapons and for homicide has been documented since ancient times. The first use of chemicals in terms of weapons of mass destruction goes back to World War I, when on April 22, 1915 large amounts of chlorine were released by German military forces at Ypres, Belgium. Until around the 1970s of the 20th century, the awareness of the threat by chemical and biological agents had been mainly confined to the military sector. In the following time, the development of increasing range delivery systems by chemical and biological agents possessors sensitised public attention to the threat emanating from these agents. Their proliferation to the terrorists field during the 1990s with the expanding scale and globalisation of terrorist attacks suggested that these agents are becoming an increasing threat to the whole world community. The following article gives a condensed overview on the history of use and development of the more prominent chemical and biological warfare agents. PMID:16111798

  11. Intelligent agents for e-commerce applications

    NASA Astrophysics Data System (ADS)

    Vuppala, Krishna

    1999-12-01

    This thesis focuses on development of intelligent agent solutions for e-commerce applications. E-Commerce has several complexities like: lack of information about the players, learning the nature of one's business partners/competitors, finding the right business partner to do business with, using the right strategy to get best profit out of the negotiations etc. The agent models developed can be used in any agent solution for e-commerce. Concepts and techniques from Game Theory and Artificial Intelligence are used. The developed models have several advantages over the existing ones as: the models assume the non-availability of information about other players in the market, the models of players get updated over the time as and when new information comes about the players, the negotiation model incorporates the patience levels of the players and expectations from other players in the market. Power industry has been chosen as the application area for the demonstration of the capabilities and usage of the developed agent models. Two e-commerce scenarios where sellers and buyers can go through the power exchanges to bid in auctions, or make bilateral deals outside of the exchange are addressed. In the first scenario agent helps market participants in coordinating strategies with other participants, bidding in auctions by analyzing and understanding the behavior of other participants. In the second scenario, called "Power Traders Assistant" agent helps power trader, who buys and sells power through bilateral negotiations, in negotiating deals with his customers.

  12. Ultrasonic mixing of epoxy curing agents

    NASA Technical Reports Server (NTRS)

    Hodges, W. T.; St.clair, T. L.

    1983-01-01

    A new technique for mixing solid curing agents into liquid epoxy resins using ultrasonic energy was developed. This procedure allows standard curing agents such as 4,4 prime-diaminodiphenyl sulfone (4,4 prime-DDS) and its 3,3 prime-isomer, (3,3 prime-DDS) to be mixed without prior melting of the curing agent. It also allows curing agents such as 4,4 prime-diaminodiphenyl sulfone (4,4 prime-DDS) and its 3,3 prime-isomer, (3,3 prime-DDS) to be mixed without prior melting of the curing agent. It also allows curing agents with very high melt temperatures such as 4,4 prime-diaminobenzophenone (4,4 prime-DABP) (242 C) to be mixed without premature curing. Four aromatic diamines were ultrasonically blended into MY-720 epoxy resin. These were 4,4 prime-DDS; 3,3 prime-DDA; 4,4 prime-DABP and 3,3 prime-DABP. Unfilled moldings were cast and cured for each system and their physical and mechanical properties compared.

  13. Hydrogels for combination delivery of antineoplastic agents.

    PubMed

    Bouhadir, K H; Alsberg, E; Mooney, D J

    2001-10-01

    The systemic delivery of anticancer agents has been widely investigated during the past decade but localized delivery may offer a safer and more effective delivery approach. We have designed and synthesized a novel hydrogel to locally deliver antineoplastic agents, and demonstrate the different types of release that can be achieved from these hydrogels using three model drugs: methotrexate, doxorubicin, and mitoxantrone. Alginate was chemically modified into low molecular weight oligomers and cross-linked with a biodegradable spacer (adipic dihydrazide) to form biodegradable hydrogels. The model antineoplastic agents were loaded into the hydrogel via three different mechanisms. Methotrexate was incorporated within the pores of the hydrogel and was released by diffusion into the surrounding medium. Doxorubicin was covalently attached to the polymer backbone via a hydrolytically labile linker and was released following the chemical hydrolysis of the linker. Mitoxantrone was ionically complexed to the polymer and was released after the dissociation of this complex. These three release mechanisms could potentially be used to deliver a wide selection of antineoplastic agents, based on their chemical structure. This novel delivery system allows for the release of single or combinations of antineoplastic agents, and may find utility in localized antineoplastic agent delivery. PMID:11519782

  14. NESTA: NASA Engineering Shuttle Telemetry Agent

    NASA Technical Reports Server (NTRS)

    Semmel, Glenn S.; Davis, Steven R.; Leucht, Kurt W.; Rowe, Dan A.; Smith, Kevin E.; Boloni, Ladislau

    2005-01-01

    The Spaceport Processing Systems Branch at NASA Kennedy Space Center has developed and deployed an agent based tool to monitor the Space Shuttle's ground processing telemetry stream. The application, the NASA Engineering Shuttle Telemetry Agent, increases situational awareness for system and hardware engineers during ground processing of the Shuttle's subsystems. The agent provides autonomous monitoring of the telemetry stream and automatically alerts system engineers when predefined criteria have been met. Efficiency and safety are improved through increased automation. Sandia National Labs' Java Expert System Shell is employed as the rule engine. The shell's predicate logic lends itself well to capturing the heuristics and specifying the engineering rules of this spaceport domain. The declarative paradigm of the rule-based agent yields a highly modular and scalable design spanning multiple subsystems of the Shuttle. Several hundred monitoring rules have been written thus far with corresponding notifications sent to Shuttle engineers. This paper discusses the rule-based telemetry agent used for Space Shuttle ground processing and explains the problem domain, development of the agent software, benefits of AT technology, and deployment and sustaining engineering of the product.

  15. Bidding Agents That Perpetrate Auction Fraud

    NASA Astrophysics Data System (ADS)

    Trevathan, Jarrod; McCabe, Alan; Read, Wayne

    This paper presents a software bidding agent that inserts fake bids on the seller's behalf to inflate an auction's price. This behaviour is referred to as shill bidding. Shill bidding is strictly prohibited by online auctioneers, as it defrauds unsuspecting buyers by forcing them to pay more for the item. The malicious bidding agent was constructed to aid in developing shill detection techniques. We have previously documented a simple shill bidding agent that incrementally increases the auction price until it reaches the desired profit target, or it becomes too risky to continue bidding. This paper presents an adaptive shill bidding agent which when used over a series of auctions with substitutable items, can revise its strategy based on bidding behaviour in past auctions. The adaptive agent applies a novel prediction technique referred to as the Extremum Consistency (EC) algorithm, to determine the optimal price to aspire for. The EC algorithm has successfully been used in handwritten signature verification for determining the maximum and minimum values in an input stream. The agent's ability to inflate the price has been tested in a simulated marketplace and experimental results are presented.

  16. "Basic MR Relaxation Mechanisms & Contrast Agent Design"

    PubMed Central

    De León-Rodríguez, Luis M.; Martins, André F.; Pinho, Marco; Rofsky, Neil; Sherry, A. Dean

    2015-01-01

    The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we will detail the many important considerations when pursuing the design and use of MR contrast media. We will offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand based contrast agents. We will discuss the mechanisms involved in magnetic resonance relaxation in the context of probe design strategies. A brief description of currently available contrast agents will be accompanied by an in-depth discussion that highlights promising MRI contrast agents in development for future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. PMID:25975847

  17. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... embezzlement, identity theft, misappropriation, document fraud, drug offenses, or dishonesty in carrying out a... following: (1) Certifying the identity of each applicant. Passport acceptance agents must certify that...

  18. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... embezzlement, identity theft, misappropriation, document fraud, drug offenses, or dishonesty in carrying out a... following: (1) Certifying the identity of each applicant. Passport acceptance agents must certify that...

  19. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... embezzlement, identity theft, misappropriation, document fraud, drug offenses, or dishonesty in carrying out a... following: (1) Certifying the identity of each applicant. Passport acceptance agents must certify that...

  20. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... embezzlement, identity theft, misappropriation, document fraud, drug offenses, or dishonesty in carrying out a... following: (1) Certifying the identity of each applicant. Passport acceptance agents must certify that...

  1. Proceedings of the Agent 2002 Conference on Social Agents : Ecology, Exchange, and Evolution

    SciTech Connect

    Macal, C., ed.; Sallach, D., ed.

    2003-04-10

    Welcome to the ''Proceedings'' of the third in a series of agent simulation conferences cosponsored by Argonne National Laboratory and The University of Chicago. The theme of this year's conference, ''Social Agents: Ecology, Exchange and Evolution'', was selected to foster the exchange of ideas on some of the most important social processes addressed by agent simulation models, namely: (1) The translation of ecology and ecological constraints into social dynamics; (2) The role of exchange processes, including the peer dependencies they create; and (3) The dynamics by which, and the attractor states toward which, social processes evolve. As stated in the ''Call for Papers'', throughout the social sciences, the simulation of social agents has emerged as an innovative and powerful research methodology. The promise of this approach, however, is accompanied by many challenges. First, modeling complexity in agents, environments, and interactions is non-trivial, and these representations must be explored and assessed systematically. Second, strategies used to represent complexities are differentially applicable to any particular problem space. Finally, to achieve sufficient generality, the design and experimentation inherent in agent simulation must be coupled with social and behavioral theory. Agent 2002 provides a forum for reviewing the current state of agent simulation scholarship, including research designed to address such outstanding issues. This year's conference introduces an extensive range of domains, models, and issues--from pre-literacy to future projections, from ecology to oligopolistic markets, and from design to validation. Four invited speakers highlighted major themes emerging from social agent simulation.

  2. Agent Based Modeling Applications for Geosciences

    NASA Astrophysics Data System (ADS)

    Stein, J. S.

    2004-12-01

    Agent-based modeling techniques have successfully been applied to systems in which complex behaviors or outcomes arise from varied interactions between individuals in the system. Each individual interacts with its environment, as well as with other individuals, by following a set of relatively simple rules. Traditionally this "bottom-up" modeling approach has been applied to problems in the fields of economics and sociology, but more recently has been introduced to various disciplines in the geosciences. This technique can help explain the origin of complex processes from a relatively simple set of rules, incorporate large and detailed datasets when they exist, and simulate the effects of extreme events on system-wide behavior. Some of the challenges associated with this modeling method include: significant computational requirements in order to keep track of thousands to millions of agents, methods and strategies of model validation are lacking, as is a formal methodology for evaluating model uncertainty. Challenges specific to the geosciences, include how to define agents that control water, contaminant fluxes, climate forcing and other physical processes and how to link these "geo-agents" into larger agent-based simulations that include social systems such as demographics economics and regulations. Effective management of limited natural resources (such as water, hydrocarbons, or land) requires an understanding of what factors influence the demand for these resources on a regional and temporal scale. Agent-based models can be used to simulate this demand across a variety of sectors under a range of conditions and determine effective and robust management policies and monitoring strategies. The recent focus on the role of biological processes in the geosciences is another example of an area that could benefit from agent-based applications. A typical approach to modeling the effect of biological processes in geologic media has been to represent these processes in

  3. Frequently asked questions: iodinated contrast agents.

    PubMed

    Bettmann, Michael A

    2004-10-01

    Although iodinated contrast agents are safe and widely used, adverse events occur and questions remain about their use, safety, and interactions. Some questions are easily answered and others still require extensive investigation. For one frequent question--is informed consent necessary before all contrast media injections--the simple answer is no. Another question concerns use of contrast media in patients with prior reactions or allergies. Contrast agents can be safely used in such patients, but special care must be taken to be aware of what the previous reaction was and to be ready to treat any reaction. The protective role of pre-treatment with steroids is well established for minor reactions, but they may not prevent major reactions. It is important to realize that even life-threatening, anaphylactoid reactions are not the result of a true allergy to contrast media. Many questions arise about contrast agent-induced nephropathy. Baseline serum creatinine values should be obtained in patients who are at risk, not all patients. The incidence and natural history of contrast agent-induced nephropathy remain unclear. It occurs only in patients with compromised renal function before contrast agent injection, but even patients with normal serum creatinine levels can have renal dysfunction. Calculated creatinine clearance is a better way to determine risk and to follow this complication. The outcome in almost all patients is benign, with progression to end-stage renal disease being rare. The major risk factors, in addition to renal dysfunction, are long-standing diabetes mellitus, dehydration, and use of other nephrotoxic medications. Recent work in preventing and ameliorating contrast agent-induced nephropathy with N-acetyl cysteine, substitution of an isosmolal nonionic contrast agent, and various hydration regimens has been promising. Another common concern is use of iodinated contrast agents in pregnant or breast-feeding women. In both cases, there is no evidence

  4. Constructing Agent Model for Virtual Training Systems

    NASA Astrophysics Data System (ADS)

    Murakami, Yohei; Sugimoto, Yuki; Ishida, Toru

    Constructing highly realistic agents is essential if agents are to be employed in virtual training systems. In training for collaboration based on face-to-face interaction, the generation of emotional expressions is one key. In training for guidance based on one-to-many interaction such as direction giving for evacuations, emotional expressions must be supplemented by diverse agent behaviors to make the training realistic. To reproduce diverse behavior, we characterize agents by using a various combinations of operation rules instantiated by the user operating the agent. To accomplish this goal, we introduce a user modeling method based on participatory simulations. These simulations enable us to acquire information observed by each user in the simulation and the operating history. Using these data and the domain knowledge including known operation rules, we can generate an explanation for each behavior. Moreover, the application of hypothetical reasoning, which offers consistent selection of hypotheses, to the generation of explanations allows us to use otherwise incompatible operation rules as domain knowledge. In order to validate the proposed modeling method, we apply it to the acquisition of an evacuee's model in a fire-drill experiment. We successfully acquire a subject's model corresponding to the results of an interview with the subject.

  5. [Decontamination of chemical and biological warfare agents].

    PubMed

    Seto, Yasuo

    2009-01-01

    Chemical and biological warfare agents (CBWA's) are diverse in nature; volatile acute low-molecular-weight toxic compounds, chemical warfare agents (CWA's, gaseous choking and blood agents, volatile nerve gases and blister agents, nonvolatile vomit agents and lacrymators), biological toxins (nonvolatile low-molecular-weight toxins, proteinous toxins) and microbes (bacteria, viruses, rickettsiae). In the consequence management against chemical and biological terrorism, speedy decontamination of victims, facilities and equipment is required for the minimization of the damage. In the present situation, washing victims and contaminated materials with large volumes of water is the basic way, and additionally hypochlorite salt solution is used for decomposition of CWA's. However, it still remains unsolved how to dispose large volumes of waste water, and the decontamination reagents have serious limitation of high toxicity, despoiling nature against the environments, long finishing time and non-durability in effective decontamination. Namely, the existing decontamination system is not effective, nonspecifically affecting the surrounding non-target materials. Therefore, it is the urgent matter to build up the usable decontamination system surpassing the present technologies. The symposiast presents the on-going joint project of research and development of the novel decontamination system against CBWA's, in the purpose of realizing nontoxic, fast, specific, effective and economical terrorism on-site decontamination. The projects consists of (1) establishment of the decontamination evaluation methods and verification of the existing technologies and adaptation of bacterial organophosphorus hydrolase, (2) development of adsorptive elimination technologies using molecular recognition tools, and (4) development of deactivation technologies using photocatalysis. PMID:19122437

  6. Dynamically sequencing an animated pedagogical agent

    SciTech Connect

    Stone, B.A.; Lester, J.C.

    1996-12-31

    One of the most promising opportunities introduced by rapid advances in knowledge-based learning environments and multimedia technologies is the possibility of creating animated pedagogical agents. These agents should exhibit three properties: timely domain coverage (they should clearly communicate fundamental concepts and relationships within the allotted time); contextuality (they should provide explanations in appropriate problem-solving contexts); and continuity (their activities and utterances should be pedagogically, visually, and aurally coherent). We have developed the coherence-structured behavior space approach to creating animated pedagogical agents. This is a two-step approach. First, we design a behavior space of animation and audio segments that are structured by prerequisite relationships and a continuity metric. Second, we navigate coherent paths through the space to dynamically sequence behaviors. This creates seamless global behaviors that communicate fundamental knowledge and provide contextualized problem-solving advice. The coherence-structured behavior space approach has been implemented in Herman the Bug, an animated pedagogical agent for Design-A-Plant, a knowledge-based learning environment for botanical anatomy and physiology. Formative evaluations of the agent with middle school students are encouraging.

  7. Agents: An approach for dynamic process modelling

    NASA Astrophysics Data System (ADS)

    Grohmann, Axel; Kopetzky, Roland; Lurk, Alexander

    1999-03-01

    With the growing amount of distributed and heterogeneous information and services, conventional information systems have come to their limits. This gave rise to the development of a Multi-Agent System (the "Logical Client") which can be used in complex information systems as well as in other advanced software systems. Computer agents are proactive, reactive and social. They form a community of independent software components that can communicate and co-operate in order to accomplish complex tasks. Thus the agent-oriented paradigm provides a new and powerful approach to programming distributed systems. The communication framework developed is based on standards like CORBA, KQML and KIF. It provides an embedded rule based system to find adequate reactions to incoming messages. The macro-architecture of the Logical Client consists of independent agents and uses artificial intelligence to cope with complex patterns of communication and actions. A set of system agents is also provided, including the Strategy Service as a core component for modelling processes at runtime, the Computer Supported Cooperative Work (CSCW) Component for supporting remote co-operation between human users and the Repository for managing and hiding the file based data flow in heterogeneous networks. This architecture seems to be capable of managing complexity in information systems. It is also being implemented in a complex simulation system that monitors and simulates the environmental radioactivity in the country Baden-Württemberg.

  8. Contrast agent choice for intravenous coronary angiography

    SciTech Connect

    Zeman, H.D.; Siddons, D.P.

    1989-01-01

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation x-rays and an iodine containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic x-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the x-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation x-rays is visualizing a coronary artery through the left ventricle or aorta which also contains a contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth.

  9. Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents?

    PubMed Central

    Meca, Olga; Cruz, María-Jesús; Sánchez-Ortiz, Mónica; González-Barcala, Francisco-Javier; Ojanguren, Iñigo; Munoz, Xavier

    2016-01-01

    Introduction The aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests. Methods Seventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed. Results OA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136–11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0–16), compared with patients with OA caused by HMW agents (0.87, range 0–72), (p = 0.024). Conclusions OA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents. PMID:27280473

  10. Joint chemical agent detector (JCAD): the future of chemical agent detection

    NASA Astrophysics Data System (ADS)

    Laljer, Charles E.

    2003-08-01

    The Joint Chemical Agent Detector (JCAD) has continued development through 2002. The JCAD has completed Contractor Validation Testing (CVT) that included chemical warfare agent testing, environmental testing, electromagnetic interferent testing, and platform integration validation. The JCAD provides state of the art chemical warfare agent detection capability to military and homeland security operators. Intelligence sources estimate that over twenty countries have active chemical weapons programs. The spread of weapons of mass destruction (and the industrial capability for manufacture of these weapons) to third world nations and terrorist organizations has greatly increased the chemical agent threat to U.S. interests. Coupled with the potential for U.S. involvement in localized conflicts in an operational or support capacity, increases the probability that the military Joint Services may encounter chemical agents anywhere in the world. The JCAD is a small (45 in3), lightweight (2 lb.) chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection component across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD detects, identifies, quantifies, and warns of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector provides local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew and other personnel in the local area with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD is capable of being upgraded to protect against future chemical agent threats. The JCAD provides the operator with the warning necessary to survive and fight in a chemical warfare agent threat environment.

  11. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

    PubMed Central

    Sinharay, Sanhita; Pagel, Mark D.

    2016-01-01

    Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

  12. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection.

    PubMed

    Sinharay, Sanhita; Pagel, Mark D

    2016-06-12

    Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized (13)C to detect the agent with outstanding sensitivity. These hyperpolarized (13)C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

  13. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

    NASA Astrophysics Data System (ADS)

    Sinharay, Sanhita; Pagel, Mark D.

    2016-06-01

    Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection.

  14. Radioprotective agents for radiation therapy: future trends.

    PubMed

    Johnke, Roberta M; Sattler, Jennifer A; Allison, Ron R

    2014-12-01

    Only two radioprotective compounds, amifostine and palifermin, currently have the US FDA approval for use in radiation therapy. However, several agents have been reported that show therapeutic promise. Many of these agents are free radical scavengers/antioxidants. Superoxide dismutase and superoxide dismutase mimetics, nitroxides and dietary antioxidants are all being investigated. Recently, alternative strategies of drug development have been evolving, which focus on targeting the series of cellular insult recognition/repair responses initiated following radiation. These agents, which include cytokines/growth factors, angiotensin-converting enzyme inhibitors and apoptotic modulators, show promise of having significant impact on the mitigation of radiation injury. Herein, we review current literature on the development of radioprotectors with emphasis on compounds with proven or potential usefulness in radiation therapy. PMID:25525844

  15. Volatility clustering in agent based market models

    NASA Astrophysics Data System (ADS)

    Giardina, Irene; Bouchaud, Jean-Philippe

    2003-06-01

    We define and study a market model, where agents have different strategies among which they can choose, according to their relative profitability, with the possibility of not participating to the market. The price is updated according to the excess demand, and the wealth of the agents is properly accounted for. Only two parameters play a significant role: one describes the impact of trading on the price, and the other describes the propensity of agents to be trend following or contrarian. We observe three different regimes, depending on the value of these two parameters: an oscillating phase with bubbles and crashes, an intermittent phase and a stable ‘rational’ market phase. The statistics of price changes in the intermittent phase resembles that of real price changes, with small linear correlations, fat tails and long-range volatility clustering. We discuss how the time dependence of these two parameters spontaneously drives the system in the intermittent region.

  16. Animals as sentinels of bioterrorism agents.

    PubMed

    Rabinowitz, Peter; Gordon, Zimra; Chudnov, Daniel; Wilcox, Matthew; Odofin, Lynda; Liu, Ann; Dein, Joshua

    2006-04-01

    We conducted a systematic review of the scientific literature from 1966 to 2005 to determine whether animals could provide early warning of a bioterrorism attack, serve as markers for ongoing exposure risk, and amplify or propagate a bioterrorism outbreak. We found evidence that, for certain bioterrorism agents, pets, wildlife, or livestock could provide early warning and that for other agents, humans would likely manifest symptoms before illness could be detected in animals. After an acute attack, active surveillance of wild or domestic animal populations could help identify many ongoing exposure risks. If certain bioterrorism agents found their way into animal populations, they could spread widely through animal-to-animal transmission and prove difficult to control. The public health infrastructure must look beyond passive surveillance of acute animal disease events to build capacity for active surveillance and intervention efforts to detect and control ongoing outbreaks of disease in domestic and wild animal populations. PMID:16704814

  17. [Antithyroid agents related agranulocytosis: Literature review].

    PubMed

    Andrès, E; Weitten, T; Mourot-Cottet, R; Keller, O; Zulfiqar, A-A; Serraj, K; Vogel, T; Tebacher, M

    2016-08-01

    The antithyroid agents (carbimazole, methimazole, thiamazole, propylthiouracil and benzylthiouracile) are the drug class that is associated with a high risk of agranulocytosis. Acute and profound (<0.5×10(9)/L) isolated neutropenia occurring in a subject treated with antithyroid agents should be considered as a drug-induced agranulocytosis, until proven otherwise. The clinical spectrum ranges from discovery of acute severe but asymptomatic neutropenia, to isolated fever, localized infections (especially ear, nose and throat, or pulmonary) or septicemia. With an optimal management (discontinuation of antithyroid agents, antibiotics in the presence of fever or a documented infection, or use of hematopoietic growth factor) the current mortality is close to 2%. PMID:27241077

  18. FIPA agent based network distributed control system

    SciTech Connect

    D. Abbott; V. Gyurjyan; G. Heyes; E. Jastrzembski; C. Timmer; E. Wolin

    2003-03-01

    A control system with the capabilities to combine heterogeneous control systems or processes into a uniform homogeneous environment is discussed. This dynamically extensible system is an example of the software system at the agent level of abstraction. This level of abstraction considers agents as atomic entities that communicate to implement the functionality of the control system. Agents' engineering aspects are addressed by adopting the domain independent software standard, formulated by FIPA. Jade core Java classes are used as a FIPA specification implementation. A special, lightweight, XML RDFS based, control oriented, ontology markup language is developed to standardize the description of the arbitrary control system data processor. Control processes, described in this language, are integrated into the global system at runtime, without actual programming. Fault tolerance and recovery issues are also addressed.

  19. Toward Agent Programs with Circuit Semantics

    NASA Technical Reports Server (NTRS)

    Nilsson, Nils J.

    1992-01-01

    New ideas are presented for computing and organizing actions for autonomous agents in dynamic environments-environments in which the agent's current situation cannot always be accurately discerned and in which the effects of actions cannot always be reliably predicted. The notion of 'circuit semantics' for programs based on 'teleo-reactive trees' is introduced. Program execution builds a combinational circuit which receives sensory inputs and controls actions. These formalisms embody a high degree of inherent conditionality and thus yield programs that are suitably reactive to their environments. At the same time, the actions computed by the programs are guided by the overall goals of the agent. The paper also speculates about how programs using these ideas could be automatically generated by artificial intelligence planning systems and adapted by learning methods.

  20. Animals as Sentinels of Bioterrorism Agents

    PubMed Central

    Gordon, Zimra; Chudnov, Daniel; Wilcox, Matthew; Odofin, Lynda; Liu, Ann; Dein, Joshua

    2006-01-01

    We conducted a systematic review of the scientific literature from 1966 to 2005 to determine whether animals could provide early warning of a bioterrorism attack, serve as markers for ongoing exposure risk, and amplify or propagate a bioterrorism outbreak. We found evidence that, for certain bioterrorism agents, pets, wildlife, or livestock could provide early warning and that for other agents, humans would likely manifest symptoms before illness could be detected in animals. After an acute attack, active surveillance of wild or domestic animal populations could help identify many ongoing exposure risks. If certain bioterrorism agents found their way into animal populations, they could spread widely through animal-to-animal transmission and prove difficult to control. The public health infrastructure must look beyond passive surveillance of acute animal disease events to build capacity for active surveillance and intervention efforts to detect and control ongoing outbreaks of disease in domestic and wild animal populations. PMID:16704814

  1. Glutamic acid as anticancer agent: An overview

    PubMed Central

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed. PMID:24227952

  2. Quantum Speedup for Active Learning Agents

    NASA Astrophysics Data System (ADS)

    Paparo, Giuseppe Davide; Dunjko, Vedran; Makmal, Adi; Martin-Delgado, Miguel Angel; Briegel, Hans J.

    2014-07-01

    Can quantum mechanics help us build intelligent learning agents? A defining signature of intelligent behavior is the capacity to learn from experience. However, a major bottleneck for agents to learn in real-life situations is the size and complexity of the corresponding task environment. Even in a moderately realistic environment, it may simply take too long to rationally respond to a given situation. If the environment is impatient, allowing only a certain time for a response, an agent may then be unable to cope with the situation and to learn at all. Here, we show that quantum physics can help and provide a quadratic speedup for active learning as a genuine problem of artificial intelligence. This result will be particularly relevant for applications involving complex task environments.

  3. NISAC Agent Based Laboratory for Economics

    SciTech Connect

    Downes, Paula; Davis, Chris; Eidson, Eric; Ehlen, Mark; Gieseler, Charles; Harris, Richard

    2006-10-11

    The software provides large-scale microeconomic simulation of complex economic and social systems (such as supply chain and market dynamics of businesses in the US economy) and their dependence on physical infrastructure systems. The system is based on Agent simulation, where each entity of inteest in the system to be modeled (for example, a Bank, individual firms, Consumer households, etc.) is specified in a data-driven sense to be individually repreented by an Agent. The Agents interact using rules of interaction appropriate to their roles, and through those interactions complex economic and social dynamics emerge. The software is implemented in three tiers, a Java-based visualization client, a C++ control mid-tier, and a C++ computational tier.

  4. Agents That Negotiate Proficiently with People

    NASA Astrophysics Data System (ADS)

    Kraus, Sarit

    Negotiation is a process by which interested parties confer with the aim of reaching agreements. The dissemination of technologies such as the Internet has created opportunities for computer agents to negotiate with people, despite being distributed geographically and in time. The inclusion of people presents novel problems for the design of autonomous agent negotiation strategies. People do not adhere to the optimal, monolithic strategies that can be derived analytically, as is the case in settings comprising computer agents alone. Their negotiation behavior is affected by a multitude of social and psychological factors, such as social attributes that influence negotiation deals (e.g., social welfare, inequity aversion) and traits of individual negotiators (e.g., altruism, trustworthiness, helpfulness). Furthermore, culture plays an important role in their decision making and people of varying cultures differ in the way they make offers and fulfill their commitments in negotiation.

  5. NISAC Agent Based Laboratory for Economics

    Energy Science and Technology Software Center (ESTSC)

    2006-10-11

    The software provides large-scale microeconomic simulation of complex economic and social systems (such as supply chain and market dynamics of businesses in the US economy) and their dependence on physical infrastructure systems. The system is based on Agent simulation, where each entity of inteest in the system to be modeled (for example, a Bank, individual firms, Consumer households, etc.) is specified in a data-driven sense to be individually repreented by an Agent. The Agents interactmore » using rules of interaction appropriate to their roles, and through those interactions complex economic and social dynamics emerge. The software is implemented in three tiers, a Java-based visualization client, a C++ control mid-tier, and a C++ computational tier.« less

  6. Heterocyclic chalcone analogues as potential anticancer agents.

    PubMed

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties. PMID:22721390

  7. Environmental mimics of chemical warfare agents.

    PubMed

    Claborn, David M

    2004-12-01

    There are several natural and artificial factors that mimic the effects of chemical warfare agents, thereby causing unwarranted alarm and confusion on the battlefield. Symptoms associated with chemical warfare include paralysis, muscle tremors, heavy salivation, severe burns, blistering, and corrosive skin injuries among others. Similar symptoms can be produced from a variety of environmental sources, artificial and natural. This article reviews several published and unpublished examples of environmental factors that produce syndromes similar to those caused by these agents. Examples of such mimics include pesticides, blistering exudates from insects and plants, various types of bites, and naturally occurring diseases. The potential for confusion caused by these factors is discussed and means of discriminating between warfare agents and naturally occurring events are identified. Recommendations for the use of this information and for needed research are also discussed. PMID:15646185

  8. Artificial agents, good care, and modernity.

    PubMed

    Coeckelbergh, Mark

    2015-08-01

    When is it ethically acceptable to use artificial agents in health care? This article articulates some criteria for good care and then discusses whether machines as artificial agents that take over care tasks meet these criteria. Particular attention is paid to intuitions about the meaning of 'care', 'agency', and 'taking over', but also to the care process as a labour process in a modern organizational and financial-economic context. It is argued that while there is in principle no objection to using machines in medicine and health care, the idea of them functioning and appearing as 'artificial agents' is problematic and attends us to problems in human care which were already present before visions of machine care entered the stage. It is recommended that the discussion about care machines be connected to a broader discussion about the impact of technology on human relations in the context of modernity. PMID:26002636

  9. Physical Agents for Soft Tissue Injury.

    PubMed

    2016-07-01

    The clinical management of soft tissue injuries of the lower limb commonly includes physical agents such as electrotherapy or ultrasound. However, the evidence about the effectiveness of physical agents varies, and their use remains controversial. A systematic review of randomized clinical trials (RCTs), published in the July 2016 issue of JOSPT, examined the benefits and safety risks of various physical agents for soft tissue injuries of the lower limb. Importantly, the review looked closely at the quality of the RCTs and focused on studies with low risk of bias. In this Perspectives for Practice, the authors explain the impact of their findings for clinicians treating patients with such musculoskeletal conditions. J Orthop Sports Phys Ther 2016;46(7):555. doi:10.2519/jospt.2016.0503. PMID:27363571

  10. An Adviser Agent for Mediator Training

    NASA Astrophysics Data System (ADS)

    Tanaka, Takahiro; Katagami, Daisuke; Nitta, Katsumi

    This paper describes an agent that shows advices for supporting mediator on our online mediation support system. The purpose of the advice is an education of mediator, and the agent presents it instead of the teacher. In this research, at first, we defined a mediation model that is an argumentation model between 3 people. Then, we defined some advice models based on the mediation model. The advice models create advice elements. The adviser agent monitors the mediation, gathers advice elements referring to advice models, and creates advice from elements according to the mediation scene. As a result, it becomes possible that is advising instead of the teacher according to the situation, education purpose and learner's level. We inspected the effectiveness of the advice by the experiment of moot mediation.

  11. Autonomous Formations of Multi-Agent Systems

    NASA Technical Reports Server (NTRS)

    Dhali, Sanjana; Joshi, Suresh M.

    2013-01-01

    Autonomous formation control of multi-agent dynamic systems has a number of applications that include ground-based and aerial robots and satellite formations. For air vehicles, formation flight ("flocking") has the potential to significantly increase airspace utilization as well as fuel efficiency. This presentation addresses two main problems in multi-agent formations: optimal role assignment to minimize the total cost (e.g., combined distance traveled by all agents); and maintaining formation geometry during flock motion. The Kuhn-Munkres ("Hungarian") algorithm is used for optimal assignment, and consensus-based leader-follower type control architecture is used to maintain formation shape despite the leader s independent movements. The methods are demonstrated by animated simulations.

  12. Cyber agent on the World Wide Web

    NASA Astrophysics Data System (ADS)

    Lee, H. C.; Dagli, Cihan H.

    1996-03-01

    The World Wide Web has brought the information from a distributed environment into a global information universe. As users keep on surfing the Web and adding their bookmarks, it is increasingly difficult for them to find their desired information even though there are many search tools available. In this paper, a smart engineering system called Cyber Agent is proposed to help users search and organize the information. It contains two major subsystems, namely, WebTracer and WebOrganizer. They adapt their behavior dynamically according to the environment and the special preferences of each individual. WebTracer is the wavefront of the Cyber Agent while WebOrganizer is the brain of the Cyber Agent.

  13. 31 CFR 10.4 - Eligibility for enrollment as enrolled agent or enrolled retirement plan agent.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Eligibility for enrollment as enrolled agent or enrolled retirement plan agent. 10.4 Section 10.4 Money and Finance: Treasury Office of the Secretary of the Treasury PRACTICE BEFORE THE INTERNAL REVENUE SERVICE Rules Governing...

  14. Linking Agent's Tool Kit. Part One: The Linking Agent: An Overview. Consortium Report Series.

    ERIC Educational Resources Information Center

    Crandall, David P.

    The first part of a 3-part guide developed as a resource for people involved in the selection and implementation of new programs in school settings, this overview describes a wide range of linking agent roles and skills, and discusses training and support mechanisms for linking agents. Chapters address (1) the assumptions underlying the overview,…

  15. Animated Pedagogical Agents: A Review of Agent Technology Software in Electronic Learning Environments

    ERIC Educational Resources Information Center

    Govindasamy, Malliga K.

    2014-01-01

    Agent technology has become one of the dynamic and most interesting areas of computer science in recent years. The dynamism of this technology has resulted in computer generated characters, known as pedagogical agent, entering the digital learning environments in increasing numbers. Commonly deployed in implementing tutoring strategies, these…

  16. Nondestructive Intervention to Multi-Agent Systems through an Intelligent Agent

    PubMed Central

    Han, Jing; Wang, Lin

    2013-01-01

    For a given multi-agent system where the local interaction rule of the existing agents can not be re-designed, one way to intervene the collective behavior of the system is to add one or a few special agents into the group which are still treated as normal agents by the existing ones. We study how to lead a Vicsek-like flocking model to reach synchronization by adding special agents. A popular method is to add some simple leaders (fixed-headings agents). However, we add one intelligent agent, called ‘shill’, which uses online feedback information of the group to decide the shill's moving direction at each step. A novel strategy for the shill to coordinate the group is proposed. It is strictly proved that a shill with this strategy and a limited speed can synchronize every agent in the group. The computer simulations show the effectiveness of this strategy in different scenarios, including different group sizes, shill speed, and with or without noise. Compared to the method of adding some fixed-heading leaders, our method can guarantee synchronization for any initial configuration in the deterministic scenario and improve the synchronization level significantly in low density groups, or model with noise. This suggests the advantage and power of feedback information in intervention of collective behavior. PMID:23658695

  17. From Agents to Continuous Change via Aesthetics: Learning Mechanics with Visual Agent-Based Computational Modeling

    ERIC Educational Resources Information Center

    Sengupta, Pratim; Farris, Amy Voss; Wright, Mason

    2012-01-01

    Novice learners find motion as a continuous process of change challenging to understand. In this paper, we present a pedagogical approach based on agent-based, visual programming to address this issue. Integrating agent-based programming, in particular, Logo programming, with curricular science has been shown to be challenging in previous research…

  18. Non-halogenated alternative cleaning agents

    SciTech Connect

    Nigrey, P.J.

    1992-01-01

    The cleaning efficiency of five alternative cleaning agents have been evaluated as possible replacements chlorofluorocarbon (CFC) and chlorohydrocarbon (CHC) solvents used in the manufacture of certain electronic components. These cleaning agents were evaluated in the first phase (Phase I) of a two-phase program to remove various simulated manufacturing contaminants such as oils, greases, mold release, and body oils. Results showed that a decyl acetate (EXXATE 1000) and a terpene (BIOACT EC-7) were both able to effectively remove these contaminants form copper board substrates.

  19. Non-halogenated alternative cleaning agents

    SciTech Connect

    Nigrey, P.J.

    1992-09-01

    The cleaning efficiency of five alternative cleaning agents have been evaluated as possible replacements chlorofluorocarbon (CFC) and chlorohydrocarbon (CHC) solvents used in the manufacture of certain electronic components. These cleaning agents were evaluated in the first phase (Phase I) of a two-phase program to remove various simulated manufacturing contaminants such as oils, greases, mold release, and body oils. Results showed that a decyl acetate (EXXATE 1000) and a terpene (BIOACT EC-7) were both able to effectively remove these contaminants form copper board substrates.

  20. Approaches to detection of airborne biological agents

    NASA Astrophysics Data System (ADS)

    Chang, An-Cheng; Tabacco, Mary Beth

    2009-05-01

    Three approaches to detection of biological agents based on biological processes will be presented. The first example demonstrates the use of dendrimers to deliver a membrane-impermeable fluorescent dye into live bacteria, similar to viral infection and delivery of DNA/RNA into a bacterial cell. The second example mimics collection and capture of airborne biological particles by the respiratory mucosa through the use of a hygroscopic sensing membrane. The third example is based on the use of multiple fluorescent probes with diverse functionalities to detect airborne biological agents in a manner similar to the olfactory receptors in the nasal tract.

  1. Detection of electrophilic and nucleophilic chemical agents

    DOEpatents

    McElhanon, James R.; Shepodd, Timothy J.

    2014-08-12

    A "real time" method for detecting chemical agents generally and particularly electrophilic and nucleophilic species by employing tunable, precursor sensor materials that mimic the physiological interaction of these agents to form highly florescent berberine-type alkaloids that can be easily and rapidly detected. These novel precursor sensor materials can be tuned for reaction with both electrophilic (chemical species, toxins) and nucleophilic (proteins and other biological molecules) species. By bonding or otherwise attaching these precursor molecules to a surface or substrate they can be used in numerous applications.

  2. Intelligent Agents: The Measure of their Intelligence

    NASA Astrophysics Data System (ADS)

    Arlabosse, François

    2002-09-01

    This paper presents an original attempt for testing the level of autonomy of intelligent physical agents. After a short review of the architectural problematic of designing such artefacts, we try to situate the place of uncertainty modelling in mobile robotic and complex control systems. We then briefly describe a design for giving to an industrial control problem the highest level of autonomy for performing its tasks. We give some hints how to extend these tests on physical agents exhibiting adaptive behaviours. Future works for applying this methodology will be illustrated.

  3. An enzymatic approach to bifunctional chelating agents.

    PubMed

    Minazzi, Paolo; Lattuada, Luciano; Menegotto, Ivan G; Giovenzana, Giovanni B

    2014-09-21

    Bifunctional chelating agents (BFCAs) combine the complexing properties of a multidentate ligand with the presence of a free reactive functional group, mainly devoted to conjugation purposes. Indeed, products obtained by conjugation of a BFCA to a biomolecule and coordination of a suitable metal ion are widely applied in medicine nowadays as diagnostic and therapeutic agents. BFCAs are generally prepared through multi-step syntheses and with extensive application of protection-deprotection strategies, due to the large number of functional groups involved. Hydrolytic enzymes, with their unique chemoselectivity, provided the best results in the preparation of three different BFCAs based on very useful and well known ligand platforms. PMID:25060174

  4. Contrast agent choice for intravenous coronary angiography

    NASA Astrophysics Data System (ADS)

    Zeman, H. D.; Siddons, D. P.

    1990-05-01

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation X-rays and an iodine-containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic X-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron radiation source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the X-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation X-rays is visualizing a coronary artery through the left ventricle or aorta which also contain contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth. The X-ray energy spectrum of the X-17 superconduction wiggler beam line at the National Synchrotron Light Source at Brookhaven National Laboratory has been used for these calculations. Both perfect Si crystals and Si crystals with a small mosaic spread are considered as monochromators. Contrast agents containing Gd or Yb seem to have about the optimal calculated signal to noise ratio. Gd-DTPA is already approved for use as a contrast agent for

  5. Radio-protective role of antioxidant agents

    PubMed Central

    Shirazi, Alireza; Mihandoost, Ehsan; Mahdavi, Seied Rabie; Mohseni, Mehran

    2012-01-01

    Ionizing radiation interacts with biological systems to produce reactive oxygen species and reactive nitrogen species which attack various cellular components. Radio-protectors act as prophylactic agents to shield healthy cells and tissues from the harmful effects of radiation. Past research on synthetic radio-protectors has brought little success, primarily due to the various toxicity-related problems. Results of experimental research show that antioxidant nutrients, such as vitamin E and herbal products and melatonin, are protective against the damaging effects of radiation, with less toxicity and side effects. Therefore, we propose that in the future, antioxidant radio-protective agents may improve the therapeutic index in radiation oncology treatments. PMID:25992214

  6. Development of polyimide foams with blowing agents

    NASA Technical Reports Server (NTRS)

    Gagliani, John (Inventor); Sorathia, Usman A. K. (Inventor); Lee, Raymond (Inventor)

    1985-01-01

    A method of preparing a polyimide foam which includes the steps of: preparing, foaming, and curing a precursor containing at least one alkyl ester of 3,3'4,4'-benzophenonetetracarboxylic acid; a meta- or para-substituted aromatic diamine; a heterocyclic diamine; an aliphatic diamine; and a solid blowing agent. The blowing agent is added to said precursor in a concentration which is sufficient to effect at least one of the following attributes of the foam: cell size, proportion of open cells, cell density, and indentation load deflection.

  7. Bacterial spores and chemical sporicidal agents.

    PubMed Central

    Russell, A D

    1990-01-01

    Bacterial spores are among the most resistant of all living cells to biocides, although the response depends on the stage of sporulation. The development of resistance to some agents such as chlorhexidine occurs much earlier in sporulation than does resistance to glutaraldehyde, which is a very late event. During germination or outgrowth or both, resistance is lost and the cells become as susceptible to biocides as nonsporulating bacteria. Mechanisms of spore resistance to, and the action of, biocides are discussed, and possible means of enhancing antispore activity are considered. The clinical and other uses of sporicidal and sporostatic chemical agents are described. Images PMID:2187595

  8. Intelligent Software Agents: Sensor Integration and Response

    SciTech Connect

    Kulesz, James J; Lee, Ronald W

    2013-01-01

    Abstract In a post Macondo world the buzzwords are Integrity Management and Incident Response Management. The twin processes are not new but the opportunity to link the two is novel. Intelligent software agents can be used with sensor networks in distributed and centralized computing systems to enhance real-time monitoring of system integrity as well as manage the follow-on incident response to changing, and potentially hazardous, environmental conditions. The software components are embedded at the sensor network nodes in surveillance systems used for monitoring unusual events. When an event occurs, the software agents establish a new concept of operation at the sensing node, post the event status to a blackboard for software agents at other nodes to see , and then react quickly and efficiently to monitor the scale of the event. The technology addresses a current challenge in sensor networks that prevents a rapid and efficient response when a sensor measurement indicates that an event has occurred. By using intelligent software agents - which can be stationary or mobile, interact socially, and adapt to changing situations - the technology offers features that are particularly important when systems need to adapt to active circumstances. For example, when a release is detected, the local software agent collaborates with other agents at the node to exercise the appropriate operation, such as: targeted detection, increased detection frequency, decreased detection frequency for other non-alarming sensors, and determination of environmental conditions so that adjacent nodes can be informed that an event is occurring and when it will arrive. The software agents at the nodes can also post the data in a targeted manner, so that agents at other nodes and the command center can exercise appropriate operations to recalibrate the overall sensor network and associated intelligence systems. The paper describes the concepts and provides examples of real-world implementations

  9. A Diversified Investment Strategy Using Autonomous Agents

    NASA Astrophysics Data System (ADS)

    Barbosa, Rui Pedro; Belo, Orlando

    In a previously published article, we presented an architecture for implementing agents with the ability to trade autonomously in the Forex market. At the core of this architecture is an ensemble of classification and regression models that is used to predict the direction of the price of a currency pair. In this paper, we will describe a diversified investment strategy consisting of five agents which were implemented using that architecture. By simulating trades with 18 months of out-of-sample data, we will demonstrate that data mining models can produce profitable predictions, and that the trading risk can be diminished through investment diversification.

  10. Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

    SciTech Connect

    Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika; Edwards, Carol C.; Fleming, Christopher D.; MacDonald, Mary; Cashman, John R.; Potter, Philip M.; Cerasoli, Douglas M.; Redinbo, Matthew R.

    2010-10-28

    Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex with the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the P{sub R} enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the P{sub S} isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic P{sub S} isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification.

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

    NASA Astrophysics Data System (ADS)

    Laljer, Charles E.; Owen, Jeffery L.

    2002-06-01

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

  12. Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

    PubMed Central

    Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika; Edwards, Carol C.; Fleming, Christopher D.; MacDonald, Mary; Cashman, John R.; Potter, Philip M.; Cerasoli, Douglas M.

    2010-01-01

    Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex with the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the PR enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the PS isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic PS isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification. PMID:20051531

  13. CATS-based Air Traffic Controller Agents

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.

    2002-01-01

    This report describes intelligent agents that function as air traffic controllers. Each agent controls traffic in a single sector in real time; agents controlling traffic in adjoining sectors can coordinate to manage an arrival flow across a given meter fix. The purpose of this research is threefold. First, it seeks to study the design of agents for controlling complex systems. In particular, it investigates agent planning and reactive control functionality in a dynamic environment in which a variety perceptual and decision making skills play a central role. It examines how heuristic rules can be applied to model planning and decision making skills, rather than attempting to apply optimization methods. Thus, the research attempts to develop intelligent agents that provide an approximation of human air traffic controller behavior that, while not based on an explicit cognitive model, does produce task performance consistent with the way human air traffic controllers operate. Second, this research sought to extend previous research on using the Crew Activity Tracking System (CATS) as the basis for intelligent agents. The agents use a high-level model of air traffic controller activities to structure the control task. To execute an activity in the CATS model, according to the current task context, the agents reference a 'skill library' and 'control rules' that in turn execute the pattern recognition, planning, and decision-making required to perform the activity. Applying the skills enables the agents to modify their representation of the current control situation (i.e., the 'flick' or 'picture'). The updated representation supports the next activity in a cycle of action that, taken as a whole, simulates air traffic controller behavior. A third, practical motivation for this research is to use intelligent agents to support evaluation of new air traffic control (ATC) methods to support new Air Traffic Management (ATM) concepts. Current approaches that use large, human

  14. 49 CFR 375.205 - May I have agents?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false May I have agents? 375.205 Section 375.205... General Responsibilities § 375.205 May I have agents? (a) You may have agents provided you comply with... performs such services only on an emergency or temporary basis. (b) If you have agents, you must...

  15. 49 CFR 375.205 - May I have agents?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 false May I have agents? 375.205 Section 375.205... General Responsibilities § 375.205 May I have agents? (a) You may have agents provided you comply with... performs such services only on an emergency or temporary basis. (b) If you have agents, you must...

  16. 49 CFR 375.205 - May I have agents?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 5 2012-10-01 2012-10-01 false May I have agents? 375.205 Section 375.205... General Responsibilities § 375.205 May I have agents? (a) You may have agents provided you comply with... performs such services only on an emergency or temporary basis. (b) If you have agents, you must...

  17. 49 CFR 375.205 - May I have agents?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false May I have agents? 375.205 Section 375.205... General Responsibilities § 375.205 May I have agents? (a) You may have agents provided you comply with... performs such services only on an emergency or temporary basis. (b) If you have agents, you must...

  18. 49 CFR 375.205 - May I have agents?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 5 2011-10-01 2011-10-01 false May I have agents? 375.205 Section 375.205... General Responsibilities § 375.205 May I have agents? (a) You may have agents provided you comply with... performs such services only on an emergency or temporary basis. (b) If you have agents, you must...

  19. SURFACE TREATMENT AGENTS FOR PROTECTION OF SHORELINES FROM OIL SPILLS

    EPA Science Inventory

    A literature review and laboratory tests were conducted to provide a basis for analyzing the results of previous tests on surface treatment agents, compare agent effectiveness, and recommend agents for preliminary field tests. The surface treatment agents evaluated during the pre...

  20. Intelligent Agents: It's Nice To Get Stuff Done for You.

    ERIC Educational Resources Information Center

    Perez, Ernest

    2002-01-01

    Explains intelligent agents, special software tools that help make the Web more interactive by helping with information retrieval. Describes major types of agents, including search agents and agents for specialized tasks including monitors and knowledge management; and lists relevant Web sites. (LRW)

  1. 46 CFR 193.15-50 - Clean agent systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Clean agent systems. 193.15-50 Section 193.15-50 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS FIRE PROTECTION EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-50 Clean agent systems. A clean agent system complying with...

  2. Petri Nets as Modeling Tool for Emergent Agents

    NASA Technical Reports Server (NTRS)

    Bergman, Marto

    2004-01-01

    Emergent agents, those agents whose local interactions can cause unexpected global results, require a method of modeling that is both dynamic and structured Petri Nets, a modeling tool developed for dynamic discrete event system of mainly functional agents, provide this, and have the benefit of being an established tool. We present here the details of the modeling method here and discuss how to implement its use for modeling agent-based systems. Petri Nets have been used extensively in the modeling of functional agents, those agents who have defined purposes and whose actions should result in a know outcome. However, emergent agents, those agents who have a defined structure but whose interaction causes outcomes that are unpredictable, have not yet found a modeling style that suits them. A problem with formally modeling emergent agents that any formal modeling style usually expects to show the results of a problem and the results of problems studied using emergent agents are not apparent from the initial construction. However, the study of emergent agents still requires a method to analyze the agents themselves, and have sensible conversation about the differences and similarities between types of emergent agents. We attempt to correct this problem by applying Petri Nets to the characterization of emergent agents. In doing so, the emergent properties of these agents can be highlighted, and conversation about the nature and compatibility of the differing methods of agent creation can begin.

  3. Applications of Multi-Agent Technology to Power Systems

    NASA Astrophysics Data System (ADS)

    Nagata, Takeshi

    Currently, agents are focus of intense on many sub-fields of computer science and artificial intelligence. Agents are being used in an increasingly wide variety of applications. Many important computing applications such as planning, process control, communication networks and concurrent systems will benefit from using multi-agent system approach. A multi-agent system is a structure given by an environment together with a set of artificial agents capable to act on this environment. Multi-agent models are oriented towards interactions, collaborative phenomena, and autonomy. This article presents the applications of multi-agent technology to the power systems.

  4. Economic Path Scheduling for Mobile Agent System on Computer Network

    NASA Astrophysics Data System (ADS)

    Olajubu, E. A.

    Mobile agent technology has a lot of gains to offer network-centric applications. The technology promises to be very suitable for narrow-bandwidth networks by reducing network latency and allowing transparent per-to-per computing. Multi-agent technology had been proposed for many network-centric applications with little or no path scheduling algorithms. This paper describes the need for path scheduling algorithms for agents in multi-agent systems. Traveling salesman problem (TSP) scheme is used to model ordered agents and the unordered agents schedule their path based on random distribution. The two types of agents were modeled and simulated based on bandwidth usage and response time as performance metrics. Our simulation results shows that ordered agents have superior performance against unordered agents. The ordered agents exhibit lower bandwidth usage and higher response time.

  5. 12 CFR 725.4 - Agent membership.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS NATIONAL CREDIT UNION ADMINISTRATION CENTRAL LIQUIDITY FACILITY § 725.4 Agent membership. (a) A central credit union or a group of... credit unions, each central credit union in the group must do each of the following except for...

  6. 12 CFR 725.4 - Agent membership.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS NATIONAL CREDIT UNION ADMINISTRATION CENTRAL LIQUIDITY FACILITY § 725.4 Agent membership. (a) A central credit union or a group of... credit unions, each central credit union in the group must do each of the following except for...

  7. 12 CFR 725.4 - Agent membership.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS NATIONAL CREDIT UNION ADMINISTRATION CENTRAL LIQUIDITY FACILITY § 725.4 Agent membership. (a) A central credit union or a group of... credit unions, each central credit union in the group must do each of the following except for...

  8. 7 CFR 966.88 - Agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Agents. 966.88 Section 966.88 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Order...

  9. 7 CFR 1430.210 - MILC agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS DAIRY PRODUCTS Milk Income Loss Contract Program § 1430.210 MILC agents. (a) MILC benefits may be disbursed by a dairy marketing cooperative that serves special groups or communities, such as an Amish or Mennonite community. Producers in such groups in a...

  10. 40 CFR 745.115 - Agent responsibilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... CONTROL ACT LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Disclosure of Known Lead-Based Paint and/or Lead-Based Paint Hazards Upon Sale or Lease of Residential Property § 745.115...-based paint and/or lead-based paint hazards known by a seller or lessor but not disclosed to the agent....

  11. Incretin agents in type 2 diabetes

    PubMed Central

    Ross, Stuart A.; Ekoé, Jean-Marie

    2010-01-01

    Abstract OBJECTIVE To evaluate the emerging classes of antihyperglycemic agents that target the incretin pathway, including their therapeutic efficacy and side effect profiles, in order to help identify their place among the treatment options for patients with type 2 diabetes. QUALITY OF EVIDENCE MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched. Most evidence is level I and II. MAIN MESSAGE Two classes of incretin agents are currently available: glucagonlike peptide 1 (GLP1) receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, both of which lower hyperglycemia considerably without increasing the risk of hypoglycemia. The GLP1 receptor agonists have a greater effect on patients’ glycated hemoglobin A1c levels and cause sustained weight loss, whereas the DPP4 inhibitors are weight-neutral. CONCLUSION The GLP1 and DPP4 incretin agents, promising and versatile antihyperglycemic agents, are finding their way into the therapeutic algorithm for treating type 2 diabetes. They can be used in patients not adequately controlled by metformin monotherapy or as initial therapy in those for whom metformin is contraindicated. PMID:20631270

  12. 7 CFR 932.72 - Agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Agents. 932.72 Section 932.72 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order...

  13. 7 CFR 932.72 - Agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Agents. 932.72 Section 932.72 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order...

  14. 7 CFR 932.72 - Agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Agents. 932.72 Section 932.72 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order...

  15. 7 CFR 932.72 - Agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Agents. 932.72 Section 932.72 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order...

  16. 7 CFR 932.72 - Agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Agents. 932.72 Section 932.72 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order...

  17. Conversational Agents in Virtual Worlds: Bridging Disciplines

    ERIC Educational Resources Information Center

    Veletsianos, George; Heller, Robert; Overmyer, Scott; Procter, Mike

    2010-01-01

    This paper examines the effective deployment of conversational agents in virtual worlds from the perspective of researchers/practitioners in cognitive psychology, computing science, learning technologies and engineering. From a cognitive perspective, the major challenge lies in the coordination and management of the various channels of information…

  18. 7 CFR 905.86 - Agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Agents. 905.86 Section 905.86 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE ORANGES, GRAPEFRUIT, TANGERINES, AND TANGELOS GROWN IN FLORIDA Order...

  19. 7 CFR 905.86 - Agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Agents. 905.86 Section 905.86 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ORANGES, GRAPEFRUIT, TANGERINES, AND TANGELOS GROWN IN FLORIDA Order...

  20. 7 CFR 906.59 - Agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Agents. 906.59 Section 906.59 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE ORANGES AND GRAPEFRUIT GROWN IN LOWER RIO GRANDE VALLEY IN TEXAS Order...